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Sample records for predicting glucose intolerance

  1. Glucose Homeostatic Law: Insulin Clearance Predicts the Progression of Glucose Intolerance in Humans

    PubMed Central

    Uda, Shinsuke; Kubota, Hiroyuki; Iwaki, Toshinao; Fukuzawa, Hiroki; Komori, Yasunori; Fujii, Masashi; Toyoshima, Yu; Sakaguchi, Kazuhiko; Ogawa, Wataru; Kuroda, Shinya

    2015-01-01

    Homeostatic control of blood glucose is regulated by a complex feedback loop between glucose and insulin, of which failure leads to diabetes mellitus. However, physiological and pathological nature of the feedback loop is not fully understood. We made a mathematical model of the feedback loop between glucose and insulin using time course of blood glucose and insulin during consecutive hyperglycemic and hyperinsulinemic-euglycemic clamps in 113 subjects with variety of glucose tolerance including normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). We analyzed the correlation of the parameters in the model with the progression of glucose intolerance and the conserved relationship between parameters. The model parameters of insulin sensitivity and insulin secretion significantly declined from NGT to IGT, and from IGT to T2DM, respectively, consistent with previous clinical observations. Importantly, insulin clearance, an insulin degradation rate, significantly declined from NGT, IGT to T2DM along the progression of glucose intolerance in the mathematical model. Insulin clearance was positively correlated with a product of insulin sensitivity and secretion assessed by the clamp analysis or determined with the mathematical model. Insulin clearance was correlated negatively with postprandial glucose at 2h after oral glucose tolerance test. We also inferred a square-law between the rate constant of insulin clearance and a product of rate constants of insulin sensitivity and secretion in the model, which is also conserved among NGT, IGT and T2DM subjects. Insulin clearance shows a conserved relationship with the capacity of glucose disposal among the NGT, IGT and T2DM subjects. The decrease of insulin clearance predicts the progression of glucose intolerance. PMID:26623647

  2. Prediction of glucose intolerance at 24-28 weeks of gestation by glucose and insulin level measurements in the first trimester

    PubMed Central

    Fahami, Fariba; Torabi, Sahar; Abdoli, Samereh

    2015-01-01

    Background: Gestational diabetes is the second common disorder in pregnancy period, which is detected in 24-28 weeks of gestational age through screening tests in low-risk women. The women with gestational diabetes are prone to prenatal mortality and development of future diabetes. Therefore, detection of these individuals in the first trimester and conducting preventive interventions is of great importance. This study aimed to define the predictive value of fasting plasma glucose (FPG) and fasting plasma insulin (FPI) test in first trimester concerning the positive result of oral glucose challenge test (OGCT). Materials and Methods: This is a prospective and observational study conducted on 88 pregnant women in Tehran. After FPG and FPI measurements in these women in the first trimester, a screening test of GCT with 50 g oral glucose was conducted in 24-28 weeks of gestational age. Diagnostic value of FPG and in these two groups of positive and normal GCT results was evaluated through receiver operator characteristic (ROC) curve. P < 0.05 was considered significant. Results: In this study, 15 subjects (17%) were detected with a positive GCT result. The sub-curve area of ROC diagram for FPG and FPI was calculated to be 0.573and 0.592, respectively, which reveals that FPG and FPI cannot have a proper predictive value for the positive result of GCT. Based on the results, the best cutoff points for FPG and FPI are 79.5 mg/dl and 7.55 μIU/ml, with accuracy of 60-67% and specificity of 45.2-47%. Conclusions: Only higher fasting glucose levels in early pregnancy, within the normoglycemic range, would predict the development of glucose intolerance with limited sensitivity and specificity. PMID:25709695

  3. Glucose intolerance states in women with the polycystic ovary syndrome.

    PubMed

    Pasquali, R; Gambineri, A

    2013-09-01

    The polycystic ovary syndrome (PCOS), the most common hyperandrogenic disorder affecting 4-7% of women, is often associated with metabolic alterations, chiefly insulin resistance and obesity. Based on available scientific evidence, PCOS should be regarded as an independent risk for the development of glucose intolerance states. This short review summarizes the available literature on the prevalence and incidence of impaired glucose tolerance and Type 2 diabetes in this disorder. In addition, some insights on potential factors responsible for individual susceptibility are discussed. Targeted intervention studies focused on prevention and treatment of glucose intolerance states in PCOS are warranted.

  4. Aldosterone aggravates glucose intolerance induced by high fructose.

    PubMed

    Sherajee, Shamshad J; Rafiq, Kazi; Nakano, Daisuke; Mori, Hirohito; Kobara, Hideki; Hitomi, Hirofumi; Fujisawa, Yoshihide; Kobori, Hiroyuki; Masaki, Tsutomu; Nishiyama, Akira

    2013-11-15

    We previously reported that aldosterone impaired vascular insulin signaling in vivo and in vitro. Fructose-enriched diet induces metabolic syndrome including hypertension, insulin resistance, hyperlipidemia and diabetes in animal. In the current study, we hypothesized that aldosterone aggravated fructose feeding-induced glucose intolerance in vivo. Rats were divided into five groups for six-week treatment; uninephrectomy (Unx, n=8), Unx+aldosterone (aldo, 0.75 µg/h, s.c., n=8), Unx+fructose (fruc, 10% in drinking water, n=8), Unx+aldo+fruc, (aldo+fruc, n=8), and Unx+aldo+fruc+spironolactone, a mineralocorticoid receptor antagonist (aldo+fruc+spiro, 20mg/kg/day, p.o., n=8). Aldo+fruc rats manifested the hypertension, and induced glucose intolerance compared to fruc intake rats assessed by oral glucose tolerance test, homeostasis model assessment of insulin resistance and hyperinsulinemic-euglycemic clamp study. Spironolactone, significantly improved the aldosterone-accelerated glucose intolerance. Along with improvement in insulin resistance, spironolactone suppressed upregulated mineralocorticoid receptor (MR) target gene, serum and glucocorticoid-regulated kinases-1 mRNA expression in skeletal muscle in aldo+fruc rats. In conclusion, these data suggested that aldosterone aggravates fructose feeding-induced glucose intolerance through MR activation.

  5. Artificial sweeteners induce glucose intolerance by altering the gut microbiota.

    PubMed

    Suez, Jotham; Korem, Tal; Zeevi, David; Zilberman-Schapira, Gili; Thaiss, Christoph A; Maza, Ori; Israeli, David; Zmora, Niv; Gilad, Shlomit; Weinberger, Adina; Kuperman, Yael; Harmelin, Alon; Kolodkin-Gal, Ilana; Shapiro, Hagit; Halpern, Zamir; Segal, Eran; Elinav, Eran

    2014-10-01

    Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage.

  6. Healthy diet and lifestyle clustering and glucose intolerance.

    PubMed

    Perry, I J

    2002-11-01

    Glucose intolerance represents a spectrum of abnormalities, including impaired fasting glucose, impaired glucose tolerance and type 2 diabetes. It is a major public health challenge worldwide, with rapidly increasing prevalence rates in both developed and developing countries. This global epidemic of diabetes is largely driven by the globalisation of Western culture and lifestyles. Specifically, there is now evidence from large-scale observational studies, and from intervention studies, of powerful synergistic interactions between diet, obesity, exercise, smoking and alcohol in the development of glucose intolerance. It is estimated that >90% of cases of type 2 diabetes in the population could be prevented with the adoption of a prudent diet (high in cereal fibre and polyunsaturated fatty acids and low in trans-fatty acids and glycaemic load), avoidance of overweight and obesity (BMI<25 kg/m2), engagement in moderate to vigorous physical activity for at least 0.5 h/d, non-smoking and moderate alcohol consumption. These findings are biologically plausible and have major public health implications. They form the basis for a clear, simple and coherent message for health promotion and public policy. However, to make progress on these issues health will need to be placed at the centre of public policy and relevant vested interests tackled, notably in the food, entertainment, tobacco and automobile industries. PMID:12691184

  7. Healthy diet and lifestyle clustering and glucose intolerance.

    PubMed

    Perry, I J

    2002-11-01

    Glucose intolerance represents a spectrum of abnormalities, including impaired fasting glucose, impaired glucose tolerance and type 2 diabetes. It is a major public health challenge worldwide, with rapidly increasing prevalence rates in both developed and developing countries. This global epidemic of diabetes is largely driven by the globalisation of Western culture and lifestyles. Specifically, there is now evidence from large-scale observational studies, and from intervention studies, of powerful synergistic interactions between diet, obesity, exercise, smoking and alcohol in the development of glucose intolerance. It is estimated that >90% of cases of type 2 diabetes in the population could be prevented with the adoption of a prudent diet (high in cereal fibre and polyunsaturated fatty acids and low in trans-fatty acids and glycaemic load), avoidance of overweight and obesity (BMI<25 kg/m2), engagement in moderate to vigorous physical activity for at least 0.5 h/d, non-smoking and moderate alcohol consumption. These findings are biologically plausible and have major public health implications. They form the basis for a clear, simple and coherent message for health promotion and public policy. However, to make progress on these issues health will need to be placed at the centre of public policy and relevant vested interests tackled, notably in the food, entertainment, tobacco and automobile industries.

  8. Artificial sweeteners induce glucose intolerance by altering the gut microbiota.

    PubMed

    Suez, Jotham; Korem, Tal; Zeevi, David; Zilberman-Schapira, Gili; Thaiss, Christoph A; Maza, Ori; Israeli, David; Zmora, Niv; Gilad, Shlomit; Weinberger, Adina; Kuperman, Yael; Harmelin, Alon; Kolodkin-Gal, Ilana; Shapiro, Hagit; Halpern, Zamir; Segal, Eran; Elinav, Eran

    2014-10-01

    Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage. PMID:25231862

  9. Human Gut Microbiota Changes Reveal the Progression of Glucose Intolerance

    PubMed Central

    Zhang, Xiuying; Shen, Dongqian; Fang, Zhiwei; Jie, Zhuye; Qiu, Xinmin; Zhang, Chunfang; Chen, Yingli; Ji, Linong

    2013-01-01

    To explore the relationship of gut microbiota with the development of type 2 diabetes (T2DM), we analyzed 121 subjects who were divided into 3 groups based on their glucose intolerance status: normal glucose tolerance (NGT; n = 44), prediabetes (Pre-DM; n = 64), or newly diagnosed T2DM (n = 13). Gut microbiota characterizations were determined with 16S rDNA-based high-throughput sequencing. T2DM-related dysbiosis was observed, including the separation of microbial communities and a change of alpha diversity between the different glucose intolerance statuses. To assess the correlation between metabolic parameters and microbiota diversity, clinical characteristics were also measured and a significant association between metabolic parameters (FPG, CRP) and gut microbiota was found. In addition, a total of 28 operational taxonomic units (OTUs) were found to be related to T2DM status by the Kruskal-Wallis H test, most of which were enriched in the T2DM group. Butyrate-producing bacteria (e.g. Akkermansia muciniphila ATCCBAA-835, and Faecalibacterium prausnitzii L2-6) had a higher abundance in the NGT group than in the pre-DM group. At genus level, the abundance of Bacteroides in the T2DM group was only half that of the NGT and Pre-DM groups. Previously reported T2DM-related markers were also compared with the data in this study, and some inconsistencies were noted. We found that Verrucomicrobiae may be a potential marker of T2DM as it had a significantly lower abundance in both the pre-DM and T2DM groups. In conclusion, this research provides further evidence of the structural modulation of gut microbiota in the pathogenesis of diabetes. PMID:24013136

  10. Vitamin E and Vitamin C supplementation does not prevent glucose intolerance in obese-prone rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity-induced glucose intolerance affects over 70 million Americans. Elevated oxidative stress is associated with development of glucose intolerance. In this work, we tested the hypothesis that supplementation with the anti-oxidants vitamin E (d-alpha-tocopherol acetate; 0.4 g/kg diet) and vitamin...

  11. Effects of exercise and metformin on the prevention of glucose intolerance: a comparative study

    PubMed Central

    Molena-Fernandes, C.; Bersani-Amado, C. A.; Ferraro, Z. M.; Hintze, L. J.; Nardo, N.; Cuman, R. K. N.

    2015-01-01

    We aimed to evaluate the effects of aerobic exercise training (4 days) and metformin exposure on acute glucose intolerance after dexamethasone treatment in rats. Forty-two adult male Wistar rats (8 weeks old) were divided randomly into four groups: sedentary control (SCT), sedentary dexamethasone-treated (SDX), training dexamethasone-treated (DPE), and dexamethasone and metformin treated group (DMT). Glucose tolerance tests and in situ liver perfusion were undertaken on fasting rats to obtain glucose profiles. The DPE group displayed a significant decrease in glucose values compared with the SDX group. Average glucose levels in the DPE group did not differ from those of the DMT group, so we suggest that exercise training corrects dexamethasone-induced glucose intolerance and improves glucose profiles in a similar manner to that observed with metformin. These data suggest that exercise may prevent the development of glucose intolerance induced by dexamethasone in rats to a similar magnitude to that observed after metformin treatment. PMID:26421869

  12. Intermittent hypoxia-induced glucose intolerance is abolished by α-adrenergic blockade or adrenal medullectomy

    PubMed Central

    Shin, Mi-Kyung; Devera, Ronald; Yao, Qiaoling; Mesarwi, Omar; Bevans-Fonti, Shannon; Polotsky, Vsevolod Y.

    2014-01-01

    Obstructive sleep apnea causes intermittent hypoxia (IH) during sleep and is associated with dysregulation of glucose metabolism. We developed a novel model of clinically realistic IH in mice to test the hypothesis that IH causes hyperglycemia, glucose intolerance, and insulin resistance via activation of the sympathetic nervous system. Mice were exposed to acute hypoxia of graded severity (21, 14, 10, and 7% O2) or to IH of graded frequency [oxygen desaturation index (ODI) of 0, 15, 30, or 60, SpO2 nadir 80%] for 30 min to measure levels of glucose fatty acids, glycerol, insulin, and lactate. Glucose tolerance tests and insulin tolerance tests were then performed under each hypoxia condition. Next, we examined these outcomes in mice that were administered phentolamine (α-adrenergic blockade) or propranolol (β-adrenergic blockade) or that underwent adrenal medullectomy before IH exposure. In all experiments, mice were maintained in a thermoneutral environment. Sustained and IH induced hyperglycemia, glucose intolerance, and insulin resistance in a dose-dependent fashion. Only severe hypoxia (7% O2) increased lactate, and only frequent IH (ODI 60) increased plasma fatty acids. Phentolamine or adrenal medullectomy both prevented IH-induced hyperglycemia and glucose intolerance. IH inhibited glucose-stimulated insulin secretion, and phentolamine prevented the inhibition. Propranolol had no effect on glucose metabolism but abolished IH-induced lipolysis. IH-induced insulin resistance was not affected by any intervention. Acutely hypoxia causes hyperglycemia, glucose intolerance, and insulin resistance in a dose-dependent manner. During IH, circulating catecholamines act upon α-adrenoreceptors to cause hyperglycemia and glucose intolerance. PMID:25315697

  13. Hepatic ATGL knockdown uncouples glucose intolerance from liver TAG accumulation.

    PubMed

    Ong, Kuok Teong; Mashek, Mara T; Bu, So Young; Mashek, Douglas G

    2013-01-01

    Adipose triglyceride lipase (ATGL) is the predominant triacylglycerol (TAG) hydrolase in mammals; however, the tissue-specific effects of ATGL outside of adipose tissue have not been well characterized. Hence, we tested the contribution of hepatic ATGL on mediating glucose tolerance and insulin action. Glucose or insulin tolerance tests and insulin signaling were performed in C57BL/6 mice administered control (nongene specific shRNA) or Atgl shRNA adenoviruses. Glucose and lipid metabolism assays were conducted in primary hepatocytes isolated from mice transduced with control or Atgl shRNA adenoviruses. Knocking down hepatic ATGL completely abrogated the increase in serum insulin following either 1 or 12 wk of feeding a high-fat (HF) diet despite higher hepatic TAG content. Glucose tolerance tests demonstrated that ATGL knockdown normalized glucose tolerance in HF-diet-fed mice. The observed improvements in glucose tolerance were present despite unaltered hepatic insulin signaling and increased liver TAG. Mice with suppressed hepatic ATGL had reduced hepatic glucose production in vivo, and hepatocytes isolated from Atgl shRNA-treated mice displayed a 26% decrease in glucose production and a 38% increase in glucose oxidation compared to control cells. Taken together, these data suggest that hepatic ATGL knockdown enhances glucose tolerance by increasing hepatic glucose utilization and uncouples impairments in insulin action from hepatic TAG accumulation.

  14. Ferritin as a Risk Factor for Glucose Intolerance amongst Men and Women Originating from the Indian Subcontinent

    PubMed Central

    Hughes, Elizabeth A.; Patel, Jeetesh V.; Bredow, Zosia; Gill, Paramjit S.; Chackathayil, Julia; Agaoglu, Elif S.; Flinders, Paul; Mirrielees, Rebecca

    2015-01-01

    Background. Serum ferritin predicts the onset of diabetes; however, this relationship is not clear amongst South Asians, a population susceptible to glucose intolerance and anaemia. Objective. This study tests whether ferritin levels reflect glucose tolerance in South Asians, independent of lifestyle exposures associated with Indian or British residence. Methods. We randomly sampled 227 Gujaratis in Britain (49.8 (14.4) years, 50% men) and 277 contemporaries living in Gujarati villages (47.6 (11.8) years, 41% men). Both groups underwent a 75 g oral-glucose-tolerance test. We evaluated lifestyle parameters with standardised questionnaires and conducted comprehensive clinical and lab measurements. Results. Across sites, the age-adjusted prevalence of diabetes was 9.8%. Serum ferritin was higher amongst diabetics (P = 0.005), irrespective of site, gender, and central obesity (P ≤ 0.02), and was associated with fasting and postchallenge glucose, anthropometry, blood pressure, triglycerides, and nonesterified fatty acids (P < 0.001). Diabetes was less in those with low ferritin (<20 mg/mL), P < 0.008, and risk estimate = 0.35 (95% CI 0.15–0.81), as were blood pressure and metabolic risk factors. On multivariate analysis, diabetes was independently associated with ferritin (P = 0.001) and age (P < 0.001). Conclusion. Ferritin levels are positively associated with glucose intolerance in our test groups, independent of gender and Indian or UK lifestyle factors. PMID:26347777

  15. Glucose intolerance associated with hypoxia in people living at high altitudes in the Tibetan highland

    PubMed Central

    Okumiya, Kiyohito; Sakamoto, Ryota; Ishimoto, Yasuko; Kimura, Yumi; Fukutomi, Eriko; Ishikawa, Motonao; Suwa, Kuniaki; Imai, Hissei; Chen, Wenling; Kato, Emiko; Nakatsuka, Masahiro; Kasahara, Yoriko; Fujisawa, Michiko; Wada, Taizo; Wang, Hongxin; Dai, Qingxiang; Xu, Huining; Qiao, Haisheng; Ge, Ri-Li; Norboo, Tsering; Tsering, Norboo; Kosaka, Yasuyuki; Nose, Mitsuhiro; Yamaguchi, Takayoshi; Tsukihara, Toshihiro; Ando, Kazuo; Inamura, Tetsuya; Takeda, Shinya; Ishine, Masayuki; Otsuka, Kuniaki; Matsubayashi, Kozo

    2016-01-01

    Objectives To clarify the association between glucose intolerance and high altitudes (2900–4800 m) in a hypoxic environment in Tibetan highlanders and to verify the hypothesis that high altitude dwelling increases vulnerability to diabetes mellitus (DM) accelerated by lifestyle change or ageing. Design Cross-sectional epidemiological study on Tibetan highlanders. Participants We enrolled 1258 participants aged 40–87 years. The rural population comprised farmers in Domkhar (altitude 2900–3800 m) and nomads in Haiyan (3000–3100 m), Ryuho (4400 m) and Changthang (4300–4800 m). Urban area participants were from Leh (3300 m) and Jiegu (3700 m). Main outcome measure Participants were classified into six glucose tolerance-based groups: DM, intermediate hyperglycaemia (IHG), normoglycaemia (NG), fasting DM, fasting IHG and fasting NG. Prevalence of glucose intolerance was compared in farmers, nomads and urban dwellers. Effects of dwelling at high altitude or hypoxia on glucose intolerance were analysed with the confounding factors of age, sex, obesity, lipids, haemoglobin, hypertension and lifestyle, using multiple logistic regression. Results The prevalence of DM (fasting DM)/IHG (fasting IHG) was 8.9% (6.5%)/25.1% (12.7%), respectively, in all participants. This prevalence was higher in urban dwellers (9.5% (7.1%)/28.5% (11.7%)) and in farmers (8.5% (6.1%)/28.5% (18.3%)) compared with nomads (8.2% (5.7%)/15.7% (9.7%)) (p=0.0140/0.0001). Dwelling at high altitude was significantly associated with fasting IHG+fasting DM/fasting DM (ORs for >4500 and 3500–4499 m were 3.59/4.36 and 2.07/1.76 vs <3500 m, respectively). After adjusting for lifestyle change, hypoxaemia and polycythaemia were closely associated with glucose intolerance. Conclusions Socioeconomic factors, hypoxaemia and the effects of altitudes >3500 m play a major role in the high prevalence of glucose intolerance in highlanders. Tibetan highlanders may be vulnerable to glucose

  16. Population screening for glucose intolerant subjects using decision tree analyses.

    PubMed

    Barriga, K J; Hamman, R F; Hoag, S; Marshall, J A; Shetterly, S M

    1996-10-01

    The purpose of this study was to develop a method of screening for impaired glucose tolerance and previously undiagnosed NIDDM that could be used preliminary to the administration of an oral glucose tolerance test (OGTT) for final classification of glucose tolerance status. The purpose of a preliminary screening of this type would be to reduce the number of OGTT's needed to identify cases of IGT and NIDDM in the population. We used NIDDM risk indicators and decision tree analysis methods (CART software) to identify subgroups of the population at increased risk. We examined a population of Hispanic (n = 583) and non-Hispanic white (n = 768) subjects without a prior history of diabetes. Subjects were classified as normal, IGT or NIDDM (WHO criteria) based on results from a 75 g oral glucose tolerance test (OGTT). Sensitivity (SEN) and specificity (SPE) of the CART models were calculated using the OGTT as the 'gold standard.' Two approaches to screening were simulated. In the simultaneous approach all risk variables were entered into CART models at once. In the serial approach, risk variables were grouped according to degree of effort required for data collection, and were entered into CART models in stages. Fasting glucose, age and body mass index (BMI) were selected as risk variables by CART when simulating the simultaneous approach (SEN = 91%, SPE = 55%). In the serial approach, CART used age and BMI to eliminate 35% of the population from further screening, and then used fasting glucose, glycohemoglobin, age and BMI to classify the remaining higher risk subjects (SEN = 85%, SPE = 64%). These models suggest that screening for IGT and previously undiagnosed NIDDM can be based on measurement of relatively simple indicators, and yet maintain a level of both sensitivity and specificity acceptable for this type of preliminary screening. PMID:9015666

  17. AHNAK KO mice are protected from diet-induced obesity but are glucose intolerant.

    PubMed

    Ramdas, M; Harel, C; Armoni, M; Karnieli, E

    2015-04-01

    AHNAK is a 700 KD phosphoprotein primarily involved in calcium signaling in various cell types and regulating cytoskeletal organization and cell membrane architecture. AHNAK expression has also been associated with obesity. To investigate the role of AHNAK in regulating metabolic homeostasis, we studied whole body AHNAK knockout mice (KO) on either regular chow or high-fat diet (HFD). KO mice had a leaner phenotype and were resistant to high-fat diet-induced obesity (DIO), as reflected by a reduction in adipose tissue mass in conjunction with higher lean mass compared to wild-type controls (WT). However, KO mice exhibited higher fasting glucose levels, impaired glucose tolerance, and diminished serum insulin levels on either diet. Concomitantly, KO mice on HFD displayed defects in insulin signaling, as evident from reduced Akt phosphorylation and decreased cellular glucose transporter (Glut4) levels. Glucose intolerance and insulin resistance were also associated with changes in expression of genes regulating fat, glucose, and energy metabolism in adipose tissue and liver. Taken together, these data demonstrate that (a) AHNAK is involved in glucose homeostasis and weight balance (b) under normal feeding KO mice are insulin sensitive yet insulin deficient; and (c) AHNAK deletion protects against HFD-induced obesity, but not against HFD-induced insulin resistance and glucose intolerance in vivo.

  18. Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance

    PubMed Central

    Bertato, Marina P; Oliveira, Carolina P; Wajchenberg, Bernardo L; Lerario, Antonio C; Maranhão, Raul C

    2012-01-01

    OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE) labeled with 14C-cholesteryl ester and 3H-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the 3H-free- cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in atherogenic

  19. Glucose intolerance induced by blockade of central FGF receptors is linked to an acute stress response

    PubMed Central

    Rojas, Jennifer M.; Matsen, Miles E.; Mundinger, Thomas O.; Morton, Gregory J.; Stefanovski, Darko; Bergman, Richard N.; Kaiyala, Karl J.; Taborsky, Gerald J.; Schwartz, Michael W.

    2015-01-01

    Objective Central administration of ligands for fibroblast growth factor receptors (FGFRs) such as fibroblast growth factor-19 (FGF19) and FGF21 exert glucose-lowering effects in rodent models of obesity and type 2 diabetes (T2D). Conversely, intracerebroventricular (icv) administration of the non-selective FGFR inhibitor (FGFRi) PD173074 causes glucose intolerance, implying a physiological role for neuronal FGFR signaling in glucose homeostasis. The current studies were undertaken to identify neuroendocrine mechanisms underlying the glucose intolerance induced by pharmacological blockade of central FGFRs. Methods Overnight fasted, lean, male, Long-Evans rats received icv injections of either PD173074 or vehicle (Veh) followed 30 min later by performance of a frequently sampled intravenous glucose tolerance test (FSIGT). Minimal model analysis of glucose and insulin data from the FSIGT was performed to estimate insulin-dependent and insulin-independent components of glucose disposal. Plasma levels of lactate, glucagon, corticosterone, non-esterified free fatty acids (NEFA) and catecholamines were measured before and after intravenous (iv) glucose injection. Results Within 20 min of icv PD173074 injection (prior to the FSIGT), plasma levels of lactate, norepinephrine and epinephrine increased markedly, and each returned to baseline rapidly (within 8 min) following the iv glucose bolus. In contrast, plasma glucagon levels were not altered by icv FGFRi at either time point. Consistent with a previous report, glucose tolerance was impaired following icv PD173074 compared to Veh injection and, based on minimal model analysis of FSIGT data, this effect was attributable to reductions of both insulin secretion and the basal insulin effect (BIE), consistent with the inhibitory effect of catecholamines on pancreatic β-cell secretion. By comparison, there were no changes in glucose effectiveness at zero insulin (GEZI) or the insulin sensitivity index (SI). To determine if

  20. Glycemic Effects of Rebaudioside A and Erythritol in People with Glucose Intolerance

    PubMed Central

    Shin, Dong Hee; Lee, Ji Hye; Kang, Myung Shin; Kim, Tae Hoon; Jeong, Su Jin; Kim, Sang Soo

    2016-01-01

    Background Rebaudioside A and erythritol are nonnutritive sweeteners. There have been several studies of their glycemic effects, but the outcomes remain controversial. The purpose of this study was to evaluate the glycemic effects of rebaudioside A and erythritol as a sweetener in people with glucose intolerance. Methods This trial evaluated the glycemic effect after 2 weeks of consumption of rebaudioside A and erythritol as sweeteners in a pre-diabetic population. The patients were evaluated for fructosamine, fasting plasma glucose, C-peptide, insulin, and 2-hour plasma glucose before and after consumption of sweetener. The primary outcome was a change in fructosamine levels from the baseline to the end of treatment. Secondary outcomes were the changes in levels of fasting plasma glucose and 2-hour plasma glucose. Results From the baseline to the end of experiment, the changes in fructosamine levels after consumption of rebaudioside A and erythritol, did not differ significantly (244.00±19.57 vs. 241.68±23.39 µmol/L, P=0.366). The change in levels from the baseline to end of the study for rebaudioside A and erythritol were fasting plasma glucose (102.56±10.72 vs. 101.32±9.20 mg/dL), 2-hour plasma glucose (154.92±54.53 vs. 141.92±42.22 mg/dL), insulin (7.56±4.29 vs. 7.20±5.12 IU/mL), and C-peptide (2.92±1.61 vs. 2.73±1.31 ng/mL), respectively, and also did not differ significantly (P>0.05 for all). Conclusion Our study suggests that consumption of rebaudioside A and erythritol does not alter the glucose homeostasis in people with glucose intolerance. PMID:27352150

  1. Arsenic Exposure and Glucose Intolerance/Insulin Resistance in Estrogen-Deficient Female Mice

    PubMed Central

    Huang, Chun-Fa; Yang, Ching-Yao; Chan, Ding-Cheng; Wang, Ching-Chia; Huang, Kuo-How; Wu, Chin-Ching; Tsai, Keh-Sung; Yang, Rong-Sen

    2015-01-01

    Background Epidemiological studies have reported that the prevalence of diabetes in women > 40 years of age, especially those in the postmenopausal phase, was higher than in men in areas with high levels of arsenic in drinking water. The detailed effect of arsenic on glucose metabolism/homeostasis in the postmenopausal condition is still unclear. Objectives We investigated the effects of arsenic at doses relevant to human exposure from drinking water on blood glucose regulation in estrogen-deficient female mice. Methods Adult female mice who underwent ovariectomy or sham surgery were exposed to drinking water contaminated with arsenic trioxide (0.05 or 0.5 ppm) in the presence or absence of 17β-estradiol supplementation for 2–6 weeks. Assays related to glucose metabolism were performed. Results Exposure of sham mice to arsenic significantly increased blood glucose, decreased plasma insulin, and impaired glucose tolerance, but did not induce insulin resistance. Blood glucose and insulin were higher, and glucose intolerance, insulin intolerance, and insulin resistance were increased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Furthermore, liver phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was increased and liver glycogen content was decreased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Glucose-stimulated insulin secretion in islets isolated from arsenic-treated ovariectomized mice was also significantly decreased. Arsenic treatment significantly decreased plasma adiponectin levels in sham and ovariectomized mice. Altered glucose metabolism/homeostasis in arsenic-treated ovariectomized mice was reversed by 17β-estradiol supplementation. Conclusions Our findings suggest that estrogen deficiency plays an important role in arsenic-altered glucose metabolism/homeostasis in females. Citation Huang CF, Yang CY, Chan DC, Wang CC, Huang KH, Wu CC, Tsai KS, Yang RS, Liu SH. 2015. Arsenic

  2. Fish oil consumption prevents glucose intolerance and hypercorticosteronemy in footshock-stressed rats

    PubMed Central

    2011-01-01

    Background Environmental stress plays an important role in the development of glucose intolerance influencing lipid and glucose metabolism through sympathetic nervous system, cytokines and hormones such as glucocorticoids, catecholamines and glucagon. Otherwise, fish oil prevents glucose intolerance and insulin resistance. Although the mechanisms involved are not fully understood, it is known that sympathetic and HPA responses are blunted and catecholamines and glucocorticoids concentrations can be modulated by fish consumption. The aim of the present study was to evaluate whether fish oil, on a normal lipidic diet: 1) could prevent the effect of footshock-stress on the development of glucose intolerance; 2) modified adiponectin receptor and serum concentration; and 3) also modified TNF-α, IL-6 and interleukin-10 (IL-10) levels in adipose tissue and liver. The study was performed in thirty day-old male Wistar randomly assigned into four groups: no stressed (C) and stressed (CS) rats fed with control diet, and no stressed (F) and stressed (FS) rats fed with a fish oil rich diet. The stress was performed as a three daily footshock stress sessions. Results Body weight, carcass fat and protein content were not different among groups. FS presented a reduction on the relative weight of RET. Basal serum glucose levels were higher in CS and FS but 15 min after glucose load just CS remained with higher levels than other groups. Serum corticosterone concentration was increased in CS, this effect was inhibited in FS. However, 15 min after footshock-stress, corticosterone levels were similar among groups. IL-6 was increased in EPI of CS but fish oil consumption prevented IL-6 increase in FS. Similar levels of TNF-α and IL-10 in RET, EPI, and liver were observed among groups. Adipo R1 protein concentration was not different among groups. Footshock-stress did not modify AdipoR2 concentration, but fish oil diet increases AdipoR2 protein concentration. Conclusions Footshock

  3. Glucose Intolerance, Insulin Resistance and Alzheimer’s Disease Pathology in the Baltimore Longitudinal Study of Aging

    PubMed Central

    Thambisetty, M.; Metter, E.J.; Yang, A.; Dolan, H.; Marano, C.; Zonderman, A.B.; Troncoso, J.; Zhou, Y; Wong, D.F.; Ferrucci, L.; Egan, J.M.; Resnick, S.M.; OBrien, R.

    2014-01-01

    Objective To investigate associations between serial measures of glucose intolerance and insulin resistance with in vivo amyloid burden, measured with 11C-PiB, and Alzheimer’s disease (AD) pathology at autopsy in a prospective cohort from the Baltimore Longitudinal Study of Aging. Methods Brain CERAD and Braak scores were correlated with measures of hyperglycemia, hyperinsulinemia, glucose intolerance and insulin resistance in 197 participants who had come to autopsy and had two or more oral glucose tolerance tests (OGTT) during life. Glucose intolerance was measured by fasting and 120-minute post-load glucose values. Insulin resistance was measured by fasting and 120-minute post-load serum insulin values and the ratio of serum glucose to insulin at baseline and following a glucose load. In addition, the same measures of glucose intolerance and insulin resistance were correlated with brain 11C-PiB retention in 53 living subjects. Results There were no significant correlations between measures of brain AD pathology or 11C-PiB derived amyloid load and either glucose intolerance or insulin resistance in subjects who had a mean of 6.4 ± 3.2 (S.D.) OGTT evaluations over 22.1 ± 8.0 (S.D.) years of follow-up. Thirty subjects with frank diabetes on medication also had AD pathology scores that were similar to the cohort as a whole. Conclusions In this prospective cohort with multiple assessments of glucose intolerance and insulin resistance, measures of glucose and insulin homeostasis were not associated with AD pathology. PMID:23897112

  4. Fructose malabsorption and intolerance: effects of fructose with and without simultaneous glucose ingestion.

    PubMed

    Latulippe, Marie E; Skoog, Suzanne M

    2011-08-01

    Concern exists that increasing fructose consumption, particularly in the form of high-fructose corn syrup, is resulting in increasing rates of fructose intolerance and aggravation of clinical symptoms in individuals with irritable bowel syndrome. Most clinical trials designed to test this hypothesis have used pure fructose, a form not commonly found in the food supply, often in quantities and concentrations that exceed typical fructose intake levels. In addition, the amount of fructose provided in tests for malabsorption, which is thought to be a key cause of intolerance, often exceeds the normal physiological absorption capacity for this sugar. To help health professionals accurately identify and treat this condition, this article reviews clinical data related to understanding fructose malabsorption and intolerance (i.e., malabsorption that manifests with symptoms) relative to usual fructose and other carbohydrate intake. Because simultaneous consumption of glucose attenuates fructose malabsorption, information on the fructose and glucose content of foods, beverages, and ingredients representing a variety of food categories is provided.

  5. Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats

    SciTech Connect

    Bass, V.; Gordon, C.J.; Jarema, K.A.; MacPhail, R.C.; Cascio, W.E.; Phillips, P.M.; Ledbetter, A.D.; Schladweiler, M.C.; Andrews, D.; Miller, D.; Doerfler, D.L.; Kodavanti, U.P.

    2013-12-15

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased α{sub 2}-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2 > 1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation. - Highlights: • Air pollutants have been associated with increased diabetes in humans. • Acute ozone exposure produces profound metabolic alterations in rats. • Age influences metabolic risk factors in aging BN rats. • Acute metabolic effects are reversible and repeated exposure reduces these effects. • Ozone

  6. Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study

    PubMed Central

    Houston, Thomas K; Kiefe, Catarina I; Person, Sharina D; Pletcher, Mark J; Liu, Kiang; Iribarren, Carlos

    2006-01-01

    Objective To assess whether active and passive smokers are more likely than non-smokers to develop clinically relevant glucose intolerance or diabetes. Design Coronary artery risk development in young adults (CARDIA) is a prospective cohort study begun in 1985-6 with 15 years of follow-up. Setting Participants recruited from Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California, USA. Participants Black and white men and women aged 18-30 years with no glucose intolerance at baseline, including 1386 current smokers, 621 previous smokers, 1452 never smokers with reported exposure to secondhand smoke (validated by serum cotinine concentrations 1-15 ng/ml), and 1113 never smokers with no exposure to secondhand smoke. Main outcome measure Time to development of glucose intolerance (glucose ≥ 100 mg/dl or taking antidiabetic drugs) during 15 years of follow-up. Results Median age at baseline was 25, 55% of participants were women, and 50% were African-American. During follow-up, 16.7% of participants developed glucose intolerance. A graded association existed between smoking exposure and the development of glucose intolerance. The 15 year incidence of glucose intolerance was highest among smokers (21.8%), followed by never smokers with passive smoke exposure (17.2%), and then previous smokers (14.4%); it was lowest for never smokers with no passive smoke exposure (11.5%). Current smokers (hazard ratio 1.65, 95% confidence interval 1.27 to 2.13) and never smokers with passive smoke exposure (1.35, 1.06 to 1.71) remained at higher risk than never smokers without passive smoke exposure after adjustment for multiple baseline sociodemographic, biological, and behavioural factors, but risk in previous smokers was similar to that in never smokers without passive smoke exposure. Conclusion These findings support a role of both active and passive smoking in the development of glucose intolerance in young adulthood. PMID:16603565

  7. Transgenic Mice Overexpressing Renin Exhibit Glucose Intolerance and Diet-Genotype Interactions

    PubMed Central

    Fletcher, Sarah J.; Kalupahana, Nishan S.; Soltani-Bejnood, Morvarid; Kim, Jung Han; Saxton, Arnold M.; Wasserman, David H.; De Taeye, Bart; Voy, Brynn H.; Quignard-Boulange, Annie; Moustaid-Moussa, Naima

    2013-01-01

    Numerous animal and clinical investigations have pointed to a potential role of the renin-angiotensin system (RAS) in the development of insulin resistance and diabetes in conditions of expanded fat mass. However, the mechanisms underlying this association remain unclear. We used a transgenic mouse model overexpressing renin in the liver (RenTgMK) to examine the effects of chronic activation of RAS on adiposity and insulin sensitivity. Hepatic overexpression of renin resulted in constitutively elevated plasma angiotensin II (four- to six-fold increase vs. wild-type, WT). Surprisingly, RenTgMK mice developed glucose intolerance despite low levels of adiposity and insulinemia. The transgenics also had lower plasma triglyceride levels. Glucose intolerance in transgenic mice fed a low-fat diet was comparable to that observed in high-fat fed WT mice. These studies demonstrate that overexpression of renin and associated hyperangiotensinemia impair glucose tolerance in a diet-dependent manner and further support a consistent role of RAS in the pathogenesis of diabetes and insulin resistance, independent of changes in fat mass. PMID:23308073

  8. High prevalence of glucose intolerance even among young adults in south India

    PubMed Central

    Raghupathy, Palany; Antonisamy, Belavendra; Fall, Caroline H.D.; Geethanjali, Finney S.; Leary, Samantha D.; Saperia, Julia; Priya, G; Rajaratnam, Abel; Richard, Joseph

    2012-01-01

    India is experiencing an epidemic of type 2 diabetes (DM) in young adults. This study reports the prevalence of glucose intolerance, and insulin profiles, and their relationship to lifestyle factors in 2,218 young adults (aged 26-32 years; 997 urban, 1221 rural) in South India. They were drawn from a cohort of 10,691 individuals born during 1969-1973 in Vellore and nearby villages. Family history, socio-economic status, physical activity and tobacco and alcohol use were recorded. Oral glucose tolerance tests were performed for diagnosis (WHO recommendations). Insulin resistance and secretion were derived from plasma insulin concentrations. Median BMI was 20.0 kg/m2. The prevalence of type 2 DM and IGT was higher in urban than in rural subjects (3.7% vs 2.1%, p=0.02; 18.9% vs 14.3%, p=0.002 respectively), while prevalence of IFG was similar in urban and rural populations (3.8% vs 3.4%, p=0.04). Type 2 DM, IGT, IFG or higher insulin resistance and increment were associated with higher socio-economic status (more household possessions) and higher percentage body fat, body mass index and waist/hip ratio. Insulin increment was lower in men with higher alcohol consumption. Our data suggest high levels of glucose intolerance in young rural and urban adults highlighting an urgent need for preventive action to avert a public health catastrophe in India. PMID:17229484

  9. Reduced insulin secretion and glucose intolerance are involved in the fasting susceptibility of common vampire bats.

    PubMed

    Freitas, Mariella B; Queiroz, Joicy F; Dias Gomes, Carolinne I; Collares-Buzato, Carla B; Barbosa, Helena C; Boschero, Antonio C; Gonçalves, Carlos A; Pinheiro, Eliana C

    2013-03-01

    Susceptibility during fasting has been reported for the common vampire bat (Desmodus rotundus), to the point of untimely deaths after only 2-3 nights of fasting. To investigate the underlying physiology of this critical metabolic condition, we analyzed serum insulin levels, pancreatic islets morphometry and immunocytochemistry (ICC), static insulin secretion in pancreas fragments, and insulin signaling mechanism in male vampire bats. A glucose tolerance test (ipGTT) was also performed. Serum insulin was found to be lower in fed vampires compared to other mammals, and was significantly reduced after 24h fasting. Morphometrical analyses revealed small irregular pancreatic islets with reduced percentage of β-cell mass compared to other bats. Static insulin secretion analysis showed that glucose-stimulated insulin secretion was impaired, as insulin levels did not reach significance under high glucose concentrations, whereas the response to the amino acid leucin was preserved. Results from ipGTT showed a failure on glucose clearance, indicating glucose intolerance due to diminished pancreatic insulin secretion and/or decreased β-cell response to glucose. In conclusion, data presented here indicate lower insulinemia and impaired insulin secretion in D. rotundus, which is consistent with the limited ability to store body energy reserves, previously reported in these animals. Whether these metabolic and hormonal features are associated with their blood diet remains to be determined. The peculiar food sharing through blood regurgitation, reported to this species, might be an adaptive mechanism overcoming this metabolic susceptibility. PMID:23262275

  10. Reduced insulin secretion and glucose intolerance are involved in the fasting susceptibility of common vampire bats.

    PubMed

    Freitas, Mariella B; Queiroz, Joicy F; Dias Gomes, Carolinne I; Collares-Buzato, Carla B; Barbosa, Helena C; Boschero, Antonio C; Gonçalves, Carlos A; Pinheiro, Eliana C

    2013-03-01

    Susceptibility during fasting has been reported for the common vampire bat (Desmodus rotundus), to the point of untimely deaths after only 2-3 nights of fasting. To investigate the underlying physiology of this critical metabolic condition, we analyzed serum insulin levels, pancreatic islets morphometry and immunocytochemistry (ICC), static insulin secretion in pancreas fragments, and insulin signaling mechanism in male vampire bats. A glucose tolerance test (ipGTT) was also performed. Serum insulin was found to be lower in fed vampires compared to other mammals, and was significantly reduced after 24h fasting. Morphometrical analyses revealed small irregular pancreatic islets with reduced percentage of β-cell mass compared to other bats. Static insulin secretion analysis showed that glucose-stimulated insulin secretion was impaired, as insulin levels did not reach significance under high glucose concentrations, whereas the response to the amino acid leucin was preserved. Results from ipGTT showed a failure on glucose clearance, indicating glucose intolerance due to diminished pancreatic insulin secretion and/or decreased β-cell response to glucose. In conclusion, data presented here indicate lower insulinemia and impaired insulin secretion in D. rotundus, which is consistent with the limited ability to store body energy reserves, previously reported in these animals. Whether these metabolic and hormonal features are associated with their blood diet remains to be determined. The peculiar food sharing through blood regurgitation, reported to this species, might be an adaptive mechanism overcoming this metabolic susceptibility.

  11. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease.

    PubMed

    Baker, Laura D; Frank, Laura L; Foster-Schubert, Karen; Green, Pattie S; Wilkinson, Charles W; McTiernan, Anne; Cholerton, Brenna A; Plymate, Stephen R; Fishel, Mark A; Watson, G Stennis; Duncan, Glen E; Mehta, Pankaj D; Craft, Suzanne

    2010-01-01

    Impaired glucose regulation is a defining characteristic of type 2 diabetes mellitus (T2DM) pathology and has been linked to increased risk of cognitive impairment and dementia. Although the benefits of aerobic exercise for physical health are well-documented, exercise effects on cognition have not been examined for older adults with poor glucose regulation associated with prediabetes and early T2DM. Using a randomized controlled design, twenty-eight adults (57-83 y old) meeting 2-h tolerance test criteria for glucose intolerance completed 6 months of aerobic exercise or stretching, which served as the control. The primary cognitive outcomes included measures of executive function (Trails B, Task Switching, Stroop, Self-ordered Pointing Test, and Verbal Fluency). Other outcomes included memory performance (Story Recall, List Learning), measures of cardiorespiratory fitness obtained via maximal-graded exercise treadmill test, glucose disposal during hyperinsulinemic-euglycemic clamp, body fat, and fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulin-like growth factor-1, amyloid-β (Aβ40 and Aβ42). Six months of aerobic exercise improved executive function (MANCOVA, p=0.04), cardiorespiratory fitness (MANOVA, p=0.03), and insulin sensitivity (p=0.05). Across all subjects, 6-month changes in cardiorespiratory fitness and insulin sensitivity were positively correlated (p=0.01). For Aβ42, plasma levels tended to decrease for the aerobic group relative to controls (p=0.07). The results of our study using rigorous controlled methodology suggest a cognition-enhancing effect of aerobic exercise for older glucose intolerant adults. Although replication in a larger sample is needed, our findings potentially have important therapeutic implications for a growing number of adults at increased risk of cognitive decline.

  12. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease.

    PubMed

    Baker, Laura D; Frank, Laura L; Foster-Schubert, Karen; Green, Pattie S; Wilkinson, Charles W; McTiernan, Anne; Cholerton, Brenna A; Plymate, Stephen R; Fishel, Mark A; Watson, G Stennis; Duncan, Glen E; Mehta, Pankaj D; Craft, Suzanne

    2010-01-01

    Impaired glucose regulation is a defining characteristic of type 2 diabetes mellitus (T2DM) pathology and has been linked to increased risk of cognitive impairment and dementia. Although the benefits of aerobic exercise for physical health are well-documented, exercise effects on cognition have not been examined for older adults with poor glucose regulation associated with prediabetes and early T2DM. Using a randomized controlled design, twenty-eight adults (57-83 y old) meeting 2-h tolerance test criteria for glucose intolerance completed 6 months of aerobic exercise or stretching, which served as the control. The primary cognitive outcomes included measures of executive function (Trails B, Task Switching, Stroop, Self-ordered Pointing Test, and Verbal Fluency). Other outcomes included memory performance (Story Recall, List Learning), measures of cardiorespiratory fitness obtained via maximal-graded exercise treadmill test, glucose disposal during hyperinsulinemic-euglycemic clamp, body fat, and fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulin-like growth factor-1, amyloid-β (Aβ40 and Aβ42). Six months of aerobic exercise improved executive function (MANCOVA, p=0.04), cardiorespiratory fitness (MANOVA, p=0.03), and insulin sensitivity (p=0.05). Across all subjects, 6-month changes in cardiorespiratory fitness and insulin sensitivity were positively correlated (p=0.01). For Aβ42, plasma levels tended to decrease for the aerobic group relative to controls (p=0.07). The results of our study using rigorous controlled methodology suggest a cognition-enhancing effect of aerobic exercise for older glucose intolerant adults. Although replication in a larger sample is needed, our findings potentially have important therapeutic implications for a growing number of adults at increased risk of cognitive decline. PMID:20847403

  13. Arsenate-induced maternal glucose intolerance and neural tube defects in a mouse model

    SciTech Connect

    Hill, Denise S.; Wlodarczyk, Bogdan J.; Mitchell, Laura E.; Finnell, Richard H.

    2009-08-15

    Background: Epidemiological studies have linked environmental arsenic (As) exposure to increased type 2 diabetes risk. Periconceptional hyperglycemia is a significant risk factor for neural tube defects (NTDs), the second most common structural birth defect. A suspected teratogen, arsenic (As) induces NTDs in laboratory animals. Objectives: We investigated whether maternal glucose homeostasis disruption was responsible for arsenate-induced NTDs in a well-established dosing regimen used in studies of arsenic's teratogenicity in early neurodevelopment. Methods: We evaluated maternal intraperitoneal (IP) exposure to As 9.6 mg/kg (as sodium arsenate) in LM/Bc/Fnn mice for teratogenicity and disruption of maternal plasma glucose and insulin levels. Selected compounds (insulin pellet, sodium selenate (SS), N-acetyl cysteine (NAC), L-methionine (L-Met), N-tert-Butyl-{alpha}-phenylnitrone (PBN)) were investigated for their potential to mitigate arsenate's effects. Results: Arsenate caused significant glucose elevation during an IP glucose tolerance test (IPGTT). Insulin levels were not different between arsenate and control dams before (arsenate, 0.55 ng/dl; control, 0.48 ng/dl) or after glucose challenge (arsenate, 1.09 ng/dl; control, 0.81 ng/dl). HOMA-IR index was higher for arsenate (3.9) vs control (2.5) dams (p = 0.0260). Arsenate caused NTDs (100%, p < 0.0001). Insulin pellet and NAC were the most successful rescue agents, reducing NTD rates to 45% and 35%. Conclusions: IPGTT, insulin assay, and HOMA-IR results suggest a modest failure of glucose stimulated insulin secretion and insulin resistance characteristic of glucose intolerance. Insulin's success in preventing arsenate-induced NTDs provides evidence that these arsenate-induced NTDs are secondary to elevated maternal glucose. The NAC rescue, which did not restore maternal glucose or insulin levels, suggests oxidative disruption plays a role.

  14. The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance.

    PubMed

    Gautheron, Jérémie; Vucur, Mihael; Schneider, Anne T; Severi, Ilenia; Roderburg, Christoph; Roy, Sanchari; Bartneck, Matthias; Schrammen, Peter; Diaz, Mauricio Berriel; Ehling, Josef; Gremse, Felix; Heymann, Felix; Koppe, Christiane; Lammers, Twan; Kiessling, Fabian; Van Best, Niels; Pabst, Oliver; Courtois, Gilles; Linkermann, Andreas; Krautwald, Stefan; Neumann, Ulf P; Tacke, Frank; Trautwein, Christian; Green, Douglas R; Longerich, Thomas; Frey, Norbert; Luedde, Mark; Bluher, Matthias; Herzig, Stephan; Heikenwalder, Mathias; Luedde, Tom

    2016-01-01

    Receptor-interacting protein kinase 3 (RIPK3) mediates necroptosis, a form of programmed cell death that promotes inflammation in various pathological conditions, suggesting that it might be a privileged pharmacological target. However, its function in glucose homeostasis and obesity has been unknown. Here we show that RIPK3 is over expressed in the white adipose tissue (WAT) of obese mice fed with a choline-deficient high-fat diet. Genetic inactivation of Ripk3 promotes increased Caspase-8-dependent adipocyte apoptosis and WAT inflammation, associated with impaired insulin signalling in WAT as the basis for glucose intolerance. Similarly to mice, in visceral WAT of obese humans, RIPK3 is overexpressed and correlates with the body mass index and metabolic serum markers. Together, these findings provide evidence that RIPK3 in WAT maintains tissue homeostasis and suppresses inflammation and adipocyte apoptosis, suggesting that systemic targeting of necroptosis might be associated with the risk of promoting insulin resistance in obese patients. PMID:27323669

  15. The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance

    PubMed Central

    Gautheron, Jérémie; Vucur, Mihael; Schneider, Anne T.; Severi, Ilenia; Roderburg, Christoph; Roy, Sanchari; Bartneck, Matthias; Schrammen, Peter; Diaz, Mauricio Berriel; Ehling, Josef; Gremse, Felix; Heymann, Felix; Koppe, Christiane; Lammers, Twan; Kiessling, Fabian; Van Best, Niels; Pabst, Oliver; Courtois, Gilles; Linkermann, Andreas; Krautwald, Stefan; Neumann, Ulf P.; Tacke, Frank; Trautwein, Christian; Green, Douglas R.; Longerich, Thomas; Frey, Norbert; Luedde, Mark; Bluher, Matthias; Herzig, Stephan; Heikenwalder, Mathias; Luedde, Tom

    2016-01-01

    Receptor-interacting protein kinase 3 (RIPK3) mediates necroptosis, a form of programmed cell death that promotes inflammation in various pathological conditions, suggesting that it might be a privileged pharmacological target. However, its function in glucose homeostasis and obesity has been unknown. Here we show that RIPK3 is over expressed in the white adipose tissue (WAT) of obese mice fed with a choline-deficient high-fat diet. Genetic inactivation of Ripk3 promotes increased Caspase-8-dependent adipocyte apoptosis and WAT inflammation, associated with impaired insulin signalling in WAT as the basis for glucose intolerance. Similarly to mice, in visceral WAT of obese humans, RIPK3 is overexpressed and correlates with the body mass index and metabolic serum markers. Together, these findings provide evidence that RIPK3 in WAT maintains tissue homeostasis and suppresses inflammation and adipocyte apoptosis, suggesting that systemic targeting of necroptosis might be associated with the risk of promoting insulin resistance in obese patients. PMID:27323669

  16. Microflora Disturbance during Progression of Glucose Intolerance and Effect of Sitagliptin: An Animal Study

    PubMed Central

    2016-01-01

    Background. Emerging evidences have shown a close interplay between obesity, diabetes, and intestinal flora disturbance. Dipeptidyl peptidase-4 inhibitor, exemplified by sitagliptin, is highly efficacious in treating type 2 diabetes (T2DM), yet little is known if sitagliptin exerts beneficial effects on microbiota associated with obesity and T2DM. We evaluated changes of gut microbiota following the induction of obesity and T2DM in a streptozotocin treated high fat/high carbohydrate fed (HF/HC-STZ) rat model and explored the effect of sitagliptin on gut microbiota for HF/HC-STZ rats. Methods. Sitagliptin was administered via oral gavage to diabetic rats. Fecal DNA extraction and 454 pyrosequencing based on analysis of 16S rRNA genes was utilized to determine the overall structure of microbiota in fecal DNA samples. Results. Results showed that, at the level of phylum, there was higher abundance of Firmicutes and Tenericutes and less abundance of Bacteroidetes in obese rats compared to their lean counterparts. At the level of genus, short-chain fatty acid- (SCFA-) producing bacteria, Blautia, Roseburia, and Clostridium, and probiotics Lactobacillus, Bifidobacterium, and so forth were identified significantly different from each other among conditions. Conclusion. Marked shifts of the gut microbiota structure were observed in the rats during development of glucose intolerance. Intestinal flora changed in the process of glucose intolerance, and treatment of sitagliptin moderately corrected the dysbiosis of microbiota in T2DM. PMID:27631013

  17. Microflora Disturbance during Progression of Glucose Intolerance and Effect of Sitagliptin: An Animal Study.

    PubMed

    Yan, Xinfeng; Feng, Bo; Li, Peicheng; Tang, Zhaosheng; Wang, Lin

    2016-01-01

    Background. Emerging evidences have shown a close interplay between obesity, diabetes, and intestinal flora disturbance. Dipeptidyl peptidase-4 inhibitor, exemplified by sitagliptin, is highly efficacious in treating type 2 diabetes (T2DM), yet little is known if sitagliptin exerts beneficial effects on microbiota associated with obesity and T2DM. We evaluated changes of gut microbiota following the induction of obesity and T2DM in a streptozotocin treated high fat/high carbohydrate fed (HF/HC-STZ) rat model and explored the effect of sitagliptin on gut microbiota for HF/HC-STZ rats. Methods. Sitagliptin was administered via oral gavage to diabetic rats. Fecal DNA extraction and 454 pyrosequencing based on analysis of 16S rRNA genes was utilized to determine the overall structure of microbiota in fecal DNA samples. Results. Results showed that, at the level of phylum, there was higher abundance of Firmicutes and Tenericutes and less abundance of Bacteroidetes in obese rats compared to their lean counterparts. At the level of genus, short-chain fatty acid- (SCFA-) producing bacteria, Blautia, Roseburia, and Clostridium, and probiotics Lactobacillus, Bifidobacterium, and so forth were identified significantly different from each other among conditions. Conclusion. Marked shifts of the gut microbiota structure were observed in the rats during development of glucose intolerance. Intestinal flora changed in the process of glucose intolerance, and treatment of sitagliptin moderately corrected the dysbiosis of microbiota in T2DM. PMID:27631013

  18. Microflora Disturbance during Progression of Glucose Intolerance and Effect of Sitagliptin: An Animal Study

    PubMed Central

    2016-01-01

    Background. Emerging evidences have shown a close interplay between obesity, diabetes, and intestinal flora disturbance. Dipeptidyl peptidase-4 inhibitor, exemplified by sitagliptin, is highly efficacious in treating type 2 diabetes (T2DM), yet little is known if sitagliptin exerts beneficial effects on microbiota associated with obesity and T2DM. We evaluated changes of gut microbiota following the induction of obesity and T2DM in a streptozotocin treated high fat/high carbohydrate fed (HF/HC-STZ) rat model and explored the effect of sitagliptin on gut microbiota for HF/HC-STZ rats. Methods. Sitagliptin was administered via oral gavage to diabetic rats. Fecal DNA extraction and 454 pyrosequencing based on analysis of 16S rRNA genes was utilized to determine the overall structure of microbiota in fecal DNA samples. Results. Results showed that, at the level of phylum, there was higher abundance of Firmicutes and Tenericutes and less abundance of Bacteroidetes in obese rats compared to their lean counterparts. At the level of genus, short-chain fatty acid- (SCFA-) producing bacteria, Blautia, Roseburia, and Clostridium, and probiotics Lactobacillus, Bifidobacterium, and so forth were identified significantly different from each other among conditions. Conclusion. Marked shifts of the gut microbiota structure were observed in the rats during development of glucose intolerance. Intestinal flora changed in the process of glucose intolerance, and treatment of sitagliptin moderately corrected the dysbiosis of microbiota in T2DM.

  19. Delayed β-cell response and glucose intolerance in young women with Turner syndrome

    PubMed Central

    2011-01-01

    Background To investigate glucose homeostasis in detail in Turner syndrome (TS), where impaired glucose tolerance (IGT) and type 2 diabetes are frequent. Methods Cross sectional study of women with Turner syndrome (TS)(n = 13) and age and body mass index matched controls (C) (n = 13), evaluated by glucose tolerance (oral and intravenous glucose tolerance test (OGTT and IVGTT)), insulin sensitivity (hyperinsulinemic, euglycemic clamp), beta-cell function (hyperglycaemic clamp, arginine and GLP-1 stimulation) and insulin pulsatility. Results Fasting glucose and insulin levels were similar. Higher glucose responses was seen in TS during OGTT and IVGTT, persisting after correction for body weight or muscle mass, while insulin responses were similar in TS and C, despite the higher glucose level in TS, leading to an insufficient increase in insulin response during dynamic testing. Insulin sensitivity was comparable in the two groups (TS vs. control: 8.6 ± 1.8 vs. 8.9 ± 1.8 mg/kg*30 min; p = 0.6), and the insulin responses to dynamic β-cell function tests were similar. Insulin secretion patterns examined by deconvolution analysis, approximate entropy, spectral analysis and autocorrelation analysis were similar. In addition we found low IGF-I, higher levels of cortisol and norepinephrine and an increased waist-hip ratio in TS. Conclusions Young normal weight TS women show significant glucose intolerance in spite of normal insulin secretion during hyperglycaemic clamping and normal insulin sensitivity. We recommend regularly testing for diabetes in TS. Trial Registration Registered with http://clinicaltrials.com, ID nr: NCT00419107 PMID:21406078

  20. Glucose Intolerance after a Recent History of Gestational Diabetes Based on the 2013 WHO Criteria

    PubMed Central

    Benhalima, Katrien; Jegers, Katleen; Devlieger, Roland; Verhaeghe, Johan; Mathieu, Chantal

    2016-01-01

    Aims Uncertainty exists on the prevalence of glucose intolerance in women with a recent diagnosis of gestational diabetes (GDM) based on a two-step screening strategy and the 2013 World Health Organization (WHO) criteria. Our aim was to evaluate the uptake of postpartum screening, the prevalence and the risk factors for glucose intolerance in women with a recent history of GDM. Methods Retrospective analysis of the medical records of women with a recent history of GDM diagnosed in a universal two-step screening strategy with the 2013 WHO criteria. All women with a history of GDM are advised to undergo a 75g oral glucose tolerance test (OGTT) around 12 weeks postpartum. Indices of insulin sensitivity (the Matsuda index and the reciprocal of the homeostasis model assessment of insulin resistance, 1/HOMA-IR) and an index of beta-cell function, the Insulin Secretion-Sensitivity Index-2 (ISSI-2) were calculated based on the OGTT postpartum. Multivariable logistic regression was used to adjust for confounders such as age, BMI, ethnicity and breastfeeding. Results Of the 191 women with GDM, 29.3% (56) did not attend the scheduled postpartum OGTT. These women had a higher BMI (28.6 ±6.8 vs. 26.2 ± 5.6, p = 0.015), were more often from an ethnic minority (EM) background (41.1% vs. 25.2%, p = 0.029) and smoked more often during pregnancy (14.3% vs. 2.2%, p = 0.001) than women who attended the OGTT postpartum. Of all women (135) who received an OGTT postpartum, 42.2% (57) had prediabetes (11.9% impaired fasting glucose, 24.4% impaired glucose tolerance and 5.9% both impaired fasting and impaired glucose tolerance) and 1.5% (2) had overt diabetes. Compared to women with a normal OGTT postpartum, women with glucose intolerance were older (32.5±4.3 vs. 30.8±4.8 years, p = 0.049), were more often obese (34.5% vs. 17.3%, p = 0.023), were more often from an EM background (33.9% vs. 18.4%, p = 0.040), less often breastfed (69.5% vs. 84.2%, p = 0.041) and had more often an

  1. Transgenerational changes of metabolic phenotypes in two selectively bred mouse colonies for different susceptibilities to diet-induced glucose intolerance.

    PubMed

    Nagao, Mototsugu; Asai, Akira; Sugihara, Hitoshi; Oikawa, Shinichi

    2015-01-01

    We recently established 2 mouse lines with different susceptibilities (prone and resistant) to high-fat diet (HFD)-induced glucose intolerance by selective breeding (designated selectively bred diet-induced glucose intolerance-prone [SDG-P] and -resistant [SDG-R], respectively). In the present study, we analyzed transgenerational changes in metabolic phenotypes in these 2 mouse colonies to explore how the distinct phenotypes have emerged through the repetitive selection. Using C57BL/6, C3H, and AKR as background strains, mice showing inferior and superior glucose tolerance after HFD feeding were selected and bred repetitively over 20 generations to produce SDG-P and SDG-R, respectively. In addition to the blood glucose levels, HFD intake and body weight were also measured over the selective breeding period. As the generations proceeded, SDG-P mice became more susceptible to HFD-induced glucose intolerance and body weight gain, whereas SDG-R mice had gradually reduced HFD intake. The differences in fasting and post-glucose challenge blood glucose levels, body weight, and HFD intake became more evident between the 2 colonies through the selective breeding, mainly due to the HFD-induced glucose metabolism impairment and body weight gain in SDG-P mice and the reduction of HFD intake in SDG-R mice. These transgenerational changes in the metabolic phenotypes suggest that the genetic loci associated with the quantitative traits have been selectively enriched in SDG-P and SDG-R.

  2. Alagebrium attenuates acute methylglyoxal-induced glucose intolerance in Sprague-Dawley rats

    PubMed Central

    Dhar, Arti; Desai, Kaushik M; Wu, Lingyun

    2010-01-01

    Background and purpose: Alagebrium is a breaker of cross-links in advanced glycation endproducts. However, the acute effects of alagebrium on methylglyoxal (MG), a major precursor of advanced glycation endproducts have not been reported. MG is a highly reactive endogenous metabolite, and its levels are elevated in diabetic patients. We investigated whether alagebrium attenuated the acute effects of exogenous MG on plasma MG levels, glucose tolerance and distribution of administered MG in different organs in Sprague-Dawley rats. Experimental approach: We measured MG levels (by HPLC), glucose tolerance, adipose tissue glucose uptake, GLUT4, insulin receptor and insulin receptor substrate 1 (IRS-1) protein expression, and phosporylated IRS-1 in rats treated with MG at doses of either 17.25 mg·kg−1 i.p. (MG-17 i.p.) or 50 mg·kg−1 i.v. (MG-50 i.v.) with or without alagebrium, 100 mg·kg−1 i.p. Key results: Alagebrium attenuated the increased MG levels in the plasma, aorta, heart, kidney, liver, lung and urine after MG administration. In MG-treated rats, glucose tolerance was impaired, plasma insulin levels were higher and insulin-stimulated glucose uptake by adipose tissue was reduced, relative to the corresponding control groups. In rats treated with MG-50 i.v., GLUT4 protein expression and IRS-1 tyrosine phosphorylation were decreased. Alagebrium pretreatment attenuated these effects of MG. In an in vitro assay, alagebrium reduced the amount of detectable MG. Conclusions and implications: Alagebrium acutely attenuated MG-induced glucose intolerance, suggesting a possible preventive role for alagebrium against the harmful effects of MG. PMID:20002105

  3. Glucose transporter-8 (GLUT8) mediates glucose intolerance and dyslipidemia in high-fructose diet-fed male mice.

    PubMed

    DeBosch, Brian J; Chen, Zhouji; Finck, Brian N; Chi, Maggie; Moley, Kelle H

    2013-11-01

    Members of the glucose transporter (GLUT) family of membrane-spanning hexose transporters are subjects of intensive investigation for their potential as modifiable targets to treat or prevent obesity, metabolic syndrome, and type 2 diabetes mellitus. Mounting evidence suggests that the ubiquitously expressed class III dual-specificity glucose and fructose transporter, GLUT8, has important metabolic homeostatic functions. We therefore tested the hypothesis that GLUT8 mediates the deleterious metabolic effects of chronic high-fructose diet exposure. Here we demonstrate resistance to high-fructose diet-induced glucose intolerance and dyslipidemia concomitant with enhanced oxygen consumption and thermogenesis in GLUT8-deficient male mice. Independent of diet, significantly lower systolic blood pressure both at baseline and after high-fructose diet feeding was also observed by tail-cuff plethysmography in GLUT8-deficient mice vs wild-type controls. Resistance to fructose-induced metabolic dysregulation occurred in the context of enhanced hepatic peroxisome proliferator antigen receptor-γ (PPARγ) protein abundance, whereas in vivo hepatic adenoviral GLUT8 overexpression suppressed hepatic PPARγ expression. Taken together, these findings suggest that GLUT8 blockade prevents fructose-induced metabolic dysregulation, potentially by enhancing hepatic fatty acid metabolism through PPARγ and its downstream targets. We thus establish GLUT8 as a promising target in the prevention of diet-induced obesity, metabolic syndrome, and type 2 diabetes mellitus in males.

  4. Mechanisms of impaired fasting glucose and glucose intolerance induced by an approximate 50% pancreatectomy.

    PubMed

    Matveyenko, Aleksey V; Veldhuis, Johannes D; Butler, Peter C

    2006-08-01

    Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) often coexist and as such represent a potent risk factor for subsequent development of type 2 diabetes. beta-Cell mass is approximately 50% deficient in IFG and approximately 65% deficient in type 2 diabetes. To establish the effect of a approximately 50% deficit in beta-cell mass on carbohydrate metabolism, we performed a approximately 50% partial pancreatectomy versus sham surgery in 14 dogs. Insulin secretion was quantified from insulin concentrations measured in the portal vein at 1-min sampling intervals under basal conditions, after a 30-g oral glucose, and during a hyperglycemic clamp. Insulin sensitivity was measured by a hyperinsulinemic-euglycemic clamp combined with isotope dilution. Partial pancreatectomy resulted in IFG and IGT. After partial pancreatectomy both basal and glucose-stimulated insulin secretion were decreased through the mechanism of a selective approximately 50 and approximately 80% deficit in insulin pulse mass, respectively (P < 0.05). These defects in insulin secretion were partially offset by decreased hepatic insulin clearance (P < 0.05). Partial pancreatectomy also caused a approximately 40% decrease in insulin-stimulated glucose disposal (P < 0.05), insulin sensitivity after partial pancreatectomy being related to insulin pulse amplitude (r = 0.9, P < 0.01). We conclude that a approximately 50% deficit in beta-cell mass can recapitulate the alterations in glucose-mediated insulin secretion and insulin action in humans with IFG and IGT. These data support a mechanistic role of a deficit in beta-cell mass in the evolution of IFG/IGT and subsequently type 2 diabetes. PMID:16873700

  5. Nutritional recovery with okara diet prevented hypercholesterolemia, hepatic steatosis and glucose intolerance.

    PubMed

    Lemes, Simone Ferreira; Lima, Faena Moura; de Almeida, Ana Paula Carli; Ramalho, Albina de Fátima Silva; Reis, Silvia Regina de Lima; Michelotto, Letícia Fonseca; Amaya-Farfán, Jayme; Carneiro, Everardo Magalhães; Boschero, Antonio Carlos; Latorraca, Márcia Queiroz; Veloso, Roberto Vilela

    2014-09-01

    We assessed the biological value of an okara diet and its effects on the hormonal and metabolic profile of rats submitted to protein restriction during intra-uterine life and lactation and recovered after weaning. Male rats from mothers fed either 17% or 6% protein during pregnancy and lactation were maintained on 17% casein (CC, LC), 17% okara (CO, LO) or 6% casein (LL) diets over 60 d. The nutritional quality of the okara protein was similar to that of casein. The okara diet was effective in the nutritional recovery of rats in growing that were malnourished in early life. Furthermore, the okara diet reversed the hypercholesterolemia and the hepatic steatosis observed in the malnutrition and prevented glucose intolerance in an animal model prone to diabetes mellitus. PMID:24655214

  6. Morinda citrifolia fruit juice prevents ischemic neuronal damage through suppression of the development of post-ischemic glucose intolerance.

    PubMed

    Harada, Shinichi; Fujita-Hamabe, Wakako; Kamiya, Kohei; Mizushina, Yoshiyuki; Satake, Toshiko; Tokuyama, Shogo

    2010-10-01

    Fruit juice of Morinda citrifolia (Noni juice) is a well-known health drink and has various pharmacological properties including antioxidant and anti-inflammatory effects. We have hitherto found the protective effect of Noni juice on brain damage caused by ischemic stress in mice. In addition, we also recently reported that regulation of post-ischemic glucose intolerance might be important for good prognosis. Here, we focused on the effect of Noni juice on the development of the post-ischemic glucose intolerance as a cerebral protective mechanism. Noni juice was obtained from the mature fruit grown in Okinawa (about 1.5 L/4 kg of fruit; 100% ONJ). Male ddY mice were given 10% ONJ in drinking water for 7 days. Then, mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Ingestion of 10% ONJ suppressed the development of neuronal damage after MCAO. Interestingly, glucose intolerance observed on the 1st day after MCAO completely disappeared after 10% ONJ administration. Furthermore, ONJ treatment significantly increased serum insulin levels much further than the control group on the 1st day, while serum adiponectin levels were not affected at all. These results suggest that ONJ could facilitate insulin secretion after ischemic stress and may attenuate the development of glucose intolerance. These mechanisms may contribute to the neuronal protective effect of ONJ against ischemic stress.

  7. Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice.

    PubMed

    De Angelis, Katia; Senador, Danielle D; Mostarda, Cristiano; Irigoyen, Maria C; Morris, Mariana

    2012-04-15

    Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 ± 2 and F60: 118 ± 2 mmHg) and dark periods (F15: 136 ± 4 and F60: 136 ± 5 mmHg) compared with controls (light: 111 ± 2 and dark: 117 ± 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.

  8. Fructose consumption during pregnancy and lactation induces fatty liver and glucose intolerance in rats.

    PubMed

    Zou, Mi; Arentson, Emily J; Teegarden, Dorothy; Koser, Stephanie L; Onyskow, Laurie; Donkin, Shawn S

    2012-08-01

    Nutritional insults during pregnancy and lactation are health risks for mother and offspring. Both fructose (FR) and low-protein (LP) diets are linked to hepatic steatosis and insulin resistance in nonpregnant animals. We hypothesized that dietary FR or LP intake during pregnancy may exacerbate the already compromised glucose homeostasis to induce gestational diabetes and fatty liver. Therefore, we investigated and compared the effects of LP or FR intake on hepatic steatosis and insulin resistance in unmated controls (CTs) and pregnant and lactating rats. Sprague-Dawley rats were fed a CT, or a 63% FR, or an 8% LP diet. Glucose tolerance test at day 17 of the study revealed greater (P < .05) blood glucose at 10 (75.6 mg/dL vs 64.0 ± 4.8 mg/dL) minutes and 20 (72.4 mg/dL vs 58.6 ± 4.0 mg/dL) minutes after glucose dose and greater area under the curve (4302.3 mg∙dL(-1)∙min(-1) vs 3763.4 ± 263.6 mg∙dL(-1)∙min(-1)) for FR-fed dams compared with CT-fed dams. The rats were euthanized at 21 days postpartum. Both the FR- and LP-fed dams had enlarged (P < .05) livers (9.3%, 7.1% body weight vs 4.8% ± 0.2% body weight) and elevated (P < .05) liver triacylglycerol (216.0, 130.0 mg/g vs 19.9 ± 12.6 mg/g liver weight) compared with CT-fed dams. Fructose induced fatty liver and glucose intolerance in pregnant and lactating rats, but not unmated CT rats. The data demonstrate a unique physiological status response to diet resulting in the development of gestational diabetes coupled with hepatic steatosis in FR-fed dams, which is more severe than an LP diet.

  9. A Transient Metabolic Recovery from Early Life Glucose Intolerance in Cystic Fibrosis Ferrets Occurs During Pancreatic Remodeling.

    PubMed

    Yi, Yaling; Sun, Xingshen; Gibson-Corley, Katherine; Xie, Weiliang; Liang, Bo; He, Nan; Tyler, Scott R; Uc, Aliye; Philipson, Louis H; Wang, Kai; Hara, Manami; Ode, Katie Larson; Norris, Andrew W; Engelhardt, John F

    2016-05-01

    Cystic fibrosis (CF)-related diabetes in humans is intimately related to exocrine pancreatic insufficiency, yet little is known about how these 2 disease processes simultaneously evolve in CF. In this context, we examined CF ferrets during the evolution of exocrine pancreatic disease. At 1 month of age, CF ferrets experienced a glycemic crisis with spontaneous diabetic-level hyperglycemia. This occurred during a spike in pancreatic inflammation that was preceded by pancreatic fibrosis and loss of β-cell mass. Surprisingly, there was spontaneous normalization of glucose levels at 2-3 months, with intermediate hyperglycemia thereafter. Mixed meal tolerance was impaired at all ages, but glucose intolerance was not detected until 4 months. Insulin secretion in response to hyperglycemic clamp and to arginine was impaired. Insulin sensitivity, measured by euglycemic hyperinsulinemic clamp, was normal. Pancreatic inflammation rapidly diminished after 2 months of age during a period where β-cell mass rose and gene expression of islet hormones, peroxisome proliferator-activated receptor-γ, and adiponectin increased. We conclude that active CF exocrine pancreatic inflammation adversely affects β-cells but is followed by islet resurgence. We predict that very young humans with CF may experience a transient glycemic crisis and postulate that pancreatic inflammatory to adipogenic remodeling may facilitate islet adaptation in CF. PMID:26862997

  10. Gender differences of regional abdominal fat distribution and their relationships with insulin sensitivity in healthy and glucose-intolerant Thais.

    PubMed

    Rattarasarn, Chatchalit; Leelawattana, Rattana; Soonthornpun, Supamai; Setasuban, Worawong; Thamprasit, Atchara

    2004-12-01

    To determine gender differences of regional abdominal fat distribution and their relationships with insulin sensitivity in healthy and glucose-intolerant Thais, 44 subjects, 22 men and 22 body mass index-matched women, with normal and abnormal glucose tolerance, which included subjects with impaired glucose tolerance and diabetes, were studied. Total body fat and total abdominal fat (TAF) at L1-L4 were measured by dual-energy x-ray absorptiometry. Regional abdominal fat, which consists of sc abdominal fat and visceral abdominal fat, was determined by single-slice computerized tomography of the abdomen at L4-L5 disc space level. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp and expressed as glucose infusion rate (GIR). With comparable body mass index, visceral abdominal fat was most strongly correlated with GIR after adjustment with percent total body fat in both healthy (r = -0.8155; P = 0.007) and glucose-intolerant women (r = -0.7597; P = 0.011), whereas TAF was most strongly correlated with GIR in both healthy (r = -0.8114; P = 0.008) and glucose-intolerant men (r = -0.6194; P = 0.101). By linear regression analysis, visceral abdominal fat accounted for 35.0% (beta = -3.53 x 10(-2); P = 0.001) of GIR variance in women, whereas TAF accounted for 39.3% (beta = -1.28 x 10(-4); P < 0.0001) of GIR variance in men. We conclude that there are gender differences in the relationships of regional abdominal fat and insulin sensitivity in slightly obese healthy and glucose-intolerant Thais, the difference of which may possibly be in part due to the difference of abdominal fat patterning between genders.

