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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. Postprandial Hypertriglyceridemia Predicts Development of Insulin Resistance Glucose Intolerance and Type 2 Diabetes

    PubMed Central

    Aslam, Mohammad; Aggarwal, Sarla; Sharma, Krishna Kumar; Galav, Vikas; Madhu, Sri Venkata

    2016-01-01

    Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) have been found to be associated with postprandial hypertriglyceridemia (PPHTg). However, whether PPHTg can cause IR and diabetes is not clear. We therefore investigated the role of PPHTg in development of T2DM in rat model of T2DM. 96 male Wistar rats were randomized into four groups (24 rats each). Control Group A, high sucrose diet (HSD) Group B, HSD+Pioglitazone (10mg/kg/day) Group C and HSD+Atorvastatin (20mg/kg/day) Group D. Fat and glucose tolerance tests were done at regular intervals in all groups besides insulin and body weight measurement. At 26 weeks, low dose streptozotocin (15mg/kg,i.p.) was given to half of the rats. All rats were followed up till 48 weeks. PPHTg developed as early as week 2 in Group B and stabilized by week 14. Group B displayed highest PPHTg compared to other groups. Atorvastatin treatment (Group D) abolished PPHTg which became comparable to controls, pioglitazone treatment partially blunted PPHTg resulting in intermediate PPHTg. Group B with highest PPHTg showed highest subsequent IR, glucose intolerance (GI) and highest incidence of prediabetes at week 26 and diabetes at week 34 and 46 compared to other groups. Group D rats displayed lower IR, GI, low incidence of prediabetes and diabetes at these time points compared to Groups B and C. ROC analysis showed that triglyceride area under the curve of each time point significantly predicts the risk of diabetes. Present study provides the evidence that PPHTg predicts the development of IR, GI and T2DM in rat model of diet induced T2DM. PMID:26808523

  3. Postprandial Hypertriglyceridemia Predicts Development of Insulin Resistance Glucose Intolerance and Type 2 Diabetes.

    PubMed

    Aslam, Mohammad; Aggarwal, Sarla; Sharma, Krishna Kumar; Galav, Vikas; Madhu, Sri Venkata

    2016-01-01

    Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) have been found to be associated with postprandial hypertriglyceridemia (PPHTg). However, whether PPHTg can cause IR and diabetes is not clear. We therefore investigated the role of PPHTg in development of T2DM in rat model of T2DM. 96 male Wistar rats were randomized into four groups (24 rats each). Control Group A, high sucrose diet (HSD) Group B, HSD+Pioglitazone (10 mg/kg/day) Group C and HSD+Atorvastatin (20 mg/kg/day) Group D. Fat and glucose tolerance tests were done at regular intervals in all groups besides insulin and body weight measurement. At 26 weeks, low dose streptozotocin (15 mg/kg, i.p.) was given to half of the rats. All rats were followed up till 48 weeks. PPHTg developed as early as week 2 in Group B and stabilized by week 14. Group B displayed highest PPHTg compared to other groups. Atorvastatin treatment (Group D) abolished PPHTg which became comparable to controls, pioglitazone treatment partially blunted PPHTg resulting in intermediate PPHTg. Group B with highest PPHTg showed highest subsequent IR, glucose intolerance (GI) and highest incidence of prediabetes at week 26 and diabetes at week 34 and 46 compared to other groups. Group D rats displayed lower IR, GI, low incidence of prediabetes and diabetes at these time points compared to Groups B and C. ROC analysis showed that triglyceride area under the curve of each time point significantly predicts the risk of diabetes. Present study provides the evidence that PPHTg predicts the development of IR, GI and T2DM in rat model of diet induced T2DM. PMID:26808523

  4. 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

  5. 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...

  6. 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

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

    PubMed

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

    2015-12-01

    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

  8. Glucose intolerance in early postpartum in women with gestational diabetes: Who is at increased risk?

    PubMed

    Leuridan, Liesbeth; Wens, Johan; Devlieger, Roland; Verhaeghe, Johan; Mathieu, Chantal; Benhalima, Katrien

    2015-08-01

    Women with a history of gestational diabetes (GDM) have an increased risk for developing type 2 diabetes in the years after the index pregnancy. Some women with GDM already develop glucose intolerance in early postpartum. The best screening strategy for glucose intolerance in early postpartum among women with a history of GDM is still debated. We review the most important risk factors of women with GDM to develop glucose intolerance within one year postpartum. We also discuss the current recommendations for screening in early postpartum and the many challenges to organize postpartum follow up in primary care. PMID:25899304

  9. Acinetobacter infection is associated with acquired glucose intolerance in burn patients.

    PubMed

    Furniss, Dominic; Gore, Sinclair; Azadian, Berge; Myers, Simon R

    2005-01-01

    Infection with antibiotic-resistant Acinetobacter spp. is an increasing problem in critical care environments worldwide. Acinetobacter spp. are known to produce an insulin-cleaving protease. We hypothesized that infection with Acinetobacter spp. was associated with the acquisition of glucose intolerance in burn patients. Data were collected prospectively on all 473 patients admitted to the Burns Centre between January 2002 and March 2003. A total of 3.4% of patients acquired glucose intolerance during admission. Patients with Acinetobacter spp. infection were 9.8 times more likely to develop glucose intolerance than those without the infection (P < .0001). The association persisted after controlling for TBSA (P < .001). In patients with deep Acinetobacter spp. infection, 47% had glucose intolerance, compared with 12% in those with infection of the burn only (P = .03). In patients with pre-existing diabetes mellitus, 27% developed Acinetobacter spp. infection compared with only 8.5% of patients without diabetes (P = .04). This study demonstrates a clear association between Acinetobacter spp. infection and glucose intolerance in burns patients. PMID:16151285

  10. Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs β-Cell Function

    PubMed Central

    Muscogiuri, Giovanna; Salmon, Adam B.; Aguayo-Mazzucato, Cristina; Li, Mengyao; Balas, Bogdan; Guardado-Mendoza, Rodolfo; Giaccari, Andrea; Reddick, Robert L.; Reyna, Sara M.; Weir, Gordon; DeFronzo, Ralph A.; Van Remmen, Holly; Musi, Nicolas

    2013-01-01

    Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. β-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo β-cell insulin secretion and decreased β-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow–fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to β-cell dysfunction. PMID:24009256

  11. 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

  12. Muscle Histidine-Containing Dipeptides Are Elevated by Glucose Intolerance in Both Rodents and Men

    PubMed Central

    Stegen, Sanne; Everaert, Inge; Deldicque, Louise; Vallova, Silvia; de Courten, Barbora; Ukropcova, Barbara; Ukropec, Jozef; Derave, Wim

    2015-01-01

    Objective Muscle carnosine and its methylated form anserine are histidine-containing dipeptides. Both dipeptides have the ability to quench reactive carbonyl species and previous studies have shown that endogenous tissue levels are decreased in chronic diseases, such as diabetes. Design and Methods Rodent study: Skeletal muscles of rats and mice were collected from 4 different diet-intervention studies, aiming to induce various degrees of glucose intolerance: 45% high-fat feeding (male rats), 60% high-fat feeding (male rats), cafeteria feeding (male rats), 70% high-fat feeding (female mice). Body weight, glucose-tolerance and muscle histidine-containing dipeptides were assessed. Human study: Muscle biopsies were taken from m. vastus lateralis in 35 males (9 lean, 8 obese, 9 prediabetic and 9 newly diagnosed type 2 diabetic patients) and muscle carnosine and gene expression of muscle fiber type markers were measured. Results Diet interventions in rodents (cafeteria and 70% high-fat feeding) induced increases in body weight, glucose intolerance and levels of histidine-containing dipeptides in muscle. In humans, obese, prediabetic and diabetic men had increased muscle carnosine content compared to the lean (+21% (p>0.1), +30% (p<0.05) and +39% (p<0.05), respectively). The gene expression of fast-oxidative type 2A myosin heavy chain was increased in the prediabetic (1.8-fold, p<0.05) and tended to increase in the diabetic men (1.6-fold, p = 0.07), compared to healthy lean subjects. Conclusion Muscle histidine-containing dipeptides increases with progressive glucose intolerance, in male individuals (cross-sectional). In addition, high-fat diet-induced glucose intolerance was associated with increased muscle histidine-containing dipeptides in female mice (interventional). Increased muscle carnosine content might reflect fiber type composition and/or act as a compensatory mechanism aimed at preventing cell damage in states of impaired glucose tolerance. PMID:25803044

  13. Body Iron Stores and Glucose Intolerance in Premenopausal Women

    PubMed Central

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

    2009-01-01

    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 (R2 = 0.18, P < 0.0001) retained menstrual dysfunction (β = 0.14, P = 0.035), free testosterone (β = 0.14, P = 0.052), insulin sensitivity index (β = −0.12, P = 0.012), the His63Asp variant in HFE (β = 0.16, P = 0.008), and abnormal glucose tolerance (β = 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 TNFα, TNFRSF1B, IL6, IL6ST, IL6Rα, 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. PMID:19401444

  14. Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia

    PubMed Central

    Shu, Xiaoliang; Zhang, Yongsheng; Xu, Han; Kang, Kai; Cai, Donglian

    2013-01-01

    Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the decrease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance. PMID:25206547

  15. Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice.

    PubMed

    Ahlkvist, Linda; Omar, Bilal; Valeur, Anders; Fosgerau, Keld; Ahrén, Bo

    2016-03-01

    Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized; however, the effect of long-term GCGR activation on β-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2 weeks) infused with the stable glucagon analog ZP-GA-1 and challenged with oral glucose and intravenous glucose±glucagon-like peptide 1 (GLP1). Islets were isolated to evaluate the insulin secretory response to glucose±GLP1 and their pancreas were collected for immunohistochemical analysis. Two weeks of ZP-GA-1 infusion reduced insulin secretion both after oral and intravenous glucose challenges in vivo and in isolated islets. These inhibitory effects were corrected for by GLP1. Also, we observed increased β-cell area and islet size. We conclude that induction of chronic ZP-GA-1 levels in glucose intolerant mice markedly reduces insulin secretion, and thus, we suggest that chronic activation of the GCGR may contribute to the failure of β-cell function during development of type 2 diabetes. PMID:26698567

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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. PMID:21793722

  1. 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

  2. Frequency of diabetes, impaired fasting glucose, and glucose intolerance in high-risk groups identified by a FINDRISC survey in Puebla City, Mexico

    PubMed Central

    García-Alcalá, Hector; Genestier-Tamborero, Christelle Nathalie; Hirales-Tamez, Omara; Salinas-Palma, Jorge; Soto-Vega, Elena

    2012-01-01

    Background As a first step in the prevention of diabetes, the International Diabetes Federation recommends identification of persons at risk using the Finnish type 2 Diabetes Risk Assessment (FINDRISC) survey. The frequency of diabetes mellitus, impaired fasting glucose, and glucose intolerance in high-risk groups identified by FINDRISC is unknown in our country. The aim of this study was to determine the frequency of diabetes mellitus, impaired fasting glucose, and glucose intolerance in higher-risk groups using a FINDRISC survey in an urban population. Methods We used a television program to invite interested adults to fill out a survey at a television station. An oral glucose tolerance test was performed in all persons with a FINDRISC score ≥ 15 points (high-risk and very high-risk groups). Patients were classified as normal (fasting glucose < 100 mg/dL and 2-hour glucose < 140 mg/dL), or having impaired fasting glucose (fasting glucose 100–125 mg/dL and 2-hour glucose < 140 mg/dL), glucose intolerance (fasting glucose < 126 mg/dL and 2-hour glucose 140–199 mg/dL), and diabetes mellitus (fasting glucose ≥ 126 mg/dL or 2-hour glucose ≥ 200 mg/dL). We describe the frequency of each diagnostic category in this selected population according to gender and age. Results A total of 186 patients had a score ≥ 15. The frequencies of diabetes mellitus, impaired fasting glucose, glucose intolerance, and normal glucose levels were 28.6%, 25.9%, 29.2%, and 16.2%, respectively. We found a higher frequency of diabetes mellitus and impaired fasting glucose in men than in women (33% versus 27% and 40% versus 21%, respectively) and more glucose intolerance in women than in men (34% versus 16%, P < 0.05). Patients with diabetes mellitus (52.55 ± 9.2 years) were older than those with impaired fasting glucose (46.19 ± 8.89 years), glucose intolerance (46.15 ± 10.9 years), and normal levels (41.9 ± 10.45 years, P < 0.05). We found a higher frequency of diabetes

  3. Insulin resistance, glucose intolerance and diabetes mellitus in obstructive sleep apnoea

    PubMed Central

    Kent, Brian D.; McNicholas, Walter T.

    2015-01-01

    Obstructive sleep apnoea (OSA) is a highly prevalent disorder, which conveys an increased risk of cardiovascular disease and death. Type 2 diabetes mellitus (T2DM), glucose intolerance and insulin resistance (IR) are common in subjects with OSA, but a shared intimate relationship with obesity makes discerning an independent link challenging. Nonetheless, mechanistic studies suggest that OSA could contribute to impaired glucose metabolism via the effects of sleep fragmentation, sympathetic excitation and intermittent hypoxia (IH) on pancreatic B-cell function, insulin sensitivity, and systemic inflammation. In particular, emerging data suggest that IH may have an important detrimental effect on adipose tissue function and inflammation. Similarly, data from population—and clinic-level studies suggest that OSA is independently related with the prevalence and incidence of T2DM and IR, and may also lead to worse glycaemic control in diabetics. However, the ability of continuous positive airway pressure (CPAP) therapy to make a meaningful impact on T2DM or IR remains uncertain. In this review we explore the available evidence linking OSA with IR, glucose intolerance and T2DM, and discuss potential pathobiological mechanisms by which sleep disordered breathing can affect metabolic health. PMID:26380761

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. Insulin improves β-cell function in glucose-intolerant rat models induced by feeding a high-fat diet.

    PubMed

    Li, Hui-qing; Wang, Bao-ping; Deng, Xiu-Ling; Zhang, Jiao-yue; Wang, Yong-bo; Zheng, Juan; Xia, Wen-fang; Zeng, Tian-shu; Chen, Lu-lu

    2011-11-01

    Insulin therapy has been shown to contribute to extended glycemia remission in newly diagnosed patients with type 2 diabetes mellitus. This study investigated the effects of insulin treatment on pancreatic lipid content, and β-cell apoptosis and proliferation in glucose-intolerant rats to explore the protective role of insulin on β-cell function. A rat glucose-intolerant model was induced by streptozotocin and a high-fat diet. Plasma and pancreatic triglycerides, free fatty acids, and insulin were measured; and pancreatic β-cell cell apoptosis and proliferation were detected by a propidium iodide cell death assay and immunofluorescence for proliferating cell nuclear antigen. Relative β-cell area was determined by immunohistochemistry for insulin, whereas insulin production in pancreas was assessed by reverse transcriptase polymerase chain reaction. Islet β-cell secreting function was assessed by the index ΔI30/ΔG30. Glucose-intolerant rats had higher pancreatic lipid content, more islet β-cell apoptosis, lower β-cell proliferation, and reduced β-cell area in pancreas when compared with controls. Insulin therapy reduced blood glucose, inhibited pancreatic lipid accumulation and islet β-cell apoptosis, and increased β-cell proliferation and β-cell area in glucose-intolerant rats. Furthermore, impaired insulin secretion and insulin production in glucose-intolerant rats were improved by insulin therapy. Insulin can preserve β-cell function by protecting islets from glucotoxicity and lipotoxicity. It can also ameliorate β-cell area by enhancing β-cell proliferation and reducing β-cell apoptosis. PMID:21550078

  12. A minor role for lipocalin 2 in high-fat diet-induced glucose intolerance.

    PubMed

    Jun, Lucy S; Siddall, C Parker; Rosen, Evan D

    2011-11-01

    Adipose tissue controls energy homeostasis and systemic insulin sensitivity through the elaboration of a series of cytokines and hormones, collectively termed "adipokines." We and others have identified Lcn2 as a novel adipokine, but its exact role in obesity-induced insulin resistance remains controversial. The aim of this study was to examine the metabolic phenotype of Lcn2(-/-) mice to clarify the role of Lcn2 in metabolism. Male and female Lcn2(-/-) and wild-type (WT) littermates were placed on either chow or high-fat diet (HFD) to characterize their metabolic phenotype. Studies included body weight and body composition, glucose and insulin tolerance tests, and adipokine expression studies in serum and in white adipose tissue (WAT). Neither chow nor HFD cohorts showed any differences in body weight or body composition. Chow-fed Lcn2(-/-) mice did not exhibit any difference in glucose homeostasis compared with WT mice. Fasting serum glucose levels were lower in the chow-fed Lcn2(-/-) mice, but this finding was not seen in the HFD cohort. Serum adiponectin, leptin, resistin, and RBP4 levels were not different between WT and Lcn2(-/-) on chow diet. HFD-fed male Lcn2(-/-) mice did display a small improvement in glucose tolerance, but no difference in insulin sensitivity was seen in either male or female Lcn2(-/-) mice on HFD. We conclude that the global ablation of Lcn2 has a minimal effect on obesity-associated glucose intolerance but does not appear to affect either age- or obesity-mediated insulin resistance in vivo. PMID:21771968

  13. A minor role for lipocalin 2 in high-fat diet-induced glucose intolerance

    PubMed Central

    Jun, Lucy S.; Siddall, C. Parker

    2011-01-01

    Adipose tissue controls energy homeostasis and systemic insulin sensitivity through the elaboration of a series of cytokines and hormones, collectively termed “adipokines.” We and others have identified Lcn2 as a novel adipokine, but its exact role in obesity-induced insulin resistance remains controversial. The aim of this study was to examine the metabolic phenotype of Lcn2−/− mice to clarify the role of Lcn2 in metabolism. Male and female Lcn2−/− and wild-type (WT) littermates were placed on either chow or high-fat diet (HFD) to characterize their metabolic phenotype. Studies included body weight and body composition, glucose and insulin tolerance tests, and adipokine expression studies in serum and in white adipose tissue (WAT). Neither chow nor HFD cohorts showed any differences in body weight or body composition. Chow-fed Lcn2−/− mice did not exhibit any difference in glucose homeostasis compared with WT mice. Fasting serum glucose levels were lower in the chow-fed Lcn2−/− mice, but this finding was not seen in the HFD cohort. Serum adiponectin, leptin, resistin, and RBP4 levels were not different between WT and Lcn2−/− on chow diet. HFD-fed male Lcn2−/− mice did display a small improvement in glucose tolerance, but no difference in insulin sensitivity was seen in either male or female Lcn2−/− mice on HFD. We conclude that the global ablation of Lcn2 has a minimal effect on obesity-associated glucose intolerance but does not appear to affect either age- or obesity-mediated insulin resistance in vivo. PMID:21771968

  14. The effect of combined treatment with canagliflozin and teneligliptin on glucose intolerance in Zucker diabetic fatty rats.

    PubMed

    Oguma, Takahiro; Kuriyama, Chiaki; Nakayama, Keiko; Matsushita, Yasuaki; Yoshida, Kumiko; Kiuchi, Satoko; Ikenaga, Yuka; Nakamaru, Yoshinobu; Hikida, Kumiko; Saito, Akira; Arakawa, Kenji; Oka, Kozo; Ueta, Kiichiro; Shiotani, Masaharu

    2015-04-01

    To assess the impact of concomitant inhibition of sodium-glucose cotransporter (SGLT) 2 and dipeptidyl peptidase IV (DPP4) for the treatment of type 2 diabetes mellitus (T2DM), the effect of combined treatment with canagliflozin, a novel SGLT2 inhibitor, and teneligliptin, a DPP4 inhibitor, on glucose intolerance was investigated in Zucker diabetic fatty (ZDF) rats. Canagliflozin potently inhibited human and rat SGLT2 and moderately inhibited human and rat SGLT1 activities but did not affect DPP4 activity. In contrast, teneligliptin inhibited human and rat DPP4 activities but not SGLT activities. A single oral treatment of canagliflozin and teneligliptin suppressed plasma glucose elevation in an oral glucose tolerance test in 13 week-old ZDF rats. This combination of agents elevated plasma active GLP-1 levels in a synergistic manner, probably mediated by intestinal SGLT1 inhibition, and further improved glucose intolerance. In the combination-treated animals, there was no pharmacokinetic interaction of the drugs and no further inhibition of plasma DPP4 activity compared with that in the teneligliptin-treated animals. These results suggest that the inhibition of SGLT2 and DPP4 improves glucose intolerance and that combined treatment with canagliflozin and teneligliptin is a novel therapeutic option for glycemic control in T2DM. PMID:25892328

  15. Changes in hippocampal synaptic functions and protein expression in monosodium glutamate-treated obese mice during development of glucose intolerance.

    PubMed

    Sasaki-Hamada, Sachie; Hojo, Yuki; Koyama, Hajime; Otsuka, Hayuma; Oka, Jun-Ichiro

    2015-05-01

    Glucose is the sole neural fuel for the brain and is essential for cognitive function. Abnormalities in glucose tolerance may be associated with impairments in cognitive function. Experimental obese model mice can be generated by an intraperitoneal injection of monosodium glutamate (MSG; 2 mg/g) once a day for 5 days from 1 day after birth. MSG-treated mice have been shown to develop glucose intolerance and exhibit chronic neuroendocrine dysfunction associated with marked cognitive malfunctions at 28-29  weeks old. Although hippocampal synaptic plasticity is impaired in MSG-treated mice, changes in synaptic transmission remain unknown. Here, we investigated whether glucose intolerance influenced cognitive function, synaptic properties and protein expression in the hippocampus. We demonstrated that MSG-treated mice developed glucose intolerance due to an impairment in the effectiveness of insulin actions, and showed cognitive impairments in the Y-maze test. Moreover, long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal synapses in hippocampal slices was impaired, and the relationship between the slope of extracellular field excitatory postsynaptic potential and stimulus intensity of synaptic transmission was weaker in MSG-treated mice. The protein levels of vesicular glutamate transporter 1 and GluA1 glutamate receptor subunits decreased in the CA1 region of MSG-treated mice. These results suggest that deficits in glutamatergic presynapses as well as postsynapses lead to impaired synaptic plasticity in MSG-treated mice during the development of glucose intolerance, though it remains unknown whether impaired LTP is due to altered inhibitory transmission. It may be important to examine changes in glucose tolerance in order to prevent cognitive malfunctions associated with diabetes. PMID:25851080

  16. 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

  17. Glucose intolerance and pancreatic β-cell dysfunction in the anorectic anx/anx mouse.

    PubMed

    Lindfors, Charlotte; Katz, Abram; Selander, Lars; Johansen, Jeanette E; Marconi, Giulia; Schalling, Martin; Hökfelt, Tomas; Berggren, Per-Olof; Zaitsev, Sergei; Nilsson, Ida A K

    2015-08-15

    Inflammation and impaired mitochondrial oxidative phosphorylation are considered key players in the development of several metabolic disorders, including diabetes. We have previously shown inflammation and mitochondrial dysfunction in the hypothalamus of an animal model for anorexia, the anx/anx mouse. Moreover, increased incidence of eating disorders, e.g., anorexia nervosa, has been observed in diabetic individuals. In the present investigation we evaluated whether impaired mitochondrial phosphorylation and inflammation also occur in endocrine pancreas of anorectic mice, and if glucose homeostasis is disturbed. We show that anx/anx mice exhibit marked glucose intolerance associated with reduced insulin release following an intraperitoneal injection of glucose. In contrast, insulin release from isolated anx/anx islets is increased after stimulation with glucose or KCl. In isolated anx/anx islets there is a strong downregulation of the mitochondrial complex I (CI) assembly factor, NADH dehydrogenase (ubiquinone) 1α subcomplex, assembly factor 1 (Ndufaf1), and a reduced CI activity. In addition, we show elevated concentrations of free fatty acids (FFAs) in anx/anx serum and increased macrophage infiltration (indicative of inflammation) in anx/anx islets. However, isolated islets from anx/anx mice cultured in the absence of FFAs do not exhibit increased inflammation. We conclude that the phenotype of the endocrine pancreas of the anx/anx mouse is characterized by increased levels of circulating FFAs, as well as inflammation, which can inhibit insulin secretion in vivo. The anx/anx mouse may represent a useful tool for studying molecular mechanisms underlying the association between diabetes and eating disorders. PMID:26126683

  18. Beneficial effect of dietary Ephedra sinica on obesity and glucose intolerance in high-fat diet-fed mice.

    PubMed

    Song, Moon-Koo; Um, Jae-Young; Jang, Hyeung-Jin; Lee, Byung-Cheol

    2012-04-01

    Obesity is a major contributor to both glucose intolerance and metabolic syndrome. In this study, we investigated the anti-obesity and anti-hyperglycemic effects of Ephedra sinica on high-fat diet-fed mice. Male ICR mice were divided into four groups; the normal group, the obese and diabetic control group treated with a high-fat diet, the positive control group treated with a high-fat diet containing acarbose, and the experimental group treated with a high-fat diet containing Ephedra sinica. The effects of Ephedra sinica on obesity and glucose intolerance were measured by an oral glucose tolerance test (OGTT), plasma biochemistry, body and epididymal fat weight; the expression of adiponectin, peroxisome-proliferator-activated receptor α (PPAR-α), tumor necrosis factor α (TNF-α) and leptin was also determined. Ephedra sinica reduced weight gain and epididymal fat accumulation, improved glucose intolerance on the OGTT, decreased triglycerides and increased high-density lipoprotein cholesterol compared to the controls. Moreover, it reduced weight gain and fasting glucose levels and improved HDL-cholesterol levels more than acarbose. Gene expression analysis revealed that Ephedra sinica upregulated the expression of adiponectin and PPAR-α, and downregulated the expression of TNF-α. From these results, we suggest that Ephedra sinica may reduce obesity and hyperglycemia by increasing PPAR-α and adiponectin and reducing TNF-α, and that it may have the potential to be used clinically as an ingredient in food or drugs effective in obesity-related glucose intolerance treatments. PMID:22969956

  19. Glucose concentration in parotid saliva after glucose/food intake in individuals with glucose intolerance and diabetes mellitus.

    PubMed

    Borg Andersson, A; Birkhed, D; Berntorp, K; Lindgärde, F; Matsson, L

    1998-10-01

    The concentration of glucose in parotid saliva was measured after glucose/food intake in two separate studies (A and B). In Study A, 10 subjects with impaired glucose tolerance (IGT), 10 subjects with newly diagnosed Type 2 diabetes and 12 healthy controls were included. Study B comprised 15 subjects with Type 1 or Type 2 diabetes on insulin treatment, nine subjects with Type 2 diabetes on treatment with oral antidiabetic drugs and 12 healthy controls. After a 10-h overnight fast, the participants in Study A were given a 75 g oral glucose load, while those in Study B received a standardized breakfast. Citric acid-stimulated parotid saliva was collected up to two hours after the intake. Capillary blood and gingival exudate samples were also taken. On the basis of AUC values (area under the curve over baseline), the glucose concentration in parotid saliva increased significantly in individuals with IGT and Type 2 diabetes compared with controls in Study A and in diabetic patients on treatment with insulin and oral antidiabetic drugs compared with controls in Study B. No effect by the glucose/food intake on the glucose concentration in gingival exudate could be demonstrated in any of the studies. The correlation coefficient between the AUC values of glucose in saliva and blood, when all three groups were combined, was 0.38 in Study A and 0.52 in Study B. It is concluded that the concentration of glucose in parotid saliva is elevated at least 2 h after glucose/food intake in individuals with both IGT and manifest diabetes mellitus. PMID:9786322

  20. 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

  1. 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

  2. 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

  3. 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

  4. CGI-58 knockdown in mice causes hepatic steatosis but prevents diet-induced obesity and glucose intolerance[S

    PubMed Central

    Brown, J. Mark; Betters, Jenna L.; Lord, Caleb; Ma, Yinyan; Han, Xianlin; Yang, Kui; Alger, Heather M.; Melchior, John; Sawyer, Janet; Shah, Ramesh; Wilson, Martha D.; Liu, Xiuli; Graham, Mark J.; Lee, Richard; Crooke, Rosanne; Shulman, Gerald I.; Xue, Bingzhong; Shi, Hang; Yu, Liqing

    2010-01-01

    Mutations of Comparative Gene Identification-58 (CGI-58) in humans cause triglyceride (TG) accumulation in multiple tissues. Mice genetically lacking CGI-58 die shortly after birth due to a skin barrier defect. To study the role of CGI-58 in integrated lipid and energy metabolism, we utilized antisense oligonucleotides (ASOs) to inhibit CGI-58 expression in adult mice. Treatment with two distinct CGI-58-targeting ASOs resulted in ∼80–95% knockdown of CGI-58 protein expression in both liver and white adipose tissue. In chow-fed mice, ASO-mediated depletion of CGI-58 did not alter weight gain, plasma TG, or plasma glucose, yet raised hepatic TG levels ∼4-fold. When challenged with a high-fat diet (HFD), CGI-58 ASO-treated mice were protected against diet-induced obesity, but their hepatic contents of TG, diacylglycerols, and ceramides were all elevated, and intriguingly, their hepatic phosphatidylglycerol content was increased by 10-fold. These hepatic lipid alterations were associated with significant decreases in hepatic TG hydrolase activity, hepatic lipoprotein-TG secretion, and plasma concentrations of ketones, nonesterified fatty acids, and insulin. Additionally, HFD-fed CGI-58 ASO-treated mice were more glucose tolerant and insulin sensitive. Collectively, this work demonstrates that CGI-58 plays a critical role in limiting hepatic steatosis and maintaining hepatic glycerophospholipid homeostasis and has unmasked an unexpected role for CGI-58 in promoting HFD-induced obesity and insulin resistance. PMID:20802159

  5. 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. PMID:10884714

  6. Periodontal Bacteria and Prediabetes Prevalence in ORIGINS: The Oral Infections, Glucose Intolerance, and Insulin Resistance Study.

    PubMed

    Demmer, R T; Jacobs, D R; Singh, R; Zuk, A; Rosenbaum, M; Papapanou, P N; Desvarieux, M

    2015-09-01

    Periodontitis and type 2 diabetes mellitus are known to be associated. The relationship between periodontal microbiota and early diabetes risk has not been studied. We investigated the association between periodontal bacteria and prediabetes prevalence among diabetes-free adults. ORIGINS (the Oral Infections, Glucose Intolerance and Insulin Resistance Study) cross sectionally enrolled 300 diabetes-free adults aged 20 to 55 y (mean ± SD, 34 ± 10 y; 77% female). Prediabetes was defined as follows: 1) hemoglobin A1c values ranging from 5.7% to 6.4% or 2) fasting plasma glucose ranging from 100 to 125 mg/dL. In 1,188 subgingival plaque samples, 11 bacterial species were assessed at baseline, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Actinomyces naeslundii. Full-mouth clinical periodontal examinations were performed, and participants were defined as having no/mild periodontitis vs. moderate/severe periodontitis per the definition of the Centers for Disease Control and Prevention / American Academy of Periodontology. Modified Poisson regression evaluated prediabetes prevalence across bacterial tertiles. Prevalence ratios and 95% confidence intervals for third vs. first tertiles are presented. All analyses were adjusted for cardiometabolic risk factors. All results presented currently arise from the baseline cross section. Prediabetes prevalence was 18%, and 58% of participants had moderate/severe periodontitis. Prevalence ratios (95% confidence intervals) summarizing associations between bacterial levels and prediabetes were as follows: A. actinomycetemcomitans, 2.48 (1.34, 4.58), P = 0.004; P. gingivalis, 3.41 (1.78, 6.58), P = 0.0003; T. denticola, 1.99 (0.992, 4.00), P = 0.052; T. forsythia, 1.95 (1.0, 3.84), P = 0.05; A. naeslundii, 0.46 (0.25, 0.85), P = 0.01. The prevalence ratio for prediabetes among participants with moderate/severe vs. no/mild periodontitis was 1.47 (0.78, 2.74), P

  7. 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

  8. Deletion of GαZ protein protects against diet-induced glucose intolerance via expansion of β-cell mass.

    PubMed

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

    2012-06-01

    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 G(z) protein, Gα(z), impairs insulin secretion by suppressing production of cAMP. Pancreatic islets from Gα(z)-null mice also exhibit constitutively increased cAMP production and augmented glucose-stimulated insulin secretion, suggesting that Gα(z) 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 Gα(z) 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 Gα(z) 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 Gα(z) to both major aspects of β-cell decompensation: insufficient β-cell function and mass. PMID:22457354

  9. Aerobic Exercise Improves Cognition for Older Adults with Glucose Intolerance, A Risk Factor for Alzheimer’s Disease

    PubMed Central

    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

    2011-01-01

    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

  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. F0 maternal BPA exposure induced glucose intolerance of F2 generation through DNA methylation change in Gck.

    PubMed

    Li, Gengqi; Chang, Huailong; Xia, Wei; Mao, Zhenxing; Li, Yuanyuan; Xu, Shunqing

    2014-08-01

    BPA, a common environmental endocrine disruptor, has been reported to induce epigenetic changes and disrupt glucose homeostasis in F1 offspring through maternal exposure. However, no studies have examined whether maternal BPA exposure can exert multigenerational effects of glucose metabolic disorder on F2 generation through the altered epigenetic information. The aim of the current study was to investigate whether BPA exposure can disrupt glucose homeostasis in F2 offspring and the underlying epigenetic mechanism. In the present study, F0 pregnant dams were orally administered at a daily dose of 40μg/kg body weight during gestation and lactation. The F1 and F2 generations were obtained and not exposed to BPA anymore. The glucose and insulin tolerance tests were carried out to evaluate the glucose homeostasis level. The relative hormone level and the relative gene expression were also examined. F2 generation was found to exhibited glucose intolerance and insulin resistance in ipGTT and ipITT, as well as the downregulation of glucokinase (Gck) gene in liver. DNA methylation pattern of Gck promoter in the F2 generation of hepatic tissue and F1 generation of sperm was then performed. The Gck promoter in F2 hepatic tissue became completely methylated in the all CpG sites compared with five unmethylated sites in controls. In the F1 sperm, the global DNA methylation was decreased. However, there is only CpG site -314 was differently methylated between BPA and controls in sperm. In conclusion, F0 maternal BPA exposure during gestation and lactation can induce impaired glucose homeostasis in the F2 offspring through the transmission of sperm. The underlying epigenetic modifications in the sperm of F1 generation remain to be further elucidated. PMID:24793715

  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. PMID:27216413

  13. 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

  14. 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.

  15. Exposure to Common Food Additive Carrageenan Alone Leads to Fasting Hyperglycemia and in Combination with High Fat Diet Exacerbates Glucose Intolerance and Hyperlipidemia without Effect on Weight

    PubMed Central

    Bhattacharyya, Sumit; Feferman, Leo; Unterman, Terry; Tobacman, Joanne K.

    2015-01-01

    Aims. Major aims were to determine whether exposure to the commonly used food additive carrageenan could induce fasting hyperglycemia and could increase the effects of a high fat diet on glucose intolerance and dyslipidemia. Methods. C57BL/6J mice were exposed to either carrageenan, high fat diet, or the combination of high fat diet and carrageenan, or untreated, for one year. Effects on fasting blood glucose, glucose tolerance, lipid parameters, weight, glycogen stores, and inflammation were compared. Results. Exposure to carrageenan led to glucose intolerance by six days and produced elevated fasting blood glucose by 23 weeks. Effects of carrageenan on glucose tolerance were more severe than from high fat alone. Carrageenan in combination with high fat produced earlier onset of fasting hyperglycemia and higher glucose levels in glucose tolerance tests and exacerbated dyslipidemia. In contrast to high fat, carrageenan did not lead to weight gain. In hyperinsulinemic, euglycemic clamp studies, the carrageenan-exposed mice had higher early glucose levels and lower glucose infusion rate and longer interval to achieve the steady-state. Conclusions. Carrageenan in the Western diet may contribute to the development of diabetes and the effects of high fat consumption. Carrageenan may be useful as a nonobese model of diabetes in the mouse. PMID:25883986

  16. Transgenerational Glucose Intolerance of Tumor Necrosis Factor with Epigenetic Alteration in Rat Perirenal Adipose Tissue Induced by Intrauterine Hyperglycemia

    PubMed Central

    Su, Rina; Yan, Jie; Yang, Huixia

    2016-01-01

    Changes in DNA methylation may play a role in the genetic mechanism underlying glucose intolerance in the offspring of mothers with diabetes. Here, we established a rat model of moderate intrauterine hyperglycemia induced by streptozotocin to detect glucose and lipid metabolism of first-generation (F1) and second-generation (F2) offspring. Moderate intrauterine hyperglycemia induced high body weight in F1 and F2 offspring of diabetic mothers. F1 offspring had impaired glucose tolerance and abnormal insulin level. Additionally, F1 and F2 offspring that were exposed to intrauterine hyperglycemia had impaired insulin secretion from the islets. The tumor necrosis factor (Tnf) gene was upregulated in perirenal adipose tissue from F1 offspring and relatively increased in F2 offspring. Both F1 and F2 offspring showed similar hypomethylation level at the −1952 site of Tnf. We confirmed that DNA methylation occurs in offspring exposed to intrauterine hyperglycemia and that the DNA methylation is intergenerational and inherited. PMID:26881249

  17. Young and old genetically heterogeneous HET3 mice on a rapamycin diet are glucose intolerant but insulin sensitive.

    PubMed

    Lamming, Dudley W; Ye, Lan; Astle, Clinton M; Baur, Joseph A; Sabatini, David M; Harrison, David E

    2013-08-01

    Rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, extends the life span of yeast, worms, flies, and mice. Interventions that promote longevity are often correlated with increased insulin sensitivity, and it therefore is surprising that chronic rapamycin treatment of mice, rats, and humans is associated with insulin resistance (J Am Soc Nephrol., 19, 2008, 1411; Diabetes, 00, 2010, 00; Science, 335, 2012, 1638). We examined the effect of dietary rapamycin treatment on glucose homeostasis and insulin resistance in the genetically heterogeneous HET3 mouse strain, a strain in which dietary rapamycin robustly extends mean and maximum life span. We find that rapamycin treatment leads to glucose intolerance in both young and old HET3 mice, but in contrast to the previously reported effect of injected rapamycin in C57BL/6 mice, HET3 mice treated with dietary rapamycin responded normally in an insulin tolerance test. To gauge the overall consequences of rapamycin treatment on average blood glucose levels, we measured HBA1c. Dietary rapamycin increased HBA1c over the first 3 weeks of treatment in young animals, but the effect was lost by 3 months, and no effect was detected in older animals. Our results demonstrate that the extended life span of HET3 mice on a rapamycin diet occurs in the absence of major changes in insulin sensitivity and highlight the importance of strain background and delivery method in testing effects of longevity interventions. PMID:23648089

  18. Glucose intolerance with low-, medium-, and high-carbohydrate formulas during nighttime enteral feedings in cystic fibrosis patients.

    PubMed

    Kane, R E; Black, P

    1989-04-01

    Ten young adult cystic fibrosis (CF) patients over 16 years of age (average 21.4 years) began nighttime enteral feedings as a method of nutritional rehabilitation to regain and maintain body weight. Patients received nighttime feedings of 1,000 kcal/M2 of a low- (Pulmocare), medium- (Ensure Plus), or high-carbohydrate (Vivonex) formula for at least 2 nights each with pancreatic enzyme therapy. Five of ten young adult CF patients developed nocturnal hyperglycemia (serum glucose greater than 300 mg/dl) and glucosuria (1-3% glucose) with varying degrees of polyuria during enteral feedings. No patient developed ketonuria despite serum glucoses at times greater than 600 mg %. There was no difference between the hyperglycemic and normoglycemic groups in median age, percent of ideal body weight, NIH score, Brasfield scores, pulmonary function tests, or family history of diabetes. All normoglycemic and four of five hyperglycemic patients had normal fasting blood sugars. The percent hemoglobin A1c was greater in the glucose intolerant group than the normoglycemic patients (11.2 +/- 0.8% vs. 6.8 +/- 1.1%, mean +/- SE, p less than 0.005). Twelve to 15 units of NPH insulin prior to initiation of feedings provided adequate therapy in most hyperglycemic patients. There was no apparent difference in the elevation of early morning serum glucoses with the low- medium- and high-carbohydrate formulas. We concluded that hyperglycemia requiring insulin therapy was common in young adult CF patients using nighttime enteral feedings. A hemoglobin A1c appeared to be a useful screening test before initiating such therapy. PMID:2496215

  19. Influence of Metformin on Glucose Intolerance and Muscle Catabolism Following Severe Burn Injury

    PubMed Central

    Gore, Dennis C.; Wolf, Steven E.; Sanford, Arthur; Herndon, David N.; Wolfe, Robert R.

    2005-01-01

    Summary Background Data: Hyperglycemia and accelerated muscle catabolism have been shown to adversely affect immune response and survival. The purpose of this study was to determine the effect of metformin on glucose kinetics and muscle protein metabolism in severely burned patients and assess any potential benefit of metformin in this clinical setting. Methods: In a double-blind, randomized manner, 8 adult burn patients received metformin (850 mg every 8 hours × 7 days), while 5 burn patients received placebo. Infusions of 6,6d2 glucose, d5 phenylalanine, sequential muscle biopsies, and femoral arterial, venous blood sampling allowed determination of glucose and muscle protein kinetics. Measurements were obtained immediately prior and at the conclusion of 7 days of treatment (metformin versus placebo). All patients received enteral feeds of comparable amounts during study. Results: Patients receiving metformin had a significant decrease in their plasma glucose concentration, the rate of glucose production, and an increase in glucose clearance. Metformin administration was also associated with a significant increase in the fractional synthetic rate of muscle protein and improvement in net muscle protein balance. Glucose kinetics and muscle protein metabolism were not significantly altered in the patients receiving placebo. Conclusions: Metformin attenuates hyperglycemia and increases muscle protein synthesis in severely burned patients, thereby indicating a metabolic link between hyperglycemia and muscle loss following severe injury. Therefore, therapies that improve glucose tolerance such as metformin may be of clinical value in ameliorating muscle catabolism in critically injured patients. PMID:15650645

  20. The Development of Diet-Induced Obesity and Glucose Intolerance in C57Bl/6 Mice on a High-Fat Diet Consists of Distinct Phases

    PubMed Central

    Williams, Lynda M.; Campbell, Fiona M.; Drew, Janice E.; Koch, Christiane; Hoggard, Nigel; Rees, William D.; Kamolrat, Torkamol; Thi Ngo, Ha; Steffensen, Inger-Lise; Gray, Stuart R.; Tups, Alexander

    2014-01-01

    High–fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable. PMID:25170916

  1. 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

  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. The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects

    PubMed Central

    Niemi, M; Kervinen, K; Rantala, A; Kauma, H; Paivansalo, M; Savolainen, M; Lilja, M; Kesaniemi, Y

    1999-01-01

    BACKGROUND—The polymorphism of apolipoprotein E has been suggested to be associated with the cholesterol content of gallstones, the crystallisation rate of gall bladder bile, and the prevalence of gallstone disease (GSD). 
AIMS—To investigate whether apolipoprotein E polymorphism modulates the susceptibility to GSD at the population level and to study the possible associations between impaired glucose tolerance, diabetes, and GSD. 
METHODS—Apolipoprotein E phenotypes were determined in a middle aged cohort of 261 randomly selected hypertensive men, 259 control men, 257 hypertensive women, and 267 control women. All subjects without a documented history of diabetes were submitted to a two hour oral glucose tolerance test (OGTT). GSD was verified by ultrasonography. 
RESULTS—In women with apolipoprotein E2 (phenotypes E2/2, 2/3, and 2/4) compared with women without E2 (E3/3, 4/3, and 4/4), the odds ratio for GSD was 0.28 (95% confidence interval 0.08-0.92). There was no protective effect in men. The relative risk for GSD was 1.2 (0.8-1.7) for hypertensive women and 1.8(1.0-2.7) for hypertensive men. In a stepwise multiple logistic regression model, E2 protected against GSD in women, whereas two hour blood glucose in the OGTT, serum insulin, and plasma triglycerides were risk factors. Elevated blood glucose during the OGTT was also a significant risk factor for GSD in men. 
CONCLUSIONS—The data suggest that apolipoprotein E2 is a genetic factor providing protection against GSD in women. In contrast, impaired glucose tolerance and frank diabetes are associated with the risk of GSD. 

