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Sample records for glucose intolerance hypertension

  1. Hyperinsulinemia. A link between hypertension obesity and glucose intolerance.

    PubMed Central

    Modan, M; Halkin, H; Almog, S; Lusky, A; Eshkol, A; Shefi, M; Shitrit, A; Fuchs, Z

    1985-01-01

    Hypertension and glucose intolerance, determined in a random population sample (n = 2,475), showed a highly significant (P less than 0.001) association from the mildest levels of both conditions, independent of the confounding effects of age, sex, obesity, and antihypertensive medications. Summary rate ratios for hypertension were 1.48 (1.18-1.87) in abnormal tolerance and 2.26 (1.69-2.84) in diabetes compared with normal tolerance. Altogether, 83.4% of the hypertensives were either glucose-intolerant or obese--both established insulin-resistant conditions. Fasting and post-load insulin levels in a representative subgroup (n = 1,241) were significantly elevated in hypertension independent of obesity, glucose intolerance, age, and antihypertensive medications. The mean increment in summed 1- and 2-h insulin levels (milliunits per liter) compared with nonobese normotensives with normal tolerance was 12 for hypertension alone, 47 for obesity alone, 52 for abnormal tolerance alone, and 124 when all three conditions were present. The prevalence of concentrations (milliequivalents per liter) of erythrocyte Na+ greater than or equal to 7.0, K+ less than 92.5, and plasma K+ greater than or equal to 4.5 in a subsample of 59 individuals with all combinations of abnormal tolerance obesity and hypertension was compared with those in 30 individuals free of these conditions. Altogether, 88.1% of the former vs. 40.0% of the latter group presented at least one of these three markers of internal cation imbalance (P less than 0.001). We conclude that insulin resistance and/or hyperinsulinemia (a) are present in the majority of hypertensives, (b) constitute a common pathophysiologic feature of obesity, glucose intolerance, and hypertension, possibly explaining their ubiquitous association, and (c) may be linked to the increased peripheral vascular resistance of hypertension, which is putatively related to elevated intracellular sodium concentration. Images PMID:3884667

  2. Fatty acid nitroalkenes ameliorate glucose intolerance and pulmonary hypertension in high-fat diet-induced obesity

    PubMed Central

    Kelley, Eric E.; Baust, Jeff; Bonacci, Gustavo; Golin-Bisello, Franca; Devlin, Jason E.; St. Croix, Claudette M.; Watkins, Simon C.; Gor, Sonia; Cantu-Medellin, Nadiezhda; Weidert, Eric R.; Frisbee, Jefferson C.; Gladwin, Mark T.; Champion, Hunter C.; Freeman, Bruce A.; Khoo, Nicholas K.H.

    2014-01-01

    Aims Obesity is a risk factor for diabetes and cardiovascular diseases, with the incidence of these disorders becoming epidemic. Pathogenic responses to obesity have been ascribed to adipose tissue (AT) dysfunction that promotes bioactive mediator secretion from visceral AT and the initiation of pro-inflammatory events that induce oxidative stress and tissue dysfunction. Current understanding supports that suppressing pro-inflammatory and oxidative events promotes improved metabolic and cardiovascular function. In this regard, electrophilic nitro-fatty acids display pleiotropic anti-inflammatory signalling actions. Methods and results It was hypothesized that high-fat diet (HFD)-induced inflammatory and metabolic responses, manifested by loss of glucose tolerance and vascular dysfunction, would be attenuated by systemic administration of nitrooctadecenoic acid (OA-NO2). Male C57BL/6j mice subjected to a HFD for 20 weeks displayed increased adiposity, fasting glucose, and insulin levels, which led to glucose intolerance and pulmonary hypertension, characterized by increased right ventricular (RV) end-systolic pressure (RVESP) and pulmonary vascular resistance (PVR). This was associated with increased lung xanthine oxidoreductase (XO) activity, macrophage infiltration, and enhanced expression of pro-inflammatory cytokines. Left ventricular (LV) end-diastolic pressure remained unaltered, indicating that the HFD produces pulmonary vascular remodelling, rather than LV dysfunction and pulmonary venous hypertension. Administration of OA-NO2 for the final 6.5 weeks of HFD improved glucose tolerance and significantly attenuated HFD-induced RVESP, PVR, RV hypertrophy, lung XO activity, oxidative stress, and pro-inflammatory pulmonary cytokine levels. Conclusions These observations support that the pleiotropic signalling actions of electrophilic fatty acids represent a therapeutic strategy for limiting the complex pathogenic responses instigated by obesity. PMID:24385344

  3. Beneficial Effects of Calcitriol on Hypertension, Glucose Intolerance, Impairment of Endothelium-Dependent Vascular Relaxation, and Visceral Adiposity in Fructose-Fed Hypertensive Rats

    PubMed Central

    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 tolerance, and visceral adiposity in fructose-fed rats. PMID:25774877

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

    PubMed

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

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose tolerance, and visceral adiposity in fructose-fed rats. PMID:25774877

  5. Aldosterone aggravates glucose intolerance induced by high fructose

    PubMed Central

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

    2013-01-01

    We previously reported that aldosterone impaired vascular insulin signaling in vivo and in vitro. Fructose-enriched diet induces metabolic syndrome including hypertension, insulin resistance, hyperlipidemia and diabetes in animal. In the current study, we hypothesized that aldosterone aggravated fructose feeding-induced glucose intolerance in vivo. Rats were divided into five groups for six-week treatment; uninephrectomy (Unx, n=8), Unx+aldosterone (aldo, 0.75 μg/h, s.c., n=8), Unx+fructose (fruc, 10% in drinking water, n=8), Unx+aldo+fruc, (aldo+fruc, n=8), and Unx+aldo+fruc+spironolactone, a mineralocorticoid receptor antagonist (aldo+fruc+spiro, 20 mg/kg/day, p.o., n=8). Aldo+fruc rats manifested the hypertension, and induced glucose intolerance compared to fruc intake rats assessed by oral glucose tolerance test, homeostasis model assessment of insulin resistance and hyperinsulinemic-euglycemic clamp study. Spironolactone, significantly improved the aldosterone-accelerated glucose intolerance. Along with improvement in insulin resistance, spironolactone suppressed upregulated mineralocorticoid receptor (MR) target gene, serum and glucocorticoid-regulated kinases-1 mRNA expression in skeletal muscle in aldo+fruc rats. In conclusion, these data suggested that aldosterone aggravates fructose feeding-induced glucose intolerance through MR activation. PMID:24201309

  6. 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 ameliorated insulin sensitivity and beta-cell function, decreased BP, and increased FMD in IGT hypertensive patients. These findings suggest flavanol-rich, low-energy cocoa food products may have a positive impact on CVD risk factors. PMID:18716168

  7. 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 12months, 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 12months 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 12months of age the reduction in body weight in the Restricted offspring is not a consequence of circulating adipokines. Skeletal muscle PGC-1? levels were unaltered in 12-month-old male and female rats, which indicate improvements in lean muscle mass by 12months 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

  8. 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 12months, 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 12months 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 12months of age the reduction in body weight in the Restricted offspring is not a consequence of circulating adipokines. Skeletal muscle PGC-1? levels were unaltered in 12-month-old male and female rats, which indicate improvements in lean muscle mass by 12months 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

  9. Glucose intolerance in Chinese patients with chronic hepatitis C

    PubMed Central

    Chen, Liang-Kung; Hwang, Shinn-Jang; Tsai, Shih-Tzer; Luo, Jiing-Chyuan; Lee, Shou-Dong; Chang, Full-Young

    2003-01-01

    AIM: To investigate the prevalence and the risk factors of glucose intolerance in Chinese patients with chronic hepatitis C and to evaluate the relationship between interferon (IFN) treatment and glucose intolerance in these patients. METHODS: Prospective cross-sectional study was done to evaluate the prevalence of glucose intolerance in Chinese patients with chronic hepatitis C virus (HCV) infection from the outpatient clinic of Department of Family Medicine, Taipei Veterans General Hospital. Chronic hepatitis C was defined as persistent presence of anti-HCV and persistent elevation of liver transaminase for at least 1.5 folds for at least 6 months. Moreover, patients were further categorized into normal fasting glucose and glucose intolerance (diabetes mellitus (DM) and impaired fasting glucose) according to the diagnostic criteria of American Diabetic Association. RESULTS: Totally, 359 Chinese patients with chronic hepatitis C were enrolled (212 males and 147 females, mean age = 58.1 13.0 years). One hundred and twenty-three patients (34.3%) had received various forms of IFN treatment. One hundred and twenty-five patients (34.6%) had glucose intolerance, including 99 patients (27.6%) with DM and 26 patients (7.0%) with impaired fasting glucose. In comparison with those with normal fasting glucose levels, patients with chronic hepatitis C with glucose intolerance were significantly older, had a significantly higher body mass index, and they were more likely to suffer from obesity, to have family history of diabetes and to have had previous IFN treatment. Stepwise multivariate logistic regression revealed significantly that age 57 years, obesity, previous history of IFN treatment and the presence of family history of diabetes were independent risk factors associated with the presence of glucose intolerance in chronic hepatitis C patients. CONCLUSION: In conclusion, 34.6% of Chinese patients with chronic hepatitis C had glucose intolerance. Chronic hepatitis C patients who were older in age, obese, had previous IFN treatment history and had family history of diabetes were prone to develop glucose intolerance. To our knowledge, this is the first population-based report to confirm that interferon treatment to be an independent risk factor to develop glucose intolerance. PMID:12632506

  10. High fat programming induces glucose intolerance in weanling Wistar rats.

    PubMed

    Cerf, M E; Louw, J

    2010-05-01

    We sought to determine whether maintenance on a high fat diet during defined periods of gestation and lactation induced glucose intolerance in weanling Wistar rats or affected food intake, weight, and glucose concentrations in mothers. Experimental groups comprised mothers and their weanling offspring maintained on a high fat diet during gestation and lactation (HFGL), during gestation only (HFG), or during lactation only (HFL). Maternal food intake, body weight, and fasting blood glucose concentrations were determined during lactation. Glucose tolerance was measured in the three-week-old weanling offspring. After overnight fasting, oral glucose tolerance tests were performed in the weanlings. Glucose was collected at (0), 10, 15, 30 and 60 min. HFGL and HFL weanlings had greater glucose concentrations compared to control weanlings at 10, 15, 30 and 60 min. For HFG weanlings, greater glucose concentrations were only found at 30 min, which normalized at 60 min. In all of the experimental groups, the highest glucose concentrations were demonstrated at 30 min, whereas the peak was achieved at 15 min in the control weanlings. Overt glucose intolerance was induced in weanlings maintained on a high fat diet throughout both gestation and lactation or throughout lactation only. Further, weanlings maintained on a high fat diet solely throughout gestation displayed milder glucose intolerance. Developmental programming with a high fat diet during defined periods of gestation and lactation induces glucose intolerance in weanling rats. PMID:20195946

  11. Hepatic lipase deficiency produces glucose intolerance, inflammation and hepatic steatosis.

    PubMed

    Andrs-Blasco, Irene; Herrero-Cervera, Andrea; Vinu, ngela; Martnez-Hervs, Sergio; Piqueras, Laura; Sanz, Mara Jess; Burks, Deborah Jane; Gonzlez-Navarro, Herminia

    2015-12-01

    Metabolic syndrome and type 2 diabetes mellitus constitute a major problem to global health, and their incidence is increasing at an alarming rate. Non-alcoholic fatty liver disease, which affects up to 90% of obese people and nearly 70% of the overweight, is commonly associated with MetS characteristics such as obesity, insulin resistance, hypertension and dyslipidemia. In the present study, we demonstrate that hepatic lipase (HL)-inactivation in mice fed with a high-fat, high-cholesterol diet produced dyslipidemia including hypercholesterolemia, hypertriglyceridemia and increased non-esterified fatty acid levels. These changes were accompanied by glucose intolerance, pancreatic and hepatic inflammation and steatosis. In addition, compared with WT mice, HL(-/-) mice exhibited enhanced circulating MCP1 levels, monocytosis and higher percentage of CD4+Th17+ cells. Consistent with increased inflammation, livers from HL(-/-) mice had augmented activation of the stress SAPK/JNK- and p38-pathways compared with the activation levels of the kinases in livers from WT mice. Analysis of HL(-/-) and WT mice fed regular chow diet showed dyslipidemia and glucose intolerance in HL(-/-) mice without any other changes in inflammation or hepatic steatosis. Altogether, these results indicate that dyslipidemia induced by HL-deficiency in combination with a high-fat, high-cholesterol diet promotes hepatic steatosis and inflammation in mice which are, at least in part, mediated by the activation of the stress SAPK/JNK- and p38-pathways. Future studies are warranted to asses the viability of therapeutic strategies based on the modulation of these kinases to reduce hepatic steatosis associated to lipase dysfunction. PMID:26423094

  12. Thyroid hormone excess and glucose intolerance.

    PubMed

    Dimitriadis, G D; Raptis, S A

    2001-01-01

    The elevated plasma glucose levels in hyperthyroidism may be explained by increased rates of endogenous glucose production, due mainly to increased gluconeogenesis. The rates of insulin-stimulated glucose disposal in peripheral tissues in hyperthyroidism have been found, in general, either normal or increased. Skeletal muscle is the most important tissue for the disposal of glucose in response to insulin. In this tissue, insulin increases glucose disposal by stimulating glucose transport, glucose phosphorylation/glycolysis, glycogen synthesis and glucose oxidation. Studies examining insulin-stimulated glucose metabolism in skeletal muscle have suggested that, in the hyperthyroid state, it may be of primary importance to increase the rates of glycolysis and lactate formation relative to glucose oxidation in this tissue in order to provide substrate for gluconeogenesis (increase Cori cycle activity). This effect will be achieved primarily by a decrease in glycogen synthesis and an increase in glycogenolysis. When hyperthyroidism becomes more severe, an increased rate of glucose uptake into muscle may then be necessary since the increased conversion of glycogen to lactate could not be sustained for prolonged periods and might lead to a depletion in glycogen stores. This mechanism would ensure that the level of glucose in plasma is kept normal or slightly increased. Thus, an increased Cori cycle activity may be a necessary mechanism to provide optimal conditions in hyperthyroidism for the control of glucose utilization without increasing the risk of hypoglycemia. In addition to lactate, increased rates of gluconeogenesis in hyperthyroidism can also be sustained by increased plasma concentrations of amino acids (mostly glutamine and alanine) and glycerol, as well as by increased plasma concentrations of free fatty acids. PMID:11460573

  13. Perceived psychosocial stress and glucose intolerance among pregnant Hispanic women

    PubMed Central

    Silveira, M.L.; Whitcomb, B.W.; Pekow, P.; Braun, B.; Markenson, G.; Dole, N.; Manson, J.E.; Solomon, C.G.; Carbone, E.T.; Chasan-Taber, L.

    2016-01-01

    Aim Prior literature suggests a positive association between psychosocial stress and the risk of diabetes in non-pregnant populations, but studies during pregnancy are sparse. We evaluated the relationship between stress and glucose intolerance among 1115 Hispanic (predominantly Puerto Rican) prenatal care patients in Proyecto Buena Salud, a prospective cohort study in Western Massachusetts (2006–2011). Methods Cohen’s Perceived Stress Scale (PSS-14) was administered in early (mean = 12.3 weeks gestation; range 4.1–18 weeks) and mid-(mean = 21.3 weeks gestation; range 18.1–26 weeks) pregnancy. Participants were classified as having a pregnancy complicated by gestational diabetes mellitus, impaired glucose tolerance, and abnormal glucose tolerance, based on the degree of abnormality on glucose tolerance testing between 24 and 28 weeks of gestation. Results The prevalence of gestational diabetes mellitus, impaired glucose tolerance, and abnormal glucose tolerance was 4.1%, 7.2%, and 14.5%, respectively. Absolute levels of early or mid-pregnancy stress were not significantly associated with glucose intolerance. However, participants with an increase in stress from early to mid-pregnancy had a 2.6-fold increased odds of gestational diabetes mellitus (95% confidence intervals: 1.0–6.9) as compared to those with no change or a decrease in stress after adjusting for age and pre-pregnancy body mass index. In addition, every one-point increase in stress scores was associated with a 5.5 mg/dL increase in screening glucose level (β = 5.5; standard deviation = 2.8; P = 0.05), after adjusting for the same variables. Conclusion In this population of predominantly Puerto Rican women, stress patterns during pregnancy may influence the risk of glucose intolerance. PMID:24948416

  14. 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 intolerance, with polycythaemia as a sign of poor hypoxic adaptation, accelerated by lifestyle change and ageing. PMID:26908520

  15. Healthy diet and lifestyle clustering and glucose intolerance.

    PubMed

    Perry, I J

    2002-11-01

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

  16. An Evaluation of Glucose Tolerance in Essential Hypertension

    PubMed Central

    Guldiken, Sibel; Ugur-Altun, Betul; Arikan, Ender

    2009-01-01

    Purpose This study aimed to determine the impaired glucose tolerance and diabetes prevalence in patients with essential hypertension (HT) and to compare the developed microvascular complications of these groups. Materials and Methods An oral glucose tolerance test (OGTT) was performed on 338 essential hypertensive cases and glucose tolerances were classified according to ADA-2002 criteria. Results Of the 338 cases, 32 people had diabetes (DM, 9.46%), 78 people had glucose intolerance (IGT, 23.1%), and 228 people had only hypertension but not IGT and DM (67.4%). Both the mean ages of the DM group (56.9 6.7 years, p = 0.002) and IGT group (56.3 8.4 years, p = 0.003) were older than the mean age of the control group (51.1 6.4 years). The risk of IGT development was found to be four times greater in male cases than female cases when compared to the control group (p = 0.004, add ratio = 4.194). There were no significant differences in the body mass indexes (BMI's), hypertension durations, and microvascular complications between the groups. Conclusion In conclusion, the risk of IGT and DM development in hypertensive cases increases with aging and longer hypertension duration. The risk of IGT development in hypertensive cases is four times more in males. PMID:19430550

  17. 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

  18. 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

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

    PubMed Central

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

    2013-01-01

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

  20. Human gut microbiota changes reveal the progression of glucose intolerance.

    PubMed

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

    2013-01-01

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

  1. 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...

  2. 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

  3. 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

  4. Intermittent hypoxia-induced glucose intolerance is abolished by ?-adrenergic blockade or adrenal medullectomy

    PubMed Central

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

    2014-01-01

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

  5. Cassia cinnamon for the attenuation of glucose intolerance and insulin resistance resulting from sleep loss.

    PubMed

    Jitomir, Jean; Willoughby, Darryn S

    2009-06-01

    Epidemiological investigations reveal a concomitant increase in sleep loss and metabolic diseases, including type 2 diabetes mellitus, over the past several decades. An increasing body of scientific evidence indicates that acute sleep loss induces insulin resistance and glucose intolerance profiles similar to those of type 2 diabetes mellitus patients. Experimentally, cassia cinnamon (Cinnamomum cassia) supplementation facilitates glucose disposal in healthy humans, which may be achieved by enhancing (1) insulin sensitivity via increased phosphorylation of signaling proteins and (2) insulin-sensitive glucose transporter 4-mediated glucose uptake into muscle cells. Because peripheral insulin resistance is primarily a consequence of reduced muscle insulin sensitivity, C. cassia and C. cassia extracts may attenuate insulin resistance and glucose intolerance observed following sleep loss. PMID:19627193

  6. 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 17?-estradiol supplementation for 26 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 17?-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 exposure and glucose intolerance/insulin resistance in estrogen-deficient female mice. Environ Health Perspect 123:11381144;?http://dx.doi.org/10.1289/ehp.1408663 PMID:25859628

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

    PubMed Central

    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.

    2015-01-01

    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 ?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. PMID:24103449

  8. 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

  9. Pregravid Physical Activity, Dietary Intake, and Glucose Intolerance During Pregnancy

    PubMed Central

    Ghosh, Payal; Nicholson, Wanda K.

    2011-01-01

    Abstract Objectives To ascertain prepregnancy physical activity and dietary intake from a sample of women in early pregnancy and estimate the effect of prepregnancy lifestyle behaviors on the 1-hour glucose challenge test (GCT). Methods We conducted a prospective analysis of a racially diverse urban-based sample of 152 pregnant women in the first trimester who were participants in the Parity, Inflammation and Diabetes (PID) study. Dietary intake before pregnancy was assessed using a modified version of the Block Rapid Food Screener, and leisure time physical activity before pregnancy was assessed using the Baecke questionnaire. Test results from a nonfasting oral GCT conducted between 26 and 28 weeks were abstracted from the medical record. Participants were classified as having a positive GCT if the blood glucose measurement was ?140?mg/dL and as negative with a blood glucose measurement <140?mg/dL. We constructed a series of multiple logistic regression models, adjusting for potential confounders to determine if prepregnancy dietary intake and leisure activity were associated with response to the GCT. Results Women with higher prepregnancy leisure activity scores were 68% less likely to have a 1-hour GCT response ?140mg/dL. However, there was no association between dietary intake and response to the GCT. Conclusions Our data suggest that prevention of an abnormal GCT result should include practices to encourage women of reproductive age to engage in leisure physical activity in advance of planning a pregnancy. PMID:21951267

  10. 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

  11. 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 iv glucose (given during the FSIGT) contributed to the rapid resolution of the sympathoadrenal response induced by icv FGFRi, we performed an additional study comparing groups that received iv saline or iv glucose 30 min after icv FGFRi. Our finding that elevated plasma catecholamine levels returned rapidly to baseline irrespective of whether rats subsequently received an iv bolus of saline or glucose indicates that the rapid reversal of sympathoadrenal activation following icv FGFRi was unrelated to the subsequent glucose bolus. Conclusions The effect of acute inhibition of central FGFR signaling to impair glucose tolerance likely involves a stress response associated with pronounced, but transient, sympathoadrenal activation and an associated reduction of insulin secretion. Whether this effect is a true consequence of FGFR blockade or involves an off-target effect of the FGFR inhibitor requires additional study. PMID:26266088

  12. Population Health: Modest Glycaemic Improvements in a Pregnant Cohort with Mild Glucose Intolerance Decreased Adverse Outcomes

    PubMed Central

    Berggren, Erica K.; Boggess, Kim A.; Funk, Michele Jonsson

    2015-01-01

    Background Adverse perinatal outcomes are common with pregnancy-related mild glucose intolerance. The perinatal impact of improving this populations health, instead of individual health, has not been quantified. Methods We estimated this impact among women with mild glucose intolerance, delivered at The University of North Carolina Womens Hospital from April 1996 to May 2010. We compared observed with predicted risks of perinatal outcomes after simulating a cohort with a one standard deviation decrease in each glucose value. We estimated absolute and adjusted risks, relative risks, and risk differences with Poisson regression and bootstrapped 95% confidence intervals [CI]. Results Among 3217 women, mean (SD) 1-h screening result was 157 (16) mg/dL; 3-h diagnostic results were 81 (10), 154 (28), 130 (25), and 104 (26) mg/dL for fasting, 1-h, 2-h, and 3-h, respectively. Compared with observed, predicted risks decreased for preeclampsia (9.1% vs. 6.6%, risk ratio [RR] 0.73 [95% CI 0.60, 0.88]), caesarean delivery (30.1% vs. 26.4%, RR 0.88 [95% CI 0.81, 0.96]), preterm birth (13.0% vs. 9.8%, RR 0.75 [95% CI 0.64, 0.87]), birthweight >4000 g (13.4% vs. 10.5%, RR 0.78 [95% CI 0.67, 0.90]), and shoulder dystocia (3.5% vs. 2.2%, RR 0.61 [95% CI 0.46, 0.83]). Conclusions Modestly improved population distribution of glucose tolerance in pregnancies affected by mild glucose intolerance translated to meaningful improvements in perinatal outcomes. PMID:24731066

  13. 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-?, 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-? 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-stress promotes glucose intolerance associated to corticosterone serum level and epididymal white adipose tissue IL-6 concentration increase. The fish oil consumption by stressed rats normalized the stress responses. These results suggested that fish oil intake could be useful to minimize or prevent the development of diseases associated to the stress. PMID:21569357

  14. Fructose Malabsorption and Intolerance: Effects of Fructose with and without Simultaneous Glucose Ingestion

    PubMed Central

    Latulippe, Marie E.; Skoog, Suzanne M.

    2011-01-01

    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

  15. 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 metabolic effects are only slightly exacerbated in geriatric rats.

  16. Delayed effects of proton irradiation in Macaca mulatta. III. Glucose intolerance. Interim report 1964-1983

    SciTech Connect

    Salmon, Y.L.; Yochmowitz, M.G.; Wood, D.H.

    1984-03-01

    A group of rhesus monkeys is being studied in a lifetime survey of the delayed effects of proton irradiation. The animals were exposed during the period 1964 - 1969 to single total-body doses of protons covering the spectrum of energies and total doses that might be expected to occur in space during a major solar flare event. This report describes the results of intravenous glucose tolerance test and the insulin response to glucose challenge in 106 irradiated animals, their control group of 42, and 10 younger control animals. The results indicate that the clearance rate of blood glucose is influenced by the age of the animal and by the type and energy of the radiation. Animals receiving greater than 360 rads of proton irradiation of energies above 138 MeV had significantly slower glucose clearance than nonirradiated controls. Seventeen-twenty-year-old controls were less glucose tolerant than 9-11-year-old controls. Animals with normal glucose tolerance showed considerable individual variation in insulin response, while in animals with marked glucose intolerance (clearance rate < 1.0 %/min), low insulin response was a consistent finding.

  17. Overproduction of Angiotensinogen from adipose Tissue Induces adipose Infammation, Glucose Intolerance, and Insulin Resistance

    PubMed Central

    Kalupahana, Nishan S.; Massiera, Florence; Quignard-Boulange, Annie; Ailhaud, Grard; Voy, Brynn H.; Wasserman, David H.; Moustaid-Moussa, Naima

    2015-01-01

    Although obesity is associated with overactivation of the white adipose tissue (WAT) reninangiotensin system (RAS), a causal link between the latter and systemic insulin resistance is not established. We tested the hypothesis that overexpression of angiotensinogen (Agt) from WAT causes systemic insulin resistance via modulation of adipose inflammation. Glucose tolerance, systemic insulin sensitivity, and WAT inflammatory markers were analyzed in mice overexpressing Agt in the WAT (aP2-Agt mice). Proteomic studies and in vitro studies using 3T3-L1 adipocytes were performed to build a mechanistic framework. Male aP2-Agt mice exhibited glucose intolerance, insulin resistance, and lower insulin-stimulated glucose uptake by the skeletal muscle. The difference in glucose tolerance between genotypes was normalized by high-fat (HF) feeding, and was significantly improved by treatment with angiotensin-converting enzyme (ACE) inhibitor captopril. aP2-Agt mice also had higher monocyte chemotactic protein-1 (MCP-1) and lower interleukin-10 (IL-10) in the WAT, indicating adipose inflammation. Proteomic studies in WAT showed that they also had higher monoglyceride lipase (MGL) and glycerol-3-phosphate dehydrogenase levels. Treatment with angiotensin II (Ang II) increased MCP-1 and resistin secretion from adipocytes, which was prevented by cotreating with inhibitors of the nuclear factor-?B (NF-?B) pathway or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In conclusion, we show for the first time that adipose RAS overactivation causes glucose intolerance and systemic insulin resistance. The mechanisms appear to be via reduced skeletal muscle glucose uptake, at least in part due to Ang II-induced, NADPH oxidase and NF ?B-dependent increases in WAT inflammation. PMID:21979391

  18. Overproduction of angiotensinogen from adipose tissue induces adipose inflammation, glucose intolerance, and insulin resistance.

    PubMed

    Kalupahana, Nishan S; Massiera, Florence; Quignard-Boulange, Annie; Ailhaud, Grard; Voy, Brynn H; Wasserman, David H; Moustaid-Moussa, Naima

    2012-01-01

    Although obesity is associated with overactivation of the white adipose tissue (WAT) renin-angiotensin system (RAS), a causal link between the latter and systemic insulin resistance is not established. We tested the hypothesis that overexpression of angiotensinogen (Agt) from WAT causes systemic insulin resistance via modulation of adipose inflammation. Glucose tolerance, systemic insulin sensitivity, and WAT inflammatory markers were analyzed in mice overexpressing Agt in the WAT (aP2-Agt mice). Proteomic studies and in vitro studies using 3T3-L1 adipocytes were performed to build a mechanistic framework. Male aP2-Agt mice exhibited glucose intolerance, insulin resistance, and lower insulin-stimulated glucose uptake by the skeletal muscle. The difference in glucose tolerance between genotypes was normalized by high-fat (HF) feeding, and was significantly improved by treatment with angiotensin-converting enzyme (ACE) inhibitor captopril. aP2-Agt mice also had higher monocyte chemotactic protein-1 (MCP-1) and lower interleukin-10 (IL-10) in the WAT, indicating adipose inflammation. Proteomic studies in WAT showed that they also had higher monoglyceride lipase (MGL) and glycerol-3-phosphate dehydrogenase levels. Treatment with angiotensin II (Ang II) increased MCP-1 and resistin secretion from adipocytes, which was prevented by cotreating with inhibitors of the nuclear factor-?B (NF-?B) pathway or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In conclusion, we show for the first time that adipose RAS overactivation causes glucose intolerance and systemic insulin resistance. The mechanisms appear to be via reduced skeletal muscle glucose uptake, at least in part due to Ang II-induced, NADPH oxidase and NF?B-dependent increases in WAT inflammation. PMID:21979391

  19. The negative association between traditional physical activities and the prevalence of glucose intolerance in Alaska Natives.

    PubMed

    Adler, A I; Boyko, E J; Schraer, C D; Murphy, N J

    1996-06-01

    The once low prevalence of non-insulin-dependent (Type 2) diabetes (NIDDM) in Eskimos and Indians has risen approximately fourfold over the past 30 years, suggesting the presence of a non-genetic factor affecting NIDDM prevalence. At the same time, traditional physical activities required of a subsistence (self-sufficiency) lifestyle have diminished. Since physical activity has been shown to prevent NIDDM in other populations, we performed a case-control study of physical activity and glucose intolerance in 666 Yup'ik Eskimos and Athabaskan Indians > or = 40 years old in 15 villages in the Yukon Kuskokwim Delta in Alaska. Self-administered questionnaires were used to determine whether subjects participated in a number of traditional activities and/or their modern counterpart (for example, dog sledding and riding motorized vehicles). Intensity values and a score were defined for the activities. Cases included known or newly discovered impaired glucose tolerance or NIDDM. Newly discovered cases were defined by oral glucose tolerance testing of those individuals were screening blood glucose values > or = 6.7 mmol l-1 by random capillary blood glucose testing. Cases included 11 newly discovered (1 with a history of IGT) and 26 known cases of NIDDM, and 17 newly discovered and 1 known cases of IGT. The results showed that, compared to a reference group with low-level physical activity, moderate level physical activity (odds ratio, OR, 0.7, 95% confidence interval [CI] 0.4-1.3) and high level activity (OR 0.2, CI 0.1-0.6) were associated with a lower prevalence of glucose intolerance, adjusted for age, ethnicity, body mass index, and sex. PMID:8799660

  20. Endothelial Function in Women with and without a History of Glucose Intolerance in Pregnancy

    PubMed Central

    Floras, John; Retnakaran, Ravi

    2013-01-01

    Background/Aims. Gestational diabetes mellitus (GDM) and milder gestational impaired glucose tolerance (GIGT) identify women who are at risk of developing cardiovascular disease. Endothelial dysfunction, as indicated by impaired flow-mediated dilatation (FMD) on brachial artery ultrasound, is an early marker of vascular disease. Thus, we sought to evaluate endothelial function in women with and without recent glucose intolerance in pregnancy. Methods. One-hundred and seventeen women underwent oral glucose tolerance testing (OGTT) in pregnancy, enabling stratification into those with normal gestational glucose tolerance (n = 59) and those with GDM or GIGT (n = 58). 6 years postpartum, they underwent a repeat of OGTT and brachial artery FMD studies, enabling assessment of FMD and 4 secondary vascular measures: FMD after 60 seconds (FMD60), baseline arterial diameter, peak shear rate, and reactive hyperemia. Results. There were no differences between the normal gestational glucose tolerance and GDM/GIGT groups in FMD (mean 8.5 versus 9.3%, P = 0.61), FMD60 (4.1 versus 5.1%, P = 0.33), baseline diameter (3.4 versus 3.4?mm, P = 0.66), peak shear rate (262.6 versus 274.8?s?1, P = 0.32), and reactive hyperemia (576.6 versus 496.7%, P = 0.07). After covariate adjustment, there were still no differences between the groups. Conclusion. Despite their long-term cardiovascular risk, women with glucose intolerance in pregnancy do not display endothelial dysfunction 6 years postpartum. PMID:23819127

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

    PubMed Central

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

    2013-01-01

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

  2. Transgenic mice overexpressing Renin exhibit glucose intolerance and diet-genotype interactions.

    PubMed

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

    2012-01-01

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

  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 populationand 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. Antidiabetic-drug combination treatment for glucose intolerance in adult female rats treated acutely with olanzapine.