  11. Glucose intolerance and physical inactivity: the relative importance of low habitual energy expenditure and cardiorespiratory fitness.

    PubMed

    Wareham, N J; Wong, M Y; Day, N E

    2000-07-15

    Glucose intolerance and diabetes mellitus are associated with physical inactivity, but it is unclear whether preventive interventions should aim at increasing overall energy expenditure or increasing participation in vigorous, fitness-enhancing activities. Studies aimed at separating and quantifying the effects of these two dimensions of physical activity should use well-validated measurement instruments and employ a study design in which the bivariate error structure of these instruments is determined. In the Isle of Ely Study (Cambridgeshire, United Kingdom), 775 individuals aged 45-70 years in 1994-1997 completed a glucose tolerance test and assessment of 4-day physical activity level (total energy expenditure/basal metabolic rate) by heart rate monitoring, a technique that has been validated against doubly labeled water and whole-body calorimetry. Cardiorespiratory fitness (maximum oxygen uptake (VO2max) per kg)) was measured in a submaximal test. To correct for measurement error, the authors had 190 individuals repeat both tests on three occasions at 4-month intervals. Two-hour glucose level was negatively correlated with physical activity level (men: r = -0.22, p < 0.001; women: r = -0.11, p < 0.05) and VO2max per kg (men: r = -0.18, p < 0.01; women: r = -0.19, p < 0.001) and was positively correlated with age and obesity. The model incorporating bivariate adjustment for measurement error showed that energy expenditure had a major effect on glucose tolerance, but there was less of an effect for cardiorespiratory fitness. These data provide support for public health strategies aimed at increasing overall energy expenditure.

  12. Development of cookie test for the simultaneous determination of glucose intolerance, hyperinsulinemia, insulin resistance and postprandial dyslipidemia.

    PubMed

    Harano, Yutaka; Miyawaki, Takeshi; Nabiki, Junko; Shibachi, Miki; Adachi, Tomomi; Ikeda, Michiko; Ueda, Fukuhiro; Nakano, Takamitsu

    2006-04-01

    A new cookie test was developed for the simultaneous evaluation of multiple risk factors such as glucose intolerance, hyperinsulinemia, insulin resistance and postprandial dyslipidemia. The cookie consisting of 75 g carbohydrate and 25 g fat is ingested and the blood samples are obtained at 0, 1 and 2 hours later. When the two carbohydrate sources, liquid glucose and test cookie, were compared as a glucose load within 3 months, the 2 hr plasma glucose levels were not statistically different, proposing the use of the same criteria at 2 hour glucose level for the diagnosis of diabetes and impaired glucose tolerance (IGT) in subjects without exocrine pancreatic dysfunction. In addition, hyperinsulinemia, insulin resistance (AUC insulin, and/or AUC insulin X AUC glucose), and postprandial hyperlipidemia (DeltaTG, Triglyceride; DeltaRLP, remnant like particles) have been simultaneously uncovered. Reactive hypoglycemia with adverse epigastric discomfort was observed in 26.3% of the control subjects with liquid glucose, while it was observed in only 1 case (5.3%) without any symptom with cookie tests. In fact, one reactive hypoglycemia out of 5 with liquid glucose turned out to be IGT with cookie test. In 64 subjects with lifestyle-related diseases, cookie test revealed hyperinsulinemia and insulin resistance in 56% respectively, postprandial hyperlipidemia in 39%, diabetes and IGT in 22-23% of each of the subjects and all showed at least one abnormal value. In contrast, in university students with exercise habit, all showed normal results with cookie test. In addition, improved insulin sensitivity over non-exercise group was obverved. In summary, the cookie test provided more informations compared with OGTT using liquid glucose and with fewer side effects. Simultaneous evaluation of glucose intolerance, hyperinsulinemia, insulin resistance, and postprandial hyperlipidemia was also possible.

  13. Glucose intolerance induced by a high-fat/low-carbohydrate diet in rats effects of nonesterified fatty acids.

    PubMed

    Wang, Yuan; Miura, Yoshikazu; Kaneko, Takashi; Li, Jue; Qin, Li-Qiang; Wang, Pei-Yu; Matsui, Hisao; Sato, Akio

    2002-04-01

    We examined the time course of effects of a high-fat/low-carbohydrate (HF/LC) diet on the impairment of glucose tolerance in rats, clarified whether insulin secretion and sensitivity were impaired by the HF/LC diet, and investigated the relationship between the increased nonesterified fatty acids (NEFA) after HF/LC diet feeding and insulin secretion and sensitivity. We found that glucose tolerance and the postglucose-loading insulin secretion were impaired after 3 and 7 d on the HF/LC diet. The glucose intolerance was accompanied by a rise in the fasting plasma NEFA level. When stimulated with 15 mmol/L of glucose, the insulin secretion was impaired in pancreatic islets from rats fed the HF/LC diet. Rats fed the HF/LC diet showed insulin resistance in vivo. The glucose-stimulated insulin secretion was inhibited in the islets following 24-h culture with palmitic acid. The 24-h infusion of palmitic acid decreased whole-body insulin sensitivity. In summary, at least 3 d on a HF/LC diet is needed to induce glucose intolerance in rats, and the impairment may be induced by decreased insulin secretion and sensitivity, which is related to the increase in the plasma NEFA level. PMID:12108518

  14. Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance

    PubMed Central

    Ringling, Rebecca E.; Gastecki, Michelle L.; Woodford, Makenzie L.; Lum-Naihe, Kelly J.; Grant, Ryan W.; Pulakat, Lakshmi; Vieira-Potter, Victoria J.; Padilla, Jaume

    2016-01-01

    We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis. PMID:27583382

  15. Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance.

    PubMed

    Ringling, Rebecca E; Gastecki, Michelle L; Woodford, Makenzie L; Lum-Naihe, Kelly J; Grant, Ryan W; Pulakat, Lakshmi; Vieira-Potter, Victoria J; Padilla, Jaume

    2016-01-01

    We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis. PMID:27583382

  16. Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance.

    PubMed

    Ringling, Rebecca E; Gastecki, Michelle L; Woodford, Makenzie L; Lum-Naihe, Kelly J; Grant, Ryan W; Pulakat, Lakshmi; Vieira-Potter, Victoria J; Padilla, Jaume

    2016-01-01

    We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis.

  17. Loss of Sodium/Hydrogen Exchanger NHA2 Exacerbates Obesity- and Aging-Induced Glucose Intolerance in Mice

    PubMed Central

    Deisl, Christine; Anderegg, Manuel; Albano, Giuseppe; Lüscher, Benjamin P.; Cerny, David; Soria, Rodrigo; Bouillet, Elisa; Rimoldi, Stefano; Scherrer, Urs

    2016-01-01

    We previously demonstrated that the sodium/hydrogen exchanger NHA2, also known as NHEDC2 or SLC9B2, is critical for insulin secretion by β–cells. To gain more insights into the role of NHA2 on systemic glucose homeostasis, we studied the impact of loss of NHA2 during the physiological aging process and in the setting of diet-induced obesity. While glucose tolerance was normal at 2 months of age, NHA2 KO mice displayed a significant glucose intolerance at 5 and 12 months of age, respectively. An obesogenic high fat diet further exacerbated the glucose intolerance of NHA2 KO mice. Insulin levels remained similar in NHA2 KO and WT mice during aging and high fat diet, but fasting insulin/glucose ratios were significantly lower in NHA2 KO mice. Peripheral insulin sensitivity, measured by insulin tolerance tests and hyperinsulinemic euglycemic clamps, was unaffected by loss of NHA2 during aging and high fat diet. High fat diet diminished insulin secretion capacity in both WT and NHA2 KO islets and reduced expression of NHA2 in WT islets. In contrast, aging was characterized by a gradual increase of NHA2 expression in islets, paralleled by an increasing difference in insulin secretion between WT and NHA2 KO islets. In summary, our results demonstrate that loss of the sodium/hydrogen exchanger NHA2 exacerbates obesity- and aging-induced glucose intolerance in mice. Furthermore, our data reveal a close link between NHA2 expression and insulin secretion capacity in islets. PMID:27685945

  18. MyD88 regulates physical inactivity-induced skeletal muscle inflammation, ceramide biosynthesis signaling, and glucose intolerance

    PubMed Central

    Kwon, Oh Sung; Tanner, Ruth E.; Barrows, Katherine M.; Runtsch, Marah; Symons, J. David; Jalili, Thunder; Bikman, Benjamin T.; McClain, Donald A.; O'Connell, Ryan M.

    2015-01-01

    Physical inactivity in older adults is a risk factor for developing glucose intolerance and impaired skeletal muscle function. Elevated inflammation and ceramide biosynthesis have been implicated in metabolic disruption and are linked to Toll-like receptor (TLR)/myeloid differentiation primary response 88 (MyD88) signaling. We hypothesize that a physical inactivity stimulus, capable of inducing glucose intolerance, would increase skeletal muscle inflammation and ceramide biosynthesis signaling and that this response would be regulated by the TLR/MyD88 pathway. Therefore, we subjected wild-type (WT) and MyD88−/− mice to hindlimb unloading (HU) for 14 days or an ambulatory control period. We observed impaired glucose uptake, muscle insulin signaling (p-Akt), and increased markers of NF-κB signaling (p-IκBα), inflammation (p-JNK, IL-6), TLR4, and the rate-limiting enzyme of ceramide biosynthesis, SPT2, with HU WT (P < 0.05), but not in HU MyD88−/− mice. Concurrently, we found that 5 days of bed rest in older adults resulted in whole body glucose dysregulation, impaired skeletal muscle insulin signaling, and upregulation of muscle IL-6 and SPT2 (P < 0.05). Post-bed rest TLR4 abundance was tightly correlated with impaired postprandial insulin and glucose levels. In conclusion, MyD88 signaling is necessary for the increased inflammation, ceramide biosynthesis signaling, and compromised metabolic function that accompanies physical inactivity. PMID:25968578

  19. MyD88 regulates physical inactivity-induced skeletal muscle inflammation, ceramide biosynthesis signaling, and glucose intolerance.

    PubMed

    Kwon, Oh Sung; Tanner, Ruth E; Barrows, Katherine M; Runtsch, Marah; Symons, J David; Jalili, Thunder; Bikman, Benjamin T; McClain, Donald A; O'Connell, Ryan M; Drummond, Micah J

    2015-07-01

    Physical inactivity in older adults is a risk factor for developing glucose intolerance and impaired skeletal muscle function. Elevated inflammation and ceramide biosynthesis have been implicated in metabolic disruption and are linked to Toll-like receptor (TLR)/myeloid differentiation primary response 88 (MyD88) signaling. We hypothesize that a physical inactivity stimulus, capable of inducing glucose intolerance, would increase skeletal muscle inflammation and ceramide biosynthesis signaling and that this response would be regulated by the TLR/MyD88 pathway. Therefore, we subjected wild-type (WT) and MyD88(-/-) mice to hindlimb unloading (HU) for 14 days or an ambulatory control period. We observed impaired glucose uptake, muscle insulin signaling (p-Akt), and increased markers of NF-κB signaling (p-IκBα), inflammation (p-JNK, IL-6), TLR4, and the rate-limiting enzyme of ceramide biosynthesis, SPT2, with HU WT (P < 0.05), but not in HU MyD88(-/-) mice. Concurrently, we found that 5 days of bed rest in older adults resulted in whole body glucose dysregulation, impaired skeletal muscle insulin signaling, and upregulation of muscle IL-6 and SPT2 (P < 0.05). Post-bed rest TLR4 abundance was tightly correlated with impaired postprandial insulin and glucose levels. In conclusion, MyD88 signaling is necessary for the increased inflammation, ceramide biosynthesis signaling, and compromised metabolic function that accompanies physical inactivity.

  20. Mice Lacking the p43 Mitochondrial T3 Receptor Become Glucose Intolerant and Insulin Resistant during Aging

    PubMed Central

    Bertrand, Christelle; Blanchet, Emilie; Pessemesse, Laurence; Annicotte, Jean Sébastien; Feillet-Coudray, Christine; Chabi, Béatrice; Levin, Jonathan; Fajas, Lluis; Cabello, Gérard; Wrutniak-Cabello, Chantal; Casas, François

    2013-01-01

    Thyroid hormones (TH) play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3) receptor (p43) which acts as a mitochondrial transcription factor of the organelle genome, which leads in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated mice carrying a specific p43 invalidation. At 2 months of age, we reported that p43 depletion in mice induced a major defect in insulin secretion both in vivo and in isolated pancreatic islets, and a loss of glucose-stimulated insulin secretion. The present study was designed to determine whether p43 invalidation influences life expectancy and modulates blood glucose and insulin levels as well as glucose tolerance or insulin sensitivity during aging. We report that from 4 months old onwards, mice lacking p43 are leaner than wild-type mice. p43−/− mice also have a moderate reduction of life expectancy compared to wild type. We found no difference in blood glucose levels, excepted at 24 months old where p43−/− mice showed a strong hyperglycemia in fasting conditions compared to controls animals. However, the loss of glucose-stimulated insulin secretion was maintained whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance remained unchanged, beyond this age p43−/− mice became increasingly glucose intolerant. In addition, if up to 12 months old p43 deficient animals were more sensitive to insulin, after this age we observed a loss of this capacity, culminating in 24 months old mice with a decreased sensitivity to the hormone. In conclusion, we demonstrated that during aging the depletion of the mitochondrial T3 receptor p43 in mice progressively induced an increased glycemia in the fasted state, glucose intolerance and an insulin-resistance several features of type-2 diabetes. PMID:24098680

  1. Erythropoietin inhibits gluconeogenesis and inflammation in the liver and improves glucose intolerance in high-fat diet-fed mice.

    PubMed

    Meng, Ran; Zhu, Dalong; Bi, Yan; Yang, Donghui; Wang, Yaping

    2013-01-01

    Erythropoietin (EPO) has multiple biological functions, including the modulation of glucose metabolism. However, the mechanisms underlying the action of EPO are still obscure. This study is aimed at investigating the potential mechanisms by which EPO improves glucose tolerance in an animal model of type 2 diabetes. Male C57BL/6 mice were fed with high-fat diet (HFD) for 12 weeks and then treated with EPO (HFD-EPO) or vehicle saline (HFD-Con) for two week. The levels of fasting blood glucose, serum insulin and glucose tolerance were measured and the relative levels of insulin-related phosphatidylinositol 3-kinase (PI3K)/Akt, insulin receptor (IR) and IR substrate 1 (IRS1) phosphorylation were determined. The levels of phosphoenolpyruvate carboxykinase (PEPCK), glucose-6- phosphatase (G6Pase), toll like receptor 4 (TLR4), tumor necrosis factor (TNF)-α and IL-6 expression and nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK), extracellular-signal-regulated kinase (ERK) and p38 MAPK activation in the liver were examined. EPO treatment significantly reduced the body weights and the levels of fasting blood glucose and serum insulin and improved the HFD-induced glucose intolerance in mice. EPO treatment significantly enhanced the levels of Akt, but not IR and IRS1, phosphorylation, accompanied by inhibiting the PEPCK and G6Pase expression in the liver. Furthermore, EPO treatment mitigated the HFD-induced inflammatory TNF-α and IL-6 production, TLR4 expression, NF-κB and JNK, but not ERK and p38 MAPK, phosphorylation in the liver. Therefore, our data indicated that EPO treatment improved glucose intolerance by inhibiting gluconeogenesis and inflammation in the livers of HFD-fed mice. PMID:23326455

  2. A cross-sectional study of dietary patterns with glucose intolerance and other features of the metabolic syndrome.

    PubMed

    Williams, D E; Prevost, A T; Whichelow, M J; Cox, B D; Day, N E; Wareham, N J

    2000-03-01

    Previous epidemiological studies have demonstrated relationships between individual nutrients and glucose intolerance and type 2 diabetes, but the association with the overall pattern of dietary intake has not previously been described. In order to characterize this association, 802 subjects aged 40-65 years were randomly selected from a population-based sampling frame and underwent a 75 g oral glucose-tolerance test. Principal component analysis was used to identify four dietary patterns explaining 31.7% of the dietary variation in the study cohort. These dietary patterns were associated with other lifestyle factors including socio-economic group, smoking, alcohol intake and physical activity. Component 1 was characterized by a healthy balanced diet with a frequent intake of raw and salad vegetables, fruits in both summer and winter, fish, pasta and rice and low intake of fried foods, sausages, fried fish, and potatoes. This component was negatively correlated with central obesity, fasting plasma glucose, 120 min non-esterified fatty acid and triacylglycerol, and positively correlated with HDL-cholesterol. It therefore appears to be protective for the metabolic syndrome. Component 1 was negatively associated with the risk of having undiagnosed diabetes, and this association was independent of age, sex, smoking and obesity. The findings support the hypothesis that dietary patterns are associated with other lifestyle factors and with glucose intolerance and other features of the metabolic syndrome. The results provide further evidence for the recommendation of a healthy balanced diet as one of the main components of chronic disease prevention.

  3. Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease

    PubMed Central

    Kunkel, Steven D.; Elmore, Christopher J.; Bongers, Kale S.; Ebert, Scott M.; Fox, Daniel K.; Dyle, Michael C.; Bullard, Steven A.; Adams, Christopher M.

    2012-01-01

    Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness. PMID:22745735

  4. The phospholipase A2 inhibitor methyl indoxam suppresses diet-induced obesity and glucose intolerance in mice

    PubMed Central

    Hui, DY; Cope, MJ; Labonté, ED; Chang, H-T; Shao, J; Goka, E; Abousalham, A; Charmot, D; Buysse, J

    2009-01-01

    Background and purpose: Previous results have shown that mice lacking in the group 1B phospholipase A2 (Pla2g1b) are resistant to obesity and diabetes induced by feeding a diabetogenic high-fat/high-carbohydrate diet. This study examined the potential of using the Pla2g1b inhibitor methyl indoxam as therapy to suppress diet-induced obesity and diabetes. Experimental approach: Male C57BL/6 mice were fed the diabetogenic diet with or without methyl indoxam supplementation. Body weight gain, fasting plasma glucose levels, glucose tolerance and postprandial lysophospholipid absorption were compared. Key results: Wild-type C57BL/6 mice fed the diabetogenic diet without Pla2g1b inhibitor showed 31 and 69% body weight gain after 4 and 10 weeks respectively. These animals also showed elevated plasma glucose levels and were glucose intolerant. In contrast, C57BL/6 mice fed the diabetogenic diet with 90 mg·kg−1 of methyl indoxam gained only 5% body weight after 10 weeks. These animals were also euglycaemic and displayed normal glucose excursion rates in glucose tolerance test. Methyl indoxam suppression of diet-induced body weight gain and glucose intolerance was correlated with the inhibition of Pla2g1b-mediated postprandial lysophospholipid absorption. Conclusions and implications: These results show that oral supplementation of a diabetogenic diet with the Pla2g1b inhibitor methyl indoxam effectively suppresses diet-induced obesity and diabetes in mice. This suggests that Pla2g1b inhibition may be a potentially effective oral therapeutic option for treatment of obesity and diabetes. PMID:19563529

  5. Identification of matrine as a promising novel drug forhepatic steatosis and glucose intolerance with HSP72 as an upstream target

    PubMed Central

    Zeng, Xiao-Yi; Wang, Hao; Bai, Fang; Zhou, Xiu; Li, Song-Pei; Ren, Lu-Ping; Sun, Ruo-Qiong; Xue, Charlie C L; Jiang, Hua-Liang; Hu, Li-Hong; Ye, Ji-Ming

    2015-01-01

    Background and Purpose Matrine is a small molecule drug used in humans for the treatment of chronic viral infections and tumours in the liver with little adverse effects. The present study investigated its therapeutic efficacy for insulin resistance and hepatic steatosis in high-fat-fed mice. Experimental Approach C57BL/J6 mice were fed a chow or high-fat diet for 10 weeks and then treated with matrine or metformin for 4 weeks. The effects on lipid metabolism and glucose tolerance were evaluated. Key Results Our results first showed that matrine reduced glucose intolerance and plasma insulin level, hepatic triglyceride content and adiposity in high-fat-fed mice without affecting caloric intake. This reduction in hepatosteatosis was attributed to suppressed lipid synthesis and increased fatty acid oxidation. In contrast to metformin, matrine neither suppressed mitochondrial respiration nor activated AMPK in the liver. A computational docking simulation revealed HSP90, a negative regulator of HSP72, as a potential binding target of matrine. Consistent with the simulation results, matrine, but not metformin, increased the hepatic protein level of HSP72 and this effect was inversely correlated with both liver triglyceride level and glucose intolerance. Conclusions and Implications Taken together, these results indicate that matrine may be used for the treatment of type 2 diabetes and hepatic steatosis, and the molecular action of this hepatoprotective drug involves the activation of HSP72 in the liver. PMID:26040411

  6. Deletion of GαZ Protein Protects against Diet-induced Glucose Intolerance via Expansion of β-Cell Mass*

    PubMed Central

    Kimple, Michelle E.; Moss, Jennifer B.; Brar, Harpreet K.; Rosa, Taylor C.; Truchan, Nathan A.; Pasker, Renee L.; Newgard, Christopher B.; Casey, Patrick J.

    2012-01-01

    Insufficient plasma insulin levels caused by deficits in both pancreatic β-cell function and mass contribute to the pathogenesis of type 2 diabetes. This loss of insulin-producing capacity is termed β-cell decompensation. Our work is focused on defining the role(s) of guanine nucleotide-binding protein (G protein) signaling pathways in regulating β-cell decompensation. We have previously demonstrated that the α-subunit of the heterotrimeric Gz protein, Gαz, impairs insulin secretion by suppressing production of cAMP. Pancreatic islets from Gαz-null mice also exhibit constitutively increased cAMP production and augmented glucose-stimulated insulin secretion, suggesting that Gαz is a tonic inhibitor of adenylate cyclase, the enzyme responsible for the conversion of ATP to cAMP. In the present study, we show that mice genetically deficient for Gαz are protected from developing glucose intolerance when fed a high fat (45 kcal%) diet. In these mice, a robust increase in β-cell proliferation is correlated with significantly increased β-cell mass. Further, an endogenous Gαz signaling pathway, through circulating prostaglandin E activating the EP3 isoform of the E prostanoid receptor, appears to be up-regulated in insulin-resistant, glucose-intolerant mice. These results, along with those of our previous work, link signaling through Gαz to both major aspects of β-cell decompensation: insufficient β-cell function and mass. PMID:22457354

  7. Do Metacognitions and Intolerance of Uncertainty Predict Worry in Everyday Life? An Ecological Momentary Assessment Study.

    PubMed

    Thielsch, Carolin; Andor, Tanja; Ehring, Thomas

    2015-07-01

    Cognitive models of generalized anxiety disorder (GAD) suggest that excessive worry is due to positive and negative metacognitive beliefs and/or intolerance of uncertainty. Empirical support mainly derives from cross-sectional studies with limited conclusiveness, using self-report measures and thereby possibly causing recall biases. The aim of the present study therefore was to examine the power of these cognitive variables to predict levels of worry in everyday life using Ecological Momentary Assessment (EMA). Metacognitions and intolerance of uncertainty were assessed using well-established self-report questionnaires in 41 nonclinical participants who subsequently completed ratings on worry intensity and burden on a portable device for 1week at seven times a day once every 2hours. Results showed significant associations of negative metacognitive beliefs and intolerance of uncertainty, but not positive metacognitive beliefs, with worry in everyday life. In multilevel regression analyses, a substantial proportion of variance of everyday worry could be accounted for by negative metacognitions over and above trait worry and daily hassles. Intolerance of uncertainty likewise emerged as a valid predictor when tested in isolation, but did not explain additional variance once negative metacognitions were controlled. The findings support current cognitive models of excessive worry and highlight the role of negative metacognitions. By using EMA to assess levels of worry in everyday life, they extend earlier findings focusing exclusively on retrospective questionnaire measures.

  8. The “Metabolic Syndrome” Is Less Useful than Random Plasma Glucose to Screen for Glucose Intolerance

    PubMed Central

    El Bassuoni, Eman A.; Ziemer, David C.; Kolm, Paul; Rhee, Mary K.; Vaccarino, Viola; Tsui, Circe W.; Kaufman, Jack M.; Osinski, G. Eileen; Koch, David D.; Venkat Narayan, K. M.; Weintraub, William S.; Phillips, Lawrence S.

    2008-01-01

    Aims To compare the utility of metabolic syndrome (MetS) to random plasma glucose (RPG) in identifying people with diabetes or prediabetes. Methods RPG was measured and an OGTT was performed in 1,155 adults. Test performance was measured by are under the receiver-operating-characteristic curve (AROC). Results Diabetes was found in 5.1% and prediabetes in 20.0%. AROC for MetS with FPG was 0.80 to detect diabetes, and 0.76 for diabetes or prediabetes – similar to RPG (0.82 and 0.72). However, the AROC for MetS excluding fasting plasma glucose (FPG) was lower: 0.69 for diabetes (p<0.01 vs. both RPG and MetS with FPG), and 0.69 for diabetes or prediabetes. AROCs for MetS with FPG and RPG were comparable and higher for recognizing diabetes in blacks vs. whites, and females vs. males. MetS with FPG was superior to RPG for identifying diabetes only in subjects with age <40 or BMI <25. Conclusions MetS features can be used to identify risk of diabetes, but predictive usefulness is driven largely by FPG. Overall, to identify diabetes or prediabetes in blacks and whites with varying age and BMI, MetS is no better than RPG – a more convenient and less expensive test. PMID:18779039

  9. Remodelling of the hepatic epigenetic landscape of glucose-intolerant rainbow trout (Oncorhynchus mykiss) by nutritional status and dietary carbohydrates.

    PubMed

    Marandel, Lucie; Lepais, Olivier; Arbenoits, Eva; Véron, Vincent; Dias, Karine; Zion, Marie; Panserat, Stéphane

    2016-08-26

    The rainbow trout, a carnivorous fish, displays a 'glucose-intolerant' phenotype revealed by persistent hyperglycaemia when fed a high carbohydrate diet (HighCHO). Epigenetics refers to heritable changes in gene activity and is closely related to environmental changes and thus to metabolism adjustments governed by nutrition. In this study we first assessed in the trout liver whether and how nutritional status affects global epigenome modifications by targeting DNA methylation and histone marks previously reported to be affected in metabolic diseases. We then examined whether dietary carbohydrates could affect the epigenetic landscape of duplicated gluconeogenic genes previously reported to display changes in mRNA levels in trout fed a high carbohydrate diet. We specifically highlighted global hypomethylation of DNA and hypoacetylation of H3K9 in trout fed a HighCHO diet, a well-described phenotype in diabetes. g6pcb2 ohnologs were also hypomethylated at specific CpG sites in these animals according to their up-regulation. Our findings demonstrated that the hepatic epigenetic landscape can be affected by both nutritional status and dietary carbohydrates in trout. The mechanism underlying the setting up of these epigenetic modifications has now to be explored in order to improve understanding of its impact on the glucose intolerant phenotype in carnivorous teleosts.

  10. Remodelling of the hepatic epigenetic landscape of glucose-intolerant rainbow trout (Oncorhynchus mykiss) by nutritional status and dietary carbohydrates.

    PubMed

    Marandel, Lucie; Lepais, Olivier; Arbenoits, Eva; Véron, Vincent; Dias, Karine; Zion, Marie; Panserat, Stéphane

    2016-01-01

    The rainbow trout, a carnivorous fish, displays a 'glucose-intolerant' phenotype revealed by persistent hyperglycaemia when fed a high carbohydrate diet (HighCHO). Epigenetics refers to heritable changes in gene activity and is closely related to environmental changes and thus to metabolism adjustments governed by nutrition. In this study we first assessed in the trout liver whether and how nutritional status affects global epigenome modifications by targeting DNA methylation and histone marks previously reported to be affected in metabolic diseases. We then examined whether dietary carbohydrates could affect the epigenetic landscape of duplicated gluconeogenic genes previously reported to display changes in mRNA levels in trout fed a high carbohydrate diet. We specifically highlighted global hypomethylation of DNA and hypoacetylation of H3K9 in trout fed a HighCHO diet, a well-described phenotype in diabetes. g6pcb2 ohnologs were also hypomethylated at specific CpG sites in these animals according to their up-regulation. Our findings demonstrated that the hepatic epigenetic landscape can be affected by both nutritional status and dietary carbohydrates in trout. The mechanism underlying the setting up of these epigenetic modifications has now to be explored in order to improve understanding of its impact on the glucose intolerant phenotype in carnivorous teleosts. PMID:27561320

  11. Aspartame intake is associated with greater glucose intolerance in individuals with obesity.

    PubMed

    Kuk, Jennifer L; Brown, Ruth E

    2016-07-01

    This study examined whether sucrose, fructose, aspartame, and saccharin influences the association between obesity and glucose tolerance in 2856 adults from the NHANES III survey. Aspartame intake significantly influenced the association between body mass index (BMI) and glucose tolerance (interaction: P = 0.004), wherein only those reporting aspartame intake had a steeper positive association between BMI and glucose tolerance than those reporting no aspartame intake. Therefore, consumption of aspartame is associated with greater obesity-related impairments in glucose tolerance. PMID:27216413

  12. Aspartame intake is associated with greater glucose intolerance in individuals with obesity.

    PubMed

    Kuk, Jennifer L; Brown, Ruth E

    2016-07-01

    This study examined whether sucrose, fructose, aspartame, and saccharin influences the association between obesity and glucose tolerance in 2856 adults from the NHANES III survey. Aspartame intake significantly influenced the association between body mass index (BMI) and glucose tolerance (interaction: P = 0.004), wherein only those reporting aspartame intake had a steeper positive association between BMI and glucose tolerance than those reporting no aspartame intake. Therefore, consumption of aspartame is associated with greater obesity-related impairments in glucose tolerance.

  13. Aerobic Fitness Does Not Contribute to Prediction of Orthostatic Intolerance

    NASA Technical Reports Server (NTRS)

    Convertino, Victor A.; Sather, Tom M.; Goldwater, Danielle J.; Alford, William R.

    1986-01-01

    Several investigations have suggested that orthostatic tolerance may be inversely related to aerobic fitness (VO (sub 2max)). To test this hypothesis, 18 males (age 29 to 51 yr) underwent both treadmill VO(sub 2max) determination and graded lower body negative pressures (LBNP) exposure to tolerance. VO(2max) was measured during the last minute of a Bruce treadmill protocol. LBNP was terminated based on pre-syncopal symptoms and LBNP tolerance (peak LBNP) was expressed as the cumulative product of LBNP and time (torr-min). Changes in heart rate, stroke volume cardiac output, blood pressure and impedance rheographic indices of mid-thigh-leg initial accumulation were measured at rest and during the final minute of LBNP. For all 18 subjects, mean (plus or minus SE) fluid accumulation index and leg venous compliance index at peak LBNP were 139 plus or minus 3.9 plus or minus 0.4 ml-torr-min(exp -2) x 10(exp 3), respectively. Pearson product-moment correlations and step-wise linear regression were used to investigate relationships with peak LBNP. Variables associated with endurance training, such as VO(sub 2max) and percent body fat were not found to correlate significantly (P is less than 0.05) with peak LBNP and did not add sufficiently to the prediction of peak LBNP to be included in the step-wise regression model. The step-wise regression model included only fluid accumulation index leg venous compliance index, and blood volume and resulted in a squared multiple correlation coefficient of 0.978. These data do not support the hypothesis that orthostatic tolerance as measured by LBNP is lower in individuals with high aerobic fitness.

  14. Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

    NASA Astrophysics Data System (ADS)

    Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

    2006-03-01

    Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

  15. N-Acetyl-L-Cysteine inhibits the development of glucose intolerance and hepatic steatosis in diabetes-prone mice

    PubMed Central

    Falach-Malik, Alona; Rozenfeld, Hava; Chetboun, Moria; Rozenberg, Konstantin; Elyasiyan, Uriel; Sampson, Sanford R; Rosenzweig, Tovit

    2016-01-01

    Oxidative stress is associated with different pathological conditions, including glucose intolerance and type 2 diabetes (T2D), however studies had failed to prove the benefits of antioxidants in T2D. Aim: On the assumption that the failure to demonstrate such anti-diabetic effects is a result of sub-optimal or excessive antioxidant dosage, we aimed to clarify the dose-response effect of the antioxidant N-Acetyl-L-Cysteine (NAC) on the progression of T2D in-vivo. Methods: Experiments were conducted on KK-Ay mice and HFD-fed mice given NAC at different concentrations (200-1800 and 60-600 mg/kg/day, respectively). Glucose and insulin tolerance tests were performed and plasma insulin and lipid peroxidation were measured. Insulin signaling pathway was followed in muscle and liver. Hepatic TG accumulation and mRNA expression of genes involved in glucose metabolism were measured. Results: While 600-1800 mg/kg/day NAC all improved glucose tolerance in KK-Ay mice, only the 1200 mg/kg/day treatment increased insulin sensitivity. Hepatic function was not affected, however; microsteatosis rather than macrosteatosis was observed in NAC-treated mice compared to control. Glucose tolerance was improved in NAC-treated HFD-fed mice as well; the best results obtained with a dose of 400 mg NAC/kg/day. This was followed by lower weight gain and hepatic TG. Plasma lipid peroxidation was not correlated with the glucose-lowering effects of NAC in either model. Conclusion: Identification of the optimal dose of NAC and the population that would benefit the most from such intervention is essential in order to apply preventive and/or therapeutic use of NAC and similar agents in the future. PMID:27725855

  16. Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance.

    PubMed

    Nagao, Mototsugu; Asai, Akira; Inaba, Wataru; Kawahara, Momoyo; Shuto, Yuki; Kobayashi, Shunsuke; Sanoyama, Daisuke; Sugihara, Hitoshi; Yagihashi, Soroku; Oikawa, Shinichi

    2014-01-01

    Hereditary predisposition to diet-induced type 2 diabetes has not yet been fully elucidated. We recently established 2 mouse lines with different susceptibilities (resistant and prone) to high-fat diet (HFD)-induced glucose intolerance by selective breeding (designated selectively bred diet-induced glucose intolerance-resistant [SDG-R] and -prone [SDG-P], respectively). To investigate the predisposition to HFD-induced glucose intolerance in pancreatic islets, we examined the islet morphological features and functions in these novel mouse lines. Male SDG-P and SDG-R mice were fed a HFD for 5 weeks. Before and after HFD feeding, glucose tolerance was evaluated by oral glucose tolerance test (OGTT). Morphometry and functional analyses of the pancreatic islets were also performed before and after the feeding period. Before HFD feeding, SDG-P mice showed modestly higher postchallenge blood glucose levels and lower insulin increments in OGTT than SDG-R mice. Although SDG-P mice showed greater β cell proliferation than SDG-R mice under HFD feeding, SDG-P mice developed overt glucose intolerance, whereas SDG-R mice maintained normal glucose tolerance. Regardless of whether it was before or after HFD feeding, the isolated islets from SDG-P mice showed impaired glucose- and KCl-stimulated insulin secretion relative to those from SDG-R mice; accordingly, the expression levels of the insulin secretion-related genes in SDG-P islets were significantly lower than those in SDG-R islets. These findings suggest that the innate predispositions in pancreatic islets may determine the susceptibility to diet-induced diabetes. SDG-R and SDG-P mice may therefore be useful polygenic animal models to study the gene-environment interactions in the development of type 2 diabetes.

  17. Male mice produced by in vitro culture have reduced fertility and transmit organomegaly and glucose intolerance to their male offspring.

    PubMed

    Calle, Alexandra; Miranda, Alberto; Fernandez-Gonzalez, Raul; Pericuesta, Eva; Laguna, Ricardo; Gutierrez-Adan, Alfonso

    2012-08-01

    It has been reported that suboptimal in vitro culture (IVC) of mouse embryos can affect the postnatal expression of epigenetically sensitive alleles, resulting in altered postnatal growth, organ dimensions, health, and behavior in the offspring. Although these detrimental impacts on the offspring are well described, the relative contribution of the IVC-produced fathers is unclear. In this work, we have analyzed if suboptimal IVC (achieved by altering the culture medium by the addition of FCS) can affect male fertility and if organ size and glucose clearance, two of the adverse effects produced by suboptimal IVC conditions, were transmitted to the next two generations. IVC-produced males had lower sperm concentrations (5.8 × 10(6) spermatozoa in IVC vs. 14.5 × 10(6) spermatozoa in control), and these sperm exhibited decreased overall motility (49.6% vs. 72.8% in control) and progressive motility (22.6% vs. 32.2% in control). Fertility tests demonstrated that the percentage of pregnancies was reduced for IVC males (35% for IVC-produced males vs. 86% for in vivo controls). These features were related to a modified gene expression pattern in adult male testes, showing an altered gene expression in genes involved in DNA repair and apoptosis that was confirmed by TUNEL assay. Regarding the IVC related adverse phenotype transmitted to offspring, male glucose intolerance was shown only in F1 and F2 male but not female offspring. The same occurred with male abnormalities in the organ size of the liver, which were transmitted to F1 and F2 males but not to F1 females; moreover, analysis of the F0, F1, and F2 males revealed greater coefficients of variance in body weight and glucose intolerance than the control group. Finally, we analyzed, through gene silencing, the effect of IVC on the mRNA expression at the blastocyst stage for 11 known gene expression modifiers of epigenetic reprogramming. Suboptimal IVC reduced the expression of Kap1, Sox2, Hdac1, Dnmt1, and Dnmt3a

  18. In vivo JNK activation in pancreatic β-cells leads to glucose intolerance caused by insulin resistance in pancreas.

    PubMed

    Lanuza-Masdeu, Jordi; Arévalo, M Isabel; Vila, Cristina; Barberà, Albert; Gomis, Ramon; Caelles, Carme

    2013-07-01

    Insulin resistance is a key condition in the development of type 2 diabetes. It is well established that exacerbated Jun NH2-terminal kinase (JNK) activity is involved in promoting insulin resistance in peripheral insulin-target tissues; however, this involvement is less documented in pancreatic β-cells. Using a transgenic mouse model, here we show that JNK activation in β-cells led to glucose intolerance as a result of impaired capacity to increase insulinemia in response to hyperglycemia. Pancreatic islets from these mice showed no obvious morphostructural abnormalities or decreased insulin content. In contrast, these islets failed to secrete insulin in response to glucose or insulin but were competent in succinate-, ketoisocaproate-, 3-isobutyl-1-methylxanthine (IBMX-), KCl-, and tolbutamide-induced insulin secretion. At the molecular level, JNK activation in β-cells inhibited insulin-induced Akt phosphorylation, pancreatic and duodenal homeobox 1 nucleocytoplasmic shuttling, and transcription of insulin-target genes. Remarkably, rosiglitazone restored insulin secretion in response to hyperglycemia in mice and insulin-induced insulin secretion and signaling in isolated islets. In conclusion, the mere activation of JNK suffices to induce insulin resistance in pancreatic β-cells by inhibition of insulin signaling in these cells, but it is not sufficient to elicit β-cell death. In addition, we provide the first evidence that thiazolidinediones exert insulin-sensitizing action directly on pancreatic β-cells.

  19. Remodelling of the hepatic epigenetic landscape of glucose-intolerant rainbow trout (Oncorhynchus mykiss) by nutritional status and dietary carbohydrates

    PubMed Central

    Marandel, Lucie; Lepais, Olivier; Arbenoits, Eva; Véron, Vincent; Dias, Karine; Zion, Marie; Panserat, Stéphane

    2016-01-01

    The rainbow trout, a carnivorous fish, displays a ‘glucose-intolerant’ phenotype revealed by persistent hyperglycaemia when fed a high carbohydrate diet (HighCHO). Epigenetics refers to heritable changes in gene activity and is closely related to environmental changes and thus to metabolism adjustments governed by nutrition. In this study we first assessed in the trout liver whether and how nutritional status affects global epigenome modifications by targeting DNA methylation and histone marks previously reported to be affected in metabolic diseases. We then examined whether dietary carbohydrates could affect the epigenetic landscape of duplicated gluconeogenic genes previously reported to display changes in mRNA levels in trout fed a high carbohydrate diet. We specifically highlighted global hypomethylation of DNA and hypoacetylation of H3K9 in trout fed a HighCHO diet, a well-described phenotype in diabetes. g6pcb2 ohnologs were also hypomethylated at specific CpG sites in these animals according to their up-regulation. Our findings demonstrated that the hepatic epigenetic landscape can be affected by both nutritional status and dietary carbohydrates in trout. The mechanism underlying the setting up of these epigenetic modifications has now to be explored in order to improve understanding of its impact on the glucose intolerant phenotype in carnivorous teleosts. PMID:27561320

  20. GAD65 antibodies among Greenland Inuit and its relation to glucose intolerance.

    PubMed

    Pedersen, Michael Lynge; Bjerregaard, Peter; Jørgensen, Marit Eika

    2014-08-01

    The aim of this study was to compare the prevalence of circulating Glutamin-Acid-decarboxylase 65 antibodies in a sample of Greenlanders (Inuit) with clinically verified diabetes with samples of participants from a population survey. The study population included participants with known diabetes from a population-based study (sample 1) and patients with clinically verified diabetes in Nuuk Greenland (sample 2). In addition, age- and gender-matched participants from the population study without known diabetes were categorized in groups with (1) normal glucose tolerance test, (2) with impaired fasting glycemia, (3) with impaired glucose tolerance and (4) with previously unknown diabetes based on oral glucose tolerance test and were enrolled in the study. Presence of circulating Glutamin-Acid-decarboxylase 65 antibodies were measured in all participants. A total of 484 persons were enrolled in the study. Six individuals had circulating Glutamin-Acid-decarboxylase 65 antibodies: four of them had known diabetes, one had impaired glucose tolerance and one normal glucose tolerance test. The prevalence of circulating Glutamin-Acid-decarboxylase 65 antibodies among Greenlanders with diabetes was 4.3 % and less than 1 % among Greenlanders without diabetes (p = 0.001). The prevalence of circulating Glutamin-Acid-decarboxylase 65 antibodies among Greenlanders with and without diabetes is relatively low in a global perspective in accordance with one former study among Inuit. Autoimmune diabetes seems to be uncommon in Greenland .

  1. Insulin sensitivity decreases with obesity, and lean cats with low insulin sensitivity are at greatest risk of glucose intolerance with weight gain.

    PubMed

    Appleton, D J; Rand, J S; Sunvold, G D

    2001-12-01

    This study quantifies the effects of marked weight gain on glucose and insulin metabolism in 16 cats which increased their weight by an average of 44.2% over 10 months. Significantly, the development of feline obesity was accompanied by a 52% decrease in tissue sensitivity to insulin and diminished glucose effectiveness. In addition, glucose intolerance and abnormal insulin response occurred in some cats. An important finding was that normal weight cats with low insulin sensitivity and glucose effectiveness were at increased risk of developing impaired glucose tolerance with obesity. High basal insulin concentrations or low acute insulin response to glucose also independently increased the risk for developing impaired glucose tolerance. Male cats gained more weight relative to females and this, combined with their tendency to lower insulin sensitivity and higher insulin concentrations, may explain why male cats are at greater risk for diabetes. Results suggest an underlying predisposition for glucose intolerance in some cats, which is exacerbated by obesity. These cats may be more at risk of progressing to overt type 2 diabetes mellitus.

  2. Hepatic Branch Vagus Nerve Plays a Critical Role in the Recovery of Post-Ischemic Glucose Intolerance and Mediates a Neuroprotective Effect by Hypothalamic Orexin-A

    PubMed Central

    Harada, Shinichi; Yamazaki, Yui; Koda, Shuichi; Tokuyama, Shogo

    2014-01-01

    Orexin-A (a neuropeptide in the hypothalamus) plays an important role in many physiological functions, including the regulation of glucose metabolism. We have previously found that the development of post-ischemic glucose intolerance is one of the triggers of ischemic neuronal damage, which is suppressed by hypothalamic orexin-A. Other reports have shown that the communication system between brain and peripheral tissues through the autonomic nervous system (sympathetic, parasympathetic and vagus nerve) is important for maintaining glucose and energy metabolism. The aim of this study was to determine the involvement of the hepatic vagus nerve on hypothalamic orexin-A-mediated suppression of post-ischemic glucose intolerance development and ischemic neuronal damage. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Intrahypothalamic orexin-A (5 pmol/mouse) administration significantly suppressed the development of post-ischemic glucose intolerance and neuronal damage on day 1 and 3, respectively after MCAO. MCAO-induced decrease of hepatic insulin receptors and increase of hepatic gluconeogenic enzymes on day 1 after was reversed to control levels by orexin-A. This effect was reversed by intramedullary administration of the orexin-1 receptor antagonist, SB334867, or hepatic vagotomy. In the medulla oblongata, orexin-A induced the co-localization of cholin acetyltransferase (cholinergic neuronal marker used for the vagus nerve) with orexin-1 receptor and c-Fos (activated neural cells marker). These results suggest that the hepatic branch vagus nerve projecting from the medulla oblongata plays an important role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A. PMID:24759941

  3. Ozone Induces Glucose Intolerance and Systemic Metabolic Effects in Young and Aged Brown Norway Rats

    EPA Science Inventory

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone could impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in very young and aged rats. Brown Norway (BN) rats, 1,4, 12, and 24 months ol...

  4. Comparison of glycosylated hemoglobin with the oral glucose tolerance test. A study in subjects with normoglycemia, glucose intolerance and non-insulin-dependent diabetes mellitus.

    PubMed

    Cederholm, J; Ronquist, G; Wibell, L

    1984-10-01

    At a health survey of 819 subjects, 47-54 years old, the rate of glucose intolerance (GI) was 6.2% (51 subjects) according to 75 g oral glucose tolerance tests (OGTT) and WHO criteria. In GI-subjects, the mean HbA1 was 7.3% (10th-90th percentile range 6.2-8.3%), and significantly higher than the mean HbA1 in 150 subjects with normal OGTT, which was 6.5% (10th-90th percentile range 5.7-7.4%). With an upper normal limit of 7.8% (mean + 2 SD) only 20% of all GI-subjects had a raised HbA1. The differences between 31 GI-subjects, with low HbA1 (mean 6.9%), and 20 GI-subjects, with relatively high HbA1 (mean 7.9%), were not significant with respect to fasting and 2-hour blood glucose, area under glucose curve, body mass index, index of physical activity, rate of hypertension or rate of first degree relatives with diabetes. In an unselected group of 157 subjects, sampled consecutively during the first part of the survey, the mean HbA1 was 6.6% (10th-90th percentile range 5.8-7.5 %) 150 subjects were those with normal OGTT, 6 subjects had GI and only one subject had previously unknown diabetes. No distinct correlations between HbA1 and OGTT fasting or 2 hour values were found in this sample. No correlation was found within the separate groups of 51 GI-subjects and 150 normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Relationship of serum adiponectin and resistin to glucose intolerance and fat topography in south-Asians

    PubMed Central

    Wasim, Hanif; Al-Daghri, Nasser M; Chetty, Raja; McTernan, Phillip G; Barnett, A H; Kumar, Sudhesh

    2006-01-01

    Objectives South-Asians have lower adiponectin levels compared to Caucasians. It was not clear however, if this intrinsic feature is related to aspects of glucose metabolism. This study aims to determine the relationship between body fat distribution and adipocytokine in South-Asian subjects by measuring serum adipocytokines, adiposity, insulinemia, and glucose tolerance levels. Methods In this cross-sectional study, 150 South-Asians (80 males, 70 females) were included, 60 had NGT (Control group, Age 51.33 ± 11.5, BMI 27 ± 2.3), 60 had IGT (Age 57.7 ± 12.5, BMI 27.2 ± 2.7), 30 had type 2 DM (Age 49.5 ± 10.9, BMI 28 ± 1.7). Measures of adiposity, adipocytokines and other metabolic parameters were determined. Parameters were measured using the following: a) Plasma glucose by glucose oxidase method b) CRP by immunoturbidimetric method (Roche/Hitachi analyser) c) insulin by Medgenix INS-ELISA immunoenzymetric assay by Biosource (Belgium) d) Leptin, Adiponectin by radioimmunoassay kits by Linco Research (St. Charles MO) e) Resistin by immunoassay kits by Phoenix Pharmaceuticals INC (530 Harbor Boulevard, Belmont CA 94002, USA). Results Adiponectin concentrations were highest in NGT, decreased in IGT and lowest in DMT2, (both p < 0.01). Leptin was significantly higher in DMT2 than IGT and NGT p = 0.02 and 0.04 respectively. There was a significant positive relationships between log adiponectin and 2-hr insulin values, p = 0.028 and history of hypertensions and a ischemic heart disease p = 0.008 with R = 0.65. There was a significant inverse correlation between log adiponectin and resistin, p < 0.01. Conclusion Resistin levels had an inverse correlation with adiponectin levels, indicating an inverse relationship between pro-inflammatory cytokines and adiponectin. Adiponectin levels were related to glucose tolerance. PMID:16669997

  6. An iTRAQ proteomic study reveals an association between diet-induced enhanced fatty acid metabolism and the development of glucose intolerance in prediabetic mice.

    PubMed

    Ho, Jennifer H; Lee, Oscar K; Fu, Yun-Ju; Shih, Hung-Ta; Tseng, Chien-Yu; Chung, Cheng-Chih; Han, Chia-Li; Chen, Yu-Ju

    2013-03-01

    High-fat diet (HFD)-induced glucose intolerance and insulin resistance increases the chances of developing type-2 diabetes and cardiovascular disease. To study the mechanism(s) by which a HFD impairs glucose tolerance, we used a quantitative proteomic platform that integrated pI-based OFFGEL fractionation and iTRAQ labeling to profile the temporal changes in adipose membrane protein expression in mice fed a HFD for up to 8 months. Within 2 months of starting the diet, the mice adipose and liver tissues accumulated fat droplets, which contributed to subsequent insulin resistance and glucose intolerance within 6 months. The membrane proteomic delineation of such phenotypic expression resulted in quantification of 1713 proteins with 266, 343, and 125 differentially expressed proteins in 2-, 6-, and 8-month HFD-fed versus control mice, respectively. Pathway analysis of these differentially expressed proteins revealed the interplay between upregulation of fatty acid metabolism and downregulation of glucose metabolism. Substantial upregulation of adipose and liver carnitine palmitoyltransferase (Cpt) 1, the rate-limiting enzyme in the transport of long-chain fatty acids into mitochondria, occurred by 2 months. The increase in hepatic Cpt 1a expression was associated with a progressive decrease in glucose uptake as evidenced by downregulation of the liver glucose transporter protein (Glut) 2. Loss of glycogen storage was found in those hepatocytes full of fat droplets. Intriguingly, skeletal muscle Cpt 1b expression was unaltered by the HFD, whereas skeletal muscle Glut 4 and tyrosine phosphoryated insulin receptor substrate 1 (p-IRS1) were substantially upregulated at the same time as abnormal glucose metabolism developed in adipose and liver tissues. This study defines some of the molecular mechanisms as well as the relationship among adipose tissue, liver and skeletal muscle during development of HFD-induced glucose intolerance in vivo and identifies Cpt 1 as a

  7. Prenatal Testosterone Exposure Leads to Gonadal Hormone-Dependent Hyperinsulinemia and Gonadal Hormone-Independent Glucose Intolerance in Adult Male Rat Offspring.

    PubMed

    More, Amar S; Mishra, Jay S; Gopalakrishnan, Kathirvel; Blesson, Chellakkan S; Hankins, Gary D; Sathishkumar, Kunju

    2016-01-01

    Elevated testosterone levels during prenatal life lead to hyperandrogenism and insulin resistance in adult females. This study evaluated whether prenatal testosterone exposure leads to the development of insulin resistance in adult male rats in order to assess the influence of gonadal hormones on glucose homeostasis in these animals. Male offspring of pregnant rats treated with testosterone propionate or its vehicle (control) were examined. A subset of male offspring was orchiectomized at 7 wk of age and reared to adulthood. At 24 wk of age, fat weights, plasma testosterone, glucose homeostasis, pancreas morphology, and gastrocnemius insulin receptor (IR) beta levels were examined. The pups born to testosterone-treated mothers were smaller at birth and remained smaller through adult life, with levels of fat deposition relatively similar to those in controls. Testosterone exposure during prenatal life induced hyperinsulinemia paralleled by an increased HOMA-IR index in a fasting state and glucose intolerance and exaggerated insulin responses following a glucose tolerance test. Prenatal androgen-exposed males had more circulating testosterone during adult life. Gonadectomy prevented hyperandrogenism, reversed hyperinsulinemia, and attenuated glucose-induced insulin responses but did not alter glucose intolerance in these rats. Prenatal androgen-exposed males had decreased pancreatic islet numbers, size, and beta-cell area along with decreased expression of IR in gastrocnemius muscles. Gonadectomy restored pancreatic islet numbers, size, and beta-cell area but did not normalize IRbeta expression. This study shows that prenatal testosterone exposure leads to a defective pancreas and skeletal muscle function in male offspring. Hyperinsulinemia during adult life is gonad-dependent, but glucose intolerance appears to be independent of postnatal testosterone levels. PMID:26586841

  8. Weight loss results in a small decrease in follicle stimulating hormone in overweight glucose-intolerant postmenopausal women

    PubMed Central

    Kim, Catherine; Randolph, John F.; Golden, Sherita H.; Labrie, Fernand; Kong, Shengchun; Nan, Bin; Barrett-Connor, Elizabeth

    2014-01-01

    Structured Abstract Objective To examine the impact of a weight loss intervention upon follicle stimulating hormone (FSH) levels in postmenopause. Design and Methods Participants were postmenopausal, overweight, glucose-intolerant women not using exogenous estrogen (n=382) in the Diabetes Prevention Program. Women were randomized to intensive lifestyle change (ILS) with the goals of weight reduction of at least 7% of initial weight and 150 minutes per week of moderate intensity exercise, metformin 850 mg, or placebo administered twice a day. Results Randomization to ILS led to small increases in FSH between baseline and 1-year follow-up vs. placebo (2.3 IU/l vs. -0.81 IU/l, p<0.01). Increases in FSH were correlated with decreases in weight (r=-0.165, p<0.01) and E2 (r=-0.464, p<0.0001) after adjustment for age, race/ethnicity, and randomization arm. Changes in FSH were still significantly associated with changes in weight even after adjustment for E2 levels. Metformin users had reductions in weight but non-significant changes in FSH and E2 levels vs. placebo. Conclusions Weight loss leads to small increases in FSH among overweight, postmenopausal women, potentially through pathways mediated by endogenous estrogen as well as other pathways. PMID:25294746

  9. Glucose intolerance in dairy goats with pregnancy toxemia: Lack of correlation between blood pH and beta hydroxybutyric acid values.

    PubMed

    Lima, Miguel S; Cota, João B; Vaz, Yolanda M; Ajuda, Inês G; Pascoal, Rita A; Carolino, Nuno; Hjerpe, Charles A

    2016-06-01

    This study assessed the response to a glucose tolerance test in dairy goats with pregnancy toxemia (PT), in healthy, pregnant, non-lactating dairy goats in the last month of gestation (HP), and in healthy, lactating, non-pregnant, dairy goats in mid-lactation (HL). A 500 mL volume of a 5% glucose solution was administered by the IV route. Blood glucose concentrations returned to pre-infusion levels by 90 min in all 8 HL goats, and by 180 min in all 8 HP goats. In contrast, concentrations of blood glucose were still significantly above pre-infusion levels at 180 min post-infusion in all 8 PT goats. Thus, marked glucose intolerance was demonstrated in the PT goats, and mild intolerance was noted in the HP goats. In 25 goats diagnosed with PT and having blood beta hydroxybutyric acid (BHBA) values ≥ 2.9 mmol/L, the correlation coefficient for BHBA with blood pH was non-significant. PMID:27247464

  10. Lactose intolerance

    MedlinePlus

    Lactase deficiency; Milk intolerance; Disaccharidase deficiency; Dairy product intolerance ... make the lactase enzyme so they can digest milk, including breast milk. Babies born too early (premature) ...

  11. Acute Overactive Endocannabinoid Signaling Induces Glucose Intolerance, Hepatic Steatosis, and Novel Cannabinoid Receptor 1 Responsive Genes

    PubMed Central

    Ruby, Maxwell A.; Nomura, Daniel K.; Hudak, Carolyn S. S.; Barber, Anne; Casida, John E.; Krauss, Ronald M.

    2011-01-01

    Endocannabinoids regulate energy balance and lipid metabolism by stimulating the cannabinoid receptor type 1 (CB1). Genetic deletion and pharmacological antagonism have shown that CB1 signaling is necessary for the development of obesity and related metabolic disturbances. However, the sufficiency of endogenously produced endocannabinoids to cause hepatic lipid accumulation and insulin resistance, independent of food intake, has not been demonstrated. Here, we show that a single administration of isopropyl dodecylfluorophosphonate (IDFP), perhaps the most potent pharmacological inhibitor of endocannabinoid degradation, increases hepatic triglycerides (TG) and induces insulin resistance in mice. These effects involve increased CB1 signaling, as they are mitigated by pre-administration of a CB1 antagonist (AM251) and in CB1 knockout mice. Despite the strong physiological effects of CB1 on hepatic lipid and glucose metabolism, little is known about the downstream targets responsible for these effects. To elucidate transcriptional targets of CB1 signaling, we performed microarrays on hepatic RNA isolated from DMSO (control), IDFP and AM251/IDFP-treated mice. The gene for the secreted glycoprotein lipocalin 2 (lcn2), which has been implicated in obesity and insulin resistance, was among those most responsive to alterations in CB1 signaling. The expression pattern of IDFP mice segregated from DMSO mice in hierarchal cluster analysis and AM251 pre-administration reduced (>50%) the majority (303 of 533) of the IDFP induced alterations. Pathway analysis revealed that IDFP altered expression of genes involved in lipid, fatty acid and steroid metabolism, the acute phase response, and amino acid metabolism in a CB1-dependent manner. PCR confirmed array results of key target genes in multiple independent experiments. Overall, we show that acute IDFP treatment induces hepatic TG accumulation and insulin resistance, at least in part through the CB1 receptor, and identify novel

  12. Disturbed intestinal nitrogen homeostasis in a mouse model of high-fat diet-induced obesity and glucose intolerance.

    PubMed

    Do, Thi Thu Huong; Hindlet, Patrick; Waligora-Dupriet, Anne-Judith; Kapel, Nathalie; Neveux, Nathalie; Mignon, Virginie; Deloménie, Claudine; Farinotti, Robert; Fève, Bruno; Buyse, Marion

    2014-03-01

    The oligopeptide transporter peptide cotransporter-1 Slc15a1 (PEPT1) plays a major role in the regulation of nitrogen supply, since it is responsible for 70% of the dietary nitrogen absorption. Previous studies demonstrated that PEPT1 expression and function in jejunum are reduced in diabetes and obesity, suggesting a nitrogen malabsorption from the diet. Surprisingly, we reported here a decrease in gut nitrogen excretion in high-fat diet (HFD)-fed mice and further investigated the mechanisms that could explain this apparent contradiction. Upon HFD, mice exhibited an increased concentration of free amino acids (AAs) in the portal vein (60%) along with a selective increase in the expression of two AA transporters (Slc6a20a, Slc36a1), pointing to a specific and adaptive absorption of some AAs. A delayed transit time (+40%) and an increased intestinal permeability (+80%) also contribute to the increase in nitrogen absorption. Besides, HFD mice exhibited a 2.2-fold decrease in fecal DNA resulting from a reduction in nitrogen catabolism from cell desquamation and/or in the intestinal microbiota. Indeed, major quantitative (2.5-fold reduction) and qualitative alterations of intestinal microbiota were observed in feces of HFD mice. Collectively, our results strongly suggest that both increased AA transporters, intestinal permeability and transit time, and changes in gut microbiota are involved in the increased circulating AA levels. Modifications in nitrogen homeostasis provide a new insight in HFD-induced obesity and glucose intolerance; however, whether these modifications are beneficial or detrimental for the HFD-associated metabolic complications remains an open issue.

  13. The Association of Elective Hormone Therapy with Changes in Lipids Among Glucose Intolerant Postmenopausal Women in the Diabetes Prevention Program

    PubMed Central

    Golden, Sherita H.; Kim, Catherine; Barrett-Connor, Elizabeth; Nan, Bin; Kong, Shengchun; Goldberg, Ronald

    2013-01-01

    Objective It is unclear how lipids change in response to lifestyle modification or metformin among postmenopausal glucose intolerant women using and not using hormone therapy (HT). We examined the one-year changes in lipids among postmenopausal, prediabetic women in the Diabetes Prevention Program (DPP), and whether changes were mediated by sex hormones. Materials/Methods We performed a secondary analysis of a randomized controlled trial of 342 women who used HT at baseline and year 1 and 382 women who did not use HT at either time point. Interventions included intensive lifestyle (ILS) with goals of weight reduction of at least 7% of initial weight and 150 minutes per week of moderate intensity exercise, or metformin or placebo administered 850 mg up to twice a day. Women were not randomized to HT. Main outcome measures were changes between baseline and study year 1 in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Results Compared to placebo, both ILS and metformin significantly reduced LDL-C and raised HDL-C among HT users, changes partially explained by change in estradiol and testosterone but independent of changes in waist circumference and 1/fasting insulin. In contrast, DPP interventions had no effect on LDL-C and HDL-C among non-HT users. ILS significantly lowered triglycerides among non-users but did not significantly change triglycerides among HT users. Metformin did not significantly change triglycerides among non-users but increased triglycerides among HT users. Conclusions The beneficial effects of ILS and metformin on lowering LDL-C and raising HDL-C differ depending upon concurrent HT use. PMID:23660512

  14. The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity

    PubMed Central

    Wang, Quanli; Halvorsen, Matt; Han, Yujun; Weir, William H.; Allen, Andrew S.; Goldstein, David B.

    2015-01-01

    Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory mutations are notoriously difficult to recognize. Most fundamentally, we are not yet adept at recognizing the sequence stretches in the human genome that are most important in regulating the expression of genes. For this reason, it is difficult to apply to the regulatory regions the same kinds of analytical paradigms that are being successfully applied to identify mutations among protein-coding regions that influence risk. To determine whether dosage sensitive genes have distinct patterns among their noncoding sequence, we present two primary approaches that focus solely on a gene’s proximal noncoding regulatory sequence. The first approach is a regulatory sequence analogue of the recently introduced residual variation intolerance score (RVIS), termed noncoding RVIS, or ncRVIS. The ncRVIS compares observed and predicted levels of standing variation in the regulatory sequence of human genes. The second approach, termed ncGERP, reflects the phylogenetic conservation of a gene’s regulatory sequence using GERP++. We assess how well these two approaches correlate with four gene lists that use different ways to identify genes known or likely to cause disease through changes in expression: 1) genes that are known to cause disease through haploinsufficiency, 2) genes curated as dosage sensitive in ClinGen’s Genome Dosage Map, 3) genes judged likely to be under purifying selection for mutations that change expression levels because they are statistically depleted of loss-of-function variants in the general population, and 4) genes judged unlikely to cause disease based on the presence of copy number variants in the general population. We find that both noncoding scores are highly predictive of dosage sensitivity using any of these criteria. In a similar way to ncGERP, we assess two ensemble-based predictors of regional noncoding importance

  15. Intolerance for withdrawal discomfort and motivation predict voucher-based smoking treatment outcomes for smokers with substance use disorders.

    PubMed

    Rohsenow, Damaris J; Tidey, Jennifer W; Kahler, Christopher W; Martin, Rosemarie A; Colby, Suzanne M; Sirota, Alan D

    2015-04-01

    Identifying predictors of abstinence with voucher-based treatment is important for improving its efficacy. Smokers with substance use disorders have very low smoking cessation rates so identifying predictors of smoking treatment response is particularly important for these difficult-to-treat smokers. Intolerance for Smoking Abstinence Discomfort (IDQ-S), motivation to quit smoking, nicotine dependence severity (FTND), and cigarettes per day were examined as predictors of smoking abstinence during and after voucher-based smoking treatment with motivational counseling. We also investigated the relationship between IDQ-S and motivation to quit smoking. Smokers in residential substance treatment (n=184) were provided 14days of vouchers for complete smoking abstinence (CV) after a 5-day smoking reduction lead-in period or vouchers not contingent on abstinence. Carbon monoxide readings indicated about 25% of days abstinent during the 14days of vouchers for abstinence in the CV group; only 3-4% of all participants were abstinent at follow-ups. The IDQ-S Withdrawal Intolerance scale and FTND each significantly predicted fewer abstinent days during voucher treatment; FTND was nonsignificant when controlling for variance shared with withdrawal intolerance. The one significant predictor of 1-month abstinence was pretreatment motivation to quit smoking, becoming marginal (p<.06) when controlling for FTND. Lower withdrawal intolerance significantly predicted 3month abstinence when controlling for FTND. Higher withdrawal intolerance pretreatment correlated with less motivation to quit smoking. Implications for voucher-based treatment include the importance of focusing on reducing these expectancies of anticipated smoking withdrawal discomfort, increasing tolerance for abstinence discomfort, and increasing motivation.

  16. Intolerance for Withdrawal Discomfort and Motivation Predict Voucher-Based Smoking Treatment Outcomes for Smokers with Substance Use Disorders

    PubMed Central

    Rohsenow, Damaris J.; Tidey, Jennifer W.; Kahler, Christopher W.; Martin, Rosemarie A.; Colby, Suzanne M.; Sirota, Alan D.

    2014-01-01

    Identifying predictors of abstinence with voucher-based treatment is important for improving its efficacy. Smokers with substance use disorders have very low smoking cessation rates so identifying predictors of smoking treatment response is particularly important for these difficult-to-treat smokers. Intolerance for Smoking Abstinence Discomfort (IDQ-S), motivation to quit smoking, nicotine dependence severity (FTND), and cigarettes per day were examined as predictors of smoking abstinence during and after voucher-based smoking treatment with motivational counseling. We also investigated the relationship between IDQ-S and motivation to quit smoking. Smokers in residential substance treatment (n = 184) were provided 14 days of vouchers for complete smoking abstinence (CV) after a 5-day smoking reduction lead-in period or vouchers not contingent on abstinence. Carbon monoxide readings indicated about 25% of days abstinent during the 14 days of vouchers for abstinence in the CV group; only 3–4% of all participants were abstinent at follow-ups. The IDQ-S Withdrawal Intolerance scale and FTND each significantly predicted fewer abstinent days during voucher treatment; FTND was non-significant when controlling for variance shared with Withdrawal Intolerance. The one significant predictor of 1-month abstinence was pretreatment motivation to quit smoking, becoming marginal (p < .06) when controlling for FTND. Lower Withdrawal Intolerance significantly predicted 3 month abstinence when controlling for FTND. Higher Withdrawal Intolerance pretreatment correlated with less motivation to quit smoking. Implications for voucher-based treatment include the importance of focusing on reducing these expectancies of anticipated smoking withdrawal discomfort, increasing tolerance for abstinence discomfort, and increasing motivation. PMID:25531536

  17. Reversal of glucose intolerance in rat offspring exposed to ethanol before birth through reduction of nuclear skeletal muscle HDAC expression by the bile acid TUDCA

    PubMed Central

    Yao, Xing‐Hai; Nguyen, Khanh H.; Nyomba, B. L. Grégoire

    2014-01-01

    Abstract Prenatal ethanol exposure causes cellular stress, insulin resistance, and glucose intolerance in adult offspring, with increased gluconeogenesis and reduced muscle glucose transporter‐4 (glut4) expression. Impaired insulin activation of Akt and nuclear translocation of histone deacetylases (HDACs) in the liver partly explain increased gluconeogenesis. The mechanism for the reduced glut4 is unknown. Pregnant rats were gavaged with ethanol over the last week of gestation and adult female offspring were studied. Some ethanol exposed offspring was treated with tauroursodeoxycholic acid (TUDCA) for 3 weeks. All these rats underwent intraperitoneal glucose tolerance and insulin tolerance tests. The expression of glut4, HDACs, and markers of endoplasmic reticulum (ER) unfolded protein response (XBP1, CHOP, ATF6) was examined in the gastrocnemius muscle fractions, and in C2C12 muscle cells cultured with ethanol, TUDCA, and HDAC inhibitors. Non‐TUDCA‐treated rats exposed to prenatal ethanol were insulin resistant and glucose intolerant with reduced muscle glut4 expression, increased ER marker expression, and increased nuclear HDACs, whereas TUDCA‐treated rats had normal insulin sensitivity and glucose tolerance with normal glut4 expression, ER marker expression, and HDAC levels. In C2C12 cells, ethanol reduced glut4 expression, but increased ER makers. While TUDCA restored glut4 and ER markers to control levels and HDAC inhibition rescued glut4 expression, HDAC inhibition had no effect on ER markers. The increase in nuclear HDAC levels consequent to prenatal ethanol exposure reduces glut4 expression in adult rat offspring, and this HDAC effect is independent of ER unfolded protein response. HDAC inhibition by TUDCA restores glut4 expression, with improvement in insulin sensitivity and glucose tolerance. PMID:25538147

  18. An inverse U-shaped association of late and peak insulin levels during an oral glucose load with glucose intolerance in a Japanese population: a cross-sectional study.

    PubMed

    Takahara, Mitsuyoshi; Katakami, Naoto; Matsuoka, Taka-Aki; Noguchi, Midori; Shimomura, Iichiro

    2015-01-01

    The current study investigated the association of post-load insulin levels with glucose tolerance in a Japanese population. A total of 1450 Japanese employees who underwent a 75-g oral glucose tolerance test (OGTT) were included. Glucose tolerance was assessed by 120-min glucose levels during a 75-g OGTT. A penalized cubic regression spline model analysis revealed that the 60- and 120-min insulin levels, but not 0- or 30-min insulin levels, had an inverse U-shaped relationship to the 120-min glucose level. Furthermore, peak insulin level followed an inverse U shape in relation to the 120-min glucose level, whereas the peak of insulin appeared at a later point in time as the 120-min glucose level increased. These associations were similarly observed in both obese and non-obese subgroups, although obesity was associated with higher insulin levels. Peak insulin levels also demonstrated an inverse U shape in association with 0-min glucose levels and indices of β cell function, assessed by the disposition index and the β-cell function index. In conclusion, peak insulin levels followed an inverse U shape in relation to glucose intolerance in a Japanese population, whereas the impairment of glucose tolerance was associated with a delay in the time to reach peak insulin levels.

  19. What Is Going On Around Here? Intolerance of Uncertainty Predicts Threat Generalization

    PubMed Central

    Morriss, Jayne; Macdonald, Birthe; van Reekum, Carien M.

    2016-01-01

    Attending to stimuli that share perceptual similarity to learned threats is an adaptive strategy. However, prolonged threat generalization to cues signalling safety is considered a core feature of pathological anxiety. One potential factor that may sustain over-generalization is sensitivity to future threat uncertainty. To assess the extent to which Intolerance of Uncertainty (IU) predicts threat generalization, we recorded skin conductance in 54 healthy participants during an associative learning paradigm, where threat and safety cues varied in perceptual similarity. Lower IU was associated with stronger discrimination between threat and safety cues during acquisition and extinction. Higher IU, however, was associated with generalized responding to threat and safety cues during acquisition, and delayed discrimination between threat and safety cues during extinction. These results were specific to IU, over and above other measures of anxious disposition. These findings highlight: (1) a critical role of uncertainty-based mechanisms in threat generalization, and (2) IU as a potential risk factor for anxiety disorder development. PMID:27167217

  20. Boehmeria nivea Stimulates Glucose Uptake by Activating Peroxisome Proliferator-Activated Receptor Gamma in C2C12 Cells and Improves Glucose Intolerance in Mice Fed a High-Fat Diet

    PubMed Central

    Kim, Sung Hee; Sung, Mi Jeong; Park, Jae Ho; Yang, Hye Jeong; Hwang, Jin-Taek

    2013-01-01

    We examined the antidiabetic property of Boehmeria nivea (L.) Gaud. Ethanolic extract of Boehmeria nivea (L.) Gaud. (EBN) increased the uptake of 2-[N-(nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose in C2C12 myotubes. To examine the mechanisms underlying EBN-mediated increase in glucose uptake, we examined the transcriptional activity and expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), a pivotal target for glucose metabolism in C2C12 myotubes. We found that the EBN increased both the transcriptional activity and mRNA expression levels of PPAR-γ. In addition, we measured phosphorylation and expression levels of other targets of glucose metabolism, such as AMP-activated protein kinase (AMPK) and protein kinase B (Akt/PKB). We found that EBN did not alter the phosphorylation or expression levels of these proteins in a time- or dose-dependent manner, which suggested that EBN stimulates glucose uptake through a PPAR-γ-dependent mechanism. Further, we investigated the antidiabetic property of EBN using mice fed a high-fat diet (HFD). Administration of 0.5% EBN reduced the HFD-induced increase in body weight, total cholesterol level, and fatty liver and improved the impaired fasting glucose level, blood insulin content, and glucose intolerance. These results suggest that EBN had an antidiabetic effect in cell culture and animal systems and may be useful for preventing diabetes. PMID:23690860

  1. Glucose intolerance and reduced islet blood flow in transgenic mice expressing the FRK tyrosine kinase under the control of the rat insulin promoter.

    PubMed

    Annerén, Cecilia; Welsh, Michael; Jansson, Leif

    2007-04-01

    The FRK tyrosine kinase has previously been shown to transduce beta-cell cytotoxic signals in response to cytokines and streptozotocin and to promote beta-cell proliferation and an increased beta-cell mass. We therefore aimed to further evaluate the effects of overexpression of FRK tyrosine kinase in beta-cells. A transgenic mouse expressing kinase-active FRK under control of the insulin promoter (RIP-FRK) was studied with regard to islet endocrine function and vascular morphology. Mild glucose intolerance develops in RIP-FRK male mice of at least 4 mo of age. This effect is accompanied by reduced glucose-stimulated insulin secretion in vivo and reduced second-phase insulin secretion in response to glucose and arginine upon pancreas perfusion. Islets isolated from the FRK transgenic mice display a glucose-induced insulin secretory response in vitro similar to that of control islets. However, islet blood flow per islet volume is decreased in the FRK transgenic mice. These mice also exhibit a reduced islet capillary lumen diameter as shown by electron microscopy. Total body weight and pancreas weight are not significantly affected, but the beta-cell mass is increased. The data suggest that long-term expression of active FRK in beta-cells causes an in vivo insulin-secretory defect, which may be the consequence of islet vascular abnormalities that yield a decreased islet blood flow.

  2. Postprandial glucagon-like peptide-1 secretion is increased during the progression of glucose intolerance and obesity in high-fat/high-sucrose diet-fed rats.

    PubMed

    Nakajima, Shingo; Hira, Tohru; Hara, Hiroshi

    2015-05-14

    Glucagon-like peptide-1 (GLP-1) is secreted by distal enteroendocrine cells in response to luminal nutrients, and exerts insulinotropic and anorexigenic effects. Although GLP-1 secretory responses under established obese or diabetic conditions have been studied, it has not been investigated whether or how postprandial GLP-1 responses were affected during the progression of diet-induced obesity. In the present study, a meal tolerance test was performed every week in rats fed a high-fat and high-sucrose (HF/HS) diet to evaluate postprandial glycaemic, insulin and GLP-1 responses. In addition, gastric emptying was assessed by the acetaminophen method. After 8 weeks of HF/HS treatment, portal vein and intestinal mucosa were collected to examine GLP-1 production. Postprandial glucose in response to normal meal ingestion was increased in the HF/HS group within 2 weeks, and its elevation gradually returned close to that of the control group until day 50. Slower postprandial gastric emptying was observed in the HF/HS group on days 6, 13 and 34. Postprandial GLP-1 and insulin responses were increased in the HF/HS group at 7 weeks. Higher portal GLP-1 and insulin levels were observed in the HF/HS group, but mucosal gut hormone mRNA levels were unchanged. These results revealed that the postprandial GLP-1 response to meal ingestion is enhanced during the progression of diet-induced glucose intolerance and obesity in rats. The boosted postprandial GLP-1 secretion by chronic HF/HS diet treatment suggests increased sensitivity to luminal nutrients in the gut, and this may slow the establishment of glucose intolerance and obesity. PMID:25827219

  3. Postprandial glucagon-like peptide-1 secretion is increased during the progression of glucose intolerance and obesity in high-fat/high-sucrose diet-fed rats.