 Keywords: apolipoprotein E; gallstone disease; diabetes; impaired glucose tolerance; cholesterol PMID:10075965

  4. 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

  5. Tissue Inhibitor Of Matrix Metalloproteinase-1 Is Required for High-Fat Diet-Induced Glucose Intolerance and Hepatic Steatosis in Mice

    PubMed Central

    Myrmel, Lene Secher; Petersen, Rasmus Koefoed; Hansen, Jakob Bondo; Tastesen, Hanne Sørup; Mandrup-Poulsen, Thomas; Brünner, Nils; Kristiansen, Karsten

    2015-01-01

    Background Plasma levels of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are elevated in obesity and obesity-related disorders, such as steatosis, but the metabolic role of TIMP-1 is unclear. Here we investigated how the presence or absence of TIMP-1 affected the development of diet-induced glucose intolerance and hepatic steatosis using the Timp1 null mice. Methods Timp1 knockout (TKO) and wild type (TWT) mice were fed chow, high-fat diet (HFD) or intermediate fat and sucrose diet (IFSD). We determined body weight, body composition, lipid content of the liver, energy intake, energy expenditure, oral glucose tolerance, as well as insulin tolerance. In addition, the histology of liver and adipose tissues was examined and expression of selected genes involved in lipid metabolism and inflammation in liver and adipose tissues was determined by RT-qPCR. Results TKO mice gained less weight and had lower energy efficiency than TWT mice when fed HFD, but not when fed chow or IFSD. Importantly, TKO mice were protected from development of HFD- as well as IFSD-induced glucose intolerance, hepatic steatosis, and altered expression of genes involved in hepatic lipid metabolism and inflammation. Conclusion Collectively, our results indicate that TIMP-1 contributes to the development of diet-induced hepatic steatosis and glucose intolerance and may be a potential therapeutic target. PMID:26168159

  6. [Disaccharide intolerance].

    PubMed

    Radlović, Nedeljko

    2010-01-01

    Disaccharide intolerance presents a pathogenic heterogeneous and most complex clinical entity. It usually occurs due to primary or secondary deficit of disaccharide activity, and rarely because of disorders of absorption or monomer metabolism. Symptomatology of disaccharide maldigestion and/or malabsorption depends on the severity of the basic disorder, the level of its overload and the patient's age. In the youngest children, due to a rapid gastrointestinal transit and a low compensatory capacity of the colon, osmotic-fermentative diarrhoea forms the basis of clinical features. Diarrhoeal disorder can be occasionally so intensive that it disturbs not only water and electrolytic balance, but also the nutritive status of the child. In older children and adults, as well as in milder forms of the disorder, the symptomatology, most often without diarrhoea, is dominated by abdominal colic, loud peristaltic sounds, meteorism and increased flatulence. Metabolic disorders followed by conversion disorders of galactose and fructose into glucose are characterized by a hypoglycaemic crisis, as well as by various multisystemic damages due to the deposit of toxic metabolic products. The diagnosis of gastrointestinal forms of disaccharide intolerance is based on the pathologic clinical and laboratory response during the overload test, while that of the metabolic form is based on the confirmed presence of specific enzyme and/or genetic defect. Treatment of disaccharide intolerance is based on the elimination diet. Besides, in the secondary forms of the disorder, it is also necessary to apply the treatment of the basic disease. PMID:21365893

  7. 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

  8. Alteration of NCoR Corepressor Splicing in Mice Causes Increased Body Weight and Hepatosteatosis without Glucose Intolerance

    PubMed Central

    Goodson, Michael L.; Young, Briana M.; Snyder, Chelsea A.; Schroeder, Amy C.

    2014-01-01

    Alternative mRNA splicing is an important means of diversifying function in higher eukaryotes. Notably, both NCoR and SMRT corepressors are subject to alternative mRNA splicing, yielding a series of distinct corepressor variants with highly divergent functions. Normal adipogenesis is associated with a switch in corepressor splicing from NCoRω to NCoRδ, which appears to help regulate this differentiation process. We report here that mimicking this development switch in mice by a splice-specific whole-animal ablation of NCoRω is very different from a whole-animal or tissue-specific total NCoR knockout and produces significantly enhanced weight gain on a high-fat diet. Surprisingly, NCoRω−/− mice are protected against diet-induced glucose intolerance despite enhanced adiposity and the presence of multiple additional, prodiabetic phenotypic changes. Our results indicate that the change in NCoR splicing during normal development both helps drive normal adipocyte differentiation and plays a key role in determining a metabolically appropriate storage of excess calories. We also conclude that whole-gene “knockouts” fail to reveal how important gene products are customized, tailored, and adapted through alternative mRNA splicing and thus do not reveal all the functions of the protein products of that gene. PMID:25182530

  9. Lactose Intolerance

    MedlinePlus

    Lactose intolerance means that you cannot digest foods with lactose in them. Lactose is the sugar found in ... find out if your problems are due to lactose intolerance. Lactose intolerance is not serious. Eating less food ...

  10. Transplantation of betacellulin-transduced islets improves glucose intolerance in diabetic mice

    PubMed Central

    Song, Mi-Young; Bae, Ui-Jin; Jang, Kyu Yun; Park, Byung-Hyun

    2014-01-01

    Type 1 diabetes is an autoimmune disease caused by permanent destruction of insulin-producing pancreatic β cells and requires lifelong exogenous insulin therapy. Recently, islet transplantation has been developed, and although there have been significant advances, this approach is not widely used clinically due to the poor survival rate of the engrafted islets. We hypothesized that improving survival of engrafted islets through ex vivo genetic engineering could be a novel strategy for successful islet transplantation. We transduced islets with adenoviruses expressing betacellulin, an epidermal growth factor receptor ligand, which promotes β-cell growth and differentiation, and transplanted these islets under the renal capsule of streptozotocin-induced diabetic mice. Transplantation with betacellulin-transduced islets resulted in prolonged normoglycemia and improved glucose tolerance compared with those of control virus-transduced islets. In addition, increased microvascular density was evident in the implanted islets, concomitant with increased endothelial von Willebrand factor immunoreactivity. Finally, cultured islets transduced with betacellulin displayed increased proliferation, reduced apoptosis and enhanced glucose-stimulated insulin secretion in the presence of cytokines. These experiments suggest that transplantation with betacellulin-transduced islets extends islet survival and preserves functional islet mass, leading to a therapeutic benefit in type 1 diabetes. PMID:24875130

  11. 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) ...

  12. Indomethacin Treatment Prevents High Fat Diet-induced Obesity and Insulin Resistance but Not Glucose Intolerance in C57BL/6J Mice*

    PubMed Central

    Fjære, Even; Aune, Ulrike L.; Røen, Kristin; Keenan, Alison H.; Ma, Tao; Borkowski, Kamil; Kristensen, David M.; Novotny, Guy W.; Mandrup-Poulsen, Thomas; Hudson, Brian D.; Milligan, Graeme; Xi, Yannan; Newman, John W.; Haj, Fawaz G.; Liaset, Bjørn; Kristiansen, Karsten; Madsen, Lise

    2014-01-01

    Chronic low grade inflammation is closely linked to obesity-associated insulin resistance. To examine how administration of the anti-inflammatory compound indomethacin, a general cyclooxygenase inhibitor, affected obesity development and insulin sensitivity, we fed obesity-prone male C57BL/6J mice a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo and in vitro using MIN6 β-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose output was significantly increased. Indomethacin had no effect on adipose tissue mass, glucose tolerance, or GSIS when included in a regular diet. Indomethacin administration to obese mice did not reduce adipose tissue mass, and the compensatory increase in GSIS observed in obese mice was not affected by treatment with indomethacin. We demonstrate that indomethacin did not inhibit GSIS per se, but activation of GPR40 in the presence of indomethacin inhibited glucose-dependent insulin secretion in MIN6 cells. We conclude that constitutive high hepatic glucose output combined with impaired GSIS in response to activation of GPR40-dependent signaling in the HF/HS+INDO-fed mice contributed to the impaired glucose clearance during a glucose challenge and that the resulting lower levels of plasma insulin prevented the obesogenic action of the HF/HS diet. PMID:24742673

  13. 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

  14. Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice.

    PubMed

    Ellenbroek, Johanne H; van Dijck, Laura; Töns, Hendrica A; Rabelink, Ton J; Carlotti, Françoise; Ballieux, Bart E P B; de Koning, Eelco J P

    2014-03-01

    High-fat, low-carbohydrate ketogenic diets (KD) are used for weight loss and for treatment of refractory epilepsy. Recently, short-time studies in rodents have shown that, besides their beneficial effect on body weight, KD lead to glucose intolerance and insulin resistance. However, the long-term effects on pancreatic endocrine cells are unknown. In this study we investigate the effects of long-term KD on glucose tolerance and β- and α-cell mass in mice. Despite an initial weight loss, KD did not result in weight loss after 22 wk. Plasma markers associated with dyslipidemia and inflammation (cholesterol, triglycerides, leptin, monocyte chemotactic protein-1, IL-1β, and IL-6) were increased, and KD-fed mice showed signs of hepatic steatosis after 22 wk of diet. Long-term KD resulted in glucose intolerance that was associated with insufficient insulin secretion from β-cells. After 22 wk, insulin-stimulated glucose uptake was reduced. A reduction in β-cell mass was observed in KD-fed mice together with an increased number of smaller islets. Also α-cell mass was markedly decreased, resulting in a lower α- to β-cell ratio. Our data show that long-term KD causes dyslipidemia, a proinflammatory state, signs of hepatic steatosis, glucose intolerance, and a reduction in β- and α-cell mass, but no weight loss. This indicates that long-term high-fat, low-carbohydrate KD lead to features that are also associated with the metabolic syndrome and an increased risk for type 2 diabetes in humans. PMID:24398402

  15. 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

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

    PubMed

    Petrovski, Slavé; Gussow, Ayal B; Wang, Quanli; Halvorsen, Matt; Han, Yujun; Weir, William H; Allen, Andrew S; Goldstein, David B

    2015-09-01

    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, nc

  17. 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

  18. 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. PMID:25531536

  19. 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

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

    PubMed

    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

  1. 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

  2. Dimethylesculetin ameliorates maternal glucose intolerance and fetal overgrowth in high-fat diet-fed pregnant mice via constitutive androstane receptor.

    PubMed

    Masuyama, Hisashi; Mitsui, Takashi; Maki, Jota; Tani, Kazumasa; Nakamura, Keiichiro; Hiramatsu, Yuji

    2016-08-01

    The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance along with obesity. 6,7-dimethylesculetin (DE) is an active component of Yin Zhi Huang which is a traditional Asian medicine used to treat neonatal jaundice via CAR. In this study, we examined whether DE could affect the expression of gluconeogenic and lipogenic genes via human CAR pathway using human HepG2 cells in vitro. We also studied whether DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in high-fat diet (HFD)-induced obese pregnant mice. Dimethylesculetin suppressed the mRNA expression of gluconeogenic genes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, and lipogenic genes, sterol regulatory element-binding protein 1 and stearoyl-CoA desaturase 1, and enhanced CAR-mediated transcription. Blocking the CAR-mediated pathway abolished the effect of DE in vitro. DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in HFD-induced obese pregnant mice in vivo. Our data indicate that DE might be a potential therapeutic agent for obese pregnant patients with insulin resistance through CAR to prevent the perinatal outcomes such as preeclampsia, gestational diabetes, and macrosomia. Further analysis of possible complications and side effects using animal models is required. PMID:27426490

  3. Alleviation of high-fat diet-induced atherosclerosis and glucose intolerance by a novel GLP-1 fusion protein in ApoE(-/-) mice.

    PubMed

    Kong, Yuelin; Tong, Yue; Chen, Chen; Gao, Mingming; Gao, Xiangdong; Yao, Wenbing

    2016-07-01

    We have previously constructed an engineered anti-diabetic fusion protein using glucagon-like peptide-1 and the globular domain of adiponectin. Herein, we evaluated the therapeutic effects of this fusion protein (GAD) on high-fat diet (HFD)-fed ApoE(-/-) mice. The lipid-lowering effect of GAD was determined in C57BL/6 mice using a lipid tolerance test. The effects of GAD on HFD-induced glucose intolerance, atherosclerosis, and hepatic steatosis were evaluated in HFD-fed ApoE(-/-) mice using glucose tolerance test, histological examinations and real-time quantitative PCR. The anti-inflammation activity of GAD was assessed in vitro on macrophages. GAD improved lipid metabolism in C57BL/6 mice. GAD treatment alleviated glucose intolerance, reduced blood lipid level, and attenuated atherosclerotic lesion in HFD-fed ApoE(-/-) mice, which was associated with a repressed macrophage infiltration in the vessel wall. GAD treatment also blocked hepatic macrophage infiltration and prevented hepatic inflammation. GAD suppressed lipopolysaccharide-triggered inflammation responses on macrophages, which can be abolished by H89, an inhibitor of protein kinase A. These findings demonstrate that GAD is able to generate a variety of metabolic benefits in HFD-fed ApoE(-/-) mice and indicate that this engineered fusion protein is a promising lead structure for anti-atherosclerosis drug discovery. PMID:26832342

  4. Carbenoxolone Treatment Ameliorated Metabolic Syndrome in WNIN/Ob Obese Rats, but Induced Severe Fat Loss and Glucose Intolerance in Lean Rats

    PubMed Central

    Prasad Sakamuri, Siva Sankara Vara; Sukapaka, Mahesh; Prathipati, Vijay Kumar; Nemani, Harishankar; Putcha, Uday Kumar; Pothana, Shailaja; Koppala, Swarupa Rani; Ponday, Lakshmi Raj Kumar; Acharya, Vani; Veetill, Giridharan Nappan; Ayyalasomayajula, Vajreswari

    2012-01-01

    Background 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates local glucocorticoid action in tissues by catalysing conversion of inactive glucocorticoids to active glucocorticoids. 11β-HSD1 inhibition ameliorates obesity and associated co-morbidities. Here, we tested the effect of 11β-HSD inhibitor, carbenoxolone (CBX) on obesity and associated comorbidities in obese rats of WNIN/Ob strain, a new animal model for genetic obesity. Methodology/Principal Findings Subcutaneous injection of CBX (50 mg/kg body weight) or volume-matched vehicle was given once daily for four weeks to three month-old WNIN/Ob lean and obese rats (n = 6 for each phenotype and for each treatment). Body composition, plasma lipids and hormones were assayed. Hepatic steatosis, adipose tissue morphology, inflammation and fibrosis were also studied. Insulin resistance and glucose intolerance were determined along with tissue glycogen content. Gene expressions were determined in liver and adipose tissue. CBX significantly inhibited 11β-HSD1 activity in liver and adipose tissue of WNIN/Ob lean and obese rats. CBX significantly decreased body fat percentage, hypertriglyceridemia, hypercholesterolemia, insulin resistance in obese rats. CBX ameliorated hepatic steatosis, adipocyte hypertrophy, adipose tissue inflammation and fibrosis in obese rats. Tissue glycogen content was significantly decreased by CBX in liver and adipose tissue of obese rats. Severe fat loss and glucose- intolerance were observed in lean rats after CBX treatment. Conclusions/Significance We conclude that 11β-HSD1 inhibition by CBX decreases obesity and associated co-morbidities in WNIN/Ob obese rats. Our study supports the hypothesis that inhibition of 11β-HSD1 is a key strategy to treat metabolic syndrome. Severe fat loss and glucose -intolerance by CBX treatment in lean rats suggest that chronic 11β-HSD1 inhibition may lead to insulin resistance in normal conditions. PMID:23284633

  5. 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

  6. 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

  7. Glucagon-Like Peptide-1 Receptor Agonist Treatment Prevents Glucocorticoid-Induced Glucose Intolerance and Islet-Cell Dysfunction in Humans

    PubMed Central

    van Raalte, Daniël H.; van Genugten, Renate E.; Linssen, Margot M.L.; Ouwens, D. Margriet; Diamant, Michaela

    2011-01-01

    OBJECTIVE Glucocorticoids (GCs) are regarded as diabetogenic because they impair insulin sensitivity and islet-cell function. This study assessed whether treatment with the glucagon-like peptide receptor agonist (GLP-1 RA) exenatide (EXE) could prevent GC-induced glucose intolerance. RESEARCH DESIGN AND METHODS A randomized, placebo-controlled, double-blind, crossover study in eight healthy men (age: 23.5 [20.0–28.3] years; BMI: 26.4 [24.3–28.0] kg/m2) was conducted. Participants received three therapeutic regimens for 2 consecutive days: 1) 80 mg of oral prednisolone (PRED) every day (q.d.) and intravenous (IV) EXE infusion (PRED+EXE); 2) 80 mg of oral PRED q.d. and IV saline infusion (PRED+SAL); and 3) oral placebo-PRED q.d. and intravenous saline infusion (PLB+SAL). On day 1, glucose tolerance was assessed during a meal challenge test. On day 2, participants underwent a clamp procedure to measure insulin secretion and insulin sensitivity. RESULTS PRED+SAL treatment increased postprandial glucose levels (vs. PLB+SAL, P = 0.012), which was prevented by concomitant EXE (vs. PLB+SAL, P = NS). EXE reduced PRED-induced hyperglucagonemia during the meal challenge (P = 0.018) and decreased gastric emptying (vs. PRED+SAL, P = 0.028; vs. PLB+SAL, P = 0.046). PRED+SAL decreased first-phase glucose- and arginine-stimulated C-peptide secretion (vs. PLB+SAL, P = 0.017 and P = 0.05, respectively), whereas PRED+EXE improved first- and second-phase glucose- and arginine-stimulated C-peptide secretion (vs. PLB+SAL; P = 0.017, 0.012, and 0.093, respectively). CONCLUSIONS The GLP-1 RA EXE prevented PRED-induced glucose intolerance and islet-cell dysfunction in healthy humans. Incretin-based therapies should be explored as a potential strategy to prevent steroid diabetes. PMID:21216851

  8. Naringenin prevents obesity, hepatic steatosis, and glucose intolerance in male mice independent of fibroblast growth factor 21.

    PubMed

    Assini, Julia M; Mulvihill, Erin E; Burke, Amy C; Sutherland, Brian G; Telford, Dawn E; Chhoker, Sanjiv S; Sawyez, Cynthia G; Drangova, Maria; Adams, Andrew C; Kharitonenkov, Alexei; Pin, Christopher L; Huff, Murray W

    2015-06-01

    The molecular mechanisms and metabolic pathways whereby the citrus flavonoid, naringenin, reduces dyslipidemia and improves glucose tolerance were investigated in C57BL6/J wild-type mice and fibroblast growth factor 21 (FGF21) null (Fgf21(-/-)) mice. FGF21 regulates energy homeostasis and the metabolic adaptation to fasting. One avenue of this regulation is through induction of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc1a), a regulator of hepatic fatty acid oxidation and ketogenesis. Because naringenin is a potent activator of hepatic FA oxidation, we hypothesized that induction of FGF21 might be an integral part of naringenin's mechanism of action. Furthermore, we predicted that FGF21 deficiency would potentiate high-fat diet (HFD)-induced metabolic dysregulation and compromise metabolic protection by naringenin. The absence of FGF21 exacerbated the response to a HFD. Interestingly, naringenin supplementation to the HFD robustly prevented obesity in both genotypes. Gene expression analysis suggested that naringenin was not primarily targeting fatty acid metabolism in white adipose tissue. Naringenin corrected hepatic triglyceride concentrations and normalized hepatic expression of Pgc1a, Cpt1a, and Srebf1c in both wild-type and Fgf21(-/-) mice. HFD-fed Fgf21(-/-) mice displayed greater muscle triglyceride deposition, hyperinsulinemia, and impaired glucose tolerance as compared with wild-type mice, confirming the role of FGF21 in insulin sensitivity; however, naringenin supplementation improved these metabolic parameters in both genotypes. We conclude that FGF21 deficiency exacerbates HFD-induced obesity, hepatic steatosis, and insulin resistance. Furthermore, FGF21 is not required for naringenin to protect mice from HFD-induced metabolic dysregulation. Collectively these studies support the concept that naringenin has potent lipid-lowering effects and may act as an insulin sensitizer in vivo. PMID:25774553

  9. 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

  10. 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. PMID:19394055

  11. 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.

  12. Imidazoline-like drugs improve insulin sensitivity through peripheral stimulation of adiponectin and AMPK pathways in a rat model of glucose intolerance.

    PubMed

    Weiss, Maud; Bouchoucha, Soumaya; Aiad, Farouk; Ayme-Dietrich, Estelle; Dali-Youcef, Nassim; Bousquet, Pascal; Greney, Hugues; Niederhoffer, Nathalie

    2015-07-15

    Altered adiponectin signaling and chronic sympathetic hyperactivity have both been proposed as key factors in the pathogenesis of metabolic syndrome. We recently reported that activation of I1 imidazoline receptors (I1R) improves several symptoms of the metabolic syndrome through sympathoinhibition and increases adiponectin plasma levels in a rat model of metabolic syndrome (Fellmann L, Regnault V, Greney H, et al. J Pharmacol Exp Ther 346: 370-380, 2013). The present study was designed to explore the peripheral component of the beneficial actions of I1R ligands (i.e., sympathoinhibitory independent effects). Aged rats displaying insulin resistance and glucose intolerance were treated with LNP509, a peripherally acting I1R agonist. Glucose tolerance, insulin sensitivity, and adiponectin signaling were assessed at the end of the treatment. Direct actions of the ligand on hepatocyte and adipocyte signaling were also studied. LNP509 reduced the area under the curve of the intravenous glucose tolerance test and enhanced insulin hypoglycemic action and intracellular signaling (Akt phosphorylation), indicating improved glucose tolerance and insulin sensitivity. LNP509 stimulated adiponectin secretion acting at I1R on adipocytes, resulting in increased plasma levels of adiponectin; it also enhanced AMPK phosphorylation in hepatic tissues. Additionally, I1R activation on hepatocytes directly enhanced AMPK phosphorylation. To conclude, I1R ligands can improve insulin sensitivity acting peripherally, independently of sympathoinhibition; stimulation of adiponectin and AMPK pathways at insulin target tissues may account for this effect. This may open a promising new way for the treatment of the metabolic syndrome. PMID:26015433

  13. Glucoregulatory, endocrine and morphological effects of [P5K]hymenochirin-1B in mice with diet-induced glucose intolerance and insulin resistance.

    PubMed

    Owolabi, Bosede O; Ojo, Opeolu O; Srinivasan, Dinesh K; Conlon, J Michael; Flatt, Peter R; Abdel-Wahab, Yasser H A

    2016-07-01

    The frog skin host-defence peptide hymenochirin-1B has been shown to stimulate insulin release in vitro from isolated pancreatic islets and BRIN-BD11 clonal β-cells. This study examines the effects of 28-day administration of a more potent analogue [P5K]hymenochirin-1B ([P5K]hym-1B) (75 nmol·kg(-1) body weight) to high-fat-fed mice with obesity, glucose intolerance and insulin resistance. Treatment with [P5K]hym-1B significantly decreased plasma glucose concentrations and improved glucose tolerance, insulin secretion, insulin sensitivity and increased the magnitude of the incretin effect (difference in response to oral vs intraperitoneal glucose loads). Responses to established insulin secretagogues were greater in islets isolated from treated animals compared with saline-treated controls. [P5K]hym-1B administration significantly decreased total islet area and β- and α-cell areas, and resulted in lower concentrations of circulating triglycerides and plasma and pancreatic glucagon. Peptide treatment had no effect on food intake, body weight, indirect calorimetry or circulating concentrations of amylase and marker enzymes of liver and kidney function. RT-PCR demonstrated that the Insr (insulin receptor) gene and genes involved in insulin signalling (Slc2a4, Irs1, Pik3ca, Akt1 and Pkd1) were significantly up-regulated in skeletal muscle from animals treated with [P5K]hym-1B. Expression of the Glp1r (GLP-1 receptor) and Gipr (GIP receptor) genes was significantly elevated in islets from peptide-treated mice. These data suggest that [P5K]hym-1B shows potential for development into an agent for treating patients with type 2 diabetes. PMID:27068334

  14. LA and ALA prevent glucose intolerance in obese male rats without reducing reactive lipid content, but cause tissue-specific changes in fatty acid composition.

    PubMed

    Matravadia, Sarthak; Zabielski, Piotr; Chabowski, Adrian; Mutch, David M; Holloway, Graham P

    2016-04-01

    While the cause of Type 2 diabetes remains poorly defined, the accumulation of reactive lipids within white adipose tissue, skeletal muscle, and liver have been repeatedly implicated as underlying mechanisms. The ability of polyunsaturated fatty acids (PUFAs) to prevent the development of insulin resistance has gained considerable interest in recent years; however, the mechanisms-of-action remain poorly described. Therefore, we determined the efficacy of diets supplemented with either linoleic acid (LA) or α-linolenic acid (ALA) in preventing insulin resistance and reactive lipid accumulation in key metabolic tissues of the obese Zucker rat. Obese Zucker rats displayed impaired glucose homeostasis and reduced n-3 and n-6 PUFA content in the liver and epididymal white adipose tissue (EWAT). After the 12-wk feeding intervention, both LA- and ALA-supplemented diets prevented whole body glucose and insulin intolerance; however, ALA had a more pronounced effect. These changes occurred in association with n-3 and n-6 accumulation in all tissues studied, albeit to different extents (EWAT > liver > muscle). Triacylglycerol (TAG), diacylglycerol (DAG), ceramide, and sphingolipid accumulation were not attenuated in obese animals supplemented with either LA or ALA, suggesting that preservation of glucose homeostasis occurred independent of changes in reactive lipid content. However, PUFA-supplemented diets differentially altered the fatty acid composition of TAGs, DAGs, and PLs in a tissue-specific manner, suggesting essential fatty acid metabolism differs between tissues. Together, our results indicate that remodeling of the fatty acid composition of various lipid fractions may contribute to the improved glucose tolerance observed in obese rats fed PUFA-supplemented diets. PMID:26764053

  15. Cold intolerance

    MedlinePlus

    ... intolerance is an abnormal sensitivity to a cold environment or cold temperatures. ... can be a symptom of a problem with metabolism. Some people (often very thin women) do not tolerate cold environments because they have very little body fat and ...

  16. Lactose Intolerance

    MedlinePlus

    ... consuming enough essential nutrients, such as calcium and vitamin D. People with lactose intolerance may not get enough ... cause people to take in less calcium and vitamin D than they need. See the “Calcium and Vitamin ...

  17. 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 ...

  18. Cold Intolerance

    MedlinePlus

    ... from the Handbook on the Late Effects of Poliomyelitis for Physicians and Survivors © Cold Intolerance Many polio ... index of Handbook on the Late Effects of Poliomyelitis for Physicians and Survivors © Back to top Contact ...

  19. 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

  20. 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

  1. Hyperinsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition of phosphoinositide 3-kinase signaling in the liver.

    PubMed

    Miyake, Kazuaki; Ogawa, Wataru; Matsumoto, Michihiro; Nakamura, Takehiro; Sakaue, Hiroshi; Kasuga, Masato

    2002-11-01

    The physiological relevance of phosphoinositide 3-kinase (PI 3-K) signaling in the liver to fuel homeostasis was investigated. Systemic infusion of an adenovirus encoding a dominant negative mutant of PI 3-K ((Delta)p85) resulted in liver-specific expression of this protein and in inhibition of the insulin-induced activation of PI 3-K in the liver within 3 days, without affecting insulin signaling in skeletal muscle. Hepatic expression of (Delta)p85 led to hyperinsulinemia and to a marked increase in blood glucose concentration in response to oral glucose intake. The increases in both glycogen and glucose 6-phosphate content, as well as in Akt and glycogen synthase activities in the liver, that were induced by glucose intake were markedly impaired in mice expressing (Delta)p85. Despite an upregulation of mRNAs for gluconeogenic enzymes apparent in the liver of these animals, the fasting blood glucose concentration was increased only slightly, and the serum concentrations of gluconeogenic precursors were reduced. However, administration of pyruvate, a substrate for gluconeogenesis, resulted in an exaggerated increase in blood glucose concentration. In the fasted state, the mass of adipose tissue of the mice was about 1.5 times that in control mice. The mice also exhibited marked decreases in the serum concentrations of FFAs and triglyceride and suppression of insulin-induced PI 3-K activation in adipose tissue, probably due to the associated hyperinsulinemia. PI 3-K activity in the liver is thus essential for normal carbohydrate and lipid metabolism in living animals. PMID:12438446

  2. 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

  3. Hydrolysis enhances bioavailability of proanthocyanidin-derived metabolites and improves β-cell function in glucose intolerant rats.

    PubMed

    Yang, Kaiyuan; Hashemi, Zohre; Han, Wei; Jin, Alena; Yang, Han; Ozga, Jocelyn; Li, Liang; Chan, Catherine B

    2015-08-01

    Proanthocyanidins (PAC) are a highly consumed class of flavonoids and their consumption has been linked to beneficial effects in type 2 diabetes. However, limited gastrointestinal absorption occurs due to the polymeric structure of PAC. We hypothesized that hydrolysis of the PAC polymer would increase bioavailability, thus leading to enhanced beneficial effects on glucose homeostasis and pancreatic β-cell function. PAC-rich pea seed coats (PSC) were supplemented to a high-fat diet (HFD) either in native (PAC) or hydrolyzed (HPAC) form fed to rats for 4 weeks. HFD or low-fat diet groups were controls. PAC-derived compounds were characterized in both PSC and serum. Glucose and insulin tolerance tests were conducted. Pancreatic α-cell and β-cell areas and glucose-stimulated insulin secretion (GSIS) from isolated islets were measured. Increased PAC-derived metabolites were detected in the serum of HPAC-fed rats compared to PAC-fed rats, suggesting hydrolysis of PSC-enhanced PAC bioavailability. This was associated with ~18% less (P<.05) weight gain compared to HFD without affecting food intake, as well as improvement in glucose disposal in vivo. There was a 2-fold decrease of α/β-cell area ratio and a 2.5-fold increase in GSIS from isolated islets of HPAC-fed rats. These results demonstrate that hydrolysis of PSC-derived PAC increased the bioavailability of PAC-derived products, which is critical for enhancing beneficial effects on glucose homeostasis and pancreatic β-cell function. PMID:25987165

  4. [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

  5. 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.

  6. 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

    2015-01-01

    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

  7. 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

  8. Distinct neurohumoral biomarker profiles in children with hemodynamically defined orthostatic intolerance may predict treatment options.

    PubMed

    Wagoner, Ashley L; Shaltout, Hossam A; Fortunato, John E; Diz, Debra I

    2016-02-01

    Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10-18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic β-cell function

    PubMed Central

    Izumoto-Akita, Takako; Tsunekawa, Shin; Yamamoto, Akihito; Uenishi, Eita; Ishikawa, Kota; Ogata, Hidetada; Iida, Atsushi; Ikeniwa, Makoto; Hosokawa, Kaori; Niwa, Yasuhiro; Maekawa, Ryuya; Yamauchi, Yuichiro; Seino, Yusuke; Hamada, Yoji; Hibi, Hideharu; Arima, Hiroshi; Ueda, Minoru; Oiso, Yutaka

    2015-01-01

    Objective Many studies have reported that stem cell transplantation promotes propagation and protection of pancreatic β-cells in streptozotocin (STZ)-induced diabetic mice without the differentiation of transplanted cells into pancreatic β-cells, suggesting that the improvement is due to a paracrine effect of the transplanted cells. We investigated the effects of factors secreted by dental pulp stem cells from human exfoliated deciduous teeth (SHED) on β-cell function and survival. Research design and methods Conditioned medium from SHED (SHED-CM) was collected 48 h after culturing in serum-free Dulbecco's modified Eagle's medium (DMEM). The insulin levels in SHED-CM and serum-free conditioned media from human bone marrow-derived mesenchymal stem cells (BM-CM) were undetectable. STZ-induced diabetic male C57B/6J mice were injected with DMEM as a control, SHED-CM, exendin-4 (Ex-4), or BM-CM for 14 days. Mouse pancreatic β-cell line MIN6 cells were incubated with different concentrations of STZ with SHED-CM, DMEM, Ex-4, or BM-CM for 6 h. Results Administration of 1 mL of SHED-CM twice a day improved glucose intolerance in STZ-induced diabetic mice and the effect continued for 20 days after the end of treatment. SHED-CM treatment increased pancreatic insulin content and β-cell mass through proliferation and an intraperitoneal glucose tolerance test revealed enhanced insulin secretion. Incubation of MIN6 cells (a mouse pancreatic β-cell line) with SHED-CM enhanced insulin secretion in a glucose concentration-dependent manner and reduced STZ-induced cell death, indicating that the amelioration of hyperglycemia was caused by the direct effects of SHED-CM on β-cell function and survival. These effects were more pronounced than with the use of Ex-4, a conventional incretin-based drug, and BM-CM, which is a medium derived from other stem cells. Conclusions These findings suggest that SHED-CM provides direct protection and encourages the propagation of

  15. Monoclonal Antibody Targeting of Fibroblast Growth Factor Receptor 1c Ameliorates Obesity and Glucose Intolerance via Central Mechanisms

    PubMed Central

    Lelliott, Christopher J.; Ahnmark, Andrea; Admyre, Therese; Ahlstedt, Ingela; Irving, Lorraine; Keyes, Feenagh; Patterson, Laurel; Mumphrey, Michael B.; Bjursell, Mikael; Gorman, Tracy; Bohlooly-Y, Mohammad; Buchanan, Andrew; Harrison, Paula; Vaughan, Tristan; Berthoud, Hans-Rudolf; Lindén, Daniel

    2014-01-01

    We have generated a novel monoclonal antibody targeting human FGFR1c (R1c mAb) that caused profound body weight and body fat loss in diet-induced obese mice due to decreased food intake (with energy expenditure unaltered), in turn improving glucose control. R1c mAb also caused weight loss in leptin-deficient ob/ob mice, leptin receptor-mutant db/db mice, and in mice lacking either the melanocortin 4 receptor or the melanin-concentrating hormone receptor 1. In addition, R1c mAb did not change hypothalamic mRNA expression levels of Agrp, Cart, Pomc, Npy, Crh, Mch, or Orexin, suggesting that R1c mAb could cause food intake inhibition and body weight loss via other mechanisms in the brain. Interestingly, peripherally administered R1c mAb accumulated in the median eminence, adjacent arcuate nucleus and in the circumventricular organs where it activated the early response gene c-Fos. As a plausible mechanism and coinciding with the initiation of food intake suppression, R1c mAb induced hypothalamic expression levels of the cytokines Monocyte chemoattractant protein 1 and 3 and ERK1/2 and p70 S6 kinase 1 activation. PMID:25427253

  16. Transgenerational glucose intolerance with Igf2/H19 epigenetic alterations in mouse islet induced by intrauterine hyperglycemia.

    PubMed

    Ding, Guo-Lian; Wang, Fang-Fang; Shu, Jing; Tian, Shen; Jiang, Ying; Zhang, Dan; Wang, Ning; Luo, Qiong; Zhang, Yu; Jin, Fan; Leung, Peter C K; Sheng, Jian-Zhong; Huang, He-Feng

    2012-05-01

    Gestational diabetes mellitus (GDM) has been shown to be associated with high risk of diabetes in offspring. However, the mechanisms involved and the possibilities of transgenerational transmission are still unclear. We intercrossed male and female adult control and first-generation offspring of GDM (F1-GDM) mice to obtain the second-generation (F2) offspring in four groups: C♂-C♀, C♂-GDM♀, GDM♂-C♀, and GDM♂-GDM♀. We found that birth weight significantly increased in F2 offspring through the paternal line with impaired glucose tolerance (IGT). Regardless of birth from F1-GDM with or without IGT, high risk of IGT appeared as early as 3 weeks in F2 offspring and progressed through both parental lineages, especial the paternal line. IGT in male offspring was more obvious than that in females, with parental characteristics and sex-specific transmission. In both F1 and F2 offspring of GDM, the expression of imprinted genes Igf2 and H19 was downregulated in pancreatic islets, caused by abnormal methylation status of the differentially methylated region, which may be one of the mechanisms for impaired islet ultrastructure and function. Furthermore, altered Igf2 and H19 gene expression was found in sperm of adult F1-GDM, regardless of the presence of IGT, indicating that changes of epigenetics in germ cells contributed to transgenerational transmission. PMID:22447856

  17. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process?

    PubMed

    Gabriely, Ilan; Ma, Xiao Hui; Yang, Xiao Man; Atzmon, Gil; Rajala, Michael W; Berg, Anders H; Scherer, Phillip; Rossetti, Luciano; Barzilai, Nir

    2002-10-01

    Age-dependent changes in insulin action and body fat distribution are risk factors for the development of type 2 diabetes. To examine whether the accumulation of visceral fat (VF) could play a direct role in the pathophysiology of insulin resistance and type 2 diabetes, we monitored insulin action, glucose tolerance, and the expression of adipo-derived peptides after surgical removal of VF in aging (20-month-old) F344/Brown Norway (FBN) and in Zucker Diabetic Fatty (ZDF) rats. As expected, peripheral and hepatic insulin action were markedly impaired in aging FBN rats, and extraction of VF (accounting for approximately 18% of their total body fat) was sufficient to restore peripheral and hepatic insulin action to the levels of young rats. When examined at the mechanistic level, removal of VF in ZDF rats prevented the progressive decrease in insulin action and delayed the onset of diabetes, but VF extraction did not alter plasma free fatty acid levels. However, the expression of tumor necrosis factor-alpha and leptin in subcutaneous (SC) adipose tissue were markedly decreased after VF removal (by approximately three- and twofold, respectively). Finally, extracted VF retained approximately 15-fold higher resistin mRNA compared with SC fat. Our data suggest that insulin resistance and the development of diabetes can be significantly reduced in aging rats by preventing the age-dependent accumulation of VF. This study documents a cause-and-effect relationship between VF and major components of the metabolic syndrome. PMID:12351432

  18. Predicting subcutaneous glucose concentration in humans: data-driven glucose modeling.

    PubMed

    Gani, Adiwinata; Gribok, Andrei V; Rajaraman, Srinivasan; Ward, W Kenneth; Reifman, Jaques

    2009-02-01

    The combination of predictive data-driven models with frequent glucose measurements may provide for an early warning of impending glucose excursions and proactive regulatory interventions for diabetes patients. However, from a modeling perspective, before the benefits of such a strategy can be attained, we must first be able to quantitatively characterize the behavior of the model coefficients as well as the model predictions as a function of prediction horizon. We need to determine if the model coefficients reflect viable physiologic dependencies of the individual glycemic measurements and whether the model is stable with respect to small changes in noise levels, leading to accurate near-future predictions with negligible time lag. We assessed the behavior of linear autoregressive data-driven models developed under three possible modeling scenarios, using continuous glucose measurements of nine subjects collected on a minute-by-minute basis for approximately 5 days. Simulation results indicated that stable and accurate models for near-future glycemic predictions (< 60 min) with clinically acceptable time lags are attained only when the raw glucose measurements are smoothed and the model coefficients are regularized. This study provides a starting point for further needed investigations before real-time deployment can be considered. PMID:19272928

  19. 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. PMID:8051515

  20. Reduced cortical BACE1 content with one bout of exercise is accompanied by declines in AMPK, Akt, and MAPK signaling in obese, glucose-intolerant mice.

    PubMed

    MacPherson, R E K; Baumeister, P; Peppler, W T; Wright, D C; Little, J P

    2015-11-15

    Obesity and type 2 diabetes are significant risk factors in the development of neurodegenerative diseases, such as Alzheimer's disease. A variety of cellular mechanisms, such as altered Akt and AMPK and increased inflammatory signaling, contribute to neurodegeneration. Exercise training can improve markers of neurodegeneration, but the underlying mechanisms remain unknown. The purpose of this study was to determine the effects of a single bout of exercise on markers of neurodegeneration and inflammation in brains from mice fed a high-fat diet. Male C57BL/6 mice were fed a low (LFD; 10% kcal from lard)- or a high-fat diet (HFD; 60% kcal from lard) for 7 wk. HFD mice underwent an acute bout of exercise (treadmill running: 15 m/min, 5% incline, 120 min) followed by a recovery period of 2 h. The HFD increased body mass and glucose intolerance (both P < 0.05). This was accompanied by an approximately twofold increase in the phosphorylation of Akt, ERK, and GSK in the cortex (P < 0.05). Following exercise, there was a decrease in beta-site amyloid precursor protein cleaving enzyme 1 (BACE1; P < 0.05) and activity (P < 0.001). This was accompanied by a reduction in AMPK phosphorylation, indicative of a decline in cellular stress (P < 0.05). Akt and ERK phosphorylation were decreased following exercise in HFD mice to a level similar to that of the LFD mice (P < 0.05). This study demonstrates that a single bout of exercise can reduce BACE1 content and activity independent of changes in adiposity. This effect is associated with reductions in Akt, ERK, and AMPK signaling in the cortex. PMID:26404616

  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. PMID:26715083

  3. Deficiency of ACE2 in Bone-Marrow-Derived Cells Increases Expression of TNF-α in Adipose Stromal Cells and Augments Glucose Intolerance in Obese C57BL/6 Mice.