    PubMed

    Boyda, Heidi N; Procyshyn, Ric M; Asiri, Yahya; Wu, Claire; Wang, Cathy K; Lo, Ryan; Pang, Catherine C Y; Honer, William G; Barr, Alasdair M

    2014-01-01

    Second generation antipsychotic drugs are routinely used as treatment for psychotic disorders. Many of these compounds, including olanzapine, cause metabolic side-effects such as impaired glucose tolerance and insulin resistance. Individual antidiabetic drugs can help control elevated glucose levels in patients treated with antipsychotics, but the effects of combining antidiabetics, which routinely occurs with Type 2 diabetes mellitus patients, have never been studied. Presently, we compared the effects of the three different antidiabetics metformin (500mg/kg, p.o.), rosiglitazone (30mg/kg, p.o.) and glyburide (10mg/kg, p.o.) on metabolic dysregulation in adult female rats treated acutely with olanzapine. In addition, dual combinations of each of these antidiabetics were compared head-to-head against each other and the individual drugs. The animals received two daily treatments with antidiabetics and were then treated acutely with olanzapine (10mg/kg, i.p.). Fasting glucose and insulin levels were measured, followed by a 2h glucose tolerance test. Olanzapine caused a large and highly significant glucose intolerance compared to vehicle treated rats. Rosiglitazone decreased glucose levels non-significantly, while both metformin and glyburide significantly decreased glucose levels compared to olanzapine-only treated animals. For antidiabetic dual-drug combinations, the rosiglitazone-metformin group showed an unexpected increase in glucose levels compared to all of the single antidiabetic drugs. However, both the metformin-glyburide and rosiglitazone-glyburide groups showed significantly greater reductions in glucose levels following olanzapine than with single drug treatment alone for metformin or rosiglitazone, bringing glucose levels down to values equivalent to vehicle-only treated animals. These findings indicate that further study of antidiabetic dual-drug combinations in patients treated with antipsychotic drugs is warranted. PMID:24140931

  5. 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

  6. Glucokinase gene polymorphisms: a genetic marker for glucose intolerance in a cohort of elderly Finnish men.

    PubMed

    McCarthy, M I; Hitman, G A; Hitchins, M; Riikonen, A; Stengrd, J; Nissinen, A; Tuomilehto-Wolf, E; Tuomilehto, J

    1994-03-01

    Although mutations in the glucokinase gene are implicated in the pathogenesis of glucose intolerance in pedigrees with maturity-onset diabetes of the young, the role of such mutations in typical Type 2 diabetes is poorly characterized. We studied a cohort of elderly men born (between 1900 and 1919) in two Finnish communities and exhibiting a continuous spectrum of glucose tolerance at assessments made in 1984 and 1989. Individuals were typed at two polymorphic microsatellites straddling the glucokinase gene, GCK(3') (n = 169) and GCK(5') (n = 166): these two markers were in linkage equilibrium in this cohort. Significant associations between alleles at the GCK(3') marker and glucose tolerance were evident (p = 0.002), the frequency of the (z + 2) allele rising from zero in control subjects (n = 88 chromosomes) to 6.5% (n = 62) in subjects with impaired tolerance and 12.2% (n = 188) in subjects with diabetes. Mean 2-h glucose levels were 10.5 (9.6-11.4, 95% confidence interval) mmol l-1 in individuals with the (z + 2) allele and 8.1 (7.6-8.7) mmol l-1 in those without (p = 0.01, corrected for multiple comparisons). No association was evident between GCK(5') alleles and glucose tolerance. The GCK(3') microsatellite is a marker for abnormal glucose tolerance in this cohort of elderly Finnish men. PMID:8200207

  7. Hepatic Glucose Intolerance Precedes Hepatic Steatosis in the Male Aromatase Knockout (ArKO) Mouse

    PubMed Central

    Van Sinderen, Michelle L.; Steinberg, Gregory R.; Jørgensen, Sebastian B.; To, Sarah Q.; Knower, Kevin C.; Clyne, Colin D.; Honeyman, Jane; Chow, Jenny D.; Herridge, Kerrie A.; Jones, Margaret E. E.; Simpson, Evan R.; Boon, Wah Chin

    2014-01-01

    Estrogens are known to play a role in modulating metabolic processes within the body. The Aromatase knockout (ArKO) mice have been shown to harbor factors of Metabolic syndrome with central adiposity, hyperinsulinemia and male-specific hepatic steatosis. To determine the effects of estrogen ablation and subsequent replacement in males on whole body glucose metabolism, three- and six-month-old male ArKO mice were subjected to whole body glucose, insulin and pyruvate tolerance tests and analyzed for ensuing metabolic changes in liver, adipose tissue, and skeletal muscle. Estrogen-deficient male ArKO mice showed increased gonadal adiposity which was significantly reduced upon 17β-estradiol (E2) treatment. Concurrently, elevated ArKO serum leptin levels were significantly reduced upon E2 treatment and lowered serum adiponectin levels were restored to wild type levels. Three-month-old male ArKO mice were hyperglycemic, and both glucose and pyruvate intolerant. These phenotypes continued through to 6 months of age, highlighting a loss of glycemic control. ArKO livers displayed changes in gluconeogenic enzyme expression, and in insulin signaling pathways upon E2 treatment. Liver triglycerides were increased in the ArKO males only after 6 months of age, which could be reversed by E2 treatment. No differences were observed in insulin-stimulated ex vivo muscle glucose uptake nor changes in ArKO adipose tissue and muscle insulin signaling pathways. Therefore, we conclude that male ArKO mice develop hepatic glucose intolerance by the age of 3 months which precedes the sex-specific development of hepatic steatosis. This can be reversed upon the administration of exogenous E2. PMID:24520329

  8. 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.

  9. Effect of acarbose on glucose intolerance in patients with non-insulin-dependent diabetes mellitus.

    PubMed

    Noda, K; Umeda, F; Nawata, H

    1997-08-01

    We evaluated the effect of acarbose, an alpha-glucosidase inhibitor, on glucose intolerance in patients with non-insulin-dependent diabetes mellitus (NIDDM). Acarbose was given orally (300 mg/day) for 24 weeks to 20 NIDDM patients. Data in an oral glucose tolerance test (OGTT) were evaluated before and after 24 weeks of treatment using principal component analysis. Acarbose administration significantly reduced the postprandial plasma glucose level over 24 weeks of treatment. Principal component analysis suggested that the patients were separated into responders and non-responders. There was a significant improvement of fasting and postprandial glucose levels after 12 and 24 weeks in the responders, but not in the non-responders. Plasma glucose level following the OGTT improved significantly after 24 weeks of treatment in the responders (Hotelling T2 value = 47.098, P = 0.022500), but not in the non-responders. The immunoreactive insulin level did not change in either group. Results thus suggest that acarbose improved insulin resistance in some patients with NIDDM (responders as classified by principal component analysis). PMID:9279483

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

    PubMed Central

    SONG, MOON-KOO; UM, JAE-YOUNG; JANG, HYEUNG-JIN; LEE, BYUNG-CHEOL

    2012-01-01

    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 ? (PPAR-?), tumor necrosis factor ? (TNF-?) 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-?, and downregulated the expression of TNF-?. From these results, we suggest that Ephedra sinica may reduce obesity and hyperglycemia by increasing PPAR-? and adiponectin and reducing TNF-?, 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

  11. An asymptomatic, normotensive sipple syndrome patient with glucose intolerance and hypercholesterolemia, and her kindred.

    PubMed

    Wakasugi, T; Aoyama, T; Hirai, J; Saga, T

    1991-01-01

    The proband, a 42-year-old woman without any symptoms or hypertension, was admitted for examination of accidentally discovered bilateral adrenal masses. Physical examination disclosed bilateral nodular goiter and mild sinus tachycardia. Pheochromocytomas and medullary thyroid carcinomas were revealed by biochemical and histopathological examinations. Hypercholesterolemia and abnormal glucose metabolism returned to normal after bilateral total adrenalectomy and thyroidectomy. Screening examination showed four affected family members. Three of them were also asymptomatic and normotensive. In pheochromocytoma patients, normotension, hypercholesterolemia, and impaired glucose metabolism might be signs of excess secretion of epinephrine rather than norepinephrine. PMID:1678022

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

    PubMed Central

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

    2010-01-01

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

  13. Liraglutide counteracts obesity and glucose intolerance in a mouse model of glucocorticoid-induced metabolic syndrome

    PubMed Central

    2014-01-01

    Background Glucocorticoid excess is commonly associated with diabetogenic effects, including insulin resistance and glucose intolerance. The effects of the long-term glucagon-like peptide 1 receptor agonist treatment on the metabolic syndrome-like conditions are not yet fully elucidated. Thus, we aimed to test whether long-term liraglutide treatment could be effective as a therapy to counteract the metabolic dysfunctions induced by chronic glucocorticoid exposure. Methods Mice were given corticosterone or vehicle via their drinking water for five consecutive weeks. In addition, mice were treated with once-daily injections of either PBS or liraglutide. Results Liraglutide treatment slowed progression towards obesity and ectopic fat deposition in liver that otherwise occurred in corticosterone-treated mice. The drug reduced the increment in serum insulin caused by corticosterone, but did not affect the reduction of insulin sensitivity. Furthermore, liraglutide improved glucose control in mice exposed to corticosterone as evident by a delay in the progression towards post-prandial hyperglycemia and enhanced glucose clearance during a glucose tolerance test. Glucose-stimulated C-peptide levels were higher in those mice that had received liraglutide and corticosterone compared to mice that had been treated with corticosterone alone, indicating a positive role of liraglutide for beta-cell function. Morphometric analysis revealed increased beta- and alpha-cell masses that were associated with more Ki67-positive islet cells in corticosterone-treated mice irrespective of whether they were co-treated with liraglutide or not. Liraglutide had no discernible effect on alpha-cell mass. Conclusion Liraglutide can be beneficial for subjects at risk of developing metabolic complications as a result of glucocorticoid excess. PMID:24423471

  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; 2mg/g) once a day for 5days from 1day 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. Glucose Intolerance and Lipid Metabolic Adaptations in Response to Intrauterine and Postnatal Calorie Restriction in Male Adult Rats

    PubMed Central

    Thamotharan, Manikkavasagar; Dai, Yun; Lagishetty, Venu; Matveyenko, Aleksey V.; Lee, W. N. Paul

    2013-01-01

    Enhanced de novo lipogenesis (DNL), an adult hepatic adaption, is seen with high carbohydrate or low-fat diets. We hypothesized that ad libitum intake after prenatal calorie restriction will result in adult-onset glucose intolerance and enhanced DNL with modified lipid metabolic gene expression profile. Stable isotopes were used in 15-month-old adult male rat offspring exposed to prenatal (IUGR), pre- and postnatal (IPGR), or postnatal (PNGR) caloric restriction vs. controls (CON). IUGR vs. CON were heavier with hepatomegaly but unchanged visceral white adipose tissue (WAT), glucose intolerant with reduced glucose-stimulated insulin secretion (GSIS), pancreatic ?-cell mass, and total glucose clearance rate but unsuppressed hepatic glucose production. Liver glucose transporter (Glut) 1 and DNL increased with decreased hepatic acetyl-CoA carboxylase (ACC) and fatty acid synthase but increased WAT fatty acid transport protein-1 and peroxisomal proliferator-activated receptor-?, resistin, and visfatin gene expression. In contrast, PNGR and IPGR were lighter, had reduced visceral WAT, and were glucose tolerant with unchanged hepatic glucose production but with increased GSIS, ?-cell mass, glucose clearance rate, and WAT insulin receptor. Hepatic Glut1 and DNL were also increased in lean IPGR and PNGR with increased hepatic ACC, phosphorylated ACC, and pAMPK and reduced WAT fatty acid transport protein-1, peroxisomal proliferator-activated receptor-?, and ACC?. We conclude the following: 1) the heavy, glucose-intolerant and insulin-resistant IUGR adult phenotype is ameliorated by postnatal caloric restriction; 2) increased DNL paralleling hepatic Glut1 is a biomarker of exposure to early caloric restriction rather than the adult metabolic status; 3) hepatic lipid enzyme expression reflects GSIS rather than DNL; and 4) WAT gene expression reflects an obesogenic vs. lean phenotype. PMID:23183174

  17. Role of parathyroid hormone in the glucose intolerance of chronic renal failure.

    PubMed Central

    Akmal, M; Massry, S G; Goldstein, D A; Fanti, P; Weisz, A; DeFronzo, R A

    1985-01-01

    Evidence has accumulated suggesting that the state of secondary hyperparathyroidism and the elevated blood levels of parathyroid hormone (PTH) in uremia participate in the genesis of many uremic manifestations. The present study examined the role of PTH in glucose intolerance of chronic renal failure (CRF). Intravenous glucose tolerance tests (IVGTT) and euglycemic and hyperglycemic clamp studies were performed in dogs with CRF with (NPX) and without parathyroid glands (NPX-PTX). There were no significant differences among the plasma concentrations of electrolytes, degree of CRF, and its duration. The serum levels of PTH were elevated in NPX and undetectable in NPX-PTX. The NPX dogs displayed glucose intolerance after CRF and blood glucose concentrations during IVGTT were significantly (P less than 0.01) higher than corresponding values before CRF. In contrast, blood glucose levels after IVGTT in NPX-PTX before and after CRF were not different. K-g rate fell after CRF from 2.86 +/- 0.48 to 1.23 +/- 0.18%/min (P less than 0.01) in NPX but remained unchanged in NPX-PTX (from 2.41 +/- 0.43 to 2.86 +/- 0.86%/min) dogs. Blood insulin levels after IVGTT in NPX-PTX were more than twice higher than in NPX animals (P less than 0.01) and for any given level of blood glucose concentration, the insulin levels were higher in NPX-PTX than NPX dogs. Clamp studies showed that the total amount of glucose utilized was significantly lower (P less than 0.025) in NPX (6.64 +/- 1.13 mg/kg X min) than in NPX-PTX (10.74 +/- 1.1 mg/kg X min) dogs. The early, late, and total insulin responses were significantly (P less than 0.025) greater in the NPX-PTX than NPX animals. The values for the total response were 143 +/- 28 vs. 71 +/- 10 microU/ml, P less than 0.01. There was no significant difference in the ratio of glucose metabolized to the total insulin response, a measure of tissue sensitivity to insulin, between the two groups. The glucose metabolized to total insulin response ratio in NPX (5.12 +/- 0.76 mg/kg X min per microU/ml) and NPX-PTX (5.18 +/- 0.57 mg/kg X min per microU/ml) dogs was not different but significantly (P less than 0.01) lower than in normal animals (9.98 +/- 1.26 mg/kg X min per microU/ml). The metabolic clearance rate of insulin was significantly (P less than 0.02) reduced in both NPX (12.1 +/- 0.7 ml/kg X min) and NPX-PTX (12.1 +/- 0.9 ml/kg X min) dogs, as compared with normal animals (17.4 +/- 1.8 ml/kg X min). The basal hepatic glucose production was similar in both groups of animals and nor different from normal dogs; both the time course and the magnitude of suppression of hepatic glucose production by insulin were similar in both in groups. There were no differences in the binding affinity, binding sites concentration, and binding capacity of monocytes to insulin among NPX, NPX-PTX, and normal dogs. The data show that (a) glucose intolerance does not develop with CRF in the absence of PTH, (b) PTH does not affect metabolic clearance of insulin or tissue resistance to insulin in CRF, and (c) the normalization of metabolism in CRF in the absence of PTH is due to increased insulin secretion. The results indicate that excess PTH in CRF interferes with the ability of the beta-cells to augment insulin secretion appropriately in response to the insulin-resistant state. Images PMID:3884663

  18. The Metabolic Syndrome Is Less Useful than Random Plasma Glucose to Screen for Glucose Intolerance

    PubMed Central

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

    2008-01-01

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

  19. [Polymorphism of glucose intolerance and insulin resistance susceptibility genes in oncological patients].

    PubMed

    Ulybina, Iu M; Imianitov, E N; Vasil'ev, D A; Bershte?n, L M

    2008-01-01

    Glucose intolerance and insulin resistance belong to the group of leading risk factors for breast (BC) and endometrial cancer (EC). Differences in the intensity of association of these endocrine disturbances with BC and EC may at least partly be explained by non-identity in polygenic nature of the mentioned hormone-metabolic shifts and oncological diseases themselves as well. In this study, which included 105 healthy postmenopausal women and 301 female cancer patients (110 BC and 191 EC) without overt diabetes mellitus, we compared the frequency of the following genetic polymorphisms: insulin receptor substrate-1, IRS Gly972Arg; leptin receptor, LEPR Lys109Arg and Gln223Arg; mitochondrial uncoupling protein-2, UCP2_866G/A; and gene ND3 of mitochondrial DNA, mtDNA 10398A/G. Genotyping was performed with allele-specific real-time PCR. According to data received, certain genetic markers associated with impaired glucose tolerance and/or insulin resistance (namely, leptin receptor genotypes 223 Gln/Arg and Gln/Gln) are revealed in oncological patients more often than in females without cancer. Other markers (like genotype UCP2 866AA and polymorphism mtDNA 10398A) appeared to be relatively more frequent in EC than in BC providing one of the interpretations for the lower insulin sensitivity and higher incidence of carbohydrate metabolism disturbances in the first of these two diseases. PMID:19140314

  20. Glucose intolerance and diabetes mellitus in ulcerative colitis: Pathogenetic and therapeutic implications

    PubMed Central

    Maconi, Giovanni; Furfaro, Federica; Sciurti, Roberta; Bezzio, Cristina; Ardizzone, Sandro; de Franchis, Roberto

    2014-01-01

    Diabetes mellitus is one of the most frequent co-morbidities of ulcerative colitis patients. The epidemiological association of these diseases suggested a genetic sharing and has challenged gene identification. Diabetes co-morbidity in ulcerative colitis has also relevant clinical and therapeutic implications, with potential clinical impact on the follow up and outcome of patients. These diseases share specific complications, such as neuropathy, hepatic steatosis, osteoporosis and venous thrombosis. It is still unknown whether the coexistence of these diseases may increase their occurrence. Diabetes and hyperglycaemia represent relevant risk factors for postoperative complications and pouch failure in ulcerative colitis. Medical treatment of ulcerative colitis in patients with diabetes mellitus may be particularly challenging. Corticosteroids are the treatment of choice of active ulcerative colitis. Their use may be associated with the onset of glucose intolerance and diabetes, with difficult control of glucose levels and with complications in diabetic patients. Epidemiologic and genetic evidences about diabetes co-morbidity in ulcerative colitis patients and shared complications and treatment of patients with these diseases have been discussed in the present review. PMID:24707133

  1. Long-term ketogenic diet causes glucose intolerance and reduced ?- and ?-cell mass but no weight loss in mice.

    PubMed

    Ellenbroek, Johanne H; van Dijck, Laura; Tns, Hendrica A; Rabelink, Ton J; Carlotti, Franoise; 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 ?- and ?-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-1?, 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 ?-cells. After 22 wk, insulin-stimulated glucose uptake was reduced. A reduction in ?-cell mass was observed in KD-fed mice together with an increased number of smaller islets. Also ?-cell mass was markedly decreased, resulting in a lower ?- to ?-cell ratio. Our data show that long-term KD causes dyslipidemia, a proinflammatory state, signs of hepatic steatosis, glucose intolerance, and a reduction in ?- and ?-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

  2. Glucose intolerance by race and ethnicity in the U.S. Virgin Islands.

    PubMed Central

    Tull, Eugene S.; LaPorte, Ronald; Kriska, Andrea; Mark, Joseph; Hatcher, Ann T.

    2002-01-01

    This study describes the prevalence on glucose intolerance by race and ethnicity in the United States Virgin Islands. A population-based sample of 1026 individuals 20 years of age or older was recruited on the island of St. Croix, U.S. Virgin Islands, where 80% of the population classify their race as African American and 20% indicate their ethnicity as Hispanic. American Diabetes Association (ADA) criteria was used to classify glucose tolerance for the entire sample. Persons 40 years of age or older (405) were also administered a 2-h oral glucose tolerance test. Among the major race/ethnic groups, the prevalence of diabetes in patients 20 years of age or older (age-adjusted to the 1995 world population) was 14.1% for non-Hispanic blacks (n = 712), 12.1% for Hispanic blacks (n = 145), 13.5% for Hispanic whites (n = 70) and 1.2% for non-Hispanic whites (n = 37). In each group, the prevalence of diabetes increased with age and appeared higher for men. Among individuals 40 years of age or older a slightly higher prevalence of newly diagnosed diabetes was found when using World Health Organization (WHO) criteria compared to ADA criteria (WHO 10.3%, ADA 7.7% for black non-Hispanic persons and WHO 10.4%, ADA 6.0% for all other groups combined). The prevalence of diabetes for African Americans residing in the U.S. Virgin Islands is similar to rates for the African-American population on the United States mainland and is double that of estimates for blacks on neighboring islands. PMID:11918382

  3. 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

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

    PubMed Central

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

    2015-01-01

    Background. Serum ferritin predicts the onset of diabetes; however, this relationship is not clear amongst South Asians, a population susceptible to glucose intolerance and anaemia. Objective. This study tests whether ferritin levels reflect glucose tolerance in South Asians, independent of lifestyle exposures associated with Indian or British residence. Methods. We randomly sampled 227 Gujaratis in Britain (49.8 (14.4) years, 50% men) and 277 contemporaries living in Gujarati villages (47.6 (11.8) years, 41% men). Both groups underwent a 75?g oral-glucose-tolerance test. We evaluated lifestyle parameters with standardised questionnaires and conducted comprehensive clinical and lab measurements. Results. Across sites, the age-adjusted prevalence of diabetes was 9.8%. Serum ferritin was higher amongst diabetics (P = 0.005), irrespective of site, gender, and central obesity (P ? 0.02), and was associated with fasting and postchallenge glucose, anthropometry, blood pressure, triglycerides, and nonesterified fatty acids (P < 0.001). Diabetes was less in those with low ferritin (<20?mg/mL), P < 0.008, and risk estimate = 0.35 (95% CI 0.150.81), as were blood pressure and metabolic risk factors. On multivariate analysis, diabetes was independently associated with ferritin (P = 0.001) and age (P < 0.001). Conclusion. Ferritin levels are positively associated with glucose intolerance in our test groups, independent of gender and Indian or UK lifestyle factors. PMID:26347777

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

    PubMed

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

    2015-07-01

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

  6. Pregnancy complications and glucose intolerance in women with polycystic ovary syndrome.

    PubMed

    Sawada, Mari; Masuyama, Hisashi; Hayata, Kei; Kamada, Yasuhiko; Nakamura, Keiichiro; Hiramatsu, Yuji

    2015-11-28

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by insulin resistance and hyperandrogenism. The interaction of these factors might result in increased risks of miscarriage and pregnancy complications such as gestational diabetes mellitus (GDM). To examine the pregnancy risks in women with PCOS, we compared obstetrical outcomes between patients with and without PCOS. We also studied the differences in maternal characteristics, glucose intolerance and pregnancy complications between PCOS patients with and without GDM, with and without obesity, and between successful pregnancies and miscarriages. We observed a high incidence of GDM and prevalence of GDM diagnosis in the first trimester in PCOS. Patients with GDM had higher body mass index (BMI) and lower homeostasis model assessment of ?-cell function (HOMA-?) at preconception than those without GDM. Obese pregnant women with PCOS demonstrated a high incidence of GDM with severe insulin resistance, including high fasting insulin, HOMA of insulin resistance (HOMA-IR), and HOMA-? at preconception compared with normal-weight patients. BMI was significantly correlated with HOMA-IR or HOMA-?, and both indices were lower in PCOS patients with than without GDM for the same BMI. There were no significant differences in maternal characteristics (excluding maternal age) between PCOS patients with successful pregnancy and PCOS patients with miscarriages. Our data suggest that pregnant women with PCOS have an increased risk of GDM, especially if they have obesity and/or poorer insulin secretion. Measure of ?-cell function, such as HOMA-?, at preconception might be a useful predictor of the risk of GDM in pregnant PCOS patients. PMID:26370557

  7. 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 = 0.23. Higher colonization levels of specific periodontal microbiota are associated with higher prediabetes prevalence among diabetes-free adults. PMID:26082387

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

    PubMed Central

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

    2012-01-01

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

  9. NF-κB–inducing kinase (NIK) promotes hyperglycemia and glucose intolerance in obesity by augmenting glucagon action.

    PubMed

    Sheng, Liang; Zhou, Yingjiang; Chen, Zheng; Ren, Decheng; Cho, Kae Won; Jiang, Lin; Shen, Hong; Sasaki, Yoshiteru; Rui, Liangyou

    2012-06-01

    The canonical inhibitor of nuclear factor κB kinase subunit β (IKK-β)–nuclear factor of κ light polypeptide gene enhancer in B cells 1 (NF-κB1) pathway has been well documented to promote insulin resistance; however, the noncanonical NF-κB–inducing kinase (NIK)–NF-κB2 pathway is not well understood in obesity. Additionally, the contribution of counter-regulatory hormones, particularly glucagon, to hyperglycemia in obesity is unclear. Here we show that NIK promotes glucagon responses in obesity. Hepatic NIK was abnormally activated in mice with dietary or genetic obesity. Systemic deletion of Map3k14, encoding NIK, resulted in reduced glucagon responses and hepatic glucose production (HGP). Obesity is associated with high glucagon responses, and liver-specific inhibition of NIK led to lower glucagon responses and HGP and protected against hyperglycemia and glucose intolerance in obese mice. Conversely, hepatocyte-specific overexpression of NIK resulted in higher glucagon responses and HGP. In isolated mouse livers and primary hepatocytes, NIK also promoted glucagon action and glucose production, at least in part by increasing cAMP response element-binding (CREB) stability. Therefore, overactivation of liver NIK in obesity promotes hyperglycemia and glucose intolerance by increasing the hyperglycemic response to glucagon and other factors that activate CREB. PMID:22581287

  10. Hepatocyte-specific Deletion of Janus Kinase 2 (JAK2) Protects against Diet-induced Steatohepatitis and Glucose Intolerance*

    PubMed Central

    Shi, Sally Yu; Martin, Rubn Garca; Duncan, Robin E.; Choi, Diana; Lu, Shun-Yan; Schroer, Stephanie A.; Cai, Erica P.; Luk, Cynthia T.; Hopperton, Kathryn E.; Domenichiello, Anthony F.; Tang, Christine; Naples, Mark; Dekker, Mark J.; Giacca, Adria; Adeli, Khosrow; Wagner, Kay-Uwe; Bazinet, Richard P.; Woo, Minna

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of chronic liver disease and is now considered to be the hepatic manifestation of the metabolic syndrome. However, the role of steatosis per se and the precise factors required in the progression to steatohepatitis or insulin resistance remain elusive. The JAK-STAT pathway is critical in mediating signaling of a wide variety of cytokines and growth factors. Mice with hepatocyte-specific deletion of Janus kinase 2 (L-JAK2 KO mice) develop spontaneous steatosis as early as 2 weeks of age. In this study, we investigated the metabolic consequences of jak2 deletion in response to diet-induced metabolic stress. To our surprise, despite the profound hepatosteatosis, deletion of hepatic jak2 did not sensitize the liver to accelerated inflammatory injury on a prolonged high fat diet (HFD). This was accompanied by complete protection against HFD-induced whole-body insulin resistance and glucose intolerance. Improved glucose-stimulated insulin secretion and an increase in ?-cell mass were also present in these mice. Moreover, L-JAK2 KO mice had progressively reduced adiposity in association with blunted hepatic growth hormone signaling. These mice also exhibited increased resting energy expenditure on both chow and high fat diet. In conclusion, our findings indicate a key role of hepatic JAK2 in metabolism such that its absence completely arrests steatohepatitis development and confers protection against diet-induced systemic insulin resistance and glucose intolerance. PMID:22275361

  11. Supplementation of SK1 from Platycodi radix ameliorates obesity and glucose intolerance in mice fed a high-fat diet.

    PubMed

    Kim, Jae-Yong; Moon, Kwang-Deog; Seo, Kwon-Il; Park, Kyung-Wuk; Choi, Myung-Sook; Do, Gyeong-Min; Jeong, Yong-Kee; Cho, Young-Su; Lee, Mi-Kyung

    2009-06-01

    This study investigated the beneficial effects of SK1 on obesity and insulin resistance in C57BL/6 mice, which were fed a high-fat diet (37% calories from fat). SK1 is an edible saponin-rich compound from Platycodi radix. The mice were supplemented with two doses of SK1 (0.5% and 1.0%, wt/wt) for 9 weeks. The body weight, visceral fat mass, and adipocyte area were significantly decreased in the SK1 supplemented-groups in a dose-dependent manner compared to the high-fat group. The SK1 supplement significantly lowered plasma triglycerides, total cholesterol, and free fatty acid levels, whereas it significantly elevated the fecal excretion of lipids in the diet-induced obese mice. Supplementation of SK1 decreased the triglyceride and cholesterol levels and the accumulation of lipid droplets in the liver compared to the high-fat control group. High-fat diet induced glucose intolerance and insulin resistance with the elevation of blood glucose levels compared to the normal group; however, the SK1 supplement significantly improved postprandial glucose levels and insulin resistance index. After 9 weeks of being fed a high-fat diet, the mice presented with significantly increased activities of hepatic fatty acid synthase, fatty acid beta-oxidation, and glucokinase; however, both 0.5% and 1.0% SK1 supplementation normalized these activities. Notably, SK1 supplementation effectively diminished the ratio of fatty acid biosynthesis to fatty acid oxidation compared to the high-fat group. These results indicate that SK1 exhibits a potential anti-obesity effect and may prevent glucose intolerance by reducing body weight and fat accumulation, increasing fecal lipid excretions, and regulating hepatic lipid and glucose metabolism in high-fat fed mice. PMID:19627213

  12. 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

  13. Anoxia tolerance in rice seedlings: exogenous glucose improves growth of an anoxia-'intolerant', but not of a 'tolerant' genotype.