    PubMed

    Nakajima, Shingo; Hira, Tohru; Hara, Hiroshi

    2015-05-14

    Glucagon-like peptide-1 (GLP-1) is secreted by distal enteroendocrine cells in response to luminal nutrients, and exerts insulinotropic and anorexigenic effects. Although GLP-1 secretory responses under established obese or diabetic conditions have been studied, it has not been investigated whether or how postprandial GLP-1 responses were affected during the progression of diet-induced obesity. In the present study, a meal tolerance test was performed every week in rats fed a high-fat and high-sucrose (HF/HS) diet to evaluate postprandial glycaemic, insulin and GLP-1 responses. In addition, gastric emptying was assessed by the acetaminophen method. After 8 weeks of HF/HS treatment, portal vein and intestinal mucosa were collected to examine GLP-1 production. Postprandial glucose in response to normal meal ingestion was increased in the HF/HS group within 2 weeks, and its elevation gradually returned close to that of the control group until day 50. Slower postprandial gastric emptying was observed in the HF/HS group on days 6, 13 and 34. Postprandial GLP-1 and insulin responses were increased in the HF/HS group at 7 weeks. Higher portal GLP-1 and insulin levels were observed in the HF/HS group, but mucosal gut hormone mRNA levels were unchanged. These results revealed that the postprandial GLP-1 response to meal ingestion is enhanced during the progression of diet-induced glucose intolerance and obesity in rats. The boosted postprandial GLP-1 secretion by chronic HF/HS diet treatment suggests increased sensitivity to luminal nutrients in the gut, and this may slow the establishment of glucose intolerance and obesity.

  4. Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

    PubMed

    Chou, Chu-Lin; Pang, Cheng-Yoong; Lee, Tony J F; Fang, Te-Chao

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose

  5. Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

    PubMed

    Chou, Chu-Lin; Pang, Cheng-Yoong; Lee, Tony J F; Fang, Te-Chao

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose

  6. Intra-uterine undernutrition amplifies age-associated glucose intolerance in pigs via altered DNA methylation at muscle GLUT4 promoter.

    PubMed

    Wang, Jun; Cao, Meng; Yang, Mei; Lin, Yan; Che, Lianqiang; Fang, Zhengfeng; Xu, Shengyu; Feng, Bin; Li, Jian; Wu, De

    2016-08-01

    The present study aimed to investigate the effect of maternal malnutrition on offspring glucose tolerance and the epigenetic mechanisms involved. In total, twelve primiparous Landrace×Yorkshire gilts were fed rations providing either 100 % (control (CON)) or 75 % (undernutrition (UN)) nutritional requirements according to the National Research Council recommendations, throughout gestation. Muscle samples of offspring were collected at birth (dpn1), weaning (dpn28) and adulthood (dpn189). Compared with CON pigs, UN pigs showed lower serum glucose concentrations at birth, but showed higher serum glucose and insulin concentrations as well as increased area under the blood glucose curve during intravenous glucose tolerance test at dpn189 (P<0·05). Compared with CON pigs, GLUT-4 gene and protein expressions were decreased at dpn1 and dpn189 in the muscle of UN pigs, which was accompanied by increased methylation at the GLUT4 promoter (P<0·05). These alterations in methylation concurred with increased mRNA levels of DNA methyltransferase (DNMT) 1 at dpn1 and dpn28, DNMT3a at dpn189 and DNMT3b at dpn1 in UN pigs compared with CON pigs (P<0·05). Interestingly, although the average methylation levels at the muscle GLUT4 promoter were decreased at dpn189 compared with dpn1 in pigs exposed to a poor maternal diet (P<0·05), the methylation differences in individual CpG sites were more pronounced with age. Our results indicate that in utero undernutrition persists to silence muscle GLUT4 likely through DNA methylation during the ageing process, which may lead to the amplification of age-associated glucose intolerance. PMID:27265204

  7. Fish oil and argan oil intake differently modulate insulin resistance and glucose intolerance in a rat model of dietary-induced obesity.

    PubMed

    Samane, Samira; Christon, Raymond; Dombrowski, Luce; Turcotte, Stéphane; Charrouf, Zoubida; Lavigne, Charles; Levy, Emile; Bachelard, Hélène; Amarouch, Hamid; Marette, André; Haddad, Pierre Selim

    2009-07-01

    We investigated the potential metabolic benefits of fish oil (FO) or vegetable argan oil (AO) intake in a dietary model of obesity-linked insulin resistance. Rats were fed a standard chow diet (controls), a high-fat/high-sucrose (HFHS) diet, or an HFHS diet in which 6% of the fat was replaced by either FO or AO feeding, respectively. The HFHS diet increased adipose tissue weight and insulin resistance as revealed by increased fasting glucose and exaggerated glycemic and insulin responses to a glucose tolerance test (intraperitoneal glucose tolerance test). Fish oil feeding prevented fat accretion, reduced fasting glycemia, and normalized glycemic or insulin responses to intraperitoneal glucose tolerance test as compared with HFHS diet. Unlike FO consumption, AO intake failed to prevent obesity, yet restored fasting glycemia back to chow-fed control values. Insulin-induced phosphorylation of Akt and Erk in adipose tissues, skeletal muscles, and liver was greatly attenuated in HFHS rats as compared with chow-fed controls. High-fat/high-sucrose diet-induced insulin resistance was also confirmed in isolated hepatocytes. Fish oil intake prevented insulin resistance by improving or fully restoring insulin signaling responses in all tissues and isolated hepatocytes. Argan oil intake also improved insulin-dependent phosphorylations of Akt and Erk; and in adipose tissue, these responses were increased even beyond values observed in chow-fed controls. Taken together, these results strongly support the beneficial action of FO on diet-induced insulin resistance and glucose intolerance, an effect likely explained by the ability of FO to prevent HFHS-induced adiposity. Our data also show for the first time that AO can improve some of the metabolic and insulin signaling abnormalities associated with HFHS feeding.

  8. Estimate of prevalence of glucose intolerance in chronic liver disease. Degree of agreement among some diagnostic criteria.

    PubMed

    Buzzelli, G; Chiarantini, E; Cotrozzi, G; Relli, P; Matassi, L; Romanelli, R G; Gentilini, P

    1988-12-01

    In patients with chronic liver disease, the reliability of various criteria generally used to diagnose impaired glucose tolerance and diabetes was evaluated. Twenty-one patients with chronic persistent hepatitis, 68 patients with chronic active hepatitis and 57 patients with liver cirrhosis were studied. All subjects underwent an oral glucose tolerance test (75 g). Impaired glucose tolerance and diabetes were diagnosed according to the criteria established by: the National Diabetes Study Group; Fajans and Conn; the European Diabetes Study Group; Deutsche Diabetes Gesellschaft; Kobberling & Creutzfeld criteria 1 and 2; Wilkerson; and the University Group Diabetes Program. The results obtained are in partial agreement with other reported data, showing a high prevalence of both impaired glucose tolerance and diabetes in chronic liver disease, with a positive correlation to the severity of hepatic involvement. However, our results show that the agreement among the criteria most frequently used for diagnosing impaired glucose tolerance and diabetes is still far from satisfactory.

  9. Fish oil ameliorates trimethylamine N-oxide-exacerbated glucose intolerance in high-fat diet-fed mice.

    PubMed

    Gao, Xiang; Xu, Jie; Jiang, Chengzi; Zhang, Yi; Xue, Yong; Li, Zhaojie; Wang, Jingfeng; Xue, Changhu; Wang, Yuming

    2015-04-01

    Trimethylamine N-oxide (TMAO), a component commonly present in seafood, has been found to have a harmful impact on glucose tolerance in high-fat diet (HFD)-fed mice. However, seafood also contains fish oil (FO), which has been shown to have beneficial effects on metabolism. Here, we investigated the effect of FO on TMAO-induced impaired glucose tolerance in HFD-fed mice. Male C57BL/6 mice were randomly assigned to the high fat (HF), TMAO, and fish oil groups. The HF group was fed a diet containing 25% fat, the TMAO group was fed the HFD plus 0.2% TMAO, and the FO group was fed the HFD plus 0.2% TMAO and 2% fish oil for 12 weeks. After 10 weeks of feeding, oral glucose tolerance tests were performed. Dietary FO improved the fasting glucose level, the fasting insulin level, HOMA-IR value, QUICKI score and ameliorated TMAO-induced exacerbated impaired glucose tolerance in HFD-fed mice. These effects were associated with the expression of genes related to the insulin signalling pathway, glycogen synthesis, gluconeogenesis, and glucose transport in peripheral tissues. Dietary fish oil also decreased TMAO-aggravated adipose tissue inflammation. Our results suggested that dietary FO ameliorated TMAO-induced impaired glucose tolerance, insulin signal transduction in peripheral tissue, and adipose tissue inflammation in HFD-fed mice.

  10. Blood and urine responses to ingesting fluids of various salt and glucose concentrations. [to combat orthostatic intolerance

    NASA Technical Reports Server (NTRS)

    Frey, Mary A.; Riddle, Jeanne; Charles, John B.; Bungo, Michael W.

    1991-01-01

    To compensate for the reduced blood and fluid volumes that develop during weightlessness, the Space Shuttle crewmembers consume salt tablets and water equivalent to 1 l of normal saline, about 2 hrs before landing. This paper compares the effects on blood, urine, and cardiovascular variables of the ingestion of 1 l of normal (0.9 percent) saline with the effects of distilled water, 1 percent glucose, 0.74 percent saline with 1 percent glucose, 0.9 percent saline with 1 percent glucose, and 1.07 percent saline. It was found that the expansion of plasma volume and the concentration of urine were greater 4 hrs after ingestion of 1.07 percent saline solution than after ingestion of normal saline and that the solutions containig glucose did not enhance any variables as compared with normal saline.

  11. Relationship of glycemic control markers - 1,5 anhydroglucitol, fructosamine, and glycated hemoglobin among Asian Indians with different degrees of glucose intolerance

    PubMed Central

    Pramodkumar, Thyparambil Aravindakshan; Jayashri, Ramamoorthy; Gokulakrishnan, Kuppan; Velmurugan, Kaliyaperumal; Pradeepa, Rajendra; Anjana, Ranjit Mohan; Mohan, Viswanathan

    2016-01-01

    Objective: 1,5 anhydroglucitol (1,5 AG) is emerging as a marker of short-term glycemic control. We measured levels of 1,5 AG, fructosamine (FA), and glycated hemoglobin (HbA1c) in Asian Indians with different degrees of glucose intolerance. Materials and Methods: We recruited 210 individuals with normal glucose tolerance (NGT; n = 60), impaired glucose tolerance (IGT; n = 50), and Type 2 diabetes mellitus (T2DM; n = 100) from a large tertiary diabetes center in Chennai in Southern India. Anthropometric measurements were obtained using standardized techniques. Serum 1,5 AG (enzymatic colorimetric assay), FA (NBT/kinetic), and HbA1c (high-performance liquid chromatography) estimations were performed. Results: 1,5 AG levels were significantly lower in the T2DM followed by IGT compared with the NGT group (7.9 vs. 18.8 vs. 21.8 µg/ml, P < 0.05). FA and HbA1c were higher in T2DM and IGT compared with NGT individuals (313 vs. 237 vs. 200 µmol/L, P < 0.001) (8.3 vs. 5.8 vs. 5.3%, P < 0.001).1,5 AG showed a significant negative correlation with FA (r = −0.618, P < 0.001) and HbA1c (r = −0.700, P < 0.001). 1,5 AG decreased with increasing quartiles of postprandial glucose (P for trend <0.001). However, even among individuals with HbA1c ≤7%, 27% individuals had decreased 1,5 AG plasma level (<10 µg/ml). Conclusion: Circulatory levels of 1,5 AG correlate negatively with FA and HbA1c, and may provide an additional marker to assess glycemic control in patients with Type 2 diabetes. PMID:27730082

  12. Mice Deficient in Proglucagon-Derived Peptides Exhibit Glucose Intolerance on a High-Fat Diet but Are Resistant to Obesity.

    PubMed

    Takagi, Yusuke; Kinoshita, Keita; Ozaki, Nobuaki; Seino, Yusuke; Murata, Yoshiharu; Oshida, Yoshiharu; Hayashi, Yoshitaka

    2015-01-01

    Homozygous glucagon-GFP knock-in mice (Gcggfp/gfp) lack proglucagon derived-peptides including glucagon and GLP-1, and are normoglycemic. We have previously shown that Gcggfp/gfp show improved glucose tolerance with enhanced insulin secretion. Here, we studied glucose and energy metabolism in Gcggfp/gfp mice fed a high-fat diet (HFD). Male Gcggfp/gfp and Gcggfp/+ mice were fed either a normal chow diet (NCD) or an HFD for 15-20 weeks. Regardless of the genotype, mice on an HFD showed glucose intolerance, and Gcggfp/gfp mice on HFD exhibited impaired insulin secretion whereas Gcggfp/+ mice on HFD exhibited increased insulin secretion. A compensatory increase in β-cell mass was observed in Gcggfp/+mice on HFD, but not in Gcggfp/gfp mice on the same diet. Weight gain was significantly lower in Gcggfp/gfp mice than in Gcggfp/+mice. Oxygen consumption was enhanced in Gcggfp/gfp mice compared to Gcggfp/+ mice on an HFD. HFD feeding significantly increased uncoupling protein 1 mRNA expression in brown adipose and inguinal white adipose tissues of Gcggfp/gfp mice, but not of Gcggfp/+mice. Treatment with the glucagon-like peptide-1 receptor agonist liraglutide (200 mg/kg) improved glucose tolerance in Gcggfp/gfp mice and insulin content in Gcggfp/gfp and Gcggfp/+ mice was similar after liraglutide treatment. Our findings demonstrate that Gcggfp/gfp mice develop diabetes upon HFD-feeding in the absence of proglucagon-derived peptides, although they are resistant to diet-induced obesity.

  13. Developmental Programming by Maternal Insulin Resistance: Hyperinsulinemia, Glucose Intolerance, and Dysregulated Lipid Metabolism in Male Offspring of Insulin-Resistant Mice

    PubMed Central

    Isganaitis, Elvira; Woo, Melissa; Ma, Huijuan; Chen, Michael; Kong, Wen; Lytras, Aristides; Sales, Vicencia; DeCoste-Lopez, Jennifer; Lee, Kyung-Ju; Leatherwood, Cianna; Lee, Deborah; Fitzpatrick, Connor; Gall, Walter; Watkins, Steven; Patti, Mary-Elizabeth

    2014-01-01

    Maternal obesity and gestational diabetes mellitus (GDM) are associated with obesity and diabetes risk in offspring. We tested whether maternal insulin resistance, which frequently coexists with GDM and obesity, could independently contribute to dysregulation of offspring metabolism. Female mice haploinsufficient for insulin receptor substrate-1 (IRS1-het) are hyperinsulinemic and insulin resistant during pregnancy, despite normal plasma glucose and body weight, and thus serve as a model of isolated maternal insulin resistance. Wild-type (WT) offspring of IRS1-het dams insulin resistance-exposed [IR-exposed] were compared with WT offspring of WT dams. Despite no differences in adiposity, male IR-exposed pups were glucose intolerant (P = 0.04) and hyperinsulinemic (1.3-fold increase, P = 0.02) by 1 month of age and developed progressive fasting hyperglycemia. Moreover, male IR-exposed pups challenged with high-fat diet exhibited insulin resistance. Liver lipidomic analysis of 3-week-old IR-exposed males revealed increases in the 16:1n7 fraction of several lipid classes, suggesting increased Scd1 activity. By 6 months of age, IR-exposed males had increased lipid accumulation in liver as well as increased plasma refed fatty acids, consistent with disrupted lipid metabolism. Our results indicate that isolated maternal insulin resistance, even in the absence of hyperglycemia or obesity, can promote metabolic perturbations in male offspring. PMID:24186867

  14. αB-crystallin and HspB2 deficiency is protective from diet-induced glucose intolerance.

    PubMed

    Toft, Daniel J; Fuller, Miles; Schipma, Matthew; Chen, Feng; Cryns, Vincent L; Layden, Brian T

    2016-09-01

    Emerging evidence suggests molecular chaperones have a role in the pathogenesis of obesity and diabetes. As αB-crystallin and HspB2 are molecular chaperones and data suggests their expression is elevated in the skeletal muscle of diabetic and obese animals, we sought to determine if αB-crystallin and HspB2 collectively play a functional role in the metabolic phenotype of diet-induced obesity. Using αB-crystallin/HspB2 knockout and littermate wild-type controls, it was observed that mice on the high fat diet gained more weight as compared to the normal chow group and genotype did not impact this weight gain. To test if the genotype and/or diet influenced glucose homeostasis, intraperitoneal glucose challenge was performed. While similar on normal chow diet, wild-type mice on the high fat diet exhibited higher glucose levels during the glucose challenge compared to the αB-crystallin/HspB2 knockout mice. Although wild-type mice had higher glucose levels, insulin levels were similar for both genotypes. Insulin tolerance testing revealed that αB-crystallin/HspB2 knockout mice were more sensitive to insulin, leading to lower glucose levels over time, which is indicative of a difference in insulin sensitivity between the genotypes on a high fat diet. Transcriptome analyses of skeletal muscle in αB-crystallin/HspB2 knockout and wild-type mice on a normal or high fat diet revealed reductions in cytokine pathway genes in αB-crystallin/HspB2 knockout mice, which may contribute to their improved insulin sensitivity. Collectively, these data reveal that αB-crystallin/HspB2 plays a role in development of insulin resistance during a high fat diet challenge. PMID:27330996

  15. Heat intolerance

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003094.htm Heat intolerance To use the sharing features on this ... must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Contact Us Get ...

  16. Cold intolerance

    MedlinePlus

    Some causes of cold intolerance are: Anemia Anorexia nervosa Blood vessel problems, such as Raynaud phenomenon Chronic severe illness General poor health Underactive thyroid ( hypothyroidism ) Problem with the hypothalamus (a part ...

  17. Comparison of lymphomononuclear cell energy metabolism between healthy, impaired glucose intolerance and type 2 diabetes mellitus patients.

    PubMed

    Ozsari, L; Karadurmus, N; Sahin, M; Uckaya, G; Ural, A U; Kutlu, M

    2010-02-01

    Diabetes mellitus (DM) is a complex disease that affects many systems. The most important cells of the immune system are lymphomononuclear (LMN) cells. Here, we aimed to evaluate the energy metabolism of LMN cells in patients with diabetes and impaired glucose tolerance. We measured LMN cell energy metabolism in patients with type 2 diabetes mellitus, impaired glucose tolerance (IGT) and healthy subjects. Cells were freshly isolated from peripheral blood and the subgroups were determined by flow cytometric method. Lactate production and glycogen utilization were significantly increased in the LMN cells of patients with type 2 DM and IGT when compared with healthy volunteers. No statistical difference was observed between the patients with type 2 DM and IGT. There was a significant correlation between fasting plasma glucose and lactate production in LMN cells. LMN cells changed their energy pathway in a diabetic state and preferred anaerobic glycolysis. Prediabetic range also affected energy metabolism in LMN cells. This abnormal energy production might cause dysfunction in LMN cells and the immune system in diabetic and prediabetic patients. In conclusion, we concluded that impaired glucose metabolism could change energy metabolism.

  18. Intrauterine protein restriction combined with early postnatal overfeeding was not associated with adult-onset obesity but produced glucose intolerance by pancreatic dysfunction

    PubMed Central

    2013-01-01

    We investigated if whether intrauterine protein restriction in combination with overfeeding during lactation would cause adult-onset obesity and metabolic disorders. After birth, litters from dams fed with control (17% protein) and low protein (6% protein) diets were adjusted to a size of four (CO and LO groups, respectively) or eight (CC and LC groups, respectively) pups. All of the offspring were fed a diet containing 12% protein from the time of weaning until they were 90 d old. Compared to the CC and LC groups, the CO and LO groups had higher relative and absolute food intakes, oxygen consumption and carbon dioxide production; lower brown adipose tissue weight and lipid content and greater weight gain and absolute and relative white adipose tissue weight and absolute lipid content. Compared with the CO and CC rats, the LC and LO rats exhibited higher relative food intake, brown adipose tissue weight and lipid content, reduced oxygen consumption, carbon dioxide production and spontaneous activity, increased relative retroperitoneal adipose tissue weight and unaltered absolute white adipose tissue weight and lipid content. The fasting serum glucose was similar among the groups. The area under the glucose curve was higher in the LO and CO rats than in the LC and CC rats. The basal insulinemia and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in the LO group than in the other groups. The total area under the insulin curve for the LO rats was similar to the CC rats, and both were lower than the CO and LC rats. Kitt was higher in the LO, LC and CO groups than in the CC group. Thus, intrauterine protein restriction followed by overfeeding during lactation did not induce obesity, but produced glucose intolerance by impairing pancreatic function in adulthood. PMID:23305533

  19. Intrauterine protein restriction combined with early postnatal overfeeding was not associated with adult-onset obesity but produced glucose intolerance by pancreatic dysfunction.

    PubMed

    Coutinho, Grazielle Vitória Ponti; Coutinho, Felipe Rodrigues; Faiad, Jaline Zandonato; Taki, Marina Satie; de Lima Reis, Silvia Regina; Ignácio-Souza, Letícia Martins; Paiva, Adriene Alexandra; Latorraca, Márcia Queiroz; Gomes-da-Silva, Maria Helena Gaíva; Martins, Maria Salete Ferreira

    2013-01-01

    We investigated if whether intrauterine protein restriction in combination with overfeeding during lactation would cause adult-onset obesity and metabolic disorders. After birth, litters from dams fed with control (17% protein) and low protein (6% protein) diets were adjusted to a size of four (CO and LO groups, respectively) or eight (CC and LC groups, respectively) pups. All of the offspring were fed a diet containing 12% protein from the time of weaning until they were 90 d old. Compared to the CC and LC groups, the CO and LO groups had higher relative and absolute food intakes, oxygen consumption and carbon dioxide production; lower brown adipose tissue weight and lipid content and greater weight gain and absolute and relative white adipose tissue weight and absolute lipid content. Compared with the CO and CC rats, the LC and LO rats exhibited higher relative food intake, brown adipose tissue weight and lipid content, reduced oxygen consumption, carbon dioxide production and spontaneous activity, increased relative retroperitoneal adipose tissue weight and unaltered absolute white adipose tissue weight and lipid content. The fasting serum glucose was similar among the groups. The area under the glucose curve was higher in the LO and CO rats than in the LC and CC rats. The basal insulinemia and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in the LO group than in the other groups. The total area under the insulin curve for the LO rats was similar to the CC rats, and both were lower than the CO and LC rats. Kitt was higher in the LO, LC and CO groups than in the CC group. Thus, intrauterine protein restriction followed by overfeeding during lactation did not induce obesity, but produced glucose intolerance by impairing pancreatic function in adulthood. PMID:23305533

  20. A dietary pattern including nopal, chia seed, soy protein, and oat reduces serum triglycerides and glucose intolerance in patients with metabolic syndrome.

    PubMed

    Guevara-Cruz, Martha; Tovar, Armando R; Aguilar-Salinas, Carlos A; Medina-Vera, Isabel; Gil-Zenteno, Lidia; Hernández-Viveros, Isaac; López-Romero, Patricia; Ordaz-Nava, Guillermo; Canizales-Quinteros, Samuel; Guillen Pineda, Luz E; Torres, Nimbe

    2012-01-01

    Metabolic syndrome (MetS) is a health problem throughout the world and is associated with cardiovascular disease and diabetes. Thus, the purpose of the present work was to evaluate the effects of a dietary pattern (DP; soy protein, nopal, chia seed, and oat) on the biochemical variables of MetS, the AUC for glucose and insulin, glucose intolerance (GI), the relationship of the presence of certain polymorphisms related to MetS, and the response to the DP. In this randomized trial, the participants consumed their habitual diet but reduced by 500 kcal for 2 wk. They were then assigned to the placebo (P; n = 35) or DP (n = 32) group and consumed the reduced energy diet plus the P or DP beverage (235 kcal) minus the energy provided by these for 2 mo. All participants had decreases in body weight (BW), BMI, and waist circumference during the 2-mo treatment (P < 0.0001); however, only the DP group had decreases in serum TG, C-reactive protein (CRP), and AUC for insulin and GI after a glucose tolerance test. Interestingly, participants in the DP group with MetS and the ABCA1 R230C variant had a greater decrease in BW and an increase in serum adiponectin concentration after 2 mo of dietary treatment than those with the ABCA1 R230R variant. The results from this study suggest that lifestyle interventions involving specific DP for the treatment of MetS could be more effective if local foods and genetic variations of the population are considered. PMID:22090467

  1. A dietary pattern including nopal, chia seed, soy protein, and oat reduces serum triglycerides and glucose intolerance in patients with metabolic syndrome.

    PubMed

    Guevara-Cruz, Martha; Tovar, Armando R; Aguilar-Salinas, Carlos A; Medina-Vera, Isabel; Gil-Zenteno, Lidia; Hernández-Viveros, Isaac; López-Romero, Patricia; Ordaz-Nava, Guillermo; Canizales-Quinteros, Samuel; Guillen Pineda, Luz E; Torres, Nimbe

    2012-01-01

    Metabolic syndrome (MetS) is a health problem throughout the world and is associated with cardiovascular disease and diabetes. Thus, the purpose of the present work was to evaluate the effects of a dietary pattern (DP; soy protein, nopal, chia seed, and oat) on the biochemical variables of MetS, the AUC for glucose and insulin, glucose intolerance (GI), the relationship of the presence of certain polymorphisms related to MetS, and the response to the DP. In this randomized trial, the participants consumed their habitual diet but reduced by 500 kcal for 2 wk. They were then assigned to the placebo (P; n = 35) or DP (n = 32) group and consumed the reduced energy diet plus the P or DP beverage (235 kcal) minus the energy provided by these for 2 mo. All participants had decreases in body weight (BW), BMI, and waist circumference during the 2-mo treatment (P < 0.0001); however, only the DP group had decreases in serum TG, C-reactive protein (CRP), and AUC for insulin and GI after a glucose tolerance test. Interestingly, participants in the DP group with MetS and the ABCA1 R230C variant had a greater decrease in BW and an increase in serum adiponectin concentration after 2 mo of dietary treatment than those with the ABCA1 R230R variant. The results from this study suggest that lifestyle interventions involving specific DP for the treatment of MetS could be more effective if local foods and genetic variations of the population are considered.

  2. Acute inhibition of central c-Jun N-terminal kinase restores hypothalamic insulin signalling and alleviates glucose intolerance in diabetic mice.

    PubMed

    Benzler, J; Ganjam, G K; Legler, K; Stöhr, S; Krüger, M; Steger, J; Tups, A

    2013-05-01

    The hypothalamus has been identified as a main insulin target tissue for regulating normal body weight and glucose metabolism. Recent observations suggest that c-Jun-N-terminal kinase (JNK)-signalling plays a crucial role in the development of obesity and insulin resistance because neuronal JNK-1 ablation in the mouse prevented high-fat diet-induced obesity (DIO) and increased energy expenditure, as well as insulin sensitivity. In the present study, we investigated whether central JNK inhibition is associated with sensitisation of hypothalamic insulin signalling in mice fed a high-fat diet for 3 weeks and in leptin-deficient mice. We determined whether i.c.v. injection of a pharmacological JNK-inhibitor (SP600125) improved impaired glucose homeostasis. By immunohistochemistry, we first observed that JNK activity was increased in the arcuate nucleus (ARC) and the ventromedial hypothalamus (VMH) in both mouse models, relative to normoglycaemic controls. This suggests that up-regulation of JNK in these regions is associated with glucose intolerance and obesity, independent of leptin levels. Acute i.c.v. injection of SP600125 ameliorated glucose tolerance within 30 min in both leptin-deficient and DIO mice. Given the acute nature of i.c.v. injections, these effects cannot be attributed to changes in food intake or energy balance. In a hypothalamic cell line, and in the ARC and VMH of leptin-deficient mice, JNK inhibition by SP600125 consistently improved impaired insulin signalling. This was determined by a reduction of phospho-insulin receptor substrate-1 [IRS-1(Ser612)] protein in a hypothalamic cell line and a decline in the number of pIRS-1(Ser612) immunoreactive cells in the ARC and VMH. Serine 612 phosphorylation of IRS-1 is assumed to negatively regulate insulin signalling. In leptin-deficient mice, in both nuclei, central inhibition of JNK increased the number of cells immunoreactive for phospho-Akt (Ser473) and phospho-GSK-3β (Ser9), which are important

  3. Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice.

    PubMed

    Deprez-Poulain, Rebecca; Hennuyer, Nathalie; Bosc, Damien; Liang, Wenguang G; Enée, Emmanuelle; Marechal, Xavier; Charton, Julie; Totobenazara, Jane; Berte, Gonzague; Jahklal, Jouda; Verdelet, Tristan; Dumont, Julie; Dassonneville, Sandrine; Woitrain, Eloise; Gauriot, Marion; Paquet, Charlotte; Duplan, Isabelle; Hermant, Paul; Cantrelle, François-Xavier; Sevin, Emmanuel; Culot, Maxime; Landry, Valerie; Herledan, Adrien; Piveteau, Catherine; Lippens, Guy; Leroux, Florence; Tang, Wei-Jen; van Endert, Peter; Staels, Bart; Deprez, Benoit

    2015-09-23

    Insulin-degrading enzyme (IDE) is a protease that cleaves insulin and other bioactive peptides such as amyloid-β. Knockout and genetic studies have linked IDE to Alzheimer's disease and type-2 diabetes. As the major insulin-degrading protease, IDE is a candidate drug target in diabetes. Here we have used kinetic target-guided synthesis to design the first catalytic site inhibitor of IDE suitable for in vivo studies (BDM44768). Crystallographic and small angle X-ray scattering analyses show that it locks IDE in a closed conformation. Among a panel of metalloproteases, BDM44768 selectively inhibits IDE. Acute treatment of mice with BDM44768 increases insulin signalling and surprisingly impairs glucose tolerance in an IDE-dependent manner. These results confirm that IDE is involved in pathways that modulate short-term glucose homeostasis, but casts doubt on the general usefulness of the inhibition of IDE catalytic activity to treat diabetes.

  4. Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice

    SciTech Connect

    Deprez-Poulain, Rebecca; Hennuyer, Nathalie; Bosc, Damien; Liang, Wenguang G.; Enée, Emmanuelle; Marechal, Xavier; Charton, Julie; Totobenazara, Jane; Berte, Gonzague; Jahklal, Jouda; Verdelet, Tristan; Dumont, Julie; Dassonneville, Sandrine; Woitrain, Eloise; Gauriot, Marion; Paquet, Charlotte; Duplan, Isabelle; Hermant, Paul; Cantrelle, François- Xavier; Sevin, Emmanuel; Culot, Maxime; Landry, Valerie; Herledan, Adrien; Piveteau, Catherine; Lippens, Guy; Leroux, Florence; Tang, Wei-Jen; van Endert, Peter; Staels, Bart; Deprez, Benoit

    2015-09-23

    Insulin-degrading enzyme (IDE) is a protease that cleaves insulin and other bioactive peptides such as amyloid-β. Knockout and genetic studies have linked IDE to Alzheimer’s disease and type-2 diabetes. As the major insulin-degrading protease, IDE is a candidate drug target in diabetes. Here we have used kinetic target-guided synthesis to design the first catalytic site inhibitor of IDE suitable for in vivo studies (BDM44768). Crystallographic and small angle X-ray scattering analyses show that it locks IDE in a closed conformation. Among a panel of metalloproteases, BDM44768 selectively inhibits IDE. Acute treatment of mice with BDM44768 increases insulin signalling and surprisingly impairs glucose tolerance in an IDE-dependent manner. These results confirm that IDE is involved in pathways that modulate short-term glucose homeostasis, but casts doubt on the general usefulness of the inhibition of IDE catalytic activity to treat diabetes.

  5. Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice

    PubMed Central

    Deprez-Poulain, Rebecca; Hennuyer, Nathalie; Bosc, Damien; Liang, Wenguang G.; Enée, Emmanuelle; Marechal, Xavier; Charton, Julie; Totobenazara, Jane; Berte, Gonzague; Jahklal, Jouda; Verdelet, Tristan; Dumont, Julie; Dassonneville, Sandrine; Woitrain, Eloise; Gauriot, Marion; Paquet, Charlotte; Duplan, Isabelle; Hermant, Paul; Cantrelle, François- Xavier; Sevin, Emmanuel; Culot, Maxime; Landry, Valerie; Herledan, Adrien; Piveteau, Catherine; Lippens, Guy; Leroux, Florence; Tang, Wei-Jen; van Endert, Peter; Staels, Bart; Deprez, Benoit

    2015-01-01

    Insulin-degrading enzyme (IDE) is a protease that cleaves insulin and other bioactive peptides such as amyloid-β. Knockout and genetic studies have linked IDE to Alzheimer's disease and type-2 diabetes. As the major insulin-degrading protease, IDE is a candidate drug target in diabetes. Here we have used kinetic target-guided synthesis to design the first catalytic site inhibitor of IDE suitable for in vivo studies (BDM44768). Crystallographic and small angle X-ray scattering analyses show that it locks IDE in a closed conformation. Among a panel of metalloproteases, BDM44768 selectively inhibits IDE. Acute treatment of mice with BDM44768 increases insulin signalling and surprisingly impairs glucose tolerance in an IDE-dependent manner. These results confirm that IDE is involved in pathways that modulate short-term glucose homeostasis, but casts doubt on the general usefulness of the inhibition of IDE catalytic activity to treat diabetes. PMID:26394692

  6. [Lactose intolerance].

    PubMed

    Rosado, Jorge L

    2016-09-01

    The most common problem limiting milk consumption worldwide is lactose intolerance (LI), which is defined as the experience of gastrointestinal symptoms due to the intake of lactose-containing food. When symptoms ensue the intake of milk, the condition is referred as milk intolerance, and it may or may not be due to LI. The most common cause of LI is primary lactase deficiency which occurs in 30% of Mexican adults when one glass of milk is consumed (12-18 g of lactose). LI occurs in less than 15% of adults after the intake of this dose of lactose. Another cause of lactose intolerance is due to secondary lactase deficiency, which occurs because lactase is reduced due to diseases that affect the intestinal mucosa. Lactose intolerance can be eliminated or significantly reduced by elimination or reduction of the intake of milk and milk containing products. Recent studies demonstrate that when β-casein-A1 contained in milk is hydrolyzed it produces β-casomorphine-7 which is an opioid associated with milk intolerance.

  7. Lactose intolerance.

    PubMed

    Swagerty, Daniel L; Walling, Anne D; Klein, Robert M

    2002-05-01

    Persons with lactose intolerance are unable to digest significant amounts of lactose because of a genetically inadequate amount of the enzyme lactase. Common symptoms include abdominal pain and bloating, excessive flatus, and watery stool following the ingestion of foods containing lactose. Lactase deficiency is present in up to 15 percent of persons of northern European descent, up to 80 percent of blacks and Latinos, and up to 100 percent of American Indians and Asians. A sizable number of adults believe they are lactose intolerant but do not actually have impaired lactose digestion, and some persons with lactase deficiency can tolerate moderate amounts of ingested lactose. A diagnosis of lactose intolerance can usually be made with a careful history supported by dietary manipulation. If necessary, diagnosis can be confirmed by using a breath hydrogen or lactose tolerance test. Treatment consists primarily of avoiding lactose-containing foods. Lactase enzyme supplements may be helpful. The degree of lactose malabsorption varies greatly among patients with lactose intolerance, but most of them can ingest up to 12 oz of milk daily without symptoms. Lactose-intolerant patients must ensure adequate calcium intake. PMID:12018807

  8. [Lactose intolerance].

    PubMed

    Rosado, Jorge L

    2016-09-01

    The most common problem limiting milk consumption worldwide is lactose intolerance (LI), which is defined as the experience of gastrointestinal symptoms due to the intake of lactose-containing food. When symptoms ensue the intake of milk, the condition is referred as milk intolerance, and it may or may not be due to LI. The most common cause of LI is primary lactase deficiency which occurs in 30% of Mexican adults when one glass of milk is consumed (12-18 g of lactose). LI occurs in less than 15% of adults after the intake of this dose of lactose. Another cause of lactose intolerance is due to secondary lactase deficiency, which occurs because lactase is reduced due to diseases that affect the intestinal mucosa. Lactose intolerance can be eliminated or significantly reduced by elimination or reduction of the intake of milk and milk containing products. Recent studies demonstrate that when β-casein-A1 contained in milk is hydrolyzed it produces β-casomorphine-7 which is an opioid associated with milk intolerance. PMID:27603891

  9. Adipose tissue hypoxia and low-grade inflammation: a possible mechanism for ethanol-related glucose intolerance?

    PubMed

    He, Zhen; Li, Min; Zheng, Dongmei; Chen, Qing; Liu, Wenwen; Feng, Li

    2015-05-14

    The exact mechanism of ethanol's effects on glucose tolerance has not been well determined. The present study focuses for the first time on hypoxia and low-grade inflammation in adipose tissue (AT). In the in vivo experiments, twenty-four male Wistar rats were randomly allocated into control and ethanol feeding groups. Ethanol-treated rats received edible ethanol once a day at a total dosage of 5 g/kg per d, and the controls received distilled water. Ethanol volumes were adjusted every week. At the end of 8 weeks, we carried out an oral glucose tolerance test. Blood and AT were collected for measuring hypoxia-inducible factor-1α (HIF-1α), GLUT1, TNF-α, IL-6, leptin and vascular endothelial growth factor (VEGF). In the in vitro experiments, differentiated OP9 adipocytes were incubated with 100 mm of ethanol for 48 h; the media and cells were then collected for measuring HIF-1α, GLUT1, TNF-α and IL-6. The results showed that long-term ethanol consumption impaired glucose tolerance in rats. Ethanol consumption had little influence on body weight, but both epididymal and perirenal AT were markedly enlarged in the ethanol-treated rats as compared to the controls. Visceral adipose tissue (VAT) had accumulated, and the protein levels of HIF-1α and GLUT1, the indicators of hypoxia in rat epididymal AT and OP9 adipocytes, were elevated. Secondary to the AT hypoxia, the levels of inflammation-related adipokines, such as TNF-α, IL-6, leptin and VEGF, were increased. Based on these findings, we conclude that VAT hypoxia and low-grade inflammation might be a new mechanism in the treatment of ethanol-related diabetes.

  10. Effects of combined olmesartan and pravastatin on glucose intolerance and cardiovascular remodeling in a metabolic-syndrome model.

    PubMed

    Mizukawa, Mizuki; Ohmori, Koji; Obayashi, Ayumi; Ishihara, Yasuhiro; Yoshida, Junji; Noma, Takahisa; Yukiiri, Kazushi; Kosaka, Hiroaki; Kohno, Masakazu

    2009-07-01

    Hypertension and dyslipidemia frequently coexist in patients with progressive insulin resistance and thus constitute metabolic syndrome. We sought to determine the merits of combining an angiotensin II receptor blocker and a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor in treating this pathological condition. Five-week-old Otsuka Long-Evans Tokushima Fatty rats, a model of metabolic syndrome, were untreated or treated with olmesartan 3 mg kg(-1) per day, pravastatin 30 mg kg(-1) per day or their combination for 25 weeks. Long-Evans Tokushima Otsuka rats served as normal controls. The antihypertensive effect of olmesartan and the lipid-lowering properties of pravastatin were both augmented by the combination. The oral glucose tolerance test revealed that only the combined treatment significantly reduced the area under the time-glucose curve, which was accompanied by augmented adiponectin messenger RNA expression in epididymal adipose tissue. Although the total cardiac endothelial nitric oxide synthetase (eNOS) content did not significantly differ among the groups, the combined treatment significantly increased the content of dihydrofolate reductase, a key eNOS coupler. Dihydroethidium staining of the aorta showed that the combination most significantly attenuated superoxide production. Moreover, Azan-Mallory staining revealed that the combination most significantly limited the perivascular fibrosis and wall thickening of intramyocardial coronary arteries. In conclusion, the combination of olmesartan and pravastatin augmented adiponectin expression in white adipose tissue and improved glucose tolerance in a rat model of metabolic syndrome, which was associated with more significant ameliorations of cardiovascular redox state and remodeling than those by treatments with either agent alone. PMID:19461650

  11. Intestine-specific Deletion of Acyl-CoA:Monoacylglycerol Acyltransferase (MGAT) 2 Protects Mice from Diet-induced Obesity and Glucose Intolerance*

    PubMed Central

    Nelson, David W.; Gao, Yu; Yen, Mei-I; Yen, Chi-Liang Eric

    2014-01-01

    The absorption of dietary fat involves the re-esterification of digested triacylglycerol in the enterocytes, a process catalyzed by acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2. Mice without a functional gene encoding MGAT2 (Mogat2−/−) are protected from diet-induced obesity. Surprisingly, these mice absorb normal amounts of dietary fat but increase their energy expenditure. MGAT2 is expressed in tissues besides intestine, including adipose tissue in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, we generated and characterized mice deficient in MGAT2 specifically in the small intestine (Mogat2IKO). We found that, like Mogat2−/− mice, Mogat2IKO mice also showed a delay in fat absorption, a decrease in food intake, and a propensity to use fatty acids as fuel when first exposed to a high fat diet. Mogat2IKO mice increased energy expenditure although to a lesser degree than Mogat2−/− mice and were protected against diet-induced weight gain and associated comorbidities, including hepatic steatosis, hypercholesterolemia, and glucose intolerance. These findings illustrate that intestinal lipid metabolism plays a crucial role in the regulation of systemic energy balance and may be a feasible intervention target. In addition, they suggest that MGAT activity in extraintestinal tissues may also modulate energy metabolism. PMID:24784138

  12. Pathological Type-2 Immune Response, Enhanced Tumor Growth, and Glucose Intolerance in Retnlβ (RELMβ) Null Mice: A Model of Intestinal Immune System Dysfunction in Disease Susceptibility.

    PubMed

    Wernstedt Asterholm, Ingrid; Kim-Muller, Ja Young; Rutkowski, Joseph M; Crewe, Clair; Tao, Caroline; Scherer, Philipp E

    2016-09-01

    Resistin, and its closely related homologs, the resistin-like molecules (RELMs) have been implicated in metabolic dysregulation, inflammation, and cancer. Specifically, RELMβ, expressed predominantly in the goblet cells in the colon, is released both apically and basolaterally, and is hence found in both the intestinal lumen in the mucosal layer as well as in the circulation. RELMβ has been linked to both the pathogenesis of colon cancer and type 2 diabetes. RELMβ plays a complex role in immune system regulation, and the impact of loss of function of RELMβ on colon cancer and metabolic regulation has not been fully elucidated. We therefore tested whether Retnlβ (mouse ortholog of human RETNLβ) null mice have an enhanced or reduced susceptibility for colon cancer as well as metabolic dysfunction. We found that the lack of RELMβ leads to increased colonic expression of T helper cell type-2 cytokines and IL-17, associated with a reduced ability to maintain intestinal homeostasis. This defect leads to an enhanced susceptibility to the development of inflammation, colorectal cancer, and glucose intolerance. In conclusion, the phenotype of the Retnlβ null mice unravels new aspects of inflammation-mediated diseases and strengthens the notion that a proper intestinal barrier function is essential to sustain a healthy phenotype. PMID:27397737

  13. Intestine-specific deletion of acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2 protects mice from diet-induced obesity and glucose intolerance.

    PubMed

    Nelson, David W; Gao, Yu; Yen, Mei-I; Yen, Chi-Liang Eric

    2014-06-20

    The absorption of dietary fat involves the re-esterification of digested triacylglycerol in the enterocytes, a process catalyzed by acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2. Mice without a functional gene encoding MGAT2 (Mogat2(-/-)) are protected from diet-induced obesity. Surprisingly, these mice absorb normal amounts of dietary fat but increase their energy expenditure. MGAT2 is expressed in tissues besides intestine, including adipose tissue in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, we generated and characterized mice deficient in MGAT2 specifically in the small intestine (Mogat2(IKO)). We found that, like Mogat2(-/-) mice, Mogat2(IKO) mice also showed a delay in fat absorption, a decrease in food intake, and a propensity to use fatty acids as fuel when first exposed to a high fat diet. Mogat2(IKO) mice increased energy expenditure although to a lesser degree than Mogat2(-/-) mice and were protected against diet-induced weight gain and associated comorbidities, including hepatic steatosis, hypercholesterolemia, and glucose intolerance. These findings illustrate that intestinal lipid metabolism plays a crucial role in the regulation of systemic energy balance and may be a feasible intervention target. In addition, they suggest that MGAT activity in extraintestinal tissues may also modulate energy metabolism.

  14. Amelioration of obesity and glucose intolerance in high-fat-fed C57BL/6 mice by anthocyanins and ursolic acid in Cornelian cherry (Cornus mas).

    PubMed

    Jayaprakasam, Bolleddula; Olson, L Karl; Schutzki, Robert E; Tai, Mei-Hui; Nair, Muraleedharan G

    2006-01-11

    Much attention has been focused on food that may be beneficial in preventing diet-induced body fat accumulation and possibly reduce the risk of diabetes and heart disease. Cornelian cherries (Cornus mas) are used in the preparation of beverages in Europe and also to treat diabetes-related disorders in Asia. In this study, the most abundant bioactive compounds in C. mas fruits, the anthocyanins and ursolic acid, were purified, and their ability to ameliorate obesity and insulin resistance in C57BL/6 mice fed a high-fat diet was evaluated. Mice were initially fed a high-fat diet for 4 weeks and then switched to a high-fat diet containing anthocyanins (1 g/kg of high-fat diet) and ursolic acid (500 mg/kg of high-fat diet) for an additional 8 weeks. The high-fat diet induced glucose intolerance, and this was prevented by anthocyanins and ursolic acid. The anthocyanin-treated mice showed a 24% decrease in weight gain. These mice also showed decreased lipid accumulation in the liver, including a significant decrease in liver triacylglycerol concentration. Anthocyanin and ursolic acid treated mice exhibited extremely elevated insulin levels. Both treatments, however, showed preserved islet architecture and insulin staining. Overall, these data suggest that anthocyanins and ursolic acid purified from C. mas fruits have biological activities that improve certain metabolic parameters associated with diets high in saturated fats and obesity. PMID:16390206

  15. Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice

    PubMed Central

    DiSilvestro, David J.; Melgar-Bermudez, Emiliano; Yasmeen, Rumana; Fadda, Paolo; Lee, L. James; Kalyanasundaram, Anuradha; Gilor, Chen L.; Ziouzenkova, Ouliana

    2016-01-01

    The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin. PMID:27055280

  16. Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice

    DOE PAGESBeta

    Deprez-Poulain, Rebecca; Hennuyer, Nathalie; Bosc, Damien; Liang, Wenguang G.; Enée, Emmanuelle; Marechal, Xavier; Charton, Julie; Totobenazara, Jane; Berte, Gonzague; Jahklal, Jouda; et al

    2015-09-23

    Insulin-degrading enzyme (IDE) is a protease that cleaves insulin and other bioactive peptides such as amyloid-β. Knockout and genetic studies have linked IDE to Alzheimer’s disease and type-2 diabetes. As the major insulin-degrading protease, IDE is a candidate drug target in diabetes. Here we have used kinetic target-guided synthesis to design the first catalytic site inhibitor of IDE suitable for in vivo studies (BDM44768). Crystallographic and small angle X-ray scattering analyses show that it locks IDE in a closed conformation. Among a panel of metalloproteases, BDM44768 selectively inhibits IDE. Acute treatment of mice with BDM44768 increases insulin signalling and surprisinglymore » impairs glucose tolerance in an IDE-dependent manner. These results confirm that IDE is involved in pathways that modulate short-term glucose homeostasis, but casts doubt on the general usefulness of the inhibition of IDE catalytic activity to treat diabetes.« less

  17. Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice.

    PubMed

    DiSilvestro, David J; Melgar-Bermudez, Emiliano; Yasmeen, Rumana; Fadda, Paolo; Lee, L James; Kalyanasundaram, Anuradha; Gilor, Chen L; Ziouzenkova, Ouliana

    2016-01-01

    The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin. PMID:27055280

  18. The effective fraction isolated from Radix Astragali alleviates glucose intolerance, insulin resistance and hypertriglyceridemia in db/db diabetic mice through its anti-inflammatory activity

    PubMed Central

    2010-01-01

    Background Macrophage infiltration in adipose tissue together with the aberrant production of pro-inflammatory cytokines has been identified as the key link between obesity and its related metabolic disorders. This study aims to isolate bioactive ingredients from the traditional Chinese herb Radix Astragali (Huangqi) that alleviate obesity-induced metabolic damage through inhibiting inflammation. Methods Active fraction (Rx) that inhibits pro-inflammatory cytokine production was identified from Radix Astragali by repeated bioactivity-guided high-throughput screening. Major constituents in Rx were identified by column chromatography followed by high-performance liquid chromatography (HPLC) and mass-spectrometry. Anti-diabetic activity of Rx was evaluated in db/db mice. Results Treatment with Rx, which included calycosin-7-β-D-glucoside (0.9%), ononin (1.2%), calycosin (4.53%) and formononetin (1.1%), significantly reduced the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and MCP-1) in human THP-1 macrophages and lipopolysaccharide (LPS)-induced activation of NF-κB in mouse RAW-Blue macrophages in a dose-dependent manner. Chronic administration of Rx in db/db obese mice markedly decreased the levels of both fed and fasting glucose, reduced serum triglyceride, and also alleviated insulin resistance and glucose intolerance when compared to vehicle-treated controls. The mRNA expression levels of inflammatory cell markers CD68 and F4/80, and cytokines MCP-1, TNF-α and IL-6 were significantly reduced in epididymal adipose tissue while the alternatively activated macrophage marker arginase I was markedly increased in the Rx-treated mice. Conclusion These findings suggest that suppression of the inflammation pathways in macrophages represents a valid strategy for high-throughput screening of lead compounds with anti-diabetic and insulin sensitizing properties, and further support the etiological role of inflammation in the pathogenesis of obesity

  19. Statin intolerance.

    PubMed

    Ahmad, Zahid

    2014-05-15

    The term statin intolerance refers to an inability to use statins because of muscle symptoms or elevated creatine kinase, and the major diagnostic challenge is to unambiguously link these to statin use. Roughly 5% to 10% of statin users develop statin intolerance, and because statin use is expected to increase--especially after recent updated guidelines have expanded the statin benefit groups--adverse effects from statins will become a growing issue. Unfortunately, the pathophysiology--and even the terminology--of statin-related muscle injury lacks clarity. Several risk factors have been identified, including advanced age, family history of myopathy and statin dose; many cases manifest only after patients are administered an interacting medication (e.g., azole antifungals, cimetidine, clarithromycin, erythromycin and cyclosporine). The diagnosis of myopathy remains challenging, especially because some patients can have normal serum creatine kinase levels despite demonstrable weakness and muscle biopsy-proven statin-induced myopathy. A statin withdrawal and rechallenge helps patients distinguish whether their myalgia symptoms are because of statins, but, in at least 1 clinical trial, even 5% of placebo-treated patients developed myalgias during a controlled withdrawal and rechallenge. No consensus exists for management of patients with statin intolerance. Many patients can eventually tolerate a statin but often at suboptimal doses. A subset of patients do well with nondaily regimens such as every other day or once weekly dosing. Some patients cannot tolerate statins at all, requiring nonstatin lipid-lowering medications--the benefit of which remains unclear with regard to preventing atherosclerotic events. Ultimately, statin intolerance undermines the drug adherence that is critical for achieving the benefits of lifelong lipid-lowering therapy. In conclusion, statin myopathy is a common challenge in lipid management, and further work is needed to establish a

  20. Intolerant tolerance.

    PubMed

    Khushf, G

    1994-04-01

    The Hyde Amendment and Roman Catholic attempts to put restrictions on Title X funding have been criticized for being intolerant. However, such criticism fails to appreciate that there are two competing notions of tolerance, one focusing on the limits of state force and accepting pluralism as unavoidable, and the other focusing on the limits of knowledge and advancing pluralism as a good. These two types of tolerance, illustrated in the writings of John Locke and J.S. Mill, each involve an intolerance. In a pluralistic context where the free exercise of religion is respected, John Locke's account of tolerance is preferable. However, it (in a reconstructed form) leads to a minimal state. Positive entitlements to benefits like artificial contraception or nontherapeutic abortions can legitimately be resisted, because an intolerance has already been shown with respect to those that consider the benefit immoral, since their resources have been coopted by taxation to advance an end that is contrary to their own. There is a sliding scale from tolerance (viewed as forbearance) to the affirmation of communal integrity, and this scale maps on to the continuum from negative to positive rights.

  1. Usefulness of C-Reactive Protein Plasma Levels to Predict Exercise Intolerance in Patients With Chronic Systolic Heart Failure.

    PubMed

    Canada, Justin McNair; Fronk, Daniel Taylor; Cei, Laura Freeman; Carbone, Salvatore; Erdle, Claudia Oddi; Abouzaki, Nayef Antar; Melchior, Ryan David; Thomas, Christopher Scott; Christopher, Sanah; Turlington, Jeremy Shane; Trankle, Cory Ross; Thurber, Clinton Joseph; Evans, Ronald Kenneth; Dixon, Dave L; Van Tassell, Benjamin Wallace; Arena, Ross; Abbate, Antonio

    2016-01-01

    Patients with heart failure (HF) have evidence of chronic systemic inflammation. Whether inflammation contributes to the exercise intolerance in patients with HF is, however, not well established. We hypothesized that the levels of C-reactive protein (CRP), an established inflammatory biomarker, predict impaired cardiopulmonary exercise performance, in patients with chronic systolic HF. We measured CRP using high-sensitivity particle-enhanced immunonephelometry in 16 patients with ischemic heart disease (previous myocardial infarction) and chronic systolic HF, defined as a left ventricular ejection fraction ≤ 50% and New York Heart Association class II-III symptoms. All subjects with CRP >2 mg/L, reflecting systemic inflammation, underwent cardiopulmonary exercise testing using a symptom-limited ramp protocol. CRP levels predicted shorter exercise times (R = -0.65, p = 0.006), lower oxygen consumption (VO2) at the anaerobic threshold (R = -0.66, p = 0.005), and lower peak VO2 (R = -0.70, p = 0.002), reflecting worse cardiovascular performance. CRP levels also significantly correlated with an elevated ventilation/carbon dioxide production slope (R = +0.64, p = 0.008), a reduced oxygen uptake efficiency slope (R = -0.55, p = 0.026), and reduced end-tidal CO2 level at rest and with exercise (R = -0.759, p = 0.001 and R = -0.739, p = 0.001, respectively), reflecting impaired gas exchange. In conclusion, the intensity of systemic inflammation, measured as CRP plasma levels, is associated with cardiopulmonary exercise performance, in patients with ischemic heart disease and chronic systolic HF. These data provide the rationale for targeted anti-inflammatory treatments in HF. PMID:26546248

  2. Lactose intolerance.

    PubMed

    Vandenplas, Yvan

    2015-01-01

    Lactose is the main carbohydrate in infant feeding, but its impact decreases as the child gets older and consumes less milk and dairy products. Congenital lactose intolerance is a very rare condition. However, lactase activity may be low and need to mature during the first weeks of life in many infants. However, the evidence that unabsorbed lactose is causing infantile crying and colic is contradictory. Unabsorbed lactose has a bifidogenic effect and improves calcium absorption. Lactose malabsorption may occur secondary and thus temporally to other etiologies such as infectious gastroenteritis, cow's milk allergy and celiac disease. One the cause is treated, lactase activity will gradually return to normal. The vast majority of Asian children will develop late onset congenital lactase deficiency. However, this entity only exceptionally causes symptoms before the age of 4-5 years. Symptoms are abdominal cramps, flatulence and watery, acid stools, and decrease the quality of life but lactose intolerance is not associated with "true disease". The diagnosis is made on clinical grounds and confirmed with a lactose breath test, if needed. These patients need to have a lifetime long reduced lactose intake to improve their quality of life.

  3. Lactose intolerance.

    PubMed

    Vandenplas, Yvan

    2015-01-01

    Lactose is the main carbohydrate in infant feeding, but its impact decreases as the child gets older and consumes less milk and dairy products. Congenital lactose intolerance is a very rare condition. However, lactase activity may be low and need to mature during the first weeks of life in many infants. However, the evidence that unabsorbed lactose is causing infantile crying and colic is contradictory. Unabsorbed lactose has a bifidogenic effect and improves calcium absorption. Lactose malabsorption may occur secondary and thus temporally to other etiologies such as infectious gastroenteritis, cow's milk allergy and celiac disease. One the cause is treated, lactase activity will gradually return to normal. The vast majority of Asian children will develop late onset congenital lactase deficiency. However, this entity only exceptionally causes symptoms before the age of 4-5 years. Symptoms are abdominal cramps, flatulence and watery, acid stools, and decrease the quality of life but lactose intolerance is not associated with "true disease". The diagnosis is made on clinical grounds and confirmed with a lactose breath test, if needed. These patients need to have a lifetime long reduced lactose intake to improve their quality of life. PMID:26715083

  4. The H1-receptor antagonist cetirizine ameliorates high-fat diet-induced glucose intolerance in male C57BL/6 mice, but not diabetes outcome in female non-obese diabetic (NOD) mice

    PubMed Central

    Anvari, Ebrahim; Wang, Xuan; Sandler, Stellan

    2015-01-01

    Background It has been proposed that the histamine 1-receptor (H1-receptor) not only promotes allergic reactions, but also modulates innate immunity and autoimmune reactions. In line with this, we have recently reported that the H1-receptor antagonist cetirizine partially counteracts cytokine-induced beta-cell signaling and destruction. Therefore, the aim of this study was to determine whether cetirizine affects diabetes in NOD mice, a model for human type 1 diabetes, and glucose intolerance in high-fat diet C57BL/6 mice, a model for human glucose intolerance. Methods Female NOD mice were treated with cetirizine in the drinking water (25 mg/kg body weight) from 9 until 30 weeks of age during which precipitation of diabetes was followed. Male C57BL/6 mice were given a high-fat diet from 5 weeks of age. When the mice were 12 weeks of age cetirizine was given for 2 weeks in the drinking water. The effects of cetirizine were analyzed by blood glucose determinations, glucose tolerance tests, and insulin sensitivity tests. Results Cetirizine did not affect diabetes development in NOD mice. On the other hand, cetirizine treatment for 1 week protected against high-fat diet-induced hyperglycemia. The glucose tolerance after 2 weeks of cetirizine treatment was improved in high-fat diet mice. We observed no effect of cetirizine on the insulin sensitivity of high-fat diet mice. Conclusion Our results suggest a protective effect of cetirizine against high-fat diet-induced beta-cell dysfunction, but not against autoimmune beta-cell destruction. PMID:25291144

  5. Potentiation of insulin secretion and improvement of glucose intolerance by combining a novel G protein-coupled receptor 40 agonist DS-1558 with glucagon-like peptide-1 receptor agonists.

    PubMed

    Nakashima, Ryutaro; Yano, Tatsuya; Ogawa, Junko; Tanaka, Naomi; Toda, Narihiro; Yoshida, Masao; Takano, Rieko; Inoue, Masahiro; Honda, Takeshi; Kume, Shoen; Matsumoto, Koji

    2014-08-15

    G protein-coupled receptor 40 (GPR40) is a Gq-coupled receptor for free fatty acids predominantly expressed in pancreatic β-cells. In recent years, GPR40 agonists have been investigated for use as novel therapeutic agents in the treatment of type 2 diabetes. We discovered a novel small molecule GPR40 agonist, (3S)-3-ethoxy-3-(4-{[(1R)-4-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy}phenyl)propanoic acid (DS-1558). The GPR40-mediated effects of DS-1558 on glucose-stimulated insulin secretion were evaluated in isolated islets from GPR40 knock-out and wild-type (littermate) mice. The GPR40-mediated effects on glucose tolerance and insulin secretion were also confirmed by an oral glucose tolerance test in these mice. Furthermore, oral administration of DS-1558 (0.03, 0.1 and 0.3mg/kg) significantly and dose-dependently improved hyperglycemia and increased insulin secretion during the oral glucose tolerance test in Zucker fatty rats, the model of insulin resistance and glucose intolerance. Next, we examined the combination effects of DS-1558 with glucagon like peptide-1 (GLP-1). DS-1558 not only increased the glucose-stimulated insulin secretion by GLP-1 but also potentiated the maximum insulinogenic effects of GLP-1 after an intravenous glucose injection in normal Sprague Dawley rats. Furthermore, the glucose lowering effects of exendin-4, a GLP-1 receptor agonist, were markedly potentiated by the DS-1558 (3mg/kg) add-on in diabetic db/db mice during an intraperitoneal glucose tolerance test. In conclusion, our results indicate that add-on GPR40 agonists to GLP-1 related agents might be a potential treatment compared to single administration of these compounds. Therefore the combinations of these agents are a novel therapeutic option for type 2 diabetes.

  6. Rationale, design, and method of the Diabetes & Women's Health study--a study of long-term health implications of glucose intolerance in pregnancy and their determinants.

    PubMed

    Zhang, Cuilin; Hu, Frank B; Olsen, Sjurdur F; Vaag, Allan; Gore-Langton, Robert; Chavarro, Jorge E; Bao, Wei; Yeung, Edwina; Bowers, Katherine; Grunnet, Louise G; Sherman, Seth; Kiely, Michele; Strøm, Marin; Hansen, Susanne; Liu, Aiyi; Mills, James; Fan, Ruzong

    2014-11-01

    Women who develop gestational diabetes mellitus or impaired glucose tolerance during pregnancy are at substantially increased risk for type 2 diabetes and comorbidities after pregnancy. Little is known about the role of genetic factors and their interactions with environmental factors in determining the transition from gestational diabetes mellitus to overt type 2 diabetes mellitus. These critical data gaps served as the impetus for this Diabetes & Women's Health study with the overall goal of investigating genetic factors and their interactions with risk factors amenable to clinical or public health interventions in relation to the transition of gestational diabetes mellitus to type 2 diabetes mellitus. To achieve the goal efficiently, we are applying a hybrid design enrolling and collecting data longitudinally from approximately 4000 women with a medical history of gestational diabetes mellitus in two existing prospective cohorts, the Nurses' Health Study II and the Danish National Birth Cohort. Women who had a medical history of gestational diabetes mellitus in one or more of their pregnancies are eligible for the present study. After enrollment, we follow study participants for an additional 2 years to collect updated information on major clinical and environmental factors that may predict type 2 diabetes mellitus risk as well as with biospecimens to measure genetic and biochemical markers implicated in glucose metabolism. Newly collected data will be appended to the relevant existing data for the creation of a new database inclusive of genetic, epigenetic and environmental data. Findings from the study are critical for the development of targeted and more effective strategies to prevent type 2 diabetes mellitus and its complications in this high-risk population.

  7. Sterol regulatory element-binding factor 2 (SREBF-2) predicts 7-year NAFLD incidence and severity of liver disease and lipoprotein and glucose dysmetabolism.

    PubMed

    Musso, Giovanni; Cassader, Maurizio; Bo, Simona; De Michieli, Franco; Gambino, Roberto

    2013-04-01

    We prospectively assessed the impact of a sterol regulatory element-binding factor-2 (SREBF-2) polymorphism on the risk of developing nonalcoholic fatty liver disease (NAFLD) and on liver histology and lipoprotein and glucose metabolism in biopsy-proven NAFLD. In a population-based study, we followed 175 nonobese, nondiabetic participants without NAFLD or metabolic syndrome at baseline, characterized for the SREBF-2 rs133291 C/T polymorphism, dietary habits, physical activity, adipokines, C-reactive protein (CRP), and endothelial adhesion molecules. A comparable cohort of NAFLD patients underwent liver biopsy, an oral glucose tolerance test with minimal model analysis to yield glucose homeostasis parameters, and an oral fat tolerance test with measurement of plasma lipoproteins, adipokines, and cytokeratin-18 fragments. After 7 years, 27% of subjects developed NAFLD and 5% developed diabetes. SREBF-2 predicted incident NAFLD and diabetes and CRP and endothelial adhesion molecule changes. In biopsy-proven NAFLD patients, SREBF-2 predicted nonalcoholic steatohepatitis (odds ratio 2.92 [95% CI 2.08-4.18], P = 0.002) and the severity of tissue insulin resistance, β-cell dysfunction, and oral fat intolerance (characterized by higher postprandial lipemia, cholesterol enrichment of triglyceride-rich lipoproteins and oxidized LDLs, HDL cholesterol fall, adipokine imbalance, and postprandial apoptosis activation). An SREBF-2 polymorphism predisposes individuals to NAFLD and associated cardiometabolic abnormalities and affects liver histology and glucose and lipid metabolism in biopsy-proven NAFLD.

  8. A predictive and feedback control algorithm maintains a constant glucose concentration in fed-batch fermentations.

    PubMed

    Kleman, G L; Chalmers, J J; Luli, G W; Strohl, W R

    1991-04-01

    A combined predictive and feedback control algorithm based on measurements of the concentration of glucose on-line has been developed to control fed-batch fermentations of Escherichia coli. The predictive control algorithm was based on the on-line calculation of glucose demand by the culture and plotting a linear regression to the next datum point to obtain a predicted glucose demand. This provided a predictive "coarse" control for the glucose-based nutrient feed. A direct feedback control using a proportional controller, based on glucose measurements every 2 min, fine-tuned the feed rate. These combined control schemes were used to maintain glucose concentrations in fed-batch fermentations as tight as 0.49 +/- 0.04 g/liter during growth of E. coli to high cell densities. PMID:2059049

  9. A predictive and feedback control algorithm maintains a constant glucose concentration in fed-batch fermentations.

    PubMed Central

    Kleman, G L; Chalmers, J J; Luli, G W; Strohl, W R

    1991-01-01

    A combined predictive and feedback control algorithm based on measurements of the concentration of glucose on-line has been developed to control fed-batch fermentations of Escherichia coli. The predictive control algorithm was based on the on-line calculation of glucose demand by the culture and plotting a linear regression to the next datum point to obtain a predicted glucose demand. This provided a predictive "coarse" control for the glucose-based nutrient feed. A direct feedback control using a proportional controller, based on glucose measurements every 2 min, fine-tuned the feed rate. These combined control schemes were used to maintain glucose concentrations in fed-batch fermentations as tight as 0.49 +/- 0.04 g/liter during growth of E. coli to high cell densities. PMID:2059049

  10. Evidence for Association between Polycystic Ovary Syndrome (PCOS) and TCF7L2 and Glucose Intolerance in Women with PCOS and TCF7L2

    PubMed Central

    Biyasheva, Assel; Legro, Richard S.; Dunaif, Andrea; Urbanek, Margrit

    2009-01-01

    Context and Objective: Of the recently identified type 2 diabetes mellitus (T2D) susceptibility loci, transcription factor 7-like 2 (TCF7L2) confers the greatest relative risk for T2D and significantly predicts conversion to T2D in persons with impaired glucose tolerance. TCF7L2 is, therefore, also a strong candidate gene for polycystic ovary syndrome (PCOS), a common endocrine disorder characterized by androgen excess and menstrual irregularities and associated with insulin resistance and a 7-fold increased risk for T2D. Research Design and Methods: We tested for association between 58 single nucleotide polymorphisms mapping to TCF7L2 and PCOS in 624 index (PCOS) cases and 553 control women of European ancestry. Furthermore, in the women with PCOS, we tested for association with seven reproductive and metabolic quantitative traits. Results: Although we did not detect evidence for association between the previously described TCF7L2 T2D locus, the proinsulin:insulin molar ratio, a marker of pancreatic β-cell dysfunction, was strongly associated with this locus (P = 2.1 × 10−4). We also observed evidence for association between PCOS and two single nucleotide polymorphisms, rs11196236 (P = 9.0 × 10−4) and rs11196229 (P = 0.0027) mapping more than 100 kb centromeric to the previously published T2D susceptibility loci. Conclusions: We have observed evidence of association with two independent TCF7L2 loci in a PCOS cohort: 1) association between the proinsulin:insulin molar ratio and the T2D locus; and 2) association with reproductive PCOS phenotype and a novel locus. This study suggests that variation in different regions of a susceptibility gene contributes to distinct phenotypes. PMID:19351735

  11. An assessment by the Statin Intolerance Panel: 2014 update.

    PubMed

    Guyton, John R; Bays, Harold E; Grundy, Scott M; Jacobson, Terry A; The National Lipid Association Statin Intolerance Panel

    2014-01-01

    This article from the National Lipid Association Statin Intolerance Panel provides a framework for understanding statin intolerance and makes general recommendations for health professionals. For specific guidance on adverse events related to muscle, liver, cognition, and glucose metabolism, one should refer to the other reports of the Statin Safety Task Force for those topics. Although statin adverse effects rarely lead to permanent sequelae, symptomatic intolerance frequently hinders cardiovascular risk reduction by statins. We emphasize here the advisory role of the clinician helping each patient to make personal decisions on statin tolerability. We identify a pressing need for further research on statin intolerance and make suggestions for research design.

  12. The importance of diabetes heredity in lean subjects on insulin secretion, blood lipids and oxygen uptake in the pathogenesis of glucose intolerance.

    PubMed

    Berntorp, K; Eriksson, K F; Lindgärde, F

    1986-06-01

    Insulin secretion, work capacity and plasma lipids were evaluated in 52 middle-aged men with impaired glucose tolerance (IGT), and the values were compared with those of 23 normoglycemic subjects with family histories of Type 2 diabetes and of 22 non-hereditary normoglycemic controls. All subjects were non-obese males of comparable age. Estimated maximal oxygen uptake was significantly lower (p less than 0.01) and triglyceride concentrations significantly higher (p less than 0.01) in IGT individuals than in subjects of the non-hereditary normoglycemic group, while no significant differences were noted in comparison with the hereditary group. IGT individuals showed an impaired insulin response to glucose with significantly lower absolute values of insulin and C-peptide during the early phase of the oral glucose tolerance test (OGTT) than in non-hereditary normoglycemic subjects, but not significantly lower than in the hereditary group. Similarly, at most time points of the OGTT the ratios of insulin and C-peptide to glucose were significantly lower in the IGT group than in the non-hereditary group, while these differences were less pronounced in comparison with the hereditary group. These findings suggest some similarities of metabolic disturbances in lean normoglycemics with positive family histories of Type 2 diabetes and in lean IGT individuals. Family history of diabetes (both first degree and second degree only) was significantly more prevalent among IGT individuals than among normals.

  13. Body iron stores and glucose intolerance in premenopausal women: role of hyperandrogenism, insulin resistance, and genomic variants related to inflammation, oxidative stress, and iron metabolism.

    PubMed

    Martínez-García, M Angeles; Luque-Ramírez, Manuel; San-Millán, José L; Escobar-Morreale, Héctor F

    2009-08-01

    OBJECTIVE Increased serum ferritin levels and iron stores may be involved in the development of abnormal glucose tolerance in women presenting with obesity and/or polycystic ovary syndrome (PCOS). We aimed to study the determinants of serum ferritin levels in premenopausal women among indexes of insulin resistance, adiposity, hyperandrogenism, and genotypes pertaining to inflammation, oxidative stress, and iron metabolism. RESEARCH DESIGN AND METHODS A total of 257 premenopausal women, classified depending on the presence or absence of PCOS, obesity, and/or abnormal glucose tolerance, underwent a complete metabolic evaluation, serum ferritin, haptoglobin, and C-reactive protein (CRP) measurements, and genotyping for proinflammatory and prooxidant variants and mutations in the HFE gene. RESULTS Serum ferritin concentrations were increased in women presenting with PCOS and/or abnormal glucose tolerance, independent of obesity. A stepwise multivariate linear regression analysis (R(2) = 0.18, P < 0.0001) retained menstrual dysfunction (beta = 0.14, P = 0.035), free testosterone (beta = 0.14, P = 0.052), insulin sensitivity index (beta = -0.12, P = 0.012), the His63Asp variant in HFE (beta = 0.16, P = 0.008), and abnormal glucose tolerance (beta = 0.15, P = 0.015) as significant predictors of the logarithm of ferritin levels, whereas CRP, haptoglobin, waist-to-hip ratio, or variants in the TNFalpha, TNFRSF1B, IL6, IL6ST, IL6Ralpha, PON1, and HFE Cys282Tyr mutation exerted no influence. CONCLUSIONS Androgen excess (partly because of hyperandrogenemia and partly because of menstrual dysfunction), insulin resistance, abnormal glucose tolerance, and the HFE His63Asp variant correlate with ferritin levels in premenopausal women.

  14. Glucocorticoid antagonism limits adiposity rebound and glucose intolerance in young male rats following the cessation of daily exercise and caloric restriction.

    PubMed

    Teich, Trevor; Dunford, Emily C; Porras, Deanna P; Pivovarov, Jacklyn A; Beaudry, Jacqueline L; Hunt, Hazel; Belanoff, Joseph K; Riddell, Michael C

    2016-07-01

    Severe caloric restriction (CR), in a setting of regular physical exercise, may be a stress that sets the stage for adiposity rebound and insulin resistance when the food restriction and exercise stop. In this study, we examined the effect of mifepristone, a glucocorticoid (GC) receptor antagonist, on limiting adipose tissue mass gain and preserving whole body insulin sensitivity following the cessation of daily running and CR. We calorically restricted male Sprague-Dawley rats and provided access to voluntary running wheels for 3 wk followed by locking of the wheels and reintroduction to ad libitum feeding with or without mifepristone (80 mg·kg(-1)·day(-1)) for 1 wk. Cessation of daily running and CR increased HOMA-IR and visceral adipose mass as well as glucose and insulin area under the curve during an oral glucose tolerance test vs. pre-wheel lock exercised rats and sedentary rats (all P < 0.05). Insulin sensitivity and glucose tolerance were preserved and adipose tissue mass gain was attenuated by daily mifepristone treatment during the post-wheel lock period. These findings suggest that following regular exercise and CR there are GC-induced mechanisms that promote adipose tissue mass gain and impaired metabolic control in healthy organisms and that this phenomenon can be inhibited by the GC receptor antagonist mifepristone.

  15. Dietary fructose intolerance, fructan intolerance and FODMAPs.

    PubMed

    Fedewa, Amy; Rao, Satish S C

    2014-01-01

    Dietary intolerances to fructose, fructans and FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) are common, yet poorly recognized and managed. Over the last decade, they have come to the forefront because of new knowledge on the mechanisms and treatment of these conditions. Patients with these problems often present with unexplained bloating, belching, distension, gas, abdominal pain, or diarrhea. Here, we have examined the most up-to-date research on these food-related intolerances, discussed controversies, and have provided some guidelines for the dietary management of these conditions. Breath testing for carbohydrate intolerance appears to be standardized and essential for the diagnosis and management of these conditions, especially in the Western population. While current research shows that the FODMAP diet may be effective in treating some patients with irritable bowel syndrome, additional research is needed to identify more foods items that are high in FODMAPs, and to assess the long-term efficacy and safety of dietary interventions.

  16. Dietary fructose intolerance, fructan intolerance and FODMAPs

    PubMed Central

    Fedewa, Amy; Rao, Satish S. C.

    2014-01-01

    Dietary intolerances to fructose, fructans and FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) are common, yet poorly recognized and managed. Over the last decade, they have come to the forefront because of new knowledge on the mechanisms and treatment of these conditions. Patients with these problems often present with unexplained bloating, belching, distension, gas, abdominal pain or diarrhea. Here, we have examined the most up-to-date research on these food-related intolerances, discussed controversies, and have provided some guidelines for the dietary management of these conditions. Breath testing for carbohydrate intolerance appears to be standardized and essential for the diagnosis and management of these conditions, especially in the Western population. While current research shows that the FODMAP diet may be effective in treating irritable bowel syndrome, additional research is needed to identify more foods items that are high in FODMAPs, and to assess the long-term efficacy and safety of dietary interventions. PMID:24357350

  17. [Efficacy of treatment-and-prophylactic diets including soya-based food in elderly patients with atherogenic dislipidemia and glucose intolerance].

    PubMed

    Shatylo, V B; Korkushko, O V; Borovs'kyĭ, V R; Anisimova, Iu M; Tarasenko, O B; Ivanova, A O

    2007-01-01

    47 elderly patients aged 60-74 with stable exertional angina of I-II functional classes and 2a type dislipidemia have been observed. The authors studied the efficacy of hypocholesteremic diet (HD) including soya-based food in comparison with the use of HD without soya-based food. Patients of the main group were prescribed HD, soya-based food (29 g of soya protein per day) and medications of a based therapy during four weeks. Patients of the control group were given HD and medications of a based therapy during the same period. The use of HD with soya-based food decreased considerably frequency and duration of exertional angina attack, increased the tolerance to physical activity resulted in more considerable decrease in concentration of blood serum common cholesterin and cholesterin of low density lipoprotein in comparison with indices of patients of the control group. Soya-based food together with HD in patients with disturbed tolerance to glucose normalized the tolerance test to glucose.

  18. Predictive roles of intraoperative blood glucose for post-transplant outcomes in liver transplantation.

    PubMed

    Park, Chul Soo

    2015-06-14

    Diabetogenic traits in patients undergoing liver transplantation (LT) are exacerbated intraoperatively by exogenous causes, such as surgical stress, steroids, blood transfusions, and catecholamines, which lead to intraoperative hyperglycemia. In contrast to the strict glucose control performed in the intensive care unit, no systematic protocol has been developed for glucose management during LT. Intraoperative blood glucose concentrations typically exceed 200 mg/dL in LT, and extreme hyperglycemia (> 300 mg/dL) is common during the neohepatic phase. Only a few retrospective studies have examined the relationship between intraoperative hyperglycemia and post-transplant complications, with reports of infectious complications or mortality. However, no prospective studies have been conducted regarding the influence of intraoperative hyperglycemia in LT on post-transplant outcome. In addition to absolute blood glucose values, the temporal patterns in blood glucose levels during LT may serve as prognostic features. Persistent neohepatic hyperglycemia (without a decline) throughout LT is a useful indicator of early graft dysfunction. Moreover, intraoperative variability in glucose levels may predict the need for reoperation for hemorrhage after LT. Thus, there is an urgent need for guidelines for glucose control in these patients, as well as prospective studies on the impact of glucose control on various post-transplant complications. This report highlights some of the recent studies related to perioperative blood glucose management focused on LT and liver disease. PMID:26078559

  19. Liver AMP/ATP ratio and fructokinase expression are related to gender differences in AMPK activity and glucose intolerance in rats ingesting liquid fructose.