    PubMed

    Thatcher, Sean E; Gupte, Manisha; Hatch, Nicholas; Cassis, Lisa A

    2012-01-01

    Deficiency of ACE2 in macrophages has been suggested to promote the development of an inflammatory M1 macrophage phenotype. We evaluated effects of ACE2 deficiency in bone-marrow-derived stem cells on adipose inflammation and glucose tolerance in C57BL/6 mice fed a high fat (HF) diet. ACE2 activity was increased in the stromal vascular fraction (SVF) isolated from visceral, but not subcutaneous adipose tissue of HF-fed mice. Deficiency of ACE2 in bone marrow cells significantly increased mRNA abundance of F4/80 and TNF-α in the SVF isolated from visceral adipose tissue of HF-fed chimeric mice, supporting increased presence of inflammatory macrophages in adipose tissue. Moreover, deficiency of ACE2 in bone marrow cells modestly augmented glucose intolerance in HF-fed chimeric mice and increased blood levels of glycosylated hemoglobin. In summary, ACE2 deficiency in bone marrow cells promotes inflammation in adipose tissue and augments obesity-induced glucose intolerance. PMID:22518292

  4. Differentially regulated protein kinase A (PKA) activity in adipose tissue and liver is associated with resistance to diet-induced obesity and glucose intolerance in mice that lack PKA regulatory subunit type IIα.

    PubMed

    London, Edra; Nesterova, Maria; Sinaii, Ninet; Szarek, Eva; Chanturiya, Tatyana; Mastroyannis, Spyridon A; Gavrilova, Oksana; Stratakis, Constantine A

    2014-09-01

    The cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism in all organ systems affected by obesity. PKA has four regulatory (RIα, RIIα, RIβ, RIIβ) and four catalytic (Cα, Cβ, Cγ, Prkx) subunit isoforms that have tissue-specific expression profiles. In mice, knockout (KO) of RIIβ, the primary PKA regulatory subunit in adipose tissue or knockout of the catalytic subunit Cβ resulted in a lean phenotype that resists diet-induced obesity and associated metabolic complications. Here we report that the disruption of the ubiquitously expressed PKA RIIα subunit in mice (RIIαKO) confers resistance to diet-induced obesity, glucose intolerance, and hepatic steatosis. After 2-week high-fat diet exposure, RIIαKO mice weighed less than wild-type littermates. Over time this effect was more pronounced in female mice that were also leaner than their wild-type counterparts, regardless of the diet. Decreased intake of a high-fat diet contributed to the attenuated weight gain in RIIαKO mice. Additionally, RIIα deficiency caused differential regulation of PKA in key metabolic organs: cAMP-stimulated PKA activity was decreased in liver and increased in gonadal adipose tissue. We conclude that RIIα represents a potential target for therapeutic interventions in obesity, glucose intolerance, and nonalcoholic fatty liver disease. PMID:24914943

  5. In utero growth restriction and catch-up adipogenesis after developmental di (2-ethylhexyl) phthalate exposure cause glucose intolerance in adult male rats following a high-fat dietary challenge.

    PubMed

    Strakovsky, Rita S; Lezmi, Stéphane; Shkoda, Ielyzaveta; Flaws, Jodi A; Helferich, William G; Pan, Yuan-Xiang

    2015-11-01

    Phthalates impact adipocyte morphology in vitro, but the sex-specific adipogenic signature immediately after perinatal di(2-ethylhexyl) phthalate (DEHP) exposure and adulthood physiology following a high-fat (HF) dietary challenge are unknown. In the current study, pregnant and lactating dams received DEHP (300 mg/kg body weight) or oil. At weaning [postnatal day (PND) 21], adipose tissue was sampled for real-time polymerase chain reaction. The remaining offspring consumed a control or HF diet. DEHP decreased % fat in males at birth from 13.9%±0.2 to 11.8%±0.6 (mean±S.E.M.), representing a 15.1% decrease in fat by DEHP, and these males caught up in adiposity to controls by PND21. Adult DEHP-exposed males had a 27.5% increase in fat (12.5%±0.9% in controls vs. 15.9%±1.5% in the DEHP group); adipocyte perimeter was increased as well, with fewer small/medium-sized adipocytes, and decreased cell number compared to oil controls. HF diet intake in DEHP-exposed males further increased male energy intake and body weight and led to glucose intolerance. In PND21 males, DEHP increased the expression of adipogenic markers (Pparg1, Cebpa, Adipoq, Ppard, Fabp4, Fasn, Igf1), decreased Lep, and decreased markers of mesenchymal stem cell commitment to the adipogenic lineage (Bmp2, Bmp4, Stat1, Stat5a) compared to oil controls. These data suggest that DEHP may decrease the adipocyte pool at birth, which initially increases adaptive adipocyte maturation and lipid accumulation, but leads to adipose tissue dysfunction in adulthood, decreasing the capacity to adapt to a HF diet, and leading to systemic glucose intolerance. PMID:26188368

  6. 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

  7. 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

  8. 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

  9. 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. PMID:27143556

  10. Glucan-rich polysaccharides from Pleurotus sajor-caju (Fr.) Singer prevents glucose intolerance, insulin resistance and inflammation in C57BL/6J mice fed a high-fat diet

    PubMed Central

    2012-01-01

    Background Pleurotus sajor-caju (P. sajor-caju) has been extremely useful in the prevention of diabetes mellitus due to its low fat and high soluble fiber content for thousands of years. Insulin resistance is a key component in the development of diabetes mellitus which is caused by inflammation. In this study, we aimed to investigate the in vivo efficacy of glucan-rich polysaccharide of P. sajor-caju (GE) against diabetes mellitus and inflammation in C57BL/6J mice fed a high-fat diet. Methods Diabetes was induced in C57BL/6J mice by feeding a high-fat diet. The mice were randomly assigned to 7 groups (n=6 per group). The control groups in this study were ND (for normal diet) and HFD (for high-fat diet). The treated groups were ND240 (for normal diet) (240 mg/kg b.w) and HFD60, HFD120 and HFD240 (for high-fat), where the mice were administrated with three dosages of GE (60, 120, 240 mg GE/kg b.w respectively). Metformin (2 mg/kg b.w) served as positive control. The glucose tolerance test, glucose and insulin levels were measured at the end of 16 weeks. Expressions of genes for inflammatory markers, GLUT-4 and adiponectin in the adipose tissue of the mice were assessed. One-way ANOVA and Duncan’s multiple range tests (DMRT) were used to determine the significant differences between groups. Results GE treated groups improved the glucose tolerance, attenuated hyperglycemia and hyperinsulinemia in the mice by up-regulating the adiponectin and GLUT-4 gene expressions. The mice in GE treated groups did not develop insulin resistance. GE also down-regulated the expression of inflammatory markers (IL-6, TNF-α, SAA2, CRP and MCP-1) via attenuation of nuclear transcription factors (NF-κB). Conclusion Glucan-rich polysaccharide of P. sajor-caju can serve as a potential agent for prevention of glucose intolerance, insulin resistance and inflammation. PMID:23259700

  11. Elevated IgG levels against specific bacterial antigens in obese patients with diabetes and in mice with diet-induced obesity and glucose intolerance.

    PubMed

    Mohammed, Nadeem; Tang, Lihua; Jahangiri, Anisa; de Villiers, Willem; Eckhardt, Erik

    2012-09-01

    High fat diets increase the risk for insulin resistance by promoting inflammation. The cause of inflammation is unclear, but germfree mouse studies have implicated commensal gut bacteria. We tested whether diet-induced obesity, diabetes, and inflammation are associated with anti-bacterial IgG. Blood from lean and obese healthy volunteers or obese patients with diabetes were analyzed by ELISA for IgG against extracts of potentially pathogenic and pro-biotic strains of Escherichia coli (LF-82 and Nissle), Bacteroides thetaiotaomicron, and Lactobacillus acidophilus, and for circulating tumor necrosis factor α (TNFα). C57Bl/6 mice were fed low- or high-fat diets (10% or 60% kcal from fat) for 10 weeks and tested for anti-bacterial IgG, bodyweight, fasting glucose, and inflammation. Obese diabetic patients had significantly more IgG against extracts of E. coli LF-82 compared with lean controls, whereas IgG against extracts of the other bacteria was unchanged. Circulating TNFα was elevated and correlated with IgG against the LF-82 extract. Mice fed high-fat diets had increased fasting glucose levels, elevated TNFα and neutrophils, and significantly more IgG against the LF-82 extracts. Diabetes in obesity is characterized by increased IgG against specific bacterial antigens. Specific commensal bacteria may mediate inflammatory effects of high-fat diets. PMID:22424821

  12. Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate.

    PubMed

    Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; Lippi, Cristina; Casale, Raffaele; Properzi, Giuliana; Blumberg, Jeffrey B; Ferri, Claudio

    2008-09-01

    Flavanols from chocolate appear to increase nitric oxide bioavailability, protect vascular endothelium, and decrease cardiovascular disease (CVD) risk factors. We sought to test the effect of flavanol-rich dark chocolate (FRDC) on endothelial function, insulin sensitivity, beta-cell function, and blood pressure (BP) in hypertensive patients with impaired glucose tolerance (IGT). After a run-in phase, 19 hypertensives with IGT (11 males, 8 females; 44.8 +/- 8.0 y) were randomized to receive isocalorically either FRDC or flavanol-free white chocolate (FFWC) at 100 g/d for 15 d. After a wash-out period, patients were switched to the other treatment. Clinical and 24-h ambulatory BP was determined by sphygmometry and oscillometry, respectively, flow-mediated dilation (FMD), oral glucose tolerance test, serum cholesterol and C-reactive protein, and plasma homocysteine were evaluated after each treatment phase. FRDC but not FFWC ingestion decreased insulin resistance (homeostasis model assessment of insulin resistance; P < 0.0001) and increased insulin sensitivity (quantitative insulin sensitivity check index, insulin sensitivity index (ISI), ISI(0); P < 0.05) and beta-cell function (corrected insulin response CIR(120); P = 0.035). Systolic (S) and diastolic (D) BP decreased (P < 0.0001) after FRDC (SBP, -3.82 +/- 2.40 mm Hg; DBP, -3.92 +/- 1.98 mm Hg; 24-h SBP, -4.52 +/- 3.94 mm Hg; 24-h DBP, -4.17 +/- 3.29 mm Hg) but not after FFWC. Further, FRDC increased FMD (P < 0.0001) and decreased total cholesterol (-6.5%; P < 0.0001), and LDL cholesterol (-7.5%; P < 0.0001). Changes in insulin sensitivity (Delta ISI - Delta FMD: r = 0.510, P = 0.001; Delta QUICKI - Delta FMD: r = 0.502, P = 0.001) and beta-cell function (Delta CIR(120) - Delta FMD: r = 0.400, P = 0.012) were directly correlated with increases in FMD and inversely correlated with decreases in BP (Delta ISI - Delta 24-h SBP: r = -0.368, P = 0.022; Delta ISI - Delta 24-h DBP r = -0.384, P = 0.017). Thus, FRDC

  13. 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 ...

  14. CYP1B1 deficiency ameliorates obesity and glucose intolerance induced by high fat diet in adult C57BL/6J mice.

    PubMed

    Liu, Xiaocong; Huang, Tingting; Li, Lu; Tang, Yumeng; Tian, Yatao; Wang, Suqing; Fan, Cuifang

    2015-01-01

    Cytochrome P450 1B1 (CYP1B1) expression increases in multi-potential mesenchymal stromal cells C3H10T1/2 during adipogenesis, which parallel with PPARγ, a critical transcriptional factor in adipogenic process. To assess the role of CYP1B1 in fatty acid metabolism, adult C57BL/6J wild-type and CYP1B1 deficiency mice were fed with high fat diets (HFD) for 6 weeks. CYP1B1 deficiency attenuated HFD-induced obesity when compared with their wild type counterparts, and improve glucose tolerance. The reduction in body weight gain and white adipose tissue in CYP1B1 deficient mice exhibited coordinate decreases in fatty acid synthesis (PPARγ, CD36, FAS, SCD-1) and increases in fatty acid oxidation (UCP-2, CPT-1a) when compared with wild type ones. Lower hepatocyte TG contents were consistent with hepatic Oil-Red-O staining in the CYP1B1 deficiency mice. AMPK, a nutrient sensors for energy homeostasis, was activated in both fat pad and liver by CYP1B1 deficiency. However, in vitro system, knock down CYP1B1 in C3H10T1/2 cells does not abolish adipogenesis induced by adipogenic agents IDM (Insulin, Dexamethasone, Methylisobutylxanthine). Our in vivo and in vitro findings of CYP1B1 deficiency in fat metabolism suggest a complex regulation network between CYP1B1 and energy homeostasis. PMID:26064443

  15. 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

  16. Prediction of blood glucose using interstitial fluid extracted by ultrasound and vacuum

    NASA Astrophysics Data System (ADS)

    Li, Dachao; Yu, Haixia; Huang, Xian; Huang, Fuxiang; Hu, Xiaotang; Xu, Kexin

    2007-02-01

    Prediction of blood glucose using interstitial fluid extracted by ultrasound and vacuum is proposed by the paper. Low-frequency ultrasound with 55 KHz is applied for about 30 seconds to enhance the skin permeability to interstitial fluid by disrupting the stratum corneum lipid bilayers and then interstitial fluid is extracted out of skin successfully by 10in.Hg vacuum for 15 minutes. The glucose concentration in the interstitial fluid is measured by an instrument with immobilized enzyme sensor. And then a method of data analysis is set up to prediction the glucose concentration in the blood by the measurement of the glucose concentration in the interstitial fluid. At last, Clarke Error Grid analysis is performed to assess if the prediction accuracy could satisfy the requirements of clinical application. The whole method and experimental system above is set up in the article and the feasibility of this way for blood glucose detecting is primarily validated for clinical application with the requirements of bloodless, painless, continuous glucose monitoring. Additional a prototype of miniature diabetes monitoring device with the technique of surface plasma resonance to measure the glucose concentration in the interstitial fluid is also being developed.

  17. 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

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

    PubMed

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

    2015-09-01

    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

  19. 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

  20. Blood glucose may be an alternative to cholesterol in CVD risk prediction charts

    PubMed Central

    2013-01-01

    Background Established risk models for the prediction of cardiovascular disease (CVD) include blood pressure, smoking and cholesterol parameters. The use of total cholesterol for CVD risk prediction has been questioned, particularly for primary prevention. We evaluated whether glucose could be used instead of total cholesterol for prediction of fatal CVD using data with long follow-up. Methods We followed-up 6,095 men and women aged ≥16 years who participated 1977-79 in a community based health study and were anonymously linked with the Swiss National Cohort until the end of 2008. During follow-up, 727 participants died of CVD. Based on the ESC SCORE methodology (Weibull regression), we used age, sex, blood pressure, smoking, and fasting glucose or total cholesterol. The mean Brier score (BS), area under the receiver-operating characteristic curve (AUC) and integrated discrimination improvement (IDI) were used for model comparison. We validated our models internally using cross-validation and externally using another data set. Results In our models, the p-value of total cholesterol was 0.046, that of glucose was p < 0.001. The model with glucose had a slightly better predictive capacity (BS: 2216x10-5 vs. 2232x10-5; AUC: 0.9181 vs. 0.9169, IDI: 0.009 with p-value 0.026) and could well discriminate the overall risk of persons with high and low concentrations. The external validation confirmed these findings. Conclusions Our study suggests that instead of total cholesterol glucose can be used in models predicting overall CVD mortality risk. PMID:23351551

  1. [Nutrition and gastrointestinal intolerance].

    PubMed

    Madl, C; Holzinger, U

    2013-06-01

    The functional integrity of the gastrointestinal tract is an essential prerequisite in intensive care patients for the sufficient administration of enteral nutrition. Up to 65% of patients in intensive care units develop symptoms of gastrointestinal dysfunction with high residual gastric volume, vomiting and abdominal distension. The pathophysiological alterations of gastrointestinal intolerance and the subsequent effect on the tolerance of enteral nutrition can affect the whole gastrointestinal tract. Gastroduodenal motility disorders in particular, with increased gastroesophageal reflux lead to intolerance. In more than 90% of intensive care patients with gastrointestinal motility disorders an adequate postpyloric enteral nutrition can be carried out using a jejunal tube. In addition to improved tolerance of enteral nutrition this leads to a reduction of gastroesophageal reflux and the incidence of ventilation-associated pneumonia. Apart from the possibility of endoscopic application of the jejunal tube, alternative techniques were developed which allow a faster positioning of the jejunal tube with less complications. Furthermore, there are therapeutic options for improvement of gastrointestinal motility disorders and apart from general measures, also medicinal options for treatment of gastrointestinal intolerance which allow a sufficient enteral nutrition for intensive care patients. PMID:23740106

  2. 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

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

    PubMed Central

    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

  4. 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

  5. Fasting glucose levels within the high normal range predict cardiovascular outcome

    PubMed Central

    Shaye, Kivity; Amir, Tirosh; Shlomo, Segev; Yechezkel, Sidi

    2016-01-01

    Background Diabetes mellitus and impaired glucose metabolism are associated with increased risk for cardiovascular disease (CVD). However, it is still not clear whether glucose levels can predict CVD risk among patients without diabetes. The primary aim of this study is to assess whether normoglycemic fasting plasma glucose (FPG) is associated with increased risk of CVD outcomes in healthy patients. Methods We obtained blood measurements, data from physical examination, and medical and lifestyle information from 10,913 men and women who were evaluated in the Institute for Preventive Medicine of Sheba Medical Center. Enrolled were participants with FPG <100 mg/dL as well as 100 to 125 mg/dL, who were free of diagnosis of CVD. The participants were actively screened for coronary disease using a stress test. Primary end points were coronary heart disease or self-reported cerebral vascular disease. Results A total of 1,119 incident cases of CVD occurred during a mean follow-up of 4.3 years. Subjects with fasting glucose levels in the high normal range (95–99 mg/dL) had an increased CVD risk when compared with levels <80 mg/dL, (HR 1.53;CI 95% [1.22–1.91], P < .001). A multivariate model, adjusted for age, sex, family history of CVD, blood pressure, body mass index, smoking status, pharmacologic treatment, serum triglycerides, and high-density lipoprotein and low-density lipoprotein cholesterol levels, revealed an independent increased risk of CVD with rising FPG levels in the normal range. Conclusion Elevated CVD risk is strongly and independently associated with glucose levels within the normoglycemic range. Fasting plasma glucose may help in identifying apparently healthy persons with early metabolic abnormalities who are at increased risk for CVD before progression to prediabetes and overt diabetes mellitus. PMID:22795290

  6. [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

  7. 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

  8. Predictability of 1-h postload plasma glucose concentration: A 10-year retrospective cohort study

    PubMed Central

    Kuang, Lifen; Huang, Zhimin; Hong, Zhenzhen; Chen, Ailing; Li, Yanbing

    2015-01-01

    Aims/Introduction Elevated 1-h postload plasma glucose concentration (1hPG) during oral glucose tolerance test has been linked to an increased risk of type 2 diabetes and a poorer cardiometabolic risk profile. The present study analyzed the predictability and cut-off point of 1hPG in predicting type 2 diabetes in normal glucose regulation (NGR) subjects, and evaluated the long-term prognosis of NGR subjects with elevated 1hPG in glucose metabolism, kidney function, metabolic states and atherosclerosis. Materials and Methods A total of 116 Han Chinese classified as NGR in 2002 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China, were investigated. Follow-up was carried out in 2012 to evaluate the progression of glucose metabolism, kidney function, metabolic syndrome and carotid atherosclerosis. Results The areas under receiver operating characteristic curves were higher for 1hPG than FPG or 2hPG (0.858 vs 0.806 vs 0.746). The cut-off value of 1hPG with the maximal sum of sensitivity and specificity in predicting type 2 diabetes in NGR subjects was 8.85 mmol/L. The accumulative incidence of type 2 diabetes in subjects with 1hPG ≥8.85 mmol/L was higher than those <8.85 mmol/L (46.2% vs 3.3%, P = 0.000; relative risk 13.846, 95% confidence interval 4.223–45.400). On follow up, the prevalence of metabolic syndrome and abnormal carotid intima-media thickness in the subjects with 1hPG ≥8.85 mmol/L tended to be higher compared with those <8.85 mmol/L. Conclusions 1hPG is a good predictor of type 2 diabetes in NGR subjects, and the best cut-off point is 8.85 mmol/L. Some tendency indicates that NGR subjects with 1hPG ≥8.85 mmol/L are more prone to metabolic syndrome and carotid atherosclerosis. PMID:26543538

  9. [Orthostatic intolerance syndromes].

    PubMed

    Gónzalez-Hermosillo, J A

    2001-01-01

    In patients with an orthostatic intolerance, the hemodynamic response to standing, may identify an abnormality know as postural orthostatic tachycardia syndrome or orthostatic hypotension, that can often be treated without further testing. When the response to standing is normal, tilt-table testing may be useful in making the diagnosis of vasovagal syncope or postural orthostatic tachycardia syndrome and guiding treatment. In evaluating the results of tilt-table testing, an important consideration is the distinction between vasovagal syncope, and the dysautonomic response to tilt characterized by a gradual and progressive decrease in blood pressure that leads to syncope. Current practice patterns suggest that beta blockers, fludrocortisone, and midodrine are commonly used to treat patients with vasovagal syncope. These also suggest that patients with the postural orthostatic tachycardia syndrome, and with the dysautonomic response, are better treated with fludrocortisone and midodrine. PMID:11565347

  10. Comparative assessment of glucose prediction models for patients with type 1 diabetes mellitus applying sensors for glucose and physical activity monitoring.

    PubMed

    Zarkogianni, K; Mitsis, K; Litsa, E; Arredondo, M-T; Ficο, G; Fioravanti, A; Nikita, K S

    2015-12-01

    The present work presents the comparative assessment of four glucose prediction models for patients with type 1 diabetes mellitus (T1DM) using data from sensors monitoring blood glucose concentration. The four models are based on a feedforward neural network (FNN), a self-organizing map (SOM), a neuro-fuzzy network with wavelets as activation functions (WFNN), and a linear regression model (LRM), respectively. For the development and evaluation of the models, data from 10 patients with T1DM for a 6-day observation period have been used. The models' predictive performance is evaluated considering a 30-, 60- and 120-min prediction horizon, using both mathematical and clinical criteria. Furthermore, the addition of input data from sensors monitoring physical activity is considered and its effect on the models' predictive performance is investigated. The continuous glucose-error grid analysis indicates that the models' predictive performance benefits mainly in the hypoglycemic range when additional information related to physical activity is fed into the models. The obtained results demonstrate the superiority of SOM over FNN, WFNN, and LRM with SOM leading to better predictive performance in terms of both mathematical and clinical evaluation criteria. PMID:26049412

  11. Intolerance of uncertainty in body dysmorphic disorder.

    PubMed

    Summers, Berta J; Matheny, Natalie L; Sarawgi, Shivali; Cougle, Jesse R

    2016-03-01

    Intolerance of uncertainty (IU) is a transdiagnostic construct associated with several anxiety and related disorders. Three studies were conducted to explore the potential relationship between IU and body dysmorphic disorder (BDD). Study 1 revealed a positive relationship between IU and BDD symptoms above symptoms of anxiety and depression in an unselected student sample (N=88). Study 2 demonstrated a similar relationship between IU and BDD symptoms above negative affectivity and intolerance of ambiguity in a community sample (N=116). Study 3 found that a clinical BDD sample (N=23) reported greater IU than healthy controls (N=20), though this relationship was accounted for by symptoms of anxiety and depression. Greater IU predicted functional impairment in the clinical sample above BDD symptoms and past-week anxiety and depression. The observed relationship between IU and BDD symptoms provides preliminary support for the relevance of IU to this population. PMID:26688272

  12. 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

  13. 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 ...

  14. 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

  15. 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

  16. Gluten intolerance (coeliac disease).

    PubMed

    Ferguson, A; Ziegler, K; Strobel, S

    1984-12-01

    Coeliac disease is a permanent condition of gluten intolerance associated with characteristic gluten-sensitive changes in the jejunal mucosa. In Edinburgh and the Lothians Region of Scotland, the prevalence of the disease is one in 1637 (61/100,000) with considerable variation in age, and sex-specific prevalence and incidence. Several lines of evidence indicate an immunologic basis for the gluten-sensitive enteropathy in coeliac disease. Animal models of intestinal T cell-mediated reactions in the gut have shown pathologic features similar to those of coeliac disease. These include changes in villus and crypt architecture with crypt hyperplasia, and increased numbers of intraepithelial lymphocytes and of intraepithelial lymphocyte mitosis. Experimental CMI reactions also influence differentiation of goblet cells and expression of Ia antigen on epithelial cells, but these factors have not yet been reported for the coeliac mucosa. In addition to this circumstantial evidence, based on animal work, other factors which suggest that CMI reactions rather than antibodies are relevant to coeliac disease include the findings of antigliadin antibodies in a proportion of normal individuals, patients without gastrointestinal disease (seen in hospital), and patients with jejunal Crohn's disease. In addition, there is a well documented patient with adult onset primary hypogammaglobulinaemia and coeliac disease. The underlying pathogenesis in coeliac disease can be envisaged as failure of the normal inhibition of immune responses to this particular food antigen in the gut. Manipulation of immunoregulatory mechanisms would provide a new approach to treatment or cure of this disease and of other food protein-sensitive enteropathies. PMID:6391293

  17. 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…

  18. [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. PMID:23224632

  19. 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

    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; Rutter, Guy A

    2016-08-01

    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 Vps13c(fl/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 Ca(2+) were significantly increased in islets from female KO mice, suggesting impaired Ca(2+) 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

  20. 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

  1. Overlap in prevalence between various types of environmental intolerance.

    PubMed

    Palmquist, Eva; Claeson, Anna-Sara; Neely, Gregory; Stenberg, Berndt; Nordin, Steven

    2014-01-01

    Environmental intolerance (EI) is characterized by attribution of several, multisystem symptoms to specific environmental exposures, such as exposure to odorous/pungent chemicals, certain buildings, electromagnetic fields (EMFs) and everyday sounds. The symptoms are medically unexplained, non-specific and the symptoms overlap between different types of EI. To approach the issue of underlying mechanisms the matter of overlap in prevalence between intolerances can provide valuable information. The aim of the study was to examine if the overlap between intolerance to odorous/pungent chemicals, certain buildings, EMFs and sounds is larger than the expected overlap if no association would exist between them. The study was using cross-sectional data from the Västerbotten Environmental Health Study in Sweden; a large questionnaire-based survey. 8520 adults (18-79 years) were randomly selected after stratification for age and sex, of whom 3406 (40%) participated. Individuals with the four types of intolerance were identified either through self-report, or by having been physician-diagnosed with a specific EI. The overlaps between the four EIs were greater than predictions based on coincidence for both self-reported and diagnosed cases (except for the overlap between diagnosed intolerance to sounds and EMFs). The results raise the question whether different types of EI share similar underlying mechanisms, or at least that the sufferers of EI share some predisposition to acquire the conditions. PMID:24029726

  2. Sodium Oxybate Intolerance Associated with Familial Serum Acylcarnitine Elevation

    PubMed Central

    Berner, Jon

    2013-01-01

    Our case describes clinical features of two families defined by joint phenotypes: sodium oxybate intolerance and elevated serum acylcarnitines. Oxybate intolerance variably presents as either cervical dystonia or sleep-related eating disorder. Our objective is to identify biological markers which predict a poor response to sodium oxybate as a treatment for disturbed sleep. Familial inheritance pattern, genotype analysis, multiorgan system involvement, and response to treatment suggest the presence of a secondary cause of fatty oxidation defect, i.e., mitochondrial disorder. Our case report supports the possible conclusion that variance in human mitochondrial metabolism may affect sodium oxybate tolerability. Citation: Berner J. Sodium oxybate intolerance associated with familial serum acylcarnitine elevation. J Clin Sleep Med 2013;9(1):71-72. PMID:23319908

  3. Glucose Variability Assessed by Low Blood Glucose Index Is Predictive of Hypoglycemic Events in Patients With Type 1 Diabetes Switched to Pump Therapy

    PubMed Central

    Crenier, Laurent; Abou-Elias, Charlotte; Corvilain, Bernard

    2013-01-01

    OBJECTIVE To determine whether subgroups of type 1 diabetic patients with different glucose variability indices respond differently to continuous subcutaneous insulin infusion (CSII) in terms of reduced hypoglycemic events. RESEARCH DESIGN AND METHODS We studied 50 adults with long-standing type 1 diabetes switched to CSII because of persistently high A1C or frequent hypoglycemia despite well-managed intensive basal-bolus therapy. We compared A1C, hypoglycemic events, and glucose variability from self-monitoring of blood glucose profiles at baseline and after 6 months of CSII. Regression analysis was performed to identify predictors of response. RESULTS In multivariate analysis, baseline low blood glucose index (LBGI) was the best independent predictor of hypoglycemia outcome on CSII (R2 = 0.195, P = 0.0013). An ROC curve analysis demonstrated a sensitivity of 70.8% (95% CI 48.9–87.4) and specificity of 73.1% (52.2–88.4) by using the LBGI cutoff of 3.34 as predictor of reduction of hypoglycemia on CSII. By grouping patients by LBGI tertiles, we found a 23.3% reduction in hypoglycemic events (<60 mg/dL [3.3 mmol/L]) in the third tertile (range 4.18–9.34) without change in A1C (P < 0.05). Conversely, the first tertile (range 0.62–2.05) demonstrated the greatest A1C reduction, −0.99% (P = 0.00001), but with increasing hypoglycemia. CONCLUSIONS Baseline LBGI predicts the outcome of type 1 diabetic patients who switch to CSII in terms of hypoglycemia. PMID:23404296

  4. 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

  5. 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

  6. 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%…

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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. PMID:26242570

  12. Food intolerance and Crohn's disease.

    PubMed Central

    Pearson, M; Teahon, K; Levi, A J; Bjarnason, I

    1993-01-01

    It has been claimed that prolonged remissions of Crohn's disease can be achieved after enteral or parenteral nutrition, by identifying and excluding foods that exacerbate a patient's symptoms. The occurrence of food intolerances were assessed after induction of remission with elemental diet in 42 eligible patients to whom single foods were introduced over five days. Suspect foods were reinvestigated with open and if possible, double blind rechallenge. Fourteen patients (33%) dropped out of the study because of relapse of disease unrelated to food (n = 8) or because of difficulties in complying with the regimen (n = 6). Twenty (48%) of the patients identified food sensitivities whereas eight (19%) did not. Seventeen of the patients who identified food sensitivities had an open rechallenge with recurrence of symptoms in 10 (24% of total). Food sensitivity was confirmed in three patients on double blind challenge. There was no significant difference in the duration of remission between patients who did or did not identify food sensitivities. During the study three cases of intolerance to the formula diet, and one of severe salicylate sensitivity were encountered. In conclusion food sensitivities are evident after treatment of Crohn's disease with elemental diet but are variable, often do not persist, and are of insufficient importance to warrant putting all patients through elimination diets. PMID:8314511

  13. Development and validation of a predictive model of acute glucose response to exercise in individuals with type 2 diabetes

    PubMed Central

    2013-01-01

    Background Our purpose was to develop and test a predictive model of the acute glucose response to exercise in individuals with type 2 diabetes. Design and methods Data from three previous exercise studies (56 subjects, 488 exercise sessions) were combined and used as a development dataset. A mixed-effects Least Absolute Shrinkage Selection Operator (LASSO) was used to select predictors among 12 potential predictors. Tests of the relative importance of each predictor were conducted using the Lindemann Merenda and Gold (LMG) algorithm. Model structure was tested using likelihood ratio tests. Model accuracy in the development dataset was assessed by leave-one-out cross-validation. Prospectively captured data (47 individuals, 436 sessions) was used as a test dataset. Model accuracy was calculated as the percentage of predictions within measurement error. Overall model utility was assessed as the number of subjects with ≤1 model error after the third exercise session. Model accuracy across individuals was assessed graphically. In a post-hoc analysis, a mixed-effects logistic regression tested the association of individuals’ attributes with model error. Results Minutes since eating, a non-linear transformation of minutes since eating, post-prandial state, hemoglobin A1c, sulfonylurea status, age, and exercise session number were identified as novel predictors. Minutes since eating, its transformations, and hemoglobin A1c combined to account for 19.6% of the variance in glucose response. Sulfonylurea status, age, and exercise session each accounted for <1.0% of the variance. In the development dataset, a model with random slopes for pre-exercise glucose improved fit over a model with random intercepts only (likelihood ratio 34.5, p < 0.001). Cross-validated model accuracy was 83.3%. In the test dataset, overall accuracy was 80.2%. The model was more accurate in pre-prandial than postprandial exercise (83.6% vs. 74.5% accuracy respectively). 31/47 subjects had

  14. 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…

  15. 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

  16. 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.

  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. One-hour versus two-hour postprandial blood glucose measurement in women with gestational diabetes mellitus: which is more predictive?

    PubMed

    Ozgu-Erdinc, A Seval; Iskender, Cantekin; Uygur, Dilek; Oksuzoglu, Aysegul; Seckin, K Doga; Yeral, M Ilkin; Kalaylioglu, Zeynep I; Yucel, Aykan; Danisman, A Nuri

    2016-06-01

    The purpose of this study is to investigate postprandial 1-h (PP1) and 2-h (PP2) blood glucose measurements' correlation with adverse perinatal outcomes. This prospective cohort study consisted of 259 women with gestational diabetes mellitus. During each antenatal visit, HbA1c and fasting plasma glucose (FPG) as well as plasma glucose at PP1 and PP2 were analyzed. There were 144 patients on insulin therapy and 115 patients on diet therapy. A total of 531 blood glucose measurements were obtained at different gestational ages between 24 and 41 gestational weeks. PP2 plasma glucose measurements (but not PP1) were positively correlated with fetal macrosomia. But on adjusted analysis, neither PP1 nor PP2 measurements predicted perinatal complications. In addition to PP1 and PP2, neither FPG nor HbA1c were able to predict perinatal complications or fetal macrosomia when controlled for confounding factors except for a positive correlation between fetal macrosomia and HbA1c in patients on diet therapy. Postprandial 1-h and postprandial 2-h plasma glucose measurements were not superior to each other in predicting fetal macrosomia or perinatal complications. Based on our findings, it can be concluded that both methods may be suitable for follow-up as there are no clear advantages of one measurement over the other. PMID:26645814

  19. 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

  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. Osteoporosis in lysinuric protein intolerance.

    PubMed

    Parto, K; Penttinen, R; Paronen, I; Pelliniemi, L; Simell, O

    1993-01-01

    Lysinuric protein intolerance (LPI) is an autosomal recessive disease characterized by defective transport of cationic amino acids. Patients have an increased incidence of fractures and their skeletal radiographs show osteoporosis. The aim of the study was to characterize the osteopenia in LPI. Twenty-nine Finnish LPI patients (age range 3.7-44.4 years) were screened for parameters of bone metabolism. Morphometric analysis of bone was carried out in specimens of 9 patients. Collagen synthesis was studied with cultured skin fibroblasts (4 patients) and collagen fibril sizes (3 patients) were measured using electron microscopy. Most histological bone specimens (8/9) showed osteoporosis. Osteomalacia was excluded. Routine clinical laboratory tests were unrevealing. The concentrations of free hydroxyproline and type III procollagen N-propeptide in serum and the urinary excretion of hydroxyproline were increased in almost all patients during their growth and in about half of adult patients. Collagen synthesis in LPI fibroblast cultures was significantly decreased compared with that in age-matched controls at 5 (p < 0.01), 14 (p < 0.01) and still at 30 years (p < 0.01), whereas no difference was observed at the age of 44 years (p = N.S.). Osteoporosis in LPI might reflect defective matrix protein synthesis caused by protein deprivation and deficiency of cationic amino acids. Increased collagen turnover can also contribute to the osteoporosis. PMID:8412005

  2. 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

  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. [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

  5. Maternal 75-g OGTT glucose levels as predictive factors for large-for-gestational age newborns in women with gestational diabetes mellitus.

    PubMed

    Brankica, Krstevska; Valentina, Velkoska Nakova; Slagjana, Simeonova Krstevska; Sasha, Jovanovska Mishevska

    2016-02-01

    Objective Our goal was to investigate which glucose measurement from the 75-g oral glucose tolerance test (OGTT) has more capability of predicting large for-gestational-age (LGA) newborns of mothers with gestational diabetes mellitus (GDM). Subjects and methods The study group consisted of 118 consecutively pregnant women with singleton pregnancy, patients of Outpatients Department of the Endocrinology, Diabetes, and Metabolic Disorders Clinic. All were prospectively screened for GDM between 24th and 28th week of pregnancy and followed to delivery. Outcome measures included: patients' ages, pre-pregnancy BMI, BMI before delivery, FPG, 1 and 2 hour OGTT glucose values, haemoglobin A1c at third trimester, gestational week of delivery, mode of delivery and baby birth weight. Results From 118 pregnancies, 78 (66.1%) women were with GDM, and 40 (33.9%) without GDM. There were statistically significant differences (30.7 versus 5.0%, p < 0.01) between LGA newborns from GDM and control group, respectively. Gestation week of delivery and fasting glucose levels were independent predictors for LGA (Beta = 0.58 and Beta = 0.37 respectively, p < 0.01). Areas under the receiver operator characteristic curve (AUC) were compared for the prediction of LGA (0.782 (0.685-0.861) for fasting, 0.719 (0.607-0.815) for 1-hour and 0.51 (0.392-0.626) for 2-hour OGTT plasma glucose levels). Conclusion Fasting and 1-hour plasma glucose levels from OGTT may predict LGA babies in GDM pregnancies. PMID:26909480

  6. 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)

  7. 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

  8. 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

  9. [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

  10. 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…

  11. 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.

  12. 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

  13. Efficacy of 2-hour post glucose insulin levels in predicting insulin resistance in polycystic ovarian syndrome with infertility

    PubMed Central

    Saxena, Pikee; Prakash, Anupam; Nigam, Aruna

    2011-01-01

    BACKGROUND: Insulin resistance (IR) is central to the pathogenesis of polycystic ovarian syndrome (PCOS), but tests for determining IR are elaborate, tedious and expensive. AIMS: To evaluate if “2-hour post-glucose insulin level” is an effective indicator of IR and can aid in diagnosing IR in infertile PCOS women. SETTINGS AND DESIGN: Observational study at infertility clinic of a tertiary care center. MATERIALS AND METHODS: 50 infertile women with PCOS and 20 females with tubal/male factor infertility were evaluated for the presence of IR, as defined by the fasting/2-hour post-glucose insulin levels cutoffs of >25/>41 μU/mL, respectively. The clinical, metabolic and endocrinologic profile was determined in both the groups. STATISTICAL ANALYSIS: Statistical analysis was performed using SPSS (Chicago, IL, USA). RESULTS: Body mass index, post load glucose, insulin, glucose/insulin ratio, area under curve (AUC) of glucose and insulin and insulinogenic index were significantly lower in the controls as compared to the PCOS group. “2-hour post-glucose insulin levels” were elevated in 88% of PCOS individuals but were normal in all females not suffering from PCOS. These levels significantly correlated with AUC of glucose and insulin, and insulinogenic index and inversely correlated with 2-hour glucose to insulin ratio (r=0.827, 0.749 and –0.732, respectively). CONCLUSIONS: “2-hour post-glucose insulin levels” appears to be a good indicator of IR. It can be a useful tool, especially in low resource setting where a single sample can confirm the diagnosis, thus reducing cost and repeat visits. PMID:21772735

  14. [Family study of patients with aspirin intolerance and rhinosinusitis].

    PubMed

    May, A; Wagner, D; Langenbeck, U; Weber, A

    2000-09-01

    The high prevalence of aspirin intolerance in asthmatics and patients with nasal polyps as well as reports of familial clustering suggest a genetic disposition of this disease. Our study aimed at obtaining further evidence of hereditary factors in this disease. We included 33 unselected patients from 28 families with aspirin intolerance and rhinosinusitis in this study. Controls were recruited from individuals treated in our ENT clinic for diseases other than aspirin intolerance (n = 52). A questionnaire focused on family histories as well as reports on diseases of the upper respiratory tract or allergies. ASS intolerance was verified either by bronchial or nasal provocation tests. We found cases of aspirin intolerance among parents, siblings, and children of ASS intolerant probands. The children of probands had nasal polyps and rhinosinusitis more often than the children of controls. We propose that ASS intolerance with nasal polyps and asthma represents a complex phenotype, with genetic and environmental factors contributing to its manifestation. PMID:11056852

  15. 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

  16. [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

  17. The Predictive Effects of Early Pregnancy Lipid Profiles and Fasting Glucose on the Risk of Gestational Diabetes Mellitus Stratified by Body Mass Index

    PubMed Central

    Wang, Chen; Zhu, Weiwei; Wei, Yumei; Su, Rina; Feng, Hui; Lin, Li; Yang, Huixia

    2016-01-01

    This study aimed at evaluating the predictive effects of early pregnancy lipid profiles and fasting glucose on the risk of gestational diabetes mellitus (GDM) in patients stratified by prepregnancy body mass index (p-BMI) and to determine the optimal cut-off values of each indicator for different p-BMI ranges. A retrospective system cluster sampling survey was conducted in Beijing during 2013 and a total of 5,265 singleton pregnancies without prepregnancy diabetes were included. The information for each participant was collected individually using questionnaires and medical records. Logistic regression analysis and receiver operator characteristics analysis were used in the analysis. Outcomes showed that potential markers for the prediction of GDM include early pregnancy lipid profiles (cholesterol, triacylglycerols, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratios [LDL-C/HDL-C], and triglyceride to high-density lipoprotein cholesterol ratios [TG/HDL-C]) and fasting glucose, of which fasting glucose level was the most accurate indicator. Furthermore, the predictive effects and cut-off values for these factors varied according to p-BMI. Thus, p-BMI should be a consideration for the risk assessment of pregnant patients for GDM development. PMID:26981541

  18. 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.