    PubMed

    Huang, Shaobai; Greenway, Hank; Colmer, Timothy D

    2003-10-01

    This study demonstrated that, in rice seedlings, genotypic difference in tolerance to anoxia only occurred when anoxia was imposed at imbibition, but not at 3 d after imbibition. When seeds were imbibed and grown in anoxia, IR22 (anoxia-'intolerant') grew much slower and had lower soluble sugar concentrations in coleoptiles and seeds than Amaroo (anoxia-'tolerant'), while Calrose was intermediate. After 3 d in anoxia, the sugar concentrations in embryos and endosperms of anoxic seedlings were nearly 4-fold lower in IR22 than in Amaroo. Sugar deficit in the embryo of IR22 is presumably due to the limitation of sugar mobilization rather than the capacity of transport as shown by similar sugar accumulation ratios of 1.8 between embryo and endosperm in IR22 and Amaroo at 3 d in anoxia. With 20 mol m-3 exogenous glucose, coleoptile extension and fresh weight increments in anoxic seedlings of IR22 were much closer to those in the two other genotypes, nevertheless protein concentration remained lowest on a fresh weight basis in the coleoptiles of IR22; indicating that protein synthesis has a lower priority for energy apportionment during anoxia than processes crucial to coleoptile extension. In contrast to these responses to anoxia imposed at imbibition, IR22 had nearly the same high tolerance to anoxia as Calrose and Amaroo, when anoxia was imposed on seedlings subsequent to 48 h aeration followed by 16 h hypoxic pretreatment. In fact, coleoptiles of anoxic IR22 had higher sugar concentrations and grew faster than Calrose, and exogenous glucose had no effect on the coleoptile extension of IR22. Excised coleoptile tips of IR22 and Amaroo with exogenous glucose had similar rates of ethanol production and were equally tolerant to anoxia. In conclusion, much of the anoxia 'intolerance' of IR22 when germinated in anoxia could be attributed to limited substrate availability to the embryo and coleoptile, presumably due to slow starch hydrolysis in the endosperm. PMID:14504303

  14. 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

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

    PubMed Central

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

    2013-01-01

    Summary Rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, extends the lifespan 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 (Johnston et al. 2008; Houde et al. 2010; Lamming et al. 2012). 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 lifespan. 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 three weeks of treatment in young animals, but the effect was lost by three months, and no effect was detected in older animals. Our results demonstrate that the extended lifespan 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

  16. Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats.

    PubMed

    Caillaud, Corinne; Mechta, Mie; Ainge, Heidi; Madsen, Andreas N; Ruell, Patricia; Mas, Emilie; Bisbal, Catherine; Mercier, Jacques; Twigg, Stephen; Mori, Trevor A; Simar, David; Barrès, Romain

    2015-05-01

    Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose levels and glucose tolerance, without altering total body weight or retroperitoneal fat mass. Concomitantly, EPO partially rescued insulin-stimulated AKT activation, reduced markers of oxidative stress, and restored heat-shock protein 72 expression in soleus muscles from HFD-fed rats. Incubation of skeletal muscle cell cultures with EPO failed to induce AKT phosphorylation and had no effect on glucose uptake or glycogen synthesis. We found that the EPO receptor gene was expressed in myotubes, but was undetectable in soleus. Together, our results indicate that EPO treatment improves glucose tolerance but does not directly activate the phosphorylation of AKT in muscle cells. We propose that the reduced systemic inflammation or oxidative stress that we observed after treatment with EPO could contribute to the improvement of whole-body glucose metabolism. PMID:25767056

  17. Hydrolysis enhances bioavailability of proanthocyanidin-derived metabolites and improves ?-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 ?-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 ?-cell and ?-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 ?/?-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 ?-cell function. PMID:25987165

  18. Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice

    PubMed Central

    Gustavsson, Natalia; Lao, Ye; Maximov, Anton; Chuang, Jen-Chieh; Kostromina, Elena; Repa, Joyce J.; Li, Cai; Radda, George K.; Sdhof, Thomas C.; Han, Weiping

    2008-01-01

    Vertebrates express at least 15 different synaptotagmins with the same domain structure but diverse localizations and tissue distributions. Synaptotagmin-1,-2, and -9 act as calcium sensors for the fast phrase of neurotransmitter release, and synaptotagmin-12 acts as a calcium-independent modulator of release. The exact functions of the remaining 11 synaptotagmins, however, have not been established. By analogy to the role of synaptotagmin-1, -2, and -9 in neurotransmission, these other synaptotagmins may serve as Ca2+ transducers regulating other Ca2+-dependent membrane processes, such as insulin secretion in pancreatic ?-cells. Of these other synaptotagmins, synaptotagmin-7 is one of the most abundant and is present in pancreatic ?-cells. To determine whether synaptotagmin-7 regulates Ca2+-dependent insulin secretion, we analyzed synaptotagmin-7 null mutant mice for glucose tolerance and insulin release. Here, we show that synaptotagmin-7 is required for the maintenance of systemic glucose tolerance and glucose-stimulated insulin secretion. Mutant mice have normal insulin sensitivity, insulin production, islet architecture and ultrastructural organization, and metabolic and calcium responses but exhibit impaired glucose-induced insulin secretion, indicating a calcium-sensing defect during insulin-containing secretory granule exocytosis. Taken together, our findings show that synaptotagmin-7 functions as a positive regulator of insulin secretion and may serve as a calcium sensor controlling insulin secretion in pancreatic ? cells. PMID:18308938

  19. 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

    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

  20. Loss of Pgc-1α expression in aging mouse muscle potentiates glucose intolerance and systemic inflammation

    PubMed Central

    Sczelecki, Sarah; Besse-Patin, Aurèle; Abboud, Alexandra; Kleiner, Sandra; Laznik-Bogoslavski, Dina; Wrann, Christiane D.; Ruas, Jorge L.; Haibe-Kains, Benjamin

    2013-01-01

    Diabetes risk increases significantly with age and correlates with lower oxidative capacity in muscle. Decreased expression of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) and target gene pathways involved in mitochondrial oxidative phosphorylation are associated with muscle insulin resistance, but a causative role has not been established. We sought to determine whether a decline in Pgc-1α and oxidative gene expression occurs during aging and potentiates the development of age-associated insulin resistance. Muscle-specific Pgc-1α knockout (MKO) mice and wild-type littermate controls were aged for 2 yr. Genetic signatures of skeletal muscle (microarray and mRNA expression) and metabolic profiles (glucose homeostasis, mitochondrial metabolism, body composition, lipids, and indirect calorimetry) of mice were compared at 3, 12, and 24 mo of age. Microarray and gene set enrichment analysis highlighted decreased function of the electron transport chain as characteristic of both aging muscle and loss of Pgc-1α expression. Despite significant reductions in oxidative gene expression and succinate dehydrogenase activity, young mice lacking Pgc-1α in muscle had lower fasting glucose and insulin. Consistent with loss of oxidative capacity during aging, Pgc-1α and Pgc-1β expression were reduced in aged wild-type mouse muscle. Interestingly, the combination of age and loss of muscle Pgc-1α expression impaired glucose tolerance and led to increased fat mass, insulin resistance, and inflammatory markers in white adipose and liver tissues. Therefore, loss of Pgc-1α expression and decreased mitochondrial oxidative capacity contribute to worsening glucose tolerance and chronic systemic inflammation associated with aging. PMID:24280126

  1. 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

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

    PubMed

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

    2016-01-01

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

  3. Sex-specific differences in progressive glucose intolerance and hip geometry: the Baltimore Longitudinal Study of Aging

    PubMed Central

    Chia, C. W.; Simonsick, E. M.; Egan, J. M.; Ferrucci, L.; Sellmeyer, D. E.

    2016-01-01

    Summary Fracture risk is increased in type 2 diabetes mellitus (T2DM). The effect of pre-diabetes and T2DM on bone macroarchitecture and strength has not been well investigated. In this study, we show that in women only, both pre-diabetes and T2DM are associated with decreased hip bending strength and mineralization which might lead to skeletal weakness. Introduction Older men and women with T2DM are at increased risk for fracture despite normal bone mineral density (BMD). The discordance between bone quantity and skeletal fragility has driven investigation into additional determinants of fracture resistance in T2DM. Additionally, the effect of pre-diabetes on bone strength has not been well described. The aim of this study was to determine differences in bone macroarchitecture and strength, measured by hip geometry, in persons with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. Methods We performed cross-sectional analyses of older (age >55 years) men (n=472) and women (n=473) participating in the Baltimore Longitudinal Study of Aging (BLSA) classified as NGT, IGT, or T2DM based on oral glucose tolerance testing. Bone strength measures included the hip geometry parameters of section modulus (Z), cross-sectional area (CSA), and buckling ratio (BR). Sex-stratified analyses were conducted using adjusted stepwise regression models. Results In women, IGT and T2DM were negatively associated with hip geometry parameters including mineralization in cross section (CSA, ? ?0.076 and ?0.073, respectively; both p<0.05) and hip bending strength (Z, ? ?0.097 and ?0.09, respectively; both p<0.05); conversely, IGT and T2DM were associated with improved compressive strength (BR, ? ?0.31 and ?0.29, respectively; both p<0.05). There was no significant association between glycemic status and hip geometry in men. Conclusions In women only, both IGT and T2DM were inversely associated with bone macroarchitecture and measures of bone mineralization and bending strength. The same association between worsening glycemic status and bone strength was not observed in men. These data suggest a differential effect of sex on hip geometry with evolving glucose intolerance. PMID:25619633

  4. 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

  5. Alteration of NCoR corepressor splicing in mice causes increased body weight and hepatosteatosis without glucose intolerance.

    PubMed

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

    2014-11-15

    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 NCoR? to NCoR?, 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 NCoR? 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, NCoR?(-/-) 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

  6. 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

  7. Differences in insulin and sympathetic responses to glucose ingestion due to family history of hypertension.

    PubMed

    Masuo, K; Mikami, H; Ogihara, T; Tuck, M L

    1996-08-01

    To evaluate the relationship of metabolic and neural factors in familial hypertension, we examined blood pressure (BP), blood glucose, and plasma insulin and norepinephrine (NE) levels before and every 30 min for 120 min after glucose ingestion in six groups with 20 subjects each: normotensive subjects (NT) with and without a family history of hypertension; borderline hypertensive patients (BHT) with and without a family history of hypertension; and established hypertensive patients (EH) with and without a family history of hypertension. The changes in blood glucose were similar in the six groups. In the subjects with a positive family history of hypertension regardless of BP levels, the basal levels and changes in insulin levels after glucose ingestion were significantly greater than those in the subjects without a family history of hypertension (F = 13.32, P = .0001). In BHT and EH subjects, regardless of family history, changes in insulin were greater than in NT (F = 16.00, P = .0001). Basal levels and changes in plasma NE were higher in BHT and EH (F = 26.55, P = .0001) than NT and changes in plasma NE were greater in subjects with a family history than those in subjects without a family history (F = 18.32, P = .0001). Thus, abnormal insulin and NE responses to glucose appear to aggregate in subjects with a history of familial hypertension, regardless of the level of BP. Furthermore, the ratio of delta NE/ delta insulin (changes from basal to peak) in NT and BHT, and in subjects with a family history were significantly greater than in EH and in subjects without a family history. Thus, we demonstrated that concomitant abnormalities in the glucose-insulin regulatory system and the sympathetic nervous system characterize the early phase in the development of hypertension and these abnormalities have an apparent genetic basis. PMID:8862219

  8. Insulin-like growth factor-I correlates more closely than growth hormone with insulin resistance and glucose intolerance in patients with acromegaly.

    PubMed

    Niculescu, Dan; Purice, Mariana; Coculescu, Mihail

    2013-06-01

    In normal subjects growth hormone (GH) and insulin-like growth factor-I (IGF-I) have opposing effects on glucose metabolism. Active acromegaly is associated with insulin resistance (IR) and glucose intolerance although both GH and IGF-I are elevated. Our objective was to compare whether GH or IGF-I correlates more closely with IR and glucose intolerance in acromegaly. Basal serum IGF-I and GH, glucose and insulin during an oral glucose tolerance test were measured in 70 normoglycemic and 44 hyperglycemic acromegalic patients (21 impaired fasting glucose, 11 impaired glucose tolerance and 12 diabetes mellitus) according to American Diabetes Association criteria. 55 patients were assessed before any treatment for acromegaly and 59 after surgery and/or radiotherapy (15 patients had normal IGF-I after treatment). Patients treated with somatostatin analogs, GH-receptor antagonists or antidiabetic drugs were excluded. IR was assessed by various basal and stimulated indices. Homeostatic Model Assessment 2-Insulin Resistance (HOMA2-IR) index correlated more closely with IGF-I (r=0.65, p<0.0001) than nadir (r=0.23, p=0.008) or random GH (r=0.26, p=0.002). HOMA2-IR correlated better with IGF-I than nadir or random GH also in normoglycemic (n=70; r=0.74, p<0.0001 vs. r=0.36, p=0.001 vs. r=0.39, p<0.001) and hyperglycemic patients (n=44; r=0.54, p=0.0002 vs. r=0.09, p=0.4 vs. r=0.14, p=0.26). In multivariate logistic regression analysis IGF-I but not GH was a significant risk factor for glucose intolerance after adjusting for age, sex, weight and acromegaly duration (OR=1.56, p=0.01). In acromegaly IGF-I correlates more closely than GH with IR. IGF-I levels but not GH are associated with glucose intolerance. PMID:22562529

  9. Lactose intolerance

    MedlinePLUS

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

  10. Increased Myocardial Uptake of Dietary Fatty Acids Linked to Cardiac Dysfunction in Glucose-Intolerant Humans

    PubMed Central

    Labb, Sbastien M.; Grenier-Larouche, Thomas; Noll, Christophe; Phoenix, Serge; Gurin, Brigitte; Turcotte, Eric E.; Carpentier, Andr C.

    2012-01-01

    Impaired cardiac systolic and diastolic function has been observed in preclinical models and in subjects with type 2 diabetes. Using a recently validated positron emission tomography (PET) imaging method with 14(R,S)-[18F]-fluoro-6-thia-heptadecanoic acid to quantify organ-specific dietary fatty acid partitioning, we demonstrate in this study that overweight and obese subjects with impaired glucose tolerance (IGT+) display significant increase in fractional myocardial dietary fatty acid uptake over the first 6 h postprandial compared with control individuals (IGT?). Measured by [11C]acetate with PET, IGT+ subjects have a significant increase in myocardial oxidative index. IGT+ subjects have significantly reduced left ventricular stroke volume and ejection fraction (LVEF) and tend to display impaired diastolic function, as assessed by PET ventriculography. We demonstrate an inverse relationship between increased myocardial dietary fatty acid partitioning and LVEF. Fractional dietary fatty acid uptake is reduced in subcutaneous abdominal and visceral adipose tissues in IGT+ directly associated with central obesity. Fractional dietary fatty acid uptake in skeletal muscles or liver is, however, similar in IGT+ versus IGT?. The current study demonstrates, for the first time, that excessive myocardial partitioning of dietary fatty acids occurs in prediabetic individuals and is associated with early impairment of left ventricular function and increased myocardial oxidative metabolism. PMID:23093657

  11. Loss of Foxd3 Results in Decreased ?-Cell Proliferation and Glucose Intolerance During Pregnancy

    PubMed Central

    Plank, Jennifer L.; Frist, Audrey Y.; LeGrone, Alison W.; Magnuson, Mark A.

    2011-01-01

    A complete molecular understanding of ?-cell mass expansion will be useful for the improvement of therapies to treat diabetic patients. During normal periods of metabolic challenges, such as pregnancy, ?-cells proliferate, or self-renew, to meet the new physiological demands. The transcription factor Forkhead box D3 (Foxd3) is required for maintenance and self-renewal of several diverse progenitor cell lineages, and Foxd3 is expressed in the pancreatic primordium beginning at 10.5 d postcoitum, becoming localized predominantly to ?-cells after birth. Here, we show that mice carrying a pancreas-specific deletion of Foxd3 have impaired glucose tolerance, decreased ?-cell mass, decreased ?-cell proliferation, and decreased ?-cell size during pregnancy. In addition, several genes known to regulate proliferation, Foxm1, Skp2, Ezh2, Akt2, and Cdkn1a, are misregulated in islets isolated from these Foxd3 mutant mice. Together, these data place Foxd3 upstream of several pathways critical for ?-cell mass expansion in vivo. PMID:21952247

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

    PubMed

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

    2014-03-01

    The oligopeptide transporter peptide cotransporter-1 Slc15a1 (PEPT1) plays a major role in the regulation of nitrogen supply, since it is responsible for 70% of the dietary nitrogen absorption. Previous studies demonstrated that PEPT1 expression and function in jejunum are reduced in diabetes and obesity, suggesting a nitrogen malabsorption from the diet. Surprisingly, we reported here a decrease in gut nitrogen excretion in high-fat diet (HFD)-fed mice and further investigated the mechanisms that could explain this apparent contradiction. Upon HFD, mice exhibited an increased concentration of free amino acids (AAs) in the portal vein (60%) along with a selective increase in the expression of two AA transporters (Slc6a20a, Slc36a1), pointing to a specific and adaptive absorption of some AAs. A delayed transit time (+40%) and an increased intestinal permeability (+80%) also contribute to the increase in nitrogen absorption. Besides, HFD mice exhibited a 2.2-fold decrease in fecal DNA resulting from a reduction in nitrogen catabolism from cell desquamation and/or in the intestinal microbiota. Indeed, major quantitative (2.5-fold reduction) and qualitative alterations of intestinal microbiota were observed in feces of HFD mice. Collectively, our results strongly suggest that both increased AA transporters, intestinal permeability and transit time, and changes in gut microbiota are involved in the increased circulating AA levels. Modifications in nitrogen homeostasis provide a new insight in HFD-induced obesity and glucose intolerance; however, whether these modifications are beneficial or detrimental for the HFD-associated metabolic complications remains an open issue. PMID:24425764

  14. 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

  15. TLR4 Expression by Liver Resident Cells Mediates the Development of Glucose Intolerance and Insulin Resistance in Experimental Periodontitis

    PubMed Central

    Ilievski, Vladimir; Cho, Yale; Katwala, Priya; Rodriguez, Heriberto; Tulowiecka, Margaret; Kurian, David; Leoni, Lara; Christman, John W.; Unterman, Terry G.; Watanabe, Keiko

    2015-01-01

    Background Results from epidemiological studies indicate a close association between periodontitis and type 2 diabetes mellitus. However, the mechanism linking periodontitis to glucose intolerance (GI) and insulin resistance (IR) is unknown. We therefore tested the hypothesis that periodontitis induces the development of GI/IR through a liver Toll-like receptor 4 (TLR4) dependent mechanism. Methods TLR4 chimeric mice were developed by bone marrow transplantation using green fluorescent protein expressing TLR4WT mouse (GFPWT) as donor and TLR4 WT or TLR4-/- as recipient mice (GFPWT:WT and GFPWT:KO chimeras respectively). These chimeras were subjected to experimental chronic periodontitis induced by repeated applications of LPS to the gingival sulci for 18 weeks. The levels of GI/IR were monitored and plasma cytokines and LPS were determined at 18 weeks when differences in glucose tolerance were most apparent. Cytokine gene expression was measured in liver tissue by qPCR. Results Alveolar bone loss was significantly greater in GFPWT:WT chimeras treated with LPS compared with chimeras treated with PBS or GFPWT:KO chimeras. However, the degree of gingival inflammation was similar between GFPWT:WT and GFPWT:KO mice with LPS application. Severe GI/IR occurred in GFPWT:WT chimeras but not in the GFPWT:KO chimeras that were subjected to 18 weeks of LPS. Serum LPS was detected only in animals to which LPS was applied and the level was similar in GFPWT:WT and GFPWT:KO mice at the 18 week time point. Surprisingly, there was no significant difference in the plasma levels of IL1?, IL6 and TNF? at 18 weeks in spite of the severe GI/IR in the GFPWT:WT chimeras with LPS application. Also, no difference in the expression of TNF? or IL6 mRNA was detected in the liver of GFPWT:WT vs GFPWT:KO mice. In contrast, liver IL1? expression was significantly greater in GFPWT:WT chimeras compared to GFPWT:KO chimeras treated with LPS. Conclusion We observed that GFPWT:WT, but not GFPWT:KO chimeras, treated with LPS developed GI/IR despite similar degrees of gingival inflammation, circulating cytokine levels, and LPS concentrations. We conclude that LPS from periodontitis sites has a pivotal role in triggering the development of GI/IR through a mechanism that involves TLR4 expression by resident macrophages/Kupffer cells in the liver. PMID:26317345

  16. The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome.

    PubMed

    Putnam, Kelly; Shoemaker, Robin; Yiannikouris, Frederique; Cassis, Lisa A

    2012-03-15

    The renin-angiotensin system (RAS) is an important therapeutic target in the treatment of hypertension. Obesity has emerged as a primary contributor to essential hypertension in the United States and clusters with other metabolic disorders (hyperglycemia, hypertension, high triglycerides, low HDL cholesterol) defined within the metabolic syndrome. In addition to hypertension, RAS blockade may also serve as an effective treatment strategy to control impaired glucose and insulin tolerance and dyslipidemias in patients with the metabolic syndrome. Hyperglycemia, insulin resistance, and/or specific cholesterol metabolites have been demonstrated to activate components required for the synthesis [angiotensinogen, renin, angiotensin-converting enzyme (ACE)], degradation (ACE2), or responsiveness (angiotensin II type 1 receptors, Mas receptors) to angiotensin peptides in cell types (e.g., pancreatic islet cells, adipocytes, macrophages) that mediate specific disorders of the metabolic syndrome. An activated local RAS in these cell types may contribute to dysregulated function by promoting oxidative stress, apoptosis, and inflammation. This review will discuss data demonstrating the regulation of components of the RAS by cholesterol and its metabolites, glucose, and/or insulin in cell types implicated in disorders of the metabolic syndrome. In addition, we discuss data supporting a role for an activated local RAS in dyslipidemias and glucose intolerance/insulin resistance and the development of hypertension in the metabolic syndrome. Identification of an activated RAS as a common thread contributing to several disorders of the metabolic syndrome makes the use of angiotensin receptor blockers and ACE inhibitors an intriguing and novel option for multisymptom treatment. PMID:22227126

  17. The renin-angiotensin system: a target of and contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome

    PubMed Central

    Putnam, Kelly; Shoemaker, Robin; Yiannikouris, Frederique

    2012-01-01

    The renin-angiotensin system (RAS) is an important therapeutic target in the treatment of hypertension. Obesity has emerged as a primary contributor to essential hypertension in the United States and clusters with other metabolic disorders (hyperglycemia, hypertension, high triglycerides, low HDL cholesterol) defined within the metabolic syndrome. In addition to hypertension, RAS blockade may also serve as an effective treatment strategy to control impaired glucose and insulin tolerance and dyslipidemias in patients with the metabolic syndrome. Hyperglycemia, insulin resistance, and/or specific cholesterol metabolites have been demonstrated to activate components required for the synthesis [angiotensinogen, renin, angiotensin-converting enzyme (ACE)], degradation (ACE2), or responsiveness (angiotensin II type 1 receptors, Mas receptors) to angiotensin peptides in cell types (e.g., pancreatic islet cells, adipocytes, macrophages) that mediate specific disorders of the metabolic syndrome. An activated local RAS in these cell types may contribute to dysregulated function by promoting oxidative stress, apoptosis, and inflammation. This review will discuss data demonstrating the regulation of components of the RAS by cholesterol and its metabolites, glucose, and/or insulin in cell types implicated in disorders of the metabolic syndrome. In addition, we discuss data supporting a role for an activated local RAS in dyslipidemias and glucose intolerance/insulin resistance and the development of hypertension in the metabolic syndrome. Identification of an activated RAS as a common thread contributing to several disorders of the metabolic syndrome makes the use of angiotensin receptor blockers and ACE inhibitors an intriguing and novel option for multisymptom treatment. PMID:22227126

  18. Low molecular weight compounds from Zoanthus sociatus impair insulin secretion via Ca(+2) influx blockade and cause glucose intolerance invivo.

    PubMed

    Diaz-Garcia, Carlos Manlio; Sanchez-Soto, Carmen; Fuentes-Silva, Deyanira; Leon-Pinzon, Carolina; Dominguez-Perez, Dany; Varela, Carlos; Rodriguez-Romero, Adela; Castaeda, Olga; Hiriart, Marcia

    2012-02-01

    Cnidarians comprise a taxon with a high biodiversity of cytolitic, neurotoxic and cardiotoxic compounds, which have not been studied on insulin release. We tested the effect of a crude extract of Zoanthus sociatus (Ellis, 1767) and the low molecular weight fraction of this extract on insulin secretion in isolated rat ?-cells and also in a glucose tolerance test in vivo. We observed that the extract inhibited insulin release by reducing the amount secreted by individual ?-cells and also by silencing a fraction of the secreting population. This effect coincided with a diminished rise of intracellular Ca(+2) in response to high glucose and high K+ -induced depolarization. Moreover intraperitoneal administration of the low molecular weight fraction produced glucose intolerance in adult rats. The active fraction exhibited molecular weights similar to the neurotoxins described in the phylum. Our results broaden the toxic effects of cnidarian venoms and show evidence of potential modulators of voltage-gated Ca(+2) channels in this group. PMID:22155304

  19. Maternal High Folic Acid Supplement Promotes Glucose Intolerance and Insulin Resistance in Male Mouse Offspring Fed a High-Fat Diet

    PubMed Central

    Huang, Yifan; He, Yonghan; Sun, Xiaowei; He, Yujie; Li, Ying; Sun, Changhao

    2014-01-01

    Maternal nutrition may influence metabolic profiles in offspring. We aimed to investigate the effect of maternal folic acid supplement on glucose metabolism in mouse offspring fed a high-fat diet (HFD). Sixty C57BL/6 female mice were randomly assigned into three dietary groups and fed the AIN-93G diet containing 2 (control), 5 (recommended folic acid supplement, RFolS) or 40 (high folic acid supplement, HFolS) mg folic acid/kg of diet. All male offspring were fed HFD for eight weeks. Physiological, biochemical and genetic variables were measured. Before HFD feeding, developmental variables and metabolic profiles were comparable among each offspring group. However, after eight weeks of HFD feeding, the offspring of HFolS dams (Off-HFolS) were more vulnerable to suffer from obesity (p = 0.009), glucose intolerance (p < 0.001) and insulin resistance (p < 0.001), compared with the controls. Off-HFolS had reduced serum adiponectin concentration, accompanied with decreased adiponectin mRNA level but increased global DNA methylation level in white adipose tissue. In conclusion, our results suggest maternal HFolS exacerbates the detrimental effect of HFD on glucose intolerance and insulin resistance in male offspring, implying that HFolS during pregnancy should be adopted cautiously in the general population of pregnant women to avoid potential deleterious effect on the metabolic diseases in their offspring. PMID:24736781

  20. Predictors for Glucose Change in Hypertensive Participants Following Short-term Treatment with Atenolol or Hydrochlorothiazide

    PubMed Central

    Moore, Mariellen J.; Gong, Yan; Hou, Wei; Hall, Karen; Schmidt, Siegfried O. F.; Curry, Robert Whitney; Beitelshees, Amber L.; Chapman, Arlene; Turner, Stephen T.; Schwartz, Gary L.; Bailey, Kent; Boerwinkle, Eric; Gums, John G.; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.

    2014-01-01

    Study Objective To develop and validate a predictive model for glucose change and risk for new-onset impaired fasting glucose in hypertensive participants following treatment with atenolol or hydrochlorothiazide (HCTZ). Design Randomized multicenter clinical trial. Patients A total of 735 white or African-American men and women with uncomplicated hypertension. Measurements and Main Results Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) is a randomized clinical trial to assess the genetic and nongenetic predictors of blood pressure response and adverse metabolic effects following treatment with atenolol or HCTZ. To develop and validate predictive models for glucose change, PEAR participants were randomly divided into a derivation cohort of 367 and a validation cohort of 368. Linear and logistic regression modeling were used to build models of drug-associated glucose change and impaired fasting glucose (IFG), respectively, in the derivation cohorts. These models were then evaluated in the validation cohorts. For glucose change after atenolol or HCTZ treatment, baseline glucose was a significant (p<0.0001) predictor, explaining 13% of the variability in glucose change after atenolol and 12% of the variability in glucose change after HCTZ. Baseline glucose was also the strongest and most consistent predictor (p<0.0001) for development of IFG after atenolol or HCTZ monotherapy. The area under the receiver operating curve was 0.77 for IFG after atenolol and 0.71 after HCTZ treatment, respectively. Conclusion Baseline glucose is the primary predictor of atenolol or HCTZ-associated glucose increase and development of IFG after treatment with either drug. PMID:25202885

  1. The association between daily physical activity and plasma B-type natriuretic peptide in patients with glucose intolerance: a cross-sectional study

    PubMed Central

    Hamasaki, Hidetaka; Yanai, Hidekatsu; Kakei, Masafumi; Noda, Mitsuhiko; Ezaki, Osamu

    2015-01-01

    Objectives In spite of accumulating evidences suggesting an inverse association between insulin resistance and plasma B-type natriuretic peptide (BNP) levels, the effect of daily physical activity on plasma BNP in individuals with glucose intolerance remains unknown. We investigated the association of physical activity level (PAL) with plasma BNP in patients with impaired fasting glucose, impaired glucose tolerance and type 2 diabetes. Design Cross-sectional study. Setting Outpatients visiting the National Center for Global Health and Medicine Kohnodai Hospital. Participants A total of 60 patients with glucose intolerance who did not take any hypoglycaemic agents, cholesterol-lowering agents and antihypertensive agents were recruited. Patients who were diagnosed as having heart failure and renal impairment, engaged in sports-like exercise and resistance training were excluded. Primary outcome measures PAL was objectively measured by a triaxial accelerometer. The association between PAL and plasma BNP levels was assessed by multiple regression analysis. Results PAL was positively correlated with plasma BNP levels (r=0.296, p=0.021). PAL was still significantly correlated with plasma BNP levels after adjustment for age (?=0.290, p=0.014), and adjustment for age and body mass index (?=0.282, p=0.018). Plasma BNP levels were inversely correlated with serum insulin levels (r=?0.350, p=0.006) and homeostasis model assessment-estimated insulin resistance (HOMA-IR; r=?0.363, p=0.004). Serum insulin levels (meanSD, 8.16.4??U/mL) and HOMA-IR (2.41.9) in the high-BNP group were significantly lower than those (11.27.4??U/mL and 3.73.0, respectively) in the low-BNP group. Conclusions Our findings propose the possibility that plasma BNP may be increased by daily physical activity and BNP is associated with insulin resistance. PMID:25596197

  2. Adult-onset deficiency of acyl CoA:monoacylglycerol acyltransferase 2 protects mice from diet-induced obesity and glucose intolerance[S

    PubMed Central

    Banh, Taylor; Nelson, David W.; Gao, Yu; Huang, Ting-Ni; Yen, Mei-I; Yen, Chi-Liang E.