    PubMed

    Vilà, Laia; Roglans, Núria; Perna, Victoria; Sánchez, Rosa M; Vázquez-Carrera, Manuel; Alegret, Marta; Laguna, Juan C

    2011-08-01

    Women, but not men, show an association between fructose consumption and an increased risk of Type 2 diabetes mellitus. As rats are considered a model for human fructose metabolism, we sought to determine whether such a gender-related difference is present in Sprague-Dawley rats and to analyze the molecular mechanism behind. Male and female Sprague-Dawley rats had free access to water or to a 10% w/v fructose solution for 14 days. Plasma analytes, liver triglycerides and enzyme activities and the expression of enzymes and transcription factors related to fatty acid metabolism, insulin signaling and glucose tolerance were determined. Fructose-fed rats had hypertriglyceridemia, steatosis and reduced fatty acid oxidation activity, although the metabolic pattern of fructose-fed female rats was different to that observed for male rats. Fructose-fed female, but not male rats, showed no change in plasma leptin; they had hyperinsulinemia, an altered glucose tolerance test and less liver insulin receptor substrate-2. Further, only fructose-fed female rats had increased adenosine 5'-monophosphate (AMP)-activated protein kinase activity, resulting in a decreased expression of hepatic nuclear factor 4 and sterol response element binding protein 1. These differences were related to the fact that liver expression of the enzyme fructokinase, controlling fructose metabolism, was markedly induced by fructose ingestion in female, but not in male rats, resulting in a significant increase in the AMP/adenosine 5'-triphosphate (ATP) ratio and, thus, AMP-activated protein kinase activation, in female rats only. The difference in fructokinase induction could explain the higher metabolic burden produced by fructose ingestion in the livers of female Sprague-Dawley rats.

  20. The molecular basis of lactose intolerance.

    PubMed

    Campbell, Anthony K; Waud, Jonathan P; Matthews, Stephanie B

    2009-01-01

    A staggering 4000 million people cannot digest lactose, the sugar in milk, properly. All mammals, apart from white Northern Europeans and few tribes in Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into galactose and glucose, after weaning. Lactose intolerance causes gut and a range of systemic symptoms, though the threshold to lactose varies considerably between ethnic groups and individuals within a group. The molecular basis of inherited hypolactasia has yet to be identified, though two polymorphisms in the introns of a helicase upstream from the lactase gene correlate closely with hypolactasia, and thus lactose intolerance. The symptoms of lactose intolerance are caused by gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial toxins may play a key role in several other diseases, such as diabetes, rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose intolerance has been exacerbated because of the addition of products containing lactose to various foods and drinks without being on the label. Lactose intolerance fits exactly the illness that Charles Darwin suffered from for over 40 years, and yet was never diagnosed. Darwin missed something else--the key to our own evolution--the Rubicon some 300 million years ago that produced lactose and lactase in sufficient amounts to be susceptible to natural selection.

  1. The molecular basis of lactose intolerance.

    PubMed

    Campbell, Anthony K; Waud, Jonathan P; Matthews, Stephanie B

    2005-01-01

    A staggering 4000 million people cannot digest lactose, the sugar in milk, properly. All mammals, apart from white Northern Europeans and few tribes in Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into galactose and glucose, after weaning. Lactose intolerance causes gut and a range of systemic symptoms, though the threshold to lactose varies considerably between ethnic groups and individuals within a group. The molecular basis of inherited hypolactasia has yet to be identified, though two polymorphisms in the introns of a helicase upstream from the lactase gene correlate closely with hypolactasia, and thus lactose intolerance. The symptoms of lactose intolerance are caused by gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial toxins may play a key role in several other diseases, such as diabetes, rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose intolerance has been exacerbated because of the addition of products containing lactose to various foods and drinks without being on the label. Lactose intolerance fits exactly the illness that Charles Darwin suffered from for over 40 years, and yet was never diagnosed. Darwin missed something else--the key to our own evolution--the Rubicon some 300 million years ago that produced lactose and lactase in sufficient amounts to be susceptible to natural selection.

  2. Ethanol extract of the Prunus mume fruits stimulates glucose uptake by regulating PPAR-γ in C2C12 myotubes and ameliorates glucose intolerance and fat accumulation in mice fed a high-fat diet.

    PubMed

    Shin, Eun Ju; Hur, Haeng Jeon; Sung, Mi Jeong; Park, Jae Ho; Yang, Hye Jeong; Kim, Myung Sunny; Kwon, Dae Young; Hwang, Jin-Taek

    2013-12-15

    In this study, we performed in vitro and in vivo studies to examine whether a 70% ethanol extract of Prunus mume fruits (EMS) exhibits anti-diabetic effects. Treatment with EMS increased glucose uptake in C2C12 myotubes, and also increased PPAR-γ activity or PPAR-γ mRNA expression. To confirm these in vitro results, we next conducted an animal experiment. A high-fat diet significantly increased the body weight, fat accumulation, and glucose levels in mice. Under the same conditions, 5% EMS attenuated the high-fat diet-induced increase in body weight and fat accumulation and improved the impaired fasting glucose level and glucose tolerance. High performance liquid chromatography analysis demonstrated that EMS contained chlorogenic acid, caffeic acid, rutin, luteolin-7-glucoside, naringin, apigenin-7-glucoside, and hesperidin. Taken together, these findings suggest that EMS exerts an anti-diabetic effect both in vitro and in vivo, which is mediated, at least in part, by the activation of PPAR-γ.

  3. Ethanol extract of the Prunus mume fruits stimulates glucose uptake by regulating PPAR-γ in C2C12 myotubes and ameliorates glucose intolerance and fat accumulation in mice fed a high-fat diet.

    PubMed

    Shin, Eun Ju; Hur, Haeng Jeon; Sung, Mi Jeong; Park, Jae Ho; Yang, Hye Jeong; Kim, Myung Sunny; Kwon, Dae Young; Hwang, Jin-Taek

    2013-12-15

    In this study, we performed in vitro and in vivo studies to examine whether a 70% ethanol extract of Prunus mume fruits (EMS) exhibits anti-diabetic effects. Treatment with EMS increased glucose uptake in C2C12 myotubes, and also increased PPAR-γ activity or PPAR-γ mRNA expression. To confirm these in vitro results, we next conducted an animal experiment. A high-fat diet significantly increased the body weight, fat accumulation, and glucose levels in mice. Under the same conditions, 5% EMS attenuated the high-fat diet-induced increase in body weight and fat accumulation and improved the impaired fasting glucose level and glucose tolerance. High performance liquid chromatography analysis demonstrated that EMS contained chlorogenic acid, caffeic acid, rutin, luteolin-7-glucoside, naringin, apigenin-7-glucoside, and hesperidin. Taken together, these findings suggest that EMS exerts an anti-diabetic effect both in vitro and in vivo, which is mediated, at least in part, by the activation of PPAR-γ. PMID:23993593

  4. Uteroplacental insufficiency leads to hypertension, but not glucose intolerance or impaired skeletal muscle mitochondrial biogenesis, in 12-month-old rats

    PubMed Central

    Tran, Melanie; Young, Margaret E; Jefferies, Andrew J; Hryciw, Deanne H; Ward, Michelle M; Fletcher, Erica L; Wlodek, Mary E; Wadley, Glenn D

    2015-01-01

    Growth restriction impacts on offspring development and increases their risk of disease in adulthood which is exacerbated with “second hits.” The aim of this study was to investigate if blood pressure, glucose tolerance, and skeletal muscle mitochondrial biogenesis were altered in 12-month-old male and female offspring with prenatal or postnatal growth restriction. Bilateral uterine vessel ligation induced uteroplacental insufficiency and growth restriction in offspring (Restricted). A sham surgery was also performed during pregnancy (Control) and some litters from sham mothers had their litter size reduced (Reduced litter), which restricted postnatal growth. Growth-restricted females only developed hypertension at 12 months, which was not observed in males. In Restricted females only homeostasis model assessment for insulin resistance was decreased, indicating enhanced hepatic insulin sensitivity, which was not observed in males. Plasma leptin was increased only in the Reduced males at 12 months compared to Control and Restricted males, which was not observed in females. Compared to Controls, leptin, ghrelin, and adiponectin were unaltered in the Restricted males and females, suggesting that at 12 months of age the reduction in body weight in the Restricted offspring is not a consequence of circulating adipokines. Skeletal muscle PGC-1α levels were unaltered in 12-month-old male and female rats, which indicate improvements in lean muscle mass by 12 months of age. In summary, sex strongly impacts the cardiometabolic effects of growth restriction in 12-month-old rats and it is females who are at particular risk of developing long-term hypertension following growth restriction. PMID:26416974

  5. Hereditary fructose intolerance

    MedlinePlus

    Fructosemia; Fructose intolerance; Fructose aldolase B-deficiency; Fructose 1, 6 bisphosphate aldolase deficiency ... B. This substance is needed to break down fructose. If a person without this substance eats fructose ...

  6. Lactose Intolerance (For Parents)

    MedlinePlus

    ... Doctors usually diagnose lactose intolerance through a simple hydrogen breath test. A person blows into a tube ... there is a higher than average level of hydrogen and methane in the breath. That's because undigested ...

  7. Gluten Intolerance Group

    MedlinePlus

    ... The Gluten Intolerance Group (GIG) empowers the gluten-free community through consumer support, advocacy, and education. • SUPPORT GIG • ... about the events taking place in your gluten-free community. Find >> Products From breads and pastas to pet ...

  8. Intolerance of Uncertainty

    PubMed Central

    Beier, Meghan L.

    2015-01-01

    Multiple sclerosis (MS) is a chronic and progressive neurologic condition that, by its nature, carries uncertainty as a hallmark characteristic. Although all patients face uncertainty, there is variability in how individuals cope with its presence. In other populations, the concept of “intolerance of uncertainty” has been conceptualized to explain this variability such that individuals who have difficulty tolerating the possibility of future occurrences may engage in thoughts or behaviors by which they attempt to exert control over that possibility or lessen the uncertainty but may, as a result, experience worse outcomes, particularly in terms of psychological well-being. This topical review introduces MS-focused researchers, clinicians, and patients to intolerance of uncertainty, integrates the concept with what is already understood about coping with MS, and suggests future steps for conceptual, assessment, and treatment-focused research that may benefit from integrating intolerance of uncertainty as a central feature. PMID:26300700

  9. [Diagnostic significance of index alpha-amylase/glucose in amniotic fluid in prediction of fetal maturity].

    PubMed

    Krasomski, G; Sałacińska, B; Broniarczyk, D; Swiatkowska, E

    2001-09-01

    An increase in alpha-amylase activity with parallel decrease in glucose concentration in amniotic fluid is observed during pregnancy. This interdependence is a theoretical basis for using an alpha-amylase/glucose index in fetal maturity evaluation. The aim of the study was to investigate usefulness of the alpha-amylase/glucose index in amniotic fluid in prenatal fetal maturity diagnosis. The study was carried out on 180 pregnant women, chosen by random selection, hospitalized in Polish Mother's Health Centre Hospital in the period from 15.06.1994 to 31.12.1995. 223 samples of amniotic fluid were tested for glucose concentration and alpha-amylase activity. It was found that the alpha-amylase/glucose < 6.0 index indicates a possibility of RDS occurring in neonates born before 72 hours of performed determination. The alpha-amylase/glucose > or = 6.0 index has high diagnostic value (95.8%) in prenatal prediction of fetal lung maturity. PMID:11757480

  10. The Research of Improved Grey GM (1, 1) Model to Predict the Postprandial Glucose in Type 2 Diabetes

    PubMed Central

    Wang, Yannian; Wei, Fenfen; Sun, Changqing; Li, Quanzhong

    2016-01-01

    Diabetes may result in some complications and increase the risk of many serious health problems. The purpose of clinical treatment is to carefully manage the blood glucose concentration. If the blood glucose concentration is predicted, treatments can be taken in advance to reduce the harm to patients. For this purpose, an improved grey GM (1, 1) model is applied to predict blood glucose with a small amount of data, and especially in terms of improved smoothness it can get higher prediction accuracy. The original data of blood glucose of type 2 diabetes is acquired by CGMS. Then the prediction model is established. Finally, 50 cases of blood glucose from the Henan Province People's Hospital are predicted in 5, 10, 15, 20, 25, and 30 minutes, respectively, in advance to verify the prediction model. The prediction result of blood glucose is evaluated by the EGA, MSE, and MAE. Particularly, the prediction results of postprandial blood glucose are presented and analyzed. The result shows that the improved grey GM (1, 1) model has excellent performance in postprandial blood glucose prediction. PMID:27314034

  11. Personalized Metabolomics for Predicting Glucose Tolerance Changes in Sedentary Women After High-Intensity Interval Training

    PubMed Central

    Kuehnbaum, Naomi L.; Gillen, Jenna B.; Gibala, Martin J.; Britz-McKibbin, Philip

    2014-01-01

    High-intensity interval training (HIIT) offers a practical approach for enhancing cardiorespiratory fitness, however its role in improving glucose regulation among sedentary yet normoglycemic women remains unclear. Herein, multi-segment injection capillary electrophoresis-mass spectrometry is used as a high-throughput platform in metabolomics to assess dynamic responses of overweight/obese women (BMI > 25, n = 11) to standardized oral glucose tolerance tests (OGTTs) performed before and after a 6-week HIIT intervention. Various statistical methods were used to classify plasma metabolic signatures associated with post-prandial glucose and/or training status when using a repeated measures/cross-over study design. Branched-chain/aromatic amino acids and other intermediates of urea cycle and carnitine metabolism decreased over time in plasma after oral glucose loading. Adaptive exercise-induced changes to plasma thiol redox and orthinine status were measured for trained subjects while at rest in a fasting state. A multi-linear regression model was developed to predict changes in glucose tolerance based on a panel of plasma metabolites measured for naïve subjects in their untrained state. Since treatment outcomes to physical activity are variable between-subjects, prognostic markers offer a novel approach to screen for potential negative responders while designing lifestyle modifications that maximize the salutary benefits of exercise for diabetes prevention on an individual level. PMID:25164777

  12. Personalized metabolomics for predicting glucose tolerance changes in sedentary women after high-intensity interval training.

    PubMed

    Kuehnbaum, Naomi L; Gillen, Jenna B; Gibala, Martin J; Britz-McKibbin, Philip

    2014-01-01

    High-intensity interval training (HIIT) offers a practical approach for enhancing cardiorespiratory fitness, however its role in improving glucose regulation among sedentary yet normoglycemic women remains unclear. Herein, multi-segment injection capillary electrophoresis-mass spectrometry is used as a high-throughput platform in metabolomics to assess dynamic responses of overweight/obese women (BMI > 25, n = 11) to standardized oral glucose tolerance tests (OGTTs) performed before and after a 6-week HIIT intervention. Various statistical methods were used to classify plasma metabolic signatures associated with post-prandial glucose and/or training status when using a repeated measures/cross-over study design. Branched-chain/aromatic amino acids and other intermediates of urea cycle and carnitine metabolism decreased over time in plasma after oral glucose loading. Adaptive exercise-induced changes to plasma thiol redox and orthinine status were measured for trained subjects while at rest in a fasting state. A multi-linear regression model was developed to predict changes in glucose tolerance based on a panel of plasma metabolites measured for naïve subjects in their untrained state. Since treatment outcomes to physical activity are variable between-subjects, prognostic markers offer a novel approach to screen for potential negative responders while designing lifestyle modifications that maximize the salutary benefits of exercise for diabetes prevention on an individual level.

  13. Continuous Glucose Monitoring in Patients with Abnormal Glucose Tolerance during Pregnancy: A Case Series.

    PubMed

    Tonoike, Mie; Kishimoto, Miyako; Yamamoto, Mayumi; Yano, Tetsu; Noda, Mitsuhiko

    2016-01-01

    Abnormal glucose tolerance during pregnancy is associated with perinatal complications. We used continuous glucose monitoring (CGM) in pregnant women with glucose intolerance to achieve better glycemic control and to evaluate the maternal glucose fluctuations. We also used CGM in women without glucose intolerance (the control cases). Furthermore, the standard deviation (SD) and mean amplitude of glycemic excursions (MAGE) were calculated for each case. For the control cases, the glucose levels were tightly controlled within a very narrow range; however, the SD and MAGE values in pregnant women with glucose intolerance were relativity high, suggesting postprandial hyperglycemia. Our results demonstrate that pregnant women with glucose intolerance exhibited greater glucose fluctuations compared with the control cases. The use of CGM may help to improve our understanding of glycemic patterns and may have beneficial effects on perinatal glycemic control, such as the detection of postprandial hyperglycemia in pregnant women. PMID:26949348

  14. 75 FR 2551 - NIH Consensus Development Conference: Lactose Intolerance and Health; Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    .... Lactose intolerance is the inability to digest significant amounts of lactose, a sugar found in milk and.... Lactase breaks milk sugar down into two simpler forms of sugar called glucose and galactose, which...

  15. A Risk Based Neural Network Approach for Predictive Modeling of Blood Glucose Dynamics.

    PubMed

    Frandes, Mirela; Timar, Bogdan; Lungeanu, Diana

    2016-01-01

    For type 1 diabetes patients, maintaining the blood glucose (BG) at normal values is a challenging task due to e.g. variable insulin reactions, diets, lifestyles, emotional conditions, etc. Hyperglycemic and hypoglycemic events can generate various complications (e.g. diabetic ketoacidosis, retinopathy, neuropathy, etc.), so predicting BG values in time is of great importance for diabetes self-management. Herein, we propose a non-linear autoregressive neural network approach, based on the minimal dataset available from a continuous glucose monitoring (CGM) sensor, with an integrated measure of intra-patient BG variability. The method kept the balance between accuracy and complexity, allowing a fast response with no additional effort or discomfort for the patient. PMID:27577449

  16. [Metabolic intolerance to exercise].

    PubMed

    Arenas, J; Martín, M A

    2003-01-01

    Exercise intolerance (EI) is a frequent cause of medical attention, although it is sometimes difficult to come to a final diagnosis. However, there is a group of patients in whom EI is due to a metabolic dysfunction. McArdle's disease (type V glucogenosis) is due to myophosphorylase (MPL) deficiency. The ischemic exercise test shows a flat lactate curve. The most frequent mutations in the PYGM gene (MPL gene) in Spanish patients with MPL deficiency are R49X and W797R. Carnitine palmitoyltransferase (CPT) II deficiency is invariably associated to repetitive episodes of myoglobinuria triggered by exercise, cold, fever or fasting. The diagnosis depends on the demonstration of CPT II deficiency in muscle. The most frequent mutation in the CPT2 gene is the S113L. Patients with muscle adenylate deaminase deficiency usually show either a mild myopathy or no symptom. The diagnosis is based on the absence of enzyme activity in muscle and the lack of rise of ammonia in the forearm ischemic exercise test. The mutation Q12X in the AMPD1 gene is strongly associated with the disease. Exercise intolerance is a common complaint in patients with mitochondrial respiratory chain (MRC) deficiencies, although it is often overshadowed by other symptoms and signs. Only recently we have come to appreciate that exercise intolerance can be the sole presentation of defects in the mtDNA, particularly in complex I, complex III, complex IV, or in some tRNAs. In addition, myoglobinuria can be observed in patients under statin treatment, particularly if associated with fibrates, due to an alteration in the assembly of the complex IV of the MRC. PMID:12838448

  17. Rationale, design, and method of the Diabetes & Women’s Health study – a study of long-term health implications of glucose intolerance in pregnancy and their determinants

    PubMed Central

    Zhang, Cuilin; Hu, Frank B.; Olsen, Sjurdur F.; Vaag, Allan; Gore-Langton, Robert; Chavarro, Jorge E.; Bao, Wei; Yeung, Edwina; Bowers, Katherine; Grunnet, Louise G.; Sherman, Seth; Kiely, Michele; Strøm, Marin; Hansen, Susanne; Liu, Aiyi; Mills, James; Fan, Ruzong

    2014-01-01

    Women who develop gestational diabetes mellitus or impaired glucose tolerance during pregnancy are at substantially increased risk for type 2 diabetes and comorbidities after pregnancy. Little is known about the role of genetic factors and their interactions with environmental factors in determining the transition from gestational diabetes mellitus to overt type 2 diabetes mellitus. These critical data gaps served as the impetus for this Diabetes & Women’s Health study with the overall goal of investigating genetic factors and their interactions with risk factors amenable to clinical or public health interventions in relation to the transition of gestational diabetes mellitus to type 2 diabetes mellitus. To achieve the goal efficiently, we are applying a hybrid design enrolling and collecting data longitudinally from approximately 4000 women with a medical history of gestational diabetes mellitus in two existing prospective cohorts, the Nurses’ Health Study II and the Danish National Birth Cohort. Women who had a medical history of gestational diabetes mellitus in one or more of their pregnancies are eligible for the present study. After enrollment, we follow study participants for an additional 2 years to collect updated information on major clinical and environmental factors that may predict type 2 diabetes mellitus risk as well as with biospecimens to measure genetic and biochemical markers implicated in glucose metabolism. Newly collected data will be appended to the relevant existing data for the creation of a new database inclusive of genetic, epigenetic and environmental data. Findings from the study are critical for the development of targeted and more effective strategies to prevent type 2 diabetes mellitus and its complications in this high-risk population. PMID:24828694

  18. Hypoglycemia Prevention and User Acceptance of an Insulin Pump System with Predictive Low Glucose Management

    PubMed Central

    Olsen, Birthe S.; Conget, Ignacio; Welsh, John B.; Vorrink, Linda; Shin, John J.

    2016-01-01

    Abstract Background: The MiniMed 640G sensor-augmented insulin pump system (Medtronic, Inc., Northridge, CA) can automatically suspend insulin delivery in advance of predicted hypoglycemia and restart it upon recovery. The aims of this analysis were to determine the rate at which predicted hypoglycemia was avoided with this strategy, as well as to assess user acceptance of the system and its insulin management features. Subjects and Methods: Forty subjects with type 1 diabetes used the system for 4 weeks. We retrospectively evaluated performance of the system, using downloaded pump and sensor data, and evaluated user acceptance via questionnaires. Results: There were 2,322 suspend before low events (2.1 per subject-day). The mean (± SD) duration of pump suspension events was 56.4 ± 9.6 min, and the mean subsequent sensor glucose (SG) nadir was 71.8 ± 5.2 mg/dL. SG values following 1,930 (83.1%) of the predictive suspensions did not reach the preset low limit. Nadir SG values of ≤50 and ≤60 mg/dL were seen in 207 (8.9%) and 356 (15.3%) of the predictive suspensions, respectively. Blood glucose (BG) and SG values before and during the study were comparable (P > 0.05). The mean absolute relative difference between paired SG and BG values was 10.9 ± 13.8%. Subjects felt confident using the system, agreed that it helped protect them from hypoglycemia, and wished to continue using it. Conclusions: Automatic insulin pump suspension as implemented in the MiniMed 640G system can help patients avoid hypoglycemia, without significantly increasing hyperglycemia. PMID:26907513

  19. Preliminary application of a novel algorithm to monitor changes in pre-flight total peripheral resistance for prediction of post-flight orthostatic intolerance in astronauts

    NASA Astrophysics Data System (ADS)

    Arai, Tatsuya; Lee, Kichang; Stenger, Michael B.; Platts, Steven H.; Meck, Janice V.; Cohen, Richard J.

    2011-04-01

    Orthostatic intolerance (OI) is a significant challenge for astronauts after long-duration spaceflight. Depending on flight duration, 20-80% of astronauts suffer from post-flight OI, which is associated with reduced vascular resistance. This paper introduces a novel algorithm for continuously monitoring changes in total peripheral resistance (TPR) by processing the peripheral arterial blood pressure (ABP). To validate, we applied our novel mathematical algorithm to the pre-flight ABP data previously recorded from twelve astronauts ten days before launch. The TPR changes were calculated by our algorithm and compared with the TPR value estimated using cardiac output/heart rate before and after phenylephrine administration. The astronauts in the post-flight presyncopal group had lower pre-flight TPR changes (1.66 times) than those in the non-presyncopal group (2.15 times). The trend in TPR changes calculated with our algorithm agreed with the TPR trend calculated using measured cardiac output in the previous study. Further data collection and algorithm refinement are needed for pre-flight detection of OI and monitoring of continuous TPR by analysis of peripheral arterial blood pressure.

  20. Initial Molecular Response at 3 Months May Predict Both Response and Event-Free Survival at 24 Months in Imatinib-Resistant or -Intolerant Patients With Philadelphia Chromosome–Positive Chronic Myeloid Leukemia in Chronic Phase Treated With Nilotinib

    PubMed Central

    Branford, Susan; Kim, Dong-Wook; Soverini, Simona; Haque, Ariful; Shou, Yaping; Woodman, Richard C.; Kantarjian, Hagop M.; Martinelli, Giovanni; Radich, Jerald P.; Saglio, Giuseppe; Hochhaus, Andreas; Hughes, Timothy P.; Müller, Martin C.

    2012-01-01

    Purpose The association between initial molecular response and longer-term outcomes with nilotinib was examined. Patients and Methods Patients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237). Results BCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months. Patients with BCR-ABL1 (IS) of > 1% to ≤ 10% at 3 months with nilotinib had higher cumulative incidence of CCyR by 24 months than patients with BCR-ABL1 (IS) of > 10% (53% v 16%). BCR-ABL1 (IS) at 3 months predicted major molecular response (MMR) by 24 months. Cumulative incidence of MMR by 24 months for patients with BCR-ABL1 (IS) of > 0.1% to ≤ 1%, > 1% to ≤ 10%, and > 10% was 65%, 27%, and 9%, respectively. These differences were observed for patients with or without baseline BCR–ABL1 mutations and for those with imatinib resistance or intolerance. Estimated event-free survival (EFS) rates at 24 months decreased with higher transcript levels at 3 months; patients with BCR-ABL1 (IS) of ≤ 1% had an estimated 24-month EFS rate of 82%, compared with 70% for patients with BCR-ABL1 (IS) of > 1% to ≤ 10% and 48% for patients with BCR-ABL1 (IS) of > 10%. Conclusion Patients with BCR-ABL1 (IS) of > 10% at 3 months had a lower cumulative incidence of CCyR and MMR and lower rates of EFS versus patients with BCR-ABL1 (IS) of ≤ 10%. Prospective studies may determine whether close monitoring or alternative therapies are warranted for patients with minimal initial molecular response. PMID:23109697

  1. Lactose intolerance: a nursing perspective.

    PubMed

    Marchiondo, Kathleen

    2009-01-01

    Deficiency of intestinal lactase, the enzyme required for lactose digestion, can result in symptoms of gastrointestinal malabsorption, or lactose intolerance. The knowledge needed for accurate nursing assessment, diagnostic procedural care, teaching, and referral of affected patients is reviewed.

  2. How Is Lactose Intolerance Diagnosed?

    MedlinePlus

    ... following tests also can help diagnose lactose intolerance: Hydrogen breath test. For this test, a person drinks ... beverage that has lactose in it. Then, the hydrogen level in the breath is measured at set ...

  3. Hereditary fructose intolerance.

    PubMed Central

    Ali, M; Rellos, P; Cox, T M

    1998-01-01

    Hereditary fructose intolerance (HFI, OMIM 22960), caused by catalytic deficiency of aldolase B (fructose-1,6-bisphosphate aldolase, EC 4.1.2.13), is a recessively inherited condition in which affected homozygotes develop hypoglycaemic and severe abdominal symptoms after taking foods containing fructose and cognate sugars. Continued ingestion of noxious sugars leads to hepatic and renal injury and growth retardation; parenteral administration of fructose or sorbitol may be fatal. Direct detection of a few mutations in the human aldolase B gene on chromosome 9q facilitates the genetic diagnosis of HFI in many symptomatic patients. The severity of the disease phenotype appears to be independent of the nature of the aldolase B gene mutations so far identified. It appears that hitherto there has been little, if any, selection against mutant aldolase B alleles in the population: in the UK, approximately 1.3% of neonates harbour one copy of the prevalent A149P disease allele. The ascendance of sugar as a major dietary nutrient, especially in western societies, may account for the increasing recognition of HFI as a nutritional disease and has shown the prevalence of mutant aldolase B genes in the general population. The severity of clinical expression correlates well with the immediate nutritional environment, age, culture, and eating habits of affected subjects. Here we review the biochemical, genetic, and molecular basis of human aldolase B deficiency in HFI, a disorder which responds to dietary therapy and in which the principal manifestations of disease are thus preventable. Images PMID:9610797

  4. Baselines representing blood glucose clearance improve in vitro prediction of the glycaemic impact of customarily consumed food quantities.

    PubMed

    Monro, John A; Mishra, Suman; Venn, Bernard

    2010-01-01

    Glycaemic responses to foods reflect the balance between glucose loading into, and its clearance from, the blood. Current in vitro methods for glycaemic analysis do not take into account the key role of glucose disposal. The present study aimed to develop a food intake-sensitive method for measuring the glycaemic impact of food quantities usually consumed, as the difference between release of glucose equivalents (GGE) from food during in vitro digestion and a corresponding estimate of clearance of them from the blood. Five foods - white bread, fruit bread, muesli bar, mashed potato and chickpeas - were consumed on three occasions by twenty volunteers to provide blood glucose response (BGR) curves. GGE release during in vitro digestion of the foods was also plotted. Glucose disposal rates estimated from downward slopes of the BGR curves allowed GGE dose-dependent cumulative glucose disposal to be calculated. By subtracting cumulative glucose disposal from cumulative in vitro GGE release, accuracy in predicting the in vivo glycaemic effect from in vitro GGE values was greatly improved. GGE(in vivo) = 0.99GGE(in vitro)+0.75 (R(2) 0.88). Furthermore, the difference between the curves of cumulative GGE release and disposal closely mimicked in vivo incremental BGR curves. We conclude that valid measurement of the glycaemic impact of foods may be obtained in vitro, and expressed as grams of glucose equivalents per food quantity, by taking account not only of GGE release from food during in vitro digestion, but also of blood glucose clearance in response to the food quantity.

  5. Food allergies and food intolerances.

    PubMed

    Ortolani, Claudio; Pastorello, Elide A

    2006-01-01

    Adverse reactions to foods, aside from those considered toxic, are caused by a particular individual intolerance towards commonly tolerated foods. Intolerance derived from an immunological mechanism is referred to as Food Allergy, the non-immunological form is called Food Intolerance. IgE-mediated food allergy is the most common and dangerous type of adverse food reaction. It is initiated by an impairment of normal Oral Tolerance to food in predisposed individuals (atopic). Food allergy produces respiratory, gastrointestinal, cutaneous and cardiovascular symptoms but often generalized, life-threatening symptoms manifest at a rapid rate-anaphylactic shock. Diagnosis is made using medical history and cutaneous and serological tests but to obtain final confirmation a Double Blind Controlled Food Challenge must be performed. Food intolerances are principally caused by enzymatic defects in the digestive system, as is the case with lactose intolerance, but may also result from pharmacological effects of vasoactive amines present in foods (e.g. Histamine). Prevention and treatment are based on the avoidance of the culprit food. PMID:16782524

  6. Discomfort Intolerance: Evaluation of a Potential Risk Factor for Anxiety Psychopathology

    ERIC Educational Resources Information Center

    Schmidt, Norman B.; Richey, J. Anthony; Cromer, Kiara R.; Buckner, Julia D.

    2007-01-01

    Discomfort intolerance, defined as an individual difference in the capacity to tolerate unpleasant bodily sensations, is a construct recently posited as a risk factor for panic and anxiety psychopathology. The present report used a biological challenge procedure to evaluate whether discomfort intolerance predicts fearful responding beyond the…

  7. Changes in the expression of the type 2 diabetes-associated gene VPS13C in the β-cell are associated with glucose intolerance in humans and mice

    PubMed Central

    Mehta, Zenobia B.; Fine, Nicholas; Pullen, Timothy J.; Cane, Matthew C.; Hu, Ming; Chabosseau, Pauline; Meur, Gargi; Velayos-Baeza, Antonio; Monaco, Anthony P.; Marselli, Lorella; Marchetti, Piero

    2016-01-01

    Single nucleotide polymorphisms (SNPs) close to the VPS13C, C2CD4A and C2CD4B genes on chromosome 15q are associated with impaired fasting glucose and increased risk of type 2 diabetes. eQTL analysis revealed an association between possession of risk (C) alleles at a previously implicated causal SNP, rs7163757, and lowered VPS13C and C2CD4A levels in islets from female (n = 40, P < 0.041) but not from male subjects. Explored using promoter-reporter assays in β-cells and other cell lines, the risk variant at rs7163757 lowered enhancer activity. Mice deleted for Vps13c selectively in the β-cell were generated by crossing animals bearing a floxed allele at exon 1 to mice expressing Cre recombinase under Ins1 promoter control (Ins1Cre). Whereas Vps13cfl/fl:Ins1Cre (βVps13cKO) mice displayed normal weight gain compared with control littermates, deletion of Vps13c had little effect on glucose tolerance. Pancreatic histology revealed no significant change in β-cell mass in KO mice vs. controls, and glucose-stimulated insulin secretion from isolated islets was not altered in vitro between control and βVps13cKO mice. However, a tendency was observed in female null mice for lower insulin levels and β-cell function (HOMA-B) in vivo. Furthermore, glucose-stimulated increases in intracellular free Ca2+ were significantly increased in islets from female KO mice, suggesting impaired Ca2+ sensitivity of the secretory machinery. The present data thus provide evidence for a limited role for changes in VPS13C expression in conferring altered disease risk at this locus, particularly in females, and suggest that C2CD4A may also be involved. PMID:27329800

  8. Strategies to overcome statin intolerance.

    PubMed

    Agouridis, Aris P; Nair, Devaki R; Mikhailidis, Dimitri P

    2015-06-01

    This editorial discusses several options to overcome statin intolerance in clinical practice. For example, switching to a different statin, changing statin dosing, using lipid-lowering drugs other than statins (e.g., ezetimibe, bile acid sequestrants and fibrates, alone or in combination), or combining statins with other lipid-lowering drugs. The authors focus on the potential mechanisms involved in statin-related myopathy. New lipid-lowering drugs currently in development (e.g., cholesterol ester transfer protein inhibitors [anacetrapib] and proprotein convertase subtilisin/kexin 9 inhibitors) inhibitors may help in the management of statin intolerance while achieving low-density lipoprotein cholesterol targets as set out by the guidelines.

  9. [Abdominal spasms, meteorism, diarrhea: fructose intolerance, lactose intolerance or IBS?].

    PubMed

    Litschauer-Poursadrollah, Margaritha; El-Sayad, Sabine; Wantke, Felix; Fellinger, Christina; Jarisch, Reinhart

    2012-12-01

    Meteorism, abdominal spasms, diarrhea, casually obstipation, flatulence and nausea are symptoms of fructose malabsorption (FIT) and/or lactose intolerance (LIT), but are also symptoms of irritable bowel syndrome (IBS). Therefore these diseases should be considered primarily in patients with digestive complaints. For diagnosis an H(2)-breath test is used.In 1,935 patients (526 m, 1,409 f) a fructose intolerance test and in 1,739 patients (518 m,1,221 f) a lactose intolerance test was done.FIT is found more frequently than LIT (57 versus 52 % in adults (p < 0,02) and in children 90 versus 62 % (p < 0,001)) and is in polyintolerances most frequently correlated to histamine intolerance (HIT). Headache (ca. 10 %), fatigue (ca. 5 %) and dizziness (ca. 3 %) may occur after the test, irrespective whether the test was positive or negative.In more than 2/3 of patients a diet reduced in fructose or lactose may lead to improvement or remission of these metabolic disorders. IBS, which is often correlated with FIT (183/221 patients = 83 %), can be improved by relevant but also not relevant diets indicating that irritable bowel disease seems to be caused primarily by psychological disorders.

  10. Lactobacillus sakei OK67 ameliorates high-fat diet-induced blood glucose intolerance and obesity in mice by inhibiting gut microbiota lipopolysaccharide production and inducing colon tight junction protein expression.

    PubMed

    Lim, Su-Min; Jeong, Jin-Ju; Woo, Kyung Hee; Han, Myung Joo; Kim, Dong-Hyun

    2016-04-01

    A high-fat diet (HFD) induces obesity and the associated increases in blood glucose and inflammation through changes in gut microbiota, endotoxemia, and increased gut permeability. To counteract this, researchers have suggested that the use of probiotics that suppress production of proinflammatory lipopolysaccharide (LPS). Here, we tested whether Lactobacillus sakei OK67, which inhibits gut microbiota LPS production selected from among the lactic acid bacteria isolated from kimchi, exerted antihypoglycemic or anti-inflammatory effects in HFD-fed mice. Mice were randomly divided into 2 groups and fed an HFD or a low-fat diet for 4 weeks. These groups were further subdivided; 1 subgroup was treated with L sakei OK67 and fed the experimental diet for 4.5 weeks, whereas the other subgroup was fed the experimental diet alone. L sakei OK67 treatment lowered HFD-elevated LPS levels in blood and colonic fluid and significantly decreased HFD-elevated fasting blood glucose levels and the area under the curve in an oral glucose tolerance test. L sakei OK67 treatment inhibited HFD-induced body and epididymal fat weight gains, suppressed HFD-induced tumor necrosis factor-α and interleukin-1β expression and nuclear factor-κB activation in the colon, and significantly increased HFD-suppressed interleukin-10 and tight junction protein expression in the colon. Oral administration of L sakei OK67 significantly downregulated HFD-induced expression of peroxisome proliferator-activated receptor γ, fatty acid synthase, and tumor necrosis factor-α in adipose tissue. In addition, L sakei OK67 treatment strongly inhibited nuclear factor-κB activation in LPS-stimulated peritoneal macrophages. We report that L sakei OK67 ameliorates HFD-induced hyperglycemia and obesity by reducing inflammation and increasing the expression of colon tight junction proteins in mice. PMID:27001279

  11. Statin Intolerance: the Clinician's Perspective.

    PubMed

    Stulc, Tomáš; Ceška, Richard; Gotto, Antonio M

    2015-12-01

    Muscle problems and other adverse symptoms associated with statin use are frequent reasons for non-adherence and discontinuation of statin therapy, which results in inadequate control of hyperlipidemia and increased cardiovascular risk. However, most patients who experience adverse symptoms during statin use are able to tolerate at least some degree of statin therapy. Given the profound cardiovascular benefits derived from statins, an adequate practical approach to statin intolerance is, therefore, of great clinical importance. Statin intolerance can be defined as the occurrence of myalgia or other adverse symptoms that are attributed to statin therapy and that lead to its discontinuation. In reality, these symptoms are actually unrelated to statin use in many patients, especially in those with atypical presentations following long periods of treatment. Thus, the first step in approaching patients with adverse symptoms during the course of statin therapy is identification of those patients for whom true statin intolerance is unlikely, since most of these patients would probably be capable of tolerating adequate statin therapy. In patients with statin intolerance, an altered dosing regimen of very low doses of statins should be attempted and, if tolerated, should gradually be increased to achieve the highest tolerable doses. In addition, other lipid-lowering drugs may be needed, either in combination with statins, or alone, if statins are not tolerated at all. Stringent control of other risk factors can aid in reducing cardiovascular risk if attaining lipid treatment goals proves difficult.

  12. Is it just lactose intolerance?

    PubMed

    Olivier, Celso Eduardo; Lorena, Sônia Letícia Silva; Pavan, Célia Regina; dos Santos, Raquel Acácia Pereira Gonçalves; dos Santos Lima, Regiane Patussi; Pinto, Daiana Guedes; da Silva, Mariana Dias; de Lima Zollner, Ricardo

    2012-01-01

    Acquired delayed-onset hypolactasia is a common autosomal recessive condition. Cow's milk allergies, conversely, are less common conditions that may manifest with equivalent symptoms and are able to simulate and/or aggravate lactose intolerance. This study was designed to evaluate the contribution of IgE-mediated cow's milk sensitization to the symptomatology of adult patients with lactose-free diet refractory lactose intolerance. Forty-six adult patients with lactose intolerance and persistent symptoms despite a lactose-free diet underwent skin-prick test to investigate cow's milk, goat's milk, and soy protein-specific-IgE. SDS-PAGE immunoblotting was used to investigate the presence of cow's milk protein-specific IgE. The percentage of patients who had skin reactions to whole cow's milk, alpha-lactalbumin, beta-lactoglobulin, caseins, goat's milk, and soy was 69.5, 36.9, 56.5, 56.5%, 54.3, and 50%, respectively. The percentage of patients with immunoblot-detected IgE specific for alpha-lactalbumin, beta-lactoglobulin, caseins, and bovine serum albumin was 21.7, 63, 67.3, and 2.1%, respectively. IgE-mediated sensitization to cow's milk is a frequent comorbidity in subjects with lactose-free diet refractory lactose intolerance and is worth consideration in patients with this condition.

  13. Gastrointestinal food allergy and intolerance.

    PubMed

    Assa'ad, Amal H

    2006-10-01

    GI symptoms are a common manifestation of food allergy and intolerance. The primary physician is the first to evaluate these symptoms. A systematic evaluation using an accurate and detailed history, tests to identify the offending food(s), and procedures that may identify underlying pathologic disorders of the GI tract would lead to an accurate diagnosis and better targeted therapeutic interventions. PMID:17048714

  14. Dynamic metabolic modeling of a microaerobic yeast co-culture: predicting and optimizing ethanol production from glucose/xylose mixtures

    PubMed Central

    2013-01-01

    Background A key step in any process that converts lignocellulose to biofuels is the efficient fermentation of both hexose and pentose sugars. The co-culture of respiratory-deficient Saccharomyces cerevisiae and wild-type Scheffersomyces stipitis has been identified as a promising system for microaerobic ethanol production because S. cerevisiae only consumes glucose while S. stipitis efficiently converts xylose to ethanol. Results To better predict how these two yeasts behave in batch co-culture and to optimize system performance, a dynamic flux balance model describing co-culture metabolism was developed from genome-scale metabolic reconstructions of the individual organisms. First a dynamic model was developed for each organism by estimating substrate uptake kinetic parameters from batch pure culture data and evaluating model extensibility to different microaerobic growth conditions. The co-culture model was constructed by combining the two individual models assuming a cellular objective of total growth rate maximization. To obtain accurate predictions of batch co-culture data collected at different microaerobic conditions, the S. cerevisiae maximum glucose uptake rate was reduced from its pure culture value to account for more efficient S. stipitis glucose uptake in co-culture. The dynamic co-culture model was used to predict the inoculum concentration and aeration level that maximized batch ethanol productivity. The model predictions were validated with batch co-culture experiments performed at the optimal conditions. Furthermore, the dynamic model was used to predict how engineered improvements to the S. stipitis xylose transport system could improve co-culture ethanol production. Conclusions These results demonstrate the utility of the dynamic co-culture metabolic model for guiding process and metabolic engineering efforts aimed at increasing microaerobic ethanol production from glucose/xylose mixtures. PMID:23548183

  15. The Health Behavior Schedule-II for Diabetes Predicts Self-Monitoring of Blood Glucose

    ERIC Educational Resources Information Center

    Frank, Maxwell T.; Cho, Sungkun; Heiby, Elaine M.; Lee, Chun-I; Lahtela, Adrienne L.

    2006-01-01

    The Health Behavior Schedule-II for Diabetes (HBS-IID) is a 27-item questionnaire that was evaluated as a predictor of self-monitoring of blood glucose (SMBG). The HBS-IID was completed by 96 adults with Type 2 diabetes. Recent glycosylated hemoglobin HbA1c and fasting blood glucose results were taken from participants' medical records. Only 31.3%…

  16. Mechanisms of orthostatic intolerance during heat stress.

    PubMed

    Schlader, Zachary J; Wilson, Thad E; Crandall, Craig G

    2016-04-01

    Heat stress profoundly and unanimously reduces orthostatic tolerance. This review aims to provide an overview of the numerous and multifactorial mechanisms by which this occurs in humans. Potential causal factors include changes in arterial and venous vascular resistance and blood distribution, and the modulation of cardiac output, all of which contribute to the inability to maintain cerebral perfusion during heat and orthostatic stress. A number of countermeasures have been established to improve orthostatic tolerance during heat stress, which alleviate heat stress induced central hypovolemia (e.g., volume expansion) and/or increase peripheral vascular resistance (e.g., skin cooling). Unfortunately, these countermeasures can often be cumbersome to use with populations prone to syncopal episodes. Identifying the mechanisms of inter-individual differences in orthostatic intolerance during heat stress has proven elusive, but could provide greater insights into the development of novel and personalized countermeasures for maintaining or improving orthostatic tolerance during heat stress. This development will be especially impactful in occuational settings and clinical situations that present with orthostatic intolerance and/or central hypovolemia. Such investigations should be considered of vital importance given the impending increased incidence of heat events, and associated cardiovascular challenges that are predicted to occur with the ensuing changes in climate. PMID:26723547

  17. Hepatic fat and abdominal adiposity in early pregnancy together predict impaired glucose homeostasis in mid-pregnancy.

    PubMed

    De Souza, L R; Berger, H; Retnakaran, R; Vlachou, P A; Maguire, J L; Nathens, A B; Connelly, P W; Ray, J G

    2016-01-01

    Hepatic fat and abdominal adiposity individually reflect insulin resistance, but their combined effect on glucose homeostasis in mid-pregnancy is unknown. A cohort of 476 pregnant women prospectively underwent sonographic assessment of hepatic fat and visceral (VAT) and total (TAT) adipose tissue at 11-14 weeks' gestation. Logistic regression was used to assess the relation between the presence of maternal hepatic fat and/or the upper quartile (Q) of either VAT or TAT and the odds of developing the composite outcome of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or gestational diabetes mellitus at 24-28 weeks' gestation, based on a 75 g OGTT. Upon adjusting for maternal age, ethnicity, family history of DM and body mass index (BMI), the co-presence of hepatic fat and quartile 4 (Q4) of VAT (adjusted odds ratio (aOR) 6.5, 95% CI: 2.3-18.5) or hepatic fat and Q4 of TAT (aOR 7.8 95% CI 2.8-21.7) were each associated with the composite outcome, relative to women with neither sonographic feature. First-trimester sonographic evidence of maternal hepatic fat and abdominal adiposity may independently predict the development of impaired glucose homeostasis and GDM in mid-pregnancy. PMID:27643724

  18. Hepatic fat and abdominal adiposity in early pregnancy together predict impaired glucose homeostasis in mid-pregnancy

    PubMed Central

    De Souza, L R; Berger, H; Retnakaran, R; Vlachou, P A; Maguire, J L; Nathens, A B; Connelly, P W; Ray, J G

    2016-01-01

    Hepatic fat and abdominal adiposity individually reflect insulin resistance, but their combined effect on glucose homeostasis in mid-pregnancy is unknown. A cohort of 476 pregnant women prospectively underwent sonographic assessment of hepatic fat and visceral (VAT) and total (TAT) adipose tissue at 11–14 weeks' gestation. Logistic regression was used to assess the relation between the presence of maternal hepatic fat and/or the upper quartile (Q) of either VAT or TAT and the odds of developing the composite outcome of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or gestational diabetes mellitus at 24–28 weeks' gestation, based on a 75 g OGTT. Upon adjusting for maternal age, ethnicity, family history of DM and body mass index (BMI), the co-presence of hepatic fat and quartile 4 (Q4) of VAT (adjusted odds ratio (aOR) 6.5, 95% CI: 2.3–18.5) or hepatic fat and Q4 of TAT (aOR 7.8 95% CI 2.8–21.7) were each associated with the composite outcome, relative to women with neither sonographic feature. First-trimester sonographic evidence of maternal hepatic fat and abdominal adiposity may independently predict the development of impaired glucose homeostasis and GDM in mid-pregnancy. PMID:27643724

  19. Near-infrared noninvasive blood glucose prediction without using multivariate analyses: introduction of imaginary spectra due to scattering change in the skin.

    PubMed

    Maruo, Katsuhiko; Yamada, Yukio

    2015-04-01

    A noninvasive measurement method is proposed and examined to continuously predict blood glucose contents using near-infrared diffuse reflection difference spectra measured at the skin tissue without using multivariate analyses. Using the modified Beer’s law, the difference spectra are assumed to be synthesized from four major components in the human skin (water, protein, glucose, and fat) and a scattering equivalent component called baseline. As a result, one of the origins of the errors in blood glucose prediction using near-infrared is found to be the similarity of the shapes of the absorption spectrum between glucose and baseline. After separating the glucose contributions from the difference spectra at the characteristic wavelengths of baseline and fat, an imaginary component combining baseline and fat is introduced by considering that both the change in the fat contribution and the generation of baseline originate from the change in scattering in the skin. The imaginary component enables us to reduce the errors in blood glucose prediction. In contrast to the methods using multivariate analyses, the calculation process of the blood glucose contents from the measured reflection spectra is clear in this method, thus, it is easy to estimate the origins of the changes and contributions of the components in the measured difference spectra. The proposed method may become a useful tool for realization of noninvasive blood glucose prediction using near-infrared spectroscopy. PMID:25859836

  20. Sediment Burial Intolerance of Marine Macroinvertebrates.

    PubMed

    Hendrick, Vicki J; Hutchison, Zoë L; Last, Kim S

    2016-01-01

    The marine environment contains suspended particulate matter which originates from natural and anthropogenic sources. Settlement of this material can leave benthic organisms susceptible to smothering, especially if burial is sudden i.e. following storms or activities such as dredging. Their survival will depend on their tolerance to, and their ability to escape from burial. Here we present data from a multi-factorial experiment measuring burial responses incorporating duration, sediment fraction and depth. Six macroinvertebrates commonly found in sediment rich environments were selected for their commercial and/or conservation importance. Assessments revealed that the brittle star (Ophiura ophiura), the queen scallop (Aequipecten opercularis) and the sea squirt (Ciona intestinalis) were all highly intolerant to burial whilst the green urchin (Psammichinus miliaris) and the anemone (Sagartiogeton laceratus), showed intermediate and low intolerance respectively, to burial. The least intolerant, with very high survival was the Ross worm (Sabellaria spinulosa). With the exception of C. intestinalis, increasing duration and depth of burial with finer sediment fractions resulted in increased mortality for all species assessed. For C. intestinalis depth of burial and sediment fraction were found to be inconsequential since there was complete mortality of all specimens buried for more than one day. When burial emergence was assessed O. ophiura emerged most frequently, followed by P. miliaris. The former emerged most frequently from the medium and fine sediments whereas P. miliaris emerged more frequently from coarse sediment. Both A. opercularis and S. laceratus showed similar emergence responses over time, with A. opercularis emerging more frequently under coarse sediments. The frequency of emergence of S. laceratus increased with progressively finer sediment and C. intestinalis did not emerge from burial irrespective of sediment fraction or depth. Finally, and perhaps

  1. Sediment Burial Intolerance of Marine Macroinvertebrates

    PubMed Central

    Hendrick, Vicki J.; Hutchison, Zoë L.; Last, Kim S.

    2016-01-01

    The marine environment contains suspended particulate matter which originates from natural and anthropogenic sources. Settlement of this material can leave benthic organisms susceptible to smothering, especially if burial is sudden i.e. following storms or activities such as dredging. Their survival will depend on their tolerance to, and their ability to escape from burial. Here we present data from a multi-factorial experiment measuring burial responses incorporating duration, sediment fraction and depth. Six macroinvertebrates commonly found in sediment rich environments were selected for their commercial and/or conservation importance. Assessments revealed that the brittle star (Ophiura ophiura), the queen scallop (Aequipecten opercularis) and the sea squirt (Ciona intestinalis) were all highly intolerant to burial whilst the green urchin (Psammichinus miliaris) and the anemone (Sagartiogeton laceratus), showed intermediate and low intolerance respectively, to burial. The least intolerant, with very high survival was the Ross worm (Sabellaria spinulosa). With the exception of C. intestinalis, increasing duration and depth of burial with finer sediment fractions resulted in increased mortality for all species assessed. For C. intestinalis depth of burial and sediment fraction were found to be inconsequential since there was complete mortality of all specimens buried for more than one day. When burial emergence was assessed O. ophiura emerged most frequently, followed by P. miliaris. The former emerged most frequently from the medium and fine sediments whereas P. miliaris emerged more frequently from coarse sediment. Both A. opercularis and S. laceratus showed similar emergence responses over time, with A. opercularis emerging more frequently under coarse sediments. The frequency of emergence of S. laceratus increased with progressively finer sediment and C. intestinalis did not emerge from burial irrespective of sediment fraction or depth. Finally, and perhaps

  2. Sediment Burial Intolerance of Marine Macroinvertebrates.

    PubMed

    Hendrick, Vicki J; Hutchison, Zoë L; Last, Kim S

    2016-01-01

    The marine environment contains suspended particulate matter which originates from natural and anthropogenic sources. Settlement of this material can leave benthic organisms susceptible to smothering, especially if burial is sudden i.e. following storms or activities such as dredging. Their survival will depend on their tolerance to, and their ability to escape from burial. Here we present data from a multi-factorial experiment measuring burial responses incorporating duration, sediment fraction and depth. Six macroinvertebrates commonly found in sediment rich environments were selected for their commercial and/or conservation importance. Assessments revealed that the brittle star (Ophiura ophiura), the queen scallop (Aequipecten opercularis) and the sea squirt (Ciona intestinalis) were all highly intolerant to burial whilst the green urchin (Psammichinus miliaris) and the anemone (Sagartiogeton laceratus), showed intermediate and low intolerance respectively, to burial. The least intolerant, with very high survival was the Ross worm (Sabellaria spinulosa). With the exception of C. intestinalis, increasing duration and depth of burial with finer sediment fractions resulted in increased mortality for all species assessed. For C. intestinalis depth of burial and sediment fraction were found to be inconsequential since there was complete mortality of all specimens buried for more than one day. When burial emergence was assessed O. ophiura emerged most frequently, followed by P. miliaris. The former emerged most frequently from the medium and fine sediments whereas P. miliaris emerged more frequently from coarse sediment. Both A. opercularis and S. laceratus showed similar emergence responses over time, with A. opercularis emerging more frequently under coarse sediments. The frequency of emergence of S. laceratus increased with progressively finer sediment and C. intestinalis did not emerge from burial irrespective of sediment fraction or depth. Finally, and perhaps

  3. Lactose intolerance and other disaccharidase deficiency.

    PubMed

    Tomar, Balvir S

    2014-09-01

    Intolerance to foods which contain lactose can cause a range of intestinal and systemic symptoms. These symptoms are caused by Lactase deficiency which is encoded by a single gene (LCT) of ≈ 50 kb located on chromosome 2q21. In some food items, lactose has been missed because of "hidden" lactose due to inadequately labeled, confusing diagnosis of lactose intolerance based on dietary restriction of dairy foods. Two polymorphisms, C/T13910 and G/A22018, linked to hypolactasia, correlate with breath hydrogen and symptoms after lactose. The key in the management of lactose intolerance is the dietary removal of lactose. Patients diagnosed as lactose intolerant must be advised of "risk" foods, inadequately labeled, including processed meats, bread, cake mixes, soft drinks, and lagers. This review highlights the types, symptoms and management of lactose intolerance and also highlights differences from milk allergy which closely mimics the symptoms of lactose intolerance.

  4. Lactose intolerance and other disaccharidase deficiency.

    PubMed

    Tomar, Balvir S

    2014-09-01

    Intolerance to foods which contain lactose can cause a range of intestinal and systemic symptoms. These symptoms are caused by Lactase deficiency which is encoded by a single gene (LCT) of ≈ 50 kb located on chromosome 2q21. In some food items, lactose has been missed because of "hidden" lactose due to inadequately labeled, confusing diagnosis of lactose intolerance based on dietary restriction of dairy foods. Two polymorphisms, C/T13910 and G/A22018, linked to hypolactasia, correlate with breath hydrogen and symptoms after lactose. The key in the management of lactose intolerance is the dietary removal of lactose. Patients diagnosed as lactose intolerant must be advised of "risk" foods, inadequately labeled, including processed meats, bread, cake mixes, soft drinks, and lagers. This review highlights the types, symptoms and management of lactose intolerance and also highlights differences from milk allergy which closely mimics the symptoms of lactose intolerance. PMID:24596060

  5. Statin intolerance: more questions than answers.

    PubMed

    Guyton, John R; Campbell, Kristen B; Lakey, Wanda C

    2014-01-01

    The dramatic effectiveness of statins in improving the course of atherosclerotic cardiovascular disease tends to overshadow questions of statin intolerance. Thus after more than 25 years of clinical statin use, intolerance remains a poorly understood, frustrating issue for patients and providers. It has been extraordinarily difficult to define statin intolerance and its implications for clinical practice. Here, we briefly summarize current knowledge and raise questions that need to be addressed.

  6. Triglycerides to High-Density Lipoprotein Cholesterol Ratio Can Predict Impaired Glucose Tolerance in Young Women with Polycystic Ovary Syndrome

    PubMed Central

    Song, Do Kyeong; Lee, Hyejin; Sung, Yeon-Ah

    2016-01-01

    Purpose The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio could be related to insulin resistance (IR). We previously reported that Korean women with polycystic ovary syndrome (PCOS) had a high prevalence of impaired glucose tolerance (IGT). We aimed to determine the cutoff value of the TG/HDL-C ratio for predicting IR and to examine whether the TG/HDL-C ratio is useful for identifying individuals at risk of IGT in young Korean women with PCOS. Materials and Methods We recruited 450 women with PCOS (24±5 yrs) and performed a 75-g oral glucose tolerance test (OGTT). IR was assessed by a homeostasis model assessment index over that of the 95th percentile of regular-cycling women who served as the controls (n=450, 24±4 yrs). Results The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in women with PCOS. Among the women with PCOS who had normal fasting glucose (NFG), the prevalence of IGT was significantly higher in the women with PCOS who had a high TG/HDL-C ratio compared with those with a low TG/HDL-C ratio (15.6% vs. 5.6%, p<0.05). Conclusion The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in young Korean women with PCOS, and women with NFG and a high TG/HDL-C ratio had a higher prevalence of IGT. Therefore, Korean women with PCOS with a TG/HDL-C ratio >2.5 are recommended to be administered an OGTT to detect IGT even if they have NFG. PMID:27593868

  7. Consumption of sweetened beverages and intakes of fructose and glucose predict type 2 diabetes occurrence.

    PubMed

    Montonen, Jukka; Järvinen, Ritva; Knekt, Paul; Heliövaara, Markku; Reunanen, Antti

    2007-06-01

    The role of intakes of different sugars in the development of type 2 diabetes was studied in a cohort of 4,304 men and women aged 40-60 y and initially free of diabetes at baseline in 1967-1972. Food consumption data were collected using a dietary history interview covering the habitual diet during the previous year. The intakes of different sugars were calculated and divided in quartiles. During a 12-y follow-up, 177 incidents of type 2 diabetes cases were identified from a nationwide register. Combined intake of fructose and glucose was associated with the risk of type 2 diabetes but no significant association was observed for intakes of sucrose, lactose, or maltose. The relative risk between the highest and lowest quartiles of combined fructose and glucose intake was 1.87 (95% [CI] = 1.19, 2.93; P = 0.003). The corresponding relative risks between the extreme quartiles of consumption of food items contributing to sugar intakes were 1.69 (95% [CI] = 1.17, 2.43; P < 0.001) for sweetened berry juice and 1.67 (95% [CI] = 0.98, 2.87; P = 0.01) for soft drinks. Our findings support the view that higher intake of fructose and glucose and sweetened beverages may increase type 2 diabetes risk. PMID:17513405

  8. Medicines, excipients and dietary intolerances.

    PubMed

    2016-08-01

    Medicinal products contain not only active drugs but also other ingredients included for a variety of purposes and collectively known as excipients.(1) People who wish to avoid a specific substance because of an allergy or intolerance may ask a healthcare professional about the constituents of a medicine and whether an alternative is available. In a previous article we discussed the issues facing people who wish to avoid certain substances for religious or cultural reasons.(2) Here, we provide an overview of several dietary conditions and the pharmaceutical issues that need to be considered by healthcare professionals advising on the suitability of a medicine. PMID:27516168

  9. [Food allergy or food intolerance?].

    PubMed

    Maître, S; Maniu, C-M; Buss, G; Maillard, M H; Spertini, F; Ribi, C

    2014-04-16

    Adverse food reactions can be classified into two main categories depending on wether an immune mechanism is involved or not. The first category includes immune mediated reactions like IgE mediated food allergy, eosinophilic oesophagitis, food protein-induced enterocolitis syndrome and celiac disease. The second category implies non-immune mediated adverse food reactions, also called food intolerances. Intoxications, pharmacologic reactions, metabolic reactions, physiologic, psychologic or reactions with an unknown mechanism belong to this category. We present a classification of adverse food reactions based on the pathophysiologic mechanism that can be useful for both diagnostic approach and management.

  10. Visit-to-Visit Glucose Variability Predicts the Development of End-Stage Renal Disease in Type 2 Diabetes

    PubMed Central

    Yang, Ya-Fei; Li, Tsai-Chung; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Yang, Sing-Yu; Chiang, Jen-Huai; Huang, Chiu-Ching; Sung, Fung-Chang; Lin, Cheng-Chieh

    2015-01-01

    Abstract The purpose of this study was to examine the association of glucose variability using coefficient of variation of fasting plasma glucose (FPG-CV) and coefficient of variation of glycated hemoglobin (HbA1c-CV) to end-stage renal disease (ESRD) in 31,841 Chinese patients with type 2 diabetes. Patients with type 2 diabetes enrolled in National Diabetes Care Management Program, aged ≧30 years, and free of ESRD (n = 31,841) in January 1, 2002 to December 31, 2004 were included. Extended Cox proportional hazards regression models with competing risk of all-cause mortality were used to evaluate risk factors on ESRD incidence. Patients were followed till 2012. After a median follow-up period of 8.23 years, 1642 patients developed ESRD, giving a crude incidence rate of 6.27/1000 person-years (6.36 for men, 6.19 for women). After the multivariate adjustment, both FPG-CV and HbA1c-CV were independent predictors of ESRD with corresponding hazard ratios of 1.20 (95% confidence interval [CI] 1.01, 1.41), 1.24 (95% CI 1.05, 1.46) in HbA1c-CV from fourth to fifth quintile and 1.23 (95% CI 1.03, 1.47) in FPG-CV from fifth quintile. One-year visit-to-visit glucose variability expressed by FPG-CV and HbA1c-CV predicted development of ESRD in patients with type 2 diabetes, suggesting therapeutic strategies toward a goal to minimize glucose fluctuation. PMID:26554779

  11. Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose Tolerance in Female and Obese Individuals

    PubMed Central

    Hatziagelaki, Erifili; Ketterer, Caroline; Heni, Martin; Machicao, Fausto; Stefan, Norbert; Staiger, Harald; Häring, Hans-Ulrich; Fritsche, Andreas

    2012-01-01

    Introduction Single nucleotide polymorphisms (SNPs) in approximately 40 genes have been associated with an increased risk for type 2 diabetes (T2D) in genome-wide association studies. It is not known whether a similar genetic impact on the risk of prediabetes (impaired glucose tolerance [IGT] or impaired fasting glycemia [IFG]) exists. Methods In our cohort of 1442 non-diabetic subjects of European origin (normal glucose tolerance [NGT] n = 1046, isolated IFG n = 142, isolated IGT n = 140, IFG+IGT n = 114), an impact on glucose homeostasis has been shown for 9 SNPs in previous studies in this specific cohort. We analyzed these SNPs (within or in the vicinity of the genes TCF7L2, KCNJ11, HHEX, SLC30A8, WFS1, KCNQ1, MTNR1B, FTO, PPARG) for association with prediabetes. Results The genetic risk load was significantly associated with the risk for IGT (p = 0.0006) in a model including gender, age, BMI and insulin sensitivity. To further evaluate potential confounding effects, we stratified the population on gender, BMI and insulin sensitivity. The association of the risk score with IGT was present in female participants (p = 0.008), but not in male participants. The risk score was significantly associated with IGT (p = 0.008) in subjects with a body mass index higher than 30 kg/m2 but not in non-obese individuals. Furthermore, only in insulin resistant subjects a significant association between the genetic load and the risk for IGT (p = 0.01) was found. Discussion We found that T2D genetic risk alleles cause an increased risk for IGT. This effect was not present in male, lean and insulin sensitive subjects, suggesting a protective role of beneficial environmental factors on the genetic risk. PMID:22768041

  12. Histamine, histamine intoxication and intolerance.

    PubMed

    Kovacova-Hanuskova, E; Buday, T; Gavliakova, S; Plevkova, J

    2015-01-01

    Excessive accumulation of histamine in the body leads to miscellaneous symptoms mediated by its bond to corresponding receptors (H1-H4). Increased concentration of histamine in blood can occur in healthy individuals after ingestion of foods with high contents of histamine, leading to histamine intoxication. In individuals with histamine intolerance (HIT) ingestion of food with normal contents of histamine causes histamine-mediated symptoms. HIT is a pathological process, in which the enzymatic activity of histamine-degrading enzymes is decreased or inhibited and they are insufficient to inactivate histamine from food and to prevent its passage to blood-stream. Diagnosis of HIT is difficult. Multi-faced, non-specific clinical symptoms provoked by certain kinds of foods, beverages and drugs are often attributed to different diseases, such as allergy and food intolerance, mastocytosis, psychosomatic diseases, anorexia nervosa or adverse drug reactions. Correct diagnosis of HIT followed by therapy based on histamine-free diet and supplementation of diamine oxidase can improve patient's quality of life.

  13. Worry, Intolerance of Uncertainty, and Statistics Anxiety

    ERIC Educational Resources Information Center

    Williams, Amanda S.

    2013-01-01

    Statistics anxiety is a problem for most graduate students. This study investigates the relationship between intolerance of uncertainty, worry, and statistics anxiety. Intolerance of uncertainty was significantly related to worry, and worry was significantly related to three types of statistics anxiety. Six types of statistics anxiety were…

  14. Space Flight Orthostatic Intolerance Protection

    NASA Technical Reports Server (NTRS)

    Luty, Wei

    2009-01-01

    This paper summarizes investigations conducted on different orthostatic intolerance protection garments. This paper emphasizes on the engineering and operational aspects of the project. The current Shuttle pneumatic Anti-G Suit or AGS at 25 mmHg (0.5 psi) and customized medical mechanical compressive garments (20-30 mmHg) were tested on human subjects. The test process is presented. The preliminary results conclude that mechanical compressive garments can ameliorate orthostatic hypotension in hypovolemic subjects. A mechanical compressive garment is light, small and works without external pressure gas source; however the current garment design does not provide an adjustment to compensate for the loss of mass and size in the lower torso during long term space missions. It is also difficult to don. Compression garments that do not include an abdominal component are less effective countermeasures than garments which do. An early investigation conducted by the Human Adaptation and Countermeasures Division at Johnson Space Center (JSC) has shown there is no significant difference between the protection function of the AGS (at 77 mmHg or 1.5 psi) and the Russian anti-g suit, Kentavr (at 25 mmHg or 0.5 psi). Although both garments successfully countered hypovolemia-induced orthostatic intolerance, the Kentavr provided protection by using lower levels of compression pressure. This more recent study with a lower AGS pressure shows that pressures at 20-30 mmHg is acceptable but protection function is not as effective as higher pressure. In addition, a questionnaire survey with flight crewmembers who used both AGS and Kentavr during different missions was also performed.

  15. Intolerance of uncertainty and decisions about delayed, probabilistic rewards.

    PubMed

    Luhmann, Christian C; Ishida, Kanako; Hajcak, Greg

    2011-09-01

    Worry is the inflated concern about potential future threats and is a hallmark feature of generalized anxiety disorder. Previous theoretical work has suggested that worry may be a consequence of intolerance of uncertainty (IU). The current study seeks to explore the behavioral consequences of IU. Specifically, we examine how IU might be associated with aspects of reward-based decision making. We utilized a simple laboratory gambling task in which participants chose between small, low-probability rewards available immediately at the beginning of each trial and large, high-probability rewards only available after some variable delay. Results demonstrate that higher levels of intolerance of uncertainty were associated with a tendency to select the immediately available, but less valuable and less probable rewards. IU also predicted decision-makers' sensitivity to outcomes. We discuss the cognitive and affective mechanisms that are likely to underlie the observed decision-making behavior and the implications for anxiety disorders.

  16. [Progress on the research of lactose intolerance].

    PubMed

    Chen, J; Sai, X Y

    2016-02-01

    Our group generalized the research development of lactose intolerance, both internationally and nationally. We systematically reviewed the pathogenesis, genetic polymorphisms of lactase deficiency, relevant progress of diagnostic methods and treatment. Through this systematic review, we undedrstood that there were insufficient research efforts made on understanding the epidemiological feature of lactose intolerance in this country. Relevant genetic mutations of people were also not clear, neither the development of simple and effective diagnosis method made. We should continue to extensively and deeply carry out the study regarding methods for early prevention and intervention on lactose intolerance.

  17. [Progress on the research of lactose intolerance].

    PubMed

    Chen, J; Sai, X Y

    2016-02-01

    Our group generalized the research development of lactose intolerance, both internationally and nationally. We systematically reviewed the pathogenesis, genetic polymorphisms of lactase deficiency, relevant progress of diagnostic methods and treatment. Through this systematic review, we undedrstood that there were insufficient research efforts made on understanding the epidemiological feature of lactose intolerance in this country. Relevant genetic mutations of people were also not clear, neither the development of simple and effective diagnosis method made. We should continue to extensively and deeply carry out the study regarding methods for early prevention and intervention on lactose intolerance. PMID:26917535

  18. The diagnosis of hereditary fructose intolerance.

    PubMed

    Steinmann, B; Gitzelmann, R

    1981-09-01

    Hereditary fructose intolerance (HFI) is a potentially life-threatening disorder and can be suspected from a detailed nutritional history. The usefulness of 2 diagnostic procedures, fructose tolerance test (FTT) and aldolase assay on biopsied liver, was studied. A standardized intravenous FTT with 200 mg/kg b.w. was done on 11 children with HFI, 17 age-matched contrast children, 6 adults with HFI and 6 adult controls. Blood glucose, phosphorus, urate, magnesium and fructose were followed for 2 hours. By the FTT, each HFI individual was reliably distinguished from controls and contrasts and even from those with acute liver disease other than HFI. Both children with non-HFI hepatopathy examined by both procedures had a normal FTT in spite of reduced liver fructaldolase activity. HFI children responded to the FTT by earlier and more pronounced hypoglycemia than adults, and one girl converted to an adult type response between the ages 12 and 181/2 years. Responses of two HFI sibling pairs and of one set of monozygotic twins were typical for age, but resemblance was no greater than within the unrelated HFI probands. The intravenous FTT is judged a reliable diagnostic tool, simple and harmless if done in hospital. Essential fructosuria is readily diagnosed by the FTT, but fructose-1,6-diphosphatase deficiency and HFI are not differentiated with certainty. Liver biopsies were obtained from 35 children with HFI, 14 contrast persons and 10 controls (of which 9 organ donors) and examined enzymatically. Deficiency of fructaldolase was observed in all HFI children but also in some contrast children suffering from acute liver disease other than HFI. In these, HFI could only be excluded when the reduced activity of reference enzymes such as fructose-1,6-diphosphatase and glucose-6-phosphatase and liver histology were included in the evaluation. In one deceased HFI infant, fructaldolase was deficient in both, liver and kidney cortex. Extent of antibody activation and of heat

  19. Predictive Value of Triglyceride Glucose Index for the Risk of Incident Diabetes: A 4-Year Retrospective Longitudinal Study

    PubMed Central

    Lee, Da Young; Lee, Eun Seo; Kim, Ji Hyun; Park, Se Eun; Park, Cheol-Young; Oh, Ki-Won; Park, Sung-Woo

    2016-01-01

    The Triglyceride Glucose Index (TyG index) is considered a surrogate marker of insulin resistance. The aim of this study is to investigate whether the TyG index has a predictive role in identifying individuals with a high risk of incident diabetes and to compare it with other indicators of metabolic health. A total 2900 non-diabetic adults who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital was divided into four subgroups using three methods: (1) baseline TyG index; (2) obesity status (body mass index ≥25 kg/m2) and cutoff value of TyG index; (3) obesity status and metabolic health, defined as having fewer than two of the five components of high blood pressure, fasting blood glucose, triglyceride, low high-density lipoprotein cholesterol, and highest decile of homeostasis model assessment-insulin resistance. The development of diabetes was assessed annually using self-questionnaire, fasting glucose, and glycated hemoglobin. We compared the risk of incident diabetes using multivariate Cox analysis. During 11623 person-years there were 101 case of incident diabetes. Subjects with high TyG index had a high risk of diabetes. For TyG index quartiles, hazard ratios (HRs) of quartiles 3 and 4 were 4.06 (p = 0.033) and 5.65 (p = 0.006) respectively. When the subjects were divided by obesity status and cutoff value of TyG index of 8.8, the subgroups with TyG index ≥ 8.8 regardless of obesity had a significantly high risk for diabetes (HR 2.40 [p = 0.024] and 2.25 [p = 0.048]). For obesity status and metabolic health, the two metabolically unhealthy subgroups regardless of obesity had a significantly high risk for diabetes (HRs 2.54 [p = 0.024] and 2.73 [p = 0.021]). In conclusion, the TyG index measured at a single time point may be an indicator of the risk for incident diabetes. The predictive value of the TyG index was comparable to that of metabolic health. PMID:27682598

  20. Mechanisms of post-flight orthostatic intolerance

    NASA Technical Reports Server (NTRS)

    Blomqvist, C. G.; Buckey, J. C.; Gaffney, F. A.; Lane, L. D.; Levine, B. D.; Watenpaugh, D. E.

    1994-01-01

    Post-flight orthostatic intolerance is a dramatic physiological consequence of human adaptation to microgravity made inappropriate by a sudden return to 1-G. The immediate mechanism is almost always a failure to maintain adequate tissue perfusion, specifically perfusion of the central nervous system, but vestibular dysfunction may occasionally be the primary cause. Orthostatic intolerance is present in a wide range of clinical disorders of the nervous and cardiovascular systems. The intolerance that is produced by spaceflight and 1-G analogs (bed rest, head-down tilt at a moderate angle, water immersion) is different from its clinical counterparts by being only transiently present in subjects who otherwise have normal cardiovascular and regulatory systems. However, the same set of basic pathophysiological elements should be considered in the analysis of any form of orthostatic intolerance.

  1. Lactose intolerance: from diagnosis to correct management.

    PubMed

    Di Rienzo, T; D'Angelo, G; D'Aversa, F; Campanale, M C; Cesario, V; Montalto, M; Gasbarrini, A; Ojetti, V

    2013-01-01

    This review discusses one of the most relevant problems in gastrointestinal clinical practice: lactose intolerance. The role of lactase-persistence alleles the diagnosis of lactose malabsorption the development of lactose intolerance symptoms and its management. Most people are born with the ability to digest lactose, the major carbohydrate in milk and the main source of nutrition until weaning. Approximately, 75% of the world's population loses this ability at some point, while others can digest lactose into adulthood. Symptoms of lactose intolerance include abdominal pain, bloating, flatulence and diarrhea with a considerable intraindividual and interindividual variability in the severity. Diagnosis is most commonly performed by the non invasive lactose hydrogen breath test. Management of lactose intolerance consists of two possible clinical choice not mutually exclusive: alimentary restriction and drug therapy.