  19. Orthostatic intolerance: a disorder of young women.

    PubMed

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

    2000-04-01

    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. PMID:10758621

  20. 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

  1. 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

  2. Exertional rhabdomyolysis and exercise intolerance revealing dystrophinopathies.

    PubMed

    Figarella-Branger, D; Baeta Machado, A M; Putzu, G A; Malzac, P; Voelckel, M A; Pellissier, J F

    1997-07-01

    Exercise intolerance associated with myalgias, muscle cramps or myoglobinuria may be associated with a dystrophinopathy. A search for abnormal dystrophin expression (using immunohistochemistry, immunoblot and DNA analysis) was carried out in a series of 15 patients. They were selected because they presented exercise intolerance, negative biochemical tests (lipid, glycogen and mitochondrial metabolism) and abnormal immunohistochemistry with at least one anti-dystrophin antibody (anti-Dys 1, rod domain; anti-Dys 2, C terminus; anti-Dys 3, N terminus). Lack of anti-Dys 1 immunoreactivity was seen in three patients and abnormal immunoreactivity with all three anti-dystrophin antibodies in two. Immunoblot confirmed the dystrophinopathy in these five patients only, and multiplex polymerase chain reaction DNA analysis revealed a deletion in the dystrophin gene in two of these patients, affecting the proximal part of the rod domain in one and the distal part of this domain in the other. The clinical, biological and histopathological features of the five patients reported here, together with the previous cases reported in the literature, are described and reveal that exercise intolerance associated with dystrophinopathy displays characteristic clinical, biological and immunohistochemical features and defines a new dystrophinopathy phenotype. The absence of staining in the rod domain provides a secure diagnosis of this syndrome. Dystrophinopathy is one etiology of idiopathic myoglobinuria, requiring genetic counseling. PMID:9224530

  3. Food intolerance and allergy--a review.

    PubMed

    Lessof, M H

    1983-01-01

    Specific food intolerance needs to be distinguished from obsessional states in which those who are affected have an aversion to numerous foods. Even in cases where specific food intolerance can be demonstrated, the diagnosis of food allergy depends on additional evidence that the patient's reaction is based on an abnormal immunological response. In food allergy, skin and laboratory tests may detect the presence of an IgE-mediated reaction, particularly in patients with asthma or eczema and especially where the foods involved are highly allergenic--such as egg, fish, nuts and milk. However, many patients with proven food intolerance have negative tests, suggesting that other immunological or non-immunological mechanisms are responsible. Laboratory tests for non-IgE reactions are unreliable. Where it is difficult to show a connection between individual foods and an allergic response--as in patients with urticaria provoked by food additives--one of the reasons for diagnostic difficulty is that the offending substances may be present in a wide range of common foods. If the diagnosis is to be firmly established in such cases, it is necessary to show that symptoms remit on an elimination diet and recur after a placebo-controlled challenge. PMID:6351151

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

    PubMed

    Prester, Ljerka

    2016-04-01

    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. PMID:26252073

  5. 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.

  6. Fasting plasma glucose 6–12 weeks after starting insulin glargine predicts likelihood of treatment success: a pooled analysis

    PubMed Central

    Karl, D; Zhou, R; Vlajnic, A; Riddle, M

    2012-01-01

    Aims To evaluate whether fasting plasma glucose values measured early during insulin therapy can identify patients with Type 2 diabetes who may not achieve adequate glycaemic control after 6 months and will require additional treatment. Methods Patient-level data from seven prospective, randomized, controlled studies using treat-to-target methods were pooled to evaluate the efficacy of insulin glargine. Fasting plasma glucose was measured at baseline, week 6 or 8 (6/8) and week 12. HbA1c was measured at week 24 to assess glycaemic control. Results One thousand and thirty-six patients (56% male, 81% white) were included in the analysis (mean age 56.3 years; duration of diabetes 8.4 years). Baseline mean fasting plasma glucose was 11.2 mmol/l and mean HbA1c was 73 mmol/mol (8.8%). After 24 weeks of treatment, mean HbA1c decreased to 53 mmol/mol (7.0%); 56% of patients reached a target HbA1c≤ 53 mmol/mol (7.0%). Significant correlations with week 24 HbA1c were obtained for fasting plasma glucose measured at week 6/8 and week 12 (r = 0.32; P < 0.0001 for both). Patients with fasting plasma glucose > 10 mmol/l at week 6/8 or week 12 were significantly less likely to achieve the HbA1c target at the end of treatment than patients with fasting plasma glucose < 8.9 mmol/l (P < 0.0001 for both). If fasting plasma glucose was > 10 mmol/l at week 6/8 or week 12, patients had only a 27% chance of reaching the HbA1c goal. Conclusions Fasting plasma glucose remaining > 10 mmol/l after 6–12 weeks of glargine therapy indicates that reaching target HbA1c≤ 53 mmol/mol (7.0%) is unlikely and calls for individualized attention to consider further therapeutic options. PMID:22413808

  7. 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

    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

  8. 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

  9. 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. PMID:22461154

  10. Prediction of gestational diabetes mellitus in the first trimester, comparison of fasting plasma glucose, two-step and one-step methods: a prospective randomized controlled trial.

    PubMed

    Yeral, M Ilkin; Ozgu-Erdinc, A Seval; Uygur, Dilek; Seckin, K Doga; Karsli, M Fatih; Danisman, A Nuri

    2014-08-01

    Our aim was to evaluate and compare the diagnostic performance of three methods commonly used for GDM screening: fasting plasma glucose (FPG), two-step 50 g glucose challenge test (GCT), and 75 g glucose tolerance test (GTT) in a randomized study design to predict GDM in the first trimester and determine the best approach in predicting GDM. In a non-blind, parallel-group prospective randomized controlled study; 736 singleton pregnant women underwent FPG testing in the first trimester and randomly assigned to two groups; two-step 50 g GCT and 75 g GTT. GDM diagnosis was made according to Carpenter-Coustan or ADA (American Diabetes Association) criteria in two-step 50 g GCT and 75 g GTT groups, respectively. Subsequent testing was performed by two-step 50 g GCT at 24-28 weeks for screen negatives. After excluding the women who were lost to follow-up or withdrawn as a result of pregnancy loss, 486 pregnant women were recruited in the study. The FPG, two-step GCT, and one-step GTT methods identified GDM in 25/486 (5.1 %), 15/248 (6.0 %), and 27/238 (11.3 %) women, respectively. Area under ROC curves were 0.623, 0.708, and 0.792, respectively. Sensitivities were 47.17, 68.18, and 87.1 %, respectively. Specificities were 77.37, 100, and 100 %, respectively. Positive predictive values were 20.33, 100, and 100 %, respectively. Negative predictive values were 92.29, 97, and 98.1 %, respectively. Until superior screening alternatives become available, the 75 g GTT may be preferred for GDM screening in the first trimester. PMID:24282036

  11. Enteral nutrition intolerance in critically ill septic burn patients.

    PubMed

    Lavrentieva, Athina; Kontakiotis, Theodore; Bitzani, Militsa

    2014-01-01

    The purpose of this study was to investigate the frequency of enteral feeding intolerance in critically ill septic burn patients, the effect of enteral feeding intolerance on the efficacy of feeding, the correlation between the infection marker (procalcitonin [PCT]) and the nutrition status marker (prealbumin) and the impact of feeding intolerance on the outcome of septic burn patients. From January 2009 to December 2012 the data of all burn patients with the diagnosis of sepsis who were placed on enteral nutrition were analyzed. Septic patients were divided into two groups: group A, septic patients who developed feeding intolerance; group B, septic patients who did not develop feeding intolerance. Demographic and clinical characteristics of patients were analyzed and compared. The diagnosis of sepsis was applied to 29% of all patients. Of these patients 35% developed intolerance to enteral feeding throughout the septic period. A statistically significant increase in mean PCT level and a decrease in prealbumin level was observed during the sepsis period. Group A patients had statistically significant lower mean caloric intake, higher PCT:prealbumin ratio, higher pneumonia incidence, higher Sequential Organ Failure Assessment Maximum Score, a longer duration of mechanical ventilation, and a higher mortality rate in comparison with the septic patients without gastric feeding intolerance. The authors concluded that a high percentage of septic burn patients developed enteral feeding intolerance. Enteral feeding intolerance seems to have a negative impact on the patients' nutritional status, morbidity, and mortality. PMID:24879397

  12. The red wine provocation test: intolerance to histamine as a model for food intolerance.

    PubMed

    Wantke, F; Götz, M; Jarisch, R

    1994-01-01

    Sneezing, flush, headache, diarrhea, skin itch, and shortness of breath are symptoms occurring in patients intolerant to wine after drinking one glass of red wine. The role of histamine in wine intolerance was evaluated by a red wine provocation test in 28 patients with a history of wine intolerance and in 10 controls with good tolerance of wine. Patients were challenged with 125 ml red wine (equivalent to 50 micrograms histamine); blood samples were drawn before and after 15 and 30 minutes. Plasma histamine was assessed by a radioimmunoassay. Lung function tests were performed before and after the wine test. Twenty-two of twenty-eight patients had symptoms showing significantly higher plasma histamine levels 30 minutes after wine challenge (p < .01) compared with asymptomatic controls. Basal histamine levels of patients were higher (p < .05) than in controls. A slight asthmatic attack as well as a 30% decrease of FEF 25 was seen in 2/22 patients. Terfenadine premedication significantly eliminated symptoms in 10/12 patients (p < .05) in a subsequent wine test. Histamine assessment was done in 52 wines (red, white, and champagne) and in 17 beers by radioimmunoassay. Histamine levels ranged from 3-120 micrograms/l in white wines; 15-670 micrograms/l in champagnes; 60-3800 micrograms/l in red wines; and 21-305 micrograms/l in beers. Histamine is causing wine intolerance. Patients intolerant to wine seem to have diminished histamine degradation probably based on a deficiency of diamine oxidase. PMID:8005453

  13. [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. PMID:23814966

  14. 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

  15. Glucose analogue inhibitors of glycogen phosphorylase: from crystallographic analysis to drug prediction using GRID force-field and GOLPE variable selection.

    PubMed

    Watson, K A; Mitchell, E P; Johnson, L N; Cruciani, G; Son, J C; Bichard, C J; Fleet, G W; Oikonomakos, N G; Kontou, M; Zographos, S E

    1995-07-01

    -activity relationship studies. The molecules in the training set are void of problems and potential errors arising from the alignment and bound conformations of each of the ligands since the coordinates were those determined experimentally from the X-ray crystallographic refined ligand-enzyme complexes. The computational procedure described in this work involves the use of the program GRID to describe the molecular structures and the progam GOLPE to obtain the partial least squares regression model with the highest prediction ability. The GRID/GOLPE procedure performed using 51 glucose analogue inhibitors of GPb has good overall predictivity [standard deviation of error predictions (SDEP) = 0.98 and Q(2) = 0.76] and has shown good agreement with the crystallographic and kinetic results by reliably selecting regions that are known to affect the binding affinity. PMID:15299833

  16. 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…

  17. Lipid storage by adipose tissue macrophages regulates systemic glucose tolerance

    PubMed Central

    Aouadi, Myriam; Vangala, Pranitha; Yawe, Joseph C.; Tencerova, Michaela; Nicoloro, Sarah M.; Cohen, Jessica L.; Shen, Yuefei

    2014-01-01

    Proinflammatory pathways in adipose tissue macrophages (ATMs) can impair glucose tolerance in obesity, but ATMs may also be beneficial as repositories for excess lipid that adipocytes are unable to store. To test this hypothesis, we selectively targeted visceral ATMs in obese mice with siRNA against lipoprotein lipase (LPL), leaving macrophages within other organs unaffected. Selective silencing of ATM LPL decreased foam cell formation in visceral adipose tissue of obese mice, consistent with a reduced supply of fatty acids from VLDL hydrolysis. Unexpectedly, silencing LPL also decreased the expression of genes involved in fatty acid uptake (CD36) and esterification in ATMs. This deficit in fatty acid uptake capacity was associated with increased circulating serum free fatty acids. Importantly, ATM LPL silencing also caused a marked increase in circulating fatty acid-binding protein-4, an adipocyte-derived lipid chaperone previously reported to induce liver insulin resistance and glucose intolerance. Consistent with this concept, obese mice with LPL-depleted ATMs exhibited higher hepatic glucose production from pyruvate and glucose intolerance. Silencing CD36 in ATMs also promoted glucose intolerance. Taken together, the data indicate that LPL secreted by ATMs enhances their ability to sequester excess lipid in obese mice, promoting systemic glucose tolerance. PMID:24986598

  18. 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

  19. [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

  20. 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

  1. Safety and efficacy of the predictive low glucose management system in the prevention of hypoglycaemia: protocol for randomised controlled home trial to evaluate the Suspend before low function

    PubMed Central

    Abraham, M B; Nicholas, J A; Ly, T T; Roby, H C; Paramalingam, N; Fairchild, J; King, B R; Ambler, G R; Cameron, F; Davis, E A; Jones, T W

    2016-01-01

    Introduction Innovations with sensor-augmented pump therapy (SAPT) to reduce hypoglycaemia in patients with type 1 diabetes are an ongoing area of research. The predictive low glucose management (PLGM) system incorporates continuous glucose sensor data into an algorithm and suspends basal insulin before the occurrence of hypoglycaemia. The system was evaluated in in-clinic studies, and has informed the parameters of a larger home trial to study its efficacy and safety in real life. Methods and analysis The aim of this report is to describe the study design and outcome measures for the trial. This is a 6-month, multicentre, randomised controlled home trial to test the PLGM system in children and adolescents with type 1 diabetes. The system is available in the Medtronic MiniMed 640G pump as the ‘Suspend before low’ feature. Following a run-in period, participants are randomised to either the control arm with SAPT alone or the intervention arm with SAPT and Suspend before low. The primary aim of this study is to evaluate the time spent hypoglycaemic (sensor glucose <3.5 mmol/L) with and without the system. The secondary aims are to determine the number of hypoglycaemic events, the time spent hyperglycaemic, and to evaluate safety with ketosis and changes in glycated haemoglobin. The study also aims to assess the changes in counter-regulatory hormone responses to hypoglycaemia evaluated by a hyperinsulinaemic hypoglycaemic clamp in a subgroup of patients with impaired awareness. Validated questionnaires are used to measure the fear of hypoglycaemia and the impact on the quality of life to assess burden of the disease. Ethics and dissemination Ethics committee permissions were gained from respective Institutional Review boards. The findings of the study will provide high quality evidence of the ability of the system in the prevention of hypoglycaemia in real life. Trial registration number ACTRN12614000510640, Pre-results. PMID:27084290

  2. 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

  3. 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

  4. 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

  5. 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

  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. 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

  8. 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 ...

  9. What I Need to Know about Lactose Intolerance

    MedlinePlus

    ... able to use these products. [ Top ] Calcium and Vitamin D If you are lactose intolerant, make sure you ... such as cereals, fruit juices, and soy milk Vitamin D helps the body absorb and use calcium. Be ...

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Glucose metabolism in patients with Cushing's syndrome.

    PubMed

    Bowes, S B; Benn, J J; Scobie, I N; Umpleby, A M; Lowy, C; Sönksen, P H

    1991-04-01

    Glucose intolerance, sometimes severe enough to cause frank diabetes mellitus, is a frequent feature of Cushing's syndrome. The primary cause of the hyperglycaemia, whether due to glucose over-production or under-utilization, remains unresolved. We therefore measured glucose turnover using an intravenous bolus of 3-3H glucose in 14 normoglycaemic patients with Cushing's syndrome and 14 control subjects. Seven of the patients with Cushing's syndrome were also restudied post-operatively. Plasma glucose concentrations were similar in all three groups whereas glucose metabolic clearance rate (MCR) (1.80 +/- 0.06 ml/min/kg) and glucose turnover rate (9.09 +/- 0.36 mumol/min/kg) were significantly reduced in patients with Cushing's syndrome compared to normal subjects (2.21 +/- 0.1; P less than 0.001; 10.90 +/- 0.50; P less than 0.01) and rose post-operatively to normal values (2.35 +/- 0.14 ml/min/kg; 11.07 +/- 0.48 mumol/min/kg). We conclude from these results that the hyperglycaemia sometimes found in Cushing's syndrome may be primarily due to decreased utilization rather than increased glucose production. PMID:1879061

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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. PMID:20719435

  3. [Special features of NSAID intolerance in children].

    PubMed

    Porto Arceo, J A

    2003-01-01

    Adverse reactions to acetylsalicylic acid (aspirin, ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) are the second most important cause of adverse drug reactions (ARDs) after beta-lactams. They produce various clinical manifestations and can affect different organs. Gastrointestinal reactions (pyrosis, vomiting, gastralgia), neurological reactions (tinnitus, deafness, vertigo), blood dyscrasias, and nephrotoxic and hepatotoxic reactions are well known.NSAIDs are the drugs of choice in the treatment of chronic arthropathies and other childhood connective-tissue diseases and are also commonly used in the treatment of febrile and acute inflammatory processes. Not all NAIDs are authorized for use in the pediatric population but their spectrum of use varies according to the entity for which they are indicated and the legislation of the country. Published studies on the prevalence of aspirin intolerance in patients with bronchial asthma show a fair amount of disagreement. This may be due to (i) the method of selecting asthmatic patients for the study, which differs according to whether all asthmatic patients are included or only those dependent on corticoids; (ii) the diagnostic method used, whether based on clinical criteria or oral provocation tests, which will affect the number of patients with a diagnosis of intolerance. In children aged less than 10 years, including children with asthma, the prevalence is low, while among children and young adults aged 10-20 years old, the prevalence is estimated at 10 %. Some hypotheses attempt to explain the mechanisms through which adverse reactions to NAIDs take place. One hypothesis attributes the reaction to a reaginic immunological mechanism but this hypothesis has only been confirmed in exceptional cases. The theory of the cyclooxygenase pathway, currently the most widely accepted, is based on the ability of NSAIDs to inhibit the cyclooxygenase pathway of arachidonic acid metabolism, leading to prostaglandin

  4. Multiple approaches to predicting oxygen and glucose consumptions by HepG2 cells on porous scaffolds in an axial-flow bioreactor.

    PubMed

    Podichetty, Jagdeep T; Bhaskar, Prasana R; Singarapu, Kumar; Madihally, Sundararajan V

    2015-02-01

    In this study, the distribution of oxygen and glucose was evaluated along with consumption by hepatocytes using three different approaches. The methods include (i) Computational Fluid Dynamics (CFD) simulation, (ii) residence time distribution (RTD) analysis using a step-input coupled with segregation model or dispersion model, and (iii) experimentally determined consumption by HepG2 cells in an open-loop. Chitosan-gelatin (CG) scaffolds prepared by freeze-drying and polycaprolactone (PCL) scaffolds prepared by salt leaching technique were utilized for RTD analyses. The scaffold characteristics were used in CFD simulations i.e. Brinkman's equation for flow through porous medium, structural mechanics for fluid induced scaffold deformation, and advection-diffusion equation coupled with Michaelis-Menten rate equations for nutrient consumption. With the assumption that each hepatocyte behaves like a micro-batch reactor within the scaffold, segregation model was combined with RTD to determine exit concentration. A flow rate of 1 mL/min was used in the bioreactor seeded with 0.6 × 10(6) HepG2 cells/cm(3) on CG scaffolds and oxygen consumption was measured using two flow-through electrodes located at the inlet and outlet. Glucose in the spent growth medium was also analyzed. RTD results showed distribution of nutrients to depend on the surface characteristics of scaffolds. Comparisons of outlet oxygen concentrations between the simulation results, and experimental results showed good agreement with the dispersion model. Outlet oxygen concentrations from segregation model predictions were lower. Doubling the cell density showed a need for increasing the flow rate in CFD simulations. This integrated approach provide a useful strategy in designing bioreactors and monitoring tissue regeneration. PMID:25116006

  5. 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

  6. When threats foreign turn domestic: Two ways for distant realistic intergroup threats to carry over into local intolerance.

    PubMed

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

    2015-09-01

    In times of economic downturn, perceived realistic intergroup threats (e.g., labour competition) often dominate political and media discourse. Although local outgroups (e.g., local immigrants) can be experienced as sources of realistic threats, we propose that such threats can also be perceived to be caused by distant outgroups (e.g., European Union members perceiving Greece to threaten their economies) and that such distant threats can carry over into local intolerance (e.g., increasing intolerance towards local immigrant groups). We predicted and found in two studies that perceived distant realistic threats carried over into local intolerance via two different pathways. First, direct reactions towards the distant outgroup can generalize to culturally similar local outgroups (the group-based association pathway). Secondly, Study 2 indicated that when the distant threat was attributed to stereotypical outgroup traits (e.g., being lazy), distant realistic threats activated local realistic threats, which subsequently influenced local intolerance (the threat-based association pathway). Taken together, our studies indicate that perceived realistic threats foreign can turn domestic, but in two different ways. PMID:25491910

  7. 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.

  8. Familial aquagenic urticaria associated with familial lactose intolerance.

    PubMed

    Treudler, Regina; Tebbe, Beate; Steinhoff, Matthias; Orfanos, Constantin E

    2002-10-01

    Aquagenic urticaria is a rare disorder characterized by the occurrence of pruritus and wheals after temporary contact with water. The familial occurrence of aquagenic urticaria over 3 generations is reported here in association with familial lactose intolerance, a condition in which the enzyme lactase encoded on chromosome 2, is deficient. In two patients, a young man and his mother, we verified the appearance of pruritic hives 5 to 10 minutes after contact with water of any temperature. Other types of physical urticaria were absent, and mastocytosis was excluded by extensive laboratory investigations; lactose intolerance was confirmed in both patients by H(2)-exhalation test. In these patients the clinical symptoms did not respond to antihistamines or UV-radiation therapy. Four other members of the family had wheals from water contact, two of whom had lactose intolerance. Two other members had lactose intolerance only. Although the association of aquagenic urticaria with lactose intolerance may be coincidental, attention is drawn to the fact that the 2 conditions, known to be familial, may coexist in the same family, possibly based on an association of gene loci. PMID:12271310

  9. [Pseudo-allergies are due to histamine intolerance].

    PubMed

    Götz, M

    1996-01-01

    Numerous undesirable reactions to alcoholic beverages, foods, drugs and other substances are characterized by allergy-like signs and symptoms and yet show unambiguously negative allergy test results. Such persons should be assessed for evidence of histamine intolerance caused by histamine overload and/or diamine oxidase deficiency. Diamine oxidase is the main histamine degrading enzyme with a predominantly gut activity. This would explain why nutritional allergies are often primarily suspected. The clinical evidence for histamine intolerance is based on chronic headache, diarrhoea, vomiting, flush, urticaria, asthma-like symptoms, rhinitis and others. Histamine restricted food, supported if necessary by H1 antihistamine blockade are simple but highly efficacious measures as shown by us in large patient groups. Intolerance to red wine probably is the most outstanding clinical characteristic and a directed question must be included into any allergy history in order to avoid missing a very major diagnostic spectrum with good therapeutic maneuverability. PMID:9012205

  10. Towards an ontological theory of substance intolerance and hypersensitivity.

    PubMed

    Hogan, William R

    2011-02-01

    A proper ontological treatment of intolerance--including hypersensitivity--to various substances is critical to patient care and research. However, existing methods and standards for documenting these conditions have flaws that inhibit these goals, especially translational research that bridges the two activities. In response, I outline a realist approach to the ontology of substance intolerance, including hypersensitivity conditions. I defend a view of these conditions as a subtype of disease. Specifically, a substance intolerance is a disease whose pathological process(es) are realized upon exposure to a quantity of substance of a particular type, and this quantity would normally not cause the realization of the pathological process(es). To develop this theory, it was necessary to build pieces of a theory of pathological processes. Overall, however, the framework of the Ontology for General Medical Science (which uses Basic Formal Ontology as its uppermost level) was a more-than-adequate foundation on which to build the theory. PMID:20152933

  11. Utility of Corrected QT Interval in Orthostatic Intolerance

    PubMed Central

    Kim, Jung Bin; Hong, Soonwoong; Park, Jin-Woo; Cho, Dong-Hyuk; Park, Ki-Jong; Kim, Byung-Jo

    2014-01-01

    We performed this study to determine whether electrocardiographic corrected QT (QTc) interval predicts alterations in sympathovagal balance during orthostatic intolerance (OI). We reviewed 1,368 patients presenting with symptoms suggestive of OI who underwent electrocardiography and composite autonomic function tests (AFTs). Patients with a positive response to the head-up tilt test were classified into orthostatic hypotension (OH), neurocardiogenic syncope (NCS), or postural orthostatic tachycardia syndrome (POTS) groups. A total of 275 patients (159 OH, 54 NCS, and 62 POTS) were included in the final analysis. Between-group comparisons of OI symptom grade, QTc interval, QTc dispersion, and each AFT measure were performed. QTc interval and dispersion were correlated with AFT measures. OH Patients had the most severe OI symptom grade and NCS patients the mildest. Patients with OH showed the longest QTc interval (448.8±33.6 msec), QTc dispersion (59.5±30.3 msec) and the lowest values in heart rate response to deep breathing (HRDB) (10.3±6.0 beats/min) and Valsalva ratio (1.3±0.2). Patients with POTS showed the shortest QTc interval (421.7±28.6 msec), the highest HRDB values (24.5±9.2 beats/min), Valsalva ratio (1.8±0.3), and proximal and distal leg sweat volumes in the quantitative sudomotor axon reflex test. QTc interval correlated negatively with HRDB (r = −0.443, p<0.001) and Valsalva ratio (r = −0.425, p<0.001). We found negative correlations between QTc interval and AFT values representing cardiovagal function in patients with OI. Our findings suggest that prolonged QTc interval may be considered to be a biomarker for detecting alterations in sympathovagal balance, especially cardiovagal dysfunction in OH. PMID:25180969

  12. An In vivo Drug Screening Model Using Glucose-6-Phosphate Dehydrogenase Deficient Mice to Predict the Hemolytic Toxicity of 8-Aminoquinolines

    PubMed Central

    Zhang, Peng; Gao, Xiugong; Ishida, Hiroshi; Amnuaysirikul, Jack; Weina, Peter J.; Grogl, Max; O'Neil, Michael T.; Li, Qigui; Caridha, Diana; Ohrt, Colin; Hickman, Mark; Magill, Alan J.; Ray, Prabhati

    2013-01-01

    Anti-malarial 8-aminoquinolines drugs cause acute hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDD). Efforts to develop non-hemolytic 8-aminoquinolines have been severely limited caused by the lack of a predictive in vivo animal model of hemolytic potential that would allow screening of candidate compounds. This report describes a G6PDD mouse model with a phenotype closely resembling the G6PDD phenotype found in the African A-type G6PDD human. These G6PDD mice, given different doses of primaquine, which used as a reference hemolytic drug, display a full array of hemolytic anemia parameters, consistently and reproducibly. The hemolytic and therapeutic indexes were generated for evaluation of hemotoxicity of drugs. This model demonstrated a complete hemolytic toxicity response to another known hemolytic antimalarial drug, pamaquine, but no response to non-hemolytic drugs, chloroquine and mefloquine. These results suggest that this model is suitable for evaluation of selected 8-AQ type candidate antimalarial drugs for their hemolytic potential. PMID:23530079

  13. Early change in glucose metabolic rate measured using FDG-PET in patients with high-grade glioma predicts response to temozolomide but not temozolomide plus radiotherapy

    SciTech Connect

    Charnley, Natalie . E-mail: natalie.charnley@mmic.man.ac.uk; West, Catharine M.; Barnett, Carolyn M.; Brock, Catherine; Bydder, Graeme M.; Glaser, Mark; Newlands, Ed S.; Swindell, Ric; Matthews, Julian; Price, Pat

    2006-10-01

    Purpose: To compare the ability of positron emission tomography (PET) to predict response to temozolomide vs. temozolomide plus radiotherapy. Methods and Materials: Nineteen patients with high-grade glioma (HGG) were studied. Patients with recurrent glioma received temozolomide 75 mg/m{sup 2} daily for 7 weeks (n = 8). Newly diagnosed patients received temozolomide 75 mg/m{sup 2} daily plus radiotherapy 60 Gy/30 fractions over 6 weeks, followed by six cycles of adjuvant temozolomide 200 mg/m{sup 2}/day (Days 1-5 q28) starting 1 month after radiotherapy (n = 11). [{sup 18}F]Fluorodeoxyglucose ([{sup 18}F]FDG) PET scan and magnetic resonance imaging (MRI) were performed at baseline, and 7 and 19 weeks after initiation of temozolomide administration. Changes in glucose metabolic rate (MRGlu) and MRI response were correlated with patient survival. Results: In the temozolomide-alone group, patients who survived >26 vs. {<=}26 weeks showed a greater reduction in MRGlu measured at 7 weeks with median changes of -34% and -4%, respectively (p = 0.02). PET responders, defined as a reduction in MRGlu {>=}25%, survived longer than nonresponders with mean survival times of 75 weeks (95% CI, 34-115 vs. 20 weeks (95% CI, 14-26) (p = 0.0067). In the small group of patients studied, there was no relationship between MRI response and survival (p = 0.52). For patients receiving temozolomide plus radiotherapy, there was no difference in survival between PET responders and nonresponders (p = 0.32). Conclusions: Early changes in MRGlu predict response to temozolomide, but not temozolomide plus radiotherapy.

  14. 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. PMID:26896939

  15. 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

  16. Pretreatment regional brain glucose uptake in the midbrain on PET may predict remission from a major depressive episode after three months of treatment.

    PubMed

    Milak, Matthew S; Parsey, Ramin V; Lee, Leilani; Oquendo, Maria A; Olvet, Doreen M; Eipper, Francoise; Malone, Kevin; Mann, J John

    2009-07-15

    In order to test the hypotheses that pretreatment metabolic activity in the midbrain and the rostral anterior cingulate may predict remission in response to medications enhancing monoaminergic transmission, we compared relative regional cerebral metabolic rate of glucose (rCMRglu) using positron emission tomography (PET) in medication-free patients with major depression who remitted after 3 months of monoaminergic medication, with non-remitters on the same treatment. [(18)F]-FDG PET was conducted in a group of 33 drug-free DSM-IV major depression subjects prior to antidepressant treatment. Patients were prescribed paroxetine initially (61%) unless they had failed paroxetine previously. Treatment was then managed by the subjects' own physician with 91% receiving a selective serotonin reuptake inhibitor and 78% another non-selective monoamine reuptake inhibitor during the 3 months of treatment. Voxel-based parametric brain maps of remitters were compared with maps of non-remitters using SPM2. Remission was defined as a >50% decrease in and a final score of predicts remission in response to 3 months of antidepressant treatment, despite no clinical differences at baseline and no difference in treatment intensity. Brain imaging is a

  17. The effects of combined vitamin D and calcium supplementation on fasting plasma glucose in non-diabetic adults age 65 and older

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Altered vitamin D and calcium homeostasis may play a role in the development of glucose intolerance. In a 3-year randomized controlled trial, we compared the effects of combined vitamin D and calcium supplementation vs. placebo on fasting plasma glucose (FPG) in healthy adults 65 years of age or old...

  18. [Oral exposure testing in non-aspirin-induced analgesic intolerance].

    PubMed

    Wiedow, O; Brasch, J; Christophers, E

    1996-12-01

    Although intolerance reaction to analgesics are not uncommon, there is still a lack of standardized procedures to diagnose the problem. We retrospectively analyzed results of scratch tests as well as oral challenges with analgesics in order to evaluate risk and diagnostic relevance of these procedures. In 1987-1992 a total of 650 patients with supposed intolerance to drugs were tested by oral challenge. Among them were 98 patients with a positive history of intolerance to non-aspirin analgesics. In 56 patients the intolerance could be verified by oral challenge. In order of decreasing frequency, the most likely agents were propyphenazone, diclofenac, metamizole, ibuprofen, carbamazepine, indomethacin, phenazone (antipyrine), and paracetamol (acteaminophen). Oral provocation showed clear dose-response relationships. For propyphenazone, the half-effective provocation dose was the same for all symptoms (cutaneous, nasal, bronchial, anaphylactoid). Scratch testing was not of diagnostic significance. Standardized test protocols starting with low dose oral challenges are suitable and helpful in minimizing the risk of severe side effects. PMID:9081936

  19. 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.

  20. 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…

  1. 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…

  2. 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)

  3. A novel imaging platform for non-invasive screening of abnormal glucose tolerance.

    PubMed

    Jeong, Bosu; Jung, Chang Hee; Lee, Yong-Ho; Shin, Il-Hyung; Kim, Hansuk; Bae, Soo-Jin; Lee, Dae-Sic; Kang, Eun Seok; Kang, Uk; Kim, Jong Jin; Park, Joong-Yeol

    2016-06-01

    Optical measurement of skin auto-fluorescence (SAF), most likely emanating from accumulated advanced glycation end-products (AGEs), has been proposed for the noninvasive diagnosis of glucose intolerance in clinical settings. Here, we developed a novel imaging system with transmission geometry for SAF measurement and compared its diagnostic performance in a Korean population. PMID:27321320

  4. 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

  5. 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

  6. 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

  7. Glucose Variability

    PubMed Central

    2013-01-01

    The proposed contribution of glucose variability to the development of the complications of diabetes beyond that of glycemic exposure is supported by reports that oxidative stress, the putative mediator of such complications, is greater for intermittent as opposed to sustained hyperglycemia. Variability of glycemia in ambulatory conditions defined as the deviation from steady state is a phenomenon of normal physiology. Comprehensive recording of glycemia is required for the generation of any measurement of glucose variability. To avoid distortion of variability to that of glycemic exposure, its calculation should be devoid of a time component. PMID:23613565

  8. Prenatal stress and stress coping style interact to predict metabolic risk in male rats.

    PubMed

    Boersma, Gretha J; Moghadam, Alexander A; Cordner, Zachary A; Tamashiro, Kellie L

    2014-04-01

    Both prenatal stress (PNS) exposure and a passive stress-coping style have been identified as risk factors for insulin resistance in rats. In the current study, we test the hypothesis that PNS and stress-coping style may interact in predicting susceptibility for metabolic disease. To test this hypothesis, adult male control and PNS offspring were behaviorally characterized using a defensive burying test to have either a passive or proactive stress-coping style. In adulthood, all rats were fed either a standard chow or a high-fat diet for 3 weeks. After 3 weeks of diet exposure, glucose and insulin levels were assessed during an oral glucose tolerance test. Under high-fat diet conditions, PNS rats display elevated glucose and insulin responses to the oral glucose tolerance test, indicative of glucose intolerance. Interestingly, these effects of PNS were far more pronounced in rats characterized by a passive stress-coping style. Additionally, the passively coping PNS rats also gained more weight on the high-fat diet than all other rats tested. This observation suggests that a stressful prenatal environment in combination with a passive stress-coping strategy may prime an individual to be sensitive to diet-induced obesity and type 2 diabetes. PMID:24467745

  9. 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...

  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. 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

  12. 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

  13. 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

  14. 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

  15. Glucose intolerance in the West African Diaspora: a skeletal muscle fibre type distribution hypothesis.

    PubMed

    Nielsen, J; Christensen, D L

    2011-08-01

    In the United States, Black Americans are largely descendants of West African slaves; they have a higher relative proportion of obesity and experience a higher prevalence of diabetes than White Americans. However, obesity rates alone cannot explain the higher prevalence of type 2 diabetes. Type 2 diabetes is characterized by insulin resistance and beta-cell dysfunction. We hypothesize that the higher prevalence of type 2 diabetes in African Americans (as compared to White Americans) is facilitated by an inherited higher percentage of skeletal muscle fibre type II and a lower percentage of skeletal muscle fibre type I. Skeletal muscle fibre type II is less oxidative and more glycolytic than skeletal muscle fibre type I. Lower oxidative capacity is associated with lower fat oxidation and a higher disposal of lipids, which are stored as muscular adipose tissue in higher amounts in Black compared to White Americans. In physically active individuals, the influence of muscle fibre composition will not be as detrimental as in physically inactive individuals. This discrepancy is caused by the plasticity in the skeletal muscle fibre characteristics towards a higher activity of oxidative enzymes as a consequence of physical activity. We suggest that a higher percentage of skeletal muscle fibre type II combined with physical inactivity has an impact on insulin sensitivity and high prevalence of type 2 diabetes in Blacks of West African ancestry. PMID:21382179

  16. Food intolerance in rheumatoid arthritis. II. Clinical and histological aspects.

    PubMed Central

    van de Laar, M A; Aalbers, M; Bruins, F G; van Dinther-Janssen, A C; van der Korst, J K; Meijer, C J

    1992-01-01

    Six patients with rheumatoid factor positive rheumatoid arthritis who had shown a marked symptomatic improvement during four weeks of hypoallergic, artificial diet were studied in greater detail. Placebo controlled rechallenges showed intolerance for specific foodstuffs in four patients. In three of these patients biopsies of both the synovial membrane and of the proximal small intestine were carried out before and during allergen free feeding. In two patients, both with raised serum IgE concentrations and specific IgE antibodies to certain foods, a marked reduction of mast cells in the synovial membrane and proximal small intestine was demonstrated. Although the number of food intolerant patients with RA remains limited and markers of allergic activity are scanty, our observations suggest an underlying immunoallergological mechanism. PMID:1575572

  17. Towards an Ontological Theory of Substance Intolerance and Hypersensitivity

    PubMed Central

    Hogan, William R.

    2010-01-01

    A proper ontological treatment of intolerance—including hypersensitivity—to various substances is critical to patient care and research. However, existing methods and standards for documenting these conditions have flaws that inhibit these goals, especially translational research that bridges the two activities. In response, I outline a realist approach to the ontology of substance intolerance, including hypersensitivity conditions. I defend a view of these conditions as a subtype of disease. Specifically, a substance intolerance is a disease whose pathological process(es) are realized upon exposure to a quantity of substance of a particular type, and this quantity would normally not cause the realization of the pathological process(es). To develop this theory, it was necessary to build pieces of a theory of pathological processes. Overall, however, the framework of the Ontology for General Medical Science (which uses Basic Formal Ontology as its uppermost level) was a more-than-adequate foundation on which to build the theory. PMID:20152933

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. Orthostatic intolerance and motion sickness after parabolic flight.

    PubMed

    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. PMID:11133895

  4. 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

  5. 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

  6. [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

  7. [Metabolic changes in patients with hereditary fructose intolerance. A contribution to the topic of fructose administration for parenteral feeding].

    PubMed

    Sachs, M; Asskali, F; Encke, A; Förster, H

    1991-11-15

    The literature contains a number of reports of death following the intravenous administration of fructose in patients with hereditary fructose intolerance (HFI). The aim of the present study was, therefore, to investigate the metabolic changes occurring during intravenous administration of fructose to patients with HFI, with the aim of identifying metabolic parameters that would permit the early diagnosis of HFI. Also, the deaths reported in the literature were analyzed. In three of our own patients with fruit intolerance known since childhood, and in volunteers with normal metabolism, a one-hour intravenous fructose tolerance test (1.7 g fructose/min) was performed. An analysis was done using the usual enzymatic and chemical methods: blood glucose, fructose, lactic acid, serum uric acid, ammonia, free fatty acids, inorganic phosphate, and serum amino acids (ion exchange chromatography). During fructose infusion, the following metabolic changes were detected: hypoglycemia (20 to 60 mg/dl), increase in blood fructose levels (up to 350 mg/dl), hypophosphatemia (2 to 3 mg/dl), hyperlacticacidemia (up to 60 mg/dl), elevation of plasma ammonia levels (up to 120 mg/dl), increased serum glutamate, and a decrease in serum glutamine, as also hyperuricemia (up to 10 mg/dl). On termination of the fructose infusion, these changes were completely reversible. Analysis of the deaths reported in the literature revealed a known intolerance to fruit or sweets, and that no regular metabolic studies were apparently performed. Although HFI is rare, use should be made of the known advantages of sugar substitutes in post-aggression metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1770897

  8. Renal Glucose Handling

    PubMed Central

    Ferrannini, Ele; Veltkamp, Stephan A.; Smulders, Ronald A.; Kadokura, Takeshi

    2013-01-01

    OBJECTIVE Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, stimulates glycosuria and lowers glycemia in patients with type 2 diabetes (T2DM). The objective of this study was to assess the pharmacodynamics of ipragliflozin in T2DM patients with impaired renal function. RESEARCH DESIGN AND METHODS Glycosuria was measured before and after a single ipragliflozin dose in 8 nondiabetic subjects and 57 T2DM patients (age 62 ± 9 years, fasting glucose 133 ± 39 mg/dL, mean ± SD) with normal renal function (assessed as the estimated glomerular filtration rate [eGFR]) (eGFR1 ≥90 mL · min–1 · 1.73 m−2), mild (eGFR2 ≥60 to <90), moderate (eGFR3 ≥30 to <60), or severe reduction in eGFR (eGFR4 ≤15 to <30). RESULTS Ipragliflozin significantly increased urinary glucose excretion in each eGFR class (P < 0.0001). However, ipragliflozin-induced glycosuria declined (median [IQR]) across eGFR class (from 46 mg/min [33] in eGFR1 to 8 mg/min [7] in eGFR4, P < 0.001). Ipragliflozin-induced fractional glucose excretion (excretion/filtration) was 39% [27] in the T2DM patients (pooled data), similar to that of the nondiabetic subjects (37% [17], P = ns). In bivariate analysis of the pooled data, ipragliflozin-induced glycosuria was directly related to eGFR and fasting glucose (P < 0.0001 for both, r2 = 0.55), predicting a decrement in 24-h glycosuria of 15 g for each 20 mL/min decline in eGFR and an increase of 7 g for each 10 mg/dL increase in glucose above fasting normoglycemia. CONCLUSIONS In T2DM patients, ipragliflozin increases glycosuria in direct, linear proportion to GFR and degree of hyperglycemia, such that its amount can be reliably predicted in the individual patient. Although absolute glycosuria decreases with declining GFR, the efficiency of ipragliflozin action (fractional glucose excretion) is maintained in patients with severe renal impairment. PMID:23359360

  9. HIV-related Social Intolerance and Risky Sexual Behavior in a High HIV Prevalence Environment

    PubMed Central

    Delavande, Adeline; Sampaio, Mafalda

    2014-01-01

    Although most countries state that fighting social intolerance against persons with HIV is part of their national HIV strategy, the impact of reducing intolerance on risky sexual behavior is largely unknown. In this paper, we estimate the effect of social intolerance against HIV+ persons on risky sexual behavior in rural Malawi using data from roughly 2,000 respondents from the 2004 and 2006 waves of the Malawi Longitudional Study of Families and Health (MLSFH). The effect of social intolerance on risky behavior is a priori ambiguous. On the one hand, higher social intolerance or stigma can lead people to disassociate from the stigmatized group and hence promote risky behavior. On the other hand, intolerance can be viewed as a social tax on being HIV+ and thus higher intolerance may reduce risky behavior. We find that a decrease in social intolerance is associated with a decrease in risky behavior, including fewer partners and a lower likelihood of having extra-marital relations. This effect is mainly driven by the impact of social intolerance on men. Overall the results suggests that reducing social intolerance might not only benefit the HIV positive but might also forestall the spread of HIV. PMID:24768779

  10. 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

  11. Neurogenin 3-Specific Dipeptidyl Peptidase-2 Deficiency Causes Impaired Glucose Tolerance, Insulin Resistance, and Visceral Obesity

    PubMed Central

    Danilova, Olga V.; Tai, Albert K.; Mele, Deanna A.; Beinborn, Martin; Leiter, Andrew B.; Greenberg, Andrew S.; Perfield, James W.; DeFuria, Jason; Singru, Praful S.; Lechan, Ronald M.; Huber, Brigitte T.