    2015-01-01

    Acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2 catalyzes triacylglycerol (TAG) synthesis, required in intestinal fat absorption. We previously demonstrated that mice without a functional MGAT2-coding gene (Mogat2−/−) exhibit increased energy expenditure and resistance to obesity induced by excess calories. One critical question raised is whether lacking MGAT2 during early development is required for the metabolic phenotypes in adult mice. In this study, we found that Mogat2−/− pups grew slower than wild-type littermates during the suckling period. To determine whether inactivating MGAT2 in adult mice is sufficient to confer resistance to diet-induced obesity, we generated mice with an inducible Mogat2-inactivating mutation. Mice with adult-onset MGAT2 deficiency (Mogat2AKO) exhibited a transient decrease in food intake like Mogat2−/− mice when fed a high-fat diet and a moderate increase in energy expenditure after acclimatization. They gained less weight than littermate controls, but the difference was smaller than that between wild-type and Mogat2−/− mice. The moderate reduction in weight gain was associated with reduced hepatic TAG and improved glucose tolerance. Similar protective effects were also observed in mice that had gained weight on a high-fat diet before inactivating MGAT2. These findings suggest that adult-onset MGAT2 deficiency mitigates metabolic disorders induced by high-fat feeding and that MGAT2 modulates early postnatal nutrition and may program metabolism later in life. PMID:25535286

  3. Muscle-specific Pikfyve gene disruption causes glucose intolerance, insulin resistance, adiposity, and hyperinsulinemia but not muscle fiber-type switching

    PubMed Central

    Ikonomov, Ognian C.; Sbrissa, Diego; Delvecchio, Khortnal; Feng, Han-Zhong; Cartee, Gregory D.; Jin, Jian-Ping

    2013-01-01

    The evolutionarily conserved kinase PIKfyve that synthesizes PtdIns5P and PtdIns(3,5)P2 has been implicated in insulin-regulated GLUT4 translocation/glucose entry in 3T3-L1 adipocytes. To decipher PIKfyve's role in muscle and systemic glucose metabolism, here we have developed a novel mouse model with Pikfyve gene disruption in striated muscle (MPIfKO). These mice exhibited systemic glucose intolerance and insulin resistance at an early age but had unaltered muscle mass or proportion of slow/fast-twitch muscle fibers. Insulin stimulation of in vivo or ex vivo glucose uptake and GLUT4 surface translocation was severely blunted in skeletal muscle. These changes were associated with premature attenuation of Akt phosphorylation in response to in vivo insulin, as tested in young mice. Starting at 1011 wk of age, MPIfKO mice progressively accumulated greater body weight and fat mass. Despite increased adiposity, serum free fatty acid and triglyceride levels were normal until adulthood. Together with the undetectable lipid accumulation in liver, these data suggest that lipotoxicity and muscle fiber switching do not contribute to muscle insulin resistance in MPIfKO mice. Furthermore, the 80% increase in total fat mass resulted from increased fat cell size rather than altered fat cell number. The observed profound hyperinsulinemia combined with the documented increases in constitutive Akt activation, in vivo glucose uptake, and gene expression of key enzymes for fatty acid biosynthesis in MPIfKO fat tissue suggest that the latter is being sensitized for de novo lipid anabolism. Our data provide the first in vivo evidence that PIKfyve is essential for systemic glucose homeostasis and insulin-regulated glucose uptake/GLUT4 translocation in skeletal muscle. PMID:23673157

  4. Management of Hypertensive Patients With Multiple Drug Intolerances: A Single-Center Experience of a Novel Treatment Algorithm.

    PubMed

    Antoniou, Sotiris; Saxena, Manish; Hamedi, Nadya; de Cates, Catherine; Moghul, Sakib; Lidder, Satnam; Kapil, Vikas; Lobo, Melvin D

    2016-02-01

    Multiple drug intolerance to antihypertensive medications (MDI-HTN) is an overlooked cause of nonadherence. In this study, 55 patients with MDI-HTN were managed with a novel treatment algorithm utilizing sequentially initiated monotherapies or combinations of maximally tolerated doses of fractional tablet doses, liquid formulations, transdermal preparations, and off-label tablet medications. A total of 10% of referred patients had MDI-HTN, resulting in insufficient pharmacotherapy and baseline office blood pressure (OBP) of 178±24/94±15 mm Hg. At baseline, patients were intolerant to 7.6±3.6 antihypertensives; they were receiving 1.4±1.1 medications. After 6 months on the novel MDI-HTN treatment algorithm, both OBP and home blood pressure (HBP) were significantly reduced, with patients receiving 2.0±1.2 medications. At 12 months, OBP was reduced from baseline by 17±5/9±3 mm Hg (P<.01, P<.05) and HBP was reduced by 11±5/12±3 mm Hg (P<.01 for both) while patients were receiving 1.9±1.1 medications. Application of a stratified medicine approach allowed patients to tolerate increased numbers of medications and achieved significant long-term lowering of blood pressure. PMID:26306794

  5. [Food intolerance].

    PubMed

    Zugasti Murillo, Ana

    2009-05-01

    Adverse food reactions are common in the general population. Nevertheless, our knowledge of the structure of food allergens and of the mechanisms involved is poor. In 1995 the European Academy of Allergology and Clinical Immunology suggested a classification based on the causative pathogenic mechanism. According to this classification, non-toxic reactions can be divided into food allergies when they recognize immunological mechanisms and food intolerance when there are no immunological implications. The treatment of food intolerance is avoidance of the particular food. There are specific treatments for some food intolerance (beta-galactosidases for the management of lactose intolerance). PMID:19627745

  6. Maternal BMI, glucose tolerance, and adverse pregnancy outcomes

    PubMed Central

    STUEBE, Alison M.; LANDON, Mark B.; LAI, Yinglei; SPONG, Catherine Y.; CARPENTER, Marshall W.; RAMIN, Susan M.; CASEY, Brian; WAPNER, Ronald J.; VARNER, Michael W.; ROUSE, Dwight J.; SCISCIONE, Anthony; CATALANO, Patrick; HARPER, Margaret; SAADE, George; SOROKIN, Yoram; PEACEMAN, Alan M.; TOLOSA, Jorge E.

    2012-01-01

    Objectives To estimate the association of pregravid body mass index (BMI), independent of 3-hour oral glucose tolerance test (OGTT) results, with pregnancy outcome. Study Design In this secondary analysis of a cohort of women with untreated mild gestational glucose intolerance, defined as 50g glucose loading test between 135 and 199 mg/dL and fasting glucose <95 mg/dL, we modeled the association between pregravid BMI, OGTT results, and both pregnancy complications and neonatal adiposity. Results Among 1250 participants, both pregravid BMI and glucose at hour 3 of the OGTT were associated with increased risk of gestational hypertension. Maternal pregravid BMI was also positively associated with LGA, and both maternal BMI and fasting glucose were associated with birth-weight z-score and neonatal fat mass. Conclusions Among women with untreated mild gestational glucose intolerance, pregravid BMI is associated with increased gestational hypertension, birth weight and neonatal fat mass, independent of OGTT values. PMID:22609018

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

    PubMed

    Samane, Samira; Christon, Raymond; Dombrowski, Luce; Turcotte, Stphane; Charrouf, Zoubida; Lavigne, Charles; Levy, Emile; Bachelard, Hlne; Amarouch, Hamid; Marette, Andr; 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

  8. Oral Supplementation with Non-Absorbable Antibiotics or Curcumin Attenuates Western Diet-Induced Atherosclerosis and Glucose Intolerance in LDLR?/? Mice Role of Intestinal Permeability and Macrophage Activation

    PubMed Central

    Ghosh, Siddhartha S.; Bie, Jinghua; Wang, Jing; Ghosh, Shobha

    2014-01-01

    Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as Type 2 Diabetes and atherosclerosis) has shifted the focus from Western diet-induced changes in gut microbiota per se to release of gut bacteria-derived products into circulation as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. Under physiological conditions, an intact intestinal barrier prevents this release of LPS underscoring the importance of examining and modulating the direct effects of Western diet on intestinal barrier function. In the present study we evaluated two strategies, namely selective gut decontamination and supplementation with oral curcumin, to modulate Western-diet (WD) induced changes in intestinal barrier function and subsequent development of glucose intolerance and atherosclerosis. LDLR?/? mice were fed WD for 16 weeks and either received non-absorbable antibiotics (Neomycin and polymyxin) in drinking water for selective gut decontamination or gavaged daily with curcumin. WD significantly increased intestinal permeability as assessed by in vivo translocation of FITC-dextran and plasma LPS levels. Selective gut decontamination and supplementation with curcumin significantly attenuated the WD-induced increase in plasma LPS levels (3.32 vs 1.90 or 1.51 EU/ml, respectively) and improved intestinal barrier function at multiple levels (restoring intestinal alkaline phosphatase activity and expression of tight junction proteins, ZO-1 and Claudin-1). Consequently, both these interventions significantly reduced WD-induced glucose intolerance and atherosclerosis in LDLR?/? mice. Activation of macrophages by low levels of LPS (50 ng/ml) and its exacerbation by fatty acids is likely the mechanism by which release of trace amounts of LPS into circulation due to disruption of intestinal barrier function induces the development of these diseases. These studies not only establish the important role of intestinal barrier function, but also identify oral supplementation with curcumin as a potential therapeutic strategy to improve intestinal barrier function and prevent the development of metabolic diseases. PMID:25251395

  9. Parathyroidectomy Ameliorates Glucose and Blood Pressure Control in a Patient with Primary Hyperparathyroidism, Type 2 Diabetes, and Hypertension

    PubMed Central

    Kumar, Alok; Singh, Sunita

    2015-01-01

    Effect of parathyroidectomy on glucose control and hypertension is controversial. Here, we report a case of a patient with primary hyperparathyroidism, type 2 diabetes mellitus, and hypertension in whom parathyroidectomy ameliorated both glucose control and blood pressure. Once high serum calcium levels were noticed, ultrasonography of neck confirmed a well-defined oval hypoechoic mass posterior to the right lobe of the thyroid, confirmed by scintiscan. Parathyroidectomy resulted in improvement of blood pressure and blood glucose. We could stop insulin and antihypertensive medications. We conclude that in patients with type 2 diabetes with vague complaints like fatigue, body ache, and refractory hypertension, as a part of the diagnostic workup, clinicians should also check serum calcium levels and parathyroid hormone to rule out hyperparathyroidism. Correction of hyperparathyroidism may result in improvement of hypertension and glucose control. PMID:26380561

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

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  11. Pharmacogenetic Association of Hypertension Candidate Genes with Fasting Glucose in the GenHAT Study

    PubMed Central

    Irvin, Marguerite R.; Lynch, Amy I.; Kabagambe, Edmond K.; Tiwari, Hemant K.; Barzilay, Joshua I.; Eckfeldt, John H.; Boerwinkle, Eric; Davis, Barry R.; Ford, Charles E.; Arnett, Donna K.

    2010-01-01

    Several clinical studies report increased risk of diabetes mellitus (DM) with pharmacologic treatment for hypertension (HTN). HTN genes may modify glycemic response to antihypertensive treatment. The current study examined the association of 24 single nucleotide polymorphisms (SNPs) in 11 HTN candidate genes with fasting glucose measured at 2, 4, and 6 years after treatment initiation. The study sample included participants free of diabetes at baseline in the Genetics of Hypertension Associated Treatment (GenHAT) study (N=9,309). GenHAT participants were randomized to receive treatment with a diuretic (chlorthalidone), calcium channel blocker (amlodipine), or ACE inhibitor (lisinopril). Mixed models for repeated measures were employed to test for gene and pharmacogenetic associations with fasting glucose during follow-up. Fasting glucose at year 2 increased on average 6.8 mg/dL, 4.8 mg/dL and 3.0 mg/dL from baseline in the chlorthalidone, amlodipine and lisinopril groups, respectively. Carrying the I allele (rs1799752) of the angiotensin-converting enzyme (ACE) I/D polymorphism was associated with lower fasting glucose levels (P=0.02). Additionally, an ACE promoter polymorphism (?262, rs4291) was associated with lower fasting glucose for the model AA/AT vs. TT which remained significant after correction for multiple testing (P=0.001). Finally, a SNP in the ?-subunit of the amiloride-sensitive epithelial sodium channel (SCNN1A, rs2228576) modified the association of amlodipine versus chlorthalidone treatment with fasting glucose (P<0.001). Further examination of these genes and their relationships with cardiometabolic disease could foster development of pharmacogenetic guidelines aimed to prevent increases in fasting glucose during antihypertensive treatment. PMID:20577119

  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. Maternal protein restriction induces early-onset glucose intolerance and alters hepatic genes expression in the peroxisome proliferator-activated receptor pathway in offspring

    PubMed Central

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Wang, Zhixin

    2015-01-01

    Aims/Introduction Maternal undernutrition during pregnancy and/or lactation can alter the offspring's response to environmental challenges, and thus increases the risk of the development of metabolic diseases at a later age. However, whether maternal protein restriction can modulate glucose metabolism in the early life of offspring is less understood. Furthermore, we explored the potential underlying mechanisms that illustrate this phenotype. Materials and Methods To test this hypothesis, we examined the offspring of C57BL/6J mice at weaning to determine the effects of feeding their mothers a low-protein diet or normal chow diet throughout pregnancy and lactation. Gene array experiments and quantitative real-time polymerase chain reaction were utilized to explore the altered hepatic genes expression. Results The offspring of dams fed a low-protein diet had a lower birthweight and bodyweight, impaired glucose tolerance, decreased insulin sensitivity, and decreased serum cholesterol at weaning. Using gene array experiments, 253 differentially expressed genes were identified in the liver tissues of the offspring between the two groups. Bioinformatic analyses showed that all differentially expressed genes were mapped to 11 pathways. We focused on the ‘peroxisome proliferator-activated receptor signaling pathway,’ because peroxisome proliferator-activated receptors have emerged as central regulators of glucose and lipid homeostasis. Quantitative real-time polymerase chain reaction was utilized for the validation of genes in the pathway. Conclusions A maternal low-protein diet during pregnancy and lactation promotes early-onset glucose intolerance in the offspring mice, and the altered hepatic genes expression in peroxisome proliferator-activated receptor signaling pathway could play role in regulating this phenomenon. PMID:25969711

  14. A choline-deficient diet exacerbates fatty liver but attenuates insulin resistance and glucose intolerance in mice fed a high-fat diet.

    PubMed

    Raubenheimer, Peter J; Nyirenda, Moffat J; Walker, Brian R

    2006-07-01

    Liver fat accumulation is proposed to link obesity and insulin resistance. To dissect the role of liver fat in the insulin resistance of diet-induced obesity, we altered liver fat using a choline-deficient diet. C57Bl/6 mice were fed a low-fat (10% of calories) or high-fat (45% of calories) diet for 8 weeks; during the final 4 weeks, diets were either choline deficient or choline supplemented. In choline replete animals, high-fat feeding induced weight gain, elevated liver triglycerides (171%), hyperinsulinemia, and glucose intolerance. Choline deficiency did not affect body or adipose depot weights but amplified liver fat accumulation with high-fat diet (281%, P < 0.01). However, choline deficiency lowered fasting plasma insulin (from 983 +/- 175 to 433 +/- 36 pmol/l, P < 0.01) and improved glucose tolerance on a high-fat diet. In mice on 30% fat diet, choline deficiency increased liver mRNA levels of the rate-limiting enzyme in phosphatidylcholine synthesis and of enzymes involved in free fatty acid esterification, without affecting those of de novo lipogenesis or fatty acid oxidation. We conclude that liver fat accumulation per se does not cause insulin resistance during high-fat feeding and that choline deficiency may shunt potentially toxic free fatty acids toward innocuous storage triglyceride in the liver. PMID:16804070

  15. Selective Elevation of Adiponectin Production by the Natural Compounds Derived from a Medicinal Herb Alleviates Insulin Resistance and Glucose Intolerance in Obese Mice

    PubMed Central

    Xu, Aimin; Wang, Hongbing; Hoo, Ruby L. C.; Sweeney, Gary; Vanhoutte, Paul. M.; Wang, Yu; Wu, Donghai; Chu, Wenjing; Qin, Guowei; Lam, Karen S. L.

    2009-01-01

    Adiponectin is an adipocyte-derived insulin-sensitizing hormone with antidiabetic, antiinflammatory, and antiatherosclerotic properties. A decreased serum level of adiponectin in obesity has been identified as an independent risk factor for diabetes and cardiovascular complications, suggesting that pharmacological intervention aimed at elevating adiponectin production might hold promise for the treatment and/or prevention of these diseases. Here we report the identification of two structurally related natural compounds (astragaloside II and isoastragaloside I) from the medicinal herb Radix Astragali that possess such an activity. Astragaloside II and isoastragaloside I selectively increased adiponectin secretion in primary adipocytes without any obvious effects on a panel of other adipokines. Furthermore, an additive effect on induction of adiponectin production was observed between these two compounds and rosiglitazone, a thiazolidinedione class of insulin-sensitizing drugs. Chronic administration of astragaloside II and isoastragaloside I in both dietary and genetic obese mice significantly elevated serum levels of total adiponectin and selectively increased the composition of its high molecular weight oligomeric complex. These changes were associated with an alleviation of hyperglycemia, glucose intolerance, and insulin resistance. By contrast, the beneficial effects of these two compounds on insulin sensitivity and glucose metabolism were diminished in adiponectin knockout mice. In conclusion, our results suggest that pharmacological elevation of circulating adiponectin alone is sufficient to ameliorate insulin resistance and diabetes and support the use of adiponectin as a biomarker for future drug discovery. The two natural compounds might provide the lead as a novel class of therapeutics for obesity-related diseases. PMID:18927219

  16. Lactose Intolerance

    MedlinePLUS

    ... when a person eats something containing lactose, an enzyme in the small intestine called lactase breaks down ... intolerance do not produce enough of the lactase enzyme to break down lactose. Instead, undigested lactose sits ...

  17. Lactose Intolerance

    MedlinePLUS

    ... lactose, the natural sugar found in milk and milk products. They have this condition because their bodies do ... people who think they are lactose intolerant avoid milk products and do not consume enough calcium and vitamin ...

  18. Cold intolerance

    MedlinePLUS

    ... intolerance is an abnormal sensitivity to a cold environment or cold temperatures. ... often very thin women) do not tolerate cold environments because they have very little body fat and are unable to keep warm.

  19. Lactose Intolerance

    MedlinePLUS

    ... foods are the best source of calcium, a mineral that's important for bone growth. Because growing teens ... Recipes for Teens With Lactose Intolerance Vitamins and Minerals Mineral Chart Smart Supermarket Shopping Nutrition & Fitness Center ...

  20. Diet supplementation with green tea extract epigallocatechin gallate prevents progression to glucose intolerance in db/db mice

    PubMed Central

    2012-01-01

    Background Green tea was suggested as a therapeutic agent for the treatment of diabetes more than 70 years ago, but the mechanisms behind its antidiabetic effect remains elusive. In this work, we address this issue by feeding a green tea extract (TEAVIGO) with a high content of epigallocatechin gallate (EGCG) or the thiazolidinedione PPAR-? agonist rosiglitazone, as positive control, to db/db mice, an animal model for diabetes. Methods Young (7 week-old) db/db mice were randomized and assigned to receive diets supplemented with or without EGCG or rosiglitazone for 10 weeks. Fasting blood glucose, body weight and food intake was measured along the treatment. Glucose and insulin levels were determined during an oral glucose tolerance test after 10 weeks of treatment. Pancreata were sampled at the end of the study for blinded histomorphometric analysis. Islets were isolated and their mRNA expression analyzed by quantitative RT-PCR. Results The results show that, in db/db mice, EGCG improves glucose tolerance and increases glucose-stimulated insulin secretion. EGCG supplementation reduces the number of pathologically changed islets of Langerhans, increases the number and the size of islets, and heightens pancreatic endocrine area. These effects occurred in parallel with a reduction in islet endoplasmic reticulum stress markers, possibly linked to the antioxidative capacity of EGCG. Conclusions This study shows that the green tea extract EGCG markedly preserves islet structure and enhances glucose tolerance in genetically diabetic mice. Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes. PMID:22333133

  1. Vitamin D and 1-hour post-load plasma glucose in hypertensive patients

    PubMed Central

    2014-01-01

    Background A plasma glucose value ≥155 mg/dl for 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high-risk for type-2 diabetes and with subclinical organ damage. We designed this study to address if 25-hydroxyvitamin D [25(OH)D] circulating levels are associated with glucose tolerance status, and in particular with 1-hour post-load plasma glucose levels. Methods We enrolled 300 consecutive Caucasian hypertensive never-treated outpatients (160 men and 140 women, aged 52.9 ± 9.2 years). Subjects underwent OGTT and measurements of 25(OH)D and standard laboratory tests. Estimated glomerular filtration rate (e-GFR) was calculated by CKD-EPI formula and insulin sensitivity was assessed by Matsuda-index. Results Among participants, 230 were NGT, 44 had impaired glucose tolerance (IGT) and 26 had type-2 diabetes. According to 1-h post-load plasma glucose cut-off point of 155 mg/dL, we divided NGT subjects into: NGT < 155 (n = 156) and NGT > 155 mg/dL (n = 74). NGT ≥ 155 had higher significant fasting and post-load glucose and insulin, parathyroid hormone and hs-CRP levels than NGT < 155. On the contrary, Matsuda-index, e-GFR, and 25(OH)D were significantly lower in NGT ≥ 155 than NGT < 155 subjects. In the multiple regression analysis, 25(OH)D levels resulted the major determinant of 1-h post-load plasma glucose in all population and in the four groups of glucose tolerance status. In the whole population, Matsuda-index, hs-CRP and e-GFR explained another 12.2%, 6.7% and 1.7% of its variation. Conclusions Our data demonstrate a significant and inverse relationship between 25(OH)D levels and glucose tolerance status, particularly with 1-h post-load glucose. PMID:24555478

  2. Role of adipose and hepatic atypical protein kinase C lambda (PKC?) in the development of obesity and glucose intolerance

    PubMed Central

    Habegger, Kirk M.; Matzke, Daniela; Ottaway, Nickki; Hembree, Jazzminn; Holland, Jenna; Raver, Christine; Mansfeld, Johannes; Mller, Timo D.; Perez-Tilve, Diego; Pfluger, Paul T.; Lee, Sang Jun; Diaz-Meco, Maria; Moscat, Jorge; Leitges, Michael; Tschp, Matthias H.; Hofmann, Susanna M.

    2012-01-01

    PKC?, an atypical member of the multifunctional protein kinase C family, has been implicated in the regulation of insulin-stimulated glucose transport and of the intracellular immune response. To further elucidate the role of this cellular regulator in diet-induced obesity and insulin resistance, we generated both liver (PKC-Alb) and adipose tissue (PKC-Ap2) specific knockout mice. Body weight, fat mass, food intake, glucose homeostasis and energy expenditure were evaluated in mice maintained on either chow or high fat diet (HFD). Ablation of PKC? from the adipose tissue resulted in mice that were indistinguishable from their wild-type littermates. However, PKC-Alb mice were resistant to diet-induced obesity (DIO). Surprisingly this DIO resistance was not associated with either a reduction in caloric intake or an increase in energy expenditure as compared with their wild-type littermates. Furthermore, these mice displayed an improvement in glucose tolerance. When maintained on chow diet, these mice were similar to wild types in respect to body weight and fat mass, yet insulin sensitivity was impaired compared with wt littermates. Taken together these data suggest that hepatic PKC? is modulating insulin-mediated glucose turnover and response to high fat diet feeding, thus offering a deeper understanding of an important target for anti-obesity therapeutics. PMID:23700535

  3. Maternal alcohol intake around the time of conception causes glucose intolerance and insulin insensitivity in rat offspring, which is exacerbated by a postnatal high-fat diet.

    PubMed

    Grdebjer, Emelie M; Anderson, Stephen T; Pantaleon, Marie; Wlodek, Mary E; Moritz, Karen M

    2015-07-01

    Alcohol consumption throughout pregnancy can cause metabolic dysregulation, including glucose intolerance in progeny. This study determined if periconceptional (PC) alcohol (12% v/v in a liquid diet) (PC:EtOH) consumed exclusively around conception results in similar outcomes in Sprague-Dawley rats. Control (C) rats were given a liquid diet containing no alcohol but matched to ensure equal caloric intake. PC maternal alcohol intake (from 4 days before conception until day 4 of gestation), resulted in offspring with elevated fasting plasma glucose (?10-25%, P < 0.05), impaired glucose tolerance (P < 0.05), and decreased insulin sensitivity (P < 0.01) at 6 months of age. This was associated with increased hepatic gluconeogenesis and sex-specific alterations in peripheral protein kinase B (AKT) signaling. These changes were accompanied by increased mRNA expression of DNA methyltransferases (DNMTs) 1, 3a, and 3b (1.5- to 1.9-fold, P < 0.05) in fetal liver in late gestation, suggesting PC:EtOH may cause epigenetic changes that predispose offspring to metabolic dysfunction. Exposure to a postnatal (PN) high-fat and cholesterol diet (HFD) from 3 months of age caused hyperinsulinemia (?2-fold increase, P < 0.001) and exacerbated the metabolic dysfunction in male offspring exposed to PC:EtOH but had no additive effects in females. Given many women may drink alcohol while planning a pregnancy, it is crucial to increase public awareness regarding the effects of alcohol consumption around conception on offspring health. PMID:25733565

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

    SciTech Connect

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

    2015-09-23

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

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

    PubMed

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

  6. 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

  7. Central inhibition of IKKβ/NF-κB signaling attenuates high-fat diet-induced obesity and glucose intolerance.

    PubMed

    Benzler, Jonas; Ganjam, Goutham K; Pretz, Dominik; Oelkrug, Rebecca; Koch, Christiane E; Legler, Karen; Stöhr, Sigrid; Culmsee, Carsten; Williams, Lynda M; Tups, Alexander

    2015-06-01

    Metabolic inflammation in the central nervous system might be causative for the development of overnutrition-induced metabolic syndrome and related disorders, such as obesity, leptin and insulin resistance, and type 2 diabetes. Here we investigated whether nutritive and genetic inhibition of the central IκB kinase β (IKKβ)/nuclear factor-κB (NF-κB) pathway in diet-induced obese (DIO) and leptin-deficient mice improves these metabolic impairments. A known prominent inhibitor of IKKβ/NF-κB signaling is the dietary flavonoid butein. We initially determined that oral, intraperitoneal, and intracerebroventricular administration of this flavonoid improved glucose tolerance and hypothalamic insulin signaling. The dose-dependent glucose-lowering capacity was profound regardless of whether obesity was caused by leptin deficiency or high-fat diet (HFD). To confirm the apparent central role of IKKβ/NF-κB signaling in the control of glucose and energy homeostasis, we genetically inhibited this pathway in neurons of the arcuate nucleus, one key center for control of energy homeostasis, via specific adeno-associated virus serotype 2-mediated overexpression of IκBα, which inhibits NF-κB nuclear translocation. This treatment attenuated HFD-induced body weight gain, body fat mass accumulation, increased energy expenditure, and reduced arcuate suppressor of cytokine signaling 3 expression, indicative for enhanced leptin signaling. These results reinforce a specific role of central proinflammatory IKKβ/NF-κB signaling in the development and potential treatment of DIO-induced comorbidities. PMID:25626735

  8. [Histamine intolerance].

    PubMed

    Hanuskov, E; Plevkov, J

    2013-01-01

    Histamine intolerance (HIT) is a pathological process that results from a disbalance between levels of released histamine and the ability of the body to metabolize it. Accumulated histamine leads to the onset of "histamine mediated" reactions which are usually excessive and decrease quality of life. Although we have a lot of knowledge about histamine intolerance, HIT is still vastly underestimated, because it manifests via the diversity of clinical symptoms, that are often misinterpreted by the patient and sometimes even by a physician. Clinical symptoms and their provocation by certain kinds of food, beverages and drugs are often attributed to the different diseases, such as food allergy and intolerance of sulfites, or other biogenic amines (eg. tyramine), mastocytosis, psychosomatic diseases or adverse drug reactions in general. Proper diagnosis of HIT followed by therapy based on histamine--free diet and supplementation of diaminooxidase can considerably improve patient's quality of life. PMID:23821960

  9. 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

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

    PubMed Central

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

    2014-01-01

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

  11. 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-related metabolic disorders. PMID:20735814

  12. Self-perceived lactose intolerance results in lower intakes of calcium and dairy foods and is associated with hypertension and diabetes in adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Self-perceived lactose intolerance may result in adverse dietary modifications; thus, more studies are needed to understand the prevalence of self-perceived lactose intolerance and how it relates to calcium intake and selected health conditions. The objective was to examine the effects of self-perce...

  13. 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

  14. Two-hour glucose predicts the development of hypertension over 5 years: the AusDiab study.

    PubMed

    Boyko, E J; Barr, E L M; Zimmet, P Z; Shaw, J E

    2008-03-01

    Elevated 2-h plasma glucose concentration (2hPG) from an oral glucose tolerance (OGTT) test more strongly predicts risk of subsequent cardiovascular disease than fasting plasma glucose (FPG), but the association between these glucose measurements and hypertension risk is less clear. We examined the association between 2hPG, FPG and risk of hypertension. We conducted a prospective observational study (The Australian Diabetes, Obesity and Lifestyle Study-AusDiab) among 4413 Australian residents who attended a baseline (1999-2000) and follow-up (2004-2005) examinations. Measurements included blood pressure (mean of two readings), 75 g OGTT, fasting insulin, anthropometrics, dietary and alcohol intake, medical history and physical activity. Hypertension was defined as a systolic blood pressure (SBP)> or =140 or a diastolic blood pressure (DBP)> or =90 mm Hg or treatment with medication for hypertension. HOMA-S was calculated as a measure of insulin sensitivity using the HOMA2 calculator. Hypertension developed in 14% of the 4306 subjects available for this analysis. Higher 2hPG was significantly related to greater risk of hypertension after adjustment for age, gender, FPG, BMI (baseline and difference), waist circumference (baseline and difference), education, exercise, alcohol intake, baseline SBP and smoking (OR (95% CI) 1.12 (1.01 to 1.23)), but no significant association was seen between FPG and hypertension in this model (1.02 (0.88-1.19)). Further adjustment for HOMA-S did not change these findings. Higher baseline 2hPG was more strongly associated with an increase in SBP than in DBP over 5 years. We conclude that higher 2hPG predicted future hypertension occurrence in this population. PMID:18046430

  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. 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 β-cells, and has potential as a novel strategy for treatment of diabetes. PMID:26504525

  17. Statin intolerance.

    PubMed

    Ahmad, Zahid

    2014-05-15

    The term statin intolerance refers to an inability to use statins because of muscle symptoms or elevated creatine kinase, and the major diagnostic challenge is to unambiguously link these to statin use. Roughly 5% to 10% of statin users develop statin intolerance, and because statin use is expected to increase--especially after recent updated guidelines have expanded the statin benefit groups--adverse effects from statins will become a growing issue. Unfortunately, the pathophysiology--and even the terminology--of statin-related muscle injury lacks clarity. Several risk factors have been identified, including advanced age, family history of myopathy and statin dose; many cases manifest only after patients are administered an interacting medication (e.g., azole antifungals, cimetidine, clarithromycin, erythromycin and cyclosporine). The diagnosis of myopathy remains challenging, especially because some patients can have normal serum creatine kinase levels despite demonstrable weakness and muscle biopsy-proven statin-induced myopathy. A statin withdrawal and rechallenge helps patients distinguish whether their myalgia symptoms are because of statins, but, in at least 1 clinical trial, even 5% of placebo-treated patients developed myalgias during a controlled withdrawal and rechallenge. No consensus exists for management of patients with statin intolerance. Many patients can eventually tolerate a statin but often at suboptimal doses. A subset of patients do well with nondaily regimens such as every other day or once weekly dosing. Some patients cannot tolerate statins at all, requiring nonstatin lipid-lowering medications--the benefit of which remains unclear with regard to preventing atherosclerotic events. Ultimately, statin intolerance undermines the drug adherence that is critical for achieving the benefits of lifelong lipid-lowering therapy. In conclusion, statin myopathy is a common challenge in lipid management, and further work is needed to establish a standard diagnostic criterion as well as treatment algorithms. PMID:24792743

  18. 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

  19. 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

  20. Lactose intolerance in a calf.

    PubMed

    Olchowy, T W; Linnabary, R D; Andrews, F M; Longshore, R C

    1993-01-01

    Lactose intolerance was identified as the cause of bovine neonatal diarrhea. Glucose and xylose oral absorptions were normal whereas lactose absorption was reduced relative to normal calves. Lactase deficiency is common in people but rarely reported in animals. The treatment of whole milk with lactase alleviated the diarrhea. PMID:8455177

  1. Maternal low-protein diet up-regulates the neuropeptide Y system in visceral fat and leads to abdominal obesity and glucose intolerance in a sex- and time-specific manner

    PubMed Central

    Han, Ruijun; Li, Aiyun; Li, Lijun; Kitlinska, Joanna B.; Zukowska, Zofia

    2012-01-01

    Neuropeptide Y (NPY) mediates stress-induced obesity in adult male mice by activating its Y2 receptor (Y2R) in visceral adipose tissue (VAT). Here, we studied whether the NPY-Y2R system is also activated by maternal low-protein diet (LPD) and linked to obesity in offspring. Prenatal LPD offspring had lower birth weights compared to normal-protein diet (NPD) offspring. Female prenatal and lactation stress (PLS) offspring from mothers fed an LPD developed abdominal adiposity and glucose intolerance associated with a 5-fold up-regulation of NPY mRNA and a 6-fold up-regulation of Y2R mRNA specifically in VAT, in addition to elevated platelet-rich-plasma (PRP) NPY, compared to control females fed a high-fat diet (HFD). Conversely, PLS male offspring showed lower NPY in PRP, a 10-fold decrease of Y2R mRNA in VAT, lower adiposity, and improved glucose tolerance compared to control males. Interestingly, prenatal LPD offspring cross-fostered to control lactating mothers had completely inverse metabolic and NPY phenotypes. Taken together, these findings suggested that maternal LPD activates the VAT NPY-Y2R system and increases abdominal adiposity and glucose intolerance in a sex- and time-specific fashion, suggesting that the peripheral NPY system is a potential mediator of programming for the offspring's vulnerability to obesity and metabolic syndrome.—Han, R., Li, A., Li, L., Kitlinska, J. B., Zukowska, Z. Maternal low-protein diet up-regulates the neuropeptide Y system in visceral fat and leads to abdominal obesity and glucose intolerance in a sex- and time-specific manner. PMID:22539639

  2. Lactose intolerance.

    PubMed

    Roberson, Charlene M

    Although lactose intolerance is very common it is not a serious health condition. The diagnosis is relatively simple and minimally invasive. Treatment is geared towards a life-long plan of management. Persons who have difficulty digesting lactose will learn by trial and error what food items cause distress and learn to avoid offending milk sugars. In addition many products are available over-the-counter to aid in digestion of lactose. Often these additives enable the person to consume lactose. Adequate amounts of calcium may be consumed by eating a carefully chosen diet containing lactose free sources of calcium in order to maintain healthy bone, nerve, and muscle development. PMID:15662762

  3. Glucose indices, frank and undetected diabetes in relation to hypertension and anthropometry in a South Indian rural population.