  2. Lactose intolerance: from diagnosis to correct management.

    PubMed

    Di Rienzo, T; D'Angelo, G; D'Aversa, F; Campanale, M C; Cesario, V; Montalto, M; Gasbarrini, A; Ojetti, V

    2013-01-01

    This review discusses one of the most relevant problems in gastrointestinal clinical practice: lactose intolerance. The role of lactase-persistence alleles the diagnosis of lactose malabsorption the development of lactose intolerance symptoms and its management. Most people are born with the ability to digest lactose, the major carbohydrate in milk and the main source of nutrition until weaning. Approximately, 75% of the world's population loses this ability at some point, while others can digest lactose into adulthood. Symptoms of lactose intolerance include abdominal pain, bloating, flatulence and diarrhea with a considerable intraindividual and interindividual variability in the severity. Diagnosis is most commonly performed by the non invasive lactose hydrogen breath test. Management of lactose intolerance consists of two possible clinical choice not mutually exclusive: alimentary restriction and drug therapy. PMID:24443063

  3. Possibility to predict early postpartum glucose abnormality following gestational diabetes mellitus based on the results of routine mid-gestational screening

    PubMed Central

    Bartáková, Vendula; Malúšková, Denisa; Mužík, Jan; Bělobrádková, Jana; Kaňková, Kateřina

    2015-01-01

    Introduction Women with previous gestational diabetes mellitus (GDM) have increased risk of developing glucose abnormality, but current diagnostic criteria are evidence-based for adverse pregnancy outcome. The aims of our study were: (i) to ascertain a frequency of early conversion of GDM into permanent glucose abnormality, (ii) to determine predictive potential of current GDM diagnostic criteria for prediction of postpartum glucose abnormality and (iii) to find optimal cut-off values of oral glucose tolerance test (oGTT) to stratify GDM population according to postpartum risk. Materials and methods Electronic medical records of an ethnically homogenous cohort of women diagnosed and treated for GDM in a single medical centre during the period 2005–2011 who completed postpartum oGTT up to 1 year after the index delivery were retrospectively analysed (N = 305). Results Postpartum glucose abnormality was detected in 16.7% subjects. Mid-trimester oGTT values, respective area under the curve and HbA1c were significantly associated with early postpartum glucose abnormality (P < 0.05, Mann-Whitney) and exhibited significant predictive potential for postpartum glucose abnormality risk assessment. Optimal cut-off values for discrimination of at-risk sub-population were identified using ROC analysis and their comparison with WHO and IADPSG criteria exhibited superiority of IADPSG for risk-stratification of GDM population. Conclusion Risk-based stratification at the time of GDM diagnosis could improve efficiency of the post-gestational screening for diabetes. IADPSG criteria seem to optimally capture both perinatal and maternal metabolic risks and are therefore medically and economically justified. PMID:26526166

  4. Predictive Value of Glucose Parameters Obtained From Oral Glucose Tolerance Tests in Identifying Individuals at High Risk for the Development of Diabetes in Korean Population.

    PubMed

    Yang, Hae Kyung; Ha, Hee-Sung; Rhee, Marie; Lee, Jin-Hee; Park, Yong-Moon; Kwon, Hyuk-Sang; Yim, Hyeon-Woo; Kang, Moo-Il; Lee, Won-Chul; Son, Ho-Young; Lee, Seung-Hwan; Yoon, Kun-Ho

    2016-03-01

    Previous studies suggest that the future risk for type 2 diabetes is not similar among subjects in the same glucose tolerance category. In this study, we aimed to evaluate simple intuitive indices to identify subjects at high risk for future diabetes development by using 0, 30, 120 minute glucose levels obtained during 75 g OGTTs from participants of a prospective community-based cohort in Korea.Among subjects enrolled at the Chungju Metabolic disease Cohort, those who performed an OGTT between 2007 and 2010 and repeated the test between 2011 and 2014 were recruited after excluding subjects with diabetes at baseline. Subjects were categorized according to their 30 minute glucose (G30) and the difference between 120 and 0 minute glucose (G(120-0)) levels with cutoffs of 9.75 and 2.50 mmol/L, respectively.Among 1126 subjects, 117 (10.39%) developed type 2 diabetes after 4 years. In diabetes nonconverters, increased insulin resistance was accompanied by compensatory insulin secretion, but this was not observed in converters during 4 years of follow-up. Subjects with G(120-0) ≥ 2.50 mmol/L or G30 ≥ 9.75 mmol/L demonstrated lower degrees of insulin secretion, higher degrees of insulin resistance, and ∼6-fold higher risk of developing future diabetes compared to their lower counterparts after adjustment for possible confounding factors. Moreover, subjects with high G(120-0) and high G30 demonstrated 22-fold higher risk for diabetes development compared to subjects with low G(120-0) and low G30.By using the G(120-0) and G30 values obtained during the OGTT, which are less complicated measurements than previously reported methods, we were able to select individuals at risk for future diabetes development. Further studies in different ethnicities are required to validate our results.

  5. Predictive Value of Glucose Parameters Obtained From Oral Glucose Tolerance Tests in Identifying Individuals at High Risk for the Development of Diabetes in Korean Population.

    PubMed

    Yang, Hae Kyung; Ha, Hee-Sung; Rhee, Marie; Lee, Jin-Hee; Park, Yong-Moon; Kwon, Hyuk-Sang; Yim, Hyeon-Woo; Kang, Moo-Il; Lee, Won-Chul; Son, Ho-Young; Lee, Seung-Hwan; Yoon, Kun-Ho

    2016-03-01

    Previous studies suggest that the future risk for type 2 diabetes is not similar among subjects in the same glucose tolerance category. In this study, we aimed to evaluate simple intuitive indices to identify subjects at high risk for future diabetes development by using 0, 30, 120 minute glucose levels obtained during 75 g OGTTs from participants of a prospective community-based cohort in Korea.Among subjects enrolled at the Chungju Metabolic disease Cohort, those who performed an OGTT between 2007 and 2010 and repeated the test between 2011 and 2014 were recruited after excluding subjects with diabetes at baseline. Subjects were categorized according to their 30 minute glucose (G30) and the difference between 120 and 0 minute glucose (G(120-0)) levels with cutoffs of 9.75 and 2.50 mmol/L, respectively.Among 1126 subjects, 117 (10.39%) developed type 2 diabetes after 4 years. In diabetes nonconverters, increased insulin resistance was accompanied by compensatory insulin secretion, but this was not observed in converters during 4 years of follow-up. Subjects with G(120-0) ≥ 2.50 mmol/L or G30 ≥ 9.75 mmol/L demonstrated lower degrees of insulin secretion, higher degrees of insulin resistance, and ∼6-fold higher risk of developing future diabetes compared to their lower counterparts after adjustment for possible confounding factors. Moreover, subjects with high G(120-0) and high G30 demonstrated 22-fold higher risk for diabetes development compared to subjects with low G(120-0) and low G30.By using the G(120-0) and G30 values obtained during the OGTT, which are less complicated measurements than previously reported methods, we were able to select individuals at risk for future diabetes development. Further studies in different ethnicities are required to validate our results. PMID:26962830

  6. Lactose intolerance in Indonesian children.

    PubMed

    Hegar, Badriul; Widodo, Ariani

    2015-01-01

    "Lactose intolerance (LI)" is considered a common problem in Asians, and in many parts of the world. Its prevalence and age of manifestation varies between by Asian country, for possible genetic or cultural reasons. Studies in Indonesian children 3-15 years old (y) are available within the past two decades, using a pure lactose tolerance test. The prevalences of lactose malabsorption (LM) in pre-elementary (3-5 y), elementary (6-11 y), and junior high (12-14 y) school-children were 21.3%, 57.8%, and 73%, respectively. An increasing trend for LM prevalence was seen within the pre-elementary group, from 9.1% at 3 y to 28.6% at 5 y. The most frequent symptoms of LI in junior high school (JHS) group were abdominal pain (64.1%), abdominal distention (22.6%), nausea (15.1%), flatulence (5.7%), and diarrhea (1.9%), mostly within one hour of lactose ingestion. In children with regular and irregular milk drinking, LM occurred in 81.2% and 69.6%; LI was found in 56.2% and 52.1%, respectively. Most JHS children with dairy-associated recurrent abdominal pain (RAP) symptoms proved to be malabsorbers. Dairy products most related to RAP were milk and yogurt. LI was found in 81% of RAP children with abdominal pain most frequently, followed by nausea, bloating, diarrhea, borborygmi, and flatulence. Symp-tom onset occurred 30 minutes after lactose ingestion, especially nausea, bloating, and abdominal pain. In RAP children LI symptoms mostly found in breath hydrogen concentration>20 ppm. More LI symptoms were found in lactose malabsorbers, but symptoms were mild and generally disappeared in 7 hours, and in most by 15 hours.

  7. Lactose intolerance in Indonesian children.

    PubMed

    Hegar, Badriul; Widodo, Ariani

    2015-01-01

    "Lactose intolerance (LI)" is considered a common problem in Asians, and in many parts of the world. Its prevalence and age of manifestation varies between by Asian country, for possible genetic or cultural reasons. Studies in Indonesian children 3-15 years old (y) are available within the past two decades, using a pure lactose tolerance test. The prevalences of lactose malabsorption (LM) in pre-elementary (3-5 y), elementary (6-11 y), and junior high (12-14 y) school-children were 21.3%, 57.8%, and 73%, respectively. An increasing trend for LM prevalence was seen within the pre-elementary group, from 9.1% at 3 y to 28.6% at 5 y. The most frequent symptoms of LI in junior high school (JHS) group were abdominal pain (64.1%), abdominal distention (22.6%), nausea (15.1%), flatulence (5.7%), and diarrhea (1.9%), mostly within one hour of lactose ingestion. In children with regular and irregular milk drinking, LM occurred in 81.2% and 69.6%; LI was found in 56.2% and 52.1%, respectively. Most JHS children with dairy-associated recurrent abdominal pain (RAP) symptoms proved to be malabsorbers. Dairy products most related to RAP were milk and yogurt. LI was found in 81% of RAP children with abdominal pain most frequently, followed by nausea, bloating, diarrhea, borborygmi, and flatulence. Symp-tom onset occurred 30 minutes after lactose ingestion, especially nausea, bloating, and abdominal pain. In RAP children LI symptoms mostly found in breath hydrogen concentration>20 ppm. More LI symptoms were found in lactose malabsorbers, but symptoms were mild and generally disappeared in 7 hours, and in most by 15 hours. PMID:26715082

  8. Design of the Health Monitoring System for the Artificial Pancreas: Low Glucose Prediction Module

    PubMed Central

    Harvey, Rebecca A.; Dassau, Eyal; Zisser, Howard; Seborg, Dale E.; Jovanovič, Lois; Doyle, Francis J.

    2012-01-01

    Background The purpose of this study was to design and evaluate a safety system for the artificial pancreas device system (APDS). Safe operation of the APDS is a critical task, where the safety system is engaged only as needed to ensure reliable operation without positive feedback to the controller. Methods The Health Monitoring System (HMS) was designed as a modular system to ensure the safety of the APDS and the user. It was designed using a large set of ambulatory data and evaluated in silico by inducing hypoglycemia with a missed meal [bolus for a 65 g carbohydrate (CHO) meal] and administering rescue CHOs per HMS alerting. The HMS was validated in-clinic with a real-life challenge of a subject who overdosed insulin prior to admission. Results The HMS was evaluated for clinical use with a 15 min prediction horizon. Retrospectively, 93.5% of episodes were detected with 2.9 false alarms per day. During in silico evaluation, the HMS reduced the time spent <70 mg/dl from 15% to 3%. When the HMS was first tested in-clinic, the subject overdosed ~3 U of insulin prior to her arrival to a closed-loop session (against protocol). The controller reduced insulin delivery, and the HMS gave four alerts that were successfully received via clinical software and text and multimedia messages. Even with insulin reduction and CHO supplements, hypoglycemia was unavoidable but manageable due to the HMS, confirming that a safety system to detect adverse events is an essential part of the APDS. Conclusions The ability of the HMS to be an effective alert system that provides a safety layer to the APDS controller has been demonstrated in a clinical setting. PMID:23294779

  9. Kinetic modeling of human hepatic glucose metabolism in type 2 diabetes mellitus predicts higher risk of hypoglycemic events in rigorous insulin therapy.

    PubMed

    König, Matthias; Holzhütter, Hermann-Georg

    2012-10-26

    A major problem in the insulin therapy of patients with diabetes type 2 (T2DM) is the increased occurrence of hypoglycemic events which, if left untreated, may cause confusion or fainting and in severe cases seizures, coma, and even death. To elucidate the potential contribution of the liver to hypoglycemia in T2DM we applied a detailed kinetic model of human hepatic glucose metabolism to simulate changes in glycolysis, gluconeogenesis, and glycogen metabolism induced by deviations of the hormones insulin, glucagon, and epinephrine from their normal plasma profiles. Our simulations reveal in line with experimental and clinical data from a multitude of studies in T2DM, (i) significant changes in the relative contribution of glycolysis, gluconeogenesis, and glycogen metabolism to hepatic glucose production and hepatic glucose utilization; (ii) decreased postprandial glycogen storage as well as increased glycogen depletion in overnight fasting and short term fasting; and (iii) a shift of the set point defining the switch between hepatic glucose production and hepatic glucose utilization to elevated plasma glucose levels, respectively, in T2DM relative to normal, healthy subjects. Intriguingly, our model simulations predict a restricted gluconeogenic response of the liver under impaired hormonal signals observed in T2DM, resulting in an increased risk of hypoglycemia. The inability of hepatic glucose metabolism to effectively counterbalance a decline of the blood glucose level becomes even more pronounced in case of tightly controlled insulin treatment. Given this Janus face mode of action of insulin, our model simulations underline the great potential that normalization of the plasma glucagon profile may have for the treatment of T2DM.

  10. Glucose and insulin metabolism in cirrhosis.

    PubMed

    Petrides, A S; DeFronzo, R A

    1989-01-01

    Glucose intolerance, overt diabetes mellitus, and insulin resistance are characteristic features of patients with cirrhosis. Insulin secretion, although increased in absolute terms, is insufficient to offset the presence of insulin resistance. The defect in insulin-mediated glucose disposal involves peripheral tissues, primarily muscle, and most likely reflects a disturbance in glycogen synthesis. Hepatic glucose production is normally sensitive to insulin; at present, it is unknown whether hepatic glucose uptake is impaired in cirrhosis. One of the more likely candidates responsible for the insulin-resistant state is insulin itself. The hyperinsulinemia results from three abnormalities: diminished hepatic extraction, portosystemic/intrahepatic shunting, and enhanced insulin secretion. PMID:2646365

  11. [Lactose intolerance: past and present. Part 1].

    PubMed

    Buzás, György Miklós

    2015-09-20

    Lactose intolerance is the most prevalent intestinal malabsorption disorder. After presentation of its history, the author describes the emergence of lactose intolerance during the evolution of species, and the biochemistry of lactose as well as features of human and bacterial lactase enzymes are then described. The unequal distribution of lactose intolerance in different continents and population is discussed, followed by presentation of past and present prevalence data in Hungary. Adult-type hypolactasia is caused by a polymorphism of the MCM6 gene located upstream from the lactase gene on the long arm of the chromosome 2. It can be determined with the polymerase chain reaction. The intestinal symptoms of lactose intolerance are well known, but its extra-intestinal manifestations are less recognised. Invasive diagnostic methods (determination of lactase activity from small intestinal biopsies, lactose tolerance test), are accurate, but have been replaced by the non-invasive methods; their gold standard is the H2 breath test. Genetic testing is being used more and more frequently in Hungary too, and, presumably, the methane breath test will be also available in the near future. Lactose intolerance can be accompanied by inflammatory bowel diseases, coeliac disease and irritable bowel syndrome; it could be established whether this association is causal or not in order to start a correct diet and therapy.

  12. [Lactose intolerance: past and present. Part 1].

    PubMed

    Buzás, György Miklós

    2015-09-20

    Lactose intolerance is the most prevalent intestinal malabsorption disorder. After presentation of its history, the author describes the emergence of lactose intolerance during the evolution of species, and the biochemistry of lactose as well as features of human and bacterial lactase enzymes are then described. The unequal distribution of lactose intolerance in different continents and population is discussed, followed by presentation of past and present prevalence data in Hungary. Adult-type hypolactasia is caused by a polymorphism of the MCM6 gene located upstream from the lactase gene on the long arm of the chromosome 2. It can be determined with the polymerase chain reaction. The intestinal symptoms of lactose intolerance are well known, but its extra-intestinal manifestations are less recognised. Invasive diagnostic methods (determination of lactase activity from small intestinal biopsies, lactose tolerance test), are accurate, but have been replaced by the non-invasive methods; their gold standard is the H2 breath test. Genetic testing is being used more and more frequently in Hungary too, and, presumably, the methane breath test will be also available in the near future. Lactose intolerance can be accompanied by inflammatory bowel diseases, coeliac disease and irritable bowel syndrome; it could be established whether this association is causal or not in order to start a correct diet and therapy. PMID:26550699

  13. High liver glycogen in hereditary fructose intolerance

    PubMed Central

    Cain, A. R. R.; Ryman, Brenda E.

    1971-01-01

    A case of hereditary fructose intolerance is reported in a girl aged 2 years at the time of her death. She had apparently progressed normally until the age of 14 months. At 19 months she was admitted to hospital with failure to thrive, hepatomegaly, and superficial infections. Investigations revealed hypoglycaemia, persistent acidosis, aminoaciduria, and a high liver glycogen level which suggested that she had glycogen storage disease. There was also some evidence of malabsorption. At necropsy the liver enzyme estimations showed that fructose 1-phosphate aldolase activity was absent and that fructose 1,6-diphosphate aldolase activity was reduced. Hereditary fructose intolerance and glycogen storage disease have been confused in the past on clinical grounds, but a high liver glycogen level has not previously been reported in hereditary fructose intolerance. PMID:5289293

  14. Dairy intake, dietary adequacy, and lactose intolerance.

    PubMed

    Heaney, Robert P

    2013-03-01

    Despite repeated emphasis in the Dietary Guidelines for Americans on the importance of calcium in the adult American diet and the recommendation to consume 3 dairy servings a day, dairy intake remains well below recommendations. Insufficient health professional awareness of the benefits of calcium and concern for lactose intolerance are among several possible reasons, This mini-review highlights both the role of calcium (and of dairy, its principal source in modern diets) in health maintenance and reviews the means for overcoming lactose intolerance (real or perceived).

  15. Blood pressure and plasma renin activity as predictors of orthostatic intolerance

    NASA Technical Reports Server (NTRS)

    Harrison, M. H.; Kravik, S. E.; Geelen, G.; Keil, L.; Greenleaf, J. E.

    1985-01-01

    The effect of 3 h standing, followed by a period of head-up tilt (HUT) on physiological response (orthostatic tolerance, blood pressure and heart rate), as well as on plasma vasopressin (PVP) and renin activity (PRA) were studied in 13 dehydrated (to 2.4 pct loss of body weight) subjects. Seven subjects showed signs of orthostatic intolerance (INT), manifested by sweating, pallor, nausea and dizziness. Prior to these symptoms, the INT subjects exhibited lower systolic (SP) and pulse (PP) pressures, and an elevated PRA, compared to the tolerant (TOL) subjects. HUT has aggravated increases of RPA in the INT subjects and caused an increase, higher than in TOL subjects, in PVP, while rehydration has greatly attenuated the PVP response to the HUT and decreased the PRA response. It is concluded that dehydration, together with measurements of SP, PP and PRA, may serve as a means of predicting orthostatic intolerance and may provide a physiological model for studying the causes of intolerance.

  16. Lactobezoar and cows' milk protein intolerance.

    PubMed

    Lemoh, J N; Watt, J

    1980-02-01

    A baby girl of an atopic family who developed eczema, asthma, and cows' milk protein intolerance was found to have a gastric lactobezoar at age 9 1/2 months. She responded well to the removal of the bezoar and to the appropriate dietary treatment.

  17. Lactobezoar and cows' milk protein intolerance.

    PubMed Central

    Lemoh, J N; Watt, J

    1980-01-01

    A baby girl of an atopic family who developed eczema, asthma, and cows' milk protein intolerance was found to have a gastric lactobezoar at age 9 1/2 months. She responded well to the removal of the bezoar and to the appropriate dietary treatment. Images Figure PMID:7189657

  18. [Lactose intolerance: past and present. Part II].

    PubMed

    Buzás, György Miklós

    2015-10-25

    The author summarises the interrelations between lactose intolerance, calcium and vitamin D metabolism and osteoporosis. Lactose intolerance enhances the risk of forearm and hip fractures in some patients. Lactase gene genotype and fracture risk are related in some populations. Calcium and vitamin D supplementation increase bone mineral content and they are justified in children, during pregnancy and lactation, and in postmenopausal women. The intake of milk and milk products could increase the risk of ovarian carcinoma. CC genotype of the lactase gene increased the risk of colorectal carcinoma in Finns; no such effect was observed in British, Spanish and Italian patients. Even small quantities of lactose in drugs (10-750 mg) could elicit intolerance symptoms due to individual susceptibility. In spite of public knowledge and advertising, controlled studies did not prove the beneficial effect of either a lactose-free diet, enzyme supplementation or probiotics in an evidence-based manner. While accepted guidelines are lacking, a personalised therapy is mandatory. In spite of increasing public interest in lactose intolerance, many unknown factors must still be studied.

  19. Adverse reactions to food: allergies and intolerances.

    PubMed

    Montalto, Massimo; Santoro, Luca; D'Onofrio, Ferruccio; Curigliano, Valentina; Gallo, Antonella; Visca, Dina; Cammarota, Giovanni; Gasbarrini, Antonio; Gasbarrini, Giovanni

    2008-01-01

    All the anomalous reactions secondary to food ingestion are defined as 'adverse reactions to food'. In 1995 the European Academy of Allergology and Clinical Immunology suggested a classification on the basis of the responsible pathogenetic mechanism; according to this classification, non-toxic reactions can be divided into 'food allergies' when they recognize immunological mechanisms, and 'food intolerances' when there are no immunological implications. The diagnostic approach to adverse reactions to food is based on accurate clinical history and objective examination, and further execution of specific tests when allergy or intolerance is suspected. The therapy for food allergies is the elimination of the food to which hypersensibility has been found; this strategy can lead, especially in pediatric age, to tolerance. If elimination diets cannot be completely performed, or if it is not possible to identify the food to eliminate, some drugs (e.g. antihistaminics, steroids, etc.) can be administered. Specific allergen immunotherapy has been recently introduced. Fundamental is food allergy prevention, especially in high-risk subjects. The therapeutic approach to secondary food intolerances is based principally on primitive disease resolution; on the other hand, some specific treatments (e.g. beta-galactosidases in lactose malabsorption) are available in case of primary intolerance. PMID:18431058

  20. Milk Intolerance and the American Indian

    ERIC Educational Resources Information Center

    Indian Historian, 1973

    1973-01-01

    The intolerance of milk by American Indians and other groups (Thais, Chinese, Filipinos, Melonesians of New Guinea, Australian Aborigines, Black groups of Africa, American Blacks, and Eskimos) due to the lack of the lactose enzyme is discussed in this article. (FF)

  1. Milk Intolerance, Beta-Casein and Lactose.

    PubMed

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen

    2015-09-01

    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows' milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows' milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows' milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  2. [Food allergy, food intolerance or functional disorder?].

    PubMed

    Wüthrich, B

    2009-04-01

    The term "food allergy" is widely misused for all sorts of symptoms and diseases caused by food. Food allergy (FA) is an adverse reaction to food (food hypersensitivity) occurring in susceptible individuals, which is mediated by a classical immune mechanism specific for the food itself. The best established mechanism in FA is due to the presence of IgE antibodies against the offending food. Food intolerance (FI) are all non-immune-mediated adverse reactions to food. The subgroups of FI are enzymatic (e.g. lactose intolerance due to lactase deficiency), pharmacological (reactions against biogenic amines, histamine intolerance), and undefined food intolerance (e.g. against some food additives). The diagnosis of an IgE-mediated FA is made by a carefully taken case history, supported by the demonstration of an IgE sensitization either by skin prick tests or by in vitro tests, and confirmed by positive oral provocation. For scientific purposes the only accepted test for the confirmation of FA/FI is a properly performed double-blind, placebo-controlled food challenge (DBPCFC). A panel of recombinant allergens, produced as single allergenic molecules, may in future improve the diagnosis of IgE-mediated FA. Due to a lack of causal treatment possibilities, the elimination of the culprit "food allergen" from the diet is the only therapeutic option for patients with real food allergy. PMID:19340768

  3. Tolerance and Intolerance in Multicultural Education.

    ERIC Educational Resources Information Center

    Heslep, Robert D.

    This essay argues that some proponents of multicultural education (ME) appear to teach intolerance of certain kinds of speech. The essay argues, in support, the down-playing of tolerance in ME as cultural respect, accommodation, and harmony are stronger candidates as virtues. The essay goes on to point out that ME does not teach cultural…

  4. Milk Intolerance, Beta-Casein and Lactose

    PubMed Central

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen

    2015-01-01

    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows’ milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed. PMID:26404362

  5. [Lactose intolerance: past and present. Part II].

    PubMed

    Buzás, György Miklós

    2015-10-25

    The author summarises the interrelations between lactose intolerance, calcium and vitamin D metabolism and osteoporosis. Lactose intolerance enhances the risk of forearm and hip fractures in some patients. Lactase gene genotype and fracture risk are related in some populations. Calcium and vitamin D supplementation increase bone mineral content and they are justified in children, during pregnancy and lactation, and in postmenopausal women. The intake of milk and milk products could increase the risk of ovarian carcinoma. CC genotype of the lactase gene increased the risk of colorectal carcinoma in Finns; no such effect was observed in British, Spanish and Italian patients. Even small quantities of lactose in drugs (10-750 mg) could elicit intolerance symptoms due to individual susceptibility. In spite of public knowledge and advertising, controlled studies did not prove the beneficial effect of either a lactose-free diet, enzyme supplementation or probiotics in an evidence-based manner. While accepted guidelines are lacking, a personalised therapy is mandatory. In spite of increasing public interest in lactose intolerance, many unknown factors must still be studied. PMID:26477616

  6. Milk Intolerance, Beta-Casein and Lactose.

    PubMed

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen

    2015-09-01

    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows' milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows' milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows' milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed. PMID:26404362

  7. Applying the Implicit Association Test to Measure Intolerance of Uncertainty.

    PubMed

    Mosca, Oriana; Dentale, Francesco; Lauriola, Marco; Leone, Luigi

    2016-08-01

    Intolerance of Uncertainty (IU) is a key trans-diagnostic personality construct strongly associated with anxiety symptoms. Traditionally, IU is measured through self-report measures that are prone to bias effects due to impression management concerns and introspective difficulties. Moreover, self-report scales are not able to intercept the automatic associations that are assumed to be main determinants of several spontaneous responses (e.g., emotional reactions). In order to overcome these limitations, the Implicit Association Test (IAT) was applied to measure IU, with a particular focus on reliability and criterion validity issues. The IU-IAT and the Intolerance of Uncertainty Inventory (IUI) were administered to an undergraduate student sample (54 females and 10 males) with a mean age of 23 years (SD = 1.7). Successively, participants were asked to provide an individually chosen uncertain event from their own lives that may occur in the future and were requested to identify a number of potential negative consequences of it. Participants' responses in terms of cognitive thoughts (i.e., cognitive appraisal) and worry reactions toward these events were assessed using the two subscales of the Worry and Intolerance of Uncertainty Beliefs Questionnaire. The IU-IAT showed an adequate level of internal consistency and a not significant correlation with the IUI. A path analysis model, accounting for 35% of event-related worry, revealed that IUI had a significant indirect effect on the dependent variable through event-related IU thoughts. By contrast, as expected, IU-IAT predicted event-related worry independently from IU thoughts. In accordance with dual models of social cognition, these findings suggest that IU can influence event-related worry through two different processing pathways (automatic vs. deliberative), supporting the criterion and construct validity of the IU-IAT. The potential role of the IU-IAT for clinical applications was discussed. PMID:27451266

  8. Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans.

    PubMed

    Pisprasert, Veeradej; Ingram, Katherine H; Lopez-Davila, Maria F; Munoz, A Julian; Garvey, W Timothy

    2013-04-01

    OBJECTIVE To examine the utility of commonly used insulin sensitivity indices in nondiabetic European Americans (EAs) and African Americans (AAs). RESEARCH DESIGN AND METHODS Two-hundred forty nondiabetic participants were studied. Euglycemic-hyperinsulinemic clamp was the gold standard approach to assess glucose disposal rates (GDR) normalized by lean body mass. The homeostatic model assessment for insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were calculated from fasting plasma glucose and insulin (FIL). Oral glucose tolerance test (OGTT) was performed to determine Matsuda index, the simple index assessing insulin sensitivity (SI(is)OGTT), Avignon index, and Stomvoll index. Relationships among these indices with GDR were analyzed by multiple regression. RESULTS GDR values were similar in EA and AA subgroups; even so, AA exhibited higher FIL and were insulin-resistant compared with EA, as assessed by HOMA-IR, QUICKI, Matsuda index, SI(is)OGTT, Avignon index, and Stumvoll index. In the overall study population, GDR was significantly correlated with all studied insulin sensitivity indices (/r/ = 0.381-0.513); however, these indices were not superior to FIL in predicting GDR. Race and gender affected the strength of this relationship. In AA males, FIL and HOMA-IR were not correlated with GDR. In contrast, Matsuda index and SI(is)OGTT were significantly correlated with GDR in AA males, and Matsuda index was superior to HOMA-IR and QUICKI in AAs overall. CONCLUSIONS Insulin sensitivity indices based on glucose and insulin levels should be used cautiously as measures of peripheral insulin sensitivity when comparing mixed gender and mixed race populations. Matsuda index and SI(is)OGTT are reliable in studies that include AA males.

  9. [Lactose intolerance: pathophysiology, clinical symptoms, diagnosis and treatment].

    PubMed

    Hutyra, Tomasz; Iwańczak, Barbara

    2009-02-01

    Lactose malabsorption and milk products intolerance symptoms are the most common alimentary tract disorders. Lactose intolerance is a result of lactase deficiency or lack of lactase and lactose malabsorption. Three types of lactase deficiency were distinguished: congenital, late-onset lactase deficiency and secondary lactase deficiency. Lactose intolerance means the appearance of clinical gastrointestinal symptoms after ingestion of lactose. To the clinical symptoms of lactose intolerance belongs: nausea, vomiting, abdominal distension, cramps, flatulence, flatus, diarrhea and abdominal pain. The diagnosis of lactose intolerance is based on the breath hydrogen test and analysis of lactase activity in the small intestine mucosa. Dietary treatment eliminates clinical symptoms.

  10. [Histamine intolerance - are the criteria of an adverse reaction met?].

    PubMed

    Reese, Imke

    2016-06-01

    Searching the internet for an explaination of recurring symptoms, many people come across the so-called histamine intolerance disorder. Also many practitioners like to diagnose this disorder without making sure that reproducibility, a prerequisite for an adverse reaction, is present. Consequently, presumably affected persons are often advised to follow a low-histamine diet. Depending on the source of information, these diets often avoid a huge variety of foods containing more or less histamine, which has a considerable impact on patient quality of life. While most persons benefit from such a diet in the beginning - this might be due to the change in dietary habits or the expectation of symptom improvement by dieting - in the long run the expected loss of symptoms will not happen. Underlying a diminished capacity for histamine degradation, the lack of partial or complete symptom improvement might be due to the fact that endogenous histamine release is responsible for reactions. The role of ingested histamine is discussed controversially. However, it is more than obvious that the histamine content of a certain food alone is not enough to predict its tolerance.If histamine intolerance is suspected, an individual diagnostic and therapeutic procedure is mandatory in order to minimize avoidance and to preserve a high quality of life. Ideally this is done in a close cooperation between allergologists and nutritionists/dieticians. PMID:27177895

  11. Prevalence and Symptom Correlation of Lactose Intolerance in the North East Part of Bangladesh.

    PubMed

    Saha, M; Shil, B C; Saha, S K; Chowdhury, M; Perveen, I; Banik, R; Rahman, M H

    2016-01-01

    This study was designed to see the prevalence of lactose intolerance and symptom correlation following oral lactose challenge in healthy volunteers in the north east part of Bangladesh. Symptoms of abdominal pain, nausea, borborygmi, flatulence, diarrhea and others were noted for 24 hours and blood glucose was estimated at 0 hour and 30 minutes after 50 gm oral lactose load to healthy volunteers. Failure to rise blood glucose level ≥1.1 mmol/l at 30 minutes after lactose intake from fasting level was taken as lactose malabsorption (LM) i.e., lactose intolerance. Sensitivity and specificity of different symptoms were then found out. A total of 171 volunteers (male 123, female 48) with a mean age 34.08 years participated in this study. Lactose intolerance was found among 82.5% (n=141, M=100, F=41) subjects. Symptoms mostly experience by the lactose malabsorbers were diarrhea 93(66.0%), borborygmi 80(56.7%), abdominal pain 31(22.0%) and flatulence 32(22.7%). LM prevalence was found to increase with increasing number of symptoms up to 3 symptoms. A week positive correlation (r=0.205, P=0.007) was found between the number of symptoms and proportion of subjects having positive lactose tolerance test. Lactose intolerance among healthy adults of North East part of our country is as common as in other Asian countries including China and Malaysia. But LM is higher than that of Europeans and south Indians. Diarrhea and borborygmi were mostly associated with LM. PMID:26931253

  12. Prevalence and Symptom Correlation of Lactose Intolerance in the North East Part of Bangladesh.

    PubMed

    Saha, M; Shil, B C; Saha, S K; Chowdhury, M; Perveen, I; Banik, R; Rahman, M H

    2016-01-01

    This study was designed to see the prevalence of lactose intolerance and symptom correlation following oral lactose challenge in healthy volunteers in the north east part of Bangladesh. Symptoms of abdominal pain, nausea, borborygmi, flatulence, diarrhea and others were noted for 24 hours and blood glucose was estimated at 0 hour and 30 minutes after 50 gm oral lactose load to healthy volunteers. Failure to rise blood glucose level ≥1.1 mmol/l at 30 minutes after lactose intake from fasting level was taken as lactose malabsorption (LM) i.e., lactose intolerance. Sensitivity and specificity of different symptoms were then found out. A total of 171 volunteers (male 123, female 48) with a mean age 34.08 years participated in this study. Lactose intolerance was found among 82.5% (n=141, M=100, F=41) subjects. Symptoms mostly experience by the lactose malabsorbers were diarrhea 93(66.0%), borborygmi 80(56.7%), abdominal pain 31(22.0%) and flatulence 32(22.7%). LM prevalence was found to increase with increasing number of symptoms up to 3 symptoms. A week positive correlation (r=0.205, P=0.007) was found between the number of symptoms and proportion of subjects having positive lactose tolerance test. Lactose intolerance among healthy adults of North East part of our country is as common as in other Asian countries including China and Malaysia. But LM is higher than that of Europeans and south Indians. Diarrhea and borborygmi were mostly associated with LM.

  13. [Impaired fasting glucose and postprandial glucose intolerance. The role of immediate family history].

    PubMed

    Romero-Mora, Luis Manuel; Durán-Íñiguez, Francisco; Castro-Barajas, Felipe de Jesús

    2013-01-01

    Objetivo: determinar la frecuencia de alteración de glucosa en ayunas (AGA) e intolerancia a la glucosa postprandial (IGP) en individuos con padre o madre diabéticos y con factores de riesgo para DM2. Método: estudio transversal en 162 hijos de padre o madre con DM2, de 30 a 35 años con factores de riesgo asociados a DM2. Se realizó glucosa plasmática de ayuno y a aquellos con AGA se les realizó curva de tolerancia a la glucosa. Resultados: se encontró prediabetes en 9.8 % (16) [de estos, el 43.8 % (7) presentó IGP] y 90.2 % (146) presentó normoglucemia. La media de edad en individuos con AGA e IGP fue 33.5 años. En los normo-glucémicos fue 32.2, t = 8.36, p = 0.004. La media del peso en AGA e IGP fue de 72.58 kg, y en normoglucémicos de 69.85 kg con t = 1.21 y p = 0.27. La media del IMC en AGA e IGP fue de 27.78, y en normoglucémicos de 26.58, t = 5.25, p = 0.02. Conclusión: Los resultados sugieren que en hijos de padre o madre diabéticos con factores de riesgo debe realizarse glucemia de ayuno para identificar tempranamente prediabetes o IGP.

  14. The change in cerebral glucose metabolism after electroacupuncture: a possible marker to predict the therapeutic effect of deep brain stimulation for refractory anorexia nervosa

    PubMed Central

    Liu, Tao-Tao; Hong, Qing-Xiong; Xiang, Hong-Bing

    2015-01-01

    Some reports have demonstrated that deep brain stimulation (DBS) is a promising treatment for patients who suffer from intractable anorexia nervosa. However, the nature of DBS may not be viewed as a standard clinical treatment option for anorexia nervosa because of the unpredictable outcome before DBS. Just like DBS in the brain, electroacupuncture at acupoints is also efficient in treating refractory anorexia nervosa. Some neuroimaging studies using functional magnetic resonance imaging, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) had revealed that both DBS and electroacupuncture at acupoints with electrical stimulation are related to the changes in cerebral glucose metabolism. Therefore, we hypothesize that the changes in cerebral glucose metabolism after electroacupuncture might be useful to predict the therapeutic effect of deep brain stimulation for refractory anorexia nervosa. PMID:26770596

  15. Toward a definition of intolerance of uncertainty: a review of factor analytical studies of the Intolerance of Uncertainty Scale.

    PubMed

    Birrell, Jane; Meares, Kevin; Wilkinson, Andrew; Freeston, Mark

    2011-11-01

    Since its emergence in the early 1990s, a narrow but concentrated body of research has developed examining the role of intolerance of uncertainty (IU) in worry, and yet we still know little about its phenomenology. In an attempt to clarify our understanding of this construct, this paper traces the way in which our understanding and definition of IU have evolved throughout the literature. This paper also aims to further our understanding of IU by exploring the latent variables measures by the Intolerance of Uncertainty Scale (IUS; Freeston, Rheaume, Letarte, Dugas & Ladouceur, 1994). A review of the literature surrounding IU confirmed that the current definitions are categorical and lack specificity. A critical review of existing factor analytic studies was carried out in order to determine the underlying factors measured by the IUS. Systematic searches yielded 9 papers for review. Two factors with 12 consistent items emerged throughout the exploratory studies, and the stability of models containing these two factors was demonstrated in subsequent confirmatory studies. It is proposed that these factors represent (i) desire for predictability and an active engagement in seeking certainty, and (ii) paralysis of cognition and action in the face of uncertainty. It is suggested that these factors may represent approach and avoidance responses to uncertainty. Further research is required to confirm the construct validity of these factors and to determine the stability of this structure within clinical samples.

  16. The biochemical basis of hereditary fructose intolerance.

    PubMed

    Bouteldja, Nadia; Timson, David J

    2010-04-01

    Hereditary fructose intolerance is a rare, but potentially lethal, inherited disorder of fructose metabolism, caused by mutation of the aldolase B gene. Treatment currently relies solely on dietary restriction of problematic sugars. Biochemical study of defective aldolase B enzymes is key to revealing the molecular basis of the disease and providing a stronger basis for improved treatment and diagnosis. Such studies have revealed changes in enzyme activity, stability and oligomerisation. However, linking these changes to disease phenotypes has not always been straightforward. This review gives a general overview of the features of hereditary fructose intolerance, then concentrates on the biochemistry of the AP variant (Ala149Pro variant of aldolase B) and molecular pathological consequences of mutation of the aldolase B gene.

  17. Orthostatic intolerance: a disorder of young women

    NASA Technical Reports Server (NTRS)

    Ali, Y. S.; Daamen, N.; Jacob, G.; Jordan, J.; Shannon, J. R.; Biaggioni, I.; Robertson, D.

    2000-01-01

    Orthostatic intolerance (OI) is a cause of significant disability in otherwise healthy women seen by gynecologists. Orthostatic tachycardia is often the most obvious hemodynamic abnormality found in OI patients, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety, and, in some cases, fainting (syncope). It is the most common disorder of blood pressure regulation after essential hypertension, and patients with OI are traditionally women of childbearing age. Estimates suggest that at least 500,000 Americans suffer from some form of OI, and such patients comprise the largest group referred to centers specialized in autonomic disorders. This article reviews recent advances made in the understanding of this condition, potential pathophysiological mechanisms contributing to orthostatic intolerance, and therapeutic alternatives currently available for the management of these patients.

  18. Intolerance to food additives - does it exist?

    PubMed

    Turner, Paul J; Kemp, Andrew S

    2012-02-01

    'Food intolerance' is often confused with a range of adverse symptoms which may be coincidental to ingestion of food. 'Food intolerance' is defined as a reaction in which symptoms must be objectively reproducible and not known to involve an immunological mechanism. A more precise term is non-allergic food hypersensitivity, which contrasts with food allergies which are due to an immunological mechanism. Some children will experience food reactions to food additives. Reported symptoms range from urticaria/angioedema to hyperactive behaviours. While parents/carers report that over one fifth of children experience of food reaction, only 1 in 20 of these are confirmed to have a non-allergic food hypersensitivity on testing.

  19. Lactose intolerance: diagnosis, genetic, and clinical factors.

    PubMed

    Mattar, Rejane; de Campos Mazo, Daniel Ferraz; Carrilho, Flair José

    2012-01-01

    Most people are born with the ability to digest lactose, the major carbohydrate in milk and the main source of nutrition until weaning. Approximately 75% of the world's population loses this ability at some point, while others can digest lactose into adulthood. This review discusses the lactase-persistence alleles that have arisen in different populations around the world, diagnosis of lactose intolerance, and its symptomatology and management. PMID:22826639

  20. Lactose intolerance: diagnosis, genetic, and clinical factors

    PubMed Central

    Mattar, Rejane; de Campos Mazo, Daniel Ferraz; Carrilho, Flair José

    2012-01-01

    Most people are born with the ability to digest lactose, the major carbohydrate in milk and the main source of nutrition until weaning. Approximately 75% of the world’s population loses this ability at some point, while others can digest lactose into adulthood. This review discusses the lactase-persistence alleles that have arisen in different populations around the world, diagnosis of lactose intolerance, and its symptomatology and management. PMID:22826639

  1. [Ocular intolerance to antiglaucoma medications is underestimated].

    PubMed

    Bresson-Dumont, H

    2010-01-01

    Since about 20 years, the large panel of the antiglaucoma eyedrops has drastically changed the management of glaucoma. Indications for filtering surgery had decreased in frequency. A great number of patients are controlled only by medications. However ocular intolerance and side effects have been reported until in 50% of the cases with 10% of severe manifestations of intolerance. Ocular side effects to topical medications may very often alter compliance. Ocular intolerance had been shown to be secondary to immunological mechanisms and direct or indirect toxicity. The immunological or allergic mechanisms are induced by a type I or IV hypersensibility and only represent 3% to 10% of all the side effects induced by topical medications. Toxic effect can be a direct through different mechanisms: pure toxic effect, acid pH, osmolarity of the solution, photosensibilisation. This will induce inflammatory reaction that will produce fibrosis in the long term. This toxic effect can be worsened by eye dryness or rosacea. Toxicity can also be indirect through an alteration of the conjunctival microbial flora and/or the lacrymal secretion. Concomitant obstruction of the lacrymal ducts may also contribute to this effect. These mechanisms could have been elucidated thank to histological studies from conjunctival mark, and more recently with confocal HRT, which gives an analysis of the ocular surface in vivo. Appropriate and early detection of intolerance to antiglaucoma medications is mandatory to adjust management strategies accordingly. These are based on the suppression or the reduction of conservative agents whenever possible, the use of fixed combinations, the reduction of the number of the instillations and the associated treatment of the ocular surface. PMID:21114054

  2. Seafood Allergy, Toxicity, and Intolerance: A Review.

    PubMed

    Prester, Ljerka

    2016-01-01

    Seafood allergies have been increasing their presence in the last 2 decades. Allergic reactions to seafood can range from mild urticarial and oral allergy syndrome to life-threatening anaphylactic reactions. Ingestion of seafood infested with Anisakis larvae can cause a disease known as anisakiasis with symptoms similar to true seafood allergy. Furthermore, some adverse reactions to seafood including histamine fish poisoning (HFP), and intolerance to histamine can trigger clinical symptoms, which, although nonallergic in origin, are similar to true immunoglobulin E (IgE)-mediated allergic reactions. Because seafood allergy usually remains a lifelong food allergy, this review focuses on the current knowledge on fish and shellfish allergens and emphasizes the importance of differentiating seafood allergy from other allergy-like reactions (anisakiasis, HFP, and intolerance to histamine). Key teaching points: • Fish and shellfish are potent allergens that can provoke serious IgE antibody-mediated adverse reactions in sensitive individuals. • Sensitization to seafood allergens can be achieved by ingestion, inhalation, or skin contact. • Shellfish major allergen, tropomyosin, shares significant homology to arthropods (dust mites and cockroaches). • Accidental exposures to seafood products cross-contaminated with fish or shellfish allergens (hidden allergens) during processing may present a health risk for sensitive individuals. • Allergens of fish parasite A. simplex present common hidden allergens in seafood, particularly in raw and undercooked home-made fish dishes. • Symptoms caused by HFP, histamine intolerance, and anisakiasis are similar to true seafood allergy.

  3. Idiopathic orthostatic intolerance and postural tachycardia syndromes

    NASA Technical Reports Server (NTRS)

    Jacob, G.; Biaggioni, I.; Robertson, D. (Principal Investigator)

    1999-01-01

    Upright posture imposes a substantial gravitational stress on the body, for which we are able to compensate, in large part because of the autonomic nervous system. Alteration in autonomic function, therefore, may lead to orthostatic intolerance. On one extreme, patients with autonomic failure caused by degenerative loss of autonomic function are severely disabled by orthostatic hypotension and may faint whenever they stand up. Fortunately, such patients are relatively rare. On the other hand, disabling orthostatic intolerance can develop in otherwise normal young people. These patients can be severely impaired by symptoms of fatigue, tachycardia, and shortness of breath when they stand up. The actual incidence of this disorder is unknown, but these patients make up the largest group of patients referred to centers that specialize in autonomic disorders. We will review recent advances made in the understanding of this condition, potential pathophysiological mechanisms that contribute to orthostatic intolerance, therapeutic alternatives currently available for the management of these patients, and areas in which more research is needed.

  4. Does the new American Diabetes Association definition for impaired fasting glucose improve its ability to predict type 2 diabetes mellitus in Spanish persons? The Asturias Study.

    PubMed

    Valdés, Sergio; Botas, Patricia; Delgado, Elías; Alvarez, Francisco; Cadórniga, Francisco Diaz

    2008-03-01

    In 2003, the American Diabetes Association reduced the lower limit defining impaired fasting glucose (IFG) to 100 mg/dL. The aim of this study was to analyze the impact of this change in the definition of IFG in a low-risk white population from northern Spain. The Asturias Study is a prospective, population-based survey of diabetes and cardiovascular risk factors. The baseline examination was carried out between 1998 and 1999 when 1034 individuals (age range, 30-75 years) were randomly selected to determine the prevalence of type 2 diabetes mellitus and prediabetes in the Principality of Asturias (northern Spain). In 2004 to 2005, these same subjects were invited for a follow-up examination. All participants without known diabetes underwent an oral glucose tolerance test both at baseline and follow-up. Application of the new American Diabetes Association definition resulted in 3 times more persons having IFG. The incidence rates of diabetes were 3.8, 19.5, and 58.0 per 1000 person-years in subjects with initial FPG values <100, 100 to 109, and 110 to 125 mg/dL, respectively. Inclusion of persons with an intermediate risk in the 100- to 109-mg/dL zone to the definition of IFG changed its positive predictive value, specificity, and sensitivity to predict diabetes from 36.5%, 94.5%, and 43.2% to 19.9%, 77.3%, and 75%, respectively. Receiver operating characteristics curve analysis including all the baseline fasting plasma glucose levels from 64 to 125 mg/dL depending on their ability to predict diabetes showed that the point closest to the ideal of 100% sensitivity and 100% specificity was 100 mg/dL. In conclusion, this study indicated that lowering the cutoff point for IFG optimizes its ability to predict diabetes in this Spanish population. The addition of other risk factors such as impaired glucose tolerance, hypertriglyceridemia, and overweight to IFG can stratify diabetes risk better.

  5. Visit-to-Visit Glucose Variability Predicts the Development of End-Stage Renal Disease in Type 2 Diabetes: 10-Year Follow-Up of Taiwan Diabetes Study.

    PubMed

    Yang, Ya-Fei; Li, Tsai-Chung; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Yang, Sing-Yu; Chiang, Jen-Huai; Huang, Chiu-Ching; Sung, Fung-Chang; Lin, Cheng-Chieh

    2015-11-01

    The purpose of this study was to examine the association of glucose variability using coefficient of variation of fasting plasma glucose (FPG-CV) and coefficient of variation of glycated hemoglobin (HbA1c-CV) to end-stage renal disease (ESRD) in 31,841 Chinese patients with type 2 diabetes.Patients with type 2 diabetes enrolled in National Diabetes Care Management Program, aged ≧30 years, and free of ESRD (n = 31,841) in January 1, 2002 to December 31, 2004 were included. Extended Cox proportional hazards regression models with competing risk of all-cause mortality were used to evaluate risk factors on ESRD incidence. Patients were followed till 2012.After a median follow-up period of 8.23 years, 1642 patients developed ESRD, giving a crude incidence rate of 6.27/1000 person-years (6.36 for men, 6.19 for women). After the multivariate adjustment, both FPG-CV and HbA1c-CV were independent predictors of ESRD with corresponding hazard ratios of 1.20 (95% confidence interval [CI] 1.01, 1.41), 1.24 (95% CI 1.05, 1.46) in HbA1c-CV from fourth to fifth quintile and 1.23 (95% CI 1.03, 1.47) in FPG-CV from fifth quintile.One-year visit-to-visit glucose variability expressed by FPG-CV and HbA1c-CV predicted development of ESRD in patients with type 2 diabetes, suggesting therapeutic strategies toward a goal to minimize glucose fluctuation. PMID:26554779

  6. Non responsive celiac disease due to coexisting hereditary fructose intolerance.

    PubMed

    Bharadia, Lalit; Shivpuri, Deepak

    2012-04-01

    Celiac disease is associated with several genetic disorders, but its association with hereditary fructose intolerance is rare. Hereditary fructose intolerance is a rare autosomal recessive disease of fructose metabolism presenting as vomiting after intake of fructose. An association between these two distinct genetic gastrointestinal disorders is important as treatment failure of celiac disease calls for careful evaluation for hereditary fructose intolerance. We report a patient with an association of these two disorders.

  7. The compelling anomaly of chemical intolerance.

    PubMed

    Miller, C S

    2001-03-01

    In science, anomalies expose the limitations of existing paradigms and drive the search for new ones. In the late 1800s, physicians observed that certain illnesses spread from sick, feverish individuals to those contacting them, paving the way for the germ theory of disease. The germ theory served as a crude, but elegant formulation that explained dozens of seemingly unrelated illnesses affecting literally every organ system. Today, we are witnessing another medical anomaly-a unique pattern of illness involving chemically exposed groups in more than a dozen countries, who subsequently report multisystem symptoms and new-onset chemical, food, and drug intolerances. These intolerances may be the hallmark for a new disease process or paradigm, just as fever is a hallmark for infection. The fact that diverse demographic groups, sharing little in common except some initial chemical exposure event, develop these intolerances is a compelling anomaly pointing to a possible new theory of disease, one that has been referred to as "Toxicant-Induced Loss of Tolerance" ("TILT"). TILT has the potential to explain certain cases of asthma, migraine headaches, and depression, as well as chronic fatigue, fibromyalgia, and "Gulf War syndrome". It appears to evolve in two stages: (1) initiation, characterized by a profound breakdown in prior, natural tolerance resulting from either acute or chronic exposure to chemicals (pesticides, solvents, indoor air contaminants, etc.), followed by (2) triggering of symptoms by small quantities of previously tolerated chemicals (traffic exhaust, fragrances, gasoline), foods, drugs, and food/drug combinations (alcohol, caffeine). While the underlying dynamic remains an enigma, observations indicating that affected individuals respond to structurally unrelated drugs and experience cravings and withdrawal-like symptoms, paralleling drug addiction, suggest that multiple neurotransmitter pathways may be involved.

  8. Threat by association: do distant intergroup threats carry-over into local intolerance?

    PubMed

    Bouman, Thijs; van Zomeren, Martijn; Otten, Sabine

    2014-09-01

    Individuals are often confronted with intergroup threats, yet many of these threats emanate from distant groups that most individuals are unlikely to encounter in their local environment. An important yet unanswered question is whether reactions to those threats, such as intolerance towards the threatening group, carry over to other groups that individuals actually do encounter in their local environment (e.g., immigrants). The main goal of our studies was to experimentally identify this carry-over effect of intergroup threat. Specifically, we hypothesized that (by definition relatively abstract) symbolic threats (e.g., threats to the ingroup's worldview) have an especially strong carry-over potential because those threats can be easily attributed to other outgroups. We tested these predictions in one correlational and two experimental studies. The results of all three studies confirmed our hypothesis that particularly distant symbolic threats were predictive of intolerance towards local outgroups.

  9. Lactose intolerance in systemic nickel allergy syndrome.

    PubMed

    Cazzato, I A; Vadrucci, E; Cammarota, G; Minelli, M; Gasbarrini, A

    2011-01-01

    Some patients affected by nickel-contact allergy present digestive symptoms in addition to systemic cutaneous manifestations, falling under the condition known as systemic nickel allergy syndrome (SNAS). A nickel-related pro-inflammatory status has been documented at intestinal mucosal level. The aim of the present study is to evaluate the prevalence of lactose intolerance in patients affected by SNAS compared to a healthy population. Consecutive patients affected by SNAS referring to our departments were enrolled. The control population consisted of healthy subjects without gastrointestinal symptoms. All subjects enrolled underwent lactose breath test under standard conditions. One hundred and seventy-eight SNAS patients and 60 healthy controls were enrolled. Positivity of lactose breath test occurred in 74.7% of the SNAS group compared to 6.6% of the control group. Lactose intolerance is highly prevalent in our series of patients affected by SNAS. Based on our preliminary results, we can hypothesize that in SNAS patients, the nickel-induced pro-inflammatory status could temporarily impair the brush border enzymatic functions, resulting in hypolactasia. Further trials evaluating the effect of a nickel-low diet regimen on lactase activity, histological features and immunological pattern are needed.

  10. [Histamine intolerance--possible dermatologic sequences].

    PubMed

    Lugović-Mihić, Liborija; Seserko, Ana; Duvancić, Tomislav; Situm, Mirna; Mihić, Josip

    2012-12-01

    Although histamine intolerance (HIT) is not very frequently encountered, it can have serious consequences. Food intolerance is a non allergic hypersensitivity to food that does not include the immune system even though the symptoms are similar to those of IgE-mediated allergic reactions. HIT apparently develops as a result of an impaired diamine oxidase (DAO) activity due to gastrointestinal disease or through DAO inhibition, as well as through a genetic predisposition which was proven in a number of patients. The intake of histamine-rich foods as well as alcohol or drugs which cause either the release of histamine or the blocking of DAO can lead to various disorders in many organs (gastrointestinal system, skin, lungs, cardiovascular system and brain), depending on the expression of histamine receptors. Dermatologic sequels can be rashes, itch, urticaria, angioedema, dermatitis, eczema and even acne, rosacea, psoriasis, and other. Recognizing the symptoms due to HIT is especially important in treating such patients. The significance of HIT in patients with atopic dermatitis in whom the benefit of a low histamine diet has been proven is becoming increasingly understood recently. Because of the possibility of symptoms affecting numerous organs, a detailed history of symptoms following the intake of histamine-rich foods or drugs that interfere with histamine metabolism is essential for making the diagnosis of HIT. Considering that such symptoms can be the result of multiple factors, the existence of HIT is usually underestimated, but considerable expectations are being made from future studies.

  11. [Intolerance to food additives: an update].

    PubMed

    Cardinale, F; Mangini, F; Berardi, M; Sterpeta Loffredo, M; Chinellato, I; Dellino, A; Cristofori, F; Di Domenico, F; Mastrototaro, M F; Cappiello, A; Centoducati, T; Carella, F; Armenio, L

    2008-12-01

    Contrary to common believing, the prevalence of the intolerance to food additives in the general population is rather low. Nowadays many doubts persist with regard both to the pathogenetic mechanisms and to the clinical and diagnostic aspects in this field. Symptoms due to, or exacerbated from, food additives usually involve non-IgE-mediate mechanisms (pseudo-allergic reactions, PAR) and are usually less severe of those induced by food allergy. The most frequent clinical feature of the intolerance to food additives still remains the urticaria-angioedema syndrome, although these substances are really involved only in a minority of patients. Other possible clinical features include anaphylaxis, atopic eczema, behaviour disturbances, asthma and non-allergic rhinitis. The diagnostic approach consists in diary cards, reporting symptoms and food habits, elimination diet and double blinded placebo-controlled oral challenge with suspected additives. However, such procedure still remains poorly standardized and numerous uncertainties persist with regard to optimal conditions for performing and interpret the challenge results. The therapeutic approach consists in the exclusion of foods and products containing the additive involved, and, in patients not compliant to the diet, in treatment with symptomatic drugs.

  12. Nutrient intake in lysinuric protein intolerance.

    PubMed

    Tanner, L M; Näntö-Salonen, K; Venetoklis, J; Kotilainen, S; Niinikoski, H; Huoponen, K; Simell, O

    2007-10-01

    Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder characterized by defective transport of cationic amino acids. Poor intestinal absorption and increased renal loss of arginine, ornithine and lysine lead to low plasma concentrations of these amino acids and, subsequently, to impaired urea cycle function. The patients therefore have decreased nitrogen tolerance, which may lead to hyperammonaemia after ingestion of normal amounts of dietary protein. As a protective mechanism, most patients develop strong aversion to protein-rich foods early in life. Oral supplementation with citrulline, which is absorbed normally and metabolized to arginine and ornithine, improves protein tolerance to some extent, as do sodium benzoate and sodium phenylbutyrate also used by some patients. Despite effective prevention of hyperammonaemia, the patients still consume a very restricted diet, which may be deficient in energy, essential amino acids and some vitamins and minerals. To investigate the potential nutritional problems of patients with lysinuric protein intolerance, 77 three- to four-day food records of 28 Finnish LPI patients aged 1.5-61 years were analysed. The data suggest that the patients are clearly at risk for many nutritional deficiencies, which may contribute to their symptoms. Their diet is highly deficient in calcium, vitamin D, iron and zinc. Individualized nutritional supplementation accompanied by regular monitoring of dietary intake is therefore an essential part of the treatment of LPI. PMID:17588131

  13. DEXA MEASURED VISCERAL ADIPOSE TISSUE PREDICTS IMPAIRED GLUCOSE TOLERANCE AND METABOLIC SYNDROME IN OBESE CAUCASIAN AND AFRICAN AMERICAN WOMEN

    PubMed Central

    Bi, X; Seabolt, L; Shibao, C; Buchowski, M; Kang, H; Keil, CD; Tyree, R; Silver, HJ

    2016-01-01

    Background and Aims New methods to measure visceral adipose tissue (VAT) by DEXA may help discern sex, race and phenotype differences in the role of VAT in cardiometabolic risk. This study was designed to: a) compare relationships between cardiometabolic risk factors and DEXA-VAT, anthropometric and body composition measures; b) determine thresholds for DEXA-VAT by race; and c) determine the most robust predictors of impaired glucose tolerance (IGT) and metabolic syndrome (MetSx) in obese women. Methods VAT area (cm2) was measured using Lunar iDXA scanner in 229 obese (BMI 30-49.9) women age 21–69 years of European American (EA = 123) and African American (AA = 106) descent. Linear regression modeling and areas under the curve (AUC) compared relationships with cardiometabolic risk. Bootstrapping with LASSO regression modeling determined thresholds and predictors of IGT and MetSx. Results DEXA-VAT explained more of the variance in triglycerides, blood pressure, glucose and HOMA-IR compared to anthropometric and body composition variables. DEXA-VAT had the highest AUC for IGT (0.767) and MetSx (0.749). Including race and interactionXrace terms in modeling did not significantly change results. Thresholds at which probability was ≥ 50% for IGT or MetSx were lower in AA women (IGT: 2120cm2 AA vs 2550cm2 EA; MetSx: 1320cm2 AA vs 1713cm2 EA). The odds for IGT or MetSx was 3-fold greater with each standard deviation increase in DEXA-VAT. Conclusion DEXA-VAT provides robust clinical information regarding cardiometabolic risk in AA and EA women and has great potential in risk reduction efforts. PMID:25335442

  14. The Intolerance of Uncertainty Scale for Children: A Psychometric Evaluation

    ERIC Educational Resources Information Center

    Comer, Jonathan S.; Roy, Amy K.; Furr, Jami M.; Gotimer, Kristin; Beidas, Rinad S.; Dugas, Michel J.; Kendall, Philip C.

    2009-01-01

    Intolerance of uncertainty (IU) has contributed to our understanding of excessive worry and adult anxiety disorders, but there is a paucity of research on IU in child samples. This gap is due to the absence of a psychometrically sound measure of IU in youth. The present study adapted parallel child- and parent-report forms of the Intolerance of…

  15. Intolerance of Uncertainty, Fear of Anxiety, and Adolescent Worry

    ERIC Educational Resources Information Center

    Dugas, Michel J.; Laugesen, Nina; Bukowski, William M.

    2012-01-01

    A 5 year, ten wave longitudinal study of 338 adolescents assessed the association between two forms of cognitive vulnerability (intolerance of uncertainty and fear of anxiety) and worry. Multilevel mediational analyses revealed a bidirectional and reciprocal relation between intolerance of uncertainty and worry in which change in one variable…

  16. Stable isotope models of sugar intake using hair, red blood cells, and plasma, but not fasting plasma glucose, predict sugar intake in a Yup'ik study population.

    PubMed

    Nash, Sarah H; Kristal, Alan R; Hopkins, Scarlett E; Boyer, Bert B; O'Brien, Diane M

    2014-01-01

    Objectively measured biomarkers will help to resolve the controversial role of sugar intake in the etiology of obesity and related chronic diseases. We recently validated a dual-isotope model based on RBC carbon (δ(13)C) and nitrogen (δ(15)N) isotope ratios that explained a large percentage of the variation in self-reported sugar intake in a Yup'ik study population. Stable isotope ratios can easily be measured from many tissues, including RBCs, plasma, and hair; however, it is not known how isotopic models of sugar intake compare among these tissues. Here, we compared self-reported sugar intake with models based on RBCs, plasma, and hair δ(13)C and δ(15)N in Yup'ik people. We also evaluated associations of sugar intake with fasting plasma glucose δ(13)C. Finally, we evaluated relations between δ(13)C and δ(15)N values in hair, plasma, RBCs, and fasting plasma glucose to allow comparison of isotope ratios across tissue types. Models using RBCs, plasma, or hair isotope ratios explained similar amounts of variance in total sugar, added sugar, and sugar-sweetened beverage intake (∼53%, 48%, and 34%, respectively); however, the association with δ(13)C was strongest for models based on RBCs and hair. There were no associations with fasting plasma glucose δ(13)C (R(2) = 0.03). The δ(13)C and δ(15)N values of RBCs, plasma, and hair showed strong, positive correlations; the slopes of these relations did not differ from 1. This study demonstrates that RBC, plasma, and hair isotope ratios predict sugar intake and provides data that will allow comparison of studies using different sample types.

  17. Lactose intolerance: an unnecessary risk for low bone density.

    PubMed

    Savaiano, Dennis

    2011-01-01

    The potential for lactose intolerance causes 25-50 million Americans and an unknown number of people around the world to avoid milk. Milk avoidance is a significant risk factor for low bone density. Individuals who avoid milk, due to intolerance or learned aversion, consume significantly less calcium and have poorer bone health and probable higher risk of osteoporosis. Lactose intolerance is easily managed by: (1) regular consumption of milk that adapts the colon bacteria and facilitates digestion of lactose; (2) consumption of yogurts and cheeses and other dairy foods low in lactose; consumption of dairy foods with meals to slow transit and maximize digestion, and use of lactose-digestive aids. As dairying spreads around the world to new markets and dairy foods become the dominant source of calcium in these markets, the potential for lactose intolerance will grow. Management of lactose intolerance globally will require both education and product development.

  18. [Calcium supplementation uncovering lactose intolerance - a case report].

    PubMed

    Trifina, Eva; Geissler, Dietmar; Zwettler, Elisabeth; Klaushofer, Klaus; Mikosch, Peter

    2012-03-01

    A 44 yr-old female with osteoporosis had no relevant gastrointestinal symptoms and did not avoid any specific food. However, after prescription of a lactose-rich calcium supplementation, clinical symptoms suspicious for lactose intolerance occurred, which were thereafter confirmed by a lactose tolerance test. Lactose intolerance may present with only slight or subtle symptoms. Drugs containing lactose may induce or increase gastrointestinal symptoms in patients with lactose intolerance. In case of gastrointestinal symptoms occurring after the initiation of drugs containing lactose, the possibility of lactose intolerance should be considered and tested by lactose tolerance test or genetic testing for the LCT (-13910) polymorphism. Due to the prevalence of about 15-25% lactose intolerance in the Austrian population, lactose free drugs should be prescribed as widely as possible.

  19. Hypothalamic NUCKS regulates peripheral glucose homoeostasis.

    PubMed

    Qiu, Beiying; Shi, Xiaohe; Zhou, Qiling; Chen, Hui Shan; Lim, Joy; Han, Weiping; Tergaonkar, Vinay

    2015-08-01

    Nuclear ubiquitous casein and cyclin-dependent kinase substrate (NUCKS) is highly expressed in the brain and peripheral metabolic organs, and regulates transcription of a number of genes involved in insulin signalling. Whole-body depletion of NUCKS (NKO) in mice leads to obesity, glucose intolerance and insulin resistance. However, a tissue-specific contribution of NUCKS to the observed phenotypes remains unknown. Considering the pivotal roles of insulin signalling in the brain, especially in the hypothalamus, we examined the functions of hypothalamic NUCKS in the regulation of peripheral glucose metabolism. Insulin signalling in the hypothalamus was impaired in the NKO mice when insulin was delivered through intracerebroventricular injection. To validate the hypothalamic specificity, we crossed transgenic mice expressing Cre-recombinase under the Nkx2.1 promoter with floxed NUCKS mice to generate mice with hypothalamus-specific deletion of NUCKS (HNKO). We fed the HNKO and littermate control mice with a normal chow diet (NCD) and a high-fat diet (HFD), and assessed glucose tolerance, insulin tolerance and metabolic parameters. HNKO mice showed mild glucose intolerance under an NCD, but exacerbated obesity and insulin resistance phenotypes under an HFD. In addition, NUCKS regulated levels of insulin receptor in the brain. Unlike HNKO mice, mice with immune-cell-specific deletion of NUCKS (VNKO) did not develop obesity or insulin-resistant phenotypes under an HFD. These studies indicate that hypothalamic NUCKS plays an essential role in regulating glucose homoeostasis and insulin signalling in vivo.

  20. Meibomian gland dysfunction and contact lens intolerance.

    PubMed

    Korb, D R; Henriquez, A S

    1980-03-01

    A study of a syndrome characterized by deficient or inadequate Meibomian gland secretions, minimal or transient symptoms suggestive of ocular dryness, fluorescein staining of the cornea (often detected only after delayed observation or sequential instillation of stain), and contact lens intolerance is described. Clinical and cytologic studies indicate that the syndrome is due to obstruction of the Meibomian gland orifices by desquamated epithelial cells that tend to aggregate in keratotic clusters, which results in alteration of the Meibomian glands' contribution to the precorneal tear film. Further complication may result from bacterial proliferation in the desquamated keratotic cells and the release of the bacteria and their toxic products into the precorneal tear film from these reservoirs in the excretory pathways of the Meibomian glands.

  1. From 'lactose intolerance' to 'lactose nutrition'.

    PubMed

    Lukito, Widjaja; Malik, Safarina G; Surono, Ingrid S; Wahlqvist, Mark L

    2015-01-01

    The concept of lactose intolerance has become embedded in Western medicine and developing economy medicine. It is based on evidence that intestinal lactase activity persists into later childhood and throughout life in only a minority of the world's population, notably northern European-derived populations. These people have the T single nucleotide polymorphism (SNP) of the rs49882359 allele (C/T), also known as C/T-13910, the MCM6 gene which positively influences the lactase LCT gene. Other lactase persistent (LP) populations are found in Africa and the Middle East with different genetic variants. These SNPs represent co-evolution with dairying since the agricultural revolution and nutrient-dependent ecological adaptation. That said, gastrointestinal symptoms considered due to small intestinal lactose malabsorption are poorly correlated with lactase non-persistence (LNP), the situation for most people. With LNP, colonic microbiome lactase enables lactose fermentation to occur so that none is found in faeces. Whether the short chain fatty acids (SCFAs) and gases (hydrogen, carbon dioxide and methane) produced cause symptoms is dose-dependent. Up to 25 g of lactose at any one time can usually be consumed by a LNP person, but its food and meal pattern context, the microbiomic characteristics, age and other factors may alter tolerance. Thus, the notion that lactose intolerance is a disorder or disease of LNP people is misplaced and has been one of cultural perspective. What actually matters is whether a particular dairy product as normally consumed give rise to symptoms. It is, therefore, proposed that lactose tolerance tests be replaced with dairy food tolerance tests.

  2. From 'lactose intolerance' to 'lactose nutrition'.

    PubMed

    Lukito, Widjaja; Malik, Safarina G; Surono, Ingrid S; Wahlqvist, Mark L

    2015-01-01

    The concept of lactose intolerance has become embedded in Western medicine and developing economy medicine. It is based on evidence that intestinal lactase activity persists into later childhood and throughout life in only a minority of the world's population, notably northern European-derived populations. These people have the T single nucleotide polymorphism (SNP) of the rs49882359 allele (C/T), also known as C/T-13910, the MCM6 gene which positively influences the lactase LCT gene. Other lactase persistent (LP) populations are found in Africa and the Middle East with different genetic variants. These SNPs represent co-evolution with dairying since the agricultural revolution and nutrient-dependent ecological adaptation. That said, gastrointestinal symptoms considered due to small intestinal lactose malabsorption are poorly correlated with lactase non-persistence (LNP), the situation for most people. With LNP, colonic microbiome lactase enables lactose fermentation to occur so that none is found in faeces. Whether the short chain fatty acids (SCFAs) and gases (hydrogen, carbon dioxide and methane) produced cause symptoms is dose-dependent. Up to 25 g of lactose at any one time can usually be consumed by a LNP person, but its food and meal pattern context, the microbiomic characteristics, age and other factors may alter tolerance. Thus, the notion that lactose intolerance is a disorder or disease of LNP people is misplaced and has been one of cultural perspective. What actually matters is whether a particular dairy product as normally consumed give rise to symptoms. It is, therefore, proposed that lactose tolerance tests be replaced with dairy food tolerance tests. PMID:26715078

  3. Anti-α-glucose-based glycan IgM antibodies predict relapse activity in multiple sclerosis after the first neurological event

    PubMed Central

    Freedman, MS; Laks, J; Dotan, N; Altstock, RT; Dukler, A; Sindic, CJM

    2009-01-01

    Background There is no specific serum-based biomarker for the diagnosis or prognosis of relapsing-remitting multiple sclerosis (RRMS). Objective We investigated whether levels of IgM antibodies to Glc(α1,4)Glc(α) (GAGA4) or to a panel of four glucose-based glycans could differentiate MS from other neurological diseases (OND) or predict risk of early relapse following first presentation (FP) of RRMS. Methods Retrospective analysis of 440 sera samples of three cohorts: A) FP-RRMS (n = 44), OND (n = 44); B) FP-RRMS (n = 167), OND (n = 85); and C) FP (n = 100). Anti-GAGA4 IgM levels were measured by enzyme immunoassay in cohort-A and cohort-B. Cohort-C IgM antibodies to glucosebased glycan panel were measured by immunofluorescence. Results FP-RRMS had higher levels of anti-GAGA4 IgM than OND patients (cohort-A, P = 0.01; cohort-B, P = 0.0001). Sensitivity and specificity were 27% and 97% for cohort-A; and 26% and 90% for cohort-B, respectively. In cohort-C, 58 patients experienced early relapse (<24 months), 31 had late relapse (≥24 months), and 11 did not experience second attack during follow-up. Kaplan– Meier curves demonstrated decrease in time to next relapse for patients positive for the antibody panel (P = 0.02, log rank). Conclusions Serum anti-GAGA4 IgM discerns FP-RRMS patients from OND patients. Higher levels of serum anti-α-glucose IgM in FP patients predict imminent early relapse. PMID:19324980

  4. [Food intolerances caused by enzyme defects and carbohydrate malassimiliations : Lactose intolerance and Co].

    PubMed

    Schäfer, Christiane

    2016-06-01

    Apart from allergic conditions, carbohydrate malassimiliations (sugar metabolism disorders) are classified within the group of food intolerances. These dose-dependent, yet non-immunological reactions require gastroenterological or internal diagnosis following nutritional therapy. Intolerances to carbohydrates such as lactose (milk sugar) and fructose (fruit sugar) in addition to sugar alcohols (sorbitol, mannitol, lactitol etc.) have been gaining increasing attention in recent decades as they are the cause of a wide range of gastrointestinal symptoms. There are currently various options for both diagnosis and therapy that differ notably in terms of effort, costs, and efficiency. Nutritional change and patient education are the bases of therapy. Non-observance of the trigger will result in increasing complaints and possibly even more infections, e.g., diverticula, rectal disorders, bacterial miscolonization, bile acid malabsorption). For an optimal therapy, the following sugar metabolism disorders have to be differentiated: hypolactasia versus lactose maldigestion, fructose malabsorption versus fructose overload, combined lactose and fructose intolerance, and isolated adverse reactions against sorbitol.For the medical conditions listed above, a three- or four-stage treatment regimen is recommended. Extensive dietary restrictions with regard to the relevant sugar, except for lactose, should not be maintained over a longer period of time.

  5. [Food intolerances caused by enzyme defects and carbohydrate malassimiliations : Lactose intolerance and Co].

    PubMed

    Schäfer, Christiane

    2016-06-01

    Apart from allergic conditions, carbohydrate malassimiliations (sugar metabolism disorders) are classified within the group of food intolerances. These dose-dependent, yet non-immunological reactions require gastroenterological or internal diagnosis following nutritional therapy. Intolerances to carbohydrates such as lactose (milk sugar) and fructose (fruit sugar) in addition to sugar alcohols (sorbitol, mannitol, lactitol etc.) have been gaining increasing attention in recent decades as they are the cause of a wide range of gastrointestinal symptoms. There are currently various options for both diagnosis and therapy that differ notably in terms of effort, costs, and efficiency. Nutritional change and patient education are the bases of therapy. Non-observance of the trigger will result in increasing complaints and possibly even more infections, e.g., diverticula, rectal disorders, bacterial miscolonization, bile acid malabsorption). For an optimal therapy, the following sugar metabolism disorders have to be differentiated: hypolactasia versus lactose maldigestion, fructose malabsorption versus fructose overload, combined lactose and fructose intolerance, and isolated adverse reactions against sorbitol.For the medical conditions listed above, a three- or four-stage treatment regimen is recommended. Extensive dietary restrictions with regard to the relevant sugar, except for lactose, should not be maintained over a longer period of time. PMID:27188621

  6. Blood glucose concentration for predicting poor outcomes in patients with and without impaired glucose metabolism undergoing off-pump coronary artery bypass surgery – long-term observational study

    PubMed Central

    Majstrak, Franciszek; Opolski, Grzegorz; Filipiak, Krzysztof J.

    2016-01-01

    Introduction Strict glucose control is an everyday practice in the perioperative period. Elevated glucose level has a deleterious impact on clinical results, but a therapeutic target has not been stated yet. Aim To determine a glucose concentration range affecting long-term outcomes after coronary artery bypass surgery (CABG). Material and methods This study is a retrospective evaluation of consecutive patients treated in a university hospital in Poland from 2004 to 2008. Patients were divided into 2 groups: an impaired glucose metabolism group (IGM) if they had 1) known DM or 2) perioperative hyperglycaemia defined as ≥ 200 mg/dl; and a non-IGM group. The end point (EP) was all-cause mortality. Results One thousand two hundred and eleven patients were covered by the analysis. The observation time was from 01.01.2004 until 01.08.2012. Patients who had maximal glucose concentrations < 242 mg/dl had the lowest mortality risk (EP in 21.1%); a higher risk was noted in the group with glucose concentrations 242–324 mg/dl (EP in 30.8%); and a very high risk was found for the group where glucose concentration was > 324 mg/dl (EP in 44.2%) (p = 0.041). Patients with IGM had a shorter survival at the end of the study (p < 0.001). The longest survival was observed in patients whose maximal glucose level was ≤ 242 mg/dl (p < 0.001) and the minimal glucose concentration was in the range 61–110 mg/dl (p < 0.001). Conclusions Tight glucose concentration control should be performed irrespective of a diabetes diagnosis and proper treatment introduced when necessary. Maximal glucose concentration should be kept < 242 mg/dl, while the minimum should be in the range 60–110 mg/dl. PMID:27625687

  7. Blood glucose concentration for predicting poor outcomes in patients with and without impaired glucose metabolism undergoing off-pump coronary artery bypass surgery – long-term observational study

    PubMed Central

    Majstrak, Franciszek; Opolski, Grzegorz; Filipiak, Krzysztof J.

    2016-01-01

    Introduction Strict glucose control is an everyday practice in the perioperative period. Elevated glucose level has a deleterious impact on clinical results, but a therapeutic target has not been stated yet. Aim To determine a glucose concentration range affecting long-term outcomes after coronary artery bypass surgery (CABG). Material and methods This study is a retrospective evaluation of consecutive patients treated in a university hospital in Poland from 2004 to 2008. Patients were divided into 2 groups: an impaired glucose metabolism group (IGM) if they had 1) known DM or 2) perioperative hyperglycaemia defined as ≥ 200 mg/dl; and a non-IGM group. The end point (EP) was all-cause mortality. Results One thousand two hundred and eleven patients were covered by the analysis. The observation time was from 01.01.2004 until 01.08.2012. Patients who had maximal glucose concentrations < 242 mg/dl had the lowest mortality risk (EP in 21.1%); a higher risk was noted in the group with glucose concentrations 242–324 mg/dl (EP in 30.8%); and a very high risk was found for the group where glucose concentration was > 324 mg/dl (EP in 44.2%) (p = 0.041). Patients with IGM had a shorter survival at the end of the study (p < 0.001). The longest survival was observed in patients whose maximal glucose level was ≤ 242 mg/dl (p < 0.001) and the minimal glucose concentration was in the range 61–110 mg/dl (p < 0.001). Conclusions Tight glucose concentration control should be performed irrespective of a diabetes diagnosis and proper treatment introduced when necessary. Maximal glucose concentration should be kept < 242 mg/dl, while the minimum should be in the range 60–110 mg/dl.