    2009-01-01

    The control of glucose metabolism is a complex process, and dysregulation at any level can cause impaired glucose tolerance and insulin resistance. These two defects are well-known characteristics associated with obesity and onset of type 2 diabetes. Here we introduce the N-terminal dipeptidase, DPP2, as a novel regulator of the glucose metabolism. We generated mice with a neurogenin 3 (NGN3)-specific DPP2 knockdown (kd) to explore a possible role of DPP2 in maintaining metabolic homeostasis. These mice spontaneously developed hyperinsulinemia, glucose intolerance, and insulin resistance by 4 months of age. In addition, we observed an increase in food intake in DPP2 kd mice, which was associated with a significant increase in adipose tissue mass and enhanced liver steatosis but no difference in body weight. In accordance with these findings, the mutant mice had a higher rate of respiratory exchange than the control littermates. This phenotype was exacerbated with age and when challenged with a high-fat diet. We report, for the first time, that DPP2 enzyme activity is essential for preventing hyperinsulinemia and maintaining glucose homeostasis. Interestingly, the phenotype of NGN3-DPP2 kd mice is opposite that of DPP4 knockout mice with regard to glucose metabolism, namely the former have normal glucagon-like peptide 1 levels but present with glucose intolerance, whereas the latter have increased glucagon-like peptide 1, which is accompanied by augmented glucose tolerance. PMID:19819973

  12. 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.

  13. Dopaminergic drugs in type 2 diabetes and glucose homeostasis.

    PubMed

    Lopez Vicchi, Felicitas; Luque, Guillermina Maria; Brie, Belen; Nogueira, Juan Patricio; Garcia Tornadu, Isabel; Becu-Villalobos, Damasia

    2016-07-01

    The importance of dopamine in central nervous system function is well known, but its effects on glucose homeostasis and pancreatic β cell function are beginning to be unraveled. Mutant mice lacking dopamine type 2 receptors (D2R) are glucose intolerant and have abnormal insulin secretion. In humans, administration of neuroleptic drugs, which block dopamine receptors, may cause hyperinsulinemia, increased weight gain and glucose intolerance. Conversely, treatment with the dopamine precursor l-DOPA in patients with Parkinson's disease reduces insulin secretion upon oral glucose tolerance test, and bromocriptine improves glycemic control and glucose tolerance in obese type 2 diabetic patients as well as in non diabetic obese animals and humans. The actions of dopamine on glucose homeostasis and food intake impact both the autonomic nervous system and the endocrine system. Different central actions of the dopamine system may mediate its metabolic effects such as: (i) regulation of hypothalamic noradrenaline output, (ii) participation in appetite control, and (iii) maintenance of the biological clock in the suprachiasmatic nucleus. On the other hand, dopamine inhibits prolactin, which has metabolic functions; and, at the pancreatic beta cell dopamine D2 receptors inhibit insulin secretion. We review the evidence obtained in animal models and clinical studies that posited dopamine receptors as key elements in glucose homeostasis and ultimately led to the FDA approval of bromocriptine in adults with type 2 diabetes to improve glycemic control. Furthermore, we discuss the metabolic consequences of treatment with neuroleptics which target the D2R, that should be monitored in psychiatric patients to prevent the development in diabetes, weight gain, and hypertriglyceridemia. PMID:26748034

  14. 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

  15. Altered insulin response to glucose in weight-losing cancer patients.

    PubMed

    Rofe, A M; Bourgeois, C S; Coyle, P; Taylor, A; Abdi, E A

    1994-01-01

    Cancer cachexia and the underlying metabolic disturbances are due in part to either altered insulin release and action. Glucose intolerance in cancer patients is frequently observed but the nature of the insulin response is not usually described. The aim of this study was to investigate the insulin response in fasted, weigh-losing cancer patients following an oral glucose load (75 g). All cancer patients (n = 35) showed glucose intolerance. Three types of response were identified; those with an increased insulin: glucose ratio (I:G) at 60 min, (average 12.3, n = 13), those with a normal I:G (average 7.2 n = 7) and those with a decrease I:G (average 4.2, n = 15). Fasting plasma glucose concentrations were normal in all groups prior to the glucose tolerance test. However, patients with the lowest I:G also had the lowest fasting plasma insulin concentrations, the lowest plasma albumin concentrations and the highest plasma triglyceride concentrations. Those patients with an abnormal insulin response (either high or low I:G) had significantly greater weight loss (16% for low I:G group, 13% for the high I:G) compared to the normal responders (8%). Plasma fatty acid concentrations were increased in all cancer patients and decreased appropriately after glucose administration, indicating that lipolysis remained sensitive to the action of insulin. It is concluded that weight loss in cancer is associated with glucose intolerance and an abnormal insulin response, and that this response is indicative of either insulin resistance (high I:G) or decreased pancreatic function (low I:G). These findings suggest a role for insulin replacement therapy in the latter group of patients. PMID:8010722

  16. Intolerance to topical products may be due to dermographism.

    PubMed

    Watsky, Kalman L; McGovern, Thomas

    2003-03-01

    Patients with reactions to topical products may be eliciting a physical urticaria, dermographism, by rubbing. These reactions may be misinterpreted as allergic, and three cases demonstrating this phenomenon were reviewed. All patients with reactions to topical products due to dermographism improved with counseling and antihistamine therapy. Repeat open application testing confirmed the safety of previously suspect medications in two of the three cases, preventing unnecessary changes in the medication regimens and inaccurate diagnoses of medication allergy. We observe that intolerance to topical medications due to dermographism can usually be managed without extensive testing or treatment. PMID:14744421

  17. 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.

  18. 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

  19. Unemployment and civil commitment: a test of the intolerance hypothesis.

    PubMed

    Catalano, Ralph; Snowden, Lonnie; Shumway, Martha; Kessell, Eric

    2007-01-01

    We theorize that the reported association between economic indicators and the incidence of civil commitment for mental illness may result, at least in part, from reduced tolerance in the community for impaired behavior among minorities. Earlier work suggests that economically induced intolerance will be focused primarily on minority males. Based on this literature, we hypothesize that the median level of functioning among African-American males subjected to civil commitment will vary positively with earlier changes in the unemployment rate. The test applies Box-Jenkins methods to 156 months (August 1985-July 1998) of data from California. Consistent with theory, results support the hypothesis. PMID:17444533

  20. 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 ...

  1. 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 ...

  2. 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

  3. 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. PMID:23849047

  4. Self-reported intolerance of uncertainty and behavioural decisions.

    PubMed

    Carleton, R Nicholas; Duranceau, Sophie; Shulman, Elizabeth P; Zerff, Marissa; Gonzales, Josh; Mishra, Sandeep

    2016-06-01

    Intolerance of Uncertainty (IU) appears to be a robust transdiagnostic risk factor related to anxiety and depression. Most transdiagnostic IU research has used the self-report Intolerance of Uncertainty Scale-Short Form; however, there is comparatively little research exploring presumed behavioral correlates of IU. The current study was designed to assess relationships between self-reported IU and decisions in uncertainty-based behavioral tasks (specifically, the Wisconsin Card Sorting Task, the Risky Gains Task, and the Modified Iowa Gambling Task). Participants comprised compensated community members (n = 108; 69% women) and undergraduates (n = 98; 78% women). Community member compensation was not contingent on performance, but undergraduate compensation was partially contingent on performance. Results replicated prior research, with both samples producing small (r = .19) to moderate (r = -.29) correlations (ps < .05) between self-reported IU and outcome variables from each of the behavioral tasks. The relationships were larger in the undergraduate sample, likely due to the compensation incentive. In general, the results suggest that increasing IU is associated with increasingly risk adverse behaviors; however, the relationship appears complex and in need of substantial additional research to understand how clinically-significant IU would impact pathology-related behaviours. PMID:26788617

  5. 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

  6. 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…

  7. 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…

  8. 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…

  9. 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...

  10. 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…

  11. 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…

  12. A Comparison of the 27-Item and 12-Item Intolerance of Uncertainty Scales

    ERIC Educational Resources Information Center

    Khawaja, Nigar G.; Yu, Lai Ngo Heidi

    2010-01-01

    The 27-item Intolerance of Uncertainty Scale (IUS) has become one of the most frequently used measures of Intolerance of Uncertainty. More recently, an abridged, 12-item version of the IUS has been developed. The current research used clinical (n = 50) and non-clinical (n = 56) samples to examine and compare the psychometric properties of both…

  13. 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

  14. 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

  15. 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

  16. Intolerance of uncertainty as a predictor of post-traumatic stress symptoms following a traumatic event.

    PubMed

    Oglesby, Mary E; Boffa, Joseph W; Short, Nicole A; Raines, Amanda M; Schmidt, Norman B

    2016-06-01

    Intolerance of uncertainty (IU) has been associated with elevated post-traumatic stress symptoms (PTSS) in the extant literature. However, no research to date has investigated whether pre-trauma IU predicts PTSS following trauma exposure. The current study prospectively examined the relationship between IU and PTSS within a sample of individuals with various levels of exposure to a university campus shooting. We hypothesized that pre-trauma IU would predict elevated PTSS following a campus shooting, even after covarying for anxiety sensitivity (AS), a known correlate of PTSS. Participants included undergraduates (n=77) who completed a self-report battery in Introductory Psychology. After a campus shooting, they were invited to complete measures of PTSD symptoms and level of exposure to the shooting. As anticipated, results revealed pre-trauma IU as a significant predictor of elevated PTSS following the campus shooting. These results remained significant after covarying for pre-trauma levels of AS. Our results are the first to demonstrate that elevated pre-trauma levels of IU predict later PTSS following exposure to a traumatic event. This finding is discussed in terms of promising directions for future research and treatment strategies. PMID:26803928

  17. Cold intolerance of the hand measured by the CISS questionnaire in a normative study population.

    PubMed

    Ruijs, A C J; Jaquet, J-B; Daanen, H A M; Hovius, S E R

    2006-10-01

    Cold intolerance has been recognized as one of the most disabling sequelae of upper extremity trauma, especially when neurovascular structures are involved. In this study, we aimed to describe cold intolerance in a normative study population, validate the Cold Intolerance Symptom Severity (CISS) questionnaire and define the threshold for abnormal cold intolerance. One hundred and eight volunteers participated in our study. In addition to the CISS score, information about age, gender and previous surgery or trauma to the upper extremity was obtained. There were no volunteers with previous peripheral nerve injury and subjects with a history of Raynaud's disease, upper extremity injury or surgery were excluded (n=40). The CISS scores of the study population (n=68) averaged 12.9 (SD 8.2). Age and gender were not correlated with CISS score. The upper 95% confidence interval of the CISS scores for healthy subjects is about 30. We suggest this value as a threshold for pathological cold intolerance. PMID:16808991

  18. Serotonin Transporter Availability in the Amygdala and Bed Nucleus of the Stria Terminalis Predicts Anxious Temperament and Brain Glucose Metabolic Activity

    PubMed Central

    Oler, Jonathan A; Fox, Andrew S; Shelton, Steven E; Christian, Bradley T; Murali, Dhanabalan; Oakes, Terrence R; Davidson, Richard J; Kalin, Ned H

    2009-01-01

    The serotonin transporter (5-HTT) plays a critical role in regulating serotonergic neurotransmission and is implicated in the pathophysiology of anxiety and affective disorders. PET scans using [C-11]DASB to measure 5-HTT availability (an index of receptor density and binding) were performed in 34 rhesus monkeys in which the relation between regional brain glucose metabolism and anxious temperament was previously established. 5-HTT availability in the amygdalohippocampal area and bed nucleus of the stria terminalis correlated positively with individual differences in a behavioral and neuroendocrine composite of anxious temperament. 5-HTT availability also correlated positively with stress-induced metabolic activity within these regions. Collectively, these findings suggest that serotonergic modulation of neuronal excitability in the neural circuitry associated with anxiety mediates the developmental risk for affect-related psychopathology. PMID:19675230

  19. [Old age and illness--destroying the intolerable?].

    PubMed

    Heinrich, K

    1991-05-01

    The spectacular criminal case of a nurse who because of killing seven old patients in an intensive care ward had been sentenced to jail for 11 years is shown as example of radical thinking in the face of intolerability of serious illness and age. The deficit model of age is on the one hand justly criticized and called invalid, on the other hand negative aspects of age may not be concealed in the face of hedonistic principles of the present epoch. There is no doubt about the monstrosity of the case of the guilty nurse but it may be exemplary for a frequent defensive behaviour against the phenomena of age. If this is right this singular case may be characteristic of common thinking on the unbearable presumption of age. Self defense turning into aggressivity because of foreseeing the own fate of hopeless illness in moribund aged would then have to be seen as a socially significant attitude. PMID:1869232

  20. 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.

  1. 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. PMID:25002667

  2. 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 ...

  3. 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. PMID:23982154

  4. 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

  5. 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

  6. 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

  7. 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

  8. Assessment of food chemical intolerance in adult asthmatic subjects.

    PubMed Central

    Hodge, L.; Yan, K. Y.; Loblay, R. L.

    1996-01-01

    BACKGROUND: Identification of food chemical intolerance in asthmatic subjects can be reliably assessed by changes in the forced expiratory volume in one second (FEV1) in response to double blind, placebo controlled challenges on a strict elimination diet. However, this method is cumbersome and time consuming. A study was undertaken to determine whether changes in bronchial responsiveness to histamine following food chemical challenge without an elimination diet might be a faster, more convenient method. METHODS: Eleven adult asthmatic subjects were challenged twice with metabisulphite, aspirin, monosodium glutamate, artificial food colours, sodium nitrite/ nitrate, 0.5% citric acid solution (placebo), and sucrose (placebo) on separate days. During the first set of challenges subjects consumed a normal diet. Bronchial responsiveness to histamine was assessed 90 minutes after each challenge. A greater than twofold increase in bronchial responsiveness was considered positive. For one month prior to and during the second set of challenges subjects followed a strict elimination diet and FEV1 was monitored during and for two hours after each challenge. A fall in FEV1 of 20% or more was considered positive. RESULTS: Of the 77 food chemical challenges performed on an unmodified diet, 20 were positive (six placebo responses). In two subjects it was not possible to perform a histamine test after one of the chemical challenges because of poor spirometric function. Of the 77 food chemical challenges performed on an elimination diet, 11 were positive (no placebo responses). Excluding the two challenges in which there were no corresponding histamine tests, only on two occasions did the positive responses in both methods coincide, giving the unmodified diet method a sensitivity of 22%. CONCLUSIONS: Strict dietary elimination and measurement of FEV1 after double blind food chemical challenge remains the most reliable method for the detection of food chemical intolerance in

  9. 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

  10. Validation of Point-of-Care Glucose Testing for Diagnosis of Type 2 Diabetes

    PubMed Central

    Božičević, Sandra; Pape-Medvidović, Edita; Ljubić, Spomenka

    2013-01-01

    Point-of-care (POC) glucose technology is currently considered to be insufficiently accurate for the diagnosis of diabetes. The objective of this study was to investigate the diagnostic accuracy of an innovative, interference-resistant POC glucose meter (StatStrip glucose hospital meter, Nova Biomedical, USA) in subjects with a previous history of dysglycaemia, undergoing a 75 g diagnostic oral glucose tolerance test (oGTT). Venous and capillary blood sampling for the reference laboratory procedure (RLP) and POC-glucose measurement was carried out at fasting and 2 h oGTT, and categories of glucose tolerance were classified according to 2006 WHO diagnostic criteria for the respective sample type. We found an excellent between-method correlation at fasting (r = 0.9681, P < 0.0001) and 2 h oGTT (r = 0.9768, P < 0.0001) and an almost perfect diagnostic agreement (weighted Kappa = 0.858). Within a total of 237 study subjects, 137 were diagnosed with diabetes with RLP, and only 6 of them were reclassified as having glucose intolerance with POC. The diagnostic performance of POC-fasting glucose in discriminating between the normal and any category of disturbed glucose tolerance did not differ from the RLP (P = 0.081). Results of this study indicate that StatStrip POC glucose meter could serve as a reliable tool for the diabetes diagnosis, particularly in primary healthcare facilities with dispersed blood sampling services. PMID:24382960

  11. 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

  12. 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

  13. The Relationship Between Intolerance of Uncertainty, Sensory Sensitivities, and Anxiety in Autistic and Typically Developing Children.

    PubMed

    Neil, Louise; Olsson, Nora Choque; Pellicano, Elizabeth

    2016-06-01

    Guided by a recent theory that proposes fundamental differences in how autistic individuals deal with uncertainty, we investigated the extent to which the cognitive construct 'intolerance of uncertainty' and anxiety were related to parental reports of sensory sensitivities in 64 autistic and 85 typically developing children aged 6-14 years. Intolerance of uncertainty and anxiety explained approximately half the variance in autistic children's sensory sensitivities, but only around a fifth of the variance in typical children's sensory sensitivities. In children with autism only, intolerance of uncertainty remained a significant predictor of children's sensory sensitivities once the effects of anxiety were adjusted for. Our results suggest intolerance of uncertainty is a relevant construct to sensory sensitivities in children with and without autism. PMID:26864157

  14. Abnormal pulmonary macrophages in lysinuric protein intolerance. Ultrastructural, morphometric, and x-ray microanalytic study.

    PubMed

    Parto, K; Mäki, J; Pelliniemi, L J; Simell, O

    1994-05-01

    Pediatric patients with lysinuric protein intolerance are predisposed to develop alveolar hemorrhage and pulmonary alveolar proteinosis. We evaluated the ultrastructural features of pulmonary alveolar proteinosis and the potential abnormality of pulmonary macrophages in lysinuric protein intolerance. Lung tissue specimens obtained at autopsy were examined by transmission electron microscopy. Pulmonary macrophages from bronchoalveolar lavages were studied by electron microscopy, morphometry, and x-ray microanalysis and compared with control cells. The macrophages of patients with lysinuric protein intolerance contained significantly more multilamellar structures than did control cells and showed electron-dense material identified to contain excess iron. The predisposition to develop alveolar proteinosis and the abnormal ultrastructure of pulmonary macrophages suggest altered phospholipid metabolism in patients with lysinuric protein intolerance. The marked intramacrophageal accumulations of iron might indicate altered iron metabolism or subclinical hemorrhages in lung tissue. PMID:8192561

  15. Fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and nonallergic food intolerance: FODMAPs or food chemicals?

    PubMed

    Barrett, Jacqueline S; Gibson, Peter R

    2012-07-01

    Food intolerance in irritable bowel syndrome (IBS) is increasingly being recognized, with patients convinced that diet plays a role in symptom induction. Evidence is building to implicate fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) in the onset of abdominal pain, bloating, wind and altered bowel habit through their fermentation and osmotic effects. Hypersensitivity to normal levels of luminal distension is known to occur in patients with IBS, with consideration of food chemical intolerance likely to answer many questions about this physiological process. This paper summarizes the evidence and application of the most common approaches to managing food intolerance in IBS: the low-FODMAP diet, the elimination diet for food chemical sensitivity and others including possible noncoeliac gluten intolerance. PMID:22778791

  16. 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

  17. Fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and nonallergic food intolerance: FODMAPs or food chemicals?

    PubMed Central

    Gibson, Peter R.

    2012-01-01

    Food intolerance in irritable bowel syndrome (IBS) is increasingly being recognized, with patients convinced that diet plays a role in symptom induction. Evidence is building to implicate fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) in the onset of abdominal pain, bloating, wind and altered bowel habit through their fermentation and osmotic effects. Hypersensitivity to normal levels of luminal distension is known to occur in patients with IBS, with consideration of food chemical intolerance likely to answer many questions about this physiological process. This paper summarizes the evidence and application of the most common approaches to managing food intolerance in IBS: the low-FODMAP diet, the elimination diet for food chemical sensitivity and others including possible noncoeliac gluten intolerance. PMID:22778791

  18. 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 ...

  19. 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 ...

  20. Continuous Glucose Monitoring

    MedlinePlus

    ... catalog. Additional Links ​ Alternative Devices for Taking Insulin Children and Diabetes Glucose Meters Juvenile Diabetes (Teens and Diabetes ) Know Your Blood Glucose Numbers Your Guide to Diabetes: Type 1 and Type 2 Contact Us Health Information Center ...

  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. Neuropeptides and peptide hormones in syncope and orthostatic intolerance.

    PubMed

    Krishnan, Balaji; Benditt, David G

    2014-01-01

    Syncope and orthostatic intolerance (OI) are common clinical syndromes often requiring medical attention. The former is defined as transient loss of consciousness and postural tone due to self-limited cerebral hypoperfusion, while the latter consists of inappropriate cardiovascular responses to upright posture such as occur with orthostatic hypotension (OH) or postural orthostatic tachycardia syndrome. The most frequent causes of syncope and OI are conditions that temporarily disrupt essential moment-to-moment interaction between the autonomic nervous system and cardiovascular system. In this regard, many neuropeptides (NPs) or peptide hormones (PH) exert cardioactive effects that might contribute to the pathophysiology of certain forms of syncope or OI. To date, the principal peptides that have been studied in this context are: atrial and B-type-neuropeptides, adrenomedullin, endothelin-1 (ET-1), galanin, and vasopressin. While definitive conclusions cannot yet be drawn, the intrinsic vasoconstrictor ET-1 appears to be elevated in OH, presumably to compensate for vasodilation and hypotension of other etiologies. As such elevated ET-1 may become a marker for OH. Further, elevated NT-proBNP may play a role in causing vasodilation and hypotension in some forms of OH of previously unknown cause, and may be a marker in other patients of a cardiovascular cause of syncope and OI. In the end, the study of the role of NPs and PHs in syncope and OI syndromes is at an early stage, and considerable further future effort is needed. PMID:25299506

  3. 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.

  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. PMID:24915366

  5. 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

  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. Pharmacological therapy of feed intolerance in the critically ills

    PubMed Central

    Nguyen, Nam Q

    2014-01-01

    Feed intolerance in the setting of critical illness is associated with higher morbidity and mortality, and thus requires promptly and effective treatment. Prokinetic agents are currently considered as the first-line therapy given issues relating to parenteral nutrition and post-pyloric placement. Currently, the agents of choice are erythromycin and metoclopramide, either alone or in combination, which are highly effective with relatively low incidence of cardiac, hemodynamic or neurological adverse effects. Diarrhea, however, can occur in up to 49% of patients who are treated with the dual prokinetic therapy, which is not associated with Clostridium difficile infection and settled soon after the cessation of the drugs. Hence, the use of prokinetic therapy over a long period or for prophylactic purpose must be avoided, and the indication for ongoing use of the drug(s) must be reviewed frequently. Second line therapy, such as total parenteral nutrition and post-pyloric feeding, must be considered once adverse effects relating the prokinetic therapy develop. PMID:25133043

  8. 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

  9. Salicylate intolerance: a masquerader of multiple adverse drug reactions

    PubMed Central

    Fernando, Suran Loshana; Clarke, Lesley R

    2009-01-01

    A female in her early 50s presented with a long-standing history of episodic urticaria and angioedema. She also reported urticarial reactions after ingestion of aspirin, prednisone and multiple antibiotics. These medications were all taken during upper respiratory tract infections. An elimination diet followed by a series of open challenges to food chemicals demonstrated an urticarial eruption following the ingestion of mints, which contain high levels of salicylates. A double-blinded placebo-controlled challenge to salicylate confirmed her sensitivity and explained her reaction to aspirin. The patient informed her treating physician of her copious ingestion of mints during upper respiratory tract infections. Drug hypersensitivity to antibiotics and prednisone was excluded on the basis of negative radioallergosorbent tests (RASTs) and/or absent skin-test responses and/or tolerance to oral challenges. This patient had a salicylate intolerance that caused her episodic urticaria and angioedema, and also masqueraded as a drug allergy due to the concurrent ingestion of mints. PMID:21918670

  10. Cardiac dysfunction and orthostatic intolerance in patients with myalgic encephalomyelitis and a small left ventricle.

    PubMed

    Miwa, Kunihisa

    2015-07-01

    The etiology of chronic fatigue syndrome (CFS) is unknown. Myalgic encephalomyelitis (ME) has been recently postulated to be the cause of CFS. Orthostatic intolerance (OI) has been known as an important symptom in predicting quality of life in CFS patients. Cardiac function may be impaired in patients with ME. The presence or absence of OI was determined both symptomatically and by using a 10-min stand-up test in 40 ME patients. Left ventricular (LV) dimensions and function were determined echocardiographically in the ME patients compared to 40 control subjects. OI was noted in 35 (97%) of the 36 ME patients who could stand up quickly. The mean values for the cardiothoracic ratio, systemic systolic and diastolic pressures, LV end-diastolic diameter (EDD), LV end-systolic diameter, stroke volume index, cardiac index and LV mass index were all significantly smaller in the ME group than in the controls. Both a small LVEDD (<40 mm, 45 vs. 3%) and a low cardiac index (<2 l/ min/mm2, 53 vs. 8%) were significantly more common in the ME group than in the controls. Both heart rate and LV ejection fraction were similar between the groups. In conclusion, a small LV size with a low cardiac output was common in ME patients, in whom OI was extremely common. Cardiac dysfunction with a small heart appears to be related to the symptoms of ME. PMID:24736946

  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. PMID:24079212

  12. 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 of the blood sugar level). Note: Normal value ranges may vary slightly ...

  13. 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.

  14. 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

  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. Glucose metabolism in cachectic patients with colorectal cancer.

    PubMed

    Holroyde, C P; Skutches, C L; Boden, G; Reichard, G A

    1984-12-01

    We have studied a defined group of 12 weight-losing patients with metastatic colorectal cancer to evaluate the occurrence of and possible relationship between those determinants of carbohydrate metabolism which have been reported to occur commonly in cancer cachexia. The rates of endogenous glucose production and recycling via lactate (Cori cycle) were measured following an infusion of 50 to 100 microCi of [1-14C]glucose. Compared to an age-related group of control subjects without cancer, significantly elevated rates of glucose production [136.4 +/- 9.0 (S.E.) versus 101.0 +/- 4.6 mg/kg/hr; p less than 0.01] and recycling (43.0 +/- 7.2 versus 15.4 mg/kg/hr; p less than 0.01) were observed. Values for glucose production and recycling ranged from normal to markedly elevated. Glucose tolerance was then determined following a p.o. glucose load of 40 g/sq m in 10 of the 12 patients. Compared to control subjects, all showed a significantly delayed clearance of glucose (p less than 0.01) and a blunted insulin-secretory responsiveness (p less than 0.025). Increased glucose production and recycling was only observed in the presence of carbohydrate intolerance, but the latter occurred in a manner which seemed independent of the rate of glucose turnover. In order to obtain an estimate of hepatic glycogen reserves, glucagon, 15 ng/kg/min, was infused over 40 min in seven subjects. A significantly blunted glycemic response was observed in the cancer patients compared to controls (delta 25.0 +/- 6.9 versus 57.8 +/- 8.5 mg/dl; p less than 0.025). Neither the rate of glucose production nor the glycemic response to glucagon appeared to correlate with the immediate antecedent caloric intake. An apparent relationship was observed, however, between increased glucose production and recycling and a lack of response to infused glucagon, probably reflecting decreased glycogen stores in the face of an increased glucose requirement by the patient. We have shown that diverse abnormalities

  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. PMID:27319094

  18. 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. PMID:25262317

  19. Idiopathic environmental intolerances (IEI): from molecular epidemiology to molecular medicine.

    PubMed

    De Luca, C; Scordo, G; Cesareo, E; Raskovic, D; Genovesi, G; Korkina, L

    2010-07-01

    Inherited or acquired impairment of xenobiotics metabolism is a postulated mechanism underlying environment-associated pathologies such as multiple chemical sensitivity, fibromyalgia, chronic fatigue syndrome, dental amalgam disease, and others, also collectively named idiopathic environmental intolerances (IEI). In view of the poor current knowledge of their etiology and pathogenesis, and the absence of recognised genetic and metabolic markers of the diseases. They are often considered "medically unexplained syndromes",. These disabling conditions share the features of polysymptomatic multi-organ syndromes, considered by part of the medical community to be aberrant responses triggered by exposure to low-dose organic and inorganic chemicals and metals, in concentrations far below average reference levels admitted for environmental toxicants. A genetic predisposition to altered biotransformation of environmental chemicals, drugs, and metals, and of endogenous low-molecular weight metabolites, caused by polymorphisms of genes coding for xenobiotic metabolizing enzymes, their receptors and transcription factors appears to be involved in the susceptibility to these environment-associated pathologies, along with epigenetic factors. Free radical/antioxidant homeostasis may also be heavily implicated, indirectly by affecting the regulation of xenobiotic metabolizing enzymes, and directly by causing increased levels of oxidative products, implicated in the chronic damage of cells and tissues, which is in part correlated with clinical symptoms. More systematic studies of molecular epidemiology, toxico- and pharmaco-genomics, elucidating the mechanisms of regulation, expression, induction, and activity of antioxidant/detoxifying enzymes, and the possible role of inflammatory mediators, promise a better understanding of this pathologically increased sensitivity to low-level chemical stimuli, and a solid basis for effective individualized antioxidant- and/or chelator

  20. 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).

  1. Lysine fluxes across the jejunal epithelium in lysinuric protein intolerance.

    PubMed

    Desjeux, J F; Simell, R O; Dumontier, A M; Perheentupa, J

    1980-06-01

    Lysinuric protein intolerance (LPI) is one of a group of genetic diseases in which intestinal absorption of the diamino acids lysine, arginine, and ornithine is impaired. In LPI, the clinical symptoms are more severe than in the kindred disorders. The mechanism of lysine absorption was, therefore, investigated in vitro on peroral jejunal biopsy specimens in seven patients with LPI and 27 controls. The lysine concentration ratio between cell compartment and medium was significantly higher in the LPI group (mean+/-SEM, 7.17+/-0.60) than in the controls (5.44+/-0.51). This was also true for the intracellular Na concentration (LPI, 73.6+/-10.8 mM; controls 42.3+/-3.7 mM). The rate of unidirectional influx of lysine across the luminal membrane was Na dependent and was the same in the two groups. In the absence of an electrochemical gradient, net transepithelial lysine secretion was observed in LPI. This was entirely the result of a 60% reduction of the unidirectional flux from mucosa to serosa. Calculation of unidirectional fluxes revealed the most striking difference at the basolateral membrane, where the flux from cells to serosa was reduced by 62% and the corresponding permeability coefficient reduced by 71%. A progressive reduction in short-circuit current appeared in the epithelia of all four patients with LPI tested after addition of 3 mM lysine. Thus, LPI appears to be the first disease in which a genetically determined transport defect has been demonstrated at the basolateral membrane. PMID:6773985

  2. [Celiac disease--the chameleon among the food intolerances].

    PubMed

    Ströhle, Alexander; Wolters, Maike; Hahn, Andreas

    2013-10-01

    Celiac disease is an autoimmune disorder resulting from gluten intolerance and is based on a genetically predisposition. Symptoms occur upon exposure to prolamin from wheat, rye, barley and related grain. The pathogenesis of celiac disease has not yet been sufficiently elucidated but is being considered as an autoimmune process. At its core are the deamidation of prolamin fragments, the building of specific antibodies and the activation of cytotoxic T-cells. The immunological inflammatory process is accompanied by structural damages of the enterocytes (villous atrophy, colonization and crypt hyperplasia). The symptoms and their extent depend on the type of the celiac disease; classic and non-classic forms are being distinguished (atypical, oligosymptomatic, latent and silent celiac disease). Characteristics of the classic presentation are malabsorption syndrome and intestinal symptoms such as mushy diarrhea and abdominal distension. The diagnosis of celiac disease is based on four pillars: Anamnesis and clinical presentation, serological evidence of coeliac specific antibodies (IgA-t-TG; IgA-EmA), small intestine biopsy and improvement of symptoms after institution of a gluten-free diet. The basis of the therapy is a lifelong gluten-free diet, i. e. wheat, rye, barley, spelt, green-core, faro-wheat, kamuth and conventional oats as well as food items obtained therefrom. Small amounts of up to 50 mg gluten per day are usually tolerated by most patients; amounts of > or = 100 mg/day lead mostly to symptoms. Gluten-free foods contain < or = 20 ppm or 20 mg/kg (Sign: symbol of the 'crossed ear' or label 'gluten-free'). At the beginning of the therapy the fat and lactose intake may need to be reduced; also the supplementation of single micronutrients (fat-soluble vitamins, folic acid, B12, iron, and calcium) may be required. Alternative therapies are being developed but have not yet been clinically tested. PMID:24266248

  3. 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

  4. Association between blood glucose level derived using the oral glucose tolerance test and glycated hemoglobin level

    PubMed Central

    Kim, Hyoung Joo; Kim, Young Geon; Park, Jin Soo; Ahn, Young Hwan; Ha, Kyoung Hwa; Kim, Dae Jung

    2016-01-01

    Background/Aims: Glycated hemoglobin (HbA1c) is widely used as a marker of glycemic control. Translation of the HbA1c level to an average blood glucose level is useful because the latter figure is easily understood by patients. We studied the association between blood glucose levels revealed by the oral glucose tolerance test (OGTT) and HbA1c levels in a Korean population. Methods: A total of 1,000 subjects aged 30 to 64 years from the Cardiovascular and Metabolic Diseases Etiology Research Center cohort were included. Fasting glucose levels, post-load glucose levels at 30, 60, and 120 minutes into the OGTT, and HbA1c levels were measured. Results: Linear regression of HbA1c with mean blood glucose levels derived using the OGTT revealed a significant correlation between these measures (predicted mean glucose [mg/dL] = 49.4 × HbA1c [%] − 149.6; R2 = 0.54, p < 0.001). Our linear regression equation was quite different from that of the Alc-Derived Average Glucose (ADAG) study and Diabetes Control and Complications Trial (DCCT) cohort. Conclusions: Discrepancies between our results and those of the ADAG study and DCCT cohort may be attributable to differences in the test methods used and the extent of insulin secretion. More studies are needed to evaluate the association between HbA1c and self monitoring blood glucose levels. PMID:26898598

  5. Gut microbe-derived extracellular vesicles induce insulin resistance, thereby impairing glucose metabolism in skeletal muscle

    PubMed Central

    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

  6. 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

  7. 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.

  8. Sources and severity of self-reported food intolerance after ileal pouch-anal anastomosis.

    PubMed

    Steenhagen, Elles; de Roos, Nicole M; Bouwman, Carolien A; van Laarhoven, Cees J H M; van Staveren, Wija A

    2006-09-01

    Data on food intolerance after ileal pouch-anal anastomosis are scarce. The aim of this study was to identify foods causing intolerance and to determine the nature and severity of reported symptoms. Patients from the Dutch Crohn's and Ulcerative Colitis Association were mailed a survey on food intolerance; 105 (31% men) of 137 patients took part. They all reported intolerance to one or more foods. Common symptoms (scored from 0=absent to 10=severe), included diarrhea (mean score=5.8), fatigue (mean score=5.5), and thirst (mean score=4.6). Spicy foods, cabbage, and citrus fruits (or juice) were most likely to decrease stool consistency, increase stool frequency, or cause perianal irritation. Onions, cabbage, or leeks were reported by 28% of the patients to cause flatulence. The urge to defecate was stronger after a cooked meal (45% within (1/2) hour) than after sandwiches (15% within (1/2) hour). Foods reported to increase stool consistency were potato products, bread, and bananas. This study demonstrates that food intolerance is a common, albeit mild, problem after ileal pouch-anal anastomosis. Food and nutrition professionals should encourage patients to base their food choices on individual tolerance as long as no (patho-) physiological-based evidence to the contrary is available. PMID:16963353

  9. Cold intolerance following median and ulnar nerve injuries: prognosis and predictors.

    PubMed

    Ruijs, A C J; Jaquet, J-B; van Riel, W G; Daanen, H A M; Hovius, S E R

    2007-08-01

    This study describes the predictors for cold intolerance and the relationship to sensory recovery after median and ulnar nerve injuries. The study population consisted of 107 patients 2 to 10 years after median, ulnar or combined median and ulnar nerve injuries. Patients were asked to fill out the Cold Intolerance Severity Score (CISS) questionnaire and sensory recovery was measured using Semmes-Weinstein monofilaments. Fifty-six percent of the patients with a single nerve injury and 70% with a combined nerve injury suffered abnormal cold intolerance. Patients with no return of sensation had dramatically higher CISS-scores than patients with normal sensory recovery. Females had higher CISS scores post-injury than males. Cold intolerance did not diminish over the years. Patients with higher CISS scores needed more time to return to their work. Age, additional arterial injury, site or type of the injury and dominance of the hand were not found to have a significant influence on cold intolerance. PMID:17482322

  10. 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

  11. [Acetylsalicylic acid and food additive intolerance in urticaria, bronchial asthma and rhinopathy].

    PubMed

    Wüthrich, B; Fabro, L

    1981-09-26

    Adverse reactions (urticaria, angio-edema, bronchoconstriction, purpura) to Aspirin (ASS) and food-and-drug additives such as the yellow dye tartrazine and the preservative benzoate are observed all over the world. Since the exact pathogenetic mechanisms of this condition is unknown, it is described as intolerance or pseudo-allergy and has been related to an imbalance of prostaglandin synthesis. Among 620 patients with urticaria, bronchial asthma or chronic rhinitis, oral provocation tests with ASS, tartrazine or benzoic acid revealed in 165 (26.6%) intolerance to ASS or additives. Frequency of intolerance to tartrazine varied between 6.1% in urticaria (n=308), 7.3% in asthma (n=96) and 14.5% in urticaria and asthma patients, while intolerance to benzoate varied from 2.5% in rhinitis (n=40) to 11.5% in asthma. More than two thirds of the intolerant patients were improved by an elimination diet and by the avoidance of "aspirin-like" drugs. More than one third of chronic urticaria patients became symptomfree. In Switzerland exact declaration of all food additives is urgently needed. Moreover, azo-dyes must no longer be used for colouring of drugs. PMID:7291963

  12. 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

  13. Altered glucose metabolism rather than naive type 2 diabetes mellitus (T2DM) is related to vitamin D status in severe obesity

    PubMed Central

    2014-01-01

    Context The last decades have provided insights into vitamin D physiology linked to glucose homeostasis. Uncertainties remain in obesity due to its intrinsic effects on vitamin D and glucose tolerance. Objectives To assess the relationship between vitamin D and glucose abnormalities in severely obese individuals previously unknown to suffer from abnormal glucose metabolism. Setting Tertiary care centre. Patients 524 obese patients (50.3 ± 14.9 yrs; BMI, 47.7 ± 7.3 kg/m2) screened by OGTT, HbA1c and the lipid profile. Vitamin D status was assessed by 25(OH)D3, PTH and electrolyte levels. 25(OH)D3 deficiency/insufficiency were set at 20 and 30 ng/ml, respectively. All comparative and regression analyses were controlled for age, BMI and gender. Results The prevalence of vitamin D deficiency/insufficiency and secondary hyperparathyroidism were 95% and 50.8%, respectively. Normal glucose tolerance (NGT), impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) were found in 37.8%, 40.5% and 21.7% of cases, respectively. Large variations in metabolic parameters were seen across categories of vitamin D status, but the only significant differences were found for C-peptide, tryglicerides, LDL- and HDL-cholesterol levels (p < 0.05 for all). The prevalence of vitamin D deficiency was documented to be slightly but significantly more frequent in glucose-intolerant patients (IFG + IGT + T2DM) compared to the -normotolerant counterpart (87% vs. 80%, p < 0.05). In partial correlation analyses, there was no association between vitamin D levels and glucose-related markers but for HbA1c (r = −0.091, p < 0.05), and both basal and OGTT-stimulated insulin levels (r = 0.097 and r = 0.099; p < 0.05 for all). Vitamin D levels were also correlated to HDL-cholesterol (r = 0.13, p = 0.002). Multivariate regression analysis inclusive of vitamin D, age, BMI, gender and fat mass as

  14. Use of Mycophenolate Mofetil in Patients with Severe Localized Scleroderma Resistant or Intolerant to Methotrexate.

    PubMed

    Mertens, Jorre S; Marsman, Diane; van de Kerkhof, Peter C M; Hoppenreijs, Esther P A H; Knaapen, Hanneke K A; Radstake, Timothy R D; de Jong, Elke M G J; Seyger, Marieke M B

    2016-04-12

    To assess the efficacy and safety of mycophenolate mofetil (MMF) in patients with localized scleroderma (LoS) resistant or intolerant to previous treatment with methotrexate (MTX). A case series of patients with LoS treated with MMF. Outcome was assessed through clinical examination. Adverse events were documented. Seven patients with LoS were treated with MMF. Median age at MMF initiation was 15 years (range 7-74 years). Three patients received MMF due to MTX ineffectiveness and 4 due to MTX intolerance. Disease remission was achieved in 4 patients and maintained in one patient. One patient showed a favourable response, but had to discontinue treatment due to elevated liver enzymes. The remaining patient experienced disease progression. MMF was shown to improve the clinical condition of patients with refractory LoS and may be a relatively safe alternative in patients who are intolerant to MTX. PMID:26582717

  15. Orthostatic intolerance and the postural tachycardia syndrome: genetic and environment pathophysiologies. Neurolab Autonomic Team

    NASA Technical Reports Server (NTRS)

    Robertson, D.; Shannon, J. R.; Biaggioni, I.; Ertl, A. C.; Diedrich, A.; Carson, R.; Furlan, R.; Jacob, G.; Jordan, J.