    PubMed

    Zaman, Forhad Akhtar; Pal, Ranabir; Zaman, Gaffar Sarwar; Swati, Indupalli Amruta; Kayyum, Abdul

    2011-01-01

    Diabetes has emerged as one of the world's biggest health problems and its prevalence is increasing at an alarming rate. This study was conducted to find out the magnitude of frank and undetected diabetes mellitus, including impaired glucose tolerance (IGT) among persons in rural Karnataka, and its relationship with associated risk factors like hypertension and anthropometry. This was a population-based, cross-sectional study on 1370 participants in the field practice area of KBN Medical College, conducted from April 2009 to March, 2010. Diabetes mellitus was noted among 19.78% of the participants, with an additional 12.04% with impaired glucose tolerance. Hypertension observed among participants with diabetes and impaired glucose tolerance was 65.13 and 53.94%, respectively. Effective primary prevention strategies have to be intensified among high-risk population groups, to promote awareness through behavior change communication. PMID:21727679

  4. 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

  5. Allergies and Intolerance

    MedlinePLUS

    ... and Intolerance The way in which celiac disease, gluten intolerance and wheat allergy are defined means a ... celiac disease may provide an incorrect diagnosis of gluten intolerance or wheat allergy. Understanding the differences between ...

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

    PubMed Central

    Anvari, Ebrahim; Wang, Xuan; Sandler, Stellan

    2015-01-01

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

  7. Glucose and the risk of hypertension in first-degree relatives of patients with type 2 diabetes.

    PubMed

    Janghorbani, Mohsen; Bonnet, Fabrice; Amini, Masoud

    2015-05-01

    To test the hypothesis that plasma glucose (PG) levels is associated with the incidence of hypertension (HT) in nondiabetic and non-hypertensive first-degree relatives (FDR) of people with type 2 diabetes (T2D). A total of 1089 FDR without diabetes and/or HT of consecutive patients with T2D 30-70 years old were examined and followed for a mean (s.d.) of 6.9 (1.7) years for HT incidence. At baseline and through follow-up, participants underwent a standard 75 gm 2-h oral glucose tolerance test. HT was defined according to the criteria of the Seventh Report of Joint National Committee. We used Cox proportional hazard models to estimate hazard ratio for incident HT and plotted a receiver operating characteristic curve to assess discrimination. The PG levels at baseline were associated with incidence of HT, independently of age, gender, obesity and high cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, education and systolic blood pressure. Those with impaired glucose tolerance were 54% (hazard ratio 1.54; 95% confidence interval (CI) 1.33, 1.77) more likely to develop HT than those with normal glucose tolerance. Those with impaired fasting glucose were also 23% (hazard ratio 1.23; 95% CI 1.01, 1.50) more likely to develop HT. High PG levels were consistently associated with incident HT. PMID:25693857

  8. [Insulin resistance and hypertension].

    PubMed

    He, R H; Ding, G X; Chen, J W

    1994-03-01

    In this study, we have measured plasma glucose and insulin levels at fasting and following an oral glucose load (75g) in 39 non-diabetic subjects (22 untreated hypertensive, 17 normotensive subjects). We also assessed plasma cholesterol (Ch), triglyceride (TG) levels and Na(+)-K(+)-pump activity in the membranes of their erythrocytes. Overall, hypertensive subjects have hypercholesterol, hypertriglyceride, glucose intolerance and hyperinsulinemia. These changes accorded with Syndrome X proposed by Reaven. In multivariant analysis, after correcting for age, BMI, diastolic pressure (DBP) was positively related to fasting, 1/2h insulin and insulin area under cure (AUC) (P < 0.05). Both systolic pressure (SBP) and DBP were negatively correlated to Na(+)-K(+)-pump (P < 0.01, 0.001), while Na(+)-K(+)-pump was negatively fasting, 1/2h, 1h, 2h insulin levels and insulin AUC (P < 0.05, 0.05, 0.01, 0.01, respectively). These results showed that insulin may affect Na(+)-K(+)-pump activity to develop hypertension independent of age and obese. We also postulated that insulin resistance was causal in the syndrome X, also one of factors developing coronary artery disease. PMID:7805525

  9. Chemical intolerance.

    PubMed

    Dantoft, Thomas M; Andersson, Linus; Nordin, Steven; Skovbjerg, Sine

    2015-01-01

    Chemical intolerance (CI) is a term used to describe a condition in which the sufferer experiences a complex array of recurrent unspecific symptoms attributed to low-level chemical exposure that most people regard as unproblematic. Severe CI constitutes the distinguishing feature of multiple chemical sensitivity (MCS). The symptoms reported by CI subjects are manifold, involving symptoms from multiple organs systems. In severe cases of CI, the condition can cause considerable life-style limitations with severe social, occupational and economic consequences. As no diagnostic tools for CI are available, the presence of the condition can only be established in accordance to criteria definitions. Numerous modes of action have been suggested to explain CI, with the most commonly discussed theories involving the immune system, central nervous system, olfactory and respiratory systems as well as altered metabolic capacity, behavioral conditioning and emotional regulation. However, in spite of more than 50 years of research, there is still a great deal of uncertainties regarding the event(s) and underlying mechanism( s) behind symptom elicitation. As a result, patients are often misdiagnosed or offered health care solutions with limited or no effect, and they experience being met with mistrust and doubt by health care professionals, the social care system and by friends and relatives. Evidence-based treatment options are currently unavailable, however, a person-centered care model based on a multidisciplinary treatment approach and individualized care plans have shown promising results. With this in mind, further research studies and health care solutions should be based on a multifactorial and interdisciplinary approach. PMID:26088215

  10. Hypoxia-induced glucose-6-phosphate dehydrogenase overexpression and -activation in pulmonary artery smooth muscle cells: implication in pulmonary hypertension

    PubMed Central

    Chettimada, Sukrutha; Gupte, Rakhee; Rawat, Dhwajbahadur; Gebb, Sarah A.; McMurtry, Ivan F.

    2014-01-01

    Severe pulmonary hypertension is a debilitating disease with an alarmingly low 5-yr life expectancy. Hypoxia, one of the causes of pulmonary hypertension, elicits constriction and remodeling of the pulmonary arteries. We now know that pulmonary arterial remodeling is a consequence of hyperplasia and hypertrophy of pulmonary artery smooth muscle (PASM), endothelial, myofibroblast, and stem cells. However, our knowledge about the mechanisms that cause these cells to proliferate and hypertrophy in response to hypoxic stimuli is still incomplete, and, hence, the treatment for severe pulmonary arterial hypertension is inadequate. Here we demonstrate that the activity and expression of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, are increased in hypoxic PASM cells and in lungs of chronic hypoxic rats. G6PD overexpression and -activation is stimulated by H2O2. Increased G6PD activity contributes to PASM cell proliferation by increasing Sp1 and hypoxia-inducible factor 1α (HIF-1α), which directs the cells to synthesize less contractile (myocardin and SM22α) and more proliferative (cyclin A and phospho-histone H3) proteins. G6PD inhibition with dehydroepiandrosterone increased myocardin expression in remodeled pulmonary arteries of moderate and severe pulmonary hypertensive rats. These observations suggest that altered glucose metabolism and G6PD overactivation play a key role in switching the PASM cells from the contractile to synthetic phenotype by increasing Sp1 and HIF-1α, which suppresses myocardin, a key cofactor that maintains smooth muscle cell in contractile state, and increasing hypoxia-induced PASM cell growth, and hence contribute to pulmonary arterial remodeling and pathogenesis of pulmonary hypertension. PMID:25480333

  11. [The assessment of glucose tolerance in hypertensive subjects treated with amlodipine].

    PubMed

    Panuccio, D; Romani, A; Trabatti, M R; Romanelli, R; Nardi, R

    1993-10-01

    The authors studied the side effects of amlodipine on glucose metabolism, carrying out an oral glucose tolerance test before and after 8-10 days of treatment, in a group of subjects with normal glucose tolerance. No significant variation in the average plasma glucose and insulin levels was observed. Nevertheless, in some cases, during amlodipine therapy, a decrease in glucose plasma level was found. PMID:8258265

  12. Sardine peptide with angiotensin I-converting enzyme inhibitory activity improves glucose tolerance in stroke-prone spontaneously hypertensive rats.

    PubMed

    Otani, Lila; Ninomiya, Toshio; Murakami, Megumi; Osajima, Katsuhiro; Kato, Hisanori; Murakami, Tetsuo

    2009-10-01

    An enzymatic hydrolysate of sardine protein (sardine peptide, SP) derived from sardine muscle possesses angiotensin I-converting enzyme (ACE) inhibitory activity. In the present study, we investigated the effect of SP on the blood glucose levels in stroke-prone spontaneously hypertensive rats (SHRSPs). Ten-week-old SHRSPs were assigned to three groups. The control group was given tap water for 4 weeks, while the experimental groups were given water containing SP (1 g/kg/d) or an ACE inhibitor, captopril (8 mg/kg/d). Treatment with SP and captopril decreased ACE activity in the kidney, aorta, and mesentery. There were no differences in fasting blood glucose levels among the three groups, whereas SP and captopril administration significantly suppressed the increase in blood glucose after glucose loading in the control SHRSPs. No difference was observed in plasma insulin levels among the three groups. Thus treatment with captopril and ACE-inhibitory sardine peptides ameliorated the glucose tolerance of this rat strain. PMID:19809178

  13. Lactose Intolerance (For Parents)

    MedlinePLUS

    ... to Expect Lactose Intolerance KidsHealth > Parents > Diseases & Conditions > Digestive System > Lactose Intolerance Print A A A Text Size ... THIS TOPIC Calcium and Your Child Milk Allergy Digestive System Milk Allergy in Infants About Recipes for Kids ...

  14. Amelioration of Obesity, Glucose Intolerance, and Oxidative Stress in High-Fat Diet and Low-Dose Streptozotocin-Induced Diabetic Rats by Combination Consisting of Curcumin with Piperine and Quercetin

    PubMed Central

    Kaur, Ginpreet; C, Meena

    2012-01-01

    Curcumin is an important nutraceutical that has enormous potential for a variety of diseases, but the medicinal properties of curcumin cannot be utilized due to its low in vivo bioavailability. Therefore, in view of the foregoing, there is an extensive need for combinatorial extract curcumin with piperine and quercetin which may enhance bioavailability of oral curcumin by inhibiting the enzymes responsible for the metabolism of curcumin. Thus, the present study investigated the effect of combinatorial extract of curcumin on obesity, glucose intolerance, and oxidative stress in high fat diet and low-dose streptozotocin-induced rats. Oral administration of combinatorial extract for 28 days significantly (P < 0.05) reduced PGL (64.84%), PTG (88.94%), LDL (26.38%) and PTC (50.23%) levels, respectively and improved glucose tolerance (P < 0.05) significantly to exogenously administered glucose (2?g/kg) at 60, 90, and 120?min interval on OGTT. The results for antioxidant potential indicate that at 100?mg/kg dose of combinatorial extract of curcumin significantly prevented the high-fat diet and low-dose streptozotocin-induced changes in the oxidative stress parameters (P < 0.01) which supports popular medicinal uses of this combinatorial extract as antihyperglycemic and hypolipidemic and is likely to bring this promising natural product to the forefront of therapeutic agents in the in the treatment of metabolic syndrome. PMID:22474599

  15. 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, Stphane; 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 (meanS.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

  16. Hypertension

    PubMed Central

    LePine, Todd

    2012-01-01

    Hypertension is responsible for roughly one-in-six adult deaths annually in the United States and is associated with five of the top nine causes of death.1 Ten trillion dollars is the estimated annual cost worldwide of the direct and indirect effects of hypertension.2,3 In the U.S. alone, costs estimated at almost $74 billion in 2009 placed a huge economic burden on the health care system.4 The prevalence of hypertension increases with advancing age to the point where more than half of people 60 to 69 years of age and at least three-fourths of those 70 years of age and older are affected.5 Most individuals with hypertension do not have it adequately controlled.1,6 Medication noncompliance due to avoidance of side effects is suggested to be a primary factor.6 The epidemic incidence of hypertension and its significant cost to society indicate that a well-tolerated, cost-effective approach to treatment is urgently needed. PMID:24278815

  17. Hypertension.

    PubMed

    Poulter, Neil R; Prabhakaran, Dorairaj; Caulfield, Mark

    2015-08-22

    Raised blood pressure is the biggest single contributor to the global burden of disease and to global mortality. The numbers of people affected and the prevalence of high blood pressure worldwide are expected to increase over the next decade. Preventive strategies are therefore urgently needed, especially in less developed countries, and management of hypertension must be optimised. Genetic advances in some rare causes of hypertension have been made lately, but the aggregate effect on blood pressure of all the genetic loci identified to date is small. Hence, intervention on key environmental determinants and effective implementation of trial-based therapies are needed. Three-drug combinations can control hypertension in about 90% of patients but only if resources allow identification of patients and drug delivery is affordable. Furthermore, assessment of optimal drug therapy for each ethnic group is needed. PMID:25832858

  18. Growth Hormone Receptor Antagonist Transgenic Mice Are Protected From Hyperinsulinemia and Glucose Intolerance Despite Obesity When Placed on a HF Diet

    PubMed Central

    Yang, Tianxu; Householder, Lara A.; Lubbers, Ellen R.; List, Edward O.; Troike, Katie; Vesel, Clare; Duran-Ortiz, Silvana; Kopchick, John J.

    2015-01-01

    Reduced GH levels have been associated with improved glucose metabolism and increased longevity despite obesity in multiple mouse lines. However, one mouse line, the GH receptor antagonist (GHA) transgenic mouse, defies this trend because it has reduced GH action and increased adiposity, but glucose metabolism and life span are similar to controls. Slight differences in glucose metabolism and adiposity profiles can become exaggerated on a high-fat (HF) diet. Thus, in this study, male and female GHA and wild-type (WT) mice in a C57BL/6 background were placed on HF and low-fat (LF) diets for 11 weeks, starting at 10 weeks of age, to assess how GHA mice respond to additional metabolic stress of HF feeding. On a HF diet, all mice showed significant weight gain, although GHA gained weight more dramatically than WT mice, with males gaining more than females. Most of this weight gain was due to an increase in fat mass with WT mice increasing primarily in the white adipose tissue perigonadal depots, whereas GHA mice gained in both the sc and perigonadal white adipose tissue regions. Notably, GHA mice were somewhat protected from detrimental glucose metabolism changes on a HF diet because they had only modest increases in serum glucose levels, remained glucose tolerant, and did not develop hyperinsulinemia. Sex differences were observed in many measures with males reacting more dramatically to both a reduction in GH action and HF diet. In conclusion, our findings show that GHA mice, which are already obese, are susceptible to further adipose tissue expansion with HF feeding while remaining resilient to alterations in glucose homeostasis. PMID:25406017

  19. Growth hormone receptor antagonist transgenic mice are protected from hyperinsulinemia and glucose intolerance despite obesity when placed on a HF diet.

    PubMed

    Yang, Tianxu; Householder, Lara A; Lubbers, Ellen R; List, Edward O; Troike, Katie; Vesel, Clare; Duran-Ortiz, Silvana; Kopchick, John J; Berryman, Darlene E

    2015-02-01

    Reduced GH levels have been associated with improved glucose metabolism and increased longevity despite obesity in multiple mouse lines. However, one mouse line, the GH receptor antagonist (GHA) transgenic mouse, defies this trend because it has reduced GH action and increased adiposity, but glucose metabolism and life span are similar to controls. Slight differences in glucose metabolism and adiposity profiles can become exaggerated on a high-fat (HF) diet. Thus, in this study, male and female GHA and wild-type (WT) mice in a C57BL/6 background were placed on HF and low-fat (LF) diets for 11 weeks, starting at 10 weeks of age, to assess how GHA mice respond to additional metabolic stress of HF feeding. On a HF diet, all mice showed significant weight gain, although GHA gained weight more dramatically than WT mice, with males gaining more than females. Most of this weight gain was due to an increase in fat mass with WT mice increasing primarily in the white adipose tissue perigonadal depots, whereas GHA mice gained in both the sc and perigonadal white adipose tissue regions. Notably, GHA mice were somewhat protected from detrimental glucose metabolism changes on a HF diet because they had only modest increases in serum glucose levels, remained glucose tolerant, and did not develop hyperinsulinemia. Sex differences were observed in many measures with males reacting more dramatically to both a reduction in GH action and HF diet. In conclusion, our findings show that GHA mice, which are already obese, are susceptible to further adipose tissue expansion with HF feeding while remaining resilient to alterations in glucose homeostasis. PMID:25406017

  20. Salivary melatonin levels and sleep-wake rhythms in pregnant women with hypertensive and glucose metabolic disorders: A prospective analysis.

    PubMed

    Shimada, Mieko; Seki, Hiroyuki; Samejima, Michikazu; Hayase, Mako; Shirai, Fumie

    2016-03-10

    In preeclampsia and gestational diabetes, the sympathetic nerves are activated, leading to disrupted sleep. Melatonin, which transmits information to regulate the sleep-wake rhythm and other such biorhythms, has been implicated in insulin resistance, antioxidant behaviors, and metabolic syndrome. In addition, its reduced secretion increases the risk of hypertension and diabetes. The aim of this study was to elucidate the features of melatonin secretion, sleep quality, and sleep-wake rhythms in pregnant women with complications. Fifty-eight pregnant women with pregnancy complications (hypertensive or glucose metabolic disorders) and 40 healthy pregnant women completed questionnaires, including sleep logs and the Pittsburgh Sleep Quality Index (PSQI), during the second to third trimesters. Their salivary melatonin levels were also measured. Pregnant women with complications had significantly lower morning (p < 0.001), daytime (p < 0.01), evening (p < 0.001), night (p < 0.01), daily mean (p < 0.001), peak (p < 0.001), and bottom (p < 0.01) melatonin values than healthy pregnant women. Pregnant women with complications also had significantly smaller melatonin amplitudes than healthy pregnant women (p < 0.001). Among pregnant women with complications, the duration (p < 0.05) and frequency (p < 0.01) of wake after sleep-onset were significantly greater in the poor sleep group than in the favorable sleep group which was divided by PSQI cutoff value. Pregnant women with hypertensive or glucose metabolic disorder complications had smaller circadian variation in salivary melatonin secretion, and their values were lower throughout the day than healthy pregnant women. PMID:26853813

  1. Synergistic effect of uricase blockade plus physiological amounts of fructose-glucose on glomerular hypertension and oxidative stress in rats

    PubMed Central

    Tapia, Edilia; Cristóbal, Magdalena; García-Arroyo, Fernando E.; Soto, Virgilia; Monroy-Sánchez, Fabiola; Pacheco, Ursino; Lanaspa, Miguel A.; Roncal-Jiménez, Carlos A.; Cruz-Robles, David; Ishimoto, Takuji; Madero, Magdalena; Johnson, Richard J.

    2013-01-01

    Fructose in sweetened beverages (SB) increases the risk for metabolic and cardiorenal disorders, and these effects are in part mediated by a secondary increment in uric acid (UA). Rodents have an active uricase, thus requiring large doses of fructose to increase plasma UA and to induce metabolic syndrome and renal hemodynamic changes. We therefore hypothesized that the effects of fructose in rats might be enhanced in the setting of uricase inhibition. Four groups of male Sprague-Dawley rats (n = 7/group) were studied during 8 wk: water + vehicle (V), water + oxonic acid (OA; 750 mg/k BW), sweetened beverage (SB; 11% fructose-glucose combination) + V, and SB + OA. Systemic blood pressure, plasma UA, triglycerides (TG), glucose and insulin, glomerular hemodynamics, renal structural damage, renal cortex and liver UA, TG, markers of oxidative stress, mitDNA, fructokinase, and fatty liver synthase protein expressions were evaluated at the end of the experiment. Chronic hyperuricemia and SB induced features of the metabolic syndrome, including hypertension, hyperuricemia, hyperglycemia, and systemic and hepatic TG accumulation. OA alone also induced glomerular hypertension, and SB alone induced insulin resistance. SB + OA induced a combined phenotype including metabolic and renal alterations induced by SB or OA alone and in addition also acted synergistically on systemic and glomerular pressure, plasma glucose, hepatic TG, and oxidative stress. These findings explain why high concentrations of fructose are required to induce greater metabolic changes and renal disease in rats whereas humans, who lack uricase, appear to be much more sensitive to the effects of fructose. PMID:23303409

  2. The effects of antihypertensive drugs on chromium status, glucose metabolism, and antioxidant and inflammatory indices in spontaneously hypertensive rats.

    PubMed

    Suliburska, Joanna; Krejpcio, Zbigniew; Staniek, Halina; Krl, Ewelina; Bogdanski, Pawel; Kupsz, Justyna; Hertig, Iwona

    2014-01-01

    The long-term use of hypotensive drugs may cause side effects, including impaired glucose metabolism and mineral status. This study tested the hypothesis that some hypotensive drugs can affect tissular chromium levels and indices of glucose metabolic and antioxidant potential in rats. The experiment was performed on 40 male spontaneously hypertensive rats (SHRs), which were assigned to five groups: control (C), with perindopril (PR), with metoprolol (MT), with indapamide (ID), and with amlodipine (AM). All rats were provided ad libitum standard diet (with or without drugs) and distilled water for 45 days. Glucose and insulin levels, along with total antioxidant status (TAS) and concentrations of TNF-alpha and C-reactive protein, were assayed in serum. Chromium concentrations in the liver and kidney were determined using the flame atomic absorption spectrometry method. Detailed statistical analysis was performed using Statistica for Windows 10.0 (StatSoft, Poland). One-way analysis of variance (ANOVA), followed by a post hoc Tukey test, was used to compare the data between groups. Treatment with indapamide and amlodipine resulted in significantly higher chromium concentrations in the liver and kidney (AM) of the rats, compared with the control group. A markedly higher concentration of glucose was found in the ID group. Treatment with amlodipine significantly increased TAS levels in serum and decreased TNF-alpha concentration in serum of the rats. A significant positive correlation between chromium concentration in tissues and serum TAS level was observed, as was a significant negative correlation between chromium concentration in the kidneys, and TNF-alpha and glucose levels in serum. In conclusion, the administration of amlodipine may lead to an increase in chromium accumulation in the internal organs, which is associated with increased antioxidant status and suppression of the inflammatory response of cells in SHRs. PMID:24249586

  3. Management of lactose intolerance.

    PubMed

    Tamm, A

    1994-01-01

    The management of lactose intolerance comprises two parts: (1) the basic principles of treatment in persons intolerant to a dietary dose of lactose, and (2) main manoeuvres to reduce the lactose content in food, and/or consumption of special products of milk or exogenous lactase enzyme. The tactics of management depend on the type of hypolactasia, the severity of intolerance, and on the age of the patient. Special attention is paid to the development of lactose intolerance in some patients via iatrogenic mechanisms such as certain drugs, gastric surgery and ionizing radiation. PMID:8042018

  4. The effect of oral glucose loads on tissue metabolism during angiotensin II receptor and beta-receptor blockade in obese hypertensive subjects.

    PubMed

    Boschmann, M; Kreuzberg, U; Engeli, S; Adams, F; Franke, G; Klaua, S; Scholze, J; Weidinger, G; Luft, F C; Sharma, A M; Jordan, J

    2006-05-01

    AT1 receptor blockers and ACE inhibitors decrease the risk for new onset diabetes mellitus. The phenomenon could be related to a direct angiotensin II effect on tissue metabolism. To address the issue, we recruited eighteen obese hypertensive patients. Patients were randomized to double-blind treatment with either valsartan (n = 8) or atenolol (n = 10) for thirteen weeks. They underwent an oral glucose tolerance test before and during active treatment, while metabolism was monitored through subcutaneous and intramuscular microdialysis and indirect calorimetry. After glucose ingestion, venous glucose and insulin concentrations increased rapidly while systemic free fatty acid concentrations were suppressed. Dialysate glucose and lactate concentrations increased briskly in adipose tissue and in skeletal muscle. Dialysate glycerol decreased profoundly in both tissues. Respiratory quotient increased markedly after glucose ingestion. These responses were identical at baseline and during active treatment either drug. We conclude that AT1 receptor blockade in obese hypertensive patients has no effect on interstitial glucose supply, lipolysis, and substrate oxidation. One possible explanation is that angiotensin II levels in obese hypertensives are not sufficient to elicit the metabolic changes that have been observed after direct angiotensin II application. The exact mechanism by which inhibition of the renin-angiotensin-aldosterone system decreases the diabetes risk remains unresolved and requires further study. PMID:16718629

  5. 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

  6. The heme oxygenase system attenuates pancreatic lesions and improves insulin sensitivity and glucose metabolism in deoxycorticosterone acetate hypertension.

    PubMed

    Ndisang, Joseph Fomusi; Jadhav, Ashok

    2010-01-01

    Recent clinical reports indicate that impaired glucose tolerance is a common phenomenon in primary aldosteronism. Aldosterone stimulates NF-kappaB and activating protein-1 (AP-1) to cause oxidative injury. Elevated oxidative stress impairs insulin signaling. We recently showed that the heme oxygenase (HO) system lowers blood pressure (BP) in deoxycorticosterone-acetate (DOCA)+salt hypertension, a model of primary aldosteronism. However, the effect of the HO system on insulin sensitivity in this model remains largely unclear. Here we report the effects of the HO-inducer hemin and the HO-blocker [chromium mesoporphyrin (CrMP)] on insulin sensitivity/glucose metabolism. Our experimental design included the following 10 groups: (A) controls [(i) surgery-free or normal Sprague-Dawley (SD), (ii) uninephrectomized (UnX)-sham, (iii) UnX+salt (0.9%NaCl+0.2%KCl) and (iv) UnX+DOCA]; (B) DOCA+salt; (C) hemin+DOCA+salt; (D) hemin+CrMP+DOCA+salt; (E) CrMP+DOCA+salt; (F) vehicle-treated rats and (G) normal SD+hemin. Hemin therapy lowered BP and increased plasma insulin and the insulin-sensitizing protein adiponectin with slight but significant reduction of glycemia, while CrMP abolished the hemin effects. Furthermore, hemin improved intraperitoneal glucose and insulin tolerance, suggesting that although DOCA+salt-hypertensive rats were normoglycemic, insulin signaling may be impaired. In contrast, the HO-inhibitor CrMP aggravated insulin resistance and exacerbated glucose and insulin tolerance. Interestingly, the enhanced insulin sensitization in hemin-treated animals was accompanied by reduced urinary/gastrocnemius muscle 8-iso-prostaglandin F(2alpha) (8-isoprostane), inflammatory/oxidative transcription factors like NF-kappaB, AP-1, JNK, and heme content, whereas HO-1, HO-activity, cGMP, and plasma/gastrocnemius muscle antioxidants including bilirubin, ferritin, SOD, catalase, and the total antioxidant capacity were increased. Similarly, hemin enhanced pancreatic HO, cGMP, and cAMP but suppressed 8-isoprostane and attenuated pancreatic histopathological lesions including fibrosis, interstitial edema, acinar cell necrosis, vacuolization, and mononuclear cell infiltration, with corresponding improvement of insulin production. Our results suggest that impaired insulin signaling may be a forerunner to hyperglycemia in aldosteronism. By preserving pancreatic morphology, potentiating insulin signaling, and lowering BP, the HO system may prevent metabolic and cardiovascular complications in aldosteronism. PMID:19864334

  7. Genetics Home Reference: Lactose intolerance

    MedlinePLUS

    ... with a long history of dependence on unfermented milk products as an important food source. For example, only ... do people use for lactose intolerance? alactasia dairy product intolerance hypolactasia lactose malabsorption milk sugar intolerance For more information about naming genetic ...

  8. Prevalence of Diabetes and Impaired Fasting Glucose in Hypertensive Adults in Rural China: Far from Leveling-Off

    PubMed Central

    Yu, Shasha; Sun, Zhaoqing; Zheng, Liqiang; Guo, Xiaofan; Yang, Hongmei; Sun, Yingxian

    2015-01-01

    In recent years data from many investigations has shown a leveling–off trend in diabetes incidence. In order to explain the diabetes epidemic in rural China during the past ten years, we conducted a survey from July 2012 to August 2013. Data from comprehensive questionnaires, physical examinations, and blood tests were obtained from 5919 residents with hypertension, aged ≥ 35 years. Diabetes and impaired fasting glucose (IFG) were defined according to the American Diabetes Association (ADA) criteria. The overall prevalence of diabetes and IFG were 15.3% (13.6% in men, 16.8% in women) and 40.7% (44.1% in men, 34.7% in women) in the hypertensive rural Chinese population. The prevalence of previously diagnosed diabetes was 6.5% (4.6% in men, 8.4% in women). The prevalence of undiagnosed diabetes was 8.7% (9.0% in men, 8.5% in women). Multivariate logistic regression revealed that increasing age, drinking, overweight or obesity, systolic blood pressure, low HDL-C, high total cholesterol and triglycerides increased the risk of diabetes (p < 0.05). Diabetes is thus still prevalent in rural areas of China and is manifesting an accelerating trend. It remains an important public health problem in China, especially in rural areas and routine assessment for the early detection and treatment of diabetes should be emphasized. PMID:26610531

  9. Secondary lactose intolerance in a neonatal goat.

    PubMed

    Weese, J S; Kenney, D G; O'Connor, A

    2000-08-01

    A 2-week-old Toggenburg kid was evaluated for persistent diarrhea and poor body condition. The herd had high morbidity and mortality associated with diarrhea in neonatal kids. Lactose intolerance was diagnosed on the basis of results of a lactose tolerance test and glucose absorption test. Clinically normal herdmates were used as control animals. The kid responded to lactase supplementation. Cryptosporidium organisms were detected in feces of several affected kids during episodes of acute diarrhea. Lactose intolerance was presumed to have developed secondary to intestinal cryptosporidiosis. PMID:10935043

  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 Duncans 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-?, SAA2, CRP and MCP-1) via attenuation of nuclear transcription factors (NF-?B). 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. Adult-onset deficiency of acyl CoA:monoacylglycerol acyltransferase 2 protects mice from diet-induced obesity and glucose intolerance.