  8. Clinical evaluation, biochemistry and genetic polymorphism analysis for the diagnosis of lactose intolerance in a population from northeastern Brazil

    PubMed Central

    Ponte, Paulo Roberto Lins; de Medeiros, Pedro Henrique Quintela Soares; Havt, Alexandre; Caetano, Joselany Afio; Cid, David A C; de Moura Gondim Prata, Mara; Soares, Alberto Melo; Guerrant, Richard L; Mychaleckyj, Josyf; Lima, Aldo Ângelo Moreira

    2016-01-01

    OBJECTIVE: This work aimed to evaluate and correlate symptoms, biochemical blood test results and single nucleotide polymorphisms for lactose intolerance diagnosis. METHOD: A cross-sectional study was conducted in Fortaleza, Ceará, Brazil, with a total of 119 patients, 54 of whom were lactose intolerant. Clinical evaluation and biochemical blood tests were conducted after lactose ingestion and blood samples were collected for genotyping evaluation. In particular, the single nucleotide polymorphisms C>T-13910 and G>A-22018 were analyzed by restriction fragment length polymorphism/polymerase chain reaction and validated by DNA sequencing. RESULTS: Lactose-intolerant patients presented with more symptoms of flatulence (81.4%), bloating (68.5%), borborygmus (59.3%) and diarrhea (46.3%) compared with non-lactose-intolerant patients (p<0.05). We observed a significant association between the presence of the alleles T-13910 and A-22018 and the lactose-tolerant phenotype (p<0.05). After evaluation of the biochemical blood test results for lactose, we found that the most effective cutoff for glucose levels obtained for lactose malabsorbers was <15 mg/dL, presenting an area under the receiver operating characteristic curve greater than 80.3%, with satisfactory values for sensitivity and specificity. CONCLUSIONS: These data corroborate the association of these single nucleotide polymorphisms (C>T-13910 and G>A-22018) with lactose tolerance in this population and suggest clinical management for patients with lactose intolerance that considers single nucleotide polymorphism detection and a change in the biochemical blood test cutoff from <25 mg/dL to <15 mg/dL. PMID:26934237

  9. Diagnosing and Treating Intolerance to Carbohydrates in Children

    PubMed Central

    Berni Canani, Roberto; Pezzella, Vincenza; Amoroso, Antonio; Cozzolino, Tommaso; Di Scala, Carmen; Passariello, Annalisa

    2016-01-01

    Intolerance to carbohydrates is relatively common in childhood, but still poorly recognized and managed. Over recent years it has come to the forefront because of progresses in our knowledge on the mechanisms and treatment of these conditions. Children with intolerance to carbohydrates often present with unexplained signs and symptoms. Here, we examine the most up-to-date research on these intolerances, discuss controversies relating to the diagnostic approach, including the role of molecular analysis, and provide new insights into modern management in the pediatric age, including the most recent evidence for correct dietary treatment. PMID:26978392

  10. Diagnosing and Treating Intolerance to Carbohydrates in Children.

    PubMed

    Berni Canani, Roberto; Pezzella, Vincenza; Amoroso, Antonio; Cozzolino, Tommaso; Di Scala, Carmen; Passariello, Annalisa

    2016-03-10

    Intolerance to carbohydrates is relatively common in childhood, but still poorly recognized and managed. Over recent years it has come to the forefront because of progresses in our knowledge on the mechanisms and treatment of these conditions. Children with intolerance to carbohydrates often present with unexplained signs and symptoms. Here, we examine the most up-to-date research on these intolerances, discuss controversies relating to the diagnostic approach, including the role of molecular analysis, and provide new insights into modern management in the pediatric age, including the most recent evidence for correct dietary treatment.

  11. Intolerance of uncertainty, fear of anxiety, and adolescent worry.

    PubMed

    Dugas, Michel J; Laugesen, Nina; Bukowski, William M

    2012-08-01

    A 5 year, ten wave longitudinal study of 338 adolescents assessed the association between two forms of cognitive vulnerability (intolerance of uncertainty and fear of anxiety) and worry. Multilevel mediational analyses revealed a bidirectional and reciprocal relation between intolerance of uncertainty and worry in which change in one variable partially explained change in the other. Fear of anxiety and worry also showed evidence of a bidirectional relation, although change in fear of anxiety had a much weaker mediational effect on change in worry than vice versa. The findings show that relative to fear of anxiety, intolerance of uncertainty may play a greater role in the etiology of worry in adolescents.

  12. Diagnosing and Treating Intolerance to Carbohydrates in Children.

    PubMed

    Berni Canani, Roberto; Pezzella, Vincenza; Amoroso, Antonio; Cozzolino, Tommaso; Di Scala, Carmen; Passariello, Annalisa

    2016-03-01

    Intolerance to carbohydrates is relatively common in childhood, but still poorly recognized and managed. Over recent years it has come to the forefront because of progresses in our knowledge on the mechanisms and treatment of these conditions. Children with intolerance to carbohydrates often present with unexplained signs and symptoms. Here, we examine the most up-to-date research on these intolerances, discuss controversies relating to the diagnostic approach, including the role of molecular analysis, and provide new insights into modern management in the pediatric age, including the most recent evidence for correct dietary treatment. PMID:26978392

  13. Glucose tolerance, insulin release, and insulin binding to monocytes in kidney transplant recipients

    SciTech Connect

    Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.

    1982-03-01

    In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific /sup 125/I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific /sup 125/I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity.

  14. Hypocapnia and cerebral hypoperfusion in orthostatic intolerance

    NASA Technical Reports Server (NTRS)

    Novak, V.; Spies, J. M.; Novak, P.; McPhee, B. R.; Rummans, T. A.; Low, P. A.

    1998-01-01

    BACKGROUND AND PURPOSE: Orthostatic and other stresses trigger tachycardia associated with symptoms of tremulousness, shortness of breath, dizziness, blurred vision, and, often, syncope. It has been suggested that paradoxical cerebral vasoconstriction during head-up tilt might be present in patients with orthostatic intolerance. We chose to study middle cerebral artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation during tilt in patients with orthostatic intolerance (OI). METHODS: Beat-to-beat BFV from the MCA, heart rate, CO2, blood pressure (BP), and respiration were measured in 30 patients with OI (25 women and 5 men; age range, 21 to 44 years; mean age, 31.3+/-1.2 years) and 17 control subjects (13 women and 4 men; age range, 20 to 41 years; mean age, 30+/-1.6 years); ages were not statistically different. These indices were monitored during supine rest and head-up tilt (HUT). We compared spontaneous breathing and hyperventilation and evaluated the effect of CO2 rebreathing in these 2 positions. RESULTS: The OI group had higher supine heart rates (P<0.001) and cardiac outputs (P<0.01) than the control group. In response to HUT, OI patients underwent a greater heart rate increment (P<0.001) and greater reductions in pulse pressure (P<0.01) and CO2 (P<0.001), but total systemic resistance failed to show an increment. Among the cerebrovascular indices, all BFVs (systolic, diastolic, and mean) decreased significantly more, and cerebrovascular resistance (CVR) was increased in OI patients (P<0.01) compared with control subjects. In both groups, hyperventilation induced mild tachycardia (P<0.001), a significant reduction of BFV, and a significant increase of CVR associated with a fall in CO2. Hyperventilation during HUT reproduced hypocapnia, BFV reduction, and tachycardia and worsened symptoms of OI; these symptoms and indices were improved within 2 minutes of CO2 rebreathing. The relationships between CO2 and BFV and heart rate were well described by

  15. Antroduodenal motility in neurologically handicapped children with feeding intolerance

    PubMed Central

    Werlin, Steven L

    2004-01-01

    Background Dysphagia and feeding intolerance are common in neurologically handicapped children. The aim is to determine the etiologies of feeding intolerance in neurologically handicapped children who are intolerant of tube feedings. Methods Eighteen neurologically handicapped children, followed in the Tube Feeding Clinic at the Children's Hospital of Wisconsin who were intolerant of gastrostomy feedings. The charts of these 18 patients were reviewed. Past medical history, diagnoses, history of fundoplication and results of various tests of gastrointestinal function including barium contrast radiography, endoscopy and antroduodenal manometry were documented. Results Five of 11 children had abnormal barium upper gastrointestinal series. Seven of 14 had abnormal liquid phase gastric emptying tests. Two of 16 had esophagitis on endoscopy. All 18 children had abnormal antroduodenal motility. Conclusions In neurologically handicapped children foregut dysmotility may be more common than is generally recognized and can explain many of the upper gastrointestinal symptoms in neurologically handicapped children. PMID:15341670

  16. The role of colonic metabolism in lactose intolerance.

    PubMed

    He, T; Venema, K; Priebe, M G; Welling, G W; Brummer, R-J M; Vonk, R J

    2008-08-01

    Lactose maldigestion and intolerance affect a large part of the world population. The underlying factors of lactose intolerance are not fully understood. In this review, the role of colonic metabolism is discussed, i.e. fermentation of lactose by the colonic microbiota, colonic processing of the fermentation metabolites and how these processes would play a role in the pathophysiology of lactose intolerance. We suggest that the balance between the removal and production rate of osmotic-active components (lactose, and intermediate metabolites, e.g. lactate, succinate, etc.) in the colon is a key factor in the development of symptoms. The involvement of the colon may provide the basis for designing new targeted strategies for dietary and clinical management of lactose intolerance.

  17. What I Need to Know about Lactose Intolerance

    MedlinePlus

    ... and all foods made with milk, such as ice cream cream butter cheese cottage cheese yogurt Rarely, people ... lactose intolerance with a medical, family, and diet history; a physical exam; and medical tests. Most people ...

  18. Systemic lactose intolerance: a new perspective on an old problem

    PubMed Central

    Matthews, S; Waud, J; Roberts, A; Campbell, A

    2005-01-01

    Intolerance to certain foods can cause a range of gut and systemic symptoms. The possibility that these can be caused by lactose has been missed because of "hidden" lactose added to many foods and drinks inadequately labelled, confusing diagnosis based on dietary removal of dairy foods. Two polymorphisms, C/T13910 and G/A22018, linked to hypolactasia, correlate with breath hydrogen and symptoms after lactose. This, with a 48 hour record of gut and systemic symptoms and a six hour breath hydrogen test, provides a new approach to the clinical management of lactose intolerance. The key is the prolonged effect of dietary removal of lactose. Patients diagnosed as lactose intolerant must be advised of "risk" foods, inadequately labelled, including processed meats, bread, cake mixes, soft drinks, and lagers. This review highlights the wide range of systemic symptoms caused by lactose intolerance. This has important implications for the management of irritable bowel syndrome, and for doctors of many specialties. PMID:15749792

  19. Perceived lactose intolerance in adult Canadians: a national survey.

    PubMed

    Barr, Susan I

    2013-08-01

    Although double-blind studies show that lactose-intolerant individuals can consume moderate quantities of milk products without perceptible symptoms, many who perceive that they are lactose intolerant limit or avoid milk products, potentially compromising calcium and vitamin D intakes. Adult Canadians are at risk of inadequate intakes of these nutrients, but no data exist on the prevalence, correlates, and potential impact of perceived lactose intolerance among Canadians. To address this, a Web-based survey of a population-representative sample of 2251 Canadians aged ≥19 years was conducted. Overall, 16% self-reported lactose intolerance. This was more common in women (odds ratio (OR), 1.84; 95% CI, 1.46-2.33) and in nonwhites (OR, 1.79; 95% CI, 1.24-2.58) and less common in those >50 years of age (OR, 0.71; 95% CI, 0.56-0.90) and in those completing the survey in French (OR, 0.74; 95% CI, 0.56-0.99). Those with self-reported lactose intolerance had lower covariate-adjusted milk product and alternative intakes (mean ± SE; 1.40 ± 0.08 servings·day(-1) vs. 2.33 ± 0.03 servings·day(-1), p < 0.001). A greater proportion used supplements containing calcium (52% vs. 37%, p < 0.001) and vitamin D (58% vs. 46%, p < 0.001), but calcium intakes from the combination of milk products, alternatives, and supplements were lower (739 ± 30 mg·day(-1) vs. 893 ± 13 mg·day(-1), p < 0.0001). Variation in self-reported lactose intolerance by sex, age, and language preference was unexpected and suggests that some groups may be more vulnerable to the perception that they are lactose intolerant. Regardless of whether lactose intolerance is physiologically based or perceptual, education is required to ensure that calcium intakes are not compromised. PMID:23855270

  20. Perceived lactose intolerance in adult Canadians: a national survey.

    PubMed

    Barr, Susan I

    2013-08-01

    Although double-blind studies show that lactose-intolerant individuals can consume moderate quantities of milk products without perceptible symptoms, many who perceive that they are lactose intolerant limit or avoid milk products, potentially compromising calcium and vitamin D intakes. Adult Canadians are at risk of inadequate intakes of these nutrients, but no data exist on the prevalence, correlates, and potential impact of perceived lactose intolerance among Canadians. To address this, a Web-based survey of a population-representative sample of 2251 Canadians aged ≥19 years was conducted. Overall, 16% self-reported lactose intolerance. This was more common in women (odds ratio (OR), 1.84; 95% CI, 1.46-2.33) and in nonwhites (OR, 1.79; 95% CI, 1.24-2.58) and less common in those >50 years of age (OR, 0.71; 95% CI, 0.56-0.90) and in those completing the survey in French (OR, 0.74; 95% CI, 0.56-0.99). Those with self-reported lactose intolerance had lower covariate-adjusted milk product and alternative intakes (mean ± SE; 1.40 ± 0.08 servings·day(-1) vs. 2.33 ± 0.03 servings·day(-1), p < 0.001). A greater proportion used supplements containing calcium (52% vs. 37%, p < 0.001) and vitamin D (58% vs. 46%, p < 0.001), but calcium intakes from the combination of milk products, alternatives, and supplements were lower (739 ± 30 mg·day(-1) vs. 893 ± 13 mg·day(-1), p < 0.0001). Variation in self-reported lactose intolerance by sex, age, and language preference was unexpected and suggests that some groups may be more vulnerable to the perception that they are lactose intolerant. Regardless of whether lactose intolerance is physiologically based or perceptual, education is required to ensure that calcium intakes are not compromised.

  1. Contextual Influences on Distress Intolerance: Priming Effects on Behavioral Persistence

    PubMed Central

    Szuhany, Kristin L.; Otto, Michael W.

    2015-01-01

    Distress intolerance (DI), the inability to tolerate stressful experiences, has been linked to multiple psychiatric conditions and maladaptive coping patterns. Although DI is often considered a trait-like variable, evidence indicates that self-report and behavioral indices of DI can be manipulated by contextual factors. Understanding such contextual influences is important given evidence of unexpected variability in these presumed trait-like measures over brief intervals. The current study examined the influence of context (manipulated by priming concepts of “Interminability” and “Brevity”) in predicting behavioral persistence, in relation to self-reported DI. Results indicated that priming Brevity was associated with terminating a cold-pressor task more quickly. Self-reported DI was linked to earlier termination, but there was no interaction between self-reported DI and priming condition. Results indicate that contextual cues modulate performance on behavioral measures of DI. Hence, models of DI should consider both trait-like and contextual factors in understanding variability in DI measures. PMID:26366022

  2. Endogenous circulating sympatholytic factor in orthostatic intolerance

    NASA Technical Reports Server (NTRS)

    Shapiro, R. E.; Winters, B.; Hales, M.; Barnett, T.; Schwinn, D. A.; Flavahan, N.; Berkowitz, D. E.

    2000-01-01

    Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.

  3. Postural Tachycardia Syndrome: Beyond Orthostatic Intolerance.

    PubMed

    Garland, Emily M; Celedonio, Jorge E; Raj, Satish R

    2015-09-01

    Postural tachycardia syndrome (POTS) is a form of chronic orthostatic intolerance for which the hallmark physiological trait is an excessive increase in heart rate with assumption of upright posture. The orthostatic tachycardia occurs in the absence of orthostatic hypotension and is associated with a >6-month history of symptoms that are relieved by recumbence. The heart rate abnormality and orthostatic symptoms should not be caused by medications that impair autonomic regulation or by debilitating disorders that can cause tachycardia. POTS is a "final common pathway" for a number of overlapping pathophysiologies, including an autonomic neuropathy in the lower body, hypovolemia, elevated sympathetic tone, mast cell activation, deconditioning, and autoantibodies. Not only may patients be affected by more than one of these pathophysiologies but also the phenotype of POTS has similarities to a number of other disorders, e.g., chronic fatigue syndrome, Ehlers-Danlos syndrome, vasovagal syncope, and inappropriate sinus tachycardia. POTS can be treated with a combination of non-pharmacological approaches, a structured exercise training program, and often some pharmacological support.

  4. Intolerance of uncertainty and adult separation anxiety.

    PubMed

    Boelen, Paul A; Reijntjes, Albert; Carleton, R Nicholas

    2014-01-01

    Intolerance of uncertainty (IU)-the tendency to react negatively to situations that are uncertain-is involved in different anxiety disorders and depression. No studies have yet examined the association between IU and symptoms of adult separation anxiety disorder. However, it is possible that greater difficulties tolerating uncertainties that can occur in relationships with attachment figures inflate fears and worries about the consequences of being separated from these attachment figures. The current study examined the possible role of IU in symptoms of adult separation anxiety disorder, relative to its role in symptoms of generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD), social anxiety, and depression, using self-reported data from 215 undergraduates (92% women) with elevated separation anxiety. Findings showed that IU was significantly associated with symptom levels of separation anxiety disorder, GAD, OCD, social anxiety, and depression (rs > .30). IU continued to explain variance in OCD, social anxiety, and depression (but not GAD and separation anxiety) when controlling for the association of neuroticism, attachment anxiety, and attachment avoidance with these symptoms. Additional findings indicated that IU is more strongly associated with symptoms of GAD, OCD, and social anxiety than symptoms of adult separation anxiety disorder and depression.

  5. Postural Tachycardia Syndrome: Beyond Orthostatic Intolerance

    PubMed Central

    Garland, Emily M; Celedonio, Jorge E; Raj, Satish R

    2015-01-01

    Postural Tachycardia Syndrome (POTS) is a form of chronic orthostatic intolerance for which the hallmark physiological trait is an excessive increase in heart rate with assumption of upright posture. The orthostatic tachycardia occurs in the absence of orthostatic hypotension and is associated with a >6-month history of symptoms that are relieved by recumbence. The heart rate abnormality and orthostatic symptoms should not be caused by medications that impair autonomic regulation or by debilitating disorders that can cause tachycardia. POTS is a “final common pathway” for a number of overlapping pathophysiologies, including an autonomic neuropathy in the lower body, hypovolemia, elevated sympathetic tone, mast cell activation, deconditioning, and autoantibodies. Not only may patients be affected by more than one of these pathophysiologies, but also the phenotype of POTS has similarities to a number of other disorders, e.g., chronic fatigue syndrome, Ehlers-Danlos Syndrome, vasovagal syncope, and inappropriate sinus tachycardia. POTS can be treated with a combination of non-pharmacological approaches, a structured exercise training program, and often some pharmacological support. PMID:26198889

  6. Postural Tachycardia Syndrome: Beyond Orthostatic Intolerance.

    PubMed

    Garland, Emily M; Celedonio, Jorge E; Raj, Satish R

    2015-09-01

    Postural tachycardia syndrome (POTS) is a form of chronic orthostatic intolerance for which the hallmark physiological trait is an excessive increase in heart rate with assumption of upright posture. The orthostatic tachycardia occurs in the absence of orthostatic hypotension and is associated with a >6-month history of symptoms that are relieved by recumbence. The heart rate abnormality and orthostatic symptoms should not be caused by medications that impair autonomic regulation or by debilitating disorders that can cause tachycardia. POTS is a "final common pathway" for a number of overlapping pathophysiologies, including an autonomic neuropathy in the lower body, hypovolemia, elevated sympathetic tone, mast cell activation, deconditioning, and autoantibodies. Not only may patients be affected by more than one of these pathophysiologies but also the phenotype of POTS has similarities to a number of other disorders, e.g., chronic fatigue syndrome, Ehlers-Danlos syndrome, vasovagal syncope, and inappropriate sinus tachycardia. POTS can be treated with a combination of non-pharmacological approaches, a structured exercise training program, and often some pharmacological support. PMID:26198889

  7. Lysinuric Protein Intolerance Presenting with Multiple Fractures.

    PubMed

    Posey, Jennifer E; Burrage, Lindsay C; Miller, Marcus J; Liu, Pengfei; Hardison, Matthew T; Elsea, Sarah H; Sun, Qin; Yang, Yaping; Willis, Alecia S; Schlesinger, Alan E; Bacino, Carlos A; Lee, Brendan H

    2014-01-01

    Lysinuric protein intolerance (LPI) is a rare autosomal recessive inborn error of metabolism caused by mutations in SLC7A7, which encodes a component of the dibasic amino acid transporter found in intestinal and renal tubular cells. Patients typically present with vomiting, diarrhea, irritability, failure to thrive, and symptomatic hyperammonemia after protein-rich meals. Long-term complications may include pulmonary alveolar proteinosis, renal disease, and osteoporosis. We present a 5-year-old male who was followed in our skeletal dysplasia clinic for 3 years for multiple fractures, idiopathic osteoporosis, and short stature in the absence of typical features of LPI. Whole exome sequencing performed to determine the etiology of the osteoporosis and speech delay identified a nonsense mutation in SLC7A7. Chromosome microarray analysis identified a deletion involving the second allele of the same gene, and biochemical analysis supported the diagnosis of LPI. Our patient's atypical presentation underscores the importance of maintaining a high index of suspicion for LPI in patients with unexplained fractures and idiopathic osteoporosis, even in the absence of clinical symptoms of hyperammonemia after protein rich meals or other systemic features of classical LPI. This case further demonstrates the utility of whole exome sequencing in diagnosis of unusual presentations of rare disorders for which early intervention may modify the clinical course.

  8. Lysinuric Protein Intolerance Presenting with Multiple Fractures

    PubMed Central

    Posey, Jennifer E.; Burrage, Lindsay C.; Miller, Marcus J.; Liu, Pengfei; Hardison, Matthew T.; Elsea, Sarah H.; Sun, Qin; Yang, Yaping; Willis, Alecia S.; Schlesinger, Alan E.; Bacino, Carlos A.; Lee, Brendan H.

    2014-01-01

    Lysinuric protein intolerance (LPI) is a rare autosomal recessive inborn error of metabolism caused by mutations in SLC7A7, which encodes a component of the dibasic amino acid transporter found in intestinal and renal tubular cells. Patients typically present with vomiting, diarrhea, irritability, failure to thrive, and symptomatic hyperammonemia after protein-rich meals. Long-term complications may include pulmonary alveolar proteinosis, renal disease, and osteoporosis. We present a 5-year-old male who was followed in our skeletal dysplasia clinic for 3 years for multiple fractures, idiopathic osteoporosis, and short stature in the absence of typical features of LPI. Whole exome sequencing performed to determine the etiology of the osteoporosis and speech delay identified a nonsense mutation in SLC7A7. Chromosome microarray analysis identified a deletion involving the second allele of the same gene, and biochemical analysis supported the diagnosis of LPI. Our patient’s atypical presentation underscores the importance of maintaining a high index of suspicion for LPI in patients with unexplained fractures and idiopathic osteoporosis, even in the absence of clinical symptoms of hyperammonemia after protein rich meals or other systemic features of classical LPI. This case further demonstrates the utility of whole exome sequencing in diagnosis of unusual presentations of rare disorders for which early intervention may modify the clinical course. PMID:25419514

  9. Differentiating food allergies from food intolerances.

    PubMed

    Guandalini, Stefano; Newland, Catherine

    2011-10-01

    Adverse reactions to foods are extremely common, and generally they are attributed to allergy. However, clinical manifestations of various degrees of severity related to ingestion of foods can arise as a result of a number of disorders, only some of which can be defined as allergic, implying an immune mechanism. Recent epidemiological data in North America showed that the prevalence of food allergy in children has increased. The most common food allergens in the United States include egg, milk, peanut, tree nuts, wheat, crustacean shellfish, and soy. This review examines the various forms of food intolerances (immunoglobulin E [IgE] and non-IgE mediated), including celiac disease and gluten sensitivity. Immune mediated reactions can be either IgE mediated or non-IgE mediated. Among the first group, Immediate GI hypersensitivity and oral allergy syndrome are the best described. Often, but not always, IgE-mediated food allergies are entities such as eosinophilic esophagitis and eosinophilic gastroenteropathy. Non IgE-mediated immune mediated food reactions include celiac disease and gluten sensitivity, two increasingly recognized disorders. Finally, non-immune mediated reactions encompass different categories such as disorders of digestion and absorption, inborn errors of metabolism, as well as pharmacological and toxic reactions.

  10. Fructose transporters GLUT5 and GLUT2 expression in adult patients with fructose intolerance

    PubMed Central

    Li, Xinhua; Ho, Sherry SY; Leong, Sai Mun; Wong, Reuben K; Koay, Evelyn SC; Ferraris, Ronaldo P

    2014-01-01

    Background Gastrointestinal symptoms and malabsorption following fructose ingestion (fructose intolerance) are common in functional gastrointestinal disorders (FGID). The underlying mechanism is unclear, but is hypothesized to be related an abnormality of intestinal fructose transporter proteins. Objective To assess the expression of the main intestinal fructose transporter proteins, glucose transport protein 5 (GLUT5) and 2 (GLUT2), in FGID. Methods The expression of GLUT5 and GLUT2 protein and mRNA in small intestinal biopsy tissue was investigated using real-time reverse-transcription PCR and Western immunoblotting in 11 adults with FGID and fructose intolerance ascertained by breath testing and in 15 controls. Results Median expression levels of GLUT5 mRNA normalized to beta-actin were 0.18 (interquartile range, IQR, 0.13–0.21) in patients and 0.17 (IQR 0.12–0.19) in controls (p > 0.05). Respective levels of GLUT2 mRNA were 0.26 (IQR 0.20–0.31) and 0.26 (IQR 0.19–0.31) (p > 0.05). Median expression levels of GLUT5 protein normalized to alpha-tubulin were 0.95 (IQR 0.52–1.68) in patients and 0.95 (IQR 0.59–1.15) in controls (p > 0.05). Respective protein expression levels for GLUT2 were 1.56 (IQR 1.06–2.14) and 1.35 (IQR 0.96–1.79) (p > 0.05). Conclusions Human fructose intolerance may not be associated with marked changes in GLUT5 and GLUT2 expression. Replication of these results in a larger subject group, including measures of transporter activation and membrane and subcellular localization, is warranted. PMID:24918004

  11. Transcriptional Signatures Related to Glucose and Lipid Metabolism Predict Treatment Response to the Tumor Necrosis Factor Antagonist Infliximab in Patients with Treatment-Resistant Depression

    PubMed Central

    Mehta, Divya; Raison, Charles L.; Woolwine, Bobbi J.; Haroon, Ebrahim; Binder, Elisabeth B.; Miller, Andrew H.; Felger, Jennifer C.

    2013-01-01

    The tumor necrosis factor (TNF) antagonist infliximab was recently found to reduce depressive symptoms in patients with increased baseline inflammation as reflected by a plasma C-reactive protein concentration >5mg/L. To further explore predictors and targets of response to infliximab, differential gene expression was examined in peripheral blood mononuclear cells from infliximab responders (n=13) versus non-responders (n=14) compared to placebo at baseline and 6hr, 24hr, and 2 weeks after the first infliximab infusion. Treatment response was defined as 50% reduction in depressive symptoms at any point during the 12-week trial. One-hundred-forty-eight gene transcripts were significantly associated (1.2 fold, adjusted p≤0.01) with response to infliximab and were distinct from placebo responders. Transcripts predictive of infliximab response were associated with gluconeogenesis and cholesterol transport, and were enriched in a network regulated by hepatocyte nuclear factor (HNF)4-alpha, a transcription factor involved in gluconeogenesis and cholesterol and lipid homeostasis. Of the 148 transcripts differentially expressed at baseline, 48% were significantly regulated over time in infliximab responders, including genes related to gluconeogenesis and the HNF4-alpha network, indicating that these predictive genes were responsive to infliximab. Responders also demonstrated inhibition of genes related to apoptosis through TNF signaling at 6hr and 24hr after infusion. Transcripts down-regulated in responders 2 weeks after infliximab were related to innate immune signaling and nuclear factor-kappa B. Thus, baseline transcriptional signatures reflective of alterations in glucose and lipid metabolism predicted antidepressant response to infliximab, and infliximab response involved regulation of metabolic genes and inhibition of genes related to innate immune activation. PMID:23624296

  12. Anxiety sensitivity, distress tolerance, and discomfort intolerance in relation to coping and conformity motives for alcohol use and alcohol use problems among young adult drinkers.

    PubMed

    Howell, Ashley N; Leyro, Teresa M; Hogan, Julianna; Buckner, Julia D; Zvolensky, Michael J

    2010-12-01

    Anxiety sensitivity, distress tolerance, and discomfort intolerance have been identified as important factors related to alcohol use motives and alcohol-related problems. Yet, these variables are highly correlated and little work has delineated whether these psychological vulnerability factors are differentially related to alcohol use motives and problems. To fill this gap in the existing literature, the present study evaluated whether anxiety sensitivity, distress tolerance, and discomfort intolerance were differentially related to high-risk alcohol use motives (i.e., coping and conformity motives) and alcohol use problems among 224 young adult, current drinkers (52.3% women; M(age)=21.18, SD=7.08). Results indicated that distress tolerance, but not anxiety sensitivity or discomfort intolerance, was significantly related to coping motives for alcohol use. Additionally, anxiety sensitivity, but not distress tolerance or discomfort intolerance, was significantly related to conformity motives for drinking. For both sets of analyses, the observed significant effects were evident above and beyond the variance accounted for by alcohol consumption level, smoking rate, negative affectivity, and non-criterion alcohol use motives. Additionally, discomfort intolerance and anxiety sensitivity each predicted alcohol use problems; effects were not attributable to negative affectivity, cigarettes smoked per day, or shared variance with distress tolerance. Findings are discussed in relation to the role of emotional sensitivity and intolerance in terms of the motivational bases for alcohol use and alcohol use problems among young adult drinkers.

  13. Lactose Intolerance in Adults: Biological Mechanism and Dietary Management.

    PubMed

    Deng, Yanyong; Misselwitz, Benjamin; Dai, Ning; Fox, Mark

    2015-09-18

    Lactose intolerance related to primary or secondary lactase deficiency is characterized by abdominal pain and distension, borborygmi, flatus, and diarrhea induced by lactose in dairy products. The biological mechanism and lactose malabsorption is established and several investigations are available, including genetic, endoscopic and physiological tests. Lactose intolerance depends not only on the expression of lactase but also on the dose of lactose, intestinal flora, gastrointestinal motility, small intestinal bacterial overgrowth and sensitivity of the gastrointestinal tract to the generation of gas and other fermentation products of lactose digestion. Treatment of lactose intolerance can include lactose-reduced diet and enzyme replacement. This is effective if symptoms are only related to dairy products; however, lactose intolerance can be part of a wider intolerance to variably absorbed, fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). This is present in at least half of patients with irritable bowel syndrome (IBS) and this group requires not only restriction of lactose intake but also a low FODMAP diet to improve gastrointestinal complaints. The long-term effects of a dairy-free, low FODMAPs diet on nutritional health and the fecal microbiome are not well defined. This review summarizes recent advances in our understanding of the genetic basis, biological mechanism, diagnosis and dietary management of lactose intolerance.

  14. Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment.

    PubMed

    Misselwitz, Benjamin; Pohl, Daniel; Frühauf, Heiko; Fried, Michael; Vavricka, Stephan R; Fox, Mark

    2013-06-01

    Lactose malabsorption is a common condition caused by reduced expression or activity of lactase in the small intestine. In such patients, lactose intolerance is characterized by abdominal symptoms (e.g. nausea, bloating, and pain) after ingestion of dairy products. The genetic basis of lactose malabsorption is established and several tests for this condition are available, including genetic, endoscopic, and H2-breath tests. In contrast, lactose intolerance is less well understood. Recent studies show that the risk of symptoms after lactose ingestion depends on the dose of lactose, lactase expression, intestinal flora, and sensitivity of the gastrointestinal tract. Lactose intolerance has recently been defined as symptoms developing after ingestion of lactose which do not develop after placebo challenge in a person with lactose maldigestion. Such blinded testing might be especially important in those with functional gastrointestinal diseases in whom self-reported lactose intolerance is common. However, placebo-controlled testing is not part of current clinical practice. Updated protocols and high-quality outcome studies are needed. Treatment options of lactose intolerance include lactose-reduced diet and enzyme replacement. Documenting the response to multiple doses can guide rational dietary management; however, the clinical utility of this strategy has not been tested. This review summarizes the genetic basis, diagnosis, and treatment of lactose malabsorption and intolerance.

  15. Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment

    PubMed Central

    Pohl, Daniel; Frühauf, Heiko; Fried, Michael; Vavricka, Stephan R; Fox, Mark

    2013-01-01

    Lactose malabsorption is a common condition caused by reduced expression or activity of lactase in the small intestine. In such patients, lactose intolerance is characterized by abdominal symptoms (e.g. nausea, bloating, and pain) after ingestion of dairy products. The genetic basis of lactose malabsorption is established and several tests for this condition are available, including genetic, endoscopic, and H2-breath tests. In contrast, lactose intolerance is less well understood. Recent studies show that the risk of symptoms after lactose ingestion depends on the dose of lactose, lactase expression, intestinal flora, and sensitivity of the gastrointestinal tract. Lactose intolerance has recently been defined as symptoms developing after ingestion of lactose which do not develop after placebo challenge in a person with lactose maldigestion. Such blinded testing might be especially important in those with functional gastrointestinal diseases in whom self-reported lactose intolerance is common. However, placebo-controlled testing is not part of current clinical practice. Updated protocols and high-quality outcome studies are needed. Treatment options of lactose intolerance include lactose-reduced diet and enzyme replacement. Documenting the response to multiple doses can guide rational dietary management; however, the clinical utility of this strategy has not been tested. This review summarizes the genetic basis, diagnosis, and treatment of lactose malabsorption and intolerance. PMID:24917953

  16. Lactose Intolerance in Adults: Biological Mechanism and Dietary Management.

    PubMed

    Deng, Yanyong; Misselwitz, Benjamin; Dai, Ning; Fox, Mark

    2015-09-01

    Lactose intolerance related to primary or secondary lactase deficiency is characterized by abdominal pain and distension, borborygmi, flatus, and diarrhea induced by lactose in dairy products. The biological mechanism and lactose malabsorption is established and several investigations are available, including genetic, endoscopic and physiological tests. Lactose intolerance depends not only on the expression of lactase but also on the dose of lactose, intestinal flora, gastrointestinal motility, small intestinal bacterial overgrowth and sensitivity of the gastrointestinal tract to the generation of gas and other fermentation products of lactose digestion. Treatment of lactose intolerance can include lactose-reduced diet and enzyme replacement. This is effective if symptoms are only related to dairy products; however, lactose intolerance can be part of a wider intolerance to variably absorbed, fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). This is present in at least half of patients with irritable bowel syndrome (IBS) and this group requires not only restriction of lactose intake but also a low FODMAP diet to improve gastrointestinal complaints. The long-term effects of a dairy-free, low FODMAPs diet on nutritional health and the fecal microbiome are not well defined. This review summarizes recent advances in our understanding of the genetic basis, biological mechanism, diagnosis and dietary management of lactose intolerance. PMID:26393648

  17. Lactose malabsorption and intolerance: pathogenesis, diagnosis and treatment.

    PubMed

    Misselwitz, Benjamin; Pohl, Daniel; Frühauf, Heiko; Fried, Michael; Vavricka, Stephan R; Fox, Mark

    2013-06-01

    Lactose malabsorption is a common condition caused by reduced expression or activity of lactase in the small intestine. In such patients, lactose intolerance is characterized by abdominal symptoms (e.g. nausea, bloating, and pain) after ingestion of dairy products. The genetic basis of lactose malabsorption is established and several tests for this condition are available, including genetic, endoscopic, and H2-breath tests. In contrast, lactose intolerance is less well understood. Recent studies show that the risk of symptoms after lactose ingestion depends on the dose of lactose, lactase expression, intestinal flora, and sensitivity of the gastrointestinal tract. Lactose intolerance has recently been defined as symptoms developing after ingestion of lactose which do not develop after placebo challenge in a person with lactose maldigestion. Such blinded testing might be especially important in those with functional gastrointestinal diseases in whom self-reported lactose intolerance is common. However, placebo-controlled testing is not part of current clinical practice. Updated protocols and high-quality outcome studies are needed. Treatment options of lactose intolerance include lactose-reduced diet and enzyme replacement. Documenting the response to multiple doses can guide rational dietary management; however, the clinical utility of this strategy has not been tested. This review summarizes the genetic basis, diagnosis, and treatment of lactose malabsorption and intolerance. PMID:24917953

  18. Lactose Intolerance in Adults: Biological Mechanism and Dietary Management

    PubMed Central

    Deng, Yanyong; Misselwitz, Benjamin; Dai, Ning; Fox, Mark

    2015-01-01

    Lactose intolerance related to primary or secondary lactase deficiency is characterized by abdominal pain and distension, borborygmi, flatus, and diarrhea induced by lactose in dairy products. The biological mechanism and lactose malabsorption is established and several investigations are available, including genetic, endoscopic and physiological tests. Lactose intolerance depends not only on the expression of lactase but also on the dose of lactose, intestinal flora, gastrointestinal motility, small intestinal bacterial overgrowth and sensitivity of the gastrointestinal tract to the generation of gas and other fermentation products of lactose digestion. Treatment of lactose intolerance can include lactose-reduced diet and enzyme replacement. This is effective if symptoms are only related to dairy products; however, lactose intolerance can be part of a wider intolerance to variably absorbed, fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). This is present in at least half of patients with irritable bowel syndrome (IBS) and this group requires not only restriction of lactose intake but also a low FODMAP diet to improve gastrointestinal complaints. The long-term effects of a dairy-free, low FODMAPs diet on nutritional health and the fecal microbiome are not well defined. This review summarizes recent advances in our understanding of the genetic basis, biological mechanism, diagnosis and dietary management of lactose intolerance. PMID:26393648

  19. Role of cannabinoid CB2 receptors in glucose homeostasis in rats.

    PubMed

    Bermudez-Silva, Francisco Javier; Sanchez-Vera, Irene; Suárez, Juan; Serrano, Antonia; Fuentes, Esther; Juan-Pico, Pablo; Nadal, Angel; Rodríguez de Fonseca, Fernando

    2007-06-22

    Here we show that the activation of cannabinoid CB2 receptors improved glucose tolerance after a glucose load. Blockade of cannabinoid CB2 receptors counteracted this effect, leading to glucose intolerance. Since blockade of cannabinoid CB1 receptors mimics the actions of cannabinoid CB2 receptor agonists, we propose that the endocannabinoid system modulates glucose homeostasis through the coordinated actions of cannabinoid CB1 and CB2 receptors. We also describe the presence of both cannabinoid CB1 and CB2 receptor immunoreactivity in rat pancreatic beta- and non-beta-cells, adding the endocrine pancreas to adipose tissue and the liver as potential sites for endocannabinoid regulation of glucose homeostasis.

  20. Up-regulation of the Sirtuin 1 (Sirt1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) genes in white adipose tissue of Id1 protein-deficient mice: implications in the protection against diet and age-induced glucose intolerance.

    PubMed

    Zhao, Ying; Ling, Flora; Griffin, Timothy M; He, Ting; Towner, Rheal; Ruan, Hong; Sun, Xiao-Hong

    2014-10-17

    Id1, a helix-loop-helix (HLH) protein that inhibits the function of basic HLH E protein transcription factors in lymphoid cells, has been implicated in diet- and age-induced obesity by unknown mechanisms. Here we show that Id1-deficient mice are resistant to a high fat diet- and age-induced obesity, as revealed by reduced weight gain and body fat, increased lipid oxidation, attenuated hepatosteatosis, lower levels of lipid droplets in brown adipose tissue, and smaller white adipocytes after a high fat diet feeding or in aged animals. Id1 deficiency improves glucose tolerance, lowers serum insulin levels, and reduces TNFα gene expression in white adipose tissue. Id1 deficiency also increased expression of Sirtuin 1 and peroxisome proliferator-activated receptor γ coactivator 1α, regulators of mitochondrial biogenesis and energy expenditure, in the white adipose tissue. This effect was accompanied by the elevation of several genes encoding proteins involved in oxidative phosphorylation and fatty acid oxidation, such as cytochrome c, medium-chain acyl-CoA dehydrogenase, and adipocyte protein 2. Moreover, the phenotype for Id1 deficiency was similar to that of mice expressing an E protein dominant-positive construct, ET2, suggesting that the balance between Id and E proteins plays a role in regulating lipid metabolism and insulin sensitivity. PMID:25190816

  1. Visual height intolerance and acrophobia: distressing partners for life.

    PubMed

    Kapfhammer, Hans-Peter; Fitz, Werner; Huppert, Doreen; Grill, Eva; Brandt, Thomas

    2016-10-01

    The course of illness, the degree of social impairment, and the rate of help-seeking behavior was evaluated in a sample of individuals with visual height intolerance (vHI) and acrophobia. On the basis of a previously described epidemiological sample representative of the German general population, 574 individuals with vHI were identified, 128 fulfilled the DSM-5 diagnostic criteria of acrophobia. The illness of the majority of all susceptible individuals with vHI ran a year-long chronic course. Two thirds were in the category "persistent/worse", whereas only one third was in the category "improved/remitted". Subjects with acrophobia showed significantly more traumatic triggers of onset, more signs of generalization to other height stimuli, higher rates of increasing intensity of symptom load, higher grades of social impairment, and greater overall negative impact on the quality of life than those with pure vHI. An unfavorable course of illness in pure vHI was predicted by major depression, agoraphobia, social phobia, posttraumatic stress, initial traumatic trigger, and female sex; an unfavorable course in acrophobia was predicted by major depression, chronic fatigue, panic attacks, initial traumatic trigger, social phobia, other specific phobic fears, and female sex. Help-seeking behavior was astonishingly low in the overall sample of individuals with vHI. The consequences of therapeutic interventions if complied with at all were quite modest. In adults pure vHI and even more so acrophobia are by no means only transitionally distressing states. In contrast to their occurrence in children they are more often persisting and disabling conditions. Both the utilization of and adequacy of treatment of these illnesses pose major challenges within primary and secondary neurological and psychiatric medical care.

  2. Acquired intolerance to organic solvents and results of vestibular testing

    SciTech Connect

    Gyntelberg, F.; Vesterhauge, S.; Fog, P.; Isager, H.; Zillstorff, K.

    1986-01-01

    Among 160 consecutive patients referred to the Clinic of Occupational Medicine, Rigshospitalet, for symptoms connected with exposure to organic solvents, 20 exhibited symptoms of acquired intolerance to minor amounts of organic solvents. Later, an additional 30 consecutive patients with symptoms of acquired intolerance were included, yielding a total of 43 men and 7 women. The characteristics of the clinical syndrome described are complaints of dizziness, nausea, and weakness after exposure to minimal solvent vapor concentrations. After having tolerated long-term occupational exposure to moderate or high air concentrations of various organic solvents, the patients became intolerant within a short period of time. Since dizziness was a frequent complaint, we tried to obtain a measure of the patients' complaints using vestibular tests. As a diagnostic test the combined vestibular tests had a sensitivity of 0.55 and a specificity of 0.87. No differences between patients with and without intolerance could be detected by the vestibular tests used. We conclude that acquired intolerance to organic solvents is a new but characteristic and easily recognizable syndrome, often with severe consequences for the patient's working ability.

  3. Relation of blood volume and blood pressure in orthostatic intolerance

    NASA Technical Reports Server (NTRS)

    Jacob, G.; Biaggioni, I.; Mosqueda-Garcia, R.; Robertson, R. M.; Robertson, D.

    1998-01-01

    A complex but crucial relationship exists between blood volume and blood pressure in human subjects; it has been recognized that in essential hypertension, renovascular hypertension, and pheochromocytoma, the relationship between plasma volume and diastolic blood pressure is an inverse one. This phenomenon has not been studied in individuals with low normal and reduced blood pressures. Orthostatic intolerance is a commonly encountered abnormality in blood pressure regulation often associated with tachycardia in the standing position. Most of these patients have varying degrees of reduced blood volume. We tested the hypothesis that the relationship previously found between plasma volume and diastolic blood pressure in pressor states would also hold in orthostatic intolerance. We studied 16 patients with a history of symptomatic orthostatic intolerance associated with an elevation in plasma norepinephrine in the upright posture and hypovolemia in 9 patients and normovolemia in 7 patients. Our studies demonstrate an inverse relationship between plasma volume and diastolic blood pressure in patients with orthostatic intolerance. This finding also holds for the change in diastolic blood pressure in response to upright posture. In this relationship, patients with orthostatic intolerance with high plasma norepinephrine resemble those with essential hypertension, renovascular hypertension, and pheochromocytoma. We conclude that in a variety of conditions at both ends of the blood pressure spectrum, the seemingly paradoxical association of hypovolemia and diastolic blood pressure is preserved.

  4. The five glucose-6-phosphatase paralogous genes are differentially regulated by insulin alone or combined with high level of amino acids and/or glucose in trout hepatocytes.

    PubMed

    Lucie, Marandel; Weiwei, Dai; Stéphane, Panserat; Sandrine, Skiba-Cassy

    2016-04-01

    A recent analysis of the newly sequenced rainbow trout (Oncorhynchus mykiss) genome suggested that duplicated gluconeogenic g6pc paralogues, fixed in this genome after the salmonid-specific 4th whole genome duplication, may have a role in the setting up of the glucose-intolerant phenotype in this carnivorous species. This should be due to the sub- or neo-functionalization of their regulation. In the present short communication we thus addressed the question of the regulation of these genes by insulin, hormone involved in the glucose homeostasis, and its interaction with glucose and amino acids in vitro. The stimulation of trout hepatocytes with insulin revealed an atypical up-regulation of g6pcb2 ohnologues and confirmed the sub- or neo-functionalization of the five g6pc genes at least at the regulatory level. Intriguingly, when hepatocytes were cultured with high levels of glucose and/or AAs in presence of insulin, most of the g6pc paralogues were up-regulated. It strongly suggested a cross-talk between insulin and nutrients for the regulation of these genes. Moreover these results strengthened the idea that g6pc duplicated genes may significantly contribute to the setting up of the glucose-intolerant phenotype in trout via their atypical regulation by insulin alone or in interaction with nutrients. These findings open new perspectives to better understand in vivo glucose-intolerant phenotype in trout fed a high carbohydrate diet.

  5. Rapamycin impairs HPD-induced beneficial effects on glucose homeostasis

    PubMed Central

    Chang, Geng-Ruei; Chiu, Yi-Shin; Wu, Ying-Ying; Lin, Yu-Chi; Hou, Po-Hsun; Mao, Frank Chiahung

    2015-01-01

    Background and Purpose Rapamycin, which is used clinically to treat graft rejection, has also been proposed to have an effect on metabolic syndrome; however, very little information is available on its effects in lean animals/humans. The purpose of this study was to characterize further the effects of the continuous use of rapamycin on glucose homeostasis in lean C57BL6/J mice. Experimental Approach Mice were fed a high-protein diet (HPD) for 12 weeks to develop a lean model and then were treated daily with rapamycin for 5 weeks while remaining on a HPD. Metabolic parameters, endocrine profiles, glucose tolerance tests, insulin sensitivity index, the expression of the glucose transporter GLUT4 and chromium distribution were measured in vivo. Key Results Lower body weight gain as well as a decreased caloric intake, fat pads, fatty liver scores, adipocyte size and glucose tolerance test values were observed in HPD-fed mice compared with mice fed a high-fat or standard diet. Despite these beneficial effects, rapamycin-treated lean mice showed greater glucose intolerance, reduced insulin sensitivity, lower muscle GLUT4 expression and changes in chromium levels in tissues even with high insulin levels. Conclusion and Implications Our findings demonstrate that continuous rapamycin administration may lead to the development of diabetes syndrome, as it was found to induce hyperglycaemia and glucose intolerance in a lean animal model. PMID:25884889

  6. Non coeliac gluten sensitivity - A new disease with gluten intolerance.

    PubMed

    Czaja-Bulsa, Grażyna

    2015-04-01

    Until recently gluten intolerance has been believed to be typical of celiac disease (CD) and wheat allergy (WA). In the last few years, however, several study results have been published that have proved that gluten intolerance can also affect people who do not suffer from any of the above mentioned diseases. The new syndrome has been named non-celiac gluten sensitivity (NCGS) or gluten sensitivity (GS). It has been included in the new list of gluten-related disorders published in 2012. Researchers believe that NCGS is the most common syndrome of gluten intolerance. This review discusses many aspects of NCGS epidemiology, pathophysiology, clinical spectrum, and treatment and current tools to identify patients suffering from CD, WA, and NCGS.

  7. [Lactose intolerance: changing paradigms due to molecular biology].

    PubMed

    Mattar, Rejane; Mazo, Daniel Ferraz de Campos

    2010-01-01

    In most mammals, lactase activity declines on the intestinal wall after weaning, characterizing primary hypolactasia that provokes symptoms of lactose intolerance. The intensity of symptoms of distention, flatulence, abdominal pain and diarrhea varies, according to the amount of ingested lactose, and increases with age. Hypolactasia is genetically determined; nonetheless, a mutation occurred that had made a part of mankind tolerate milk in adulthood. Diagnosis is made by a tolerance test, using the lactose challenge. With the discovery made by the Finns of polymorphism associated with lactase persistence, mainly, in Northern Europe, the genetic test was incorporated as a more comfortable diagnostic tool for the intolerant. In Brazil, 43% of Caucasian and Mulatto groups have lactase persistence allele, with hipolactasia more frequently found among Blacks and Japanese. However, in clinical practice people with hypolactasia may be advised to consume certain dairy products and food containing lactose without developing intolerance symptoms, whereas others will need a lactose restriction diet.

  8. Investigating the construct validity of intolerance of uncertainty and its unique relationship with worry.

    PubMed

    Buhr, Kristin; Dugas, Michel J

    2006-01-01

    Although recent findings suggest that intolerance of uncertainty is a fundamental construct involved in excessive worry, additional research is required to further establish the construct validity of intolerance of uncertainty and demonstrate its unique contribution to the understanding of worry. The present study examined the relationships among measures of worry, intolerance of uncertainty, intolerance of ambiguity, perfectionism, and perceived control in a sample of 197 university students. The findings indicated that intolerance of uncertainty moderately overlaps with earlier conceptualizations of intolerance of ambiguity; however, worry was more highly related to intolerance of uncertainty than to intolerance of ambiguity. Intolerance of uncertainty also emerged as the most salient predictor of worry compared to other cognitive processes such as perfectionism and perceived control. Worry and intolerance of uncertainty continued to be significantly related after controlling for intolerance of ambiguity, perfectionism, and perceived control, which implies that intolerance of uncertainty shares a unique association with worry that is not accounted for by these other cognitive factors. Overall, the findings provide evidence of construct validity and underscore the role of intolerance of uncertainty in the conceptualization of worry.

  9. Glucose control.

    PubMed

    Preiser, Jean-Charles

    2013-01-01

    Stress-related hyperglycemia is a common finding in acutely ill patients, and is related to the severity and outcome of the critical illness. The pathophysiology of stress hyperglycemia includes hormonal and neural signals, leading to increased production of glucose by the liver and peripheral insulin resistance mediated by the translocation of transmembrane glucose transporters. In one pioneering study, tight glycemic control by intensive insulin therapy in critically ill patients was associated with improved survival. However, this major finding was not confirmed in several other prospective randomized controlled trials. The reasons underlying the discrepancy between the first and the subsequent studies could include nutritional strategy (amount of calories provided, use of parenteral nutrition), case-mix, potential differences in the optimal blood glucose level (BG) in different types of patients, hypoglycemia and its correction, and the magnitude of glucose variability. Therefore, an improved understanding of the physiology and pathophysiology of glycemic regulation during acute illness is needed. Safe and effective glucose control will need improvement in the definition of optimal BG and in the measurement techniques, perhaps including continuous monitoring of insulin algorithms and closed-loop systems. PMID:23075589

  10. Clinical role of a fixed combination of standardized Berberis aristata and Silybum marianum extracts in diabetic and hypercholesterolemic patients intolerant to statins

    PubMed Central

    Di Pierro, Francesco; Bellone, Iaele; Rapacioli, Giuliana; Putignano, Pietro

    2015-01-01

    Background Statin intolerance is a medical condition often leading patients to nonadherence to the prescribed therapy or to a relevant reduction of the statin dosage. Both situations determine a totally or partially uncontrolled lipid profile, and these conditions unquestionably increase the risk of cardiovascular events. Methods We enrolled hypercholesterolemic, type 2 diabetic patients complaining of intolerance to statins. Some of them had reduced the statin dose ‘until the disappearance of symptoms’; others had opted for treatment with ezetimibe; and yet others were not undergoing any treatment at all. All patients of the three groups were then given a fixed combination of berberine and silymarin (Berberol®), known from previous papers to be able to control both lipidic and glycemic profiles. Results The tested product both as a single therapy and as add-on therapy to low-dose statin or to ezetimibe reduced triglycerides, low-density lipoprotein cholesterol, fasting blood glucose, and glycosylated hemoglobin in a significant manner without inducing toxicity conditions that might be somehow ascribed to a statin-intolerant condition. Conclusion Our study demonstrates that use of Berberol®, administered as a single or add-on therapy in statin-intolerant subjects affected by diabetes and hypercholesterolemia is a safe and effective tool capable of improving the patients’ lipidic and glycemic profiles. PMID:25678808

  11. Sleep restriction acutely impairs glucose tolerance in rats.

    PubMed

    Jha, Pawan K; Foppen, Ewout; Kalsbeek, Andries; Challet, Etienne

    2016-06-01

    Chronic sleep curtailment in humans has been related to impairment of glucose metabolism. To better understand the underlying mechanisms, the purpose of the present study was to investigate the effect of acute sleep deprivation on glucose tolerance in rats. A group of rats was challenged by 4-h sleep deprivation in the early rest period, leading to prolonged (16 h) wakefulness. Another group of rats was allowed to sleep during the first 4 h of the light period and sleep deprived in the next 4 h. During treatment, food was withdrawn to avoid a postmeal rise in plasma glucose. An intravenous glucose tolerance test (IVGTT) was performed immediately after the sleep deprivation period. Sleep deprivation at both times of the day similarly impaired glucose tolerance and reduced the early-phase insulin responses to a glucose challenge. Basal concentrations of plasma glucose, insulin, and corticosterone remained unchanged after sleep deprivation. Throughout IVGTTs, plasma corticosterone concentrations were not different between the control and sleep-deprived group. Together, these results demonstrate that independent of time of day and sleep pressure, short sleep deprivation during the resting phase favors glucose intolerance in rats by attenuating the first-phase insulin response to a glucose load. In conclusion, this study highlights the acute adverse effects of only a short sleep restriction on glucose homeostasis. PMID:27354542

  12. Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib

    PubMed Central

    Hochhaus, Andreas; le Coutre, Philipp D.; Rosti, Gianantonio; Pinilla-Ibarz, Javier; Jabbour, Elias; Gillis, Kathryn; Woodman, Richard C.; Blakesley, Rick E.; Giles, Francis J.; Kantarjian, Hagop M.; Baccarani, Michele

    2011-01-01

    Nilotinib has significant efficacy in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) and in patients with CML-CP or CML in accelerated phase (CML-AP) after imatinib failure. We investigated the occurrence of cross-intolerance to nilotinib in imatinib-intolerant patients with CML. Only 1/75 (1%) patients with nonhematologic imatinib intolerance experienced a similar grade 3/4 adverse event (AE), and 3/75 (4%) experienced a similar persistent grade 2 nonhematologic AE on nilotinib. Only 7/40 (18%) patients with hematologic imatinib intolerance discontinued nilotinib, all because of grade 3/4 thrombocytopenia. Ninety percent of imatinib-intolerant patients with CML-CP who did not have complete hematologic response (CHR) at baseline (n = 52) achieved CHR on nilotinib. Nilotinib induced a major cytogenetic response in 66% and 41% of patients with imatinib-intolerant CML-CP and CML-AP (complete cytogenetic response in 51% and 30%), respectively. Minimal cross-intolerance was confirmed in patients with imatinib-intolerant CML. The favorable tolerability of nilotinib in patients with imatinib intolerance leads to alleviation of AE-related symptoms and significant and durable responses. In addition to its established clinical benefit in patients with newly diagnosed CML and those resistant to imatinib, nilotinib is effective and well-tolerated for long-term use in patients with imatinib intolerance. This study is registered at http://www.clinicaltrials.gov as NCT00471497 PMID:21467546

  13. Are ambiguity aversion and ambiguity intolerance identical? A neuroeconomics investigation.

    PubMed

    Tanaka, Yusuke; Fujino, Junya; Ideno, Takashi; Okubo, Shigetaka; Takemura, Kazuhisa; Miyata, Jun; Kawada, Ryosaku; Fujimoto, Shinsuke; Kubota, Manabu; Sasamoto, Akihiko; Hirose, Kimito; Takeuchi, Hideaki; Fukuyama, Hidenao; Murai, Toshiya; Takahashi, Hidehiko

    2014-01-01

    In recent years, there has been growing interest in understanding a person's reaction to ambiguous situations, and two similar constructs related to ambiguity, "ambiguity aversion" and "ambiguity intolerance," are defined in different disciplines. In the field of economic decision-making research, "ambiguity aversion" represents a preference for known risks relative to unknown risks. On the other hand, in clinical psychology, "ambiguity intolerance" describes the tendency to perceive ambiguous situations as undesirable. However, it remains unclear whether these two notions derived from different disciplines are identical or not. To clarify this issue, we combined an economic task, psychological questionnaires, and voxel-based morphometry (VBM) of structural brain magnetic resonance imaging (MRI) in a sample of healthy volunteers. The individual ambiguity aversion tendency parameter, as measured by our economic task, was negatively correlated with agreeableness scores on the self-reported version of the Revised NEO Personality Inventory. However, it was not correlated with scores of discomfort with ambiguity, one of the subscales of the Need for Closure Scale. Furthermore, the ambiguity aversion tendency parameter was negatively correlated with gray matter (GM) volume of areas in the lateral prefrontal cortex and parietal cortex, whereas ambiguity intolerance was not correlated with GM volume in any region. Our results suggest that ambiguity aversion, described in decision theory, may not necessarily be identical to ambiguity intolerance, referred to in clinical psychology. Cautious applications of decision theory to clinical neuropsychiatry are recommended. PMID:25698984

  14. Rainbow Visibility: How One Catholic University Responded to Intolerance.

    ERIC Educational Resources Information Center

    Getz, Cheryl; Kirkley, Evelyn A.

    2002-01-01

    When intolerance of gays and lesbians at the University of San Diego became a problem, a group of students, staff, and faculty decided to do something about it. The result was a project called Rainbow Visibility that works on many forms to educate the campus community. (Author)

  15. Tolerance of Intolerance: Values and Virtues at Stake in Education

    ERIC Educational Resources Information Center

    Orlenius, Kennert

    2008-01-01

    The article addresses the issue of the tolerance of intolerance in an educational context. It concerns a real case in a Swedish upper secondary school some years ago, when a student was suspended from school owing to his sympathies with Nazi ideas. One hundred and twenty student teachers' responses to this decision were analysed in respect of the…

  16. A case of galactosemia misdiagnosed as cow's milk intolerance.

    PubMed

    Della Casa, Roberto; Ungaro, Carla; Acampora, Emma; Pignata, Claudio; Vajro, Pietro; Salerno, Mariacarolina; Santamaria, Francesca; Parenti, Giancarlo

    2012-09-19

    We report on a female patient affected by galactosemia in whom the diagnosis was obscured by the concomitant presence of manifestations suggesting a cow's milk intolerance. This case exemplifies the problems in reaching a correct diagnosis in patients with metabolic diseases.

  17. Preliminary Investigation of Intolerance of Uncertainty Treatment for Anxiety Disorders

    ERIC Educational Resources Information Center

    Hewitt, Sarah N.; Egan, Sarah; Rees, Clare

    2009-01-01

    Intolerance of uncertainty (IU) is the tendency to react negatively to uncertain situations or events, and it has been found to be an important maintaining factor in a number of different anxiety disorders. It is often included as a part of cognitive behavioural interventions for anxiety disorders but its specific contribution to treatment outcome…

  18. Orthostatic Intolerance and Motion Sickness After Parabolic Flight

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T.; Brown, Troy E.; Wood, Scott J.; Benavides, Edgar W.; Bondar, Roberta L.; Stein, Flo; Moradshahi, Peyman; Harm, Deborah L.; Low, Phillip A.

    1999-01-01

    Orthostatic intolerance is common in astronauts after prolonged space flight. However, the "push-pull effect" in military aviators suggests that brief exposures to transitions between hypo- and hypergravity are sufficient to induce untoward autonomic cardiovascular physiology in susceptible individuals. We therefore investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy test subjects before and after a seated 2-hr parabolic flight. At the same time, we also investigated relationships between parabolic flight-induced vomiting and changes in orthostatic and autonomic cardiovascular function. After parabolic flight, 8 of 16 subjects could not tolerate a 30-min upright tilt test, compared to 2 of 16 before flight. Whereas new intolerance in non-Vomiters resembled the clinical postural tachycardia syndrome (POTS), new intolerance in Vomiters was characterized by comparatively isolated upright hypocapnia and cerebral vasoconstriction. As a group, Vomiters also had evidence for increased postflight fluctuations in efferent vagal-cardiac nerve traffic occurring independently of any superimposed change in respiration. Results suggest that syndromes of orthostatic intolerance resembling those occurring after space flight can occur after a brief (i.e., 2-hr) parabolic flight.

  19. Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis

    PubMed Central

    Kocalis, Heidi E.; Hagan, Scott L.; George, Leena; Turney, Maxine K.; Siuta, Michael A.; Laryea, Gloria N.; Morris, Lindsey C.; Muglia, Louis J.; Printz, Richard L.; Stanwood, Gregg D.; Niswender, Kevin D.

    2014-01-01

    Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing neurons. Rictor deletion in all neurons led to increased fat mass and adiposity, glucose intolerance and behavioral leptin resistance. Disrupting Rictor in POMC neurons also caused obesity and hyperphagia, fasting hyperglycemia and pronounced glucose intolerance. AgRP neuron specific deletion did not impact energy balance but led to mild glucose intolerance. Collectively, we show that Rictor/mTORC2 signaling, especially in POMC-expressing neurons, is important for central regulation of energy and glucose homeostasis. PMID:24944899

  20. A multi-parametric protocol to study exercise intolerance in McArdle's disease.

    PubMed

    Ricci, Giulia; Bertolucci, Federica; Logerfo, Annalisa; Simoncini, Costanza; Papi, Riccardo; Franzoni, Ferdinando; Dell'Osso, Giacomo; Servadio, Adele; Masoni, Maria Chiara; Siciliano, Gabriele

    2015-12-01

    McArdle's disease is the most common metabolic myopathy of muscle carbohydrate metabolism, due to deficiency of myophosphorylase and alteration of glycogen breakdown in muscle. The clinical manifestations usually begin in young adulthood, with exercise intolerance, exercise-induced muscle cramps, pain and recurrent episodes of myoglobinuria. Many patients experience the second wind phenomenon, characterized by an improved tolerance for aerobic exercise approximately after eight minutes of motor activity, secondary to the increased availability of blood glucose and free fatty acids associated to an enhanced glucose uptake by muscle cells. In this study, we aimed to test a multi-parametric protocol in order to detect the impairment of muscular metabolism and motor performance in patients with McArdle's disease. We enrolled 5 patients and 5 age-matched healthy subjects, that were evaluated by: (01) monitoring of physical activity with an electronic armband; (02) testing of cardiopulmonary, metabolic and respiratory responses to exercise with a cardiopulmonary exercise test and analyzing muscle fatigue during exercise test by surface electromyography (04) evaluating blood lactate and oxidative stress biomarkers at rest and during exercise. The patients were tested at baseline and after three days of carbohydrate-rich diet integrated with tricarboxylic acid cycle intermediate and creatine. The multiparametric protocol proved to be useful to detect the oxidative capacity impairment and the second wind phenomenon of patients. We did not observe any significant differences of muscle metabolic response during the exercise test after three days of carbohydrate-rich diet. PMID:27199539

  1. Current treatment of dyslipidaemia: PCSK9 inhibitors and statin intolerance.

    PubMed

    Koskinas, Konstantinos; Wilhelm, Matthias; Windecker, Stephan

    2016-01-01

    Statins are the cornerstone of the management of dyslipidaemias and prevention of cardiovascular disease. Although statins are, overall, safe and well tolerated, adverse events can occur and constitute an important barrier to maintaining long-term adherence to statin treatment. In patients who cannot tolerate statins, alternative treatments include switch to another statin, intermittent-dosage regimens and non-statin lipid-lowering medications. Nonetheless, a high proportion of statin-intolerant patients are unable to achieve recommended low-density lipoprotein (LDL) cholesterol goals, thereby resulting in substantial residual cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease implicated in LDL receptor degradation and plays a central role in cholesterol metabolism. In recent studies, PCSK9 inhibition by means of monoclonal antibodies achieved LDL cholesterol reductions of 50% to 70% across various patient populations and background lipid-lowering therapies, while maintaining a favourable safety profile. The efficacy and safety of the monoclonal antibodies alirocumab and evolocumab were confirmed in statin-intolerant patients, indicating that PCSK9 inhibitors represent an attractive treatment option in this challenging clinical setting. PCSK9 inhibitors recently received regulatory approval for clinical use and may be considered in properly selected patients according to current consensus documents, including patients with statin intolerance. In this review we summarise current evidence regarding diagnostic evaluation of statin-related adverse events, particularly statin-associated muscle symptoms, and we discuss current recommendations on the management of statin-intolerant patients. In view of emerging evidence of the efficacy and safety of PCSK9 inhibitors, we further discuss the role of monoclonal PCSK9 antibodies in the management of statin-intolerant hypercholesterolaemic patients. PMID:27400448

  2. Glucose-stat, a glucose-controlled continuous culture.

    PubMed Central

    Kleman, G L; Chalmers, J J; Luli, G W; Strohl, W R

    1991-01-01

    A predictive and feedback proportional control algorithm, developed for fed-batch fermentations and described in a companion paper (G. L. Kleman, J. J. Chalmers, G. W. Luli, and W. R. Strohl, Appl. Environ. Microbiol. 57:910-917, 1991), was used in this work to control a continuous culture on the basis of the soluble-glucose concentration (called the glucose-stat). This glucose-controlled continuous-culture system was found to reach and maintain steady state for 11 to 24 residence times when four different background glucose concentrations (0.27, 0.50, 0.7, and 1.5 g/liter) were used. The predictive-plus-feedback control system yielded very tight control of the continuous nutristat cultures; glucose concentrations were maintained at the set points with less than 0.003 standard error. Acetate production by Escherichia coli B in glucose-stats was found not to be correlated with the level of steady-state soluble-glucose concentration. PMID:2059050

  3. Glucose-stat, a glucose-controlled continuous culture.

    PubMed

    Kleman, G L; Chalmers, J J; Luli, G W; Strohl, W R

    1991-04-01

    A predictive and feedback proportional control algorithm, developed for fed-batch fermentations and described in a companion paper (G. L. Kleman, J. J. Chalmers, G. W. Luli, and W. R. Strohl, Appl. Environ. Microbiol. 57:910-917, 1991), was used in this work to control a continuous culture on the basis of the soluble-glucose concentration (called the glucose-stat). This glucose-controlled continuous-culture system was found to reach and maintain steady state for 11 to 24 residence times when four different background glucose concentrations (0.27, 0.50, 0.7, and 1.5 g/liter) were used. The predictive-plus-feedback control system yielded very tight control of the continuous nutristat cultures; glucose concentrations were maintained at the set points with less than 0.003 standard error. Acetate production by Escherichia coli B in glucose-stats was found not to be correlated with the level of steady-state soluble-glucose concentration. PMID:2059050

  4. Consumption of honey, sucrose, and high fructose corn syrup produce similar metabolic effects in glucose tolerant and glucose intolerant individuals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Current public health recommendations call for reduction of added sugars; however, controversy exits over whether all nutritive sweeteners produce similar metabolic effects. Objective: To compare effects of chronic consumption of three nutritive sweeteners (honey, sucrose and high fructo...

  5. Gestational diabetes mellitus: Screening with fasting plasma glucose.

    PubMed

    Agarwal, Mukesh M

    2016-07-25

    Fasting plasma glucose (FPG) as a screening test for gestational diabetes mellitus (GDM) has had a checkered history. During the last three decades, a few initial anecdotal reports have given way to the recent well-conducted studies. This review: (1) traces the history; (2) weighs the advantages and disadvantages; (3) addresses the significance in early pregnancy; (4) underscores the benefits after delivery; and (5) emphasizes the cost savings of using the FPG in the screening of GDM. It also highlights the utility of fasting capillary glucose and stresses the value of the FPG in circumventing the cumbersome oral glucose tolerance test. An understanding of all the caveats is crucial to be able to use the FPG for investigating glucose intolerance in pregnancy. Thus, all health professionals can use the patient-friendly FPG to simplify the onerous algorithms available for the screening and diagnosis of GDM - thereby helping each and every pregnant woman. PMID:27525055

  6. Gestational diabetes mellitus: Screening with fasting plasma glucose

    PubMed Central

    Agarwal, Mukesh M

    2016-01-01

    Fasting plasma glucose (FPG) as a screening test for gestational diabetes mellitus (GDM) has had a checkered history. During the last three decades, a few initial anecdotal reports have given way to the recent well-conducted studies. This review: (1) traces the history; (2) weighs the advantages and disadvantages; (3) addresses the significance in early pregnancy; (4) underscores the benefits after delivery; and (5) emphasizes the cost savings of using the FPG in the screening of GDM. It also highlights the utility of fasting capillary glucose and stresses the value of the FPG in circumventing the cumbersome oral glucose tolerance test. An understanding of all the caveats is crucial to be able to use the FPG for investigating glucose intolerance in pregnancy. Thus, all health professionals can use the patient-friendly FPG to simplify the onerous algorithms available for the screening and diagnosis of GDM - thereby helping each and every pregnant woman. PMID:27525055

  7. Spontaneous subarachnoid hemorrhage and glucose management.

    PubMed

    Schmutzhard, Erich; Rabinstein, Alejandro A

    2011-09-01

    Although metabolic abnormalities have been linked with poor outcome after subarachnoid hemorrhage, there are limited data addressing the impact of glycemic control or benefits of glucose management after aneurysmal subarachnoid hemorrhage. A systematic literature search was conducted of English-language articles describing original research on glycemic control in patients with subarachnoid hemorrhage. Case reports and case series were excluded. A total of 22 publications were selected for this review. Among the 17 studies investigating glucose as an outcome predictor, glucose levels during hospitalization were more likely to predict outcome than admission glucose. In general, hyperglycemia was linked to worse outcome. While insulin therapy in subarachnoid hemorrhage patients was shown to effectively control plasma glucose levels, plasma glucose control was not necessarily reflective of cerebral glucose such that very tight glucose control may lead to neuroglycopenia. Furthermore, tight glycemic control was associated with an increased risk for hypoglycemia which was linked to worse outcome. PMID:21850563

  8. Glutathionylation of hepatic and visceral adipose proteins decreases in obese-prone, glucose intolerant rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity and insulin resistance are associated with increases in oxidative stress and lipid peroxidation. On the other hand, adipocytes from obese animals have elevated GSH content, and insulin resistance can be reversed by GSH depletion. Oxidation of active site cysteines of protein tyrosine phospha...

  9. Heat tolerance testing: association between heat intolerance and anthropometric and fitness measurements.

    PubMed

    Lisman, Peter; Kazman, Josh B; O'Connor, Francis G; Heled, Yuval; Deuster, Patricia A

    2014-11-01

    This study investigated associations between heat intolerance, as determined by performance on a heat tolerance test (HTT), and anthropometric measurements (body surface-to-mass ratio, percent body fat, body mass index, and waist circumference) and cardiorespiratory fitness (maximal oxygen uptake [VO2max]). Relationships between predictive variables and specific physiological measurements recorded during the HTT were examined. A total of 34 male and 12 female participants, recruited from the military community, underwent anthropometric measurements, a maximal aerobic exercise test, and a standardized HTT, which consisted of walking on a treadmill at 5 km/h at 2% grade for 120 minutes at 40°C and 40% relative humidity. VO2max negatively correlated with maximum core temperature (r = -0.30, p < 0.05) and heart rate (HR) (r = -0.48, p < 0.01) although percent body fat showed a positive correlation with maximum HR (r = 0.36, p < 0.05). VO2max was the only independent attribute that significantly influenced both the maximum HR and core temperature attained during HTT. Logistic regression analyses indicated that VO2max was the only independent parameter (OR = 0.89, p = 0.026) that significantly contributed to overall HTT performance. Low cardiorespiratory fitness was associated with heat intolerance, as defined by HTT performance, and can be addressed as a preventative measure for exertional heat illness. This study provides further evidence that the HTT can be an effective tool for assessment of thermoregulatory patterns.

  10. Spreading of intolerance under economic stress: Results from a reputation-based model

    NASA Astrophysics Data System (ADS)

    Martinez-Vaquero, Luis A.; Cuesta, José A.

    2014-08-01

    When a population is engaged in successive prisoner's dilemmas, indirect reciprocity through reputation fosters cooperation through the emergence of moral and action rules. A simplified model has recently been proposed where individuals choose between helping others or not and are judged good or bad for it by the rest of the population. The reputation so acquired will condition future actions. In this model, eight strategies (referred to as "leading eight") enforce a high level of cooperation, generate high payoffs, and are therefore resistant to invasions by other strategies. Here we show that, by assigning each individual one of two labels that peers can distinguish (e.g., political ideas, religion, and skin color) and allowing moral and action rules to depend on the label, intolerant behaviors can emerge within minorities under sufficient economic stress. We analyze the sets of conditions where this can happen and also discuss the circumstances under which tolerance can be restored. Our results agree with empirical observations that correlate intolerance and economic stress and predict a correlation between the degree of tolerance of a population and its composition and ethical stance.

  11. Effect of a single dose of lactase on symptoms and expired hydrogen after lactose challenge in lactose-intolerant subjects.

    PubMed

    Sanders, S W; Tolman, K G; Reitberg, D P

    1992-06-01

    The effect of a single dose or oral lactase on symptoms, breath hydrogen concentration, and glucose absorption in lactose-intolerant subjects challenged with lactose was studied. Volunteers underwent a lactose challenge test; those whose breath hydrogen concentrations increased 20 ppm or more and who met other criteria were admitted as subjects. After fasting, the subjects were given three chewable lactase tablets (total lactase dose, 9900 FCC units) or placebo tablets in a randomized, double-blind, crossover manner. The subjects also consumed 8 oz of whole milk in which 37.5 g of lactose powder was dissolved (total lactose content, 50 g). The washout period between lactose challenges was at least one week. Breath hydrogen and plasma glucose concentrations were measured before and at intervals after the challenges, and the subjects completed symptom-evaluation questionnaires every eight hours for four days. Twenty-four subjects completed the study. The maximum mean breath hydrogen concentration was significantly lower after lactase treatment than after placebo treatment. In 21 subjects, the area under the hydrogen concentration-time curve (AUC) was lower after lactase than after placebo; three subjects had hydrogen AUCs more than 300 ppm.hr lower. There were no significant differences in plasma glucose levels. Subjective ratings of the severity of abdominal cramping, belching, flatulence, and diarrhea were lower during the first eight hours after challenge in lactase-treated subjects; ratings for bloating were lower during the next eight hours. Single doses of a chewable lactase tablet reduced the concentration of expired hydrogen and symptoms of lactose intolerance after a lactose challenge.