    2000-01-01

    Orthostatic intolerance is a common problem for inbound space travelers. There is usually tachycardia on standing but blood pressure may be normal, low or, rarely, elevated. This condition is analogous to the orthostatic intolerance that occurs on Earth in individuals with orthostatic tachycardia, palpitations, mitral valve prolapse, and light-headedness. Our studies during the Neurolab mission indicated that sympathetic nerve traffic is raised in microgravity and that plasma norepinephrine is higher than baseline supine levels but lower than baseline upright levels. A subgroup of patients with familial orthostatic intolerance differ from inbound space travelers in that they have an alanine-to-to-proline mutation at amino acid position 457 in their norepinephrine transporter gene. This leads to poor clearance of norepinephrine from synapses, with consequent raised heart rate. Clinical features of these syndromes are presented.

  16. (51Cr)EDTA intestinal permeability in children with cow's milk intolerance

    SciTech Connect

    Schrander, J.J.; Unsalan-Hooyen, R.W.; Forget, P.P.; Jansen, J. )

    1990-02-01

    Making use of ({sup 51}Cr)EDTA as a permeability marker, we measured intestinal permeability in a group of 20 children with proven cow's milk intolerance (CMI), a group of 17 children with similar complaints where CMI was excluded (sick controls), and a group of 12 control children. ({sup 51}Cr)EDTA test results (mean +/- SD) were 6.85 +/- 3.64%, 3.42 +/- 0.94%, and 2.61 +/- 0.67% in the group with CMI, the sick control, and the control group, respectively. When compared to both control groups, patients with cow's milk intolerance (CMI) showed a significantly increased small bowel permeability. We conclude that the ({sup 51}Cr)EDTA test can be helpful for the diagnosis of cow's milk intolerance.

  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. PMID:20660065

  18. Glucose metabolism ontogenesis in rainbow trout (Oncorhynchus mykiss) in the light of the recently sequenced genome: new tools for intermediary metabolism programming.

    PubMed

    Marandel, Lucie; Véron, Vincent; Surget, Anne; Plagnes-Juan, Élisabeth; Panserat, Stéphane

    2016-03-01

    The rainbow trout (Oncorhynchus mykiss), a carnivorous fish species, displays a 'glucose-intolerant' phenotype when fed a high-carbohydrate diet. The importance of carbohydrate metabolism during embryogenesis and the timing of establishing this later phenotype are currently unclear. In addition, the mechanisms underlying the poor ability of carnivorous fish to use dietary carbohydrates as a major energy substrate are not well understood. It has recently been shown in trout that duplicated genes involved in glucose metabolism may participate in establishing the glucose-intolerant phenotype. The aim of this study was therefore to provide new understanding of glucose metabolism during ontogenesis and nutritional transition, taking into consideration the complexity of the trout genome. Trout were sampled at several stages of development from fertilization to hatching, and alevins were then fed a non-carbohydrate or a high-carbohydrate diet during first feeding. mRNA levels of all glucose metabolism-related genes increased in embryos during the setting up of the primitive liver. After the first meal, genes rapidly displayed expression patterns equivalent to those observed in the livers of juveniles. g6pcb2.a (a glucose 6-phosphatase-encoding gene) was up-regulated in alevins fed a high-carbohydrate diet, mimicking the expression pattern of gck genes. The g6pcb2.a gene may contribute to the non-inhibition of the last step of gluconeogenesis and thus to establishing the glucose-intolerant phenotype in trout fed a high-carbohydrate diet as early as first feeding. This information is crucial for nutritional programming investigations as it suggests that first feeding would be too late to programme glucose metabolism in the long term. PMID:26747908

  19. The Relationship between Frustration Intolerance and Academic Achievement in College

    ERIC Educational Resources Information Center

    Wilde, Jerry

    2012-01-01

    Traditional measures of predicting academic achievement in college such as high school grades and standardized test scores account for approximately 25% of the difference between predicted and actual grade point average (GPA). Researchers have also examined the relationship between psychological factors and academic self-efficacy which may account…

  20. 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...

  1. 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 ...

  2. Glucose monitoring during Ramadan.

    PubMed

    Jabbar, Abdul

    2015-05-01

    In patients with diabetes who intend to fast during Ramadan, self-monitoring of blood glucose (SMBG) is an important tool. During this month, a long established treatment regimen, including medications, physical activity and diet plan, is changed to achieve concordance with the rules of fasting. Without proper glucose monitoring, it is not possible to achieve good glycaemic control. PMID:26013788

  3. The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

    PubMed

    Rosario, Wilfredo; Singh, Inderroop; Wautlet, Arnaud; Patterson, Christa; Flak, Jonathan; Becker, Thomas C; Ali, Almas; Tamarina, Natalia; Philipson, Louis H; Enquist, Lynn W; Myers, Martin G; Rhodes, Christopher J

    2016-09-01

    The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia. PMID:27207534

  4. Combining plasma Epstein-Barr virus DNA and nodal maximal standard uptake values of 18F-fluoro-2-deoxy-D-glucose positron emission tomography improved prognostic stratification to predict distant metastasis for locoregionally advanced nasopharyngeal carcinoma

    PubMed Central

    Chen, Qiu-Yan; Guo, Shan-Shan; Liu, Li-Ting; Fan, Wei; Zhang, Xu; Guo, Ling; Zhao, Chong; Cao, Ka-Jia; Qian, Chao-Nan; Guo, Xiang; Xie, Dan; Zeng, Mu-Sheng; Mai, Hai-Qiang

    2015-01-01

    Background This study aimed to evaluate the value of combining the nodal maximal standard uptake values (SUVmax) of 18 F-fluoro-2-deoxy-D-glucose positron emission tomography with Epstein-Barr virus DNA(EBV DNA) levels to predict distant metastasis for nasopharyngeal carcinoma (NPC) patients Patients and Methods Eight hundred seventy-four patients with stage III-IVa-b NPC were evaluated for the effects of combining SUVmax and EBV DNA levels on distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS). Results The optimal cutoff value was 6,220 copies/mL for EBV DNA and 7.5 for SUVmax-N. Patients with lower EBV DNA levels or SUVmax-N had a significantly better 3-year DMFS, DFS, and OS. Patients were divided into four groups based on EBV DNA and SUVmax-N, as follows: low EBV DNA and low SUVmax-N (LL), low EBV DNA and high SUVmax-N (LH), high EBV DNA and low SUVmax-N (HL), and high EBV DNA and high SUVmax-N (HH). There were significant differences between the four mentioned groups in 3-year DMFS: 95.7%, 92.2%, 92.3%, and 80.1%, respectively (Ptrend < 0.001). When looking at the disease stage, the 3-year DMFS in group LL, LH, HL, HH were 94.2%, 92.9%, 95.0%, and 81.1%, respectively, in stage III patients (Ptrend < 0.001) and 92.7%, 87.2%, 86.3%, and 77.0% in stage IVa–b patients (Ptrend = 0.026). Conclusion Pretreatment EBV DNA and SUVmax of neck lymph nodes were independent prognostic factors for distant metastasis in NPC patients. Combining EBV DNA and SUVmax-N led to an improved risk stratification for distant metastasis in advanced-stage disease. PMID:26512922

  5. The Drosophila HNF4 nuclear receptor promotes glucose-stimulated insulin secretion and mitochondrial function in adults.

    PubMed

    Barry, William E; Thummel, Carl S

    2016-01-01

    Although mutations in HNF4A were identified as the cause of Maturity Onset Diabetes of the Young 1 (MODY1) two decades ago, the mechanisms by which this nuclear receptor regulates glucose homeostasis remain unclear. Here we report that loss of Drosophila HNF4 recapitulates hallmark symptoms of MODY1, including adult-onset hyperglycemia, glucose intolerance and impaired glucose-stimulated insulin secretion (GSIS). These defects are linked to a role for dHNF4 in promoting mitochondrial function as well as the expression of Hex-C, a homolog of the MODY2 gene Glucokinase. dHNF4 is required in the fat body and insulin-producing cells to maintain glucose homeostasis by supporting a developmental switch toward oxidative phosphorylation and GSIS at the transition to adulthood. These findings establish an animal model for MODY1 and define a developmental reprogramming of metabolism to support the energetic needs of the mature animal. PMID:27185732

  6. Lower body adipose tissue removal decreases glucose tolerance and insulin sensitivity in mice with exposure to high fat diet.

    PubMed

    Cox-York, K; Wei, Y; Wang, D; Pagliassotti, M J; Foster, M T

    2015-01-01

    It has been postulated that the protective effects of lower body subcutaneous adipose tissue (LBSAT) occur via its ability to sequester surplus lipid and thus serve as a "metabolic sink." However, the mechanisms that mediate this protective function are unknown thus this study addresses this postulate. Ad libitum, chow-fed mice underwent Sham-surgery or LBSAT removal (IngX, inguinal depot removal) and were subsequently provided chow (Chow; typical adipocyte expansion) or high fat diet (HFD; enhanced adipocyte expansion) for 5 weeks. Primary outcome measures included glucose tolerance and subsequent insulin response, muscle insulin sensitivity, liver and muscle triglycerides, adipose tissue gene expression, and circulating lipids and adipokines. In a follow up study the consequences of extended experiment length post-surgery (13 wks) or pre-existing glucose intolerance were examined. At 5 wks post-surgery IngX in HFD-fed mice reduced glucose tolerance and muscle insulin sensitivity and increased circulating insulin compared with HFD Sham. In Chow-fed mice, muscle insulin sensitivity was the only measurement reduced following IngX. At 13 wks circulating insulin concentration of HFD IngX mice continued to be higher than HFD Sham. Surgery did not induce changes in mice with pre-existing glucose intolerance. IngX also increased muscle, but not liver, triglyceride concentration in Chow- and HFD-fed mice 5 wks post-surgery, but chow group only at 13 wks. These data suggest that the presence of LBSAT protects against triglyceride accumulation in the muscle and HFD-induced glucose intolerance and muscle insulin resistance. These data suggest that lower body subcutaneous adipose tissue can function as a "metabolic sink." PMID:26167400

  7. Lower body adipose tissue removal decreases glucose tolerance and insulin sensitivity in mice with exposure to high fat diet

    PubMed Central

    Cox-York, K; Wei, Y; Wang, D; Pagliassotti, MJ; Foster, MT

    2014-01-01

    It has been postulated that the protective effects of lower body subcutaneous adipose tissue (LBSAT) occur via its ability to sequester surplus lipid and thus serve as a “metabolic sink.” However, the mechanisms that mediate this protective function are unknown thus this study addresses this postulate. Ad libitum, chow-fed mice underwent Sham-surgery or LBSAT removal (IngX, inguinal depot removal) and were subsequently provided chow (Chow; typical adipocyte expansion) or high fat diet (HFD; enhanced adipocyte expansion) for 5 weeks. Primary outcome measures included glucose tolerance and subsequent insulin response, muscle insulin sensitivity, liver and muscle triglycerides, adipose tissue gene expression, and circulating lipids and adipokines. In a follow up study the consequences of extended experiment length post-surgery (13 wks) or pre-existing glucose intolerance were examined. At 5 wks post-surgery IngX in HFD-fed mice reduced glucose tolerance and muscle insulin sensitivity and increased circulating insulin compared with HFD Sham. In Chow-fed mice, muscle insulin sensitivity was the only measurement reduced following IngX. At 13 wks circulating insulin concentration of HFD IngX mice continued to be higher than HFD Sham. Surgery did not induce changes in mice with pre-existing glucose intolerance. IngX also increased muscle, but not liver, triglyceride concentration in Chow- and HFD-fed mice 5 wks post-surgery, but chow group only at 13 wks. These data suggest that the presence of LBSAT protects against triglyceride accumulation in the muscle and HFD-induced glucose intolerance and muscle insulin resistance. These data suggest that lower body subcutaneous adipose tissue can function as a “metabolic sink.” PMID:26167400

  8. Computer simulation studies in fluid and calcium regulation and orthostatic intolerance

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The systems analysis approach to physiological research uses mathematical models and computer simulation. Major areas of concern during prolonged space flight discussed include fluid and blood volume regulation; cardiovascular response during shuttle reentry; countermeasures for orthostatic intolerance; and calcium regulation and bone atrophy. Potential contributions of physiologic math models to future flight experiments are examined.

  9. Autogenic-feedback training: A potential treatment for post-flight orthostatic intolerance in aerospace crews

    NASA Technical Reports Server (NTRS)

    Cowings, Patricia S.; Toscano, William B.; Miller, Neil E.; Pickering, Thomas G.; Shapiro, David

    1993-01-01

    Postflight orthostatic intolerance was identified as a serious biomedical problem associated with long duration exposure to microgravity in space. High priority was given to the development of countermeasures for this disorder which are both effective and practical. A considerable body of clinical research demonstrated that people can be taught to increase their own blood pressure voluntarily and that this is an effective treatment for chronic orthostatic intolerance in paralyzed patients. The present pilot study was designed to examine the feasibility of adding training in control of blood pressure to an existing preflight training program designed to facilitate astronaut adaptation to microgravity. Using an operant conditioning procedure, Autogenic-Feedback Training (AFT), three men and two women participated in four to nine (15-30 training sessions). At the end of training, the average increase in systolic and diastolic pressure, as well as mean arterial pressures that the subjects made, ranged between 20 and 5O mmHg under both supine and 45 deg head-up tilt conditions. These findings suggest that AFT may be a useful alternative treatment or supplement to existing approaches for preventing postflight orthostatic intolerance. Further, the use of operant conditioning methods for training cardiovascular responses may contribute to the general understanding of the mechanisms of orthostatic intolerance.

  10. 75 FR 2551 - NIH Consensus Development Conference: Lactose Intolerance and Health; Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health NIH Consensus Development Conference: Lactose Intolerance and Health; Notice Notice is hereby given by the National Institutes of Health (NIH) of the ``NIH Consensus Development Conference:...

  11. Autogenic-Feedback Training: A Potential Treatment for Orthostatic Intolerance in Aerospace Crews

    NASA Technical Reports Server (NTRS)

    Cowings, P. S.; Toscano, W. B.; Miller, N. E.; Pickering, T. G.; Shapiro, D.; Stevenson, J.; Maloney, S.; Knapp, J.

    1994-01-01

    Postflight orthostatic intolerance has been identified 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 that are both effective and practical. A considerable body of clinical research has demonstrated that people can be taught to increase their own blood pressure voluntarily, and that this is an effective treatment for chronic orthostatic intolerance in paralyzed patients. The current pilot study was designed to examine the feasibility of adding training in control of blood pressure to an existing preflight training program designed to facilitate astronaut adaptation to microgravity. Using an operant conditioning procedure, autogenic-feedback training (AFT), three men and two women participated in four to nine training (15-30-minute) sessions. At the end of training, the average increase in systolic and diastolic pressure, as well as mean arterial pressures, that the subjects made ranged between 20 and 50 mm Hg under both supine and 45 deg head-up tilt conditions. These findings indicate that AFT may be a useful alternative treatment or supplement to existing approaches for preventing postflight orthostatic intolerance. Furthermore, the use of operant conditioning methods for training cardiovascular responses may contribute to the general understanding of the mechanisms of orthostatic intolerance.

  12. Does Homeschooling or Private Schooling Promote Political Intolerance? Evidence from a Christian University

    ERIC Educational Resources Information Center

    Cheng, Albert

    2014-01-01

    Political tolerance is the willingness to extend civil liberties to people who hold views with which one disagrees. Some have claimed that private schooling and homeschooling are institutions that propagate political intolerance by fostering separatism and an unwillingness to consider alternative viewpoints. I empirically test this claim by…

  13. Sarcopenic obesity and the pathogenesis of exercise intolerance in heart failure with preserved ejection fraction.

    PubMed

    Upadhya, Bharathi; Haykowsky, Mark J; Eggebeen, Joel; Kitzman, Dalane W

    2015-06-01

    Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure (HF) in older adults. The primary chronic symptom in patients with HFpEF, even when well compensated, is severe exercise intolerance. Cardiac and peripheral functions contribute equally to exercise intolerance in HFpEF, though the latter has been the focus of fewer studies. Of note, multiple studies with exercise training have shown that exercise intolerance can improve significantly in the absence of improvements in exercise cardiac output, indicating a role of peripheral, noncardiac adaptations. In addition, clinical drug trials performed to date in HFpEF, all of which have focused on influencing cardiovascular function, have not been positive on primary clinical outcomes and most have not improved exercise capacity. Mounting evidence indicates that sarcopenic obesity, characterized by the coexistence of excess fat mass and decreased muscle mass, could contribute to the pathophysiology of exercise intolerance in older HFpEF patients and may provide avenues for novel treatments. PMID:25750186

  14. Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Cross-Intolerance Reactions.

    PubMed

    Blanca-López, N; Cornejo-García, J A; Plaza-Serón, M C; Doña, I; Torres-Jaén, M J; Canto, G; Padilla-España, L; Kidon, M; Perkins, J R; Blanca, M

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used worldwide and are responsible for several types of drug hypersensitivity reactions (DHRs) in all age groups. The 2 major groups of DHRs to NSAIDs are those induced by immunological mechanisms (selective reactions) and those where inflammatory mediators are released through activation of the prostaglandin-leukotriene pathway without specific immunological recognition (cross-intolerance). In the present review, we focus on cross-intolerance reactions, which are the most frequent DHRs and are becoming a topic of major interest in children and adolescents. Paracetamol and ibuprofen are the drugs that most frequently cause DHRs in children; other NSAIDs are responsible for reactions in adolescents. In vivo and in vitro tests are of limited diagnostic value, with some exceptions for the less common selective reactions. In cross-intolerance, the clinical history and controlled administration are in many instances the only way to establish a diagnosis and look for alternatives. The clinical history is diagnostic when consistent symptoms occur repeatedly after exposure to NSAIDs with different chemical structures. Cutaneous and respiratory symptoms often co-occur in young children. The natural history of these reactions in children is unknown, and some patients can develop tolerance over time. Atopy remains a major risk factor for cross-intolerant reactions. The increasing interest in hypersensitivity to NSAIDs with improvements in patient phenotyping and the information provided by pharmacogenetics will improve our understanding and management of these reactions in the near future. PMID:26310040

  15. Student Engagement for College Students with the Hidden Disability of Orthostatic Intolerance

    ERIC Educational Resources Information Center

    Karabin, Beverly Lynn

    2010-01-01

    This study described the factors that contribute to engagement patterns of college students with the hidden health-related disability of orthostatic intolerance. Specifically, it used a qualitative methodology and collective-case study design to explore the categories of campus physical, institutional, academic and social engagement from a student…

  16. Behavioral Manifestations and Parental Correlates of Intolerance of Ambiguity in Young Children.

    ERIC Educational Resources Information Center

    Harrington, David M.; And Others

    The phenomenon of intolerance of ambiguity in young children was investigated in this longitudinal study. Personality data for the total of 120 children in the study were obtained from: (1) descriptions of the children at both 3 and 4 years of age by their teachers, using the California Child Q-set; (2) the children's performance on the Lowenfeld…

  17. Defining Distinct Negative Beliefs about Uncertainty: Validating the Factor Structure of the Intolerance of Uncertainty Scale

    ERIC Educational Resources Information Center

    Sexton, Kathryn A.; Dugas, Michel J.

    2009-01-01

    This study examined the factor structure of the English version of the Intolerance of Uncertainty Scale (IUS; French version: M. H. Freeston, J. Rheaume, H. Letarte, M. J. Dugas, & R. Ladouceur, 1994; English version: K. Buhr & M. J. Dugas, 2002) using a substantially larger sample than has been used in previous studies. Nonclinical undergraduate…

  18. Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: a placebo effect?

    PubMed Central

    Briet, F; Pochart, P; Marteau, P; Flourie, B; Arrigoni, E; Rambaud, J

    1997-01-01

    Background—Uncontrolled studies of lactose intolerant subjects have shown that symptom severity decreases after chronic lactose consumption. Adaptation of the colonic flora might explain this improvement. 
Aims—To compare the effects of regular administration of either lactose or sucrose on clinical tolerance and bacterial adaptation to lactose. 
Methods—Forty six lactose intolerant subjects underwent two 50 g lactose challenges on days 1 and 15. Between these days they were given 34 g of lactose or sucrose per day, in a double blind protocol. Stool samples were obtained on days 0 and 14, to measure faecal β-galactosidase and pH. Symptoms, breath H2 excretion, faecal weight and electrolytes, and orofaecal transit time were assessed. 
Results—Except for faecal weight, symptoms were significantly milder during the second challenge in both groups, and covariance analysis showed no statistical difference between them. In the lactose group, but not in the sucrose group, faecal β-galactosidase activity increased, pH dropped, and breath H2 excretion decreased. 
Conclusion—Bacterial adaptation occurred when lactose intolerant subjects ingested lactose for 13 days, and all symptoms except diarrhoea regressed. Clinical improvement was also observed in the control group which displayed no signs of metabolic adaptation. This suggests that improved clinical tolerance may be just a placebo effect. 

 Keywords: lactose; lactose intolerance; colonic adaptation; lactase deficiency PMID:9414969

  19. Culture Change from Tobacco Accommodation to Intolerance: Time to Connect the Dots

    ERIC Educational Resources Information Center

    Livingood, William C., Jr.; Allegrante, John P.; Green, Lawrence W.

    2016-01-01

    Broad changes in normative health behavior are critical to overcoming many of the contemporary challenges to public health. Reduction in tobacco use during the last third of the 20th century--one of the greatest improvements in public health--illustrates such change. The culture change from accommodation to intolerance of smoking is irrefutable.…

  20. Long-term Patency of Primary Arterial Repair and the Modified Cold Intolerance Symptom Severity Questionnaire

    PubMed Central

    Lannau, Bernd; Bliley, Jacqueline; James, Isaac B.; Wang, Sheri; Sivak, Wesley; Kim, Kang; Fowler, John

    2015-01-01

    Background: The goal of this study was to assess the long-term arterial patency of repaired arteries in the upper extremity and any morbidity resulting from the subsequent occlusion of these vessels. Concurrently, a new questionnaire, the modified Cold Intolerance Symptom Severity (mod CISS) questionnaire, was developed to allow for better assessment of cold intolerance. Methods: Thirteen patients who had undergone repair of the radial (4 patients), ulnar (6 patients), brachial (1 patient), digital (1), and an undefined lower arm artery (1) were examined using questionnaires, physical examination, and high-resolution ultrasound. Results: Outcome measures that were statistically significantly worse in the group of patients who presented with nerve injuries included cold intolerance symptoms, Disabilities of the Arm, Shoulder, and Hand score, Michigan Hand Questionnaire, and grip strength (middle setting on dynamometer). The results from the mod CISS correlated with high statistical significance with the results of the CISS score for the injured hand. Of note, wrist extension was significantly better with patent arteries. Conclusions: Sixty-seven percent of arterial repairs remained patent at 6 years (mean) follow-up. The presence of nerve injury has a higher impact on the outcome metrics assessed in this study than arterial patency. Our modification of the CISS score enhances its utility as a survey of cold intolerance. PMID:26893976

  1. [Pharmaceutical drugs containing lactose can as a rule be used by persons with lactose intolerance].

    PubMed

    Vinther, Siri; Rumessen, Jöri Johannes; Christensen, Mikkel

    2015-03-01

    Lactose is often used as an excipient in pharmaceutical drugs. Current evidence indicates that the amount of lactose in most drugs is not sufficient to cause symptoms in persons with lactose intolerance, although interindividual differences in sensitivity probably exist. Patient preferences and/or suboptimal treatment adherence could be reasons for considering lactose-free drug alternatives. PMID:25786702

  2. Hate in the Ivory Tower: A Survey of Intolerance on College Campuses and Academia's Response.

    ERIC Educational Resources Information Center

    People for the American Way, Washington, DC.

    A study of institutional responses to incidents of intolerance on college and university campuses was conducted. A questionnaire was sent to the deans of student affairs and student newspaper editors at 128 four-year colleges and universities; and interviews were conducted with administrators, students, faculty, and staff from 58 institutions, 11…

  3. Intolerance, Forgiveness, and Promise in the Rhetoric of Conversion: Italian Women Defy the Mafia.

    ERIC Educational Resources Information Center

    Fabj, Valeria

    1998-01-01

    Contributes to scholarship on the rhetoric of conversion and conversion narratives by examining the narratives of Italian women who have turned state's evidence against the Mafia. Finds that the "topoi" of intolerance, forgiveness, and promise are used to describe the process of conversion, translate private experiences into public testimonies,…

  4. Statins impair glucose uptake in human cells

    PubMed Central

    Nowis, Dominika; Malenda, Agata; Furs, Karolina; Oleszczak, Bozenna; Sadowski, Radoslaw; Chlebowska, Justyna; Firczuk, Malgorzata; Bujnicki, Janusz M; Staruch, Adam D; Zagozdzon, Radoslaw; Glodkowska-Mrowka, Eliza; Szablewski, Leszek; Golab, Jakub

    2014-01-01

    Objective Considering the increasing number of clinical observations indicating hyperglycemic effects of statins, this study was designed to measure the influence of statins on the uptake of glucose analogs by human cells derived from liver, adipose tissue, and skeletal muscle. Design Flow cytometry and scintillation counting were used to measure the uptake of fluorescently labeled or tritiated glucose analogs by differentiated visceral preadipocytes, skeletal muscle cells, skeletal muscle myoblasts, and contact-inhibited human hepatocellular carcinoma cells. A bioinformatics approach was used to predict the structure of human glucose transporter 1 (GLUT1) and to identify the presence of putative cholesterol-binding (cholesterol recognition/interaction amino acid consensus (CRAC)) motifs within this transporter. Mutagenesis of CRAC motifs in SLC2A1 gene and limited proteolysis of membrane GLUT1 were used to determine the molecular effects of statins. Results Statins significantly inhibit the uptake of glucose analogs in all cell types. Similar effects are induced by methyl-β-cyclodextrin, which removes membrane cholesterol. Statin effects can be rescued by addition of mevalonic acid, or supplementation with exogenous cholesterol. Limited proteolysis of GLUT1 and mutagenesis of CRAC motifs revealed that statins induce conformational changes in GLUTs. Conclusions Statins impair glucose uptake by cells involved in regulation of glucose homeostasis by inducing cholesterol-dependent conformational changes in GLUTs. This molecular mechanism might explain hyperglycemic effects of statins observed in clinical trials. PMID:25452863

  5. Target Fortification of Breast Milk: Predicting the Final Osmolality of the Feeds.

    PubMed

    Choi, Arum; Fusch, Gerhard; Rochow, Niels; Fusch, Christoph

    2016-01-01

    For preterm infants, it is common practice to add human milk fortifiers to native breast milk to enhance protein and calorie supply because the growth rates and nutritional requirements of preterm infants are considerably higher than those of term infants. However, macronutrient intake may still be inadequate because the composition of native breast milk has individual inter- and intra-sample variation. Target fortification (TFO) of breast milk is a new nutritional regime aiming to reduce such variations by individually measuring and adding deficient macronutrients. Added TFO components contribute to the final osmolality of milk feeds. It is important to predict the final osmolality of TFO breast milk to ensure current osmolality recommendations are followed to minimize feeding intolerance and necrotizing enterocolitis. This study aims to develop and validate equations to predict the osmolality of TFO milk batches. To establish prediction models, the osmolalities of either native or supplemented breast milk with known amounts of fat, protein, and carbohydrates were analyzed. To validate prediction models, the osmolalities of each macronutrient and combinations of macronutrients were measured in an independent sample set. Additionally, osmolality was measured in TFO milk samples obtained from a previous clinical study and compared with predicted osmolality using the prediction equations. Following the addition of 1 g of carbohydrates (glucose polymer), 1 g of hydrolyzed protein, or 1 g of whey protein per 100 mL breast milk, the average increase in osmolality was 20, 38, and 4 mOsm/kg respectively. Adding fat decreased osmolality only marginally due to dilution effect. Measured and predicted osmolality of combinations of macronutrients as well as single macronutrient (R2 = 0.93) were highly correlated. Using clinical data (n = 696), the average difference between the measured and predicted osmolality was 3 ± 11 mOsm/kg and was not statistically significant. In

  6. Target Fortification of Breast Milk: Predicting the Final Osmolality of the Feeds

    PubMed Central

    Choi, Arum; Fusch, Gerhard; Rochow, Niels; Fusch, Christoph

    2016-01-01

    For preterm infants, it is common practice to add human milk fortifiers to native breast milk to enhance protein and calorie supply because the growth rates and nutritional requirements of preterm infants are considerably higher than those of term infants. However, macronutrient intake may still be inadequate because the composition of native breast milk has individual inter- and intra-sample variation. Target fortification (TFO) of breast milk is a new nutritional regime aiming to reduce such variations by individually measuring and adding deficient macronutrients. Added TFO components contribute to the final osmolality of milk feeds. It is important to predict the final osmolality of TFO breast milk to ensure current osmolality recommendations are followed to minimize feeding intolerance and necrotizing enterocolitis. This study aims to develop and validate equations to predict the osmolality of TFO milk batches. To establish prediction models, the osmolalities of either native or supplemented breast milk with known amounts of fat, protein, and carbohydrates were analyzed. To validate prediction models, the osmolalities of each macronutrient and combinations of macronutrients were measured in an independent sample set. Additionally, osmolality was measured in TFO milk samples obtained from a previous clinical study and compared with predicted osmolality using the prediction equations. Following the addition of 1 g of carbohydrates (glucose polymer), 1 g of hydrolyzed protein, or 1 g of whey protein per 100 mL breast milk, the average increase in osmolality was 20, 38, and 4 mOsm/kg respectively. Adding fat decreased osmolality only marginally due to dilution effect. Measured and predicted osmolality of combinations of macronutrients as well as single macronutrient (R2 = 0.93) were highly correlated. Using clinical data (n = 696), the average difference between the measured and predicted osmolality was 3 ± 11 mOsm/kg and was not statistically significant. In

  7. Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis

    PubMed Central

    Fan, Fan; Ji, Chen; Wu, Yumei; Ferguson, Shawn M.; Tamarina, Natalia; Philipson, Louis H.; Lou, Xuelin

    2015-01-01

    Alterations in insulin granule exocytosis and endocytosis are paramount to pancreatic β cell dysfunction in diabetes mellitus. Here, using temporally controlled gene ablation specifically in β cells in mice, we identified an essential role of dynamin 2 GTPase in preserving normal biphasic insulin secretion and blood glucose homeostasis. Dynamin 2 deletion in β cells caused glucose intolerance and substantial reduction of the second phase of glucose-stimulated insulin secretion (GSIS); however, mutant β cells still maintained abundant insulin granules, with no signs of cell surface expansion. Compared with control β cells, real-time capacitance measurements demonstrated that exocytosis-endocytosis coupling was less efficient but not abolished; clathrin-mediated endocytosis (CME) was severely impaired at the step of membrane fission, which resulted in accumulation of clathrin-coated endocytic intermediates on the plasma membrane. Moreover, dynamin 2 ablation in β cells led to striking reorganization and enhancement of actin filaments, and insulin granule recruitment and mobilization were impaired at the later stage of GSIS. Together, our results demonstrate that dynamin 2 regulates insulin secretory capacity and dynamics in vivo through a mechanism depending on CME and F-actin remodeling. Moreover, this study indicates a potential pathophysiological link between endocytosis and diabetes mellitus. PMID:26413867

  8. Noninvasive blood glucose monitoring with laser diode

    NASA Astrophysics Data System (ADS)

    Zhang, Xiqin; Chen, Jianhong; Ooi, Ean Tat; Yeo, Joon Hock

    2006-02-01

    The non-invasive measurement of blood sugar level was studied by use of near infrared laser diodes. The in vitro and in vivo experiments were carried out using six laser diodes having wavelengths range from 1550 nm to 1750nm. Several volunteers were tested for OGTT (Oral Glucose Tolerance Test) experiment. We took blood from a fingertip and measured its concentration with a glucose meter while taking signal voltage from laser diodes system. The data of signal voltage were processed to do calibration and prediction; in this paper PLS (Partial Least Square) method was used to do modeling. For in vitro experiment, good linear relationship between predicted glucose concentration and real glucose concentration was obtained. For in vivo experiments, we got the blood sugar level distributions in Clarke error grid that is a reference for doctors to do diagnosis and treatment. In the Clarke error grid, 75% of all data was in area A and 25 % was in area B. From the in vitro and in vivo results we know that multiple laser diodes are suitable for non-invasive blood glucose monitoring.

  9. Peritoneal Dialysate Glucose Load and Systemic Glucose Metabolism in Non-Diabetics: Results from the GLOBAL Fluid Cohort Study

    PubMed Central

    Chess, James; Do, Jun-Young; Noh, Hyunjin; Lee, Hi-Bahl; Kim, Yong-Lim; Summers, Angela; Williams, Paul Ford; Davison, Sara; Dorval, Marc

    2016-01-01

    Background and Objectives Glucose control is a significant predictor of mortality in diabetic peritoneal dialysis (PD) patients. During PD, the local toxic effects of intra-peritoneal glucose are well recognized, but despite large amounts of glucose being absorbed, the systemic effects of this in non-diabetic patients are not clear. We sought to clarify whether dialysate glucose has an effect upon systemic glucose metabolism. Methods and Materials We analysed the Global Fluid Study cohort, a prospective, observational cohort study initiated in 2002. A subset of 10 centres from 3 countries with high data quality were selected (368 incident and 272 prevalent non-diabetic patients), with multilevel, multivariable analysis of the reciprocal of random glucose levels, and a stratified-by-centre Cox survival analysis. Results The median follow up was 5.6 and 6.4 years respectively in incident and prevalent patients. On multivariate analysis, serum glucose increased with age (β = -0.007, 95%CI -0.010, -0.004) and decreased with higher serum sodium (β = 0.002, 95%CI 0.0005, 0.003) in incident patients and increased with dialysate glucose (β = -0.0002, 95%CI -0.0004, -0.00006) in prevalent patients. Levels suggested undiagnosed diabetes in 5.4% of prevalent patients. Glucose levels predicted death in unadjusted analyses of both incident and prevalent groups but in an adjusted survival analysis they did not (for random glucose 6–10 compared with <6, Incident group HR 0.92, 95%CI 0.58, 1.46, Prevalent group HR 1.42, 95%CI 0.86, 2.34). Conclusions In prevalent non-diabetic patients, random glucose levels at a diabetic level are under-recognised and increase with dialysate glucose load. Random glucose levels predict mortality in unadjusted analyses, but this association has not been proven in adjusted analyses. PMID:27249020

  10. Are food intolerances and allergies increasing in immigrant children coming from developing countries ?

    PubMed

    Cataldo, Francesco; Accomando, Salvatore; Fragapane, Maria L; Montaperto, Daniela

    2006-08-01

    There are not available data concerning the occurrence, the clinical features and the environmental risk factors for food intolerances and allergies in immigrant children. The aim of the study was to evaluate rates, distribution, clinical features and environmental risk factors for food intolerances and allergies in immigrant children. Hospital records of 4,130 patients with celiac disease (CD), cow milk protein intolerance (CMPI) and food allergies (FA) diagnosed in 24 Italian Centres from 1999 to 2001 were retrospectively reviewed, comparing immigrant patients with Italian ones. 78/4,130 (1.9%) patients were immigrant: 36/1,917 (1.9%) had CD, 24/1,370 (1.75%) CMPI and 18/843 (2.1%) FA. They were evenly distributed across Italy and their native areas were: East Europe (23/78), Northern Africa (23/78), Southern Asia (14/78), Saharan and Sub-Saharan Africa (9/78), Southern America (4/78), Far East (3/7), Middle East (2/78). Despite differences in their origin, the clinical features of immigrant children were similar to the ones of Italian patients and among each ethnic group. The majority of them were born in Italy (57/78) or have been residing in Italy since several years (19/78). All of them had lost dietary habits of the native countries and had acquired those of the Italian childhood population. Food intolerances and allergies are present also in children coming from developing countries, and paediatricians will need to have a full awareness of them because the number of immigrant children in Italy is quickly increasing. The clinical features of food intolerances and allergies appear the same in each ethnic group, despite differences in races. Sharing of dietary habits with the Italian childhood population seems to be an important environmental risk factor. PMID:16846455

  11. Frequency and prognostic value of resistance/intolerance to hydroxycarbamide in 890 patients with polycythaemia vera.

    PubMed

    Alvarez-Larrán, Alberto; Kerguelen, Ana; Hernández-Boluda, Juan C; Pérez-Encinas, Manuel; Ferrer-Marín, Francisca; Bárez, Abelardo; Martínez-López, Joaquín; Cuevas, Beatriz; Mata, M Isabel; García-Gutiérrez, Valentín; Aragües, Pilar; Montesdeoca, Sara; Burgaleta, Carmen; Caballero, Gonzalo; Hernández-Rivas, J Angel; Durán, M Antonia; Gómez-Casares, M Teresa; Besses, Carles

    2016-03-01

    The clinical significance of resistance/intolerance to hydroxycarbamide (HC) was assessed in a series of 890 patients with polycythaemia vera (PV). Resistance/intolerance to HC was recorded in 137 patients (15·4%), consisting of: need for phlebotomies (3·3%), uncontrolled myeloproliferation (1·6%), failure to reduce massive splenomegaly (0·8%), development of cytopenia at the lowest dose of HC to achieve a response (1·7%) and extra-haematological toxicity (9%). With a median follow-up of 4·6 years, 99 patients died, resulting in a median survival of 19 years. Fulfilling any of the resistance/intolerance criteria had no impact on survival but when the different criteria were individually assessed, an increased risk of death was observed in patients developing cytopenia [Hazard ratio (HR): 3·5, 95% confidence interval (CI): 1·5-8·3, P = 0·003]. Resistance/intolerance had no impact in the rate of thrombosis or bleeding. Risk of myelofibrotic transformation was significantly higher in those patients developing cytopenia (HR: 5·1, 95% CI: 1·9-13·7, P = 0·001) and massive splenomegaly (HR: 9·1, 95% CI: 2·3-35·9, P = 0·002). Cytopenia at the lowest dose required to achieve a response was also an independent risk factor for transformation to acute leukaemia (HR: 20·3, 95% CI: 5·4-76·5, P < 0·001). In conclusion, the unified definition of resistance/intolerance to HC delineates a heterogeneous group of PV patients, with those developing cytopenia being associated with an adverse outcome. PMID:26898196

  12. Limb venous compliance in patients with idiopathic orthostatic intolerance and postural tachycardia.

    PubMed

    Freeman, Roy; Lirofonis, Vasilios; Farquhar, William B; Risk, Marcelo

    2002-08-01

    Venous denervation and increased venous pooling may contribute to symptoms of orthostatic intolerance. We examined venous compliance in the calf and forearm in 11 orthostatic-intolerant patients and 15 age-matched controls over a range of pressures, during basal conditions and sympathetic excitation. Occlusion cuffs placed around the upper arm and thigh were inflated to 60 mmHg and deflated to 10 mmHg over 1 min. Limb volume was measured continuously with a mercury-in-Silastic strain gauge. Compliance was calculated as the numerical derivative of the pressure-volume curve. The pressure-volume relationship in the upper and lower extremities in the basal and sympathetically activated state was significantly lower in the orthostatic-intolerant patients (all P < 0.05). Sympathoexcitation lowered the pressure-volume relationship in the lower extremity in patients (P < 0.001) and controls (P < 0.01). Venous compliance was significantly less in patients in the lower extremity in the basal state over a range of pressures (P < 0.05). Venous compliance was less in patients compared with controls in the upper (P < 0.005) and lower extremities (P < 0.01) in the sympathetically activated state, but there were no differences at individual pressure levels. Sympathetic activation did not change venous compliance in the upper and lower extremity in patients and controls. Patients with orthostatic intolerance have reduced venous compliance in the lower extremity. Reduced compliance may limit the dynamic response to orthostatic change and thereby contribute to symptoms of orthostatic intolerance in this population group. PMID:12133874

  13. The Effects of Liquid Cooling Garments on Post-Space Flight Orthostatic Intolerance

    NASA Technical Reports Server (NTRS)

    Billica, Roger; Kraft, Daniel

    1997-01-01

    Post space flight orthostatic intolerance among Space Shuttle crew members following exposure to extended periods of microgravity has been of significant concern to the safety of the shuttle program. Following the Challenger accident, flight crews were required to wear launch and entry suits (LES). It was noted that overall, there appeared to be a higher degree of orthostatic intolerance among the post-Challenger crews (approaching 30%). It was hypothesized that the increased heat load incurred when wearing the LES, contributed to an increased degree of orthostatic intolerance, possibly mediated through increased peripheral vasodilatation triggered by the heat load. The use of liquid cooling garments (LCG) beneath the launch and entry suits was gradually implemented among flight crews in an attempt to decrease heat load, increase crew comfort, and hopefully improve orthostatic tolerance during reentry and landing. The hypothesis that the use of the LCG during reentry and landing would decrease the degree of orthostasis has not been previously tested. Operational stand-tests were performed pre and post flight to assess crewmember's cardiovascular system's ability to respond to gravitational stress. Stand test and debrief information were collected and databased for 27 space shuttle missions. 63 crewpersons wearing the LCG, and 70 crewpersons not wearing the LCG were entered into the database for analysis. Of 17 crewmembers who exhibited pre-syncopal symptoms at the R+O analysis, 15 were not wearing the LCG. This corresponds to a 21% rate of postflight orthostatic intolerance among those without the LCG, and a 3% rate for those wearing LCG. There were differences in these individual's average post-flight maximal systolic blood pressure, and lower minimal Systolic Blood pressures in those without LCG. Though other factors, such as type of fluid loading, and exercise have improved concurrently with LCG introduction, from this data analysis, it appears that LCG usage

  14. Vascular Glucose Sensor Symposium

    PubMed Central

    Joseph, Jeffrey I; Torjman, Marc C.; Strasma, Paul J.

    2015-01-01

    Hyperglycemia, hypoglycemia, and glycemic variability have been associated with increased morbidity, mortality, length of stay, and cost in a variety of critical care and non–critical care patient populations in the hospital. The results from prospective randomized clinical trials designed to determine the risks and benefits of intensive insulin therapy and tight glycemic control have been confusing; and at times conflicting. The limitations of point-of-care blood glucose (BG) monitoring in the hospital highlight the great clinical need for an automated real-time continuous glucose monitoring system (CGMS) that can accurately measure the concentration of glucose every few minutes. Automation and standardization of the glucose measurement process have the potential to significantly improve BG control, clinical outcome, safety and cost. PMID:26078254

  15. Recombinant glucose uptake system

    DOEpatents

    Ingrahm, Lonnie O.; Snoep, Jacob L.; Arfman, Nico

    1997-01-01

    Recombinant organisms are disclosed that contain a pathway for glucose uptake other than the pathway normally utilized by the host cell. In particular, the host cell is one in which glucose transport into the cell normally is coupled to PEP production. This host cell is transformed so that it uses an alternative pathway for glucose transport that is not coupled to PEP production. In a preferred embodiment, the host cell is a bacterium other than Z. mobilis that has been transformed to contain the glf and glk genes of Z. mobilis. By uncoupling glucose transport into the cell from PEP utilization, more PEP is produced for synthesis of products of commercial importance from a given quantity of biomass supplied to the host cells.