    PubMed

    Banh, Taylor; Nelson, David W; Gao, Yu; Huang, Ting-Ni; Yen, Mei-I; Yen, Chi-Liang E

    2015-02-01

    Acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2 catalyzes triacylglycerol (TAG) synthesis, required in intestinal fat absorption. We previously demonstrated that mice without a functional MGAT2-coding gene (Mogat2(-/-)) exhibit increased energy expenditure and resistance to obesity induced by excess calories. One critical question raised is whether lacking MGAT2 during early development is required for the metabolic phenotypes in adult mice. In this study, we found that Mogat2(-/-) pups grew slower than wild-type littermates during the suckling period. To determine whether inactivating MGAT2 in adult mice is sufficient to confer resistance to diet-induced obesity, we generated mice with an inducible Mogat2-inactivating mutation. Mice with adult-onset MGAT2 deficiency (Mogat2(AKO)) exhibited a transient decrease in food intake like Mogat2(-/-) mice when fed a high-fat diet and a moderate increase in energy expenditure after acclimatization. They gained less weight than littermate controls, but the difference was smaller than that between wild-type and Mogat2(-/-) mice. The moderate reduction in weight gain was associated with reduced hepatic TAG and improved glucose tolerance. Similar protective effects were also observed in mice that had gained weight on a high-fat diet before inactivating MGAT2. These findings suggest that adult-onset MGAT2 deficiency mitigates metabolic disorders induced by high-fat feeding and that MGAT2 modulates early postnatal nutrition and may program metabolism later in life. PMID:25535286

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

    PubMed Central

    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 PPAR?, 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 (PPAR?, 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

  13. The molecular basis of lactose intolerance.

    PubMed

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

    2005-01-01

    A staggering 4000 million people cannot digest lactose, the sugar in milk, properly. All mammals, apart from white Northern Europeans and few tribes in Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into galactose and glucose, after weaning. Lactose intolerance causes gut and a range of systemic symptoms, though the threshold to lactose varies considerably between ethnic groups and individuals within a group. The molecular basis of inherited hypolactasia has yet to be identified, though two polymorphisms in the introns of a helicase upstream from the lactase gene correlate closely with hypolactasia, and thus lactose intolerance. The symptoms of lactose intolerance are caused by gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial toxins may play a key role in several other diseases, such as diabetes, rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose intolerance has been exacerbated because of the addition of products containing lactose to various foods and drinks without being on the label. Lactose intolerance fits exactly the illness that Charles Darwin suffered from for over 40 years, and yet was never diagnosed. Darwin missed something else--the key to our own evolution--the Rubicon some 300 million years ago that produced lactose and lactase in sufficient amounts to be susceptible to natural selection. PMID:16805112

  14. The molecular basis of lactose intolerance.

    PubMed

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

    2009-01-01

    A staggering 4000 million people cannot digest lactose, the sugar in milk, properly. All mammals, apart from white Northern Europeans and few tribes in Africa and Asia, lose most of their lactase, the enzyme that cleaves lactose into galactose and glucose, after weaning. Lactose intolerance causes gut and a range of systemic symptoms, though the threshold to lactose varies considerably between ethnic groups and individuals within a group. The molecular basis of inherited hypolactasia has yet to be identified, though two polymorphisms in the introns of a helicase upstream from the lactase gene correlate closely with hypolactasia, and thus lactose intolerance. The symptoms of lactose intolerance are caused by gases and toxins produced by anaerobic bacteria in the large intestine. Bacterial toxins may play a key role in several other diseases, such as diabetes, rheumatoid arthritis, multiple sclerosis and some cancers. The problem of lactose intolerance has been exacerbated because of the addition of products containing lactose to various foods and drinks without being on the label. Lactose intolerance fits exactly the illness that Charles Darwin suffered from for over 40 years, and yet was never diagnosed. Darwin missed something else--the key to our own evolution--the Rubicon some 300 million years ago that produced lactose and lactase in sufficient amounts to be susceptible to natural selection. PMID:19960866

  15. 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 ...

  16. What Causes Lactose Intolerance?

    MedlinePLUS

    ... links Share this: Page Content Not having enough lactase in the body is the cause of lactose ... describe why a person may not have enough lactase 1 : Primary lactose intolerance . This type develops in ...

  17. 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.

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

    PubMed

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

    2013-12-15

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

  19. Determining the amounts of urea and glucose in urine of patients with renal complications from diabetes mellitus and hypertension by near-infrared Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Bispo, Jeyse A. M.; Silveira, Landulfo; Vieira, Elzo E. d. S.; Fernandes, Adriana B.

    2013-02-01

    Diabetes mellitus and hypertension diseases are frequently found in the same patient, which if untreated predispose to atherosclerotic and kidney diseases. The objective of this study was to identify potential biomarkers in the urine of diabetic and hypertensive patients through dispersive near-infrared Raman spectroscopy. Urine samples were collected from patients with diabetes and hypertension but no complications (LG), high degree of complications (HG), and control ones: one fraction was submitted to biochemical tests and another one was stored frozen (-20°C) until spectral analysis. Samples were warmed up and placed in an aluminum sample holder for Raman spectra collection using a dispersive spectrometer (830 nm wavelength, 300 mW laser power and 20 s exposure time). Spectra were then submitted to Principal Components Analysis. The PCA loading vectors 1 and 3 revealed spectral features of urea/creatinine and glucose, respectively; the PCA scores showed that patients with diabetes/hypertension (LG and HG) had higher amount of glucose in the urine compared to the normal group (p < 0.05), which can bring serious consequences to patients. Also, the PCA scores showed that the amount of urea decreased in the groups with diabetes/hypertension (p < 0.05), which generates the same concern as it is a marker that has a strong importance in the metabolic changes induced by such diseases. These results, applied to the analysis of urine of patients with diabetes/hypertension, can lead to early diagnostic information of complications and a possible disease prognosis in the patients where no complications from diabetes and hypertension were found.

  20. Loop Diuretics in the Treatment of Hypertension.

    PubMed

    Malha, Line; Mann, Samuel J

    2016-04-01

    Loop diuretics are not recommended in current hypertension guidelines largely due to the lack of outcome data. Nevertheless, they have been shown to lower blood pressure and to offer potential advantages over thiazide-type diuretics. Torsemide offers advantages of longer duration of action and once daily dosing (vs. furosemide and bumetanide) and more reliable bioavailability (vs. furosemide). Studies show that the previously employed high doses of thiazide-type diuretics lower BP more than furosemide. Loop diuretics appear to have a preferable side effect profile (less hyponatremia, hypokalemia, and possibly less glucose intolerance). Studies comparing efficacy and side effect profiles of loop diuretics with the lower, currently widely prescribed, thiazide doses are needed. Research is needed to fill gaps in knowledge and common misconceptions about loop diuretic use in hypertension and to determine their rightful place in the antihypertensive arsenal. PMID:26951244

  1. Intolerance of Uncertainty

    PubMed Central

    Beier, Meghan L.

    2015-01-01

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

  2. 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.

  3. Histamine and histamine intolerance.

    PubMed

    Maintz, Laura; Novak, Natalija

    2007-05-01

    Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation. Histamine is a biogenic amine that occurs to various degrees in many foods. In healthy persons, dietary histamine can be rapidly detoxified by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the main enzyme for the metabolism of ingested histamine. It has been proposed that DAO, when functioning as a secretory protein, may be responsible for scavenging extracellular histamine after mediator release. Conversely, histamine N-methyltransferase, the other important enzyme inactivating histamine, is a cytosolic protein that can convert histamine only in the intracellular space of cells. An impaired histamine degradation based on reduced DAO activity and the resulting histamine excess may cause numerous symptoms mimicking an allergic reaction. The ingestion of histamine-rich food or of alcohol or drugs that release histamine or block DAO may provoke diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritus, flushing, and other conditions in patients with histamine intolerance. Symptoms can be reduced by a histamine-free diet or be eliminated by antihistamines. However, because of the multifaceted nature of the symptoms, the existence of histamine intolerance has been underestimated, and further studies based on double-blind, placebo-controlled provocations are needed. In patients in whom the abovementioned symptoms are triggered by the corresponding substances and who have a negative diagnosis of allergy or internal disorders, histamine intolerance should be considered as an underlying pathomechanism. PMID:17490952

  4. Evolution and Collective Intolerance

    ERIC Educational Resources Information Center

    Willhoite, Fred H., Jr.

    1977-01-01

    Examines behavioral and intellectual conformity as major attitudes in shaping political behavior. Manifestations of coercion within human and animal social units are presented, including religious intolerance, prohibition of artistic activity and literary expression, and rejection of outsiders. Available from: Managing Editor, Department of

  5. Management of statin intolerance.

    PubMed

    Raju, Soma B; Varghese, Kiron; Madhu, K

    2013-11-01

    Statins are the revolutionary drugs in the cardiovascular pharmacotherapy. But they also possess several adverse effects like myopathy with elevation of hepatic transaminases (>3 times the upper limit of normal) or creatine kinase (>10 times the upper limit of normal) and some rare side-effects, including peripheral neuropathy, memory loss, sleep disturbances, and erectile dysfunction. Due to these adverse effects, patients abruptly withdrew statins without consulting physicians. This abrupt discontinuation of statins is termed as statin intolerance. Statin-induced myopathy constitutes two third of all side-effects from statins and is the primary reason for statin intolerance. Though statin intolerance has considerably impacted cardiovascular outcomes in the high-risk patients, it has been well effectively managed by prescribing statins either as alternate-day or once weekly dosage regimen, as combination therapy with a non-statin therapy or and by dietary intervention. The present article reviews the causes, clinical implications of statin withdrawal and management of statin intolerance. PMID:24381870

  6. Lactose intolerance in infants.

    PubMed

    Taylor, Cathy

    Cathy Taylor describes the pathophysiology and aetiology of lactose intolerance and how to diagnose and treat it. Management of the infant by the primary health care team is discussed, with emphasis on advice and nutritional support that can be recommended to parents. PMID:16700234

  7. Pulmonary 2-deoxy-2-[18F]-fluoro-d-glucose uptake is low in treated patients with idiopathic pulmonary arterial hypertension

    PubMed Central

    Ruiter, Gerrina; Wong, Yeun Ying

    2013-01-01

    Abstract Glucose metabolism measurement using 2-deoxy-2-[18F]-fluoro-d-glucose (18FDG) positron emission tomography (PET) could provide in vivo information about pulmonary vascular remodeling. The purpose of this study was to assess whether pulmonary 18FDG uptake in idiopathic pulmonary arterial hypertension (IPAH) patients changes and, if so, to determine whether the change is related to disease severity and survival. Sixteen IPAH patients who were treated with IPAH-specific therapy and 7 patients who had a myocardial infarction (MI) without pulmonary hypertension were included. IPAH disease severity was determined using the 6-minute walk test and right heart catheterization 2 days before 18FDG PET. Regions of interest were defined for left and right lungs, and standardized uptake values (SUVs), normalized to body weight, injected dose, and plasma glucose level, were derived. Mean SUVs for IPAH left and right lungs were and (), respectively. In MI patients, SUVs were and () in left and right lungs, respectively. Total lung SUVs were similar in IPAH and MI patients ( vs. ; ). There was no correlation between SUV and IPAH disease severity parameters. In addition, lung SUV did not predict survival in IPAH patients (hazard ratio, 1.155; 95% confidence interval, 0.16–8.26; ). In conclusion, pulmonary 18FDG uptake in treated IPAH patients is low and is not associated with disease severity and survival, thereby limiting its clinical use in patient care. PMID:24618549

  8. The Effect of the Missouri WISEWOMAN Program on Control of Hypertension, Hypercholesterolemia, and Elevated Blood Glucose Among Low-Income Women

    PubMed Central

    Homan, Sherri G.; McBride, David G.

    2014-01-01

    Introduction The Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) public health program is designed to reduce the risk of heart disease and stroke among low-income, underinsured or uninsured women through clinical screenings, risk factor assessment, and lifestyle interventions. We assessed the effect of the Missouri WISEWOMAN program on the control of high blood pressure, total cholesterol, and blood glucose levels. Methods We calculated the proportion of participants (N = 1,130) with abnormal blood pressure, total cholesterol, or blood glucose levels at an initial screening visit who gained control at a follow-up visit 11 to 18 months later during a 7-year period from June 30, 2005, to June 29, 2012. We used logistic regression to identify sociodemographic characteristics and other factors associated with achieving control. Results Many WISEWOMAN participants gained control of their blood pressure (41.2%), total cholesterol (24.7%), or blood glucose levels (50.0%). After controlling for sociodemographic factors, smoking status, weight status, medication use, and number of lifestyle interventions, nondiabetic women with stage II hypertension (adjusted odds ratio [AOR] = 0.36, 95% confidence interval [CI] = 0.210.60) and diabetic women with stage I (AOR = 0.54, 95% CI = 0.320.92) and stage II (AOR = 0.23, 95% CI = 0.070.77) hypertension were less likely to achieve control of their blood pressure than nondiabetic women with stage I hypertension. Women aged 45 to 64, women with less than a high school education, women who were obese in the initial visit, women who gained 7% or more of their weight, and women who did not participate in any lifestyle intervention sessions were significantly less likely to achieve total cholesterol control than their counterparts. Conclusion The Missouri WISEWOMAN program helps many participants achieve control of blood pressure, total cholesterol, and blood glucose levels; the lifestyle intervention is likely to help participants control total cholesterol. More efforts are needed for women with diabetes and stage II hypertension to achieve blood pressure control. PMID:24784910

  9. 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

  10. 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

  11. Pulmonary hypertension

    MedlinePLUS

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary hypertension

  12. Genetics Home Reference: Lysinuric protein intolerance

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Lysinuric protein intolerance On this page: Description Genetic changes Inheritance ... Glossary definitions Reviewed March 2008 What is lysinuric protein intolerance? Lysinuric protein intolerance is a disorder caused ...

  13. Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension

    PubMed Central

    Brown, Morris J; Williams, Bryan; MacDonald, Thomas M; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Salsbury, Jackie; Morant, Steve; Ford, Ian

    2015-01-01

    Introduction Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K+-depletion. We hypothesised that a K+-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K+-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide. Methods and analysis This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25–50 mg, amiloride 10–20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18–79, systolic BP on permitted background treatment ≥140 mm Hg and home BP ≥130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K+, clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators. Ethics and dissemination PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal. Trial registration numbers Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973. PMID:26253567

  14. 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

  15. 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 ...

  16. Lactose intolerance: a nursing perspective.

    PubMed

    Marchiondo, Kathleen

    2009-01-01

    Deficiency of intestinal lactase, the enzyme required for lactose digestion, can result in symptoms of gastrointestinal malabsorption, or lactose intolerance. The knowledge needed for accurate nursing assessment, diagnostic procedural care, teaching, and referral of affected patients is reviewed. PMID:19331294

  17. [Histamine intolerance mimics anorexia nervosa].

    PubMed

    Stolze, I; Peters, K-P; Herbst, R A

    2010-09-01

    Histamine intolerance is a clinically heterogeneous disease. We present a woman who suffered from weight loss, diarrhea, abdominal pain, headache, flushing and bronchial asthma for several years. When placed on a histamine-poor diet, she experienced weight gain and improvement of other all signs and symptoms, supporting the diagnosis of histamine intolerance. Therefore, this disease should be included in the differential diagnosis of anorexia nervosa. PMID:19907926

  18. Lactose intolerance and health.

    PubMed Central

    Wilt, Timothy J; Shaukat, Aasma; Shamliyan, Tatyana; Taylor, Brent C; MacDonald, Roderick; Tacklind, James; Rutks, Indulis; Schwarzenberg, Sarah Jane; Kane, Robert L; Levitt, Michael

    2010-01-01

    OBJECTIVES We systematically reviewed evidence to determine lactose intolerance (LI) prevalence, bone health after dairy-exclusion diets, tolerable dose of lactose in subjects with diagnosed LI, and management. DATA SOURCES We searched multiple electronic databases for original studies published in English from 1967-November 2009. REVIEW METHODS We extracted patient and study characteristics using author's definitions of LI and lactose malabsorption. We compared outcomes in relation to diagnostic tests, including lactose challenge, intestinal biopsies of lactase enzyme levels, genetic tests, and symptoms. Fractures, bone mineral content (BMC) and bone mineral density (BMD) were compared in categories of lactose intake. Reported symptoms, lactose dose and formulation, timing of lactose ingestion, and co-ingested food were analyzed in association with tolerability of lactose. Symptoms were compared after administration of probiotics, enzyme replacements, lactose-reduced milk and increasing lactose load. RESULTS Prevalence was reported in 54 primarily nonpopulation based studies (15 from the United States). Studies did not directly assess LI and subjects were highly selected. LI magnitude was very low in children and remained low into adulthood among individuals of Northern European descent. For African American, Hispanic, Asian, and American Indian populations LI rates may be 50 percent higher in late childhood and adulthood. Small doses of lactose were well tolerated in most populations. Low level evidence from 55 observational studies of 223,336 subjects indicated that low milk consumers may have increased fracture risk. Strength and significance varied depended on exposure definitions. Low level evidence from randomized controlled trials (RCTs) of children (seven RCTs) and adult women (two RCTs) with low lactose intake indicated that dairy interventions may improve BMC in select populations. Most individuals with LI can tolerate up to 12 grams of lactose, though symptoms became more prominent at doses above 12 grams and appreciable after 24 grams of lactose; 50 grams induced symptoms in the vast majority. A daily divided dose of 24 grams was generally tolerated. We found insufficient evidence that use of lactose reduced solution/milk, with lactose content of 0-2 grams, compared to a lactose dose of greater than 12 grams, reduced symptoms of lactose intolerance. Evidence was insufficient for probiotics (eight RCTs), colonic adaptation (two RCTs) or varying lactose doses (three RCTs) or other agents (one RCT). Inclusion criteria, interventions, and outcomes were variable. Yogurt and probiotic types studied were variable and results either showed no difference in symptom scores or small differences in symptoms that may be of low clinical relevance. CONCLUSIONS There are race and age differences in LI prevalence. Evidence is insufficient to accurately assess U.S. population prevalence of LI. Children with low lactose intake may have beneficial bone outcomes from dairy interventions. There was evidence that most individuals with presumed LI or LM can tolerate 12-15 grams of lactose (approximately 1 cup of milk). There was insufficient evidence regarding effectiveness for all evaluated agents. Additional research is needed to determine LI treatment effectiveness. PMID:20629478

  19. Fermentation, fermented foods and lactose intolerance.

    PubMed

    Solomons, N W

    2002-12-01

    Lactose (milk sugar) is a fermentable substrate. It can be fermented outside of the body to produce cheeses, yoghurts and acidified milks. It can be fermented within the large intestine in those people who have insufficient expression of lactase enzyme on the intestinal mucosa to ferment this disaccharide to its absorbable, simple hexose sugars: glucose and galactose. In this way, the issues of lactose intolerance and of fermented foods are joined. It is only at the extremes of life, in infancy and old age, in which severe and life-threatening consequences from lactose maldigestion may occur. Fermentation as part of food processing can be used for preservation, for liberation of pre-digested nutrients, or to create ethanolic beverages. Almost all cultures and ethnic groups have developed some typical forms of fermented foods. Lessons from fermentation of non-dairy items may be applicable to fermentation of milk, and vice versa. PMID:12556948

  20. Chronic Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity Decreases Hypertension, Insulin Resistance, and Hypertriglyceridemia in Metabolic Syndrome

    PubMed Central

    Schnackenberg, Christine G.; Costell, Melissa H.; Krosky, Daniel J.; Cui, Jianqi; Wu, Charlene W.; Hong, Victor S.; Harpel, Mark R.; Willette, Robert N.; Yue, Tian-Li

    2013-01-01

    Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11β-HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp), cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d), a selective inhibitor of 11β-HSD1. Compound 11 significantly decreased 11β-HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11β-HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome. PMID:23586038

  1. Overcoming the barrier of lactose intolerance to reduce health disparities.

    PubMed Central

    Jarvis, Judith K.; Miller, Gregory D.

    2002-01-01

    Federal health goals for the public have focused on reducing health disparities that exist between whites and various racial and ethnic groups. Many of the chronic diseases for which African Americans are at greater risk- hypertension, stroke, colon cancer, and obesity-may be exacerbated by a low intake of calcium and/or other dairy-related nutrients. For example, a low intake of dairy food nutrients, such as calcium, potassium, and magnesium, may contribute to the high risk of hypertension seen in African Americans. The Dietary Approaches to Stop Hypertension (DASH) study demonstrated that a low-fat diet rich in fruits and vegetables (8 to 10 servings) and low-fat dairy foods (3 servings) significantly reduced blood pressure-and was twice as effective in African-American participants. Calcium and dairy food consumption is particularly low among African-American, Hispanic, and Asian populations. Average intakes are near the threshold of 600 to 700 mg/day, below which bone loss and hypertension can result. Although lactose intolerance may be partly to blame for the low calcium intakes due to reduced dairy food consumption by minority populations, culturally determined food preferences and dietary practices learned early in life also play a role. The high incidence figures for primary lactose maldigestion among minority groups grossly overestimates the number who will experience intolerance symptoms after drinking a glass of milk with a meal. Randomized, double-blind, controlled clinical trials have demonstrated that by using a few simple dietary strategies, those who maldigest lactose (have low levels of the lactase enzyme) can easily tolerate a dairy-rich diet that meets calcium intake recommendations. Physicians and other health professionals can help their minority patients and the general public understand how to improve calcium nutrition by overcoming the surmountable barrier of lactose intolerance. At the same time they will be helping to reduce the incidence of calcium-related chronic diseases for which minority populations are at high risk. PMID:11853047

  2. Food allergies and food intolerances.

    PubMed

    Ortolani, Claudio; Pastorello, Elide A

    2006-01-01

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

  3. [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?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

  4. Dietary ribonucleic acid suppresses inflammation of adipose tissue and improves glucose intolerance that is mediated by immune cells in C57BL/6 mice fed a high-fat diet.

    PubMed

    Sakai, Tohru; Taki, Tomoyo; Nakamoto, Akiko; Tazaki, Shiho; Arakawa, Mai; Nakamoto, Mariko; Tsutsumi, Rie; Shuto, Emi

    2015-01-01

    Recent evidence suggests that immune cells play an important role in differentiation of inflammatory macrophages in adipose tissue, which contributes to systemic chronic inflammation. Dietary ribonucleic acid (RNA) has been shown to modulate immune function. We hypothesized that RNA affects immune cell function in adipose tissue and then improves inflammatory response in adipose tissue. C57/BL6 mice and recombination activating gene-1 (RAG-1) knockout mice on a C57BL/6 mice background were fed a high-fat diet containing 1% RNA for 12 wk. An oral glucose tolerance test was performed. Supplementation of dietary RNA in C57BL/6 mice fed a high-fat diet resulted in a smaller area under the curve (AUC) after oral glucose administration than that for control mice. The mRNA expression levels of inflammation-related cytokines in adipose tissue and serum interleukin-6 levels were reduced by dietary RNA supplementation. Interestingly, reduction of the AUC value by RNA supplementation was abolished in T and B cell-deficient RAG-1 knockout mice. These results indicate that RNA improves inflammation in adipose tissue and reduces the AUC value following oral glucose administration in a T and B cell-dependent manner. PMID:25994141

  5. Ocular Hypertension

    MedlinePLUS

    ... News Ask an Eye M.D. Espaol Ocular Hypertension What Is Ocular Hypertension? Ocular Hypertension Causes Ocular ... Hypertension Diagnosis Ocular Hypertension Treatment What Is Ocular Hypertension? Written by: Kierstan Boyd Reviewed by: J Kevin ...

  6. FOXO1-mediated upregulation of pyruvate dehydrogenase kinase-4 (PDK4) decreases glucose oxidation and impairs right ventricular function in pulmonary hypertension: therapeutic benefits of dichloroacetate.

    PubMed

    Piao, Lin; Sidhu, Vaninder K; Fang, Yong-Hu; Ryan, John J; Parikh, Kishan S; Hong, Zhigang; Toth, Peter T; Morrow, Erik; Kutty, Shelby; Lopaschuk, Gary D; Archer, Stephen L

    2013-03-01

    Pyruvate dehydrogenase kinase (PDK) is activated in right ventricular hypertrophy (RVH), causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. The stimulus for PDK upregulation, its isoform specificity, and the long-term effects of PDK inhibition are unknown. We hypothesize that FOXO1-mediated PDK4 upregulation causes bioenergetic impairment and RV dysfunction, which can be reversed by dichloroacetate. Adult male Fawn-Hooded rats (FHR) with pulmonary arterial hypertension (PAH) and right ventricular hypertrophy (RVH; age 6-12 months) were compared to age-matched controls. Glucose oxidation (GO) and fatty acid oxidation (FAO) were measured at baseline and after acute dichloroacetate (1 mM 40 min) in isolated working hearts and in freshly dispersed RV myocytes. The effects of chronic dichloroacetate (0.75 g/L drinking water for 6 months) on cardiac output (CO) and exercise capacity were measured in vivo. Expression of PDK4 and its regulatory transcription factor, FOXO1, were also measured in FHR and RV specimens from PAH patients (n = 10). Microarray analysis of 168 genes related to glucose or FA metabolism showed >4-fold upregulation of PDK4, aldolase B, and acyl-coenzyme A oxidase. FOXO1 was increased in FHR RV, whereas HIF-1 ? was unaltered. PDK4 expression was increased, and the inactivated form of FOXO1 decreased in human PAH RV (P < 0.01). Pyruvate dehydrogenase (PDH) inhibition in RVH increased proton production and reduced GO's contribution to the tricarboxylic acid (TCA) cycle. Acutely, dichloroacetate reduced RV proton production and increased GO's contribution (relative to FAO) to the TCA cycle and ATP production in FHR (P < 0.01). Chronically dichloroacetate decreased PDK4 and FOXO1, thereby activating PDH and increasing GO in FHR. These metabolic changes increased CO (84 14 vs. 69 14 ml/min, P < 0.05) and treadmill-walking distance (239 20 vs. 171 22 m, P < 0.05). Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores GO, leading to improved bioenergetics and RV function in RVH. PMID:23247844

  7. FOXO1-mediated Upregulation of Pyruvate Dehydrogenase Kinase-4 (PDK4) Decreases Glucose Oxidation and Impairs Right Ventricular Function in Pulmonary Hypertension: Therapeutic Benefits of Dichloroacetate

    PubMed Central

    Piao, Lin; Sidhu, Vaninder K.; Fang, Yong-Hu; Ryan, John J.; Parikh, Kishan S.; Hong, Zhigang; Toth, Peter T.; Morrow, Erik; Kutty, Shelby; Lopaschuk, Gary D.; Archer, Stephen L.

    2012-01-01

    Introduction Pyruvate dehydrogenase kinase (PDK) is activated in right ventricular hypertrophy (RVH), causing an increase in glycolysis relative to glucose oxidation that impairs RV function. The stimulus for PDK upregulation, its isoform specificity and the long-term effects of PDK inhibition are unknown. We hypothesize that FOXO1-mediated PDK4 upregulation causes bioenergetic impairment and RV dysfunction, which can be reversed by dichloroacetate. Methods Adult male Fawn-Hooded rats (FHR) with pulmonary arterial hypertension (PAH) and RVH (age 612 months) were compared to age-matched controls. Cardiac glucose and fatty acid oxidation (GO, FAO) were measured at baseline and after acute dichloroacetate (1mM40-minutes) in isolated working-hearts and in freshly dispersed RV myocytes. The effects of chronic dichloroacetate (0.75 g/L drinking water for 6 months) on cardiac output (CO) and exercise capacity were measured in vivo. Expression of PDK4 and its regulatory transcription factor, FOXO1, were also measured in FHR and RV specimens from PAH patients (n=10). Results Microarray analysis of 168 genes related to glucose or FA metabolism showed >4-fold upregulation of PDK4, aldolase B and acyl-coenzyme A oxidase. FOXO1 was increased, in FHR RV whereas HIF-1? was unaltered. PDK4 expression was increased and the inactivated form of FOXO1 decreased in human PAH RV (P<0.01). PDH inhibition in RVH increased proton production and reduced GOs contribution to the TCA cycle. Acutely, dichloroacetate reduced RV proton production and increased GOs contribution (relative to FAO) to the TCA cycle and ATP production in FHR (P<0.01). Chronically dichloroacetate decreased PDK4 and FOXO1, thereby activating PDH and increasing GO in FHR. These metabolic changes increased CO (8414 vs. 6914 ml/min, P<0.05) and treadmill-walking distance (23920 vs. 17122 m, P<0.05). Conclusion Chronic dichloroacetate inhibits FOXO1-induced PDK4 upregulation and restores GO, leading to improved bioenergetics and RV function in RVH. PMID:23247844

  8. Milk for Kids with Lactose Intolerance

    MedlinePLUS

    ... lactose intolerance: Relax. Your child can still enjoy milk products and get the nourishment that milk gives. Nutrients ... your child is lactose intolerant, you can fit milk products in! You Can Help Your Child Enjoy Milk. ...

  9. Incretins and selective renal sodium-glucose co-transporter 2 inhibitors in hypertension and coronary heart disease

    PubMed Central

    Sanchez, Ramiro A; Sanabria, Hugo; de los Santos, Cecilia; Ramirez, Agustin J

    2015-01-01

    Hyperglycemia is associated with an increased risk of cardiovascular disease, and the consequences of intensive therapy may depend on the mechanism of the anti-diabetic agent(s) used to achieve a tight control. In animal models, stable analogues of glucagon-like peptide-1 (GLP-1) were able to reduce body weight and blood pressure and also had favorable effects on ischemia following coronary reperfusion. In a similar way, dipeptidyl peptidase IV (DPP-IV) showed to have favorable effects in animal models of ischemia/reperfusion. This could be due to the fact that DPP-IV inhibitors were able to prevent the breakdown of GLP-1 and glucose-dependent insulinotropic polypeptide, but they also decreased the degradation of several vasoactive peptides. Preclinical data for GLP-1, its derivatives and inhibitors of the DPP-IV enzyme degradation suggests that these agents may be able to, besides controlling glycaemia, induce cardio-protective and vasodilator effects. Notwithstanding the many favorable cardiovascular effects of GLP-1/incretins reported in different studies, many questions remain unanswered due the limited number of studies in human beings that aim to examine the effects of GLP-1 on cardiovascular endpoints. For this reason, long-term trials searching for positive cardiovascular effects are now in process, such as the CAROLINA and CARMELINA trials, which are supported by small pilot studies performed in humans (and many more animal studies) with incretin-based therapies. On the other hand, selective renal sodium-glucose co-transporter 2 inhibitors were also evaluated in the prevention of cardiovascular outcomes in type 2 diabetes. However, it is quite early to draw conclusions, since data on cardiovascular outcomes and cardiovascular death are limited and long-term studies are still ongoing. In this review, we will analyze the mechanisms underlying the cardiovascular effects of incretins and, at the same time, we will present a critical position about the real value of these compounds in the cardiovascular system and its protection. PMID:26380062

  10. Lactose intolerance: diagnosis and management.

    PubMed

    Patel, Y T; Minocha, A

    2000-01-01

    Lactose intolerance affects hundreds of millions of people worldwide. Although the presentation is frequently atypical, it should be part of the differential diagnosis when evaluating nonspecific gastrointestinal symptoms. We review the terminology, types of lactase deficiencies, diagnostic procedures, and management. PMID:11126094

  11. Pulmonary Hypertension

    MedlinePLUS

    MENU Return to Web version Pulmonary Hypertension Overview What is pulmonary hypertension? "Pulmonary" means "in the lungs," and "hypertension" means "high blood pressure." Pulmonary hypertension is an increase ...