  12. Modeling Glucose Metabolism in the Kidney.

    PubMed

    Chen, Ying; Fry, Brendan C; Layton, Anita T

    2016-06-01

    The mammalian kidney consumes a large amount of energy to support the reabsorptive work it needs to excrete metabolic wastes and to maintain homeostasis. Part of that energy is supplied via the metabolism of glucose. To gain insights into the transport and metabolic processes in the kidney, we have developed a detailed model of the renal medulla of the rat kidney. The model represents water and solute flows, transmural fluxes, and biochemical reactions in the luminal fluid of the nephrons and vessels. In particular, the model simulates the metabolism of oxygen and glucose. Using that model, we have identified parameters concerning glucose transport and basal metabolism that yield predicted blood glucose concentrations that are consistent with experimental measurements. The model predicts substantial axial gradients in blood glucose levels along various medullary structures. Furthermore, the model predicts that in the inner medulla, owing to the relatively limited blood flow and low tissue oxygen tension, anaerobic metabolism of glucose dominates. PMID:27371260

  13. Exercise Intolerance in Heart Failure: Did We Forget the Brain?

    PubMed

    Brassard, Patrice; Gustafsson, Finn

    2016-04-01

    Exercise tolerance is affected in patients with heart failure (HF). Although the inability of the heart to pump blood to the working muscle has been the conventional mechanism proposed to explain the lowered capacity of patients with HF to exercise, evidence suggests that the pathophysiological mechanisms associated with their exercise intolerance is more complex. Recent findings indicate that lowered cerebral blood flow (CBF) and oxygenation likely represent limiting factors for exercise capacity in patients with HF. After an overview of cardiac and peripheral responses during acute and chronic exercise in healthy individuals, we succinctly review cardiac and noncardiac mechanisms by which HF influences exercise tolerance. We then consider how HF, comorbidity, and HF treatment influence CBF and oxygenation at rest and during exercise. Finally, we provide suggestions for further research to improve our understanding of the role of the brain in exercise intolerance in HF.

  14. Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency

    NASA Technical Reports Server (NTRS)

    Shannon, J. R.; Flattem, N. L.; Jordan, J.; Jacob, G.; Black, B. K.; Biaggioni, I.; Blakely, R. D.; Robertson, D.

    2000-01-01

    BACKGROUND: Orthostatic intolerance is a syndrome characterized by lightheadedness, fatigue, altered mentation, and syncope and associated with postural tachycardia and plasma norepinephrine concentrations that are disproportionately high in relation to sympathetic outflow. We tested the hypothesis that impaired functioning of the norepinephrine transporter contributes to the pathophysiologic mechanism of orthostatic intolerance. METHODS: In a patient with orthostatic intolerance and her relatives, we measured postural blood pressure, heart rate, plasma catecholamines, and systemic norepinephrine spillover and clearance, and we sequenced the norepinephrine-transporter gene and evaluated its function. RESULTS: The patient had a high mean plasma norepinephrine concentration while standing, as compared with the mean (+/-SD) concentration in normal subjects (923 vs. 439+/-129 pg per milliliter [5.46 vs. 2.59+/-0.76 nmol per liter]), reduced systemic norepinephrine clearance (1.56 vs. 2.42+/-0.71 liters per minute), impairment in the increase in the plasma norepinephrine concentration after the administration of tyramine (12 vs. 56+/-63 pg per milliliter [0.07 vs. 0.33+/-0.37 pmol per liter]), and a disproportionate increase in the concentration of plasma norepinephrine relative to that of dihydroxyphenylglycol. Analysis of the norepinephrine-transporter gene revealed that the proband was heterozygous for a mutation in exon 9 (encoding a change from guanine to cytosine at position 237) that resulted in more than a 98 percent loss of function as compared with that of the wild-type gene. Impairment of synaptic norepinephrine clearance may result in a syndrome characterized by excessive sympathetic activation in response to physiologic stimuli. The mutant allele in the proband's family segregated with the postural heart rate and abnormal plasma catecholamine homeostasis. CONCLUSIONS: Genetic or acquired deficits in norepinephrine inactivation may underlie hyperadrenergic

  15. Skeletal muscle pathology in endurance athletes with acquired training intolerance

    PubMed Central

    Grobler, L; Collins, M; Lambert, M; Sinclair-Smith, C; Derman, W; St, C; Noakes, T

    2004-01-01

    Background: It is well established that prolonged, exhaustive endurance exercise is capable of inducing skeletal muscle damage and temporary impairment of muscle function. Although skeletal muscle has a remarkable capacity for repair and adaptation, this may be limited, ultimately resulting in an accumulation of chronic skeletal muscle pathology. Case studies have alluded to an association between long term, high volume endurance training and racing, acquired training intolerance, and chronic skeletal muscle pathology. Objective: To systematically compare the skeletal muscle structural and ultrastructural status of endurance athletes with acquired training intolerance (ATI group) with asymptomatic endurance athletes matched for age and years of endurance training (CON group). Methods: Histological and electron microscopic analyses were carried out on a biopsy sample of the vastus lateralis from 18 ATI and 17 CON endurance athletes. The presence of structural and ultrastructural disruptions was compared between the two groups of athletes. Results: Significantly more athletes in the ATI group than in the CON group presented with fibre size variation (15 v 6; p = 0.006), internal nuclei (9 v 2; p = 0.03), and z disc streaming (6 v 0; p = 0.02). Conclusions: There is an association between increased skeletal muscle disruptions and acquired training intolerance in endurance athletes. Further studies are required to determine the nature of this association and the possible mechanisms involved. PMID:15562162

  16. Are ambiguity aversion and ambiguity intolerance identical? A neuroeconomics investigation

    PubMed Central

    Tanaka, Yusuke; Fujino, Junya; Ideno, Takashi; Okubo, Shigetaka; Takemura, Kazuhisa; Miyata, Jun; Kawada, Ryosaku; Fujimoto, Shinsuke; Kubota, Manabu; Sasamoto, Akihiko; Hirose, Kimito; Takeuchi, Hideaki; Fukuyama, Hidenao; Murai, Toshiya; Takahashi, Hidehiko

    2015-01-01

    In recent years, there has been growing interest in understanding a person's reaction to ambiguous situations, and two similar constructs related to ambiguity, “ambiguity aversion” and “ambiguity intolerance,” are defined in different disciplines. In the field of economic decision-making research, “ambiguity aversion” represents a preference for known risks relative to unknown risks. On the other hand, in clinical psychology, “ambiguity intolerance” describes the tendency to perceive ambiguous situations as undesirable. However, it remains unclear whether these two notions derived from different disciplines are identical or not. To clarify this issue, we combined an economic task, psychological questionnaires, and voxel-based morphometry (VBM) of structural brain magnetic resonance imaging (MRI) in a sample of healthy volunteers. The individual ambiguity aversion tendency parameter, as measured by our economic task, was negatively correlated with agreeableness scores on the self-reported version of the Revised NEO Personality Inventory. However, it was not correlated with scores of discomfort with ambiguity, one of the subscales of the Need for Closure Scale. Furthermore, the ambiguity aversion tendency parameter was negatively correlated with gray matter (GM) volume of areas in the lateral prefrontal cortex and parietal cortex, whereas ambiguity intolerance was not correlated with GM volume in any region. Our results suggest that ambiguity aversion, described in decision theory, may not necessarily be identical to ambiguity intolerance, referred to in clinical psychology. Cautious applications of decision theory to clinical neuropsychiatry are recommended. PMID:25698984

  17. Orthostatic intolerance and motion sickness after parabolic flight

    NASA Technical Reports Server (NTRS)

    Schlegel, T. T.; Brown, T. E.; Wood, S. J.; Benavides, E. W.; Bondar, R. L.; Stein, F.; Moradshahi, P.; Harm, D. L.; Fritsch-Yelle, J. M.; Low, P. A.

    2001-01-01

    Because it is not clear that the induction of orthostatic intolerance in returning astronauts always requires prolonged exposure to microgravity, we investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy subjects before and after the brief micro- and hypergravity of parabolic flight. Concomitantly, we investigated the effect of parabolic flight-induced vomiting on orthostatic tolerance, R-wave-R-wave interval and arterial pressure power spectra, and carotid-cardiac baroreflex and Valsalva responses. After parabolic flight 1) 8 of 16 subjects could not tolerate 30 min of upright tilt (compared to 2 of 16 before flight); 2) 6 of 16 subjects vomited; 3) new intolerance to upright tilt was associated with exaggerated falls in total peripheral resistance, whereas vomiting was associated with increased R-wave-R-wave interval variability and carotid-cardiac baroreflex responsiveness; and 4) the proximate mode of new orthostatic failure differed in subjects who did and did not vomit, with vomiters experiencing comparatively isolated upright hypocapnia and cerebral vasoconstriction and nonvomiters experiencing signs and symptoms reminiscent of the clinical postural tachycardia syndrome. Results suggest, first, that syndromes of orthostatic intolerance resembling those developing after space flight can develop after a brief (i.e., 2-h) parabolic flight and, second, that recent vomiting can influence the results of tests of autonomic cardiovascular function commonly utilized in returning astronauts.

  18. [Food Allergy and Intolerance : Distinction, Definitions and Delimitation].

    PubMed

    Kleine-Tebbe, Jörg; Waßmann-Otto, Anja; Mönnikes, Hubert

    2016-06-01

    Immunologically mediated hypersensitivity to foods is defined as food allergy, mainly due to immunglobulins of class E (IgE) triggering immediate reactions (type I hypersensitivity) with possible involvement of mucosa, skin, airways, intestinal tract, and the vascular system. Primary food allergy is based on (early) IgE sensitization against animal (e. g., cow's milk, hen's eggs) or plant proteins (e. g. peanut, hazelnut or wheat). In the case of secondary food allergies, IgE against pollen proteins (e. g., birch) reacts to structurally related food proteins (with cross-reactions to stone and pit fruits). Non-immunological food intolerance reactions are mostly based on carbohydrate malassimilation (e. g., lactose intolerance, fructose malabsorption) and are rarely due to pseudo-allergies (e. g., flavors, dyes, preservatives) primarily in patients with chronic urticaria. Common intestinal symptoms are mainly due to functional disorders (e. g., irritable bowel disease), rarely because of inflammatory intestinal diseases (e. g., celiac disease). Histamine intolerance, gluten hypersensitivity, and so-called food type III hypersensitivities are controversial diagnoses. The aforementioned disease entities/models are of variable importance for the affected individuals, the public health system, and society in general.

  19. Drug effects on orthostatic intolerance induced by bedrest

    NASA Technical Reports Server (NTRS)

    Vernikos, J.; Dallman, M. F.; Van Loon, G.; Keil, L. C.

    1991-01-01

    Effective and practical preventive procedures for postflight orthostatic intolerance are highly desirable. The current practice of attempts to expand plasma volume by ingestion of salt and fluids before reentry has proven benefits. This study evaluated alternative options using fludrocortisone (F) to expand plasma volume (PV), dextroamphetamine (Dex) to enhance norepinephrine (NE) release, and atropine (A) to reduce the effects of vagal stimulation. Seven subjects with proven post-bedrest orthostatic intolerance returned for a 7-day 6-deg head-down bedrest study. F (0.2 mg) was given at 8:00 AM and 8:00 PM the day before and 8:00 AM the day the subjects got out of bed (2 hours before standing). PV was measured before and 1 hour after the last dose of F. Dex (5 mg) and A (0.8 mg) were then taken orally 1 hour before the stand test. F expanded PV by 16 percent and caused sodium retention. Four of the 7 subjects stood for 1 hour post-bedrest and heart rate, plasma NE and plasma renin responses to standing were greatly enhanced and sustained. Although there was a narrowing of pulse pressure, the ability to overcome orthostatic intolerance with these countermeasures was largely due to vasoconstriction and sustained high heart rate.

  20. The nocebo effect in the context of statin intolerance.

    PubMed

    Tobert, Jonathan A; Newman, Connie B

    2016-01-01

    The nocebo effect, the inverse of the placebo effect, is a well-established phenomenon that is under-appreciated in cardiovascular medicine. It refers to adverse events, usually purely subjective, that result from expectations of harm from a drug, placebo, other therapeutic intervention or a nonmedical situation. These expectations can be driven by many factors including the informed consent form in a clinical trial, warnings about adverse effects communicated by clinicians when prescribing a drug, and information in the media about the dangers of certain treatments. The nocebo effect is the best explanation for the high rate of muscle and other symptoms attributed to statins in observational studies and clinical practice, but not in randomized controlled trials, where muscle symptoms, and rates of discontinuation due to any adverse event, are generally similar in the statin and placebo groups. Statin-intolerant patients usually tolerate statins under double-blind conditions, indicating that the intolerance has little if any pharmacological basis. Known techniques for minimizing the nocebo effect can be applied to the prevention and management of statin intolerance. PMID:27578103

  1. Midodrine prevents orthostatic intolerance associated with simulated spaceflight

    NASA Technical Reports Server (NTRS)

    Ramsdell, C. D.; Mullen, T. J.; Sundby, G. H.; Rostoft, S.; Sheynberg, N.; Aljuri, N.; Maa, M.; Mukkamala, R.; Sherman, D.; Toska, K.; Yelle, J.; Bloomfield, D.; Williams, G. H.; Cohen, R. J.

    2001-01-01

    Many astronauts after being weightless in space become hypotensive and presyncopal when they assume an upright position. This phenomenon, known as orthostatic intolerance, may interfere with astronaut function during reentry and after spaceflight and may limit the ability of an astronaut to exit a landed spacecraft unaided during an emergency. Orthostatic intolerance is more pronounced after long-term spaceflight and is a major concern with respect to the extended flights expected aboard the International Space Station and for interplanetary exploration class missions, such as a human mission to Mars. Fully effective countermeasures to this problem have not yet been developed. To test the hypothesis that alpha-adrenergic stimulation might provide an effective countermeasure, we conducted a 16-day head-down-tilt bed-rest study (an analog of weightlessness) using normal human volunteers and administered the alpha(1)-agonist drug midodrine at the end of the bed-rest period. Midodrine was found to significantly ameliorate excessive decreases in blood pressure and presyncope during a provocative tilt test. We conclude that midodrine may be an effective countermeasure for the prevention of orthostatic intolerance following spaceflight.

  2. [Food Allergy and Intolerance : Distinction, Definitions and Delimitation].

    PubMed

    Kleine-Tebbe, Jörg; Waßmann-Otto, Anja; Mönnikes, Hubert

    2016-06-01

    Immunologically mediated hypersensitivity to foods is defined as food allergy, mainly due to immunglobulins of class E (IgE) triggering immediate reactions (type I hypersensitivity) with possible involvement of mucosa, skin, airways, intestinal tract, and the vascular system. Primary food allergy is based on (early) IgE sensitization against animal (e. g., cow's milk, hen's eggs) or plant proteins (e. g. peanut, hazelnut or wheat). In the case of secondary food allergies, IgE against pollen proteins (e. g., birch) reacts to structurally related food proteins (with cross-reactions to stone and pit fruits). Non-immunological food intolerance reactions are mostly based on carbohydrate malassimilation (e. g., lactose intolerance, fructose malabsorption) and are rarely due to pseudo-allergies (e. g., flavors, dyes, preservatives) primarily in patients with chronic urticaria. Common intestinal symptoms are mainly due to functional disorders (e. g., irritable bowel disease), rarely because of inflammatory intestinal diseases (e. g., celiac disease). Histamine intolerance, gluten hypersensitivity, and so-called food type III hypersensitivities are controversial diagnoses. The aforementioned disease entities/models are of variable importance for the affected individuals, the public health system, and society in general. PMID:27215624

  3. Midodrine prevents orthostatic intolerance associated with simulated spaceflight.

    PubMed

    Ramsdell, C D; Mullen, T J; Sundby, G H; Rostoft, S; Sheynberg, N; Aljuri, N; Maa, M; Mukkamala, R; Sherman, D; Toska, K; Yelle, J; Bloomfield, D; Williams, G H; Cohen, R J

    2001-06-01

    Many astronauts after being weightless in space become hypotensive and presyncopal when they assume an upright position. This phenomenon, known as orthostatic intolerance, may interfere with astronaut function during reentry and after spaceflight and may limit the ability of an astronaut to exit a landed spacecraft unaided during an emergency. Orthostatic intolerance is more pronounced after long-term spaceflight and is a major concern with respect to the extended flights expected aboard the International Space Station and for interplanetary exploration class missions, such as a human mission to Mars. Fully effective countermeasures to this problem have not yet been developed. To test the hypothesis that alpha-adrenergic stimulation might provide an effective countermeasure, we conducted a 16-day head-down-tilt bed-rest study (an analog of weightlessness) using normal human volunteers and administered the alpha(1)-agonist drug midodrine at the end of the bed-rest period. Midodrine was found to significantly ameliorate excessive decreases in blood pressure and presyncope during a provocative tilt test. We conclude that midodrine may be an effective countermeasure for the prevention of orthostatic intolerance following spaceflight. PMID:11356789

  4. Differential Role of Insulin/IGF-1 Receptor Signaling in Muscle Growth and Glucose Homeostasis.

    PubMed

    O'Neill, Brian T; Lauritzen, Hans P M M; Hirshman, Michael F; Smyth, Graham; Goodyear, Laurie J; Kahn, C Ronald

    2015-05-26

    Insulin and insulin-like growth factor 1 (IGF-1) are major regulators of muscle protein and glucose homeostasis. To determine how these pathways interact, we generated mice with muscle-specific knockout of IGF-1 receptor (IGF1R) and insulin receptor (IR). These MIGIRKO mice showed >60% decrease in muscle mass. Despite a complete lack of insulin/IGF-1 signaling in muscle, MIGIRKO mice displayed normal glucose and insulin tolerance. Indeed, MIGIRKO mice showed fasting hypoglycemia and increased basal glucose uptake. This was secondary to decreased TBC1D1 resulting in increased Glut4 and Glut1 membrane localization. Interestingly, overexpression of a dominant-negative IGF1R in muscle induced glucose intolerance in MIGIRKO animals. Thus, loss of insulin/IGF-1 signaling impairs muscle growth, but not whole-body glucose tolerance due to increased membrane localization of glucose transporters. Nonetheless, presence of a dominant-negative receptor, even in the absence of functional IR/IGF1R, induces glucose intolerance, indicating that interactions between these receptors and other proteins in muscle can impair glucose homeostasis. PMID:25981038

  5. Energy Excess, Glucose Utilization, and Skeletal Remodeling: New Insights.

    PubMed

    Lecka-Czernik, Beata; Rosen, Clifford J

    2015-08-01

    Skeletal complications have recently been recognized as another of the several comorbidities associated with diabetes. Clinical studies suggest that disordered glucose and lipid metabolism have a profound effect on bone. Diabetes-related changes in skeletal homeostasis result in a significant increased risk of fractures, although the pathophysiology may differ from postmenopausal osteoporosis. Efforts to understand the underlying mechanisms of diabetic bone disease have focused on the direct interaction of adipose tissue with skeletal remodeling and the potential influence of glucose utilization and energy uptake on these processes. One aspect that has emerged recently is the major role of the central nervous system in whole-body metabolism, bone turnover, adipose tissue remodeling, and beta cell secretion of insulin. Importantly, the skeleton contributes to the metabolic balance inherent in physiologic states. New animal models have provided the insights necessary to begin to dissect the effects of obesity and insulin resistance on the acquisition and maintenance of bone mass. In this Perspective, we focus on potential mechanisms that underlie the complex interactions between adipose tissue and skeletal turnover by focusing on the clinical evidence and on preclinical studies indicating that glucose intolerance may have a significant impact on the skeleton. In addition, we raise fundamental questions that need to be addressed in future studies to resolve the conundrum associated with glucose intolerance, obesity, and osteoporosis.

  6. Mathematical Modeling of Renal Tubular Glucose Absorption after Glucose Load

    PubMed Central

    De Gaetano, Andrea; Panunzi, Simona; Eliopoulos, Dimitris; Hardy, Thomas; Mingrone, Geltrude

    2014-01-01

    A partial differential Progressive Tubular Reabsorption (PTR) model, describing renal tubular glucose reabsorption and urinary glucose excretion following a glucose load perturbation, is proposed and fitted to experimental data from five subjects. For each subject the Glomerular Filtration Rate was estimated and both blood and urine glucose were sampled following an Intra-Venous glucose bolus. The PTR model was compared with a model representing the conventional Renal Threshold Hypothesis (RTH). A delay bladder compartment was introduced in both formulations. For the RTH model, the average threshold for glycosuria varied between 9.90±4.50 mmol/L and 10.63±3.64 mmol/L (mean ± Standard Deviation) under different hypotheses; the corresponding average maximal transport rates varied between 0.48±0.45 mmol/min (86.29±81.22 mg/min) and 0.50±0.42 mmol/min (90.62±76.15 mg/min). For the PTR Model, the average maximal transports rates varied between 0.61±0.52 mmol/min (109.57±93.77 mg/min) and 0.83±0.95 mmol/min (150.13±171.85 mg/min). The time spent by glucose inside the tubules before entering the bladder compartment varied between 1.66±0.73 min and 2.45±1.01 min. The PTR model proved much better than RTH at fitting observations, by correctly reproducing the delay of variations of glycosuria with respect to the driving glycemia, and by predicting non-zero urinary glucose elimination at low glycemias. This model is useful when studying both transients and steady-state glucose elimination as well as in assessing drug-related changes in renal glucose excretion. PMID:24489817

  7. Determination of fructose metabolic pathways in normal and fructose-intolerant children: A sup 13 C NMR study using (U- sup 13 C)fructose

    SciTech Connect

    Gopher, A.; Lapidot, A. ); Vaisman, N. ); Mandel, H. )

    1990-07-01

    An inborn deficiency in the ability of aldolase B to split fructose 1-phosphate is found in humans with hereditary fructose intolerance (HFI). A stable isotope procedure to elucidate the mechanism of conversion of fructose to glucose in normal children and in HFI children has been developed. A constant infusion of D-(U-{sup 13}C)fructose was given nasogastrically to control and to HFI children. Hepatic fructose conversion to glucose was estimated by examination of {sup 13}C NMR spectra of plasma glucose. Significantly lower values ({approx}3-fold) for fructose conversion to glucose were obtained for the HFI patients as compared to the controls. A quantitative determination of the metabolic pathways of fructose conversion to glucose was derived from {sup 13}C NMR measurement of plasma ({sup 13}C)glucose isotopomer populations. The finding of isotopomer populations of three adjacent {sup 13}C atoms at glucose C-4 ({sup 13}C{sub 3}-{sup 13}C{sub 4}-{sup 13}C{sub 5}) suggests that there is a direct pathway from fructose, by-passing fructose-1-phosphate aldolase, to fructose 1,6-bisphosphate. The metabolism of fructose by fructose-1-phosphate aldolase activity accounts for only {approx}50% of the total amount of hepatic fructose conversion to glucose. In view of the marked decline by 67% in synthesis of glucose from fructose in HFI subjects found in this study, the extent of ({sup 13}C)glucose formation from a trace amount of (U-{sup 13}C)fructose infused into the patient can be used as a safe and noninvasive diagnostic test for inherent faulty fructose metabolism.

  8. Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity.

    PubMed

    Wang, Jiawei; Light, Kelly; Henderson, Mélanie; O'Loughlin, Jennifer; Mathieu, Marie-Eve; Paradis, Gilles; Gray-Donald, Katherine

    2014-01-01

    Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P < 0.01). No associations were observed with consumption of added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity. PMID:24198307

  9. Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity.

    PubMed

    Wang, Jiawei; Light, Kelly; Henderson, Mélanie; O'Loughlin, Jennifer; Mathieu, Marie-Eve; Paradis, Gilles; Gray-Donald, Katherine

    2014-01-01

    Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P < 0.01). No associations were observed with consumption of added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.

  10. Opinion controversy to chromium picolinate therapy's safety and efficacy: ignoring 'anecdotes' of case reports or recognising individual risks and new guidelines urgency to introduce innovation by predictive diagnostics?

    PubMed

    Golubnitschaja, Olga; Yeghiazaryan, Kristina

    2012-01-01

    Due to the important physiologic function of trivalent chromium in glucose/insulin homeostasis, some commercial organisations promote Cr3+ supplements in maintaining proper carbohydrate and lipid metabolism; regulation of reducing carbohydrate carvings and appetite; prevention of insulin resistance and glucose intolerance; regulation of body composition, including reducing fat mass and increasing lean body mass; optimal body building for athletes; losing weight; treatment of atypical depression as an antidepressant; and prevention of obesity and type 2 diabetes mellitus. On one hand, case reports are commented as 'nonevidence-based anecdotes'. On the other hand, a number of independent studies warn against adverse health outcomes assigned to chromium picolinate (CrPic) dietary application. This review analyses opinion controversies, demonstrates highly individual reactions towards CrPic dietary supplements and highlights risks when the dietary supplements are used freely as therapeutic agents, without application of advanced diagnostic tools to predict individual outcomes. PMID:23039227

  11. Prevalence and Characteristics of Chemical Intolerance: A Japanese Population-Based Study.

    PubMed

    Azuma, Kenichi; Uchiyama, Iwao; Katoh, Takahiko; Ogata, Hiromitsu; Arashidani, Keiichi; Kunugita, Naoki

    2015-01-01

    Population-based cross-sectional study was performed to estimate the prevalence of chemical intolerance and to examine the characteristics of the sample. A Web-based survey was conducted that included 7,245 adults in Japan. The criteria for chemical intolerance proposed by Skovbjerg yielded a prevalence of 7.5% that was approximately consistent with that reported from a Danish population-based survey. Female gender, older age, and renovation in the house during the past 7 years were positively associated with chemical intolerance. Improvements in the condition were observed with daily ventilation habits. Medical history of atopic dermatitis, allergic rhinitis, food allergy, multiple chemical sensitivity, and depression were associated with chemical intolerance. Fatigue, depressed mood, and somatic symptoms were also positively correlated with chemical intolerance. Better elucidation of the causes, comorbidities, concomitants, and consequences of chemical intolerance has the potential to provide effective solutions for its prevention and treatment. PMID:25137616

  12. Efficacy of Garcinia Cambogia on Body Weight, Inflammation and Glucose Tolerance in High Fat Fed Male Wistar Rats

    PubMed Central

    Sripradha, Ramalingam

    2015-01-01

    Introduction: Obesity leads to derangements in lipid and glucose homeostasis resulting in various metabolic complications. Plants containing vital phytochemicals are known to posses anti obesity properties and have proved to exert beneficial effects in obesity. Objectives: The present study was aimed to investigate the effects of Garcinia Cambogia on body weight, glucose tolerance and inflammation in high fat diet fed male Wistar rats. Materials and Methods: Five month old male wistar rats (n=40) were divided into four groups. Two groups were fed with standard rodent diet and the remaining two with 30% high fat diet. One group in each of the two sets received the crude ethanolic extract of Garcinia Cambogia at a dose of 400mg/kg body weight/day for ten weeks. Body weight, intraperitoneal glucose tolerance test, leptin, tumour necrosis factor-α (TNF-α) and renal function (urea, creatinine, uric acid) were studied. Results: High fat diet fed rats showed increased body weight gain, glucose intolerance, elevated levels of plasma leptin and TNF-α. Supplementation of Garcinia Cambogia extract (GE) along with high fat diet significantly decreased body weight gain, glucose intolerance, plasma leptin and TNF-α level. No significant changes were observed in the renal function parameters in any of the groups. Conclusion: Supplementation of the Garcinia Cambogia extract with high fat diet reduced body weight gain, inflammation and glucose intolerance. PMID:25859449

  13. Low Blood Glucose (Hypoglycemia)

    MedlinePlus

    ... Other Dental Problems Diabetic Eye Disease Low Blood Glucose (Hypoglycemia) What is hypoglycemia? Hypoglycemia, also called low ... actions can also help prevent hypoglycemia: Check blood glucose levels Knowing your blood glucose level can help ...

  14. Glucose test (image)

    MedlinePlus

    ... person with diabetes constantly manages their blood's sugar (glucose) levels. After a blood sample is taken and tested, it is determined whether the glucose levels are low or high. If glucose levels ...

  15. The association between Internet addiction and belief of frustration intolerance: the gender difference.

    PubMed

    Ko, Chih-Hung; Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Chung-Sheng; Wang, Shing-Yaw

    2008-06-01

    This study evaluated the association between Internet addiction and frustration intolerance, the gender difference of frustration intolerance, and the gender differences of the association between Internet addiction and frustration intolerance. Participants were 2,114 students (1,204 male and 910 female) who were recruited to complete the Chen Internet Addiction Scale and Frustration Discomfort scale. Females had higher scores on the subscale of entitlement and emotional intolerance and the total scale of the frustration intolerance. There was a significant gender difference on the association between Internet addiction and frustration intolerance. The association was higher in male adolescents. Regression analysis revealed male adolescents with Internet addiction had higher intolerance to frustration of entitlement and emotional discomfort, and female adolescents with it had higher intolerance to emotional discomfort and lower tolerance to frustration of achievement. Frustration intolerance should be evaluated for adolescents with Internet addiction, especially for males. Rational emotive behavior therapy focusing on different irrational beliefs should be provided to male and female adolescents with Internet addiction.

  16. A comparison of intolerance of uncertainty in analogue obsessive-compulsive disorder and generalized anxiety disorder.

    PubMed

    Holaway, Robert M; Heimberg, Richard G; Coles, Meredith E

    2006-01-01

    Intolerance of uncertainty has been defined as the unwillingness to tolerate the possibility that negative events may occur in the future, no matter how low the probability [Personality Individual Differences 17 (1994), 791-802]. Previous research suggests that intolerance of uncertainty may be more specific to worry and generalized anxiety disorder (GAD) than to other anxiety disorders [e.g., Dugas, M. J., Buhr, K., & Ladouceur, R. (2004). The role of intolerance of uncertainty in the etiology and maintenance of generalized anxiety disorder. In R. G. Heimberg, C. L. Turk, & D. S. Mennin (Eds.), Generalized anxiety disorder: Advances in research and practice (pp. 143-163). New York: Guilford Press]. However, Tolin et al. [J. Anxiety Disorders 17 (2003), 233-242] argued that intolerance of uncertainty may also play a central role in obsessive-compulsive disorder (OCD). Therefore, the current study compared intolerance of uncertainty in individuals with analogue GAD and/or OCD. Intolerance of uncertainty was strongly related to pathological worry, GAD symptoms, and OCD symptoms; however, neither worry nor GAD was found to be more strongly associated with intolerance of uncertainty than OCD. Further, individuals with analogue GAD or OCD reported more intolerance of uncertainty than controls, but they did not differ significantly from each other. These findings suggest that intolerance of uncertainty may be a central theme in a number of the anxiety disorders.

  17. Brief Report: Effects of Sensory Sensitivity and Intolerance of Uncertainty on Anxiety in Mothers of Children with Autism Spectrum Disorder.

    PubMed

    Uljarević, Mirko; Carrington, Sarah; Leekam, Susan

    2016-01-01

    This study examined the relations between anxiety and individual characteristics of sensory sensitivity (SS) and intolerance of uncertainty (IU) in mothers of children with ASD. The mothers of 50 children completed the Hospital Anxiety and Depression Scale, the Highly Sensitive Person Scale and the IU Scale. Anxiety was associated with both SS and IU and IU was also associated with SS. Mediation analyses showed direct effects between anxiety and both IU and SS but a significant indirect effect was found only in the model in which IU mediated between SS. This is the first study to characterize the nature of the IU and SS interrelation in predicting levels of anxiety.

  18. Treatment of 51 pregnancies with danaparoid because of heparin intolerance.

    PubMed

    Lindhoff-Last, Edelgard; Kreutzenbeck, Hans-Joachim; Magnani, Harry N

    2005-01-01

    Pregnant patients with acute venous thrombosis or a history of thrombosis may need alternative anticoagulation, when heparin intolerance occurs. Only limited data on the use of the heparinoid danaparoid are available in literature. We reviewed the use of danaparoid in 51 pregnancies of 49 patients identified in literature between 1981 and 2004. All patients had developed heparin intolerance (32 due to heparin-induced thrombocytopenia, 19 mainly due to heparin-induced skin rashes) and had a current and/or past history of thromboembolic complications. The initial danaparoid dose regimens ranged from 1000 to 7500 U/day administered s.c. or i.v.. The median duration of danaparoid use was 10 weeks. Danaparoid was used until delivery of a healthy infant in 37 pregnancies. In the remaining 14 pregnancies it was stopped earlier, because anticoagulant treatment was no longer required (3/14) or an adverse event led to a treatment discontinuation (11/14). Four maternal bleeding events were recorded during pregnancy, delivery or postpartum, two of them were fatal due to placental problems. Three fetal deaths were recorded, all associated with maternal complications antedating danaparoid use. Danaparoid cross-reactivity was suspected in 4 HIT patients and 5 non-HIT patients with skin reactions and was confirmed serologically in one of the two HIT patients tested. In none of five fetal cord blood- and three maternal breast milksamples anti-Xa activity transfer was observed. In conclusion danaparoid can be used as an alternative antithrombotic agent in pregnant women with high thrombotic risk and intolerance to heparins. PMID:15630492

  19. Overcoming the barrier of lactose intolerance to reduce health disparities.

    PubMed

    Jarvis, Judith K; Miller, Gregory D

    2002-02-01

    Federal health goals for the public have focused on reducing health disparities that exist between whites and various racial and ethnic groups. Many of the chronic diseases for which African Americans are at greater risk- hypertension, stroke, colon cancer, and obesity-may be exacerbated by a low intake of calcium and/or other dairy-related nutrients. For example, a low intake of dairy food nutrients, such as calcium, potassium, and magnesium, may contribute to the high risk of hypertension seen in African Americans. The Dietary Approaches to Stop Hypertension (DASH) study demonstrated that a low-fat diet rich in fruits and vegetables (8 to 10 servings) and low-fat dairy foods (3 servings) significantly reduced blood pressure-and was twice as effective in African-American participants. Calcium and dairy food consumption is particularly low among African-American, Hispanic, and Asian populations. Average intakes are near the threshold of 600 to 700 mg/day, below which bone loss and hypertension can result. Although lactose intolerance may be partly to blame for the low calcium intakes due to reduced dairy food consumption by minority populations, culturally determined food preferences and dietary practices learned early in life also play a role. The high incidence figures for primary lactose maldigestion among minority groups grossly overestimates the number who will experience intolerance symptoms after drinking a glass of milk with a meal. Randomized, double-blind, controlled clinical trials have demonstrated that by using a few simple dietary strategies, those who maldigest lactose (have low levels of the lactase enzyme) can easily tolerate a dairy-rich diet that meets calcium intake recommendations. Physicians and other health professionals can help their minority patients and the general public understand how to improve calcium nutrition by overcoming the surmountable barrier of lactose intolerance. At the same time they will be helping to reduce the incidence

  20. Autogenic-feedback training: A countermeasure for orthostatic intolerance

    NASA Technical Reports Server (NTRS)

    Cowings, Patricia S.; Toscano, William B.; Kamiya, Joe; Miller, Neal E.; Pickering, Thomas G.

    1991-01-01

    NASA has identified cardiovascular deconditioning as a serious biomedical problem associated with long-duration exposure to microgravity in space. High priority has been given to the development of countermeasures for this disorder and the resulting orthostatic intolerance experienced by crewmembers upon their return to the 1g norm of Earth. The present study was designed to examine the feasibility of training human subjects to control their own cardiovascular responses to gravitational stimulation (i.e., a tilt table). Using an operant conditioning procedure, Autogenic-Feedback Training (AFT), we would determine if subjects could learn to increase their own blood pressure voluntarily.

  1. Exercise Intolerance In Heart Failure With Preserved Ejection Fraction

    PubMed Central

    Gupte, Anisha A.; Hamilton, Dale J.

    2016-01-01

    More than 50% of Americans with heart failure have preserved ejection fraction (HFpEF). Exercise intolerance is a hallmark of HFpEF, but the pathophysiology is not well understood. Diverse etiologies and incomplete mechanistic understanding have resulted in ineffective management strategies to improve the outcomes of HFpEF. Traditional therapies that have been beneficial in the treatment of heart failure with reduced ejection fraction (HFrEF), neurohormonal blockade in particular, have not been effective in treating HFpEF. In this review, we address underlying mechanisms of HFpEF and present the rationale supporting exercise as a component of comprehensive management. PMID:27486493

  2. Optical glucose monitoring using vertical cavity surface emitting lasers (VCSELs)

    NASA Astrophysics Data System (ADS)

    Talebi Fard, Sahba; Hofmann, Werner; Talebi Fard, Pouria; Kwok, Ezra; Amann, Markus-Christian; Chrostowski, Lukas

    2009-08-01

    Diabetes Mellitus is a common chronic disease that has become a public health issue. Continuous glucose monitoring improves patient health by stabilizing the glucose levels. Optical methods are one of the painless and promising methods that can be used for blood glucose predictions. However, having accuracies lower than what is acceptable clinically has been a major concern. Using lasers along with multivariate techniques such as Partial Least Square (PLS) can improve glucose predictions. This research involves investigations for developing a novel optical system for accurate glucose predictions, which leads to the development of a small, low power, implantable optical sensor for diabetes patients.

  3. A glucose-centric perspective of hyperglycemia.

    PubMed

    Ramasarma, T; Rafi, M

    2016-02-01

    targets. Some are effective in slowing formation of glucose in intestines by inhibiting α-glucosidases (e.g., salacia/saptarangi). Knowledge gained from French lilac on active guanidine group helped developing Metformin (1,1-dimethylbiguanide) one of the popular drugs in use. One strategy of keeping sugar content in diets in check is to use artificial sweeteners with no calories, no glucose or fructose and no effect on blood glucose (e.g., steviol, erythrytol). However, the three commonly used non-caloric artificial sweeteners, saccharin, sucralose and aspartame later developed glucose intolerance, the very condition they are expected to evade. Ideal way of keeping blood glucose under 6 mM and HbA1c, the glycation marker of hemoglobin, under 7% in blood is to correct the defects in signals that allow glucose flow into glycogen, still a difficult task with drugs and diets. PMID:26934776

  4. A glucose-centric perspective of hyperglycemia.

    PubMed

    Ramasarma, T; Rafi, M

    2016-02-01

    targets. Some are effective in slowing formation of glucose in intestines by inhibiting α-glucosidases (e.g., salacia/saptarangi). Knowledge gained from French lilac on active guanidine group helped developing Metformin (1,1-dimethylbiguanide) one of the popular drugs in use. One strategy of keeping sugar content in diets in check is to use artificial sweeteners with no calories, no glucose or fructose and no effect on blood glucose (e.g., steviol, erythrytol). However, the three commonly used non-caloric artificial sweeteners, saccharin, sucralose and aspartame later developed glucose intolerance, the very condition they are expected to evade. Ideal way of keeping blood glucose under 6 mM and HbA1c, the glycation marker of hemoglobin, under 7% in blood is to correct the defects in signals that allow glucose flow into glycogen, still a difficult task with drugs and diets.

  5. Serial anthropometry predicts peripheral nerve dysfunction in a community cohort

    PubMed Central

    Ylitalo, Kelly R.; Herman, William H.; Harlow, Siobán D.

    2012-01-01

    Background Obesity is a risk factor for glucose intolerance, but the independent role of obesity in the development of peripheral neuropathy is unclear. This study assessed the impact of body size trajectories on prevalent nerve dysfunction in community-dwelling women with and without glucose intolerance. Methods Annual (1996–2008) anthropometric measures of weight, height, waist circumference, and body mass index (BMI, weight[kg]/height[m2]) were assessed in the Study of Women's Health Across the Nation – Michigan site. Glucose intolerance was defined annually based on current use of diabetes medications, self-reported diabetes diagnosis, and, when available, fasting glucose. Peripheral nerve dysfunction in 2008 was defined as abnormal monofilament testing or ≥4 symptoms or signs. Linear mixed models were used to determine trajectories of anthropometry by subsequently-identified nerve dysfunction status. Results Mean BMI was 32.4 kg/m2 at baseline and 27.8% of women had nerve dysfunction in 2008. BMI, weight, and waist circumference increased over time. Women who would have nerve dysfunction were significantly larger than women without dysfunction, independent of glucose intolerance. At mean baseline age of 46, BMI, weight, and waist circumference differed significantly (p-value<0.01) by subsequent nerve dysfunction status, independent of glucose intolerance and hypertension. These body size differences were maintained but not exacerbated over time. Conclusions Peripheral nerve dysfunction is prevalent among community-dwelling women. Twelve years before the nerve assessment, anthropometry differed between women who would and would not have nerve dysfunction, differences that were maintained over time. Obesity deserves attention as an important and potentially modifiable risk factor for peripheral nerve dysfunction. PMID:23161607

  6. Previously Associated Type 2 Diabetes Variants May Interact With Physical Activity to Modify the Risk of Impaired Glucose Regulation and Type 2 Diabetes

    PubMed Central

    Brito, Ema C.; Lyssenko, Valeriya; Renström, Frida; Berglund, Göran; Nilsson, Peter M.; Groop, Leif; Franks, Paul W.

    2009-01-01

    OBJECTIVE Recent advances in type 2 diabetes genetics have culminated in the discovery and confirmation of multiple risk variants. Two important and largely unanswered questions are whether this information can be used to identify individuals most susceptible to the adverse consequences of sedentary behavior and to predict their response to lifestyle intervention; such evidence would be mechanistically informative and provide a rationale for targeting genetically susceptible subgroups of the population. RESEARCH DESIGN AND METHODS Gene × physical activity interactions were assessed for 17 polymorphisms in a prospective population-based cohort of initially nondiabetic middle-aged adults. Outcomes were 1) impaired glucose regulation (IGR) versus normal glucose regulation determined with either fasting or 2-h plasma glucose concentrations (n = 16,003), 2) glucose intolerance (in mmol/l, n = 8,860), or 3) incident type 2 diabetes (n = 2,063 events). RESULTS Tests of gene × physical activity interactions on IGR risk for 3 of the 17 polymorphisms were nominally statistically significant:CDKN2A/B rs10811661 (Pinteraction = 0.015), HNF1B rs4430796 (Pinteraction = 0.026), and PPARG rs1801282 (Pinteraction = 0.04). Consistent interactions were observed for the CDKN2A/B (Pinteraction = 0.013) and HNF1B (Pinteraction = 0.0009) variants on 2-h glucose concentrations. Where type 2 diabetes was the outcome, only one statistically significant interaction effect was observed, and this was for the HNF1B rs4430796 variant (Pinteraction = 0.0004). The interaction effects for HNF1B on IGR risk and incident diabetes remained significant after correction for multiple testing (Pinteraction = 0.015 and 0.0068, respectively). CONCLUSIONS Our observations suggest that the genetic predisposition to hyperglycemia is partially dependent on a person's lifestyle. PMID:19324937

  7. Intolerance of sexy peers: intrasexual competition among women.

    PubMed

    Vaillancourt, Tracy; Sharma, Aanchal

    2011-01-01

    Intrasexual competition among males of different species, including humans, is well documented. Among females, far less is known. Recent nonexperimental studies suggest that women are intolerant of attractive females and use indirect aggression to derogate potential rivals. In Study 1, an experimental design was used to test the evolutionary-based hypothesis that women would be intolerant of sexy women and would censure those who seem to make sex too readily available. Results provide strong empirical support for intrasexual competition among women. Using independent raters, blind to condition, we found that almost all women were rated as reacting negatively ("bitchy") to an attractive female confederate when she was dressed in a sexually provocative manner. In contrast, when she was dressed conservatively, the same confederate was barely noticed by the participants. In Study 2, an experimental design was used to assess whether the sexy female confederate from Study 1 was viewed as a sexual rival by women. Results indicated that as hypothesized, women did not want to introduce her to their boyfriend, allow him to spend time alone with her, or be friends with her. Findings from both studies are discussed in terms of evolutionary theory.

  8. Intolerance of sexy peers: intrasexual competition among women.

    PubMed

    Vaillancourt, Tracy; Sharma, Aanchal

    2011-01-01

    Intrasexual competition among males of different species, including humans, is well documented. Among females, far less is known. Recent nonexperimental studies suggest that women are intolerant of attractive females and use indirect aggression to derogate potential rivals. In Study 1, an experimental design was used to test the evolutionary-based hypothesis that women would be intolerant of sexy women and would censure those who seem to make sex too readily available. Results provide strong empirical support for intrasexual competition among women. Using independent raters, blind to condition, we found that almost all women were rated as reacting negatively ("bitchy") to an attractive female confederate when she was dressed in a sexually provocative manner. In contrast, when she was dressed conservatively, the same confederate was barely noticed by the participants. In Study 2, an experimental design was used to assess whether the sexy female confederate from Study 1 was viewed as a sexual rival by women. Results indicated that as hypothesized, women did not want to introduce her to their boyfriend, allow him to spend time alone with her, or be friends with her. Findings from both studies are discussed in terms of evolutionary theory. PMID:21932332

  9. Differentiating intolerance of uncertainty from three related but distinct constructs.

    PubMed

    Rosen, Natalie O; Ivanova, Elena; Knäuper, Bärbel

    2014-01-01

    Individual differences in uncertainty have been associated with heightened anxiety, stress and approach-oriented coping. Intolerance of uncertainty (IU) is a trait characteristic that arises from negative beliefs about uncertainty and its consequences. Researchers have established the central role of IU in the development of problematic worry and maladaptive coping, highlighting the importance of this construct to anxiety disorders. However, there is a need to improve our understanding of the phenomenology of IU. The goal of this paper was to present hypotheses regarding the similarities and differences between IU and three related constructs--intolerance of ambiguity, uncertainty orientation, and need for cognitive closure--and to call for future empirical studies to substantiate these hypotheses. To assist with achieving this goal, we conducted a systematic review of the literature, which also served to identify current gaps in knowledge. This paper differentiates these constructs by outlining each definition and general approaches to assessment, reviewing the existing empirical relations, and proposing theoretical similarities and distinctions. Findings may assist researchers in selecting the appropriate construct to address their research questions. Future research directions for the application of these constructs, particularly within the field of clinical and health psychology, are discussed.

  10. Restraint Stress Impairs Glucose Homeostasis Through Altered Insulin Signalling in Sprague-Dawley Rat.

    PubMed

    Morakinyo, Ayodele O; Ajiboye, Kolawole I; Oludare, Gabriel O; Samuel, Titilola A

    2016-01-01

    The study investigated the potential alteration in the level of insulin and adiponectin, as well as the expression of insulin receptors (INSR) and glucose transporter 4 GLUT-4 in chronic restraint stress rats. Sprague-Dawley rats were randomly divided into two groups: the control group and stress group in which the rats were exposed to one of the four different restraint stressors; 1 h, twice daily for a period of 7 days (S7D), 14 days (S14D) and 28 days (S28D). Glucose tolerance and insulin sensitivity were evaluated following the final stress exposure. ELISA were performed to assess the level of insulin and adiponectin as well as expression of INSR and GLUT4 protein in skeletal muscle. Plasma corticosterone level was also determined as a marker of stress exposure. Restraint stress for 7 days caused transient glucose intolerance, while S14D rats demonstrated increased glucose intolerance and insulin insensitivity. However, restraint stress for 28 days had no effect on glucose tolerance, but did cause an increase in glucose response to insulin challenge. The serum level of adiponectin was significantly (p< 0.05) lower compared with the control value while insulin remained unchanged except at in S28D rats that had a significant (p<0.05) increase. The expression of INSR and GLUT4 receptors were significantly (p< 0.05) decreased in the skeletal muscle of restraint stress exposed rats. There was a significant (p< 0.05) increase in the plasma corticosterone level of the stress rats compared with their control counterparts. Restraint stress caused glucose intolerance and insulin insensitivity in male Sprague-Dawley rats, which becomes accommodated with prolonged exposure and was likely related to the blunted insulin signalling in skeletal muscle. PMID:27574760

  11. Elevated Fasting Blood Glucose Is Predictive of Poor Outcome in Non-Diabetic Stroke Patients: A Sub-Group Analysis of SMART

    PubMed Central

    Zhou, Lixin; Peng, Bin; Zhu, Yicheng; Cui, Liying

    2016-01-01

    Background Although increasing evidence suggests that hyperglycemia following acute stroke adversely affects clinical outcome, whether the association between glycaemia and functional outcome varies between stroke patients with\\without pre-diagnosed diabetes remains controversial. We aimed to investigate the relationship between the fasting blood glucose (FBG) and the 6-month functional outcome in a subgroup of SMART cohort and further to assess whether this association varied based on the status of pre-diagnosed diabetes. Methods Data of 2862 patients with acute ischemic stroke (629 with pre-diagnosed diabetics) enrolled from SMART cohort were analyzed. Functional outcome at 6-month post-stroke was measured by modified Rankin Scale (mRS) and categorized as favorable (mRS:0–2) or poor (mRS:3–5). Binary logistic regression model, adjusting for age, gender, educational level, history of hypertension and stroke, baseline NIHSS and treatment group, was used in the whole cohort to evaluate the association between admission FBG and functional outcome. Stratified logistic regression analyses were further performed based on the presence/absence of pre-diabetes history. Results In the whole cohort, multivariable logistical regression showed that poor functional outcome was associated with elevated FBG (OR1.21 (95%CI 1.07–1.37), p = 0.002), older age (OR1.64 (95% CI1.38–1.94), p<0.001), higher NIHSS (OR2.90 (95%CI 2.52–3.33), p<0.001) and hypertension (OR1.42 (95%CI 1.13–1.98), p = 0.04). Stratified logistical regression analysis showed that the association between FBG and functional outcome remained significant only in patients without pre-diagnosed diabetes (OR1.26 (95%CI 1.03–1.55), p = 0.023), but not in those with premorbid diagnosis of diabetes (p = 0.885). Conclusion The present results demonstrate a significant association between elevated FBG after stroke and poor functional outcome in patients without pre-diagnosed diabetes, but not in diabetics

  12. Blood Test: Glucose

    MedlinePlus

    ... Things to Know About Zika & Pregnancy Blood Test: Glucose KidsHealth > For Parents > Blood Test: Glucose Print A A A Text Size What's in ... de sangre: glucosa What It Is A blood glucose test measures the amount of glucose (the main ...

  13. CSF glucose test

    MedlinePlus

    Glucose test - CSF; Cerebrospinal fluid glucose test ... The glucose level in the CSF should be 50 to 80 mg/100 mL (or greater than 2/3 ... Abnormal results include higher and lower glucose levels. Abnormal ... or fungus) Inflammation of the central nervous system Tumor

  14. Promoting Good Campus Relations: Dealing with Hate Crimes and Intolerance. Guidelines

    ERIC Educational Resources Information Center

    Universities UK, 2005

    2005-01-01

    This guidance has been produced to help higher education institutions (HEIs) deal with hate crimes and intolerance. Aiming to replace the previous Committee of Vice-Chancellors and Principals' guidance on extremism and intolerance, this publication provides an overview of the ways in which HEIs can encourage tolerance and respect and ensure that…

  15. Prevalence of self-reported lactose intolerance in multiethnic sample of adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    According to the National Institute of Diabetes and Digestive and Kidney Diseases, between 30 and 50 million Americans have the potential for lactose-intolerance symptoms. However, lactose-intolerance prevalence rates in practical life settings may be lower than originally suggested. The goal of thi...

  16. Lactose Intolerance: Exploring Reaction Kinetics Governing Lactose Conversion of Dairy Products within the Undergraduate Laboratory

    ERIC Educational Resources Information Center

    Smart, Jimmy L.

    2008-01-01

    Lactose intolerance is a condition suffered by an estimated 50 million Americans. Certain ethnic and racial populations are more widely affected than others. As many as 75 percent of all African-American, Jewish, Native American, and Mexican-American adults, and 90 percent of Asian-American adults are lactose intolerant. Some populations in Africa…

  17. Relationships among Perceived Racial Stress, Intolerance of Uncertainty, and Worry in a Black Sample

    ERIC Educational Resources Information Center

    Rucker, LaTanya S.; West, Lindsey M.; Roemer, Lizabeth

    2010-01-01

    The purpose of this study was to explore the relationships among chronic worry, perceived racial stress, and intolerance of uncertainty in a sample of adults who racially identify as Black. Intolerance of uncertainty has been associated with worry and generalized anxiety disorder in predominantly White samples. Given that racial stress is likely…

  18. Intolerance and psychopathology: toward a general diagnosis for racism, sexism, and homophobia.

    PubMed

    Guindon, Mary H; Green, Alan G; Hanna, Fred J

    2003-04-01

    Racism, sexism, and homophobia do not fit into any current diagnostic category. The authors propose that those who engage in such behaviors display a form of psychopathology deserving of its own category. The common denominator seems to be intolerance. The authors explore the possibility of an intolerant personality disorder, outline likely symptoms, and suggest some possible treatment considerations.

  19. Studies on Intolerance in American Life. Program in American History and Civilization.

    ERIC Educational Resources Information Center

    Tufts Univ., Medford, MA. Lincoln Filene Center for Citizenship and Public Affairs.

    The narrative selected for this unit on intolerance illustrates the perennial and universal methods for scapegoating. The general teaching objectives are to lead the students: 1) to feelings of tolerance toward individuals and groups who are different; 2) to investigate intolerance in terms of some of its causes: fear, deprivation, threatened…

  20. HRQoL questionnaire evaluation in lactose intolerant patients with adverse reactions to foods.

    PubMed

    Erminia, Ridolo; Ilaria, Baiardini; Tiziana, Meschi; Silvia, Peveri; Antonio, Nouvenne; Pierpaolo, Dall'Aglio; Loris, Borghi

    2013-09-01

    The occurrence of patients with gastrointestinal symptoms attributed either to food allergy or intolerance has significantly increased. Nevertheless, an accurate and detailed case history, a systematic evaluation and the outcomes of specific allergy tests to identify the offending foods, including "in vivo" and "in vitro" allergy tests, are often negative for food allergy and may indicate a lactose intolerance, which is a recurrent condition affecting about 50% of adults. The aims of our study were the following: (1) What is the real incidence of the food hypersensitivity and the primary lactose intolerance in patients with gastrointestinal symptoms, initially referred to allergy or food intolerance? (2) Does lactose intolerance affect the quality of life and compliance to the therapy program? We investigated 262 consecutive patients, 72 men and 190 women. An accurate and detailed history and clinical examination were completed to investigate the offending foods. The evaluation in each patient included: allergy tests, lactose H2 breath test (LHBT) and the HRQoL questionnaire. Five years after the diagnosis of lactose intolerance, a questionnaire on the persistence of gastrointestinal symptoms after lactose ingestion and the diet compliance was distributed. Our results demonstrate an high prevalence of lactose intolerance, more frequent in women; in these patients, bloating and diarrhea are the most reported symptoms. We observe only a significant positive correlation between adverse drug reaction (ADR) and LHBT+ patients, but not an augmented prevalence of food allergy and a negative impact on the HRQoL questionnaire of lactose intolerance. PMID:21614464

  1. The Intolerance of Uncertainty Index: Replication and Extension with an English Sample

    ERIC Educational Resources Information Center

    Carleton, R. Nicholas; Gosselin, Patrick; Asmundson, Gordon J. G.

    2010-01-01

    Intolerance of uncertainty (IU) is related to anxiety, depression, worry, and anxiety sensitivity. Precedent IU measures were criticized for psychometric instability and redundancy; alternative measures include the novel 45-item measure (Intolerance of Uncertainty Index; IUI). The IUI was developed in French with 2 parts, assessing general…

  2. Pancreatic islet hormone response to oral glucose in morbidly obese patients.

    PubMed Central

    Sirinek, K R; O'Dorisio, T M; Howe, B; McFee, A S

    1985-01-01

    Pancreatic islet peptides, as well as other gastrointestinal hormones, have been implicated in both the pathogenesis of obesity and the etiology of associated metabolic derangements. This study evaluated the pancreatic islet and gastrointestinal (GI) hormone response to oral glucose in 20 morbidly obese (151% above ideal body weight) patients. Glucose intolerance, hyperinsulinism, and exaggerated gastric inhibitory polypeptide (GIP) release occurred following glucose ingestion. Significant release of PP occurred in 14 patients, while only six patients had release of somatostatin. No significant changes in plasma concentrations of glucagon occurred. Since GIP is insulinotropic in the presence of hyperglycemia, the hyperinsulinism of morbid obesity may be secondary to the abnormally high glucose-stimulated GIP levels in these patients. Failure of glucagon suppression in response to oral glucose many contribute to the hyperglycemia noted. Somatostatin and pancreatic polypeptide may be responsible for some of the metabolic derangements of morbid obesity. PMID:2860876

  3. Differential role of SH2-B and APS in regulating energy and glucose homeostasis.

    PubMed

    Li, Minghua; Ren, Decheng; Iseki, Masanori; Takaki, Satoshi; Rui, Liangyou

    2006-05-01

    SH2-B and APS, two members of a pleckstrin homology and SH2 domain-containing adaptor family, promote both insulin and leptin signaling in a similar fashion in cultured cells. In addition, APS mediates insulin-stimulated activation of the c-Cbl/CAP/TC10 pathway in cultured adipocytes. Here we characterized genetically modified mice lacking SH2-B, APS, or both to determine the physiological roles of these two proteins in animals. Disruption of the SH2-B gene resulted in obesity, hyperglycemia, hyperinsulinemia, and glucose intolerance. Conversely, deletion of the APS gene did not alter adiposity, energy balance, and glucose metabolism. Energy intake, energy expenditure, fat content, body weight, and plasma insulin, leptin, glucose, and lipid levels were similar between APS(-/-) and WT littermates fed either normal chow or a high-fat diet. Moreover, deletion of APS failed to alter insulin and glucose tolerance. APS(-/-)/SH2-B(-/-) double knockout mice also developed energy imbalance, obesity, hyperleptinemia, hyperinsulinemia, hyperglycemia, and glucose intolerance; however, plasma leptin and insulin levels were significantly lower in APS(-/-)/SH2-B(-/-) than in SH2-B(-/-) mice. These results suggest that SH2-B, but not APS, is a key positive regulator of energy and glucose metabolism in mice.

  4. Internalized racism, body fat distribution, and abnormal fasting glucose among African-Caribbean women in Dominica, West Indies.

    PubMed

    Butler, Cleve; Tull, Eugene S; Chambers, Earle C; Taylor, Jerome

    2002-03-01

    The current study examined the relationship of internalized racism to glucose intolerance in a population of Afro-Caribbean women aged 18 to 55. Also of interest was whether this relationship would be differentially influenced by the type of body fat distribution or confounded by the level of hostility. A total of 244 women were selected from a systematic sample of households on the island of Dominica, West Indies. Demographic data together with information on internalized racism were collected by questionnaire. Anthropometric information and fasting blood glucose were also measured. Women with high levels of internalized racism exhibited an increased risk of elevated fasting glucose compared to those with low levels of internalized racism (odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.1-5.5). There was no difference in mean body mass index (BMI) by level of internalized racism. However those with high internalized racism had a significantly larger waist circumference after adjusting for age, education, hostility, and elevated fasting glucose status. In multivariate analyses controlling for age, education, hostility, and either weight or BMI, internalized racism remained independently associated with elevated fasting glucose. However, once waist circumference was included in the model, the relationship of internalized racism to elevated fasting glucose was not statistically significant. This study demonstrates a significant relationship between internalized racism and abnormal levels of fasting glucose which may be mediated through abdominal fat. The exact nature of the relationship of internalized racism to glucose intolerance may be an important area of future study.

  5. Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets.

    PubMed

    Bielohuby, Maximilian; Sisley, Stephanie; Sandoval, Darleen; Herbach, Nadja; Zengin, Ayse; Fischereder, Michael; Menhofer, Dominik; Stoehr, Barbara J M; Stemmer, Kerstin; Wanke, Rüdiger; Tschöp, Matthias H; Seeley, Randy J; Bidlingmaier, Martin

    2013-11-01

    Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein "Atkins-style" LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic β-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects.

  6. Mechanisms of Orthostatic Intolerance During Real and Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Session MP1 includes short reports on: (1) Orthostatic Tests after 42 Days of Simulated Weightlessness; (2) Effects of 12 Days Exposure to Simulated Microgravity on Central Circulatory Hemodynamics in the Rhesus Monkey; (3) Increased Sensitivity and Resetting of Baroflex Control of Exercise Heart Rate After Prolonged Bed-Rest; (4) Complex Cardiovascular Dynamics and Deconditioning During Head-down Bed Rest; (5) The Cardiovascular Effects of 6 Hours of Head-down Tilt Upon Athletes and Non-athletes; (6) Individual Susceptibility to Post-spaceflight Orthostatic Intolerance: Contributions of Gender-related and Microgravity-related Factors; (7) Cassiopee Mission 1996: Comparison of Cardiovascular Alteration after Short and Long-term Spaceflights; (8) Cerebral and Femoral Flow Response to LBNP during 6 Month MIR Spaceflights (93-95); and (9) Cerebrovascular Changes due to Spaceflight and Postflight Presyncope.

  7. Fruit-induced FPIES masquerading as hereditary fructose intolerance.

    PubMed

    Fiocchi, Alessandro; Dionisi-Vici, Carlo; Cotugno, Giovanna; Koch, Pierluigi; Dahdah, Lamia

    2014-08-01

    Hereditary fructose intolerance (HFI) symptoms develop at first introduction of fruit during weaning. We report on an infant with suspected HFI who presented with repeated episodes of vomiting and hypotension after ingestion of fruit-containing meals. The first episode occurred at age 4 months. Despite negative genetic testing for HFI, strict avoidance of fruit ingestion resulted in lack of recurrence of symptoms. Oral-fructose-tolerance testing conducted with an apple mousse did not determine hypoglycemia or fructosuria but caused severe hypotension. Allergy evaluations were negative, and the history was diagnostic for fruit-induced food protein-induced enterocolitis syndrome. Because this non-immunoglobulin E-mediated gastrointestinal food hypersensitivity manifests as profuse, repetitive vomiting, often with diarrhea, leading to acute dehydration and lethargy, it may be misinterpreted as HFI. We advise pediatricians to consider food protein-induced enterocolitis syndrome in the differential diagnosis when there is a suspicion of HFI.

  8. Managing the patient with episodic sinus tachycardia and orthostatic intolerance.

    PubMed

    Narichania, Aalap D; Schleifer, J William; Shen, Win-Kuang

    2014-01-01

    Patients with episodic sinus tachycardia and associated orthostatic intolerance present a diagnostic and management dilemma to the clinician. We define this group of disorders to include sinus node reentrant tachycardia (SNRT), inappropriate sinus tachycardia (IAST), and postural orthostatic tachycardia syndrome (POTS). After a brief review of the current understanding of the pathophysiology and epidemiology of this group of disorders, we focus on the diagnosis and management of IAST and POTS. Our approach attempts to recognize the considerable overlap in pathophysiology and clinical presentation between these two heterogeneous conditions. Thus, we focus on a mechanism-based workup and therapeutic approach. Sinus tachycardia related to identifiable causes should first be ruled out in these patients. Next, a basic cardiovascular and autonomic workup is suggested to exclude structural heart disease, identify a putative diagnosis, and guide therapy. We review both nonpharmacologic and pharmacologic therapy, with a focus on recent advances. Larger randomized control trials and further mechanistic studies will help refine management in the future.

  9. Intolerance of Uncertainty: A Temporary Experimental Induction Procedure

    PubMed Central

    Mosca, Oriana; Lauriola, Marco; Carleton, R. Nicholas

    2016-01-01

    Background and Objectives Intolerance of uncertainty (IU) is a trans-diagnostic construct involved in anxiety and related disorders. Research focused on cross-sectional reporting, manipulating attitudes toward objective and impersonal events or on treatments designed to reduce IU in clinical populations. The current paper presents an experimental procedure for laboratory manipulations of IU and tests mediation hypotheses following the Intolerance of Uncertainty Model. Methods On pre-test, undergraduate volunteers (Study 1, n = 43;68% women. Study 2, n = 169;83.8% women) were asked to provide an idiosyncratic future negative life event. State-IU, Worry, Positive and Negative Affect were assessed after that a standardized procedure was used to identify event’s potential negative consequences. The same variables were assessed on post-test, after that participants were asked to read-through increasing and decreasing IU statements. Results Temporary changes on IU were consistently reproduced in both studies. Participants receiving increasing IU instructions reported greater state-IU, Worry and Negative Affect than those receiving decreasing IU instructions. However, this latter condition was not different from a control one (Study 2). Both studies revealed significant indirect effects of IU induction instructions on Worry and Negative Affect through state-IU. Limitations Both studies used undergraduate psychology students samples, younger than average population and predominantly female. Experimental manipulation and outcome measures belongs to the same semantic domain, uncertainty, potentially limiting generalizability. Conclusions Results supported the feasibility and efficacy of the proposed IU manipulation for non-clinical sample. Findings parallel clinical research showing that state-IU preceded Worry and Negative Affect states. PMID:27254099

  10. Repressive coping and alexithymia in idiopathic environmental intolerance

    PubMed Central

    Zachariae, Robert; Rasmussen, Alice; Johansen, Jeanne Duus; Elberling, Jesper

    2010-01-01

    Objective To examine if the non-expression of negative emotions (i.e., repressive coping) and differences in the ability to process and regulate emotions (i.e., alexithymia) is associated with idiopathic environmental intolerance (IEI). Methods The study included participants who had previously participated in a general population-based study and reported symptoms of environmental intolerance (n = 787) and patients with IEI (n = 237). The participants completed questionnaires assessing IEI, namely, a measure of repressive coping combining scores on the Marlowe–Crowne Social Desirability Scale (MCSDS) and the Taylor Manifest Anxiety Scale (TMAS), the Toronto Alexithymia Scale (TAS-20), and a negative affectivity scale (NAS). Multiple, hierarchical linear regression analyses were conducted using IEI variables as the dependent variables. Results The TMAS and MCSDS scores were independently associated with the IEI variables, but there was no evidence of a role of the repressive coping construct. While the total alexithymia score was unrelated to IEI, the TAS-20 subscale of difficulties identifying feelings (DIF) was independently associated with symptoms attributed to IEI. Negative affectivity was a strong independent predictor of the IEI variables and a mediator of the association between DIF and IEI. Conclusion Our results provide no evidence for a role of repressive coping in IEI, and our hypothesis of an association with alexithymia was only partly supported. In contrast, strong associations between IEI and negative emotional reactions, defensiveness and difficulties identifying feelings were found, suggesting a need for exploring the influence of these emotional reactions in IEI. PMID:21432559

  11. Neuroleptic intolerance in patients with anti-NMDAR encephalitis

    PubMed Central

    Lejuste, Florian; Thomas, Laure; Picard, Géraldine; Desestret, Virginie; Ducray, François; Rogemond, Veronique; Psimaras, Dimitri; Antoine, Jean-Christophe; Delattre, Jean-Yves; Groc, Laurent; Leboyer, Marion

    2016-01-01

    Objective: To precisely describe the initial psychiatric presentation of patients with anti-NMDA receptor (NMDAR) antibodies encephalitis (anti-NMDAR encephalitis) to identify potential clues enhancing its early diagnosis. Methods: We retrospectively studied the French Reference Centre medical records of every adult patient with anti-NMDAR encephalitis to specify the patients' initial psychiatric symptoms leading to hospitalization in a psychiatric department and the reasons underlying the diagnosis of anti-NMDAR encephalitis. Results: The medical records of 111 adult patients were reviewed. Psychiatric features were the initial presentation in 65 patients (59%). Among them, several psychiatric manifestations were observed, including visual and auditory hallucinations (n = 26, 40%), depression (n = 15, 23%), mania (n = 5, 8%), acute schizoaffective episode (n = 15, 23%), and eating disorder or addiction (n = 4; 6%). Forty-five patients (40% of total cohort) were first hospitalized in a psychiatric institution (91% women), with a median duration of stay of 9 days (range 0.25–239 days). Among them, 24 patients (53%) had associated discreet neurologic signs at the first evaluation, while 17 additional patients (38%) developed neurologic signs within a few days. Twenty-one patients (47%) were transferred to a medical unit for a suspicion of antipsychotic intolerance characterized by high temperature, muscle rigidity, mutism or coma, and biological results suggesting rhabdomyolysis. Conclusions: Several psychiatric presentations were observed in patients with anti-NMDAR encephalitis, although none was specific; however, patients, mostly women, also had discreet neurologic signs that should be carefully assessed as well as signs of antipsychotic intolerance that should raise suspicion for anti-NMDAR encephalitis.

  12. Chronic Fatigue Syndrome versus Systemic Exertion Intolerance Disease

    PubMed Central

    Jason, Leonard A.; Sunnquist, Madison; Brown, Abigail; Newton, Julia L.; Strand, Elin Bolle; Vernon, Suzanne D.

    2015-01-01

    Background The Institute of Medicine has recommended a change in the name and criteria for Chronic Fatigue Syndrome (CFS), renaming the illness Systemic Exertion Intolerance Disease (SEID). The new SEID case definition requires substantial reductions or impairments in the ability to engage in pre-illness activities, unrefreshing sleep, post-exertional malaise, and either cognitive impairment or orthostatic intolerance. Purpose In the current study, samples were generated through several different methods and were used to compare this new case definition to previous case definitions for CFS, Myalgic Encephalomyelitis (ME-ICC), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), as well as a case definition developed through empirical methods. Methods We used a cross-sectional design with samples from tertiary care settings, a biobank sample, and other forums. 796 patients from the US, Great Britain, and Norway completed the DePaul Symptom Questionnaire. Results Findings indicated that the SEID criteria identified 88% of participants in the samples analyzed, which is comparable to the 92% that met the Fukuda criteria. The SEID case definition was compared to a four item empiric criteria, and findings indicated that the four item empiric criteria identified a smaller, more functionally limited and symptomatic group of patients. Conclusion The recently developed SEID criteria appears to identify a group comparable in size to the Fukuda et al. criteria, but a larger group of patients than the Canadian ME/CFS and ME criteria, and selects more patients who have less impairment and fewer symptoms than a four item empiric criteria. PMID:26345409

  13. Neuroleptic intolerance in patients with anti-NMDAR encephalitis

    PubMed Central

    Lejuste, Florian; Thomas, Laure; Picard, Géraldine; Desestret, Virginie; Ducray, François; Rogemond, Veronique; Psimaras, Dimitri; Antoine, Jean-Christophe; Delattre, Jean-Yves; Groc, Laurent; Leboyer, Marion

    2016-01-01

    Objective: To precisely describe the initial psychiatric presentation of patients with anti-NMDA receptor (NMDAR) antibodies encephalitis (anti-NMDAR encephalitis) to identify potential clues enhancing its early diagnosis. Methods: We retrospectively studied the French Reference Centre medical records of every adult patient with anti-NMDAR encephalitis to specify the patients' initial psychiatric symptoms leading to hospitalization in a psychiatric department and the reasons underlying the diagnosis of anti-NMDAR encephalitis. Results: The medical records of 111 adult patients were reviewed. Psychiatric features were the initial presentation in 65 patients (59%). Among them, several psychiatric manifestations were observed, including visual and auditory hallucinations (n = 26, 40%), depression (n = 15, 23%), mania (n = 5, 8%), acute schizoaffective episode (n = 15, 23%), and eating disorder or addiction (n = 4; 6%). Forty-five patients (40% of total cohort) were first hospitalized in a psychiatric institution (91% women), with a median duration of stay of 9 days (range 0.25–239 days). Among them, 24 patients (53%) had associated discreet neurologic signs at the first evaluation, while 17 additional patients (38%) developed neurologic signs within a few days. Twenty-one patients (47%) were transferred to a medical unit for a suspicion of antipsychotic intolerance characterized by high temperature, muscle rigidity, mutism or coma, and biological results suggesting rhabdomyolysis. Conclusions: Several psychiatric presentations were observed in patients with anti-NMDAR encephalitis, although none was specific; however, patients, mostly women, also had discreet neurologic signs that should be carefully assessed as well as signs of antipsychotic intolerance that should raise suspicion for anti-NMDAR encephalitis. PMID:27606355

  14. Three 15-min bouts of moderate postmeal walking significantly improves 24-h glycemic control in older people at risk for impaired glucose tolerance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to compare the effectiveness of three 15-min bouts of postmeal walking with 45 min of sustained walking on 24-h glycemic control in older persons at risk for glucose intolerance. Inactive older (=60 years of age) participants (N = 10) were recruited from the community a...

  15. Lactose intolerance and African Americans: implications for the consumption of appropriate intake levels of key nutrients.

    PubMed

    2009-10-01

    Lactose intolerance is a complex condition that is complicated by cultural beliefs and perceptions about the consumption of dairy products. These attitudes about dairy may contribute to inadequate intake of key nutrients that may impact conditions that contribute to health disparities in African Americans. While a complex health problem, lactose intolerance is easy to treat. However, no treatment can improve the body's ability to produce lactase. Yet, symptoms can be controlled through dietary strategies. This position paper emphasizes the importance of using patient and provider-level strategies in order to reduce the risks to the health of African Americans that may accrue as a result of dairy nutrient deficiency. Evaluation and assessment of interventions tested is critical so that evidence-based approaches to addressing dairy nutrient deficiency and lactose Intolerance can be created. Lastly, it is essential for physicians to communicate key messages to their patients. Since dairy nutrients address important health concerns, the amelioration of lactose intolerance is an investment in health. Lactose intolerance is common, is easy to treat, and can be managed. It is possible to consume dairy even in the face of a history of maldigestion or lactose intolerant issues. Gradually increasing lactose in the diet--drinking small milk portions with food, eating yogurt, and consuming cheese--are effective strategies for managing lactose intolerance and meeting optimal dairy needs.

  16. Lactose intolerance and African Americans: implications for the consumption of appropriate intake levels of key nutrients.

    PubMed

    2009-10-01

    Lactose intolerance is a complex condition that is complicated by cultural beliefs and perceptions about the consumption of dairy products. These attitudes about dairy may contribute to inadequate intake of key nutrients that may impact conditions that contribute to health disparities in African Americans. While a complex health problem, lactose intolerance is easy to treat. However, no treatment can improve the body's ability to produce lactase. Yet, symptoms can be controlled through dietary strategies. This position paper emphasizes the importance of using patient and provider-level strategies in order to reduce the risks to the health of African Americans that may accrue as a result of dairy nutrient deficiency. Evaluation and assessment of interventions tested is critical so that evidence-based approaches to addressing dairy nutrient deficiency and lactose Intolerance can be created. Lastly, it is essential for physicians to communicate key messages to their patients. Since dairy nutrients address important health concerns, the amelioration of lactose intolerance is an investment in health. Lactose intolerance is common, is easy to treat, and can be managed. It is possible to consume dairy even in the face of a history of maldigestion or lactose intolerant issues. Gradually increasing lactose in the diet--drinking small milk portions with food, eating yogurt, and consuming cheese--are effective strategies for managing lactose intolerance and meeting optimal dairy needs. PMID:19899495

  17. [Effect of exogenous lactase on the absorption of lactose and its intolerance symptoms].

    PubMed

    He, M; Yang, Y; Bian, L; Cui, H

    1999-09-30

    The objective of this study was to evaluate the effects of lactase on lactose malabsorption and its intolerance symptoms, as well as the available way to improve lactose absorption. Healthy adults with a history of lactose intolerance were screened by 25 g lactose tolerance test. The individuals with higher H2 expired and/or lactose intolerance symptoms were selected as the subjects. Subjects were challenged twice with "400 ml low fat milk" and "400 ml low fat milk + 9000Fcc lactase" separately in 3 days interval. The breath H2 concentration and intolerance symptoms were tested in 4 hours after the challenge. The results showed that exogenous lactase can significantly decrease the incidence of lactose malabsorption (the abnormal expiration of H2 decreased from 100% to 48.9%) and milk intolerance symptoms(from 51.1% to 13.3%). The results from this study demonstrate that lactose malabsorption and intolerance symptoms are resulted from the reduced enzyme activities of individuals, and the exogenous lactase can improve lactose absorption and intolerance symptoms. Lactose supplementation may be an available way to increase the dairy consumption and promote health of people. PMID:12712706

  18. Glucose, memory, and aging.

    PubMed

    Korol, D L; Gold, P E

    1998-04-01

    Circulating glucose concentrations regulate many brain functions, including learning and memory. Much of the evidence for this view comes from experiments assessing stress-related release of epinephrine with subsequent increases in blood glucose concentrations. One application of this work has been to investigate whether age-related memory impairments result from dysfunctions in the neuroendocrine regulation of the brain processes responsible for memory. Like humans, aged rodents exhibit some memory impairments that can be reversed by administration of epinephrine or glucose. In elderly humans, ingestion of glucose enhances some cognitive functions, with effects best documented thus far on tests of verbal contextual and noncontextual information. Glucose also effectively enhances cognition in persons with Alzheimer disease or Down syndrome. Although earlier evidence suggested that glucose does not enhance cognitive function in healthy young adults, more recent findings suggest that glucose is effective in this population, provided the tests are sufficiently difficult. In college students, glucose consumption significantly enhanced memory of material in a paragraph. Glucose also appeared to enhance attentional processes in these students. Neither face and word recognition nor working memory was influenced by treatment with glucose. The neurobiological mechanisms by which glucose acts are under current investigation. Initial evidence suggests that glucose or a metabolite may activate release of the neurotransmitter acetylcholine in rats when they are engaged in learning. Consequently, the issue of nutrition and cognition becomes increasingly important in light of evidence that circulating glucose concentrations have substantial effects on brain and cognitive functions.

  19. Empirical prediction of net portal appearance of volatile fatty acids, glucose, and their secondary metabolites (beta-hydroxybutyrate, lactate) from dietary characteristics in ruminants: A meta-analysis approach.