  16. All about Blood Glucose

    MedlinePlus

    ... Blood Glucose Before meals: 80 to 130 mg/dl My Usual Results My Goals ______ to ______ ______ to ______ 2 ... the start of a meal: below 180 mg/dl below ______ below ______ What’s the best way to keep ...

  17. Blood Glucose Monitoring Devices

    MedlinePlus

    ... Glucose NIH Medline Plus - Diabetes Spotlight FDA permits marketing of first system of mobile medical apps for ... feeds Follow FDA on Twitter Follow FDA on Facebook View FDA videos on YouTube View FDA photos ...

  18. Direct electron transfer type disposable sensor strip for glucose sensing employing an engineered FAD glucose dehydrogenase.

    PubMed

    Yamashita, Yuki; Ferri, Stefano; Huynh, Mai Linh; Shimizu, Hitomi; Yamaoka, Hideaki; Sode, Koji

    2013-02-01

    The FAD-dependent glucose dehydrogenase (FADGDH) from Burkholderia cepacia has several attractive features for glucose sensing. However, expanding the application of this enzyme requires improvement of its substrate specificity, especially decreasing its high activity toward maltose. A three-dimensional structural model of the FADGDH catalytic subunit was generated by homology modeling. By comparing the predicted active site with that of glucose oxidase, the two amino acid residues serine 326 and serine 365 were targeted for site-directed mutagenesis. The single mutations that produced the highest glucose specificity were combined, leading to the creation of the S326Q/S365Y double mutant, which was virtually nonreactive to maltose while retaining high glucose dehydrogenase activity. The engineered FADGDH was used to develop a direct electron transfer-type, disposable glucose sensor strip by immobilizing the enzyme complex onto a carbon screen-printed electrode. While the electrode employing wild-type FADGDH provided dangerously flawed results in the presence of maltose, the sensor employing our engineered FADGDH showed a clear glucose concentration-dependent response that was not affected by the presence of maltose. PMID:23273282

  19. Glucose and lipid metabolism in the pancreas of rainbow trout is regulated at the molecular level by nutritional status and carbohydrate intake.

    PubMed

    Polakof, Sergio; Skiba-Cassy, Sandrine; Kaushik, Sadasivam; Seiliez, Iban; Soengas, Jose Luis; Panserat, Stephane

    2012-05-01

    Glucose and lipid metabolism in pancreatic islet organs is poorly characterized. In the present study, using as a model the carnivorous rainbow trout, a glucose-intolerant fish, we assessed mRNA expression levels of several genes involved in glucose and lipid metabolism (including ATP-citrate lyase; carnitine palmitoyltransferase-1 isoforms, CPT; the mitochondrial isoform of the phosphoenolpyrutave carboxykinase, mPEPCK and pyruvate kinase, PK) and glucosensing (glucose transporter type 2, Glut2; glucokinase, GK and the potassium channel, K(ATP)) in Brockmann bodies. We evaluated the response of these parameters to changes in feeding status (food deprived vs. fed fish) as well as to changes in the amount of carbohydrate (dextrin) in the diet. A general inhibition of the glycolytic (including the glucosensing marker GK) and β-oxidation pathways was found when comparing fed versus food-deprived fish. When comparing fish feeding on either low- or high-carbohydrate diets, we found that some genes related to lipid metabolism were more controlled by the feeding status than by the carbohydrate content (fatty acid synthase, CPTs). Findings are discussed in the context of pancreatic regulation of glucose and lipid metabolism in fish, and show that while trout pancreatic metabolism can partially adapt to a high-carbohydrate diet, some of the molecular actors studied seem to be poorly regulated (K(ATP)) and may contribute to the glucose intolerance observed in this species when fed high-carbohydrate diets. PMID:22203338

  20. Black Adzuki Bean (Vigna angularis) Extract Protects Pancreatic β Cells and Improves Glucose Tolerance in C57BL/6J Mice Fed a High-Fat Diet.

    PubMed

    Kim, Mina; Kim, Dae Keun; Cha, Youn-Soo

    2016-05-01

    Adzuki beans have long been cultivated as a food and folk medicine in East Asia. In this study, we investigated the effect of black adzuki bean (BAB) extract on pancreatic cells and determined their mechanism of action in impaired glucose tolerance in an animal model of type 2 diabetes. In addition, we performed functional gene annotation analysis to identify genes related to the regulation of glucose metabolism and insulin response. Treatment of pancreatic β cells with BAB extract (0.2 mg/mL) led to tolerance of the high glucose-induced glucotoxicity, resulting in a similar viability as cells maintained in normal glucose media. In addition, dietary supplementation with BAB extract significantly (P < .05) improved hyperglycemia and homeostasis model assessment of insulin resistance index (HOMA-IR) in high-fat diet-induced glucose-intolerant obese C57BL/6J mice. Our results suggest that BAB extract ameliorates hyperglycemia and glucose intolerance, and lowers HOMA-IR by regulating insulin secretion and response, and by maintaining the integrity of pancreatic β cells exposed to hyperglycemic conditions. PMID:27070495

  1. A polysomnographic study of sleep disturbance in community elderly with self-reported environmental chemical odor intolerance.

    PubMed

    Bell, I R; Bootzin, R R; Ritenbaugh, C; Wyatt, J K; DeGiovanni, G; Kulinovich, T; Anthony, J L; Kuo, T F; Rider, S P; Peterson, J M; Schwartz, G E; Johnson, K A

    1996-07-15

    Subjective sleep complaints and food intolerances, especially to milk products, are frequent symptoms of individuals who also report intolerance for low-level odors of various environmental chemicals. The purpose of the present study was to evaluate the objective nature of nocturnal sleep patterns during different diets, using polysomnography in community older adults with self-reported illness from chemical odors. Those high in chemical odor intolerance (n = 15) exhibited significantly lower sleep efficiency (p = .005) and lower rapid-eye-movement (REM) sleep percent (p = .04), with a trend toward longer latency to REM sleep (p = .07), than did those low in chemical intolerance (n = 15), especially on dairy-containing as compared with nondairy (soy) diets. The arousal pattern of the chemical odor intolerant group differed from the polysomnographic features of major depression, classical organophosphate toxicity, and subjective insomnia without objective findings. The findings suggest that community elderly with moderate chemical odor intolerance and minimal sleep complaints exhibit objectively poorer sleep than do their normal peers. Individual differences in underlying brain function may help generate these observations. The data support the need for similar studies in clinical populations with chemical odor intolerance, such as multiple chemical sensitivity patients and perhaps certain veterans with "Persian Gulf Syndrome." PMID:8793044

  2. Fatty liver incidence and predictive variables.

    PubMed

    Tsuneto, Akira; Hida, Ayumi; Sera, Nobuko; Imaizumi, Misa; Ichimaru, Shinichiro; Nakashima, Eiji; Seto, Shinji; Maemura, Koji; Akahoshi, Masazumi

    2010-06-01

    Although fatty liver predicts ischemic heart disease, the incidence and predictors of fatty liver need examination. The objective of this study was to determine fatty liver incidence and predictive variables. Using abdominal ultrasonography, we followed biennially through 2007 (mean follow-up, 11.6+/-4.6 years) 1635 Nagasaki atomic bomb survivors (606 men) without fatty liver at baseline (November 1990 through October 1992). We examined potential predictive variables with the Cox proportional hazard model and longitudinal trends with the Wilcoxon rank-sum test. In all, 323 (124 men) new fatty liver cases were diagnosed. The incidence was 19.9/1000 person-years (22.3 for men, 18.6 for women) and peaked in the sixth decade of life. After controlling for age, sex, and smoking and drinking habits, obesity (relative risk (RR), 2.93; 95% confidence interval (CI), 2.33-3.69, P<0.001), low high-density lipoprotein-cholesterol (RR, 1.87; 95% CI, 1.42-2.47; P<0.001), hypertriglyceridemia (RR, 2.49; 95% CI, 1.96-3.15; P<0.001), glucose intolerance (RR, 1.51; 95% CI, 1.09-2.10; P=0.013) and hypertension (RR, 1.63; 95% CI, 1.30-2.04; P<0.001) were predictive of fatty liver. In multivariate analysis including all variables, obesity (RR, 2.55; 95% CI, 1.93-3.38; P<0.001), hypertriglyceridemia (RR, 1.92; 95% CI, 1.41-2.62; P<0.001) and hypertension (RR, 1.31; 95% CI, 1.01-1.71; P=0.046) remained predictive. In fatty liver cases, body mass index and serum triglycerides, but not systolic or diastolic blood pressure, increased significantly and steadily up to the time of the diagnosis. Obesity, hypertriglyceridemia and, to a lesser extent, hypertension might serve as predictive variables for fatty liver. PMID:20379184

  3. Regulation of Glucose Tolerance and Sympathetic Activity by MC4R Signaling in the Lateral Hypothalamus

    PubMed Central

    Morgan, Donald A.; McDaniel, Latisha N.; Yin, Terry; Khan, Michael; Jiang, Jingwei; Acevedo, Michael R.; Walsh, Susan A.; Ponto, Laura L. Boles; Norris, Andrew W.; Lutter, Michael; Rahmouni, Kamal

    2015-01-01

    Melanocortin 4 receptor (MC4R) signaling mediates diverse physiological functions, including energy balance, glucose homeostasis, and autonomic activity. Although the lateral hypothalamic area (LHA) is known to express MC4Rs and to receive input from leptin-responsive arcuate proopiomelanocortin neurons, the physiological functions of MC4Rs in the LHA are incompletely understood. We report that MC4RLHA signaling regulates glucose tolerance and sympathetic nerve activity. Restoring expression of MC4Rs specifically in the LHA improves glucose intolerance in obese MC4R-null mice without affecting body weight or circulating insulin levels. Fluorodeoxyglucose-mediated tracing of whole-body glucose uptake identifies the interscapular brown adipose tissue (iBAT) as a primary source where glucose uptake is increased in MC4RLHA mice. Direct multifiber sympathetic nerve recording further reveals that sympathetic traffic to iBAT is significantly increased in MC4RLHA mice, which accompanies a significant elevation of Glut4 expression in iBAT. Finally, bilateral iBAT denervation prevents the glucoregulatory effect of MC4RLHA signaling. These results identify a novel role for MC4RLHA signaling in the control of sympathetic nerve activity and glucose tolerance independent of energy balance. PMID:25605803

  4. LPS INHIBITION OF GLUCOSE PRODUCTION THROUGH THE TLR4, MYD88, NFκB PATHWAY

    PubMed Central

    Raetzsch, Carl F.; Brooks, Natasha L.; Alderman, J. McKee; Moore, Kelli S.; Hosick, Peter A.; Klebanov, Simon; Akira, Shizuo; Bear, James E.; Baldwin, Albert S.; Mackman, Nigel; Combs, Terry P.

    2010-01-01

    Acute exposure to lipopolysaccharide (LPS) can cause hypoglycemia and insulin resistance; the underlying mechanisms however, are unclear. We set out to determine whether insulin resistance is linked to hypoglycemia through TLR4, MyD88 and NFκB, a cell signaling pathway that mediates LPS induction of the proinflammatory cytokine TNFα. LPS induction of hypoglycemia was blocked in TLR4−/− and MyD88−/− mice but not in TNFα−/− mice. Both glucose production and glucose utilization were decreased during hypoglycemia. Hypoglycemia was associated with the activation of NFκB in the liver. LPS inhibition of glucose production was blocked in hepatocytes isolated from TLR4−/− and MyD88−/− mice and hepatoma cells expressing an IκB mutant that interferes with NFκB activation. Thus, LPS-induced hypoglycemia was mediated by the inhibition of glucose production from the liver through the TLR4, MyD88, NFκB pathway, independent of LPS induced TNFα. LPS inhibition of glucose production was not blocked by pharmacologic inhibition of the insulin signaling intermediate PI3K in hepatoma cells. Insulin injection caused a similar reduction of circulating glucose in TLR4−/− and TLR4+/+ mice. These two results suggest that LPS and insulin inhibit glucose production by separate pathways. Recovery from LPS induced hypoglycemia was linked to glucose intolerance and hyperinsulinemia in TLR4+/+ mice, but not in TLR4−/− mice. Conclusion Insulin resistance is linked to the inhibition of glucose production by the TLR4, MyD88 and NFκB pathway. PMID:19492426

  5. Effects of Estrogens on Adipokines and Glucose Homeostasis in Female Aromatase Knockout Mice

    PubMed Central

    Van Sinderen, Michelle L.; Steinberg, Gregory R.; Jørgensen, Sebastian B.; Honeyman, Jane; Chow, Jenny D.; Herridge, Kerrie A.; Winship, Amy L.; Dimitriadis, Evdokia; Jones, Margaret E. E.; Simpson, Evan R.; Boon, Wah Chin

    2015-01-01

    The maintenance of glucose homeostasis within the body is crucial for constant and precise performance of energy balance and is sustained by a number of peripheral organs. Estrogens are known to play a role in the maintenance of glucose homeostasis. Aromatase knockout (ArKO) mice are estrogen-deficient and display symptoms of dysregulated glucose metabolism. We aim to investigate the effects of estrogen ablation and exogenous estrogen administration on glucose homeostasis regulation. Six month-old female wildtype, ArKO, and 17β-estradiol (E2) treated ArKO mice were subjected to whole body tolerance tests, serum examination of estrogen, glucose and insulin, ex-vivo muscle glucose uptake, and insulin signaling pathway analyses. Female ArKO mice display increased body weight, gonadal (omental) adiposity, hyperinsulinemia, and liver triglycerides, which were ameliorated upon estrogen treatment. Tolerance tests revealed that estrogen-deficient ArKO mice were pyruvate intolerant hence reflecting dysregulated hepatic gluconeogenesis. Analyses of skeletal muscle, liver, and adipose tissues supported a hepatic-based glucose dysregulation, with a down-regulation of Akt phosphorylation (a key insulin signaling pathway molecule) in the ArKO liver, which was improved with E2 treatment. Concurrently, estrogen treatment lowered ArKO serum leptin and adiponectin levels and increased inflammatory adipokines such as tumour necrosis factor alpha (TNFα) and interleukin 6 (IL6). Furthermore, estrogen deficiency resulted in the infiltration of CD45 macrophages into gonadal adipose tissues, which cannot be reversed by E2 treatment. This study describes the effects of estrogens on glucose homeostasis in female ArKO mice and highlights a primary phenotype of hepatic glucose dysregulation and a parallel estrogen modified adipokine profile. PMID:26317527

  6. EVALUATION OF THE DORSET SHEEP AS A PREDICTIVE ANIMAL MODEL FOR THE RESPONSE OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE-DEFICIENT HUMAN ERYTHOCYTES TO A PROPOSED SYSTEMIC TOXIC OZONE INTERMEDIATE, METHYL OLEATE OZONIDE

    EPA Science Inventory

    Erythrocytes of both glucose-6-phosphate dehydrogenase (G-6-PD)-deficient humans and Dorest sheep, an animal model with an erythrocyte G-6-PD deficiency, responded in a dose-dependent manner to the oxidant stress of methyl oleate ozonide (MOO) as measured by decreases in G-6-PD a...

  7. Glucose homoeostasis following injury.

    PubMed Central

    Wright, P. D.

    1979-01-01

    Metabolic changes following injury have been observed for many years, and John Hunter discussed such changes in 1794. Changes in carbohydrate metabolism have been observed for a similar length of time, and glycosuria and hyperglycaemia have been reported by a number of observers. This paper records and quantitates the extent of hyperglycaemia in patients undergoing surgery of different degrees of severity and relates them to changes in blood insulin, growth hormone, cortisol, and catecholamine concentrations. Further animal studies were performed which suggested that a fall in intracellular glucose utilisation may be a contributory factor. The use of isotope labelling of glucose in man has enabled further studies to be done to clarify changes in exchangeable glucose mass, replacement rate, and space both in the normal situation and in the presence of infusions of glucagon, noradrenaline, glucose, and amino-acids. The hyperglycaemia is clearly the result of a complex interaction of changes in the availability and activity of hormones which control glucose metabolism both within and outside the cell. PMID:496234

  8. Unilateral conjunctival chemosis as a unique symptom of nonsteroidal anti-inflammatory drug intolerance.

    PubMed

    Fuentes, V; de Frutos, C; de Barrio, M; Barranco, R; Herrero, T; Tornero, P

    2007-01-01

    Patients with nonsteroidal anti-inflammatory drug (NSAID) intolerance usually have cutanous-mucosal or/and respiratory symptoms. We report the case of a patient who developed several episodes of left-eye conjunctivitis, manifested as conjunctival chemosis, with no other symptoms, after taking metamizole and other unidentified NSAIDs. We performed both a single blind placebo-controlled oral challenge test and conjunctival challenge test with different NSAIDs. The single blind placebo-controlled oral challenge was positive to ketoprofen and diclofenac. The conjunctival challenge with diclofenac and flurbiprofen was negative. The patient tolerated celecoxib and nabumetone. We believe this to be an exceptional case of NSAID intolerance as conjunctival chemosis has not hitherto been included in any of the classic types of pseudoallergic reactions. PMID:17323868

  9. Application of infrared thermography for the analysis of rewarming in patients with cold intolerance.

    PubMed

    Ruijs, Aleid C J; Jaquet, Jean-Bart; Brandsma, Martine; Daanen, Hein A M; Hovius, Steven E R

    2008-01-01

    Cold intolerance is a serious long-term problem after injury to the ulnar and median nerves, and its pathophysiology is unclear. We investigated the use of infrared thermography for the analysis of thermoregulation after injury to peripheral nerves. Four patients with injuries to the ulnar nerve and four with injuries to the median nerve (4-12 years after injury) immersed their hands in water at 15 degrees C for 5 minutes, after which infrared pictures were taken at intervals of 2-4 minutes. The areas supplied by the injured nerves could be identified easily in the patients with symptoms of cold intolerance. At baseline temperature distribution of the hand was symmetrical, but after testing the injured side warmed up much slower. We concluded that the infrared profile of the temperature of the hand after immersion in cold water is helpful to assess thermoregulation after injury to peripheral nerves. PMID:18763198

  10. [Fiber, food intolerances, FODMAPs, gluten and functional gastrointestinal disorders--update 2014].

    PubMed

    Leiß, O

    2014-11-01

    The controversial effects of dietary fiber on symptoms in functional gastrointestinal disorders are summarized. Studies concerning adverse reaction to foods are mentioned and the possible role of food allergy and food intolerances, especially pseudoallergic reactions to biogenes amines, in symptom provocation is discussed. The known effects of lactose deficiency and fructose malabsorption are reviewed. The FODMAP concept (fermentable oligo-, di-, monosaccharides and polyols) is presented in more detail and recent studies on pathophysiological effects of FODMAP constituents and of therapeutic effects of a low FODMAP diet on symptoms in patients with irritable bowel syndrome are discussed. Finally, studies on the new disorder non-celiac gluten sensitivity (NCGS) are summarized and the state of the discussion whether wheat intolerance is due to gluten or the grains is given. PMID:25390215

  11. Reflections on the Institute of Medicine’s systemic exertion intolerance disease

    PubMed Central

    Jason, Leonard A.; Sunnquist, Madison; Brown, Abigail; McManimen, Stephanie; Furst, Jacob

    2016-01-01

    The Institute of Medicine (IOM) in the United States has recently proposed that the term systemic exertion intolerance disease (SEID) replace chronic fatigue syndrome. In addition, the IOM proposed a new case definition for SEID, which includes substantial reductions or impairments in the ability to engage in pre-illness activities, unrefreshing sleep, postexertional malaise, and either cognitive impairment or orthostatic intolerance. Unfortunately, these recommendations for a name change were not vetted with patient and professional audiences, and the new criteria were not evaluated with data sets of patients and controls. A recent poll suggests that the majority of patients reject this new name. In addition, studies have found that prevalence rates will dramatically increase with the new criteria, particularly due to the ambiguity revolving around exclusionary illnesses. Findings suggest that the new criteria select more patients who have less impairment and fewer symptoms than several other criteria. The implications of these findings are discussed in the current review. PMID:26176405

  12. In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome.

    PubMed

    Lengert, Nicor; Drossel, Barbara

    2015-07-01

    Post-exertional malaise is commonly observed in patients with myalgic encephalomyelitis/chronic fatigue syndrome, but its mechanism is not yet well understood. A reduced capacity for mitochondrial ATP synthesis is associated with the pathogenesis of CFS and is suspected to be a major contribution to exercise intolerance in CFS patients. To demonstrate the connection between a reduced mitochondrial capacity and exercise intolerance, we present a model which simulates metabolite dynamics in skeletal muscles during exercise and recovery. CFS simulations exhibit critically low levels of ATP, where an increased rate of cell death would be expected. To stabilize the energy supply at low ATP concentrations the total adenine nucleotide pool is reduced substantially causing a prolonged recovery time even without consideration of other factors, such as immunological dysregulations and oxidative stress. Repeated exercises worsen this situation considerably. Furthermore, CFS simulations exhibited an increased acidosis and lactate accumulation consistent with experimental observations. PMID:25899994

  13. EvoTol: a protein-sequence based evolutionary intolerance framework for disease-gene prioritization

    PubMed Central

    Rackham, Owen J. L.; Shihab, Hashem A.; Johnson, Michael R.; Petretto, Enrico

    2015-01-01

    Methods to interpret personal genome sequences are increasingly required. Here, we report a novel framework (EvoTol) to identify disease-causing genes using patient sequence data from within protein coding-regions. EvoTol quantifies a gene's intolerance to mutation using evolutionary conservation of protein sequences and can incorporate tissue-specific gene expression data. We apply this framework to the analysis of whole-exome sequence data in epilepsy and congenital heart disease, and demonstrate EvoTol's ability to identify known disease-causing genes is unmatched by competing methods. Application of EvoTol to the human interactome revealed networks enriched for genes intolerant to protein sequence variation, informing novel polygenic contributions to human disease. PMID:25550428

  14. How to monitor blood glucose.

    PubMed

    Dunning, Trisha

    2016-01-27

    Rationale and key points Capillary blood glucose monitoring is an essential component of diabetes care. Blood glucose tests provide important information about how the body is controlling blood glucose metabolism, and the effect of glucose-lowering medicines, illness and stress. ▶ The nurse should consider the rationale for testing blood glucose each time they perform a test, and reflect on the result, taking into consideration the patient's blood glucose target range and recommended care guidelines. ▶ Blood glucose testing times and testing frequency should be planned to suit the glucose-lowering medicine regimen and the clinical situation. Reflective activity Clinical skills articles can help update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. What you have gained from this article. 2. How this article will influence your practice when monitoring blood glucose. Subscribers can upload their reflective accounts at: rcni.com/portfolio . PMID:26967884

  15. Polarimetric glucose sensing in an artificial eye anterior chamber

    NASA Astrophysics Data System (ADS)

    Malik, Bilal H.; Pirnstill, Casey W.; Coté, Gerard L.

    2012-03-01

    The application of optical polarimetry to glucose sensing in the anterior chamber of the eye has emerged as a potential technique to noninvasively ascertain blood glucose levels. One of the major limiting factors preventing the realization of such a device is the time varying corneal birefringence due to motion artifact in the eye. The varying birefringence confounds the optical activity of glucose, and thus, needs to be taken into account in order to successfully predict the glucose concentration in the aqueous humor of the eye. Our group has developed a multi-spectral optical polarimetric approach which can minimize the effect of corneal birefringence coupled with motion artifact by treating it as common mode noise to multiple wavelengths. Here, we present the application of a real-time closed-loop dual wavelength polarimeter to ex vivo glucose sensing in excised New Zealand White rabbits' corneas mounted on an artificial anterior chamber. Our PID control system can reach stability in less than 100 ms which is fast enough to overcome motion artifact due to heart beat and respiration. The system can predict the glucose concentration with a standard error of less than 26 mg/dL in the physiologic glucose range of 0 - 500 mg/dL. Our results indicate that dualwavelength polarimetry has the potential to noninvasively probe glucose through the anterior chamber of the eye.

  16. Sex steroids and glucose metabolism.

    PubMed

    Allan, Carolyn A

    2014-01-01

    Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus (T2DM) and also predict the onset of these adverse metabolic states. Body composition (body mass index, waist circumference) is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter's syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain. PMID:24457840

  17. A genetic rat model of cholinergic hypersensitivity: implications for chemical intolerance, chronic fatigue, and asthma.

    PubMed

    Overstreet, D H; Djuric, V

    2001-03-01

    The fact that only some individuals exposed to environmental chemicals develop chemical intolerance raises the possibility that genetic factors could be contributing factors. The present communication summarizes evidence from a genetic animal model of cholinergic supersensitivity that suggests that an abnormal cholinergic system could be one predisposing genetic factor. The Flinders Sensitive Line (FSL) rats were established by selective breeding for increased responses to an organophosphate. It was subsequently found that these FSL rats were also more sensitive to direct-acting muscarinic agonists and had elevated muscarinic receptors compared to the selectively bred parallel group, the Flinders Resistant Line (FRL) rats, or randomly bred control rats. Increased sensitivity to cholinergic agents has also been observed in several human populations, including individuals suffering from chemical intolerance. Indeed, the FSL rats exhibit certain behavioral characteristics such as abnormal sleep, activity, and appetite that are similar to those reported in these human populations. In addition, the FSL rats have been reported to exhibit increased sensitivity to a variety of other chemical agents. Peripheral tissues, such as intestinal and airway smooth muscle, appear to be more sensitive to both cholinergic agonists and an antigen, ovalbumin. Hypothermia, a centrally mediated response, is more pronounced in the FSL rats after nicotine and alcohol, as well as agents that are selective for the dopaminergic and serotonergic systems. In some cases, the increased sensitivity has been detected in the absence of any changes in the receptors with which the drugs interact (dopamine receptors), while receptor changes have been seen in other cases (nicotine receptors). Therefore, there may be multiple mechanisms underlying the multiple chemical sensitivity-chemical intolerance of the FSL rats. An elucidation of these mechanisms may provide useful clues to those involved in

  18. Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin system

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

    PURPOSE: Orthostatic intolerance is the cause of significant disability in otherwise normal patients. Orthostatic tachycardia is usually the dominant hemodynamic abnormality, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety and, in some cases, syncope. It is the most common disorder of blood pressure regulation after essential hypertension. There is a predilection for younger rather than older adults and for women more than men. Its cause is unknown; partial sympathetic denervation or hypovolemia has been proposed. METHODS AND MATERIALS: We tested the hypothesis that reduced plasma renin activity, perhaps from defects in sympathetic innervation of the kidney, could underlie a hypovolemia, giving rise to these clinical symptoms. Sixteen patients (14 female, 2 male) ranging in age from 16 to 44 years were studied. Patients were enrolled in the study if they had orthostatic intolerance, together with a raised upright plasma norepinephrine (> or = 600 pg/mL). Patients underwent a battery of autonomic tests and biochemical determinations. RESULTS: There was a strong positive correlation between the blood volume and plasma renin activity (r = 0.84, P = 0.001). The tachycardic response to upright posture correlated with the severity of the hypovolemia. There was also a correlation between the plasma renin activity measured in these patients and their concomitant plasma aldosterone level. CONCLUSIONS: Hypovolemia occurs commonly in orthostatic intolerance. It is accompanied by an inappropriately low level of plasma renin activity. The degree of abnormality of blood volume correlates closely with the degree of abnormality in plasma renin activity. Taken together, these observations suggest that reduced plasma renin activity may be an important pathophysiologic component of the syndrome of orthostatic intolerance.

  19. Effect of Raw Milk on Lactose Intolerance: A Randomized Controlled Pilot Study

    PubMed Central

    Mummah, Sarah; Oelrich, Beibei; Hope, Jessica; Vu, Quyen; Gardner, Christopher D.

    2014-01-01

    PURPOSE This pilot study aimed to determine whether raw milk reduces lactose malabsorption and/or lactose intolerance symptoms relative to pasteurized milk. METHODS We performed a crossover trial involving 16 adults with self-reported lactose intolerance and lactose malabsorption confirmed by hydrogen (H2) breath testing. Participants underwent 3, 8-day milk phases (raw vs 2 controls: pasteurized, soy) in randomized order separated by 1-week washout periods. On days 1 and 8 of each phase, milk consumption was 473 mL (16 oz); on days 2 to 7, milk dosage increased daily by 118 mL (4 oz), beginning with 118 mL (4 oz) on day 2 and reaching 710 mL (24 oz) on day 7. Outcomes were area under the breath H2 curve (AUC ∆H2) and self-reported symptom severity (visual analog scales: flatulence/gas, audible bowel sounds, abdominal cramping, diarrhea). RESULTS AUC ∆H2 (mean ± standard error of the mean) was higher for raw vs pasteurized on day 1 (113 ± 21 vs 71 ± 12 ppm·min·10−2, respectively, P = .01) but not day 8 (72 ± 14 vs 74 ± 15 ppm·min·10−2, respectively, P = .9). Symptom severities were not different for raw vs pasteurized on day 7 with the highest dosage (P >.7). AUC ∆H2 and symptom severities were higher for both dairy milks compared with soy milk. CONCLUSIONS Raw milk failed to reduce lactose malabsorption or lactose intolerance symptoms compared with pasteurized milk among adults positive for lactose malabsorption. These results do not support widespread anecdotal claims that raw milk reduces the symptoms of lactose intolerance. PMID:24615309

  20. CAV3 mutations causing exercise intolerance, myalgia and rhabdomyolysis: Expanding the phenotypic spectrum of caveolinopathies.

    PubMed

    Scalco, Renata Siciliani; Gardiner, Alice R; Pitceathly, Robert D S; Hilton-Jones, David; Schapira, Anthony H; Turner, Chris; Parton, Matt; Desikan, Mahalekshmi; Barresi, Rita; Marsh, Julie; Manzur, Adnan Y; Childs, Anne-Marie; Feng, Lucy; Murphy, Elaine; Lamont, Phillipa J; Ravenscroft, Gianina; Wallefeld, William; Davis, Mark R; Laing, Nigel G; Holton, Janice L; Fialho, Doreen; Bushby, Kate; Hanna, Michael G; Phadke, Rahul; Jungbluth, Heinz; Houlden, Henry; Quinlivan, Ros

    2016-08-01

    Rhabdomyolysis is often due to a combination of environmental trigger(s) and genetic predisposition; however, the underlying genetic cause remains elusive in many cases. Mutations in CAV3 lead to various neuromuscular phenotypes with partial overlap, including limb girdle muscular dystrophy type 1C (LGMD1C), rippling muscle disease, distal myopathy and isolated hyperCKemia. Here we present a series of eight patients from seven families presenting with exercise intolerance and rhabdomyolysis caused by mutations in CAV3 diagnosed by next generation sequencing (NGS) (n = 6). Symptoms included myalgia (n = 7), exercise intolerance (n = 7) and episodes of rhabdomyolysis (n = 2). Percussion-induced rapid muscle contractions (PIRCs) were seen in five out of six patients examined. A previously reported heterozygous mutation in CAV3 (p.T78M) and three novel variants (p.V14I, p.F41S, p.F54V) were identified. Caveolin-3 immunolabeling in muscle was normal in 3/4 patients; however, immunoblotting showed more than 50% reduction of caveolin-3 in five patients compared with controls. This case series demonstrates that exercise intolerance, myalgia and rhabdomyolysis may be caused by CAV3 mutations and broadens the phenotypic spectrum of caveolinopathies. In our series, immunoblotting was a more sensitive method to detect reduced caveolin-3 levels than immunohistochemistry in skeletal muscle. Patients presenting with muscle pain, exercise intolerance and rhabdomyolysis should be routinely tested for PIRCs as this may be an important clinical clue for caveolinopathies, even in the absence of other "typical" features. The use of NGS may expand current knowledge concerning inherited diseases, and unexpected/atypical phenotypes may be attributed to well-known human disease genes. PMID:27312022

  1. Effects of two doses of glucose and a caffeine–glucose combination on cognitive performance and mood during multi-tasking

    PubMed Central

    Scholey, Andrew; Savage, Karen; O'Neill, Barry V; Owen, Lauren; Stough, Con; Priestley, Caroline; Wetherell, Mark

    2014-01-01

    Background This study assessed the effects of two doses of glucose and a caffeine–glucose combination on mood and performance of an ecologically valid, computerised multi-tasking platform. Materials and methods Following a double-blind, placebo-controlled, randomised, parallel-groups design, 150 healthy adults (mean age 34.78 years) consumed drinks containing placebo, 25 g glucose, 60 g glucose or 60 g glucose with 40 mg caffeine. They completed a multi-tasking framework at baseline and then 30 min following drink consumption with mood assessments immediately before and after the multi-tasking framework. Blood glucose and salivary caffeine were co-monitored. Results The caffeine–glucose group had significantly better total multi-tasking scores than the placebo or 60 g glucose groups and were significantly faster at mental arithmetic tasks than either glucose drink group. There were no significant treatment effects on mood. Caffeine and glucose levels confirmed compliance with overnight abstinence/fasting, respectively, and followed the predicted post-drink patterns. Conclusion These data suggest that co-administration of glucose and caffeine allows greater allocation of attentional resources than placebo or glucose alone. At present, we cannot rule out the possibility that the effects are due to caffeine alone Future studies should aim at disentangling caffeine and glucose effects. PMID:25196040

  2. Phenytoin as an effective treatment for polymorphic ventricular tachycardia due to QT prolongation in a patient with multiple drug intolerances.

    PubMed

    Yager, Neil; Wang, Katherine; Keshwani, Najiba; Torosoff, Mikhail

    2015-01-01

    We present a case of a 69-year-old woman presenting with polymorphic ventricular tachycardia caused by QT prolongation. Owing to known intolerances to a majority of antiarrhythmic medications, one remaining option was to initiate phenytoin. Phenytoin's narrow therapeutic window, multiple drug interactions and side effect profile make it an infrequently used antiarrhythmic. It is, however, a potent antiarrhythmic agent, which may be useful in treatment of ventricular tachycardia, especially in patients with multiple drug intolerances. PMID:26071440

  3. The Interrelationships between Lactose Intolerance and the Modern Dairy Industry: Global Perspectives in Evolutional and Historical Backgrounds

    PubMed Central

    Silanikove, Nissim; Leitner, Gabriel; Merin, Uzi

    2015-01-01

    Humans learned to exploit ruminants as a source of milk about 10,000 years ago. Since then, the use of domesticated ruminants as a source of milk and dairy products has expanded until today when the dairy industry has become one of the largest sectors in the modern food industry, including the spread at the present time to countries such as China and Japan. This review analyzes the reasons for this expansion and flourishing. As reviewed in detail, milk has numerous nutritional advantages, most important being almost an irreplaceable source of dietary calcium, hence justifying the effort required to increase its consumption. On the other hand, widespread lactose intolerance among the adult population is a considerable drawback to dairy-based foods consumption. Over the centuries, three factors allowed humans to overcome limitations imposed by lactose intolerance: (i) mutations, which occurred in particular populations, most notably in the north European Celtic societies and African nomads, in which carriers of the lactose intolerance gene converted from being lactose intolerant to lactose tolerant; (ii) the ability to develop low-lactose products such as cheese and yogurt; and (iii) colon microbiome adaptation, which allow lactose intolerant individuals to overcome its intolerance. However, in a few examples in the last decade, modern dairy products, such as the popular and widespread bio-cultured yogurts, were suspected to be unsuitable for lactose intolerant peoples. In addition, the use of lactose and milk-derived products containing lactose in non-dairy products has become widespread. For these reasons, it is concluded that it might be important and helpful to label food that may contain lactose because such information will allow lactose intolerant groups to control lactose intake within the physiological limitations of ~12 g per a single meal. PMID:26404364

  4. The Interrelationships between Lactose Intolerance and the Modern Dairy Industry: Global Perspectives in Evolutional and Historical Backgrounds.

    PubMed

    Silanikove, Nissim; Leitner, Gabriel; Merin, Uzi

    2015-09-01

    Humans learned to exploit ruminants as a source of milk about 10,000 years ago. Since then, the use of domesticated ruminants as a source of milk and dairy products has expanded until today when the dairy industry has become one of the largest sectors in the modern food industry, including the spread at the present time to countries such as China and Japan. This review analyzes the reasons for this expansion and flourishing. As reviewed in detail, milk has numerous nutritional advantages, most important being almost an irreplaceable source of dietary calcium, hence justifying the effort required to increase its consumption. On the other hand, widespread lactose intolerance among the adult population is a considerable drawback to dairy-based foods consumption. Over the centuries, three factors allowed humans to overcome limitations imposed by lactose intolerance: (i) mutations, which occurred in particular populations, most notably in the north European Celtic societies and African nomads, in which carriers of the lactose intolerance gene converted from being lactose intolerant to lactose tolerant; (ii) the ability to develop low-lactose products such as cheese and yogurt; and (iii) colon microbiome adaptation, which allow lactose intolerant individuals to overcome its intolerance. However, in a few examples in the last decade, modern dairy products, such as the popular and widespread bio-cultured yogurts, were suspected to be unsuitable for lactose intolerant peoples. In addition, the use of lactose and milk-derived products containing lactose in non-dairy products has become widespread. For these reasons, it is concluded that it might be important and helpful to label food that may contain lactose because such information will allow lactose intolerant groups to control lactose intake within the physiological limitations of ~12 g per a single meal. PMID:26404364

  5. Knowledge about aging and worry in older adults: Testing the mediating role of intolerance of uncertainty

    PubMed Central

    Nuevo, Roberto; Wetherell, Julie Loebach; Montorio, Ignacio; Ruiz, Miguel A.; Cabrera, Isabel

    2014-01-01

    Objectives This study aims to explore the relationship between knowledge about aging and severity of worry in older adults, and to test the potential mediational role of intolerance of uncertainty. Method The sample was composed of 120 community-dwelling older adults, with a mean of age of 71.0 years (SD = 6.3). Mediational analyses and structural equation modeling were used to analyze and compare different models. Results Greater knowledge about aging was negatively related to both intolerance of uncertainty and worry, and its effect on worry was partially mediated by intolerance of uncertainty. The mediational model obtained an excellent fit to the data (i.e. Goodness of fit index (GFI) = 0.995) and clearly had a better fit than alternative models. Conclusion These results suggest that a good knowledge of the aging process could help decrease aversive uncertainty and thus reduce the level of worry among older adults. Thus, educational programs to increase knowledge about aging could serve as one preventive strategy for anxiety in old age. PMID:19197699

  6. Effects of standing on cerebrovascular resistance in patients with idiopathic orthostatic intolerance

    NASA Technical Reports Server (NTRS)

    Jacob, G.; Atkinson, D.; Jordan, J.; Shannon, J. R.; Furlan, R.; Black, B. K.; Robertson, D.

    1999-01-01

    PURPOSE: Patients with idiopathic orthostatic intolerance often have debilitating symptoms on standing that are suggestive of cerebral hypoperfusion despite the absence of orthostatic hypotension. SUBJECTS AND METHODS: We evaluated the effects of graded head-up tilt on cerebral blood flow as determined by transcranial Doppler measurements in 10 patients with idiopathic orthostatic intolerance (nine women, one man, 22 to 47 years) and nine age- and sex-matched control subjects. RESULTS: In patients, mean (+/- SD) arterial pressure at 0 degrees head-up tilt was 90 +/- 11 mm Hg and was well maintained at all tilt angles (90 +/- 11 mm Hg at 75 degrees). In controls, mean arterial pressure was 85 +/- 7 mm Hg at 0 degrees and 82 +/- 11 mm Hg at 75 degrees head-up tilt. There was a substantial decrease in peak velocity with increasing tilt angle in patients (28% +/- 10%) but not in controls (10% +/- 10% at 75 degrees, P <0.001). Similarly, mean velocity decreased 26% +/- 13% in patients and 12% +/- 11% in controls (P = 0.01). With increasing head-up tilt, patients had a significantly greater increase in regional cerebrovascular resistance than controls. CONCLUSIONS: In patients with idiopathic orthostatic intolerance, peak and mean middle cerebral artery blood flow velocity decreased in response to head-up tilt despite well sustained arterial blood pressure. These observations indicate that in this group of patients, regulation of cerebrovascular tone may be impaired and might therefore be a target for therapeutic interventions.

  7. Aspirin-intolerant asthma: a comprehensive review of biomarkers and pathophysiology.

    PubMed

    Velazquez, Juan R; Teran, Luis M

    2013-08-01

    Aspirin-exacerbated respiratory disease is a tetrad of nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma, and sensitivity to aspirin. Unawareness of this clinical condition by patients and physicians may have grave consequences because of its association with near-fatal asthma. The pathogenesis of aspirin-intolerant asthma is not related with an immunoglobin E mechanism, but with an abnormal metabolism of the lipoxygenase (LO) and cyclooxygenase (COX) pathways. At present, a diagnosis of aspirin sensitivity can be established only by provocative aspirin challenge, which represents a health risk for the patient. This circumstance has encouraged the search for aspirin intolerance-specific biomarkers. Major attempts have focused on mediators related with inflammation and eicosanoid regulation. The use of modern laboratory techniques including high-throughput methods has facilitated the detection of dozens of biological metabolites associated with aspirin-intolerant asthma disease. Not surprisingly, the majority of these is implicated in the LO and COX pathways. However, substantial amounts of data reveal the participation of many genes deriving from different ontologies. Biomarkers may represent a powerful, noninvasive tool in the diagnosis of aspirin sensitivity; moreover, they could provide a new way to classify asthma phenotypes. PMID:23184151

  8. Decrease in TSH levels after lactose restriction in Hashimoto's thyroiditis patients with lactose intolerance.

    PubMed

    Asik, Mehmet; Gunes, Fahri; Binnetoglu, Emine; Eroglu, Mustafa; Bozkurt, Neslihan; Sen, Hacer; Akbal, Erdem; Bakar, Coskum; Beyazit, Yavuz; Ukinc, Kubilay

    2014-06-01

    We aimed to evaluate the prevalence of lactose intolerance (LI) in patients with Hashimoto's thyroiditis(HT) and the effects of lactose restriction on thyroid function in these patients. Eighty-three HT patients taking L-thyroxine (LT4) were enrolled, and lactose tolerance tests were performed on all patients. Lactose intolerance was diagnosed in 75.9 % of the patients with HT. Thirty-eight patients with LI were started on a lactose-restricted diet for 8 weeks. Thirty-eight patients with LI (30 euthyroid and 8 with subclinical hypothyroidism), and 12 patients without LI were included in the final analysis. The level of TSH significantly decreased in the euthyroid and subclinical hypothyroid patients with LI [from 2.06 ± 1.02 to 1.51 ±1.1 IU/mL and from 5.45 ± 0.74 to 2.25 ± 1.88 IU/mL,respectively (both P<0.05)]. However, the level of TSH in patients without LI did not change significantly over the 8 weeks (P>0.05). Lactose intolerance occurs at a high frequency in HT patients. Lactose restriction leads to decreased levels of TSH, and LI should be considered in hypothyroid patients who require increasing LT4 doses,have irregular TSH levels and are resistant to LT4 treatment. PMID:24078411

  9. [Nilotinib treatment for patients with imatinib-resistant or intolerant chronic myeloid leukemia].