  12. 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

  13. Colonic fermentation may play a role in lactose intolerance in humans.

    PubMed

    He, Tao; Priebe, Marion G; Harmsen, Hermie J M; Stellaard, Frans; Sun, Xiaohong; Welling, Gjalt W; Vonk, Roel J

    2006-01-01

    The results of our previous study suggested that in addition to the small intestinal lactase activity and transit time, colonic processing of lactose may play a role in lactose intolerance. We investigated whether colonic fermentation of lactose is correlated with lactose intolerance. After 28 Chinese subjects had undergone 1 glucose (placebo) and 2 lactose challenges, consistent lactose tolerant (n = 7) and intolerant (n = 5) subjects with no complaints after glucose administration were classified on the basis of the 6-h symptom scores. Before the challenges, fecal samples were collected for in vitro incubation with lactose. The incubation was carried out in a static system under anaerobic conditions for 5 h during which samples were taken for measurement of short-chain fatty acids, lactate, lactose, glucose, and galactose. Fecal bacterial composition was determined by fluorescent in situ hybridization. The tolerant and intolerant groups did not differ in the rate or degree of hydrolysis of lactose or production of glucose and galactose. The intolerant group produced d- and l-lactate, acetate, propionate, and butyrate significantly faster than the tolerant group. In the intolerant group, the amounts of acetate, propionate, butyrate, and l-lactate produced were higher than those in the tolerant group. Fecal bacterial composition did not differ between the 2 groups. The results indicate that the degree and rate of lactose hydrolysis in the colon do not play a role in lactose intolerance. However, after lactose is hydrolyzed, a faster and higher production of microbial intermediate and end metabolites may be related to the occurrence of symptoms. PMID:16365059

  14. The effect of glutathione S-transferase M1 and T1 polymorphisms on blood pressure, blood glucose, and lipid profiles following the supplementation of kale (Brassica oleracea acephala) juice in South Korean subclinical hypertensive patients

    PubMed Central

    Han, Jeong-Hwa; Lee, Hye-Jin; Kim, Tae-Seok

    2015-01-01

    BACKGROUND/OBJECTIVES Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of reactive oxygen species. This study examines whether daily supplementation of kale juice can modulate blood pressure (BP), levels of lipid profiles, and blood glucose, and whether this modulation could be affected by the GSTM1 and GSTT1 polymorphisms. SUBJECTS/METHODS 84 subclinical hypertensive patients showing systolic BP over 130 mmHg or diastolic BP over 85 mmHg received 300 ml/day of kale juice for 6 weeks, and blood samples were collected on 0-week and 6-week in order to evaluate plasma lipid profiles (total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol) and blood glucose. RESULTS Systolic and diastolic blood pressure was significantly decreased in all patients regardless of their GSTM1 or GSTT1 polymorphisms after kale juice supplementation. Blood glucose level was decreased only in the GSTM1-present genotype, and plasma lipid profiles showed no difference in both the GSTM1-null and GSTM1-present genotypes. In the case of GSTT1, on the other hand, plasma HDL-C was increased and LDL-C was decreased only in the GSTT1-present type, while blood glucose was decreased only in the GSTT1-null genotype. CONCLUSIONS These findings suggest that the supplementation of kale juice affected blood pressure, lipid profiles, and blood glucose in subclinical hypertensive patients depending on their GST genetic polymorphisms, and the improvement of lipid profiles was mainly greater in the GSTT1-present genotype and the decrease of blood glucose was greater in the GSTM1-present or GSTT1-null genotypes. PMID:25671068

  15. Urticarial intolerance reaction to cetirizine.

    PubMed

    Schrter, S; Damveld, B; Marsch, W C

    2002-05-01

    The paradoxical acute exacerbation of pre-existing chronic idiopathic urticaria accompanied by intense generalized pruritus, facial oedema, and dyspnoea in a 36-year-old-woman 3-4 h after a single oral dose of 10 mg cetirizine (Zyrtec tablets), suggested the presence of an underlying intolerance reaction. However, a type I hypersensitivity reaction also had to be excluded. Detailed allergy testing supported the view that the patient had suffered an intolerance reaction to cetirizine. This is the third known case of most probably a nonallergic generalized urticaria following the administration of cetirizine, a drug with extensive usage worldwide. However a type I sensitization to cetirizine is indeed possible, as has been demonstrated in this research with the verification of cetirizine-specific IgE antibodies in one of the control sera. PMID:12072003

  16. [Intolerance reactions of the skin].

    PubMed

    Sacher, R

    1987-07-01

    Intolerance reactions of the skin in which a decision is made on allergic and toxic genesis have increased in significance in recent years. Whereas antibodies blocking bacterial or viral antigens are formed in the normergic immune reaction, nonblocking antibodies to animal, plant or chemical heterologous substances are formed in an allergy as a result of an misdirected immunological reaction. Sensitization is favored by a) large structure and protein affinity of the allergen, b) irritation of the affected part of the skin by fungi or chemicals and c) genetic predisposition. Depending on the clinical manifestation, a distinction is made between inhaled allergens (bronchial asthma, hay fever), allergens ingested with the food (food allergy) and allergens which have come in contact with the skin (immediate reaction - urticaria, late reaction - contact eczema). Intolerance reactions of the skin which can be ruled out as the cause of an allergy are designated as toxic. Acute toxic reactions are based on violent or intensively physical (heat, cold, radiation), chemical (acids, alkalis, heavy metal salts, oils, solvents) or microbial damage to the skin (infection by fungi, bacteria, viruses). The degenerative eczema as the most important form of chronic toxic intolerance reaction arises by weak but continuously acting longterm mechanical or chemical exposures. PMID:2957865

  17. 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 linear regressions, and the slope was not different between control subjects and patients with OI. CONCLUSIONS: Cerebral vasoconstriction occurs in OI during orthostasis, which is primarily due to hyperventilation, causing significant hypocapnia. Hypocapnia and symptoms of orthostatic hypertension are reversible by CO2 rebreathing.

  18. 75 FR 2551 - NIH Consensus Development Conference: Lactose Intolerance and Health; Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    .... Lactose intolerance is the inability to digest significant amounts of lactose, a sugar found in milk and.... Lactase breaks milk sugar down into two simpler forms of sugar called glucose and galactose, which are... and successfully digest lactose provided by human milk or by infant formulas. However, by the...

  19. 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 ? 50kb 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

  20. [Food allergies and intolerances in children].

    PubMed

    Olives, J P; Breton, A

    1998-02-15

    Allergies and food intolerance together comprise the manifestations of "adverse food reaction". The best known and most common are: allergy to cow's milk proteins (prevalence 0.5% to 7.5%), intolerance to lactose (prevalence after weaning 5 to 100%) and gluten intolerance (prevalence 0.5%). Treatment of these conditions is based on management of the diet by exclusion (or reduction) of the responsible food or antigen. PMID:9781094

  1. [Lactose intolerance and consumption of milk and milk products].

    PubMed

    Sieber, R; Stransky, M; de Vrese, M

    1997-12-01

    The disaccharide lactose is present as a natural component of foods only in milk and dairy products. In the gastrointestinal tract, lactose is hydrolysed by the enzyme beta-galactosidase (lactase) into glucose and galactose. These components are absorbed. With the exception of the caucasian race, the lactase activity decreases in most people at an age of 4 to 6 years. Lactose intake can cause symptoms of bloating, flatulence, abdominal pain, and diarrhea due to the lactose reaching the large intestine. This phenomenon is called lactose intolerance. It is generally recommended to those persons that they refrain from the consumption of milk and dairy products. However, most lactose intolerant people are able to digest small amounts of milk. They can also consume cheese that contains no (hard and semi-hard) or only small amounts of lactose (present in only 10% of soft cheeses). These products are very important sources of calcium. Compared to milk, the lactose content of yogurt is usually lower by about one third. Studies during the last 10 years have shown that in spite of its lactose content yogurt is very well tolerated by lactose intolerant persons. This advantage is ascribed to the presence of living lactic acid bacteria in fermented dairy products which survive passage through the stomach and also to the lactase present in these products. PMID:9467238

  2. 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

  3. 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

  4. 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…

  5. Correlating the amount of urea, creatinine, and glucose in urine from patients with diabetes mellitus and hypertension with the risk of developing renal lesions by means of Raman spectroscopy and principal component analysis

    NASA Astrophysics Data System (ADS)

    Bispo, Jeyse Aliana Martins; de Sousa Vieira, Elzo Everton; Silveira, Landulfo; Fernandes, Adriana Barrinha

    2013-08-01

    Patients with diabetes mellitus and hypertension (HT) diseases are predisposed to kidney diseases. The objective of this study was to identify potential biomarkers in the urine of diabetic and hypertensive patients through Raman spectroscopy in order to predict the evolution to complications and kidney failure. Urine samples were collected from control subjects (CTR) and patients with diabetes and HT with no complications (lower risk, LR), high degree of complications (higher risk, HR), and doing blood dialysis (DI). Urine samples were stored frozen (-20°C) before spectral analysis. Raman spectra were obtained using a dispersive spectrometer (830-nm, 300-mW power, and 20-s accumulation). Spectra were then submitted to principal component analysis (PCA) followed by discriminant analysis. The first PCA loading vectors revealed spectral features of urea, creatinine, and glucose. It has been found that the amounts of urea and creatinine decreased as disease evoluted from CTR to LR/HR and DI (PC1, p<0.05), and the amount of glucose increased in the urine of LR/HR compared to CTR (PC3, p<0.05). The discriminating model showed better overall classification rate of 70%. These results could lead to diagnostic information of possible complications and a better disease prognosis.

  6. 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.

  7. Hypertension in rats deficient in copper

    SciTech Connect

    Klevay, L.M.

    1986-03-01

    Male weanling rats were matched into two groups of equal mean weight (48 g), were fed a diet low in copper and zinc and were supplemented with a drinking solution with 10..mu..gZn and 2/sup +/gCu per ml until they grew to approximately 300 g. Systolic blood pressure (mmHg) was measured without anesthesia with an Electro-Sphygmomanometer and pneumatic pulse transducer; no significant difference between groups was found (0 > 0.05). Then copper was omitted from the solution of the group with lower blood pressure in each of two experiments. Plasma cholesterol (mg/dl) was measured by fluorometry and blood pressure was measured again 53 to 86 days later; mean (SE), n = 14, 15. Hypercholesterolemia verified deficiency. Hypotension in copper deficient rats in experiments of others probably was the result of cardiac defects induced in weanling animals. Hypertension joins hypercholesterolemia, hyperuricemia, glucose intolerance and abnormal electrocardiograms as a stigma of copper deficiency. Copper deficiency is the only nutritional insult that induces all of these characteristics useful in predicting risk of ischemic heart disease.

  8. Metabolic syndrome in hypertensive patients: An unholy alliance.

    PubMed

    Mul, Giuseppe; Calcaterra, Ilenia; Nardi, Emilio; Cerasola, Giovanni; Cottone, Santina

    2014-09-26

    For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome (MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes. PMID:25276291

  9. Metabolic syndrome in hypertensive patients: An unholy alliance

    PubMed Central

    Mul, Giuseppe; Calcaterra, Ilenia; Nardi, Emilio; Cerasola, Giovanni; Cottone, Santina

    2014-01-01

    For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome (MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes. PMID:25276291

  10. Orthostatic intolerance and the headache patient.

    PubMed

    Mack, Kenneth J; Johnson, Jonathan N; Rowe, Peter C

    2010-06-01

    Orthostatic intolerance (OI) refers to a group of clinical conditions, including postural orthostatic tachycardia syndrome (POTS) and neurally mediated hypotension (NMH), in which symptoms worsen with upright posture and are ameliorated by recumbence. The main symptoms of chronic orthostatic intolerance syndromes include light-headedness, syncope or near syncope, blurring of vision, headaches, problems with short-term memory and concentration, fatigue, intolerance of low impact exercise, palpitations, chest pain, diaphoresis, tremulousness, dyspnea or air hunger, nausea, and vomiting. This review discusses what is known about the pathophysiology of this disorder, potential treatments, and understanding its role in the patient with chronic headache pain. PMID:20541103

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

    PubMed

    Chen, J; Sai, X Y

    2016-02-10

    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

  12. Common Syndromes of Orthostatic Intolerance

    PubMed Central

    2013-01-01

    The autonomic nervous system, adequate blood volume, and intact skeletal and respiratory muscle pumps are essential components for rapid cardiovascular adjustments to upright posture (orthostasis). Patients lacking sufficient blood volume or having defective sympathetic adrenergic vasoconstriction develop orthostatic hypotension (OH), prohibiting effective upright activities. OH is one form of orthostatic intolerance (OI) defined by signs, such as hypotension, and symptoms, such as lightheadedness, that occur when upright and are relieved by recumbence. Mild OI is commonly experienced during intercurrent illnesses and when standing up rapidly. The latter is denoted initial OH and represents a normal cardiovascular adjustment to the blood volume shifts during standing. Some people experience episodic acute OI, such as postural vasovagal syncope (fainting), or chronic OI, such as postural tachycardia syndrome, which can significantly reduce quality of life. The lifetime incidence of ?1 fainting episodes is ?40%. For the most part, these episodes are benign and self-limited, although frequent syncope episodes can be debilitating, and injury may occur from sudden falls. In this article, mechanisms for OI having components of adrenergic hypofunction, adrenergic hyperfunction, hyperpnea, and regional blood volume redistribution are discussed. Therapeutic strategies to cope with OI are proposed. PMID:23569093

  13. 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

  14. Lactose Intolerance: A Guide for Teens

    MedlinePLUS

    ... are lactose intolerant. You may also have a hydrogen breath test to confirm this diagnosis. A hydrogen breath test is done by breathing into a machine that measures the amount of hydrogen in your breath within 90 minutes of consuming ...

  15. 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.

  16. Age-related autocrine diabetogenic effects of transgenic resistin in spontaneously hypertensive rats: gene expression profile analysis

    PubMed Central

    Zdek, Vclav; Landa, Vladimr; imkov, Miroslava; Mlejnek, Petr; ilhav, Jan; Maxov, Martina; Kazdov, Ludmila; Seidman, Jonathan G.; Seidman, Christine E.; Eminaga, Seda; Gorham, Joshua; Wang, Jiaming; Kurtz, Theodore W.

    2011-01-01

    Increased circulating levels of resistin have been proposed as a possible link between obesity and insulin resistance; however, many of the potential metabolic effects of resistin remain to be investigated, including systemic versus local resistin action. We investigated potential autocrine effects of resistin on lipid and glucose metabolism in 2- and 16-mo-old transgenic spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin under control of the aP2 promoter. To search for possible molecular mechanisms, we compared gene expression profiles in adipose tissue in 6-wk-old transgenic SHR versus control rats, before development of insulin resistance, by digital transcriptional profiling using high-throughput sequencing. Both young and old transgenic rats showed moderate expression of the resistin transgene in adipose tissue but had serum resistin levels similar to control SHR and undetectable levels of transgenic resistin in the circulation. Young transgenic rats exhibited mild glucose intolerance. In contrast, older transgenic rats displayed marked glucose intolerance in association with near total resistance of adipose tissue to insulin-stimulated glucose incorporation into lipids (6 2 vs. 77 19 nmol glucoseg?12 h?1, P < 0.00001). Ingenuity Pathway Analysis of differentially expressed genes revealed calcium signaling, Nuclear factor-erythroid 2-related factor-2 (NRF2)-mediated oxidative stress response, and actin cytoskeletal signaling canonical pathways as those most significantly affected. Analysis using DAVID software revealed oxidative phosphorylation, glutathione metabolism, pyruvate metabolism, and peroxisome proliferator-activated receptor (PPAR) signaling as top Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. These results suggest that with increasing age autocrine effects of resistin in fat tissue may predispose to diabetes in part by impairing insulin action in adipose tissue. PMID:21285283

  17. 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

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

    PubMed

    Lima, William Gustavo; Martins-Santos, Maria Emlia Soares; Chaves, Valria Ernestnia

    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

  19. Treatment of lactose intolerance with exogenous beta-D-galactosidase in pellet form.

    PubMed

    Xenos, K; Kyroudis, S; Anagnostidis, A; Papastathopoulos, P

    1998-01-01

    The effectiveness of a new beta-D-galactosidase pellet formulation in the treatment of lactose intolerance was studied. The encapsuled beta-D-galactosidase (lactase) pellets were first tested in vitro for their enzymatic activity within an environment simulating gastric conditions and subsequently within an environment simulating duodenal conditions. Effectiveness was measured by the % of glucose formed by hydrolysis of lactose. The pellets were found to retain their enzymatic activity in gastric pH conditions (mean 69 +/- 1 mg/dl glucose) and were found to hydrolyse lactose in human duodenal fluid (106.35 +/- 1 mg/dl). Finally the effectiveness of the new lactase formulation on glucose absorption was studied in 8 lactose intolerant subjects in a randomized, double blind, crossover trial. After fasting, the subjects were given one capsule containing 100 u/ml beta-galactosidase (i.e. 10 pellets of 10 u/ml each) or one capsule containing placebo pellets, followed by 100 g lactose dissolved in water. The washout period between lactose challenges was one week. Plasma glucose concentrations were measured before and at intervals after the challenges and the subjects completed symptom questionnaires every eight hours for 24 hours. Results showed a statistically significant increase in plasma glucose levels 30, 60, 90 and 120 min after lactose ingestion (repeated measures analysis of variance, p<0.01). Subjective ratings of the severity of abdominal cramping, belching, flatulence, vomiting and diarrhoea were significantly decreased following ingestion of the lactase pellets and lactose (no incidence of diarrhoea) compared with after ingestion of placebo and lactose. The results of the study were considered to be very promising as the beta-D-galactosidase formulation (which was produced at very low cost and with great ease) resisted inactivation in the stomach, effectively transformed lactose to glucose in vivo and reduced symptoms of lactose intolerance. PMID:9725505

  20. Deconditioning in patients with orthostatic intolerance

    PubMed Central

    Parsaik, Ajay; Allison, Thomas G.; Singer, Wolfgang; Sletten, David M.; Joyner, Michael J.; Benarroch, Eduardo E.; Low, Phillip A.

    2012-01-01

    Objective: To study the frequency and degree of deconditioning, clinical features, and relationship between deconditioning and autonomic parameters in patients with orthostatic intolerance. Methods: We retrospectively studied all patients seen for orthostatic intolerance at Mayo Clinic between January 2006 and June 2011, who underwent both standardized autonomic and exercise testing. Results: A total of 184 patients (84 with postural orthostatic tachycardia syndrome [POTS] and 100 without orthostatic tachycardia) fulfilled the inclusion criteria. Of these, 89% were women, and median age was 27.5 years (interquartile range [IQR] 2237 years). Symptom duration was 4 years (IQR 27.8). Of the patients, 90% had deconditioning (reduced maximum oxygen uptake [VO2max%] <85%) during exercise. This finding was unrelated to age, gender, or duration of illness. The prevalence of deconditioning was similar between those with POTS (95%) and those with orthostatic intolerance (91%). VO2max% had a weak correlation with a few autonomic and laboratory parameters but adequate predictors of VO2max% could not be identified. Conclusion: Reduced VO2max% consistent with deconditioning is present in almost all patients with orthostatic intolerance and may play a central role in pathophysiology. This finding provides a strong rationale for retraining in the treatment of orthostatic intolerance. None of the autonomic indices are reliable predictors of deconditioning. PMID:22993288

  1. [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

  2. Lactose intolerance in infants, children, and adolescents.

    PubMed

    Heyman, Melvin B

    2006-09-01

    The American Academy of Pediatrics Committee on Nutrition presents an updated review of lactose intolerance in infants, children, and adolescents. Differences between primary, secondary, congenital, and developmental lactase deficiency that may result in lactose intolerance are discussed. Children with suspected lactose intolerance can be assessed clinically by dietary lactose elimination or by tests including noninvasive hydrogen breath testing or invasive intestinal biopsy determination of lactase (and other disaccharidase) concentrations. Treatment consists of use of lactase-treated dairy products or oral lactase supplementation, limitation of lactose-containing foods, or dairy elimination. The American Academy of Pediatrics supports use of dairy foods as an important source of calcium for bone mineral health and of other nutrients that facilitate growth in children and adolescents. If dairy products are eliminated, other dietary sources of calcium or calcium supplements need to be provided. PMID:16951027

  3. Food allergy and food intolerance in childhood.

    PubMed

    Sullivan, P B

    1999-01-01

    Food intolerance is a reproducible adverse reaction to a specific food ingredient that is not psychologically based. Food allergy is a form of food intolerance in which there is evidence that the response is caused by an immunological reaction to food. Other mechanisms of food intolerance include enzyme defects (e.g. lactase deficiency), pharmacological effects (e.g. histamine), toxic properties (e.g. haemagglutinating lectins) and irritants (e.g. spices). Food allergy in children is a highly contentious subject and there is often a striking lack of published evidence from which to base clinical decisions. The true prevalence of food allergy in children is unknown, although there is evidence of an increasing incidence of allergic reactions to some foods, especially peanuts. Our understanding of why some children are unable to tolerate certain foods (e.g. cow's milk, egg), or how they grow out of this intolerance, is very poor. Symptoms of food allergy in children are diverse and include vomiting, poor weight gain, abdominal pain, malabsorption, cough, wheeze, rhinitis, atopic eczema, urticaria and angioedema. Despite the lack of objective data to support the notion that food intolerance contributes to behaviour in children, this is a belief firmly held by many parents and some professionals. The gold standard for diagnosing food intolerance is the double-blind placebo-controlled food challenge (DBPCFC). There is often a poor correlation between the results of food provocation tests and those of skin prick tests of radioallergosorbent tests for specific food antibodies. For proven food allergy, elimination diets are the mainstay of management. In children these must be closely supervised to avoid nutritional deficiency and compromise of growth. Some children who have had severe (anaphylactic) reactions after food need to have a supply of self-injectable adrenaline made available to their parents and teachers and must also practice strict avoidance of the offending food. PMID:11132467

  4. The Relationships between Metabolic Disorders (Hypertension, Dyslipidemia, and Impaired Glucose Tolerance) and Computed Tomography-Based Indices of Hepatic Steatosis or Visceral Fat Accumulation in Middle-Aged Japanese Men

    PubMed Central

    Yokokawa, Hirohide; Naito, Toshio; Sasabe, Noriko; Okumura, Mitsue; Iijima, Kimiko; Shibuya, Katsuhiko; Hisaoka, Teruhiko; Fukuda, Hiroshi

    2016-01-01

    Background Most studies on the relationships between metabolic disorders (hypertension, dyslipidemia, and impaired glucose tolerance) and hepatic steatosis (HS) or visceral fat accumulation (VFA) have been cross-sectional, and thus, these relationships remain unclear. We conducted a retrospective cohort study to clarify the relationships between components of metabolic disorders and HS/VFA. Methods The participants were 615 middle-aged men who were free from serious liver disorders, diabetes, and HS/VFA and underwent multiple general health check-ups at our institution between 2009 and 2013. The data from the initial and final check-ups were used. HS and VFA were assessed by computed tomography. HS was defined as a liver to spleen attenuation ratio of ≤1.0. VFA was defined as a visceral fat cross-sectional area of ≥100 cm2 at the level of the navel. Metabolic disorders were defined using Japan’s metabolic syndrome diagnostic criteria. The participants were divided into four groups based on the presence (+) or absence (-) of HS/VFA. The onset rates of each metabolic disorder were compared among the four groups. Results Among the participants, 521, 55, 24, and 15 were classified as HS(-)/VFA(-), HS(-)/VFA(+), HS(+)/VFA(-), and HS(+)/VFA(+), respectively, at the end of the study. Impaired glucose tolerance was more common among the participants that exhibited HS or VFA (p = 0.05). On the other hand, dyslipidemia was more common among the participants that displayed VFA (p = 0.01). Conclusions It is likely that VFA is associated with impaired glucose tolerance and dyslipidemia, while HS might be associated with impaired glucose tolerance. Unfortunately, our study failed to detect associations between HS/VFA and metabolic disorders due to the low number of subjects that exhibited fat accumulation. Although our observational study had major limitations, we consider that it obtained some interesting results. HS and VFA might affect different metabolic disorders. Further large-scale longitudinal studies are needed to reveal the relationships between the components of metabolic disorders and HS/VFA. PMID:26938785

  5. 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

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

    PubMed

    Wthrich, B

    2009-04-01

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

  7. [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

  8. 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)

  9. 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 ?-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

  10. Hypertension - overview

    MedlinePLUS

    If left untreated, hypertension can lead to the thickening of arterial walls causing its lumen, or blood passage way, to narrow in diameter. ... the narrowed arterial openings. In addition, people with hypertension may be more susceptible to stroke.

  11. Malignant hypertension

    MedlinePLUS

    ... hypertension; Arteriolar nephrosclerosis; Nephrosclerosis - arteriolar; Hypertension - malignant; High blood pressure - malignant ... affects a small number of people with high blood pressure, including children and adults. It is more common ...

  12. Pulmonary Hypertension

    MedlinePLUS

    ... page from the NHLBI on Twitter. What Is Pulmonary Hypertension? Pulmonary hypertension (PULL-mun-ary HI-per-TEN-shun), or PH, is increased pressure in the pulmonary arteries. These arteries carry blood from your heart ...

  13. Pulmonary Hypertension: Types and Treatments

    PubMed Central

    Rose-Jones, Lisa J; Mclaughlin, Vallerie V

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a panvasculopathy that affects the distal pulmonary arteries and leads to restricted blood flow. This increased afterload leads to adaptive mechanisms of the right ventricle, with eventual failure once it can no longer compensate. Pulmonary hypertension from associated conditions, most importantly left heart disease, i.e. heart failure, can also lead to the same sequela. Patients often experience early vague symptoms of dyspnea and exercise intolerance, and thus PH can elude clinicians until right heart failure symptoms predominate. Evidence-based treatment options with pulmo-nary vasodilators are available for those with PAH and should be employed early. It is essential that patients be accurately categorized by their etiology of PH, as treatment strategies differ, and can potentially be dangerous if employed in the wrong clinical scenario. PMID:24251459

  14. Distress intolerance and clinical functioning in persons with schizophrenia.

    PubMed

    Nugent, Katie L; Chiappelli, Joshua; Rowland, Laura M; Daughters, Stacey B; Hong, L Elliot

    2014-12-15

    Impaired tolerance to distress may help explain part of the cognitive and functional impairments in schizophrenia (SZ). This project investigated distress intolerance in SZ patients as compared to controls, and whether distress intolerance represented an independent domain in relationship to symptoms, cognition, and functional capacity. Healthy controls (n=43) and SZ (n=65) completed a psychological distress challenge experiment and their levels of intolerance to distress were estimated. SZ showed increased distress intolerance such that they were significantly more likely to terminate the distress challenge session early compared to controls. Greater distress intolerance was associated with reduced functional capacity and worse cognitive performance in SZ. Mediation analyses suggested that distress intolerance had an independent effect on functional capacity, while some of this effect was mediated by cognitive performance. Our results suggest that distress intolerance is a promising domain for treatment research, and functional capacity may be improved by targeting treatments towards SZ patient?s ability to tolerate distress. PMID:25107316

  15. [Childhood hypertension].

    PubMed

    Takemura, Tsukasa

    2015-11-01

    For accurate diagnosis of childhood hypertension, selection of appropriate manchette size according to the child age and the circumstantial size of upper limb is essentially important. In addition, except for the emergency case of hypertension, repeated measurement of blood pressure would be desirable in several weeks interval. Recently, childhood hypertension might be closely related to the abnormality of maternal gestational period caused by the strict diet and the maternal smoking. Developmental Origins of Health and Disease(DOHaD) theory is now highlighted in the pathogenesis of adulthood hypertension. To prevent hypertension of small-for-date baby in later phase of life, maternal education for child nursing should be conducted. In children, secondary hypertension caused by renal, endocrinologic, or malignant disease is predominant rather than idiopathic hypertension. PMID:26619664

  16. 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 50gm oral lactose load to healthy volunteers. Failure to rise blood glucose level ≥1.1mmol/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

  17. 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

  18. 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

  19. Statin intolerance: now a solved problem.

    PubMed

    Sikka, P; Kapoor, S; Bindra, V K; Sharma, M; Vishwakarma, P; Saxena, K K

    2011-01-01

    Statins are the most effective and widely used drugs for treating dyslipidemia, a major risk factor for coronary heart disease. These are one of the safest hypolipidemic drugs but many patients are bound to discontinue statins due to their side effects. Hepatotoxicity, myotoxicity and peripheral neuropathy are important out of them. Discontinuation of statins leads to dylipidemia and its grave consequences. Hence, there should be enough strategies for statin intolerant patients, so that they can be saved from these consequences. These side effects can be avoided by the awareness of certain factors viz. potential drug interactions and dose adjustment according to patho-physiology of the patient. Baseline investigations for liver function and muscle toxicity should be done before initiating statin therapy. Here, we are discussing various options for statin intolerant hyperlipidemic patients such as lower and intermittent dosing of statins, alternate hypolipidemic drugs, red yeast rice, supplementation with coenzyme Q10 and vitamin D. A number of hypolipidemic drugs are in trial phases and hold promise for statin intolerant patients. PMID:22120862

  20. 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.

  1. Resistant Hypertension.

    PubMed

    Doroszko, Adrian; Janus, Agnieszka; Szahidewicz-Krupska, Ewa; Mazur, Grzegorz; Derkacz, Arkadiusz

    2016-01-01

    Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension. PMID:26935512

  2. Sucrose feeding in mouse pregnancy leads to hypertension, and sex-linked obesity and insulin resistance in female offspring

    PubMed Central

    Samuelsson, Anne-Maj; Matthews, Phillippa A.; Jansen, Eugene; Taylor, Paul D.; Poston, Lucilla

    2013-01-01

    Eating an unbalanced diet during pregnancy may induce long-term health consequences in offspring, in particular obesity, insulin resistance, and hypertension. We tested the hypothesis that a maternal diet rich in simple sugars predispose mouse offspring to obesity, glucose intolerance, and cardiovascular diseases in adulthood. Female C57BL/6J mice were fed either a standard chow or a sucrose-rich diet (26% of total energy) 6 weeks prior to mating, throughout pregnancy and lactation. Offspring of control dams (OC) and high sucrose fed dams (OSF) were weaned onto standard control chow, and metabolic and cardiovascular parameters determined at 3 months of age. Both male and female OSF were hyperphagic by 4 weeks of age and females were heavier than OC at 6 weeks. At 3 months, female OSF showed a significant increase in inguinal fat pad mass, whereas skeletal muscle mass (tibialis anterior) and locomotor activity were decreased relative to OC. A 10-fold increase in fasting serum insulin in female OSF vs. OC at 3 months (Insulin [pmol/L] mean ± SEM, OSF, 200.3 ± 16.1, vs. OC, 20.3 ± 1.8, n = 6 P < 0.001), was associated with impaired glucose tolerance (AUC [mmol/L min] mean ± SEM, OSF 1437.4 ± 124.2 vs. OC, 1076.8 ± 83.9, n = 6, P < 0.05). Both male and female OSF were hypertensive as assessed by radiotelemetry (night-time systolic arterial pressure (SAP) [mmHg] mean ± SEM, male OSF, 128 ± 1 vs. OC, 109 ± 1, n = 6, P < 0.01; female OSF, 130 ± 1 vs. OC, 118 ± 1, n = 6, P < 0.05). Analysis of heart rate variability (HRV) demonstrated an increased low:high frequency ratio in male and female OSF (P < 0.05), indicative of heightened sympathetic efferent tone. Renal tissue noradrenaline (NA) content was markedly raised in the OSF vs. OC (NA [pg/ml/mg tissue] mean ± SEM, male OSF, 2.28 ± 0.19 vs. OC 0.84 ± 0.09, n = 6, P < 0.01). Exposure to a maternal diet rich in sucrose led to obesity and glucose intolerance in female mice offspring, and hypertension in both sexes. PMID:23423541

  3. Mineralocorticoid hypertension

    PubMed Central

    Gupta, Vishal

    2011-01-01

    Hypertension affects about 10 25% of the population and is an important risk factor for cardiovascular and renal disease. The renin-angiotensin system is frequently implicated in the pathophysiology of hypertension, be it primary or secondary. The prevalence of primary aldosteronism increases with the severity of hypertension, from 2% in patients with grade 1 hypertension to 20% among resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of disorders ranging from renin-producing pathologies (renin-secreting tumors, malignant hypertension, coarctation of aorta), aldosterone-producing pathologies (primary aldosteronism Conns syndrome, familial hyperaldosteronism 1, 2, and 3), non-aldosterone mineralocorticoid producing pathologies (apparent mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting tumors, ectopic adrenocorticotropic hormones (ACTH) syndrome, congenitalvadrenal hyperplasia), and drugs with mineraocorticoid activity (locorice, carbenoxole therapy) to glucocorticoid receptor resistance syndromes. Clinical presentation includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of plasma aldosterone concentraion to plasma renin activity remains the best screening tool. Bilateral adrenal venous sampling is the best diagnostic test coupled with a CT scan. Treatment is either surgical (adrenelectomy) for unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or bilateral disease. Medical therapy focuses on blood pressure control and correction of hypokalemia using a combination of anti-hypertensives (calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers) and potassium-raising therapies (mineralcorticoid receptor antagonist or potassium sparing diuretics). Direct aldosterone synthetase antagonists represent a promising future therapy. PMID:22145132

  4. 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.