    PubMed

    Loncke, C; Ortigues-Marty, I; Vernet, J; Lapierre, H; Sauvant, D; Nozière, P

    2009-01-01

    The current trend in energy feeding systems for ruminants toward a nutrient-based system requires dietary energy supply to be determined in terms of amount and nature of absorbed energy-yielding nutrients. The objective of this study was to establish response equations on the net portal appearance (NPA) of VFA and glucose, and their secondary metabolites beta-hydroxybutyrate (BHBA) and lactate, to changes in intake level and chemical dietary characteristics based on the Institut National de la Recherche Agronomique Feed Evaluation System for Ruminants. Meta-analyses were applied on published data compiled from the FLORA database, which pools the results on net splanchnic nutrient fluxes in multi-catheterized ruminants from international publications. For each nutrient, several prediction variables were tested. We obtained robust models for intakes up to 30 g of DM x d(-1) x kg of BW(-1) and diets containing less than 70 g of concentrate per 100 g of DM. These models were designed to predict the NPA (mmol x h(-1) x kg of BW(-1)) of total VFA based on the amount of ruminally fermented OM (RfOM) intake [adjusted R(2) (R(2)(adj)) = 0.95; residual means square errors (RMSE) = 0.24], to predict VFA profile (mol/100 mol of total VFA) based on type of RfOM intake (acetate: R(2)(adj) = 0.85, RMSE = 2.2; propionate: R(2)(adj) = 0.76, RMSE = 2.2; butyrate: R(2)(adj) = 0.76, RMSE = 1.09), and to predict the NPA (mmol x h(-1) x kg of BW(-1)) of glucose based on the starch digested in the small intestine independent of ruminant species, and while presenting no interfering factors on the residuals and individual slopes. The model predicting the NPA (mmol x h(-1) x kg of BW(-1)) of BHBA based on the amount of RfOM intake (R(2)(adj) = 0.91; RMSE = 0.036) was species-dependent, and the model predicting NPA (mmol x h(-1) x kg of BW(-1)) of lactate based on starch digested in the rumen (R(2)(adj) = 0.77; RMSE = 0.042) presented a wide dispersion. However, the NPA (mmol x h(-1) x kg of

  20. Glucose-6-phosphate dehydrogenase

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003671.htm Glucose-6-phosphate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) is a type of ...

  1. Your Glucose Meter

    MedlinePlus

    ... by Audience For Women Women's Health Topics Your Glucose Meter Share Tweet Linkedin Pin it More sharing ... Español Basic Facts 7 Tips for Testing Your Blood Sugar and Caring for Your Meter Glucose meters test ...

  2. Low glucokinase activity and high rates of gluconeogenesis contribute to hyperglycemia in barn owls (Tyto alba) after a glucose challenge.

    PubMed

    Myers, M R; Klasing, K C

    1999-10-01

    Barn owls (Tyto alba) and leghorn chickens were fed a low protein high glucose (33.44% protein, 23.67% glucose) or a high protein low glucose (55.35% protein, 1.5% glucose) diet. After an intravenous glucose infusion, the peak in plasma glucose was not affected by diet in either species and was 22.6 and 39.4 mmol/L in chickens and barn owls, respectively. Glucose levels returned to normal within 30 min in chickens, but remained elevated for 3.5 h in barn owls. An oral glucose challenge also resulted in greater and longer hyperglycemia in barn owls than in chickens. The activities of hepatic glucokinase, malic enzyme and phosphoenolpyruvate carboxykinase of barn owls were 16, 35, and 333% of the levels in chickens. Malic enzyme (P = 0.024) was less affected by dietary glucose level in barn owls than in chickens. Cultured hepatocytes from chickens produced 43% more glucose from lactate than hepatocytes from barn owls and, conversely, barn owl hepatocytes produced 87% more glucose from threonine than chickens (P = 0.001). Gluconeogenesis from lactate was greatly suppressed by high media glucose in chicken hepatocytes but not in those of barn owls (P = 0.0001 for species by glucose level interaction). When threonine was the substrate, gluconeogenesis was suppressed by increased glucose in both species but to a greater relative extent in chickens (P = 0.007 for species by glucose level interaction). Owls were glucose intolerant at least in part because of low hepatic glucokinase activity and an inadequate suppression of gluconeogenesis in the presence of exogenous glucose, apparently because they evolved with large excesses of amino acids and limited glucose in their normal diet. PMID:10498765

  3. Tff3, as a Novel Peptide, Regulates Hepatic Glucose Metabolism

    PubMed Central

    Xue, Yuan; Shen, Lian; Cui, Ying; Zhang, Huabing; Chen, Qi; Cui, Anfang; Fang, Fude; Chang, Yongsheng

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder strongly associated with hepatic glucose intolerance and insulin resistance. The trefoil peptides are a family of small regulatory proteins and Tff3 is widely expressed in multiple tissues including liver. But the roles of Tff3 in regulation of glucose metabolism and insulin sensitivity in liver remain unclear. Here we show that the hepatic Tff3 expression levels were decreased in ob/ob and high-fat diet-induced obese mice. Overexpression of Tff3 in primary mouse hepatocytes inhibited the expression of gluconeogenic genes, including G6pc, PEPCK and PGC-1α, subsequently decreasing cellular glucose output. GTT and ITT experiments revealed that adenovirus-mediated overexpression of Tff3 in diabetic or obese mice improved glucose tolerance and insulin sensitivity. Collectively, our results indicated that Tff3 peptides are involved in glucose homeostasis and insulin sensitivity, providing a promising peptide on new therapies against the metabolic disorders associated with T2DM. PMID:24086476

  4. The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance.

    PubMed

    Scrimshaw, N S; Murray, E B

    1988-10-01

    1) Most humans, like other mammals, gradually lose the intestinal enzyme lactase after infancy and with it the ability to digest lactose, the principle sugar in milk. At some point in prehistory, a genetic mutation occurred and lactase activity persisted in a majority of the adult population of Northern and Central Europe. 2) Persistence of intestinal lactase, the uncommon trait worldwide, is inherited as a highly penetrant autosomal-dominant characteristic. Both types of progeny are almost equally common when one parent is a lactose maldigester and the other a lactose digester. 3) The incidence of lactose maldigestion is usually determined in adults by the administration in the fasting state of a 50-g dose of lactose in water, the equivalent of that in 1 L of milk. Measurement is made of either the subsequent rise in blood glucose or the appearance of additional hydrogen in the breath. It is also sometimes identified by measuring lactase activity directly in a biopsy sample from the jejunum. For children the test dose is reduced according to weight. Depending on the severity of the lactase deficiency and other factors, the test dose may result in abdominal distention, pain, and diarrhea. 4) The frequency of lactose maldigestion varies widely among populations but is high in nearly all but those of European origin. In North American adults lactose maldigestion is found in approximately 79% of Native Americans, 75% of blacks, 51% of Hispanics, and 21% of Caucasians. In Africa, Asia, and Latin America prevalence rates range from 15-100% depending on the population studied. 5) Whenever the lactose ingested exceeds the capacity of the intestinal lactase to split it into the simple sugars glucose and galactose, which are absorbed directly, it passes undigested to the large intestine. There it is fermented by the colonic flora, with short-chain fatty acids and hydrogen gas as major products. The gas produced can cause abdominal distention and pain and diarrhea may also

  5. Distress and avoidance in Generalized Anxiety Disorder:Exploring the relationships with intolerance of uncertainty and worry

    PubMed Central

    Lee, Jonathan K.; Orsillo, Susan M.; Roemer, Lizabeth; Allen, Laura B.

    2009-01-01

    Theory and research suggest treatments targeting experiential avoidance may enhance outcomes for patients with GAD (Roemer & Orsillo, 2002; 2007). Preliminary findings demonstrate that distress about emotions and avoidance of internal experiences share unique variance with GAD above and beyond chronic reports of worry (Roemer, Salters, Raffa, & Orsillo, 2005). The purpose of the present study was to extend previous findings to explore the role of experiential avoidance and distress about emotions in a treatment-seeking sample with a principal diagnosis of GAD compared with demographically matched non-anxious controls, and to explore their shared relationship with two putative psychopathological processes in GAD: intolerance of uncertainty and worry. Patients with GAD reported significantly higher levels of experiential avoidance and distress about emotions compared to non-clinical controls while controlling for depressive symptoms, and measures of these constructs significantly predicted GAD status. Additionally, experiential avoidance and distress about anxious, positive, and angry emotions shared unique variance with intolerance of uncertainty when negative affect was partialled out, while only experiential avoidance and distress about anxious emotions shared unique variance with worry. Discussion focuses on implications for treatment as well as future directions for research. PMID:19714542

  6. Ambivalent role of gallated catechins in glucose tolerance in humans: a novel insight into non-absorbable gallated catechin-derived inhibitors of glucose absorption.

    PubMed

    Park, J H; Jin, J Y; Baek, W K; Park, S H; Sung, H Y; Kim, Y K; Lee, J; Song, D K

    2009-12-01

    Prolonged postprandial hyperglycemia is a detrimental factor for type 2 diabetes and obesity. The benefit of green tea extract (GTE) consumption still requires confirmation. We report the effects of circulating green tea catechins on blood glucose and insulin levels. Oral glucose loading 1 h after GTE ingestion in humans led to higher blood glucose and insulin levels than in control subjects. Gallated catechins were required for these effects, although within the intestinal lumen they have been known to decrease glucose and cholesterol absorption. Treatment with epigallocatechin-3-gallate hindered 2-deoxyglucose uptake into liver, fat, pancreatic beta-cell, and skeletal muscle cell lines. The glucose intolerance was ameliorated by gallated catechin-deficient GTE or GTE mixed with polyethylene glycol, which was used as an inhibitor of intestinal absorption of gallated catechins. These findings may suggest that the gallated catechin when it is in the circulation elevates blood glucose level by blocking normal glucose uptake into the tissues, resulting in secondary hyperinsulinemia, whereas it decreases glucose entry into the circulation when they are inside the intestinal lumen. These findings encourage the development of non-absorbable derivatives of gallated catechins for preventative treatment of type 2 diabetes and obesity, which would specifically induce only the positive luminal effect.

  7. Apolipoprotein A-IV improves glucose homeostasis by enhancing insulin secretion

    PubMed Central

    Wang, Fei; Kohan, Alison B.; Kindel, Tammy L.; Corbin, Kathryn L.; Nunemaker, Craig S.; Obici, Silvana; Woods, Stephen C.; Davidson, W. Sean; Tso, Patrick

    2012-01-01

    Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine in response to fat absorption. Here we demonstrate a potential role for apoA-IV in regulating glucose homeostasis. ApoA-IV–treated isolated pancreatic islets had enhanced insulin secretion under conditions of high glucose but not of low glucose, suggesting a direct effect of apoA-IV to enhance glucose-stimulated insulin release. This enhancement involves cAMP at a level distal to Ca2+ influx into the β cells. Knockout of apoA-IV results in compromised insulin secretion and impaired glucose tolerance compared with WT mice. Challenging apoA-IV−/− mice with a high-fat diet led to fasting hyperglycemia and more severe glucose intolerance associated with defective insulin secretion than occurred in WT mice. Administration of exogenous apoA-IV to apoA-IV−/− mice improved glucose tolerance by enhancing insulin secretion in mice fed either chow or a high-fat diet. Finally, we demonstrate that exogenous apoA-IV injection decreases blood glucose levels and stimulates a transient increase in insulin secretion in KKAy diabetic mice. These results suggest that apoA-IV may provide a therapeutic target for the regulation of glucose-stimulated insulin secretion and treatment of diabetes. PMID:22619326

  8. The negative influence of high-glucose ambience on neurogenesis in developing quail embryos.

    PubMed

    Chen, Yao; Fan, Jian-xia; Zhang, Zhao-long; Wang, Guang; Cheng, Xin; Chuai, Manli; Lee, Kenneth Ka Ho; Yang, Xuesong

    2013-01-01

    Gestational diabetes is defined as glucose intolerance during pregnancy and it is presented as high blood glucose levels during the onset pregnancy. This condition has an adverse impact on fetal development but the mechanism involved is still not fully understood. In this study, we investigated the effects of high glucose on the developing quail embryo, especially its impact on the development of the nervous system. We established that high glucose altered the central nervous system mophologically, such that neural tube defects (NTDs) developed. In addition, we found that high glucose impaired nerve differentiation at dorsal root ganglia and in the developing limb buds, as revealed by neurofilament (NF) immunofluorescent staining. The dorsal root ganglia are normally derived from neural crest cells (NCCs), so we examine the delamination of NCCs from dorsal side of the neural tube. We established that high glucose was detrimental to the NCCs, in vivo and in vitro. High glucose also negatively affected neural differentiation by reducing the number and length of neurites emanating from neurons in culture. We established that high glucose exposure caused an increase in reactive oxidative species (ROS) generation by primary cultured neurons. We hypothesized that excess ROS was the factor responsible for impairing neuron development and differentiation. We provided evidence for our hypothesis by showing that the addition of vitamin C (a powerful antioxidant) could rescue the damaging effects of high glucose on cultured neurons.

  9. PKA Enhances the Acute Insulin Response Leading to the Restoration of Glucose Control

    PubMed Central

    Kaihara, Kelly A.; Dickson, Lorna M.; Ellenbroek, Johanne H.; Orr, Caitlin M.D.; Layden, Brian T.

    2015-01-01

    Diabetes arises from insufficient insulin secretion and failure of the β-cell mass to persist and expand. These deficits can be treated with ligands to Gs-coupled G-protein-coupled receptors that raise β-cell cAMP. Here we studied the therapeutic potential of β-cell cAMP-dependent protein kinase (PKA) activity in restoring glucose control using β-caPKA mice. PKA activity enhanced the acute insulin response (AIR) to glucose, which is a primary determinant of the efficacy of glucose clearance. Enhanced AIR improved peripheral insulin action, leading to more rapid muscle glucose uptake. In the setting of pre-established glucose intolerance caused by diet-induced insulin resistance or streptozotocin-mediated β-cell mass depletion, PKA activation enhanced β-cell secretory function to restore glucose control, primarily through augmentation of the AIR. Enhanced AIR and improved glucose control were maintained through 16 weeks of a high-fat diet and aging to 1 year. Importantly, improved glucose tolerance did not increase the risk for hypoglycemia, nor did it rely upon hyperinsulinemia or β-cell hyperplasia, although PKA activity was protective for β-cell mass. These data highlight that improving β-cell function through the activation of PKA has a large and underappreciated capacity to restore glucose control with minimal risk for adverse side effects. PMID:25475437

  10. The Negative Influence of High-Glucose Ambience on Neurogenesis in Developing Quail Embryos

    PubMed Central

    Wang, Guang; Cheng, Xin; Chuai, Manli; Lee, Kenneth Ka Ho; Yang, Xuesong

    2013-01-01

    Gestational diabetes is defined as glucose intolerance during pregnancy and it is presented as high blood glucose levels during the onset pregnancy. This condition has an adverse impact on fetal development but the mechanism involved is still not fully understood. In this study, we investigated the effects of high glucose on the developing quail embryo, especially its impact on the development of the nervous system. We established that high glucose altered the central nervous system mophologically, such that neural tube defects (NTDs) developed. In addition, we found that high glucose impaired nerve differentiation at dorsal root ganglia and in the developing limb buds, as revealed by neurofilament (NF) immunofluorescent staining. The dorsal root ganglia are normally derived from neural crest cells (NCCs), so we examine the delamination of NCCs from dorsal side of the neural tube. We established that high glucose was detrimental to the NCCs, in vivo and in vitro. High glucose also negatively affected neural differentiation by reducing the number and length of neurites emanating from neurons in culture. We established that high glucose exposure caused an increase in reactive oxidative species (ROS) generation by primary cultured neurons. We hypothesized that excess ROS was the factor responsible for impairing neuron development and differentiation. We provided evidence for our hypothesis by showing that the addition of vitamin C (a powerful antioxidant) could rescue the damaging effects of high glucose on cultured neurons. PMID:23818954

  11. Glucose screening tests during pregnancy

    MedlinePlus

    Oral glucose tolerance test - pregnancy; OGTT - pregnancy; Glucose challenge test - pregnancy; Gestational diabetes - glucose screening ... first step, you will have a glucose screening test: You DO NOT need to prepare or change ...

  12. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices.

    PubMed

    Jainandunsing, Sjaam; Wattimena, J L Darcos; Rietveld, Trinet; van Miert, Joram N I; Sijbrands, Eric J G; de Rooij, Felix W M

    2016-05-01

    The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the following three subgroups: normoglycemic, at risk, and T2D. We recruited South Asian and Caucasian families, and we report separate analyses if differences occurred. Plasma glucose, insulin, and C-peptide concentrations were analyzed as AUCs during OGTT, OMM estimate of renal C-peptide secretion, and OMM beta-cell and insulin sensitivity indices were calculated to obtain disposition indices. Post-glucose load glucose and C-peptide in urine were measured and related to plasma-based indices. Urinary glucose corresponded well with plasma glucose AUC (Cau r = 0.64, P < 0.01; SA r = 0.69, P < 0.01), S I (Cau r = -0.51, P < 0.01; SA r = -0.41, P < 0.01), Φ dynamic (Cau r = -0.41, P < 0.01; SA r = -0.57, P < 0.01), and Φ oral (Cau r = -0.61, P < 0.01; SA r = -0.73, P < 0.01). Urinary C-peptide corresponded well to plasma C-peptide AUC (Cau r = 0.45, P < 0.01; SA r = 0.33, P < 0.05) and OMM estimate of renal C-peptide secretion (r = 0.42, P < 0.01). In general, glucose excretion plasma threshold for the presence of glucose in urine was ~10-10.5 mmol L(-1) in non-T2D individuals, but not measurable in T2D individuals. Renal glucose secretion during OGTT did not influence OMM indices in general nor in T2D patients (renal clearance range 0-2.1 %, with median 0.2 % of plasma glucose AUC). C-indices of urinary glucose to detect various stages of glucose intolerance were excellent (Cau 0.83-0.98; SA 0.75-0.89). The limited role of renal glucose secretion validates the neglecting of urinary glucose secretion in kinetic models of glucose homeostasis using plasma glucose concentrations. Both C

  13. Diagnosis, Prevention, and Management of Statin Adverse Effects and Intolerance: Canadian Consensus Working Group Update (2016).

    PubMed

    Mancini, G B John; Baker, Steven; Bergeron, Jean; Fitchett, David; Frohlich, Jiri; Genest, Jacques; Gupta, Milan; Hegele, Robert A; Ng, Dominic; Pearson, Glen J; Pope, Janet; Tashakkor, A Yashar

    2016-07-01

    The Canadian Consensus Working Group has updated its evaluation of the literature pertaining to statin intolerance and adverse effects. This overview introduces a pragmatic definition of statin intolerance (goal-inhibiting statin intolerance) that emphasizes the effects of symptoms on achieving nationally vetted goals in patients fulfilling indications for lipid-lowering therapy and cardiovascular risk reduction. The Canadian Consensus Working Group provides a structured framework for avoiding, evaluating and managing goal-inhibiting statin intolerance. Particularly difficult practice situations are reviewed, including management in young and elderly individuals, and in athletes and labourers. Finally, targeted at specialty practitioners, more detailed analyses of specific but more unusual adverse effects ascribed to statins are updated including evidence regarding new-onset diabetes, cognitive dysfunction, cataracts, and the rare but important immune-mediated necrotizing myopathy. PMID:27342697

  14. Noninvasive glucose sensing by transcutaneous Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Shih, Wei-Chuan; Bechtel, Kate L.; Rebec, Mihailo V.

    2015-05-01

    We present the development of a transcutaneous Raman spectroscopy system and analysis algorithm for noninvasive glucose sensing. The instrument and algorithm were tested in a preclinical study in which a dog model was used. To achieve a robust glucose test system, the blood levels were clamped for periods of up to 45 min. Glucose clamping and rise/fall patterns have been achieved by injecting glucose and insulin into the ear veins of the dog. Venous blood samples were drawn every 5 min and a plasma glucose concentration was obtained and used to maintain the clamps, to build the calibration model, and to evaluate the performance of the system. We evaluated the utility of the simultaneously acquired Raman spectra to be used to determine the plasma glucose values during the 8-h experiment. We obtained prediction errors in the range of ˜1.5-2 mM. These were in-line with a best-case theoretical estimate considering the limitations of the signal-to-noise ratio estimates. As expected, the transition regions of the clamp study produced larger predictive errors than the stable regions. This is related to the divergence of the interstitial fluid (ISF) and plasma glucose values during those periods. Two key contributors to error beside the ISF/plasma difference were photobleaching and detector drift. The study demonstrated the potential of Raman spectroscopy in noninvasive applications and provides areas where the technology can be improved in future studies.

  15. Noninvasive glucose sensing by transcutaneous Raman spectroscopy

    PubMed Central

    Shih, Wei-Chuan; Bechtel, Kate L.; Rebec, Mihailo V.

    2015-01-01

    Abstract. We present the development of a transcutaneous Raman spectroscopy system and analysis algorithm for noninvasive glucose sensing. The instrument and algorithm were tested in a preclinical study in which a dog model was used. To achieve a robust glucose test system, the blood levels were clamped for periods of up to 45 min. Glucose clamping and rise/fall patterns have been achieved by injecting glucose and insulin into the ear veins of the dog. Venous blood samples were drawn every 5 min and a plasma glucose concentration was obtained and used to maintain the clamps, to build the calibration model, and to evaluate the performance of the system. We evaluated the utility of the simultaneously acquired Raman spectra to be used to determine the plasma glucose values during the 8-h experiment. We obtained prediction errors in the range of ∼1.5−2  mM. These were in-line with a best-case theoretical estimate considering the limitations of the signal-to-noise ratio estimates. As expected, the transition regions of the clamp study produced larger predictive errors than the stable regions. This is related to the divergence of the interstitial fluid (ISF) and plasma glucose values during those periods. Two key contributors to error beside the ISF/plasma difference were photobleaching and detector drift. The study demonstrated the potential of Raman spectroscopy in noninvasive applications and provides areas where the technology can be improved in future studies. PMID:25688542

  16. Insulin and glucose regulation.

    PubMed

    Ralston, Sarah L

    2002-08-01

    Abnormally high or low blood glucose and insulin concentrations after standardized glucose tolerance tests can reflect disorders such as pituitary dysfunction, polysaccharide storage myopathies, and other clinical disorders. Glucose and insulin responses, however, are modified by the diet to which the animal has adapted, time since it was last fed, and what it was fed. Body fat (obesity), fitness level, physiologic status, and stress also alter glucose and insulin metabolism. Therefore, it is important to consider these factors when evaluating glucose and insulin tests, especially if only one sample it taken. This article describes the factors affecting glucose and insulin metabolism in horses and how they might influence the interpretation of standardized tests of glucose tolerance.

  17. [Glucose Metabolism: Stress Hyperglycemia and Glucose Control].

    PubMed

    Tanaka, Katsuya; Tsutsumi, Yasuo M

    2016-05-01

    It is important for the anesthesiologists to understand pathophysiology of perioperative stress hyperglycemia, because it offers strategies for treatment of stress hyperglycemia. The effect of glucose tolerance is different in the choice of the anesthetic agent used in daily clinical setting. Specifically, the volatile anesthetics inhibit insulin secretion after glucose load and affects glucose tolerance. During minor surgery by the remifentanil anesthesia, the stress reaction is hard to be induced, suggesting that we should consider low-dose glucose load. Finally it is necessary to perform the glycemic control of the patients who fell into stress hyperglycemia depending on the individual patient. However, there are a lot of questions to be answered in the future. The prognosis of the perioperative patients is more likely to be greatly improved if we can control stress hyperglycemia.

  18. [Glucose Metabolism: Stress Hyperglycemia and Glucose Control].

    PubMed

    Tanaka, Katsuya; Tsutsumi, Yasuo M

    2016-05-01

    It is important for the anesthesiologists to understand pathophysiology of perioperative stress hyperglycemia, because it offers strategies for treatment of stress hyperglycemia. The effect of glucose tolerance is different in the choice of the anesthetic agent used in daily clinical setting. Specifically, the volatile anesthetics inhibit insulin secretion after glucose load and affects glucose tolerance. During minor surgery by the remifentanil anesthesia, the stress reaction is hard to be induced, suggesting that we should consider low-dose glucose load. Finally it is necessary to perform the glycemic control of the patients who fell into stress hyperglycemia depending on the individual patient. However, there are a lot of questions to be answered in the future. The prognosis of the perioperative patients is more likely to be greatly improved if we can control stress hyperglycemia. PMID:27319094

  19. The impact of an unpredictable context and intolerance of uncertainty on the electrocortical response to monetary gains and losses.

    PubMed

    Nelson, Brady D; Kessel, Ellen M; Jackson, Felicia; Hajcak, Greg

    2016-02-01

    There is growing evidence that unpredictability and uncertainty can alter reward system functioning. The present study examined the impact of (1) a task-irrelevant unpredictable relative to predictable context and (2) individual differences in intolerance of uncertainty (IU) on the reward-related positivity (RewP), an event-related potential (ERP) response to monetary gains relative to losses. Specifically, 64 participants listened to predictable and unpredictable tone sequences while electroencephalography was recorded during a monetary gambling task. Participants also completed the Intolerance of Uncertainty Scale, which measures both cognitive distress (prospective IU) and behavioral inhibition (inhibitory IU) elicited by uncertainty, in addition to the Depression Anxiety Stress Scale-21 and Penn State Worry Questionnaire. Results indicated that the RewP was reduced during the unpredictable relative to the predictable context. Greater self-reported anxiety elicited by the unpredictable context was associated with a decreased RewP, and a decreased RewP was associated with poorer lose-shift behavioral adjustment. Furthermore, the RewP mediated the relationship between self-reported anxiety elicited by the unpredictable context and lose-shift behavioral adjustment. The IU subscales demonstrated the opposite relationship with the RewP across both contexts-inhibitory IU was associated with an attenuated RewP and prospective IU was associated with an enhanced RewP. In contrast, anxiety, depression, stress, and worry symptomatology were not associated with the RewP. This is the first study to demonstrate that an unpredictable context and individual differences in the degree to which people cannot tolerate uncertainty impact an ERP measure of reward system functioning. PMID:26438205

  20. Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures

    NASA Technical Reports Server (NTRS)

    Convertino, Victor A.

    2002-01-01

    The development of orthostatic hypotension and instability immediately after return from spaceflight has been a significant operational problem to astronauts for more than four decades. Significant reductions in stroke volume and peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with reduced circulating blood volume, although cardiac atrophy might also contribute. Space flight and ground based experiments have demonstrated that an inability to provide adequate peripheral vasoconstriction in astronauts that become presyncopal may be associated with several mechanisms including reduced sympathetic nerve activity, arterial smooth muscle atrophy and/or hyporeactivity, hypersensitivity of beta-adrenergic receptors, etc. In addition, an inability to provide adequate tachycardia in presyncopal subjects may be associated with reduced carotid-cardiac baroreflex sensitivity. Based on the current knowledge and understanding of cardiovascular mechanisms that are altered during exposure to microgravity, a major focus of future research should be directed to the systematic evaluation of potential countermeasures that specifically target and restore the function of these mechanisms. Based on a preliminary systematic evaluation presented in this review, acute physical exercise designed to elicit maximal effort, G-suit inflation, artificial gravity, and specific pharmacological interventions, alone or in combination, have shown promise as successful countermeasures that provide protection against post-flight orthostatic intolerance.

  1. Nutritional support of malnourished lactose intolerant African patients.

    PubMed Central

    O'Keefe, S J; Adam, J K; Cakata, E; Epstein, S

    1984-01-01

    The effectiveness of two commonly available liquid diets was assessed in 40 severely malnourished black African patients. All patients were shown to have normal xylose absorption. The diets were given according to the manufacturer's recommendations. One diet was lactose containing (LC diet) (150 g/d) and high protein (112 g/d), the other normal protein and lactose free (LF diet) (protein 67 g/d), total energy content being similar. Patients were randomly divided into two equal groups and allocated (blind) to one of the diets. Tolerance and nitrogen balance were assessed over two three day periods on half and then full strength formulations. Severe intolerant symptoms were observed in 50% of patients on half strength and 94% of patients on full strength lactose containing diet with evidence of malabsorption of fluid, nitrogen, and fat. Despite high stool nitrogen losses (3.75 +/- 1.04 g/d), however, positive nitrogen balance was achieved in most patients receiving the full strength LC formulation. On the other hand, the full strength LF diet was generally well tolerated and was associated with significantly lower faecal losses and positive nitrogen balance. The results indicate that high density lactose containing liquid formulae are poorly tolerated by severely malnourished black African patients, while lactose free formulae containing approximately 10 g nitrogen/d are well tolerated and result in positive nitrogen balance. PMID:6469079

  2. Molecular evidence for compound heterozygosity in hereditary fructose intolerance.

    PubMed Central

    Dazzo, C; Tolan, D R

    1990-01-01

    Hereditary fructose intolerance (HFI) is an inborn error of metabolism, inherited as an autosomal recessive disorder and caused by a decrease in the activity of fructose-1-phosphate aldolase (aldolase B) in affected individuals. Investigation of the molecular basis of HFI is reported here by the identification of two molecular lesions in the aldolase B gene of the HFI individual. Using polymerase chain reaction to specifically amplify exons at this locus and T7 polymerase for the sequence determination of these double-stranded fragments, we show the mutational heterogeneity of the proband. One allele, previously indicated by restriction analysis, was confirmed as A149P (Ala 149 to Pro in exon 5). The other allele was identified as a 4-bp deletion found in exon 4, a deletion which causes a frameshift at codon 118, resulting in a truncated protein of 132 amino acids. Segregation of these mutant alleles in the proband's family was shown by using allele-specific oligodeoxynucleotides to probe blots of amplified DNA. The techniques employed here represent a rapid and efficient method for detection of other mutations in families with this disease. In addition, the ability to detect mutant alleles by allele-specific hybridization offers a new method for definitive diagnosis, a method which avoids a fructose loading or liver-biopsy examination. Images Figure 2 Figure 3 PMID:2339710

  3. Novel epoxy activated hydrogels for solving lactose intolerance.

    PubMed

    Elnashar, Magdy M M; Hassan, Mohamed E

    2014-01-01

    "Lactose intolerance" is a medical problem for almost 70% of the world population. Milk and dairy products contain 5-10% w/v lactose. Hydrolysis of lactose by immobilized lactase is an industrial solution. In this work, we succeeded to increase the lactase loading capacity to more than 3-fold to 36.3 U/g gel using epoxy activated hydrogels compared to 11 U/g gel using aldehyde activated carrageenan. The hydrogel's mode of interaction was proven by FTIR, DSC, and TGA. The high activity of the epoxy group was regarded to its ability to attach to the enzyme's -SH, -NH, and -OH groups, whereas the aldehyde group could only bind to the enzyme's -NH2 group. The optimum conditions for immobilization such as epoxy chain length and enzyme concentration have been studied. Furthermore, the optimum enzyme conditions were also deliberated and showed better stability for the immobilized enzyme and the Michaelis constants, K m and V max, were doubled. Results revealed also that both free and immobilized enzymes reached their maximum rate of lactose conversion after 2 h, albeit, the aldehyde activated hydrogel could only reach 63% of the free enzyme. In brief, the epoxy activated hydrogels are more efficient in immobilizing more enzymes than the aldehyde activated hydrogel.

  4. Wheat Allergy and Intolerence; Recent Updates and Perspectives.

    PubMed

    Pasha, Imran; Saeed, Farhan; Sultan, Muhammad Tauseef; Batool, Rizwana; Aziz, Mahwash; Ahmed, Waqas

    2016-01-01

    The current review paper highlights the complicacies associated with communities relying on wheat as their dietary staple. Although, wheat is an important source of nutrients but is also linked with allergenic responses in genetically susceptible subjects. The wheat proteins especially α-amylase inhibitors, ω-5 gliadins, prolamins, nonprolamin, glucoprotein, and profilins are of significance importance. The allergenic responses are further categorized into IgE-mediated and non-IgE-mediated reactions. Conjugation and degranulation of the IgEs with the allergens results in release of several mediators. In contrary, non-IgE-mediated wheat allergy depends on immune complexes formed by food and food antibodies and cell-mediated immunity. As results, different diseases tend to occur on the completion of these reactions, i.e., celiac disease, baker's asthma, diarrhea, atopic dermatitis, and urticaria. This instant paper highlighted the concept of food allergy with special reference to wheat. The models are developed that are included in this paper showing the wheat allergen, their possible routes, impact on human health, and indeed possible remedies. The paper would provide the basic information for the researchers, common man, and allied stakeholders to cater the issue in details. However, the issue needs the attention of the researchers as there is a need to clarify the issues of wheat allergy and wheat intolerance.

  5. Genes and exercise intolerance: insights from McArdle disease.

    PubMed

    Nogales-Gadea, Gisela; Godfrey, Richard; Santalla, Alfredo; Coll-Cantí, Jaume; Pintos-Morell, Guillem; Pinós, Tomàs; Arenas, Joaquín; Martín, Miguel Angel; Lucia, Alejandro

    2016-02-01

    McArdle disease (glycogen storage disease type V) is caused by inherited deficiency of a key enzyme in muscle metabolism, the skeletal muscle-specific isoform of glycogen phosphorylase, "myophosphorylase," which is encoded by the PYGM gene. Here we review the main pathophysiological, genotypic, and phenotypic features of McArdle disease and their interactions. To date, moderate-intensity exercise (together with pre-exercise carbohydrate ingestion) is the only treatment option that has proven useful for these patients. Furthermore, regular physical activity attenuates the clinical severity of McArdle disease. This is quite remarkable for a monogenic disorder that consistently leads to the same metabolic defect at the muscle tissue level, that is, complete inability to use muscle glycogen stores. Further knowledge of this disorder would help patients and enhance understanding of exercise metabolism as well as exercise genomics. Indeed, McArdle disease is a paradigm of human exercise intolerance and PYGM genotyping should be included in the genetic analyses that might be applied in the coming personalized exercise medicine as well as in future research on genetics and exercise-related phenotypes.

  6. Mitochondrial myopathies: diagnosis, exercise intolerance, and treatment options.

    PubMed

    Tarnopolsky, Mark A; Raha, Sandeep

    2005-12-01

    Mitochondrial myopathies are caused by genetic mutations that directly influence the functioning of the electron transport chain (ETC). It is estimated that 1 of 8,000 people have pathology inducing mutations affecting mitochondrial function. Diagnosis often requires a multifaceted approach with measurements of serum lactate and pyruvate, urine organic acids, magnetic resonance spectroscopy (MRS), muscle histology and ultrastructure, enzymology, genetic analysis, and exercise testing. The ubiquitous distribution of the mitochondria in the human body explains the multiple organ involvement. Exercise intolerance is a common but often an overlooked hallmark of mitochondrial myopathies. The muscle consequences of ETC dysfunction include increased reliance on anaerobic metabolism (lactate generation, phosphocreatine degradation), enhanced free radical production, reduced oxygen extraction and electron flux through ETC, and mitochondrial proliferation or biogenesis (see article by Hood in current issue). Treatments have included antioxidants (vitamin E, alpha lipoic acid), electron donors and acceptors (coenzyme Q10, riboflavin), alternative energy sources (creatine monohydrate), lactate reduction strategies (dichloroacetate) and exercise training. Exercise is a particularly important modality in diagnosis as well as therapy (see article by Taivassalo in current issue). Increased awareness of these disorders by exercise physiologists and sports medicine practitioners should lead to more accurate and more rapid diagnosis and the opportunity for therapy and genetic counseling. PMID:16331134

  7. Novel epoxy activated hydrogels for solving lactose intolerance.

    PubMed

    Elnashar, Magdy M M; Hassan, Mohamed E

    2014-01-01

    "Lactose intolerance" is a medical problem for almost 70% of the world population. Milk and dairy products contain 5-10% w/v lactose. Hydrolysis of lactose by immobilized lactase is an industrial solution. In this work, we succeeded to increase the lactase loading capacity to more than 3-fold to 36.3 U/g gel using epoxy activated hydrogels compared to 11 U/g gel using aldehyde activated carrageenan. The hydrogel's mode of interaction was proven by FTIR, DSC, and TGA. The high activity of the epoxy group was regarded to its ability to attach to the enzyme's -SH, -NH, and -OH groups, whereas the aldehyde group could only bind to the enzyme's -NH2 group. The optimum conditions for immobilization such as epoxy chain length and enzyme concentration have been studied. Furthermore, the optimum enzyme conditions were also deliberated and showed better stability for the immobilized enzyme and the Michaelis constants, K m and V max, were doubled. Results revealed also that both free and immobilized enzymes reached their maximum rate of lactose conversion after 2 h, albeit, the aldehyde activated hydrogel could only reach 63% of the free enzyme. In brief, the epoxy activated hydrogels are more efficient in immobilizing more enzymes than the aldehyde activated hydrogel. PMID:25013804

  8. Systemic exercise intolerance disease: What's in a name?

    PubMed

    Sen, Mahadev Singh; Sahoo, Swapnajeet; Aggarwal, Shivali; Singh, Shubh Mohan

    2016-08-01

    The syndrome characterized primarily by chronic, disabling fatigue without adequate explanation has been of interest to patients, clinicians and researchers. Chronic fatigue syndrome (CFS) is a widely used term for this condition in scientific and lay literature but is not acceptable to many patients because of perceived stigma due to implied psychological causation. CFS has recently been replaced by systemic exercise intolerance disease (SEID) by the Institute of medicine with the objectives of providing and disseminating evidence-based criteria and to provide a more acceptable name for this condition. Simultaneously, changes have taken place in DSM-5 with regards to this condition. Mental health professionals need to be aware of this change in the interests of patient care. The need to replace CFS with SEID and the nosological changes also indicate an inability to do away with the Descartian mind-body dualism despite efforts to the contrary and a need to debate the failure of the bio-psycho-social model to 'mainstream' and destigmatize psychiatry. PMID:27520920

  9. Odors eliciting fear: a conditioning approach to Idiopathic Environmental Intolerances.

    PubMed

    Leer, Arne; Smeets, Monique A M; Bulsing, Patricia J; van den Hout, Marcel A

    2011-06-01

    Patients suffering from Idiopathic Environmental Intolerances (IEI) report health symptoms, referable to multiple organ systems, which are triggered by harmless odors and therefore medically unexplainable. In line with previous research that predominantly points towards psychological explanations, the present study tests the hypothesis that IEI symptoms result from learning via classical conditioning of odors to fear. A differential conditioning paradigm was employed. Hedonically different odors were compared on ease of fear acquisition. Conditioned stimuli (CSs) were Dimethyl Sulfide (unpleasant) and peach (pleasant). The unconditioned stimulus (US) was an electrical shock. During acquisition one odor (CS+) was followed by shock, while the other odor (CS-) was not. Next, fear extinction was tested by presenting both CS+ and CS- without US. Electrodermal response, odor evaluation, and sniffing behavior were monitored. Results showed successful fear conditioning irrespective of hedonic character as evidenced by electrodermal response. Acquired fear did not extinguish. There was no evidence of evaluative conditioning taking place, as CS evaluation did not change during fear acquisition. Early avoidance of the CS+, as deduced from odor inhalation measures, was demonstrated, but did not sustain during the entire acquisition phase. This study suggests that a fear conditioning account of IEI is only partially satisfactory.

  10. Intolerance of uncertainty and attentional networks: Unique associations with alerting.

    PubMed

    Fergus, Thomas A; Carleton, R Nicholas

    2016-06-01

    The present study sought to extend our understanding as to how intolerance of uncertainty (IU) relates to information-processing by investigating associations between IU and attentional networks, including alerting, orienting, and executive attention. Based upon prior research, IU was expected to cluster with alerting. An unselected sample of college students (N=86; 79% women) completed self-report measures of IU and state anxiety, as well as the attention network test. Among the attentional networks, IU only shared a positive association with alerting and the association remained intact after statistically controlling for state anxiety. State anxiety did not moderate the association between IU and alerting. Although two IU dimensions (prospective and inhibitory) both shared a positive association with alerting, only prospective IU was associated with alerting after statistically controlling for state anxiety. The results provide evidence that IU relates to an overfunctioning of the alerting attentional network, which may suggest a role of hypervigilance and a greater influence of bottom-up processing in relation to IU. Implications for how these results advance our understanding of possible links between IU and anxiety disorders are discussed. PMID:27068067

  11. Lactose intolerance and health disparities among African Americans and Hispanic Americans: an updated consensus statement.

    PubMed

    Bailey, Rahn K; Fileti, Cecelia Pozo; Keith, Jeanette; Tropez-Sims, Susanne; Price, Winston; Allison-Ottey, Sharon Denise

    2013-01-01

    Dairy foods contribute nine essential nutrients to the diet including calcium, potassium and vitamin D; nutrients identified by the 2010 Dietary Guidelines for Americans as being "of public health concern" within the U.S. population. Milk and milk product intake is associated with better diet quality and has been associated with a reduced risk of chronic diseases or conditions including hypertension, cardiovascular disease, metabolic syndrome, Type 2 Diabetes and osteoporosis. Some research also indicates dairy food intake may be linked to reduced body fat, when accompanied by energy-restriction. On average, both African Americans and Hispanic Americans consume less than the recommended levels of dairy foods, and perceived or actual lactose intolerance can be a primary reason for limiting or avoiding dairy intake. True lactose intolerance prevalence is not known because healthcare providers do not routinely measure for it, and no standardized assessment method exists. Avoiding dairy may lead to shortfalls of essential nutrients and increased susceptibility to chronic disease. This updated Consensus Statement aims to provide the most current information about lactose intolerance and health, with specific relevance to the African American and Hispanic American communities. Topics covered include diagnostic considerations, actual and recommended dairy food intake and levels of consumption of key dairy nutrients among African Americans and Hispanic Americans; prevalence of self-reported lactose intolerance among various racial/ethnic groups; the association between dairy food intake, lactose intolerance and chronic disease; and research-based management recommendations for those with lactose intolerance.

  12. Fear of heights and mild visual height intolerance independent of alcohol consumption

    PubMed Central

    Huppert, Doreen; Grill, Eva; Kapfhammer, Hans-Peter; Brandt, Thomas

    2013-01-01

    Background Visual height intolerance occurs when a visual stimulus causes apprehension of losing balance and falling from some height. Affecting one-third of the population, it has a broad spectrum of symptoms, ranging from minor distress to fear of heights, which is defined as a specific phobia. Specific phobias are associated with higher alcohol consumption. This has not been specifically shown for susceptibility to the more general visual height intolerance. Methods Representative case–control study nested within a population-based cross-sectional telephone survey to assess epidemiologically 1253 individuals ≥14 years, using a questionnaire on sociodemographic data, typical symptoms, precipitating visual stimuli, and alcohol drinking patterns (overall frequency of alcohol consumption, the daily quantities, and the motives). Results Individuals susceptible or nonsusceptible to visual height intolerance showed no significant differences in drinking patterns. The daily average alcohol consumption was slightly higher in persons susceptible to visual height intolerance (4.1 g/day vs. 3.7 g/day). Of those consuming alcohol, cases and controls reported on average consuming 2.3 glasses per day. The prevalence of visual height intolerance was insignificantly higher in the small minority of those drinking 2–3 times per week versus teetotalers. Conclusions Our study does not provide evidence that visual height intolerance – contrary to various specific phobias – is significantly associated with individual alcohol consumption patterns. PMID:24392279

  13. Fear of heights and mild visual height intolerance independent of alcohol consumption.

    PubMed

    Huppert, Doreen; Grill, Eva; Kapfhammer, Hans-Peter; Brandt, Thomas

    2013-09-01

    Background Visual height intolerance occurs when a visual stimulus causes apprehension of losing balance and falling from some height. Affecting one-third of the population, it has a broad spectrum of symptoms, ranging from minor distress to fear of heights, which is defined as a specific phobia. Specific phobias are associated with higher alcohol consumption. This has not been specifically shown for susceptibility to the more general visual height intolerance. Methods Representative case-control study nested within a population-based cross-sectional telephone survey to assess epidemiologically 1253 individuals ≥14 years, using a questionnaire on sociodemographic data, typical symptoms, precipitating visual stimuli, and alcohol drinking patterns (overall frequency of alcohol consumption, the daily quantities, and the motives). Results Individuals susceptible or nonsusceptible to visual height intolerance showed no significant differences in drinking patterns. The daily average alcohol consumption was slightly higher in persons susceptible to visual height intolerance (4.1 g/day vs. 3.7 g/day). Of those consuming alcohol, cases and controls reported on average consuming 2.3 glasses per day. The prevalence of visual height intolerance was insignificantly higher in the small minority of those drinking 2-3 times per week versus teetotalers. Conclusions Our study does not provide evidence that visual height intolerance - contrary to various specific phobias - is significantly associated with individual alcohol consumption patterns.

  14. Shared Variance among Self-Report and Behavioral Measures of Distress Intolerance.

    PubMed

    McHugh, R Kathryn; Daughters, Stacey B; Lejuez, Carl W; Murray, Heather W; Hearon, Bridget A; Gorka, Stephanie M; Otto, Michael W

    2011-06-01

    Distress intolerance may be an important individual difference variable in understanding maladaptive coping responses across diagnostic categories. However, the measurement of distress intolerance remains inconsistent across studies and little evidence for convergent validity among existing measures is available. This study evaluated the overlap among self-report and behavioral measures of distress intolerance in four samples, including an unselected sample, a sample of patients with drug dependence, and two samples of cigarette smokers. Results suggested that the self-report measures were highly correlated, as were the behavioral measures; however, behavioral and self-report measures did not exhibit significant associations with each other. There was some evidence of domain specificity, with anxiety sensitivity demonstrating strong associations with somatic distress intolerance, and a lack of association between behavioral measures that elicit affective distress and those that elicit somatic distress. These findings highlight a potential divergence in the literature relative to the conceptualization of distress intolerance as either sensitivity to distress or as the inability to persist at a task when distressed. Further research is needed to elucidate the conceptualization and measurement of distress intolerance to facilitate future clinical and research applications of this construct.

  15. Impaired glucose metabolism and exercise capacity with muscle-specific glycogen synthase 1 (gys1) deletion in adult mice

    PubMed Central

    Xirouchaki, Chrysovalantou E.; Mangiafico, Salvatore P.; Bate, Katherine; Ruan, Zheng; Huang, Amy M.; Tedjosiswoyo, Bing Wilari; Lamont, Benjamin; Pong, Wynne; Favaloro, Jenny; Blair, Amy R.; Zajac, Jeffrey D.; Proietto, Joseph; Andrikopoulos, Sofianos

    2016-01-01

    Objective Muscle glucose storage and muscle glycogen synthase (gys1) defects have been associated with insulin resistance. As there are multiple mechanisms for insulin resistance, the specific role of glucose storage defects is not clear. The aim of this study was to examine the effects of muscle-specific gys1 deletion on glucose metabolism and exercise capacity. Methods Tamoxifen inducible and muscle specific gys-1 KO mice were generated using the Cre/loxP system. Mice were subjected to glucose tolerance tests, euglycemic/hyperinsulinemic clamps and exercise tests. Results gys1-KO mice showed ≥85% reduction in muscle gys1 mRNA and protein concentrations, 70% reduction in muscle glycogen levels, postprandial hyperglycaemia and hyperinsulinaemia and impaired glucose tolerance. Under insulin-stimulated conditions, gys1-KO mice displayed reduced glucose turnover and muscle glucose uptake, indicative of peripheral insulin resistance, as well as increased plasma and muscle lactate levels and reductions in muscle hexokinase II levels. gys1-KO mice also exhibited markedly reduced exercise and endurance capacity. Conclusions Thus, muscle-specific gys1 deletion in adult mice results in glucose intolerance due to insulin resistance and reduced muscle glucose uptake as well as impaired exercise and endurance capacity. In brief This study demonstrates why the body prioritises muscle glycogen storage over liver glycogen storage despite the critical role of the liver in supplying glucose to the brain in the fasting state and shows that glycogen deficiency results in impaired glucose metabolism and reduced exercise capacity. PMID:26977394

  16. BMP4-BMPR1A signaling in beta cells is required for and augments glucose-stimulated insulin secretion.

    PubMed

    Goulley, Joan; Dahl, Ulf; Baeza, Nathalie; Mishina, Yuji; Edlund, Helena

    2007-03-01

    Impaired glucose-stimulated insulin secretion (GSIS) and perturbed proinsulin processing are hallmarks of beta cell dysfunction in type 2 diabetes. Signals that can preserve and/or enhance beta cell function are therefore of great therapeutic interest. Here we show that bone morphogenetic protein 4 (Bmp4) and its high-affinity receptor, Bmpr1a, are expressed in beta cells. Mice with attenuated BMPR1A signaling in beta cells show decreased expression of key genes involved in insulin gene expression, proinsulin processing, glucose sensing, secretion stimulus coupling, incretin signaling, and insulin exocytosis and develop diabetes due to impaired insulin secretion. We also show that transgenic expression of Bmp4 in beta cells enhances GSIS and glucose clearance and that systemic administration of BMP4 protein to adult mice significantly stimulates GSIS and ameliorates glucose tolerance in a mouse model of glucose intolerance. Thus, BMP4-BMPR1A signaling in beta cells plays a key role in GSIS.

  17. A fluorescence polarization based assay for glucose sensing

    NASA Astrophysics Data System (ADS)

    Cummins, Brian M.; Coté, Gerard L.

    2012-03-01

    A fluorescence polarization (FP) assay was developed to determine concentrations of glucose using concanavalin A (ConA) and fluorescently-labeled dextran. Predictive FP responses to glucose were elicited for different assay configurations using mathematical modeling and displayed herein. Using 4 kDa FITC-dextran, we predicted a change of 0.120 P units from 0 mg/dL glucose to 500 mg/dL. This shows the potential that a homogenous, reproducible FP assay can be engineered to measure glucose concentrations using tetrameric ConA and 4k kDa FITC-dextran.

  18. Extension of the Transdiagnostic Model to Focus on Intolerance of Uncertainty: A Review of the Literature and Implications for Treatment.

    PubMed

    Einstein, Danielle A

    2014-09-01

    This study reviews research on the construct of intolerance of uncertainty (IU). A recent factor analysis (Journal of Anxiety Disorders, 25, 2012, p. 533) has been used to extend the transdiagnostic model articulated by Mansell (2005, p. 141) to focus on the role of IU as a facet of the model that is important to address in treatment. Research suggests that individual differences in IU may compromise resilience and that individuals high in IU are susceptible to increased negative affect. The model extension provides a guide for the treatment of clients presenting with uncertainty in the context of either a single disorder or several comorbid disorders. By applying the extension, the clinician is assisted to explore two facets of IU, "Need for Predictability" and "Uncertainty Arousal."

  19. Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated insulin secretion via sympathetic innervation.

    PubMed

    Tudurí, Eva; Beiroa, Daniel; Stegbauer, Johannes; Fernø, Johan; López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

    2016-11-01

    Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i.c.v.) injection with specific agonists for the three main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors: activation of KOR and DOR did not alter glucose tolerance, whereas activation of brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin secretion (GSIS), reduced insulin sensitivity, increased the expression of gluconeogenic genes in the liver and, consequently, impaired glucose tolerance. Pharmacological blockade of α2A-adrenergic receptors prevented DAMGO-induced glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit GSIS and to impair glucose tolerance in α2A-adrenoceptor knockout mice, indicating that the effects of central MOR activation on β-cells are mediated via sympathetic innervation. Our results show for the first time a new role of the central opioid system, specifically the MOR, in the regulation of insulin secretion and glucose metabolism. PMID:27511839

  20. Gut microbe-derived extracellular vesicles induce insulin resistance, thereby impairing glucose metabolism in skeletal muscle.

    PubMed

    Choi, Youngwoo; Kwon, Yonghoon; Kim, Dae-Kyum; Jeon, Jinseong; Jang, Su Chul; Wang, Taejun; Ban, Minjee; Kim, Min-Hye; Jeon, Seong Gyu; Kim, Min-Sun; Choi, Cheol Soo; Jee, Young-Koo; Gho, Yong Song; Ryu, Sung Ho; Kim, Yoon-Keun

    2015-01-01

    Gut microbes might influence host metabolic homeostasis and contribute to the pathogenesis of type 2 diabetes (T2D), which is characterized by insulin resistance. Bacteria-derived extracellular vesicles (EVs) have been suggested to be important in the pathogenesis of diseases once believed to be non-infectious. Here, we hypothesize that gut microbe-derived EVs are important in the pathogenesis of T2D. In vivo administration of stool EVs from high fat diet (HFD)-fed mice induced insulin resistance and glucose intolerance compared to regular diet (RD)-fed mice. Metagenomic profiling of stool EVs by 16S ribosomal DNA sequencing revealed an increased amount of EVs derived from Pseudomonas panacis (phylum Proteobacteria) in HFD mice compared to RD mice. Interestingly, P. panacis EVs blocked the insulin signaling pathway in both skeletal muscle and adipose tissue. Moreover, isolated P. panacis EVs induced typical diabetic phenotypes, such as glucose intolerance after glucose administration or systemic insulin injection. Thus, gut microbe-derived EVs might be key players in the development of insulin resistance and impairment of glucose metabolism promoted by HFD.

  1. Impact of Glucocorticoid Excess on Glucose Tolerance: Clinical and Preclinical Evidence

    PubMed Central

    Pasieka, Aoibhe M.; Rafacho, Alex

    2016-01-01

    Glucocorticoids (GCs) are steroid hormones that exert important physiological actions on metabolism. Given that GCs also exert potent immunosuppressive and anti-inflammatory actions, synthetic GCs such as prednisolone and dexamethasone were developed for the treatment of autoimmune- and inflammatory-related diseases. The synthetic GCs are undoubtedly efficient in terms of their therapeutic effects, but are accompanied by significant adverse effects on metabolism, specifically glucose metabolism. Glucose intolerance and reductions in insulin sensitivity are among the major concerns related to GC metabolic side effects, which may ultimately progress to type 2 diabetes mellitus. A number of pre-clinical and clinical studies have aimed to understand the repercussions of GCs on glucose metabolism and the possible mechanisms of GC action. This review intends to summarize the main alterations that occur in liver, skeletal muscle, adipose tissue, and pancreatic islets in the context of GC-induced glucose intolerance. For this, both experimental (animals) and clinical studies were selected and, whenever possible, the main cellular mechanisms involved in such GC-side effects were discussed. PMID:27527232

  2. Impact of Glucocorticoid Excess on Glucose Tolerance: Clinical and Preclinical Evidence.

    PubMed

    Pasieka, Aoibhe M; Rafacho, Alex

    2016-01-01

    Glucocorticoids (GCs) are steroid hormones that exert important physiological actions on metabolism. Given that GCs also exert potent immunosuppressive and anti-inflammatory actions, synthetic GCs such as prednisolone and dexamethasone were developed for the treatment of autoimmune- and inflammatory-related diseases. The synthetic GCs are undoubtedly efficient in terms of their therapeutic effects, but are accompanied by significant adverse effects on metabolism, specifically glucose metabolism. Glucose intolerance and reductions in insulin sensitivity are among the major concerns related to GC metabolic side effects, which may ultimately progress to type 2 diabetes mellitus. A number of pre-clinical and clinical studies have aimed to understand the repercussions of GCs on glucose metabolism and the possible mechanisms of GC action. This review intends to summarize the main alterations that occur in liver, skeletal muscle, adipose tissue, and pancreatic islets in the context of GC-induced glucose intolerance. For this, both experimental (animals) and clinical studies were selected and, whenever possible, the main cellular mechanisms involved in such GC-side effects were discussed. PMID:27527232

  3. Gut microbe-derived extracellular vesicles induce insulin resistance, thereby impairing glucose metabolism in skeletal muscle.

    PubMed

    Choi, Youngwoo; Kwon, Yonghoon; Kim, Dae-Kyum; Jeon, Jinseong; Jang, Su Chul; Wang, Taejun; Ban, Minjee; Kim, Min-Hye; Jeon, Seong Gyu; Kim, Min-Sun; Choi, Cheol Soo; Jee, Young-Koo; Gho, Yong Song; Ryu, Sung Ho; Kim, Yoon-Keun

    2015-01-01

    Gut microbes might influence host metabolic homeostasis and contribute to the pathogenesis of type 2 diabetes (T2D), which is characterized by insulin resistance. Bacteria-derived extracellular vesicles (EVs) have been suggested to be important in the pathogenesis of diseases once believed to be non-infectious. Here, we hypothesize that gut microbe-derived EVs are important in the pathogenesis of T2D. In vivo administration of stool EVs from high fat diet (HFD)-fed mice induced insulin resistance and glucose intolerance compared to regular diet (RD)-fed mice. Metagenomic profiling of stool EVs by 16S ribosomal DNA sequencing revealed an increased amount of EVs derived from Pseudomonas panacis (phylum Proteobacteria) in HFD mice compared to RD mice. Interestingly, P. panacis EVs blocked the insulin signaling pathway in both skeletal muscle and adipose tissue. Moreover, isolated P. panacis EVs induced typical diabetic phenotypes, such as glucose intolerance after glucose administration or systemic insulin injection. Thus, gut microbe-derived EVs might be key players in the development of insulin resistance and impairment of glucose metabolism promoted by HFD. PMID:26510393

  4. Cerebral vasoconstriction precedes orthostatic intolerance after parabolic flight

    NASA Technical Reports Server (NTRS)

    Serrador, J. M.; Shoemaker, J. K.; Brown, T. E.; Kassam, M. S.; Bondar, R. L.; Schlegel, T. T.

    2000-01-01

    The effects of brief but repeated bouts of micro- and hypergravity on cerebrovascular responses to head-up tilt (HUT) were examined in 13 individuals after (compared to before) parabolic flight. Middle cerebral artery mean flow velocity (MCA MFV; transcranial Doppler ultrasound), eye level blood pressure (BP) and end tidal CO(2) (P(ET)CO(2)) were measured while supine and during 80 degrees HUT for 30 min or until presyncope. In the postflight tests subjects were classified as being orthostatically tolerant (OT) (n = 7) or intolerant (OI) (n = 6). BP was diminished with HUT in the OT group in both tests (p < 0.05) whereas postflight BP was not different from supine in the OI group. Postflight compared to preflight, the reduction in P(ET)CO(2) with HUT (p < 0.05) increased in both groups, although significantly so only in the OI group (p < 0.05). The OI group also had a significant decrease in supine MCA MFV postflight (p < 0.05) that was unaccompanied by a change in supine P(ET)CO(2). The decrease in MCA MFV that occurred during HUT in both groups preflight (p < 0.05) was accentuated only in the OI group postflight, particularly during the final 30 s of HUT (p < 0.05). However, this accentuated decrease in MCA MFV was not correlated to the greater decrease in P(ET)CO(2) during the same period (R = 0.20, p = 0.42). Although cerebral vascular resistance (CVR) also increased in the OI group during the last 30 s of HUT postflight (p < 0.05), the dynamic autoregulatory gain was not simultaneously changed. Therefore, we conclude that in the OI individuals, parabolic flight was associated with cerebral hypoperfusion following a paradoxical augmentation of CVR by a mechanism that was not related to changes in autoregulation nor strictly to changes in P(ET)CO(2).

  5. Visual height intolerance and acrophobia: clinical characteristics and comorbidity patterns.

    PubMed

    Kapfhammer, Hans-Peter; Huppert, Doreen; Grill, Eva; Fitz, Werner; Brandt, Thomas

    2015-08-01

    The purpose of this study was to estimate the general population lifetime and point prevalence of visual height intolerance and acrophobia, to define their clinical characteristics, and to determine their anxious and depressive comorbidities. A case-control study was conducted within a German population-based cross-sectional telephone survey. A representative sample of 2,012 individuals aged 14 and above was selected. Defined neurological conditions (migraine, Menière's disease, motion sickness), symptom pattern, age of first manifestation, precipitating height stimuli, course of illness, psychosocial impairment, and comorbidity patterns (anxiety conditions, depressive disorders according to DSM-IV-TR) for vHI and acrophobia were assessed. The lifetime prevalence of vHI was 28.5% (women 32.4%, men 24.5%). Initial attacks occurred predominantly (36%) in the second decade. A rapid generalization to other height stimuli and a chronic course of illness with at least moderate impairment were observed. A total of 22.5% of individuals with vHI experienced the intensity of panic attacks. The lifetime prevalence of acrophobia was 6.4% (women 8.6%, men 4.1%), and point prevalence was 2.0% (women 2.8%; men 1.1%). VHI and even more acrophobia were associated with high rates of comorbid anxious and depressive conditions. Migraine was both a significant predictor of later acrophobia and a significant consequence of previous acrophobia. VHI affects nearly a third of the general population; in more than 20% of these persons, vHI occasionally develops into panic attacks and in 6.4%, it escalates to acrophobia. Symptoms and degree of social impairment form a continuum of mild to seriously distressing conditions in susceptible subjects.

  6. Do patients with lactose intolerance exhibit more frequent comorbidities than patients without lactose intolerance? An analysis of routine data from German medical practices

    PubMed Central

    Schiffner, Rebecca; Kostev, Karel; Gothe, Holger

    2016-01-01

    Background The increase in food intolerances poses a burgeoning problem in our society. Food intolerances not only lead to physical impairment of the individual patient but also result in a high socio-economic burden due to factors such as the treatment required as well as absenteeism. The present study aimed to explore whether lactose intolerant (LI) patients exhibit more frequent comorbidities than non-LI patients. Methods The study was conducted on a case-control basis and the results were determined using routine data analysis. Routine data from the IMS Disease Analyzer database were used for this purpose. A total of 6,758 data records were processed and analyzed. Results There were significant correlations between LI and the incidence of osteoporosis, changes in mental status, and the presence of additional food intolerances. Comparing 3,379 LI vs. 3,379 non-LI patients, 34.5% vs. 17.7% (P<0.0001) suffered from abdominal pain; 30.6% vs. 17.2% (P<0.0001) from gastrointestinal infections; and 20.9% vs. 16.0% (P=0.0053) from depression. Adjusted odds ratios (OR) were the highest for fructose intolerance (n=229 LI vs. n=7 non-LI; OR 31.06; P<0.0001), irritable bowel syndrome (n=247 LI vs. n=44 non-LI; OR 5.23; P<0.0001), and bloating (n=351 LI vs. n=68 non-LI; OR 4.94; P<0.0001). Conclusion The study confirms that LI should not be regarded as an isolated illness but considered a possible trigger for further diseases. Additional research is necessary to assert more precise statements. PMID:27065730

  7. Glucose metabolic adaptations in the intrauterine growth-restricted adult female rat offspring.

    PubMed

    Garg, Meena; Thamotharan, Manikkavasagar; Rogers, Lisa; Bassilian, Sara; Lee, W N Paul; Devaskar, Sherin U

    2006-06-01

    We studied glucose metabolic adaptations in the intrauterine growth-restricted (IUGR) rat offspring to decipher glucose homeostasis in metabolic programming. Glucose futile cycling (GFC), which is altered when there is imbalance between glucose production and utilization, was studied during a glucose tolerance test (GTT) in 2-day-old (n = 8), 2-mo-old (n = 22), and 15-mo-old (n = 22) female rat offspring. The IUGR rats exposed to either prenatal (CM/SP, n = 5 per age), postnatal (SM/CP, n = 6), or pre- and postnatal (SM/SP, n = 6) nutrient restriction were compared with age-matched controls (CM/CP, n = 5). At 2 days, IUGR pups (SP) were smaller and glucose intolerant and had increased hepatic glucose production and increased glucose disposal (P < 0.01) compared with controls (CP). At 2 mo, the GTT, glucose clearance, and GFC did not change. However, a decline in hepatic glucose-6-phosphatase (P < 0.05) and fructose-1,6-biphosphatase (P < 0.05) enzyme activities in the IUGR offspring was detected. At 15 mo, prenatal nutrient restriction (CM/SP) resulted in greater weight gain (P < 0.01) and hyperinsulinemia (P < 0.001) compared with postnatal nutrient restriction (SM/CP). A decline in GFC in the face of a normal GTT occurred in both the prenatal (CM/SP, P < 0.01) and postnatal calorie (SM/CP, P < 0.03) and growth-restricted offspring. The IUGR offspring with pre- and postnatal nutrient restriction (SM/SP) were smaller, hypoinsulinemic (P < 0.03), and hypoleptinemic (P < 0.03), with no change in GTT, hepatic glucose production, GFC, or glucose clearance. We conclude that there is pre- and postnatal programming that affects the postnatal compensatory adaptation of GFC and disposal initiated by changes in circulating insulin concentrations, thereby determining hepatic insulin sensitivity in a phenotype-specific manner. PMID:16449299

  8. Enzymatic Glucose Sensor Compensation for Variations in Ambient Oxygen Concentration

    PubMed Central

    Collier, Bradley B.; McShane, Michael J.

    2014-01-01

    Due to the increasing prevalence of diabetes, research toward painless glucose sensing continues. Oxygen sensitive phosphors with glucose oxidase (GOx) can be used to determine glucose levels indirectly by monitoring oxygen consumption. This is an attractive combination because of its speed and specificity. Packaging these molecules together in “smart materials” for implantation will enable non-invasive glucose monitoring. As glucose levels increase, oxygen levels decrease; consequently, the luminescence intensity and lifetime of the phosphor increase. Although the response of the sensor is dependent on glucose concentration, the ambient oxygen concentration also plays a key role. This could lead to inaccurate glucose readings and increase the risk of hyper- or hypoglycemia. To mitigate this risk, the dependence of hydrogel glucose sensor response on oxygen levels was investigated and compensation methods explored. Sensors were calibrated at different oxygen concentrations using a single generic logistic equation, such that trends in oxygen-dependence were determined as varying parameters in the equation. Each parameter was found to be a function of oxygen concentration, such that the correct glucose calibration equation can be calculated if the oxygen level is known. Accuracy of compensation will be determined by developing an overall calibration, using both glucose and oxygen sensors in parallel, correcting for oxygen fluctuations in real time by intentionally varying oxygen, and calculating the error in actual and predicted glucose levels. While this method was developed for compensation of enzymatic glucose sensors, in principle it can also be implemented with other kinds of sensors utilizing oxidases. PMID:26257458

  9. Hibernation in freshwater turtles: softshell turtles (Apalone spinifera) are the most intolerant of anoxia among North American species.

    PubMed

    Reese, S A; Jackson, D C; Ultsch, G R

    2003-04-01

    Softshell turtles (Apalone spinifera) were submerged at 3 degrees C in anoxic or normoxic water. Periodically, blood PO(2), PCO(2), pH, plasma [Cl(-)], [Na(+)], [K(+)], total Ca, total Mg, lactate, glucose, and osmolality were measured; hematocrit and body mass determined; and blood [HCO(3)(-)] calculated. On day 14 of anoxic submergence, five of eight softshell turtles were dead, one died immediately after removal, and the remaining two showed no signs of life other than a heartbeat. After 11 days of submergence in anoxic water, blood pH fell from 7.923 to 7.281 and lactate increased to 62.1 mM. Plasma [HCO(3)(-)] was titrated from 34.57 mM to 4.53 mM. Plasma [Cl(-)] fell, but [K(+)] and total Ca and Mg increased. In normoxic submergence, turtles survived over 150 days and no lactate accumulated. A respiratory alkalosis developed (pH-8.195, PCO(2)-5.49 after 10 days) early and persisted throughout; no other variables changed in normoxic submergence. Softshell turtles are very capable of extrapulmonary extraction of O(2), but are an anoxia-intolerant species of turtle forcing them to utilize hibernacula that are unlikely to become hypoxic or anoxic (e.g., large lakes and rivers). PMID:12687397

  10. Long-term disruption of maternal glucose homeostasis induced by prenatal glucocorticoid treatment correlates with miR-29 upregulation.

    PubMed

    Gomes, Patrícia R; Graciano, Maria F; Pantaleão, Lucas C; Rennó, André L; Rodrigues, Sandra C; Velloso, Licio A; Latorraca, Márcia Q; Carpinelli, Angelo R; Anhê, Gabriel F; Bordin, Silvana

    2014-01-01

    Excess of glucocorticoids (GCs) during pregnancy is strongly associated with the programming of glucose intolerance in the offspring. However, the impact of high GC levels on maternal metabolism is not clearly documented. This study aimed to test the hypothesis that mothers exposed to elevated levels of GCs might also display long-term disturbances in glucose homeostasis. Dexamethasone (DEX) was administered noninvasively to the mothers via drinking water between the 14th and the 19th days of pregnancy. Mothers were subjected to glucose and insulin tolerance tests at 1, 2, 3, 6, and 12 mo postweaning. Pregnant rats not treated with DEX and age-matched virgin rats were used as controls. Pancreatic islets were isolated at the 20th day of pregnancy and 12 mo postweaning in order to evaluate glucose-stimulated insulin secretion. The expression of the miR-29 family was also studied due to its responsiveness to GCs and its well-documented role in the regulation of pancreatic β-cell function. Rats treated with DEX during pregnancy presented long-term glucose intolerance and impaired insulin secretion. These changes correlated with 1) increased expression of miR-29 and its regulator p53, 2) reduced expression of syntaxin-1a, a direct target of miR-29, and 3) altered expression of genes related to cellular senescence. Our data demonstrate that the use of DEX during pregnancy results in deleterious outcomes to the maternal metabolism, hallmarked by reduced insulin secretion and glucose intolerance. This maternal metabolic programming might be a consequence of time-sustained upregulation of miR-29s in maternal pancreatic islets. PMID:24253049

  11. Glucose: detection and analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glucose is an aldosic monosaccharide that is centrally entrenched in the processes of photosynthesis and respiration, serving as an energy reserve and metabolic fuel in most organisms. As both a monomer and as part of more complex structures such as polysaccharides and glucosides, glucose also pla...

  12. Monitor blood glucose - slideshow

    MedlinePlus

    ... medlineplus.gov/ency/presentations/100220.htm Monitoring blood glucose - Series—Monitoring blood glucose: Using a self-test meter To use the ... A.M. Editorial team. Related MedlinePlus Health Topics Blood Sugar A.D.A.M., Inc. is accredited by ...

  13. Statin intolerance - an attempt at a unified definition. Position paper from an International Lipid Expert Panel.

    PubMed

    Banach, Maciej; Rizzo, Manfredi; Toth, Peter P; Farnier, Michel; Davidson, Michael H; Al-Rasadi, Khalid; Aronow, Wilbert S; Athyros, Vasilis; Djuric, Dragan M; Ezhov, Marat V; Greenfield, Robert S; Hovingh, G Kees; Kostner, Karam; Serban, Corina; Lighezan, Daniel; Fras, Zlatko; Moriarty, Patrick M; Muntner, Paul; Goudev, Assen; Ceska, Richard; Nicholls, Stephen J; Broncel, Marlena; Nikolic, Dragana; Pella, Daniel; Puri, Raman; Rysz, Jacek; Wong, Nathan D; Bajnok, Laszlo; Jones, Steven R; Ray, Kausik K; Mikhailidis, Dimitri P

    2015-06-01

    Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin-associated muscle symptoms (SAMS), and avoided the use of the term 'statin intolerance'. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10 - 15% of patients. In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented.

  14. FOOD INTOLERANCES AND ASSOCIATED SYMPTOMS IN PATIENTS UNDERGOING FOBI-CAPELLA TECHNIQUE WITHOUT GASTRIC RING

    PubMed Central

    MOREIRA, Marcella de Arruda; ESPÍNOLA, Patrícia Ramos Maciel; de AZEVEDO, Camila Wanderley

    2015-01-01

    Background Bariatric surgery is considered the only effective method to treat refractory obesity, and especially for those in which clinical treatment was not successful. However, the appearance of food intolerances and clinical manifestations are quite common. Aim To identify food intolerances and associated them to symptoms in patients undergoing Fobi-Capella technique without gastric ring. Methods This was a cross-sectional study of adult patients who had more than one year after surgery. Demographic, anthropometric, weight and preoperative height data were investigated. Nutritional status was classified according to the criteria established by the World Health Organization. It was considered food intolerance the presence of nausea, vomiting, diarrhea or bloating after eating a particular food. Results The sample consisted of 61 patients who attended the nutritional consultation of which 26 (42.6%) had food intolerance, mostly related to red meat (n=12; 34.3%) during the first six months of operation; there was a significant difference between the periods between 0 and 6 months, and 7 to 12 (p=0.02). Among the symptoms reported by patients, nausea was the most recurrent until the 6th month, but without significant differences between the two periods (p=0.06). Conclusions The Fobi-Capella procedure without gastric ring promoted high frequency of intolerance to meat in general, especially for the red, chicken and fish, on this sequence; nausea was the most frequent symptom. These data suggest the need for adequate nutritional monitoring throughout the postoperative period. PMID:25861067

  15. Statin intolerance - an attempt at a unified definition. Position paper from an International Lipid Expert Panel.

    PubMed

    Banach, Maciej; Rizzo, Manfredi; Toth, Peter P; Farnier, Michel; Davidson, Michael H; Al-Rasadi, Khalid; Aronow, Wilbert S; Athyros, Vasilis; Djuric, Dragan M; Ezhov, Marat V; Greenfield, Robert S; Hovingh, G Kees; Kostner, Karam; Serban, Corina; Lighezan, Daniel; Fras, Zlatko; Moriarty, Patrick M; Muntner, Paul; Goudev, Assen; Ceska, Richard; Nicholls, Stephen J; Broncel, Marlena; Nikolic, Dragana; Pella, Daniel; Puri, Raman; Rysz, Jacek; Wong, Nathan D; Bajnok, Laszlo; Jones, Steven R; Ray, Kausik K; Mikhailidis, Dimitri P

    2015-03-16

    Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term 'statin intolerance'. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10-15% of patients. In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented. PMID:25861286

  16. Saturated- and n-6 polyunsaturated-fat diets each induce ceramide accumulation in mouse skeletal muscle: reversal and improvement of glucose tolerance by lipid metabolism inhibitors.

    PubMed

    Frangioudakis, G; Garrard, J; Raddatz, K; Nadler, J L; Mitchell, T W; Schmitz-Peiffer, C

    2010-09-01

    Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg x d), or MYR (0.3 mg/kg x d) were administered by mini-pumps in the final 4 wk. Glucose homeostasis was examined by glucose tolerance test. Muscle ceramide and PA were analyzed by mass spectrometry. Expression of LASS isoforms (ceramide synthases) was evaluated by immunoblotting. Both saturated and polyunsaturated fat diets increased muscle ceramide and induced glucose intolerance. MYR and LSF reduced ceramide levels in saturated and unsaturated fat-fed mice. Both inhibitors also improved glucose tolerance in unsaturated fat-fed mice, but only LSF was effective in saturated fat-fed mice. The discrepancy between ceramide and glucose tolerance suggests these improvements may not be related directly to changes in muscle ceramide and may involve other insulin-responsive tissues. Changes in the expression of LASS1 were, however, inversely correlated with alterations in glucose tolerance. The demonstration that LSF can ameliorate glucose intolerance in vivo independent of the dietary FA type indicates it may be a novel intervention for the treatment of insulin resistance. PMID:20660065

  17. Saturated- and n-6 polyunsaturated-fat diets each induce ceramide accumulation in mouse skeletal muscle: reversal and improvement of glucose tolerance by lipid metabolism inhibitors.

    PubMed

    Frangioudakis, G; Garrard, J; Raddatz, K; Nadler, J L; Mitchell, T W; Schmitz-Peiffer, C

    2010-09-01

    Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg x d), or MYR (0.3 mg/kg x d) were administered by mini-pumps in the final 4 wk. Glucose homeostasis was examined by glucose tolerance test. Muscle ceramide and PA were analyzed by mass spectrometry. Expression of LASS isoforms (ceramide synthases) was evaluated by immunoblotting. Both saturated and polyunsaturated fat diets increased muscle ceramide and induced glucose intolerance. MYR and LSF reduced ceramide levels in saturated and unsaturated fat-fed mice. Both inhibitors also improved glucose tolerance in unsaturated fat-fed mice, but only LSF was effective in saturated fat-fed mice. The discrepancy between ceramide and glucose tolerance suggests these improvements may not be related directly to changes in muscle ceramide and may involve other insulin-responsive tissues. Changes in the expression of LASS1 were, however, inversely correlated with alterations in glucose tolerance. The demonstration that LSF can ameliorate glucose intolerance in vivo independent of the dietary FA type indicates it may be a novel intervention for the treatment of insulin resistance.

  18. Glucose and Fat Metabolism in Acromegaly: From Mice Models to Patient Care.

    PubMed

    Dal, Jakob; List, Edward O; Jørgensen, Jens Otto L; Berryman, Darlene E

    2016-01-01

    Patients with active acromegaly are frequently insulin resistant, glucose intolerant, and at risk for developing overt type 2 diabetes. At the same time, these patients have a relatively lean phenotype associated with mobilization and oxidation of free fatty acids. These features are reversed by curative surgical removal of the growth hormone (GH)-producing adenoma. Mouse models of acromegaly share many of these characteristics, including a lean phenotype and proneness to type 2 diabetes. There are, however, also species differences with respect to oxidation rates of glucose and fat as well as the specific mechanisms underlying GH-induced insulin resistance. The impact of acromegaly treatment on insulin sensitivity and glucose tolerance depends on the treatment modality (e.g. somatostatin analogs also suppress insulin secretion, whereas the GH antagonist restores insulin sensitivity). The interplay between animal research and clinical studies has proven useful in the field of acromegaly and should be continued in order to understand the metabolic actions of GH.

  19. The Role of Haemoglobin A1c in Screening Obese Children and Adolescents for Glucose Intolerance and Type 2 Diabetes.

    PubMed

    Galhardo, Júlia; Shield, Julian

    2015-01-01

    Introdução: Em 2012, um comité internacional de peritos em diabetes aconselhou a hemoglobin