    PubMed

    Pan, Liang-Qin; Liu, Wei-Xin; Zhu, Yu; Hong, Ming; Qiao, Shun; Li, Jian-Yong; Qian, Si-Xuan

    2014-12-01

    This study was purposed to evaluate the efficacy and safety of nilotinib for treating patients with imatinib-resistant or intolerant chronic myeloid leukemia (CML). A total of 23 patients with imatinib-resistant or intolerant CML were enrolled in this study. These patients received nilotinib orally 600-800 mg every day, their curative efficacy, tolerance and overal survival were evaluated. The results showed that all the patients treated with nilotinib obtained complete hematologic remission (CHR), out of them 82.6% patients achieved complete cytogenetic remission (CCyR) and 56.5% patients achieved complete molecular remission (CMR), their adverse events mostly were mild to moderate, generally were transient and easily cured; the median treatment time with nilotinib was 13.5 (1-44) months, and the median follow-up time was 40 (12-102) months. It is concluded that nilotinib has been confirmed to be effective for patients with imatinib-resistant or intolerant CML, and may be selected as a second generation of tyrosine kinase inhibitor (TKI). PMID:25543472

  10. Resolving Uncertainty About the Intolerance of Uncertainty Scale–12: Application of Modern Psychometric Strategies

    PubMed Central

    Hale, Willie; Richmond, Miranda; Bennett, Janet; Berzins, Tiffany; Fields, Alexander; Weber, David; Beck, Mark; Osman, Augustine

    2016-01-01

    In this study, we evaluated the factor structure, reliability estimates, item parameters, and differential correlates of the short form of the Intolerance of Uncertainty Scale (Carleton, Norton, & Asmundson, 2007) in samples of undergraduate women (n = 387) and men (n = 276) ranging in age from 18 to 49 years (M = 20.20, SD = 3.91). This instrument was designed to measure 2 facets of intolerance of uncertainty— prospective anxiety and inhibitory anxiety—although total scores on the measure are often used. A major objective of this study was to determine the degree to which derivation of total versus subscale scores is empirically permissible. Comparison of a bifactor model to a unidimensional model and a 2-factor correlated traits model indicated that the bifactor model exhibited superior fit to the sample data. This model provided evidence of a strong general intolerance of uncertainty factor that was more reliable and accounted for significantly more common variance than either subscale factor. Examination of the item response theory slope parameters revealed negligible bias in the measure’s items across genders. Finally, a series of simultaneous regression analyses was conducted to examine differential correlates of the measure’s total scale scores for men and women. PMID:26542301

  11. Does the use of glycerin laxatives decrease feeding intolerance in preterm infants?

    PubMed Central

    Shah, Vibhuti; Chirinian, Nevart; Lee, Shoo

    2011-01-01

    BACKGROUND: Glycerin laxatives are often prescribed in the neonatal population for meconium evacuation and to promote enteral feeding. However, the literature regarding their effectiveness has not been systematically reviewed. OBJECTIVE: To assess the effectiveness of glycerin enema or suppository in preventing feeding intolerance in preterm infants at ≤32 weeks’ gestational age or weighing ≤1500 g at birth. METHODS: The Medline, Embase, Cochrane Library, Scopus and Web of Science databases were searched to identify studies that evaluated glycerin enemas/suppositories for feeding intolerance. Using the Evidence Evaluation Worksheet adapted from the American Heart Association’s International Liaison Committee on Resuscitation, eligible studies were scored for quality, level of evidence and direction of support. RESULTS: Two clinical studies that evaluated meconium evacuation and feeding intolerance were included. One study showed no difference in the time to complete meconium evacuation or establishment of full enteral feeds, while the other showed that the times to first meconium passage and full enteral feeding were significantly shorter, and the rate of sepsis was lower in the glycerin enema group. CONCLUSION: The evidence regarding the effectiveness of glycerin laxatives for improving feeding tolerance is inconclusive in infants at ≤32 weeks’ gestational age or weighing ≤1500 g at birth. PMID:23115504

  12. Contributions of MSNA and stroke volume to orthostatic intolerance following bed rest

    NASA Technical Reports Server (NTRS)

    Shoemaker, J. K.; Hogeman, C. S.; Sinoway, L. I.

    1999-01-01

    We examined whether the altered orthostatic tolerance following 14 days of head-down tilt bed rest (HDBR) was related to inadequate sympathetic outflow or to excessive reductions in cardiac output during a 10- to 15-min head-up tilt (HUT) test. Heart rate, blood pressure (BP, Finapres), muscle sympathetic nerve activity (MSNA, microneurography), and stroke volume blood velocity (SVV, Doppler ultrasound) were assessed during supine 30 degrees (5 min) and 60 degrees (5-10 min) HUT positions in 15 individuals who successfully completed the pre-HDBR test without evidence of orthostatic intolerance. Subjects were classified as being orthostatically tolerant (OT, n = 9) or intolerant (OI, n = 6) following the post-HDBR test. MSNA, BP, and SVV during supine and HUT postures were not altered in the OT group. Hypotension during 60 degrees HUT in the post-bed rest test for the OI group (P < 0.05) was associated with a blunted increase in MSNA (P < 0.05). SVV was reduced following HDBR in the OI group (main effect of HDBR, P < 0.02). The data support the hypothesis that bed rest-induced orthostatic intolerance is related to an inadequate increase in sympathetic discharge that cannot compensate for a greater postural reduction in stroke volume.

  13. The prevalence of intolerance for low-dose acetylsalicylacid in the secondary prevention of atherothrombosis.

    PubMed

    Tournoij, E; Peters, R J G; Langenberg, M; Kanhai, K J K; Moll, F L

    2009-05-01

    Daily low-dose acetylsalicylacid (ASA) is prescribed to patients with atherothrombosis frequently to prevent vascular complications. In reports on complications and side effects of low-dose ASA use in the literature there is a range of definitions. We explored the incidence, characteristics and consequences of symptoms suggestive of ASA intolerance in patients on low-dose ASA. General practitioners and specialists in 105 centres were asked to review their patient files for the last 10 consecutive patients who were prescribed ASA. Participating patients completed a questionnaire about their current ASA use (doctors completed the questionnaire together with the patients), use of co-medication and symptoms suggestive of ASA intolerance. A total of 947 patients were included in this study. Sixty patients (6.6%) had ceased ASA treatment, predominantly because of the occurrence of side effects suspected to be caused by ASA use. A quarter of the patients concomitantly used an anti-acid agent. Of the 947 patients, 271 (30.6%) indicated symptoms during ASA intake. The most common symptoms were related to the gastrointestinal tract (25.1%). In patients prescribed a low-dose of ASA monotherapy, side effects suggestive of intolerance are common. More awareness should be created to detect and treat these symptoms, because the occurrence of side effects is the most important reason for patients to discontinue ASA treatment. PMID:19297216

  14. Intolerance for Smoking Abstinence Questionnaire: Psychometric Properties and Relationship to Tobacco Dependence and Abstinence

    PubMed Central

    Sirota, Alan D.; Rohsenow, Damaris J.; MacKinnon, Selene V.; Martin, Rosemarie A.; Eaton, Cheryl A.; Kaplan, Gary B.; Monti, Peter M.; Tidey, Jennifer W.; Swift, Robert M.

    2013-01-01

    While smokers’ ability to tolerate emotional or physical distress has been associated with length of smoking cessation, there is no measure of ability to tolerate smoking abstinence discomfort specifically, which may be more heuristic than a measure of tolerance of general emotional stress or physical discomfort. Methods Questionnaires completed by 300 smokers assessed inability to tolerate smoking abstinence discomfort (IDQ-S), general physical discomfort (IDQ-P), and general emotional discomfort (IDQ-E), so that shared variance among these measures could be assessed. Results The IDQ-S has three reliable components: Withdrawal Intolerance, Lack of Cognitive Coping, and Pain Intolerance. The 14-item IDQ-P and 9-item IDQ-E each consist of one reliable component. Intercorrelations suggest only modest shared variance. Support for construct and discriminant validity was seen. Two scales of the IDQ-S showed excellent convergent validity, correlating with smoking use, dependence, motivation, and length of past smoking cessation, while IDQ-P and IDQ-E correlated with few indices of use or dependence and not with smoking cessation. Conclusions The final 17-item IDQ-S with two scales is reliable and valid, and more heuristic than measures of general physical or emotional discomfort intolerance as a correlate of motivation and past success with smoking cessation. PMID:20381260

  15. Nitric oxide in microgravity-induced orthostatic intolerance: relevance to spinal cord injury

    NASA Technical Reports Server (NTRS)

    Vaziri, N. D.; Purdy, R. E. (Principal Investigator)

    2003-01-01

    Prolonged exposure to microgravity results in cardiovascular deconditioning which is marked by orthostatic intolerance in the returning astronauts and recovering bed-ridden patients. Recent studies conducted in our laboratories at University of California, Irvine have revealed marked elevation of nitric oxide (NO) production in the kidney, heart, brain, and systemic arteries coupled with significant reduction of NO production in the cerebral arteries of microgravity-adapted animals. We have further demonstrated that the observed alteration of NO metabolism is primarily responsible for the associated cardiovascular deconditioning. Recovery from acute spinal cord injury (SCI) is frequently complicated by orthostatic intolerance that is due to the combined effects of the disruption of efferent sympathetic pathway and cardiovascular deconditioning occasioned by prolonged confinement to bed. In this presentation, I will review the nature of altered NO metabolism and its role in the pathogenesis of microgravity-induced cardiovascular deconditioning. The possible relevance of the new findings to orthostatic intolerance in patients with acute SCI and its potential therapeutic implications will be discussed.

  16. Participatory diagnosis of a heat-intolerance syndrome in cattle in Tanzania and association with foot-and-mouth disease.

    PubMed

    Catley, A; Chibunda, R T; Ranga, E; Makungu, S; Magayane, F T; Magoma, G; Madege, M J; Vosloo, W

    2004-08-30

    A heat-intolerance (HI) syndrome in cattle in Tanzania was suspected to be associated with previous, clinical foot-and-mouth disease (FMD). A participatory appraisal (PA) method called "matrix scoring" was used to explore livestock-keeper perceptions of association between HI and cattle diseases. A PA method called 'proportional piling' was used to estimate herd incidence of FMD and other diseases, herd incidence of HI, and association between HI and other cattle diseases. Use of matrix scoring and proportional piling with pastoral Maasai informants demonstrated association between FMD and HI. With agropastoral Sukuma informants, the matrix-scoring method did not indicate an association between FMD and HI, whereas the proportional piling method indicated a weak association. Results were supported by calculation of positive predictive values for herder diagnosis of HI and FMD. Clinical examination of cattle by veterinarians was used to confirm HI cases and detection of antibody to non-structural proteins of FMD virus was used to confirm previous clinical FMD. PMID:15454324

  17. Sustained Decrease of Early-Phase Insulin Secretion in Japanese Women with Gestational Diabetes Mellitus Who Developed Impaired Glucose Tolerance and Impaired Fasting Glucose Postpartum

    PubMed Central

    Katayama, Hiroko; Tachibana, Daisuke; Hamuro, Akihiro; Misugi, Takuya; Motoyama, Koka; Morioka, Tomoaki; Fukumoto, Shinya; Emoto, Masanori; Inaba, Masaaki; Koyama, Masayasu

    2015-01-01

    OBJECTIVE The aim of this study was to compare glucose intolerance in the antenatal and the postpartum periods using a 75-g oral glucose tolerance test (OGTT) in the Japanese women with gestational diabetes mellitus (GDM) using a retrospective design. PATIENTS AND METHODS Data were obtained from 85 Japanese women with GDM who delivered from April 2011 through April 2015 and who underwent an OGTT 6–14 weeks postpartum. The women were divided into two groups based on the results of the postpartum OGTT: one group with normal glucose tolerance (NGT) and the other with impaired glucose tolerance (IGT) as well as impaired fasting glucose (IFG). We analyzed the associations between postpartum IGT–IFG and various factors. RESULTS Antenatally, a significant difference was observed between the groups only in the 1-hour plasma glucose level of the 75-g OGTT. Postpartum results of plasma glucose level were significantly higher at 0.5, 1, and 2 hours in the IGT–IFG group than those in the NGT group. Moreover, a significant decrease in the levels of 0.5-hour immunoreactive insulin and insulinogenic index was observed in the IGT–IFG group compared to those in the NGT group. Homeostasis model assessment-insulin resistance and homeostasis model assessment β-cell function of both groups were found to significantly decrease in the postpartum period; however, there was no significant change in the insulinogenic index of either group. CONCLUSIONS Our study clearly showed that the postpartum IGT and IFG levels of Japanese women with GDM are affected by impaired early-phase insulin secretion; however, insulin resistance promptly improves. PMID:26688669

  18. TAp63 is a master transcriptional regulator of lipid and glucose metabolism.

    PubMed

    Su, Xiaohua; Gi, Young Jin; Chakravarti, Deepavali; Chan, Io Long; Zhang, Aijun; Xia, Xuefeng; Tsai, Kenneth Y; Flores, Elsa R

    2012-10-01

    TAp63 prevents premature aging, suggesting a link to genes that regulate longevity. Further characterization of TAp63-/- mice revealed that these mice develop obesity, insulin resistance, and glucose intolerance similar to those seen in mice lacking two key metabolic regulators, Silent information regulator T1 (Sirt1) and AMPK. While the roles of Sirt1 and AMPK in metabolism have been well studied, their upstream regulators are not well understood. We found that TAp63 is important in regulating energy metabolism by accumulating in response to metabolic stress and transcriptionally activating Sirt1, AMPKα2, and LKB1, resulting in increased fatty acid synthesis and decreased fatty acid oxidation. Moreover, we found that TAp63 lowers blood glucose levels in response to metformin. Restoration of Sirt1, AMPKα2, and LKB1 in TAp63-/- mice rescued some of the metabolic defects of the TAp63-/- mice. Our study defines a role for TAp63 in metabolism and weight control. PMID:23040072

  19. Mandatory oral glucose tolerance tests identify more diabetics in stable patients with chronic heart failure: a prospective observational study

    PubMed Central

    2014-01-01

    Background Many patients with chronic heart failure (CHF) are believed to have unrecognized diabetes, which is associated with a worse prognosis. This study aimed to describe glucose tolerance in a general stable CHF population and to identify determinants of glucose tolerance focusing on body composition and skeletal muscle strength. Methods A prospective observational study was set up. Inclusion criteria were diagnosis of CHF, stable condition and absence of glucose-lowering medication. Patients underwent a 2 h oral glucose tolerance test (OGTT), isometric strength testing of the upper leg and dual energy x-ray absorptiometry. Health-related quality of life and physical activity level were assessed by questionnaire. Results Data of 56 participants were analyzed. Despite near-normal fasting glucose values, 55% was classified as prediabetic, 14% as diabetic, and 20% as normal glucose tolerant. Of all newly diagnosed diabetic patients, 79% were diagnosed because of 2 h glucose values only and none because of HbA1c. Univariate mixed model analysis revealed ischaemic aetiology, daily physical activity, E/E’, fat trunk/fat limbs and extension strength as possible explanatory variables for the glucose curve during the glucose tolerance test. When combined in one model, only fat trunk/fat limbs and E/E’ remained significant predictors. Furthermore, fasting insulin was correlated with fat mass/height2 (r = 0.51, p < 0.0001), extension strength (r = -0.33, p < 0.01) and triglycerides (r = 0.39, p < 0.01). Conclusions Our data confirm that a large majority of CHF patients have impaired glucose tolerance. This glucose intolerance is related to fat distribution and left ventricular end-diastolic pressure. PMID:24673860

  20. Blood glucose monitoring.

    PubMed

    Davey, Sarah

    2014-06-10

    I found the CPD article on blood glucose monitoring and management in acute stroke care interesting and informative. As I am a mental health nursing student, my knowledge of chronic physical conditions is limited, so I learned a lot. PMID:24894257

  1. Glucose Tolerance and Hyperkinesis.

    ERIC Educational Resources Information Center

    Langseth, Lillian; Dowd, Judith

    Examined were medical records of 265 hyperkinetic children (7-9 years old). Clinical blood chemistries, hematology, and 5-hour glucose tolerance test (GTT) results indicated that hematocrit levels were low in 27% of the Ss, eosinophil levels were abnormally high in 86% of the Ss, and GTT results were abnormal in a maority of Ss. (CL)

  2. Glucose urine test

    MedlinePlus

    ... with a color-sensitive pad. The color the dipstick changes to tells the provider the level of glucose in your urine. If needed, your provider may ask you to collect your urine at home over 24 hours . Your provider will tell you how to do ...

  3. Comparison of the effects of fetal hypothyroidism on glucose tolerance in male and female rat offspring.

    PubMed

    Bagheripuor, Fatemeh; Ghanbari, Mahboubeh; Zahediasl, Saleh; Ghasemi, Asghar

    2015-03-01

    Thyroid hormones are vital for survival of mammalian species and play critical roles in growth, development, and metabolism. Both fetal hypothyroidism and sex can affect carbohydrate metabolism during adult life. This study aims to assess carbohydrate metabolism in male and female offspring born from mothers who were hypothyroid during pregnancy. Pregnant rats were divided into two groups; the controls consumed water and the hypothyroid group received water containing 0.025 % 6-propyl-2-thiouracial throughout gestation. The intravenous glucose tolerance test (0.5 g/kg glucose) was carried out in 3-month-old offspring. Findings showed that compared to controls, male fetal hypothyroid rats during adulthood had glucose intolerance (area under the curve: 446.4 ± 9.7 vs. 486.4 ± 8.8, p < 0.01 in control and fetal hypothyroid groups, respectively) whereas females had improved glucose tolerance (478.1 ± 7.0 vs. 455.9 ± 8.5, p < 0.01). In conclusion, sex could modulate the effects of fetal hypothyroidism on glucose tolerance in rats. PMID:25649149

  4. Lipid-Induced Peroxidation in the Intestine Is Involved in Glucose Homeostasis Imbalance in Mice

    PubMed Central

    Marsollier, Nicolas; Masseboeuf, Myriam; Payros, Gaëlle; Kabani, Catherine; Denom, Jessica; Lacombe, Amélie; Thiers, Jean-Claude; Negre-Salvayre, Anne; Luquet, Serge; Burcelin, Rémy; Cruciani-Guglielmacci, Céline; Magnan, Christophe

    2011-01-01

    Background Daily variations in lipid concentrations in both gut lumen and blood are detected by specific sensors located in the gastrointestinal tract and in specialized central areas. Deregulation of the lipid sensors could be partly involved in the dysfunction of glucose homeostasis. The study aimed at comparing the effect of Medialipid (ML) overload on insulin secretion and sensitivity when administered either through the intestine or the carotid artery in mice. Methodology/Principal Findings An indwelling intragastric or intracarotid catheter was installed in mice and ML or an isocaloric solution was infused over 24 hours. Glucose and insulin tolerance and vagus nerve activity were assessed. Some mice were treated daily for one week with the anti-lipid peroxidation agent aminoguanidine prior to the infusions and tests. The intestinal but not the intracarotid infusion of ML led to glucose and insulin intolerance when compared with controls. The intestinal ML overload induced lipid accumulation and increased lipid peroxidation as assessed by increased malondialdehyde production within both jejunum and duodenum. These effects were associated with the concomitant deregulation of vagus nerve. Administration of aminoguanidine protected against the effects of lipid overload and normalized glucose homeostasis and vagus nerve activity. Conclusions/Significance Lipid overload within the intestine led to deregulation of gastrointestinal lipid sensing that in turn impaired glucose homeostasis through changes in autonomic nervous system activity. PMID:21698161

  5. Caenorhabditis elegans PAQR-2 and IGLR-2 Protect against Glucose Toxicity by Modulating Membrane Lipid Composition.

    PubMed

    Svensk, Emma; Devkota, Ranjan; Ståhlman, Marcus; Ranji, Parmida; Rauthan, Manish; Magnusson, Fredrik; Hammarsten, Sofia; Johansson, Maja; Borén, Jan; Pilon, Marc

    2016-04-01

    In spite of the worldwide impact of diabetes on human health, the mechanisms behind glucose toxicity remain elusive. Here we show that C. elegans mutants lacking paqr-2, the worm homolog of the adiponectin receptors AdipoR1/2, or its newly identified functional partner iglr-2, are glucose intolerant and die in the presence of as little as 20 mM glucose. Using FRAP (Fluorescence Recovery After Photobleaching) on living worms, we found that cultivation in the presence of glucose causes a decrease in membrane fluidity in paqr-2 and iglr-2 mutants and that genetic suppressors of this sensitivity act to restore membrane fluidity by promoting fatty acid desaturation. The essential roles of paqr-2 and iglr-2 in the presence of glucose are completely independent from daf-2 and daf-16, the C. elegans homologs of the insulin receptor and its downstream target FoxO, respectively. Using bimolecular fluorescence complementation, we also show that PAQR-2 and IGLR-2 interact on plasma membranes and thus may act together as a fluidity sensor that controls membrane lipid composition. PMID:27082444

  6. Caenorhabditis elegans PAQR-2 and IGLR-2 Protect against Glucose Toxicity by Modulating Membrane Lipid Composition

    PubMed Central

    Svensk, Emma; Devkota, Ranjan; Ståhlman, Marcus; Ranji, Parmida; Rauthan, Manish; Magnusson, Fredrik; Hammarsten, Sofia; Johansson, Maja; Borén, Jan; Pilon, Marc

    2016-01-01

    In spite of the worldwide impact of diabetes on human health, the mechanisms behind glucose toxicity remain elusive. Here we show that C. elegans mutants lacking paqr-2, the worm homolog of the adiponectin receptors AdipoR1/2, or its newly identified functional partner iglr-2, are glucose intolerant and die in the presence of as little as 20 mM glucose. Using FRAP (Fluorescence Recovery After Photobleaching) on living worms, we found that cultivation in the presence of glucose causes a decrease in membrane fluidity in paqr-2 and iglr-2 mutants and that genetic suppressors of this sensitivity act to restore membrane fluidity by promoting fatty acid desaturation. The essential roles of paqr-2 and iglr-2 in the presence of glucose are completely independent from daf-2 and daf-16, the C. elegans homologs of the insulin receptor and its downstream target FoxO, respectively. Using bimolecular fluorescence complementation, we also show that PAQR-2 and IGLR-2 interact on plasma membranes and thus may act together as a fluidity sensor that controls membrane lipid composition. PMID:27082444

  7. Heart rate variability and short duration spaceflight: relationship to post-flight orthostatic intolerance

    PubMed Central

    Blaber, Andrew P; Bondar, Roberta L; Kassam, Mahmood S

    2004-01-01

    Background Upon return from space many astronauts experience symptoms of orthostatic intolerance. Research has implicated altered autonomic cardiovascular regulation due to spaceflight with further evidence to suggest that there might be pre-flight autonomic indicators of post-flight orthostatic intolerance. We used heart rate variability (HRV) to determine whether autonomic regulation of the heart in astronauts who did or did not experience post-flight orthostatic intolerance was different pre-flight and/or was differentially affected by short duration (8 – 16 days) spaceflight. HRV data from ten-minute stand tests collected from the 29 astronauts 10 days pre-flight, on landing day and three days post-flight were analysed using coarse graining spectral analysis. From the total power (PTOT), the harmonic component was extracted and divided into high (PHI: >0.15 Hz) and low (PLO: = 0.15 Hz) frequency power regions. Given the distribution of autonomic nervous system activity with frequency at the sinus node, PHI/PTOT was used as an indicator of parasympathetic activity; PLO/PTOT as an indicator of sympathetic activity; and, PLO/PHI as an estimate of sympathovagal balance. Results Twenty-one astronauts were classified as finishers, and eight as non-finishers, based on their ability to remain standing for 10 minutes on landing day. Pre-flight, non-finishers had a higher supine PHI/PTOT than finishers. Supine PHI/PTOT was the same pre-flight and on landing day in the finishers; whereas, in the non-finishers it was reduced. The ratio PLO/PHI was lower in non-finishers compared to finishers and was unaffected by spaceflight. Pre-flight, both finishers and non-finishers had similar supine values of PLO/PTOT, which increased from supine to stand. Following spaceflight, only the finishers had an increase in PLO/PTOT from supine to stand. Conclusions Both finishers and non-finishers had an increase in sympathetic activity with stand on pre-flight, yet only finishers

  8. High Intensity Exercise Countermeasures does not Prevent Orthostatic Intolerance Following Prolonged Bed Rest

    NASA Technical Reports Server (NTRS)

    Platts, Steven H.; Stenger, Michael B.; Ploutz-Snyder, Lori L.; Lee, Stuart M. C.

    2014-01-01

    Approximately 20% of Space Shuttle astronauts became presyncopal during operational stand and 80deg head-up tilt tests, and the prevalence of orthostatic intolerance increases after longer missions. Greater than 60% of the US astronauts participating in Mir and early International Space Station missions experienced presyncope during post-flight tilt tests, perhaps related to limitations of the exercise hardware that prevented high intensity exercise training until later ISS missions. The objective of this study was to determine whether an intense resistive and aerobic exercise countermeasure program designed to prevent cardiovascular and musculoskeletal deconditioning during 70 d of bed rest (BR), a space flight analog, would protect against post-BR orthostatic intolerance. METHODS Twenty-six subjects were randomly assigned to one of three groups: non-exercise controls (n=11) or one of two exercise groups (ExA, n=8; ExB, n=7). Both ExA and ExB groups performed the same resistive and aerobic exercise countermeasures during BR, but one exercise group received testosterone supplementation while the other received a placebo during BR in a double-blinded fashion. On 3 d/wk, subjects performed lower body resistive exercise and 30 min of continuous aerobic exercise (=75% max heart rate). On the other 3 d/wk, subjects performed only highintensity, interval-style aerobic exercise. Orthostatic intolerance was assessed using a 15-min 80? head-up tilt test performed 2 d (BR-2) before and on the last day of BR (BR70). Plasma volume was measured using carbon monoxide rebreathing on BR-3 and before rising on the first recovery day (BR+0). The code for the exercise groups has not been broken, and results are reported here without group identification. RESULTS Only one subject became presyncopal during tilt testing on BR-2, but 7 of 11 (63%) controls, 3 of 8 (38%) ExA, and 4 of 7 (57%) ExB subjects were presyncopal on BR70. Survival analysis of post-BR tilt tests revealed no

  9. Uric acid as a modulator of glucose and lipid metabolism.

    PubMed

    Lima, William Gustavo; Martins-Santos, Maria Emília Soares; Chaves, Valéria Ernestânia

    2015-09-01

    In humans, uric acid is the final oxidation product of purine catabolism. The serum uric acid level is based on the balance between the absorption, production and excretion of purine. Uric acid is similarly produced in the liver, adipose tissue and muscle and is primarily excreted through the urinary tract. Several factors, including a high-fructose diet and the use of xenobiotics and alcohol, contribute to hyperuricaemia. Hyperuricaemia belongs to a cluster of metabolic and haemodynamic abnormalities, called metabolic syndrome, characterised by abdominal obesity, glucose intolerance, insulin resistance, dyslipidaemia and hypertension. Hyperuricaemia reduction in the Pound mouse or fructose-fed rats, as well as hyperuricaemia induction by uricase inhibition in rodents and studies using cell culture have suggested that uric acid plays an important role in the development of metabolic syndrome. These studies have shown that high uric acid levels regulate the oxidative stress, inflammation and enzymes associated with glucose and lipid metabolism, suggesting a mechanism for the impairment of metabolic homeostasis. Humans lacking uricase, the enzyme responsible for uric acid degradation, are susceptible to these effects. In this review, we summarise the current knowledge of the effects of uric acid on the regulation of metabolism, primarily focusing on liver, adipose tissue and skeletal muscle. PMID:26133655

  10. Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time.

    PubMed

    Ottosson-Laakso, Emilia; Tuomi, Tiinamaija; Forsén, Björn; Gullström, Monika; Groop, Per-Henrik; Groop, Leif; Vikman, Petter

    2016-01-01

    Familial renal glycosuria is an inherited disorder resulting in glucose excretion in the urine despite normal blood glucose concentrations. It is most commonly due to mutations in the SLC5A2 gene coding for the glucose transporter SGLT2 in the proximal tubule. Several drugs have been introduced as means to lower glucose in patients with type 2 diabetes targeting SGLT2 resulting in renal glycosuria, but no studies have addressed the potential effects of decreased renal glucose reabsorption and chronic glycosuria on the prevention of glucose intolerance. Here we present data on a large pedigree with renal glycosuria due to two mutations (c.300-303+2del and p.A343V) in the SLC5A2 gene. The mutations, which in vitro affected glucose transport in a cell line model, and the ensuing glycosuria were not associated with better glycemic control during a follow-up period of more than 10 years. One individual, who was compound heterozygous for mutations in the SLC5A2 gene suffered from severe urogenital candida infections and postprandial hypoglycemia. In conclusion, in this family with familial glycosuria we did not find any evidence that chronic loss of glucose in the urine would protect from deterioration of the glucose tolerance over time. PMID:26735923

  11. Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time

    PubMed Central

    Ottosson-Laakso, Emilia; Tuomi, Tiinamaija; Forsén, Björn; Gullström, Monika; Groop, Per-Henrik; Groop, Leif; Vikman, Petter

    2016-01-01

    Familial renal glycosuria is an inherited disorder resulting in glucose excretion in the urine despite normal blood glucose concentrations. It is most commonly due to mutations in the SLC5A2 gene coding for the glucose transporter SGLT2 in the proximal tubule. Several drugs have been introduced as means to lower glucose in patients with type 2 diabetes targeting SGLT2 resulting in renal glycosuria, but no studies have addressed the potential effects of decreased renal glucose reabsorption and chronic glycosuria on the prevention of glucose intolerance. Here we present data on a large pedigree with renal glycosuria due to two mutations (c.300-303+2del and p.A343V) in the SLC5A2 gene. The mutations, which in vitro affected glucose transport in a cell line model, and the ensuing glycosuria were not associated with better glycemic control during a follow-up period of more than 10 years. One individual, who was compound heterozygous for mutations in the SLC5A2 gene suffered from severe urogenital candida infections and postprandial hypoglycemia. In conclusion, in this family with familial glycosuria we did not find any evidence that chronic loss of glucose in the urine would protect from deterioration of the glucose tolerance over time. PMID:26735923

  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

  13. Glucose Metabolism in Neisseria gonorrhoeae

    PubMed Central

    Morse, Stephen A.; Stein, Stefanie; Hines, James

    1974-01-01

    The metabolism of glucose was examined in several clinical isolates of Neisseria gonorrhoeae. Radiorespirometric studies revealed that growing cells metabolized glucose by a combination on the Entner-Doudoroff and pentose phosphate pathways. A portion of the glyceraldehyde-3-phosphate formed via the Entner-Doudoroff pathway was recycled by conversion to glucose-6-phosphate. Subsequent catabolism of this glucose-6-phosphate by either the Entner-Doudoroff or pentose phosphate pathways yielded CO2 from the original C6 of glucose. Enzyme analyses confirmed the presence of all enzymes of the Entner-Doudoroff, pentose phosphate, and Embden-Meyerhof-Parnas pathways. There was always a high specific activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) relative to that of 6-phosphogluconate dehydrogenase (EC 1.1.1.44). The glucose-6-phosphate dehydrogenase utilized either nicotinamide adenine dinucleotide phosphate or nicotinamide adenine dinucleotide as electron acceptor. Acetate was the only detectable nongaseous end product of glucose metabolism. Following the disappearance of glucose, acetate was metabolized by the tricarboxylic acid cycle as evidenced by the preferential oxidation of [1-14C]acetate over that of [2-14C]acetate. When an aerobically grown log-phase culture was subjected to anaerobic conditions, lactate and acetate were formed from glucose. Radiorespirometric studies showed that under these conditions, glucose was dissimilated entirely by the Entner-Doudoroff pathway. Further studies determined that this anaerobic dissimilation of glucose was not growth dependent. PMID:4156358

  14. Green tea extract with polyethylene glycol-3350 reduces body weight and improves glucose tolerance in db/db and high-fat diet mice.

    PubMed

    Park, Jae-Hyung; Choi, Yoon Jung; Kim, Yong Woon; Kim, Sang Pyo; Cho, Ho-Chan; Ahn, Shinbyoung; Bae, Ki-Cheor; Im, Seung-Soon; Bae, Jae-Hoon; Song, Dae-Kyu

    2013-08-01

    Green tea extract (GTE) is regarded to be effective against obesity and type 2 diabetes, but definitive evidences have not been proven. Based on the assumption that the gallated catechins (GCs) in GTE attenuate intestinal glucose and lipid absorption, while enhancing insulin resistance when GCs are present in the circulation through inhibiting cellular glucose uptake in various tissues, this study attempted to block the intestinal absorption of GCs and prolong their residence time in the lumen. We then observed whether GTE containing the nonabsorbable GCs could ameliorate body weight (BW) gain and glucose intolerance in db/db and high-fat diet mice. Inhibition of the intestinal absorption of GCs was accomplished by co-administering the nontoxic polymer polyethylene glycol-3350 (PEG). C57BLKS/J db/db and high-fat diet C57BL/6 mice were treated for 4 weeks with drugs as follows: GTE, PEG, GTE+PEG, voglibose, or pioglitazone. GTE mixed with meals did not have any ameliorating effects on BW gain and glucose intolerance. However, the administration of GTE plus PEG significantly reduced BW gain, insulin resistance, and glucose intolerance, without affecting food intake and appetite. The effect was comparable to the effects of an α-glucosidase inhibitor and a peroxisome proliferator-activated receptor-γ/α agonist. These results indicate that prolonging the action of GCs of GTE in the intestinal lumen and blocking their entry into the circulation may allow GTE to be used as a prevention and treatment for both obesity and obesity-induced type 2 diabetes. PMID:23620335

  15. Age-dependent impairment of glucose tolerance in the 3xTg-AD mouse model of Alzheimer's disease.

    PubMed

    Vandal, Milene; White, Phillip J; Chevrier, Geneviève; Tremblay, Cyntia; St-Amour, Isabelle; Planel, Emmanuel; Marette, Andre; Calon, Frederic

    2015-10-01

    Alzheimer's disease (AD) has been associated with type II diabetes (T2D) and obesity in several epidemiologic studies. To determine whether AD neuropathology can cause peripheral metabolic impairments, we investigated metabolic parameters in the triple-transgenic (3xTg)-AD mouse model of AD, compared with those in nontransgenic (non-Tg) controls, at 6, 8, and 14 mo of age. We found a more pronounced cortical Aβ accumulation (2- and 3.5-fold increase in Aβ42 in the soluble and insoluble protein fractions, respectively) in female 3xTg-AD mice than in the males. Furthermore, female 3xTg-AD mice displayed a significant deterioration in glucose tolerance (AUC, +118% vs. non-Tg mice at 14 mo). Fasting plasma insulin levels rose 2.5-fold from 6 to 14 mo of age in female 3xTg-AD mice. Glucose intolerance and cortical amyloid pathology worsened with age, and both were more pronounced in the females. Pancreatic amyloidopathy was revealed and could underlie the observed deficit in glycemic response in 3xTg-AD mice. The present results suggest that AD-like neuropathology extends to the pancreas in the 3xTg-AD mouse, leading to glucose intolerance and contributing to a pathologic self-amplifying loop between AD and T2D. PMID:26108977

  16. Psychological predictors of short- and medium term outcome in individuals with idiopathic environmental intolerance (IEI) and individuals with somatoform disorders.

    PubMed

    Bailer, Josef; Witthöft, Michael; Rist, Fred

    2008-01-01

    Idiopathic environmental intolerance (IEI), also known as multiple chemical sensitivity (MCS), is defined as a chronic polysymptomatic condition that cannot be explained by an organic disease. Previous studies suggest that IEI may be a variant of somatoform disorders (SFD), because both disorders overlap with respect to symptoms and psychological features of somatization. However, little is known about the short- and medium-term outcome of IEI and psychological outcome predictors. Two clinical groups (IEI and SFD) and a comparison group (CG) were followed through 32 mo to assess both the outcome, and the extent to which trait anxiety and somatic symptom attribution (assessed at first examination) predict outcome presented 12 and 32 mo later. Outcome measures were the number of self-reported IEI symptoms, IEI triggers, IEI-associated functional impairments, and the number of somatoform symptoms. In addition, the course of the 2 syndromes over the 32-mo follow-up period was investigated with standardized screening scales. The 3 diagnostic groups consisted of 46 subjects with IEI, 38 subjects with SFD but without IEI, and 46 subjects (CG) with neither IEI nor SFD. Syndrome stability was high over the 32-mo follow-up period, and at both follow-ups IEI and non-IEI subjects differed on all IEI outcome measures (symptoms, triggers, functional impairments). Both trait anxiety and somatic attribution (the tendency to attribute common somatic complaints to an illness) predicted outcome. In addition, somatic attribution was found to partially mediate the effect of trait anxiety on outcome in the IEI group. In conclusion, these results suggest that IEI is a chronic and disabling condition and that trait anxiety contributes to the maintenance of the disorder via somatic attributions. PMID:18569575

  17. Glucose and Aging

    NASA Astrophysics Data System (ADS)

    Ely, John T. A.

    2008-04-01

    When a human's enzymes attach glucose to proteins they do so at specific sites on a specific molecule for a specific purpose that also can include ascorbic acid (AA) at a high level such as 1 gram per hour during exposure. In an AA synthesizing animal the manifold increase of AA produced in response to illness is automatic. In contrast, the human non-enzymatic process adds glucose haphazardly to any number of sites along available peptide chains. As Cerami clarified decades ago, extensive crosslinking of proteins contributes to loss of elasticity in aging tissues. Ascorbic acid reduces the random non-enyzmatic glycation of proteins. Moreover, AA is a cofactor for hydroxylase enzymes that are necessary for the production and replacement of collagen and other structural proteins. We will discuss the relevance of ``aging is scurvy'' to the biochemistry of human aging.

  18. Real-time dual wavelength polarimetry for glucose sensing

    NASA Astrophysics Data System (ADS)

    Malik, Bilal H.; Coté, Gerard L.

    2009-02-01

    Proper treatment of diabetes includes maintenance of near normal blood glucose levels, which can only be achieved with frequent blood glucose monitoring. Current blood finger-stick methods for glucose sensing are invasive, often resulting in low patient compliance and poor disease control. The development of a noninvasive glucose sensor has the potential to provide optimal management of diabetes. Our proposed noninvasive approach is based on an optical polarimetry system for probing the anterior chamber of the eye. The sensor would eventually be used to measure the aqueous humor glucose concentration as a means to determine the blood glucose concentration. In this report, we present the development of a near real-time (less than 1 second) dual wavelength closed-loop polarimetric system to minimize glucose prediction error in the presence of varying birefringence due to motion artifact. The new dual wavelength polarimetric system and in vitro glucose measurement results will be presented which demonstrate the sensitivity and accuracy of the system in the presence of varying birefringence.

  19. Glucose-6-phosphate isomerase.

    PubMed

    Achari, A; Marshall, S E; Muirhead, H; Palmieri, R H; Noltmann, E A

    1981-06-26

    Glucose-6-phosphate isomerase (EC 5.3.1.9) is a dimeric enzyme of molecular mass 132000 which catalyses the interconversion of D-glucose-6-phosphate and D-fructose-6-phosphate. The crystal structure of the enzyme from pig muscle has been determined at a nominal resolution of 2.6 A. The structure is of the alpha/beta type. Each subunit consists of two domains and the active site is in both the domain interface and the subunit interface (P.J. Shaw & H. Muirhead (1976), FEBS Lett. 65, 50-55). Each subunit contains 13 methionine residues so that cyanogen bromide cleavage will produce 14 fragments, most of which have been identified and at least partly purified. Sequence information is given for about one-third of the molecule from 5 cyanogen bromide fragments. One of the sequences includes a modified lysine residue. Modification of this residue leads to a parallel loss of enzymatic activity. A tentative fit of two of the peptides to the electron density map has been made. It seems possible that glucose-6-phosphate isomerase, triose phosphate isomerase and pyruvate kinase all contain a histidine and a glutamate residue at the active site. PMID:6115414

  20. Middle infrared optoelectronic absorption systems for monitoring physiological glucose solutions

    NASA Astrophysics Data System (ADS)

    Martin, W. Blake

    Tight monitoring of the glucose levels for diabetic individuals is essential to control long-term complications. A definitive diabetes management system has yet to be developed for the diabetic. This research investigates the application of middle infrared absorption frequencies for monitoring glucose levels in biological solutions. Three frequencies were identified using a Fourier transform infrared spectrometer and correlated to changes in glucose concentrations. The 1035 +/- 1 cm-1 frequency was determined to be the best representative frequency. Other biological molecules contributed no significant interference to monitoring glucose absorption. A second frequency at 1193 cm-1 was suggested as a representative background absorption frequency, which could be used for more accurate glucose absorption values. Next, a quantum cascade laser optoelectronic absorption system was designed and developed to monitor glucose. After careful alignment and design, the system was used to monitor physiological glucose concentrations. Correlation at 1036 cm-1 with glucose changes was comparable to the previous results. The use of the background absorption frequency was verified. This frequency essentially acts as a calibrating frequency to adjust in real-time to any changes in the background absorption that may alter the accuracy of the predicted glucose value. An evanescent wave cavity ring-down spectroscopy technique was explored to monitor molecules in a biological solution. Visible light at 425 nm was used to monitor hemoglobin in control urine samples. An adsorption isotherm for hemoglobin was detectable to limit of 5.8 nM. Evanescent wave cavity ring-down spectroscopy would be useful for a glucose