  5. Antihypertensive drugs and glucose metabolism

    PubMed Central

    Rizos, Christos V; Elisaf, Moses S

    2014-01-01

    Hypertension plays a major role in the development and progression of micro- and macrovascular disease. Moreover, increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance. As a result the need for a comprehensive management of hypertensive patients is critical. However, the various antihypertensive drug categories have different effects on glucose metabolism. Indeed, angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis. Calcium channel blockers (CCBs) have an overall neutral effect on glucose metabolism. However, some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis. On the other hand, diuretics and ?-blockers have an overall disadvantageous effect on glucose metabolism. Of note, carvedilol as well as nebivolol seem to differentiate themselves from the rest of the ?-blockers class, being more attractive options regarding their effect on glucose homeostasis. The adverse effects of some blood pressure lowering drugs on glucose metabolism may, to an extent, compromise their cardiovascular protective role. As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment, especially in patients which are at high risk for developing diabetes. PMID:25068013

  6. Antihypertensive drugs and glucose metabolism.

    PubMed

    Rizos, Christos V; Elisaf, Moses S

    2014-07-26

    Hypertension plays a major role in the development and progression of micro- and macrovascular disease. Moreover, increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance. As a result the need for a comprehensive management of hypertensive patients is critical. However, the various antihypertensive drug categories have different effects on glucose metabolism. Indeed, angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis. Calcium channel blockers (CCBs) have an overall neutral effect on glucose metabolism. However, some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis. On the other hand, diuretics and β-blockers have an overall disadvantageous effect on glucose metabolism. Of note, carvedilol as well as nebivolol seem to differentiate themselves from the rest of the β-blockers class, being more attractive options regarding their effect on glucose homeostasis. The adverse effects of some blood pressure lowering drugs on glucose metabolism may, to an extent, compromise their cardiovascular protective role. As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment, especially in patients which are at high risk for developing diabetes. PMID:25068013

  7. The effect of polyphenol-rich dark chocolate on fasting capillary whole blood glucose, total cholesterol, blood pressure and glucocorticoids in healthy overweight and obese subjects.

    PubMed

    Almoosawi, Suzana; Fyfe, Lorna; Ho, Clement; Al-Dujaili, Emad

    2010-03-01

    Numerous studies indicate that polyphenol-rich chocolate reduces fasting blood glucose, blood pressure (BP) and total cholesterol in healthy individuals and hypertensives with or without glucose intolerance. The aim of the present study was to investigate the effect of two doses of polyphenol-rich dark chocolate (DC) on fasting capillary whole blood glucose, total cholesterol and BP and to examine whether improvements in these parameters are associated with changes in adrenocorticoid excretion in overweight and obese individuals. The study used a randomised, single-blind, cross-over design where fourteen overweight and obese subjects were randomised to either take 20 g DC with 500 mg polyphenols then 20 g DC with 1000 mg polyphenols or vice-versa. Participants followed each diet for 2 weeks separated by a 1-week washout period. It was observed that the 500 mg polyphenol dose was equally effective in reducing fasting blood glucose levels, systolic BP (SBP) and diastolic BP (DBP) as the 1000 mg polyphenol dose suggesting that a saturation effect might occur with increasing dose of polyphenols. There was also a trend towards a reduction in urinary free cortisone levels with both groups although it did not reach statistical significance. No changes in anthropometrical measurements were seen. We suggest that more research is required to investigate the mechanism(s) by which polyphenol-rich foods influence health. PMID:19825207

  8. Hypertension exacerbates liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined diet in rats.

    PubMed

    Arima, Shiho; Uto, Hirofumi; Ibusuki, Rie; Kumamoto, Ryo; Tanoue, Shirou; Mawatari, Seiichi; Oda, Kohei; Numata, Masatsugu; Fujita, Hiroshi; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito

    2014-01-01

    The effect of hypertension on non-alcoholic fatty liver disease (NAFLD) remains unclear at the molecular level. In this study, we investigated the effects of hypertension on the degree of hepatic steatosis, liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined (CDAA) diet in spontaneously hypertensive rats (SHRs). Seven-week-old male SHRs were fed standard chow with high or normal salt concentrations for 7 weeks, followed by a CDAA diet containing high or normal salt for an additional 8 or 24 weeks. Hepatic steatosis was assessed using hepatic triglyceride levels and Oil red O staining. Hepatic fibrosis was evaluated using Sirius red and Azan staining. Systolic blood pressure (SBP) gradually increased with a high-salt diet and was significantly higher after 7 weeks of feeding with high-salt vs. normal-salt chow. After 8 weeks on the CDAA diet, the degree of hepatic steatosis did not differ between the high-salt and normal-salt groups; however, alanine aminotransferase and fasting blood glucose levels were significantly higher and hepatic mRNA levels for interleukin (IL)-10 and heme oxygenase (HO)-1 were significantly lower in the high-salt group compared with the normal-salt group. After 24 weeks on the CDAA diet, the high-salt group had significantly more severe hepatic fibrosis and a higher hepatic mRNA expression of ?-smooth muscle actin and lower hepatic IL-10 and HO-1 mRNA levels compared with the normal-salt group. In conclusion, our results indicate that hypertension is a potential risk factor for liver injury and hepatic fibrosis through glucose intolerance and decreased IL-10-mediated or HO-1-induced anti-inflammatory mechanisms. PMID:24190226

  9. The clinical significance of lactose intolerance.

    PubMed

    Neaverson, M A

    1980-10-01

    Lactose intolerance may give rise to a variety of gastro enterological symptoms depending on the degree of lactase deficiency present. A percentage of patients may be asymtomatic, but the presence of lactose in their diet leads to inadequate absorption of a variety of important nutrients resulting in deficiency disorders or less than optimal weight gain. The increase in migration from southern Europe and of late from Indo-China significantly increases the Australian population likely to be lactase-deficient. Many immigrants keen to adapt to the Australian way of life see milk as a new essential part of their diet. This, accompanied with a lack of basic English as a language, may compound the problem of diagnosis in these patients particularly if the medical practitioner is unaware of the syndrome. The ready availability of lactose-hydrolyzed milk powder as a Pharmaceutical Benefit should allow all patients to gain the nutritional advantage of milk without suffering the complications associated with lactose intolerance. PMID:6893545

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

    PubMed

    Lugovi?-Mihi?, Liborija; Seserko, Ana; Duvanci?, Tomislav; Situm, Mirna; Mihi?, 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

  11. Chemical Intolerance in Primary Care Settings: Prevalence, Comorbidity, and Outcomes

    PubMed Central

    Katerndahl, David A.; Bell, Iris R.; Palmer, Raymond F.; Miller, Claudia S.

    2012-01-01

    PURPOSE This study extends previous community-based studies on the prevalence and clinical characteristics of chemical intolerance in a sample of primary care clinic patients. We evaluated comorbid medical and psychiatric disorders, functional status, and rates of health care use. METHODS A total of 400 patients were recruited from 2 family medicine clinic waiting rooms in San Antonio, Texas. Patients completed the validated Quick Environmental Exposure and Sensitivity Inventory (QEESI) to assess chemical intolerance; the Primary Care Evaluation of Mental Disorders (PRIME-MD) screen for possible psychiatric disorders; the DartmouthNorthern New England Primary Care Cooperative Information Project (Dartmouth COOP) charts for functional status; and the Healthcare Utilization Questionnaire. RESULTS Overall, 20.3% of the sample met criteria for chemical intolerance. The chemically intolerant group reported significantly higher rates of comorbid allergies and more often met screening criteria for possible major depressive disorder, panic disorder, generalized anxiety disorder, and alcohol abuse disorder, as well as somatization disorder. The total number of possible mental disorders was correlated with chemical intolerance scores (P <.001). Controlling for demographics, patients with chemical intolerance were significantly more likely to have poorer functional status, with trends toward increased medical service use when compared with nonchemically intolerant patients. After controlling for comorbid psychiatric conditions, the groups differed significantly only regarding limitations of social activities. CONCLUSIONS Chemical intolerance occurs in 1 of 5 primary care patients yet is rarely diagnosed by busy practitioners. Psychiatric comorbidities contribute to functional limitations and increased health care use. Chemical intolerance offers an etiologic explanation. Symptoms may resolve or improve with the avoidance of salient chemical, dietary (including caffeine and alcohol), and drug triggers. Given greater medication intolerances in chemical intolerance, primary care clinicians could use the QEESI to identify patients for appropriate triage to comprehensive nonpharmacologic care. PMID:22778124

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  13. 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

  14. 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…

  15. 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 unsurprisingly, the greatest ability to emerge from burial in all other species was from shallow (2 cm) burial. Although survival was consistently highly dependent on duration and depth of burial as expected, emergence behaviour was not as easily predictable thereby confounding predictions. We conclude that responses to burial are highly species specific and therefore tolerance generalisations are likely to be oversimplifications. These data may be used to inform environmental impact models that allow forecasting of the cumulative impacts of seabed disturbance and may provide mitigation measures for the sustainable use of the seabed. PMID:26901775

  16. 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 unsurprisingly, the greatest ability to emerge from burial in all other species was from shallow (2 cm) burial. Although survival was consistently highly dependent on duration and depth of burial as expected, emergence behaviour was not as easily predictable thereby confounding predictions. We conclude that responses to burial are highly species specific and therefore tolerance generalisations are likely to be oversimplifications. These data may be used to inform environmental impact models that allow forecasting of the cumulative impacts of seabed disturbance and may provide mitigation measures for the sustainable use of the seabed. PMID:26901775

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

    PubMed

    Savaiano, Dennis

    2011-01-01

    The potential for lactose intolerance causes 25-50 million Americans and an unknown number of people around the world to avoid milk. Milk avoidance is a significant risk factor for low bone density. Individuals who avoid milk, due to intolerance or learned aversion, consume significantly less calcium and have poorer bone health and probable higher risk of osteoporosis. Lactose intolerance is easily managed by: (1) regular consumption of milk that adapts the colon bacteria and facilitates digestion of lactose; (2) consumption of yogurts and cheeses and other dairy foods low in lactose; consumption of dairy foods with meals to slow transit and maximize digestion, and use of lactose-digestive aids. As dairying spreads around the world to new markets and dairy foods become the dominant source of calcium in these markets, the potential for lactose intolerance will grow. Management of lactose intolerance globally will require both education and product development. PMID:21335997

  18. Pulmonary Hypertension

    MedlinePLUS

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

  19. Hypertension screening

    NASA Technical Reports Server (NTRS)

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  20. Renovascular hypertension

    MedlinePLUS

    ... hypertension: Therapy. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook ... and diagnosis. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook ...

  1. [Hypertensive retinopathy].

    PubMed

    Genevois, Olivier; Paques, Michel

    2010-01-20

    Acute hypertensive retinopathy should be distinguished from retinal arteriolosclerosis. The presence of microvascular abnormalities in the ocular fundus increases the risk of heart and/or brain attack. At the clinical level, the current classification of chronic hypertensive retinopathy is based on the long-term risk of stroke. In research, a great number of studies are focused on the predictive value of retinal vascular diameters related to the general micro- and macrovascular disease. PMID:20222306

  2. Pulmonary Hypertension

    PubMed Central

    Newman, John H.

    2005-01-01

    The modern era in cardiopulmonary medicine began in the 1940s, when Cournand and Richards pioneered right-heart catheterization. Until that time, no direct measurement of central vascular pressure had been performed in humans. Right-heart catheterization ignited an explosion of insights into function and dysfunction of the pulmonary circulation, cardiac performance, ventilationperfusion relationships, lungheart interactions, valvular function, and congenital heart disease. It marked the beginnings of angiocardiography with its diagnostic implications for diseases of the left heart and peripheral circulation. Pulmonary hypertension was discovered to be the consequence of a large variety of diseases that either raised pressure downstream of the pulmonary capillaries, induced vasoconstriction, increased blood flow to the lung, or obstructed the pulmonary vessels, either by embolism or in situ fibrosis. Hypoxic vasoconstriction was found to be a major cause of acute and chronic pulmonary hypertension, and surprising vasoreactivity of the pulmonary vascular bed was discovered to be present in many cases of severe pulmonary hypertension, initially in mitral stenosis. Diseases as disparate as scleroderma, cystic fibrosis, kyphoscoliosis, sleep apnea, and sickle cell disease were found to have shared consequences in the pulmonary circulation. Some of the achievements of Cournand and Richards and their scientific descendents are discussed in this article, including success in the diagnosis and treatment of idiopathic pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and management of hypoxic pulmonary hypertension. PMID:15994464

  3. Mechanisms of sympathetic regulation in orthostatic intolerance

    PubMed Central

    2012-01-01

    Sympathetic circulatory control is key to the rapid cardiovascular adjustments that occur within seconds of standing upright (orthostasis) and which are required for bipedal stance. Indeed, patients with ineffective sympathetic adrenergic vasoconstriction rapidly develop orthostatic hypotension, prohibiting effective upright activities. One speaks of orthostatic intolerance (OI) when signs, such as hypotension, and symptoms, such as lightheadedness, occur when upright and are relieved by recumbence. The experience of transient mild OI is part of daily life. However, many people experience episodic acute OI as postural faint or chronic OI in the form of orthostatic tachycardia and orthostatic hypotension that significantly reduce the quality of life. Potential mechanisms for OI are discussed including forms of sympathetic hypofunction, forms of sympathetic hyperfunction, and OI that results from regional blood volume redistribution attributable to regional adrenergic hypofunction. PMID:22678960

  4. [Lactose and gluten intolerance: which to suscept?].

    PubMed

    Van Gossum, M; Mascart, F; Rickaert, F; Codden, T; Colonius, V

    2000-09-01

    Lactose intolerance affects millions of people world-wide and should be suspected specially when evaluating gastrointestinal symptoms in ethnic populations in which it is prevalent. Fortunately, once a diagnosis is made, management is fairly straightforward. The authors discuss symptoms and methods of detection and offer their recommendations for helping patients with this common disorder. Coeliac disease is the end result of 3 processes that culminate in intestinal damage: genetic predisposition, environmental factors, and immunological based inflammation. Epidemiological studies based on serologic tests suggest that the prevalence of coeliac disease has been significantly underestimated. The classic sprue syndrome of steatorrhea and malnutrition may be less common than more subtle and often monosymptomatic presentations of the disease. The authors discuss the diagnostic criteria and the clinical utility of serologic tests. PMID:11068484

  5. 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

  6. Captopril in essential hypertension

    PubMed Central

    Estrada, E. Rabinad; Morin, M. Ingelmo; Amenos, A. Martinez; Alsina, J.; Gorina, A. Balcells

    1982-01-01

    1 Forty-one patients with essential hypertension, stages I, II, and III, were treated with captopril alone or in combination with hydrochlorothiazide. Forty two percent were responsive to captopril alone, while the remaining 58% also required the diuretic. The need for the diuretic was related to the phase of hypertension. 2 There was no significant relation between drug response and plasma renin activity. Serum concentrations of creatinine and potassium remained normal, and there were no pathological changes in serum glucose, cholesterol, uric acid concentrations, erythrocyte count, packed cell volume, haemoglobin, or heart rate. 3 Captopril was well tolerated. One patient developed a rash and another ageusia, which disappeared spontaneously. A third, who was also taking allopurinol, developed leucopenia but it disappeared after treatment was withdrawn. There were no cases of proteinuria attributable to captopril; and proteinuria disappeared in four of five patients who were proteinuric before the start of treatment. 4 These findings suggest that doses of captopril of 150 mg to 300 mg (with or without a diuretic) may be adequate for controlling the blood pressure of most patients with essential hypertension. PMID:6753890

  7. Hypothalamic NUCKS regulates peripheral glucose homoeostasis.

    PubMed

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

    2015-08-01

    Nuclear ubiquitous casein and cyclin-dependent kinase substrate (NUCKS) is highly expressed in the brain and peripheral metabolic organs, and regulates transcription of a number of genes involved in insulin signalling. Whole-body depletion of NUCKS (NKO) in mice leads to obesity, glucose intolerance and insulin resistance. However, a tissue-specific contribution of NUCKS to the observed phenotypes remains unknown. Considering the pivotal roles of insulin signalling in the brain, especially in the hypothalamus, we examined the functions of hypothalamic NUCKS in the regulation of peripheral glucose metabolism. Insulin signalling in the hypothalamus was impaired in the NKO mice when insulin was delivered through intracerebroventricular injection. To validate the hypothalamic specificity, we crossed transgenic mice expressing Cre-recombinase under the Nkx2.1 promoter with floxed NUCKS mice to generate mice with hypothalamus-specific deletion of NUCKS (HNKO). We fed the HNKO and littermate control mice with a normal chow diet (NCD) and a high-fat diet (HFD), and assessed glucose tolerance, insulin tolerance and metabolic parameters. HNKO mice showed mild glucose intolerance under an NCD, but exacerbated obesity and insulin resistance phenotypes under an HFD. In addition, NUCKS regulated levels of insulin receptor in the brain. Unlike HNKO mice, mice with immune-cell-specific deletion of NUCKS (VNKO) did not develop obesity or insulin-resistant phenotypes under an HFD. These studies indicate that hypothalamic NUCKS plays an essential role in regulating glucose homoeostasis and insulin signalling in vivo. PMID:26205492

  8. Prevalence of methotrexate intolerance in rheumatoid arthritis and psoriatic arthritis

    PubMed Central

    2013-01-01

    Introduction The aim of this study was to determine the prevalence of gastrointestinal and behavioural symptoms occurring before (anticipatory/associative) and after methotrexate (MTX) administration, termed MTX intolerance, in rheumatoid (RA) and psoriatic arthritis (PsA). Methods Methotrexate Intolerance Severity Score (MISS), previously validated in juvenile idiopathic arthritis patients, was used to determine MTX intolerance prevalence in 291 RA/PsA patients. The MISS consisted of four domains: abdominal pain, nausea, vomiting and behavioural symptoms, occurring upon, prior to (anticipatory) and when thinking of MTX (associative). MTX intolerance was defined as ?6 on the MISS with ?1 point on anticipatory and/or associative and/or behavioural items. Results A total of 123 patients (42.3%) experienced at least one gastrointestinal adverse effect. The prevalence of MTX intolerance was 11%. MTX intolerance prevalence was higher in patients on parenteral (20.6%) than on oral MTX (6.2%) (p?intolerance, in order to intervene timely and avoid discontinuation of an effective treatment. PMID:24345416

  9. Drug-induced hypertension

    MedlinePLUS

    Drug-induced hypertension is high blood pressure caused by using a chemical substance, drug, or medication. ... found. Secondary hypertension occurs because of another disorder. Drug-induced hypertension is a form of secondary hypertension ...

  10. Diagnosing hypertension

    PubMed Central

    Gelfer, Mark; Dawes, Martin; Kaczorowski, Janusz; Padwal, Raj; Cloutier, Lyne

    2015-01-01

    Abstract Objective To highlight the 2015 Canadian Hypertension Education Program (CHEP) recommendations for the diagnosis and assessment of hypertension. Quality of evidence A systematic search was performed current to August 2014 by a Cochrane Collaboration librarian using the MEDLINE and PubMed databases. The search results were critically appraised by the CHEP subcommittee on blood pressure (BP) measurement and diagnosis, and evidence-based recommendations were presented to the CHEP Central Review Committee for independent review and grading. Finally, the findings and recommendations were presented to the Recommendations Task Force for discussion, debate, approval, and voting. The main recommendations are based on level II evidence. Main message Based on the most recent evidence, CHEP has made 4 recommendations in 2 broad categories for 2015 to improve BP measurement and the way hypertension is diagnosed. A strong recommendation is made to use electronic BP measurement in the office setting to replace auscultatory BP measurement. For patients with elevated office readings, CHEP is recommending early use of out-of-office BP measurement, preferably ambulatory BP measurement, in order to identify early in the process those patients with white-coat hypertension. Conclusion Improvements in diagnostic accuracy are critical to optimizing hypertension management in Canada. The annual updates provided by CHEP ensure that practitioners have up-to-date evidence-based information to inform practice. PMID:26564654

  11. Diagnosing and Treating Intolerance to Carbohydrates in Children.

    PubMed

    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

  12. Neural Correlates of Intolerance of Uncertainty in Clinical Disorders.

    PubMed

    Wever, Mirjam; Smeets, Paul; Sternheim, Lot

    2015-01-01

    Intolerance of uncertainty is a key contributor to anxiety-related disorders. Recent studies highlight its importance in other clinical disorders. The link between its clinical presentation and the underlying neural correlates remains unclear. This review summarizes the emerging literature on the neural correlates of intolerance of uncertainty. In conclusion, studies focusing on the neural correlates of this construct are sparse, and findings are inconsistent across disorders. Future research should identify neural correlates of intolerance of uncertainty in more detail. This may unravel the neurobiology of a wide variety of clinical disorders and pave the way for novel therapeutic targets. PMID:26185902

  13. 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

  14. Exercise Hypertension

    PubMed Central

    Schultz, Martin G.; Sharman, James E.

    2014-01-01

    Irrespective of apparent ‘normal' resting blood pressure (BP), some individuals may experience an excessive elevation in BP with exercise (i.e. systolic BP ≥210 mm Hg in men or ≥190 mm Hg in women or diastolic BP ≥110 mm Hg in men or women), a condition termed exercise hypertension or a ‘hypertensive response to exercise' (HRE). An HRE is a relatively common condition that is identified during standard exercise stress testing; however, due to a lack of information with respect to the clinical ramifications of an HRE, little value is usually placed on such a finding. In this review, we discuss both the clinical importance and underlying physiological contributors of exercise hypertension. Indeed, an HRE is associated with an increased propensity for target organ damage and also predicts the future development of hypertension, cardiovascular events and mortality, independent of resting BP. Moreover, recent work has highlighted that some of the elevated cardiovascular risks associated with an HRE may be related to high-normal resting BP (pre-hypertension) or ambulatory ‘masked' hypertension and that an HRE may be an early warning signal of abnormal BP control that is otherwise undetected with clinic BP. Whilst an HRE may be amenable to treatment via pharmacological and lifestyle interventions, the exact physiological mechanism of an HRE remains elusive, but it is likely a manifestation of multiple factors including large artery stiffness, increased peripheral resistance, neural circulatory control and metabolic irregularity. Future research focus may be directed towards determining threshold values to denote the increased risk associated with an HRE and further resolution of the underlying physiological factors involved in the pathogenesis of an HRE. PMID:26587435

  15. Exercise Hypertension.

    PubMed

    Schultz, Martin G; Sharman, James E

    2014-05-01

    Irrespective of apparent 'normal' resting blood pressure (BP), some individuals may experience an excessive elevation in BP with exercise (i.e. systolic BP ?210 mm Hg in men or ?190 mm Hg in women or diastolic BP ?110 mm Hg in men or women), a condition termed exercise hypertension or a 'hypertensive response to exercise' (HRE). An HRE is a relatively common condition that is identified during standard exercise stress testing; however, due to a lack of information with respect to the clinical ramifications of an HRE, little value is usually placed on such a finding. In this review, we discuss both the clinical importance and underlying physiological contributors of exercise hypertension. Indeed, an HRE is associated with an increased propensity for target organ damage and also predicts the future development of hypertension, cardiovascular events and mortality, independent of resting BP. Moreover, recent work has highlighted that some of the elevated cardiovascular risks associated with an HRE may be related to high-normal resting BP (pre-hypertension) or ambulatory 'masked' hypertension and that an HRE may be an early warning signal of abnormal BP control that is otherwise undetected with clinic BP. Whilst an HRE may be amenable to treatment via pharmacological and lifestyle interventions, the exact physiological mechanism of an HRE remains elusive, but it is likely a manifestation of multiple factors including large artery stiffness, increased peripheral resistance, neural circulatory control and metabolic irregularity. Future research focus may be directed towards determining threshold values to denote the increased risk associated with an HRE and further resolution of the underlying physiological factors involved in the pathogenesis of an HRE. PMID:26587435

  16. Exercise Intolerance in Individuals With Postconcussion Syndrome

    PubMed Central

    Kozlowski, Karl F.; Graham, James; Leddy, John J.; Devinney-Boymel, Lee; Willer, Barry S.

    2013-01-01

    Context: Little is known about exercise intolerance or the utility of an exercise evaluation in patients with postconcussion syndrome (PCS). Objective: To assess exercise intolerance in male and female patients with PCS. Design: Cross-sectional study. Setting: Laboratory setting. Patients or Other Participants: Participants included a convenience sample of 34 patients with PCS (17 males, 17 females; age = 25.9 10.9 years) and 22 uninjured individuals on whom we gathered historical deidentified laboratory data (control group; 11 males, 11 females; age = 23.3 6.2 years). Main Outcome Measure(s): Self-reported symptoms, heart rate, systolic and diastolic blood pressures (BPs), and the Borg rating of perceived exertion were measured before, during each minute of, and immediately after a graded treadmill exercise test (Balke protocol). Exercise was stopped when participants could no longer maintain the effort or reported the onset of or increase in PCS symptoms. Results: Exercise test duration (8.5 4.4 minutes versus 17.9 3.6 minutes; t51 = 1.8, P < .001), heart rate (142.8 24.1 versus 175.2 17.4; t54 = ?5.5, P < .001), and systolic BP (142.1 18.3 mm Hg versus 155.5 24.5 mm Hg; t53 = 2.3, P = .02) were lower, and diastolic BP (78.4 10.2 mm Hg versus 73.5 11.7 mm Hg; t53 = 2.2, P = .03) was higher at test cessation in the PCS than control group. Cox regression showed the odds of a shorter exercise duration were nearly 8 times greater in the PCS than control group (hazard ratio = 7.93; 95% confidence interval = 3.39, 18.56). In the general linear models that adjusted for differences in test duration, rating of perceived exertion was the only physiologic measure to show an overall difference between groups, with the control group reporting higher ratings than the PCS group (t53 = ?6.0, P < .001). Within the PCS group, systolic BP was the only measure to show a sex effect, with males showing higher pressure readings than females throughout the exercise tests (t31 = 2.8, P = .009). Conclusions: Patients with PCS had a symptom-limited response to exercise, and the treadmill test was a potentially useful tool to monitor the recovery from PCS. PMID:23952041

  17. NMR measurements of intracellular ions in hypertension

    NASA Astrophysics Data System (ADS)

    Veniero, Joseph C.; Gupta, R. K.

    1993-08-01

    The NMR methods for the measurement of intracellular free Na+, K+, Mg2+, Ca2+, and H+ are introduced. The recent literature is then presented showing applications of these methods to cells and tissues from hypertensive animal model systems, and humans with essential hypertension. The results support the hypothesis of consistent derangement of the intracellular ionic environment in hypertension. The theory that this derangement may be a common link in the disease states of high blood pressure and abnormal insulin and glucose metabolism, which are often associated clinically, is discussed.

  18. Upregulation of NOS by simulated microgravity, potential cause of orthostatic intolerance.

    PubMed

    Vaziri, N D; Ding, Y; Sangha, D S; Purdy, R E

    2000-07-01

    Prolonged exposure to microgravity during spaceflight or extended bed rest results in cardiovascular deconditioning, marked by orthostatic intolerance and hyporesponsiveness to vasopressors. Earlier studies primarily explored fluid and electrolyte balance and baroreceptor and vasopressor systems in search of a possible mechanism. Given the potent vasodilatory and natriuretic actions of nitric oxide (NO), we hypothesized that cardiovascular adaptation to microgravity may involve upregulation of the NO system. Male Wistar rats were randomly assigned to a control group or a group subjected to simulated microgravity by hindlimb unloading (HU) for 20 days. Tissues were harvested after death for determination of total nitrate and nitrite (NOx) as well as endothelial (e), inducible (i), and neuronal (n) NO synthase (NOS) proteins by Western blot. Separate subgroups were used to test blood pressure response to norepinephrine and the iNOS inhibitor aminoguanidine. Compared with controls, the HU group showed a significant increase in tissue NOx content and an upregulation of iNOS protein abundance in thoracic aorta, heart, and kidney and of nNOS protein expression in the brain and kidney but no discernible change in eNOS expression. This was associated with marked attenuation of hypertensive response to norepinephrine and a significant increase in hypertensive response to aminoguanidine, suggesting enhanced iNOS-derived NO generation in the HU group. Upregulation of these NOS isotypes can contribute to cardiovascular adaptation to microgravity by promoting vasodilatory tone and natriuresis and depressing central sympathetic outflow. If true in humans, short-term administration of an iNOS inhibitor may ameliorate orthostatic intolerance in returning astronauts and patients after extended bed rest. PMID:10904069

  19. 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.

  20. 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 patients 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

  1. Intolerance of uncertainty and adult separation anxiety.

    PubMed

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

    2014-01-01

    Intolerance of uncertainty (IU)-the tendency to react negatively to situations that are uncertain-is involved in different anxiety disorders and depression. No studies have yet examined the association between IU and symptoms of adult separation anxiety disorder. However, it is possible that greater difficulties tolerating uncertainties that can occur in relationships with attachment figures inflate fears and worries about the consequences of being separated from these attachment figures. The current study examined the possible role of IU in symptoms of adult separation anxiety disorder, relative to its role in symptoms of generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD), social anxiety, and depression, using self-reported data from 215 undergraduates (92% women) with elevated separation anxiety. Findings showed that IU was significantly associated with symptom levels of separation anxiety disorder, GAD, OCD, social anxiety, and depression (rs > .30). IU continued to explain variance in OCD, social anxiety, and depression (but not GAD and separation anxiety) when controlling for the association of neuroticism, attachment anxiety, and attachment avoidance with these symptoms. Additional findings indicated that IU is more strongly associated with symptoms of GAD, OCD, and social anxiety than symptoms of adult separation anxiety disorder and depression. PMID:24601766

  2. 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

  3. Intolerance of Ambiguity and Student Performance in Social Work Education.

    ERIC Educational Resources Information Center

    Davis, Liane V.; Sherman, Edmund

    1987-01-01

    Social workers must assist people in coping with complex, often apparently insoluble, problems. Data are presented on the relationship between intolerance of ambiguity and a variety of performance and preference measures of 212 social work students. (Author/MH)

  4. Antroduodenal motility in neurologically handicapped children with feeding intolerance

    PubMed Central

    Werlin, Steven L

    2004-01-01

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

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

    PubMed

    Matthews, S B; Waud, J P; Roberts, A G; Campbell, A K

    2005-03-01

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

  6. The role of colonic metabolism in lactose intolerance.

    PubMed

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

    2008-08-01

    Lactose maldigestion and intolerance affect a large part of the world population. The underlying factors of lactose intolerance are not fully understood. In this review, the role of colonic metabolism is discussed, i.e. fermentation of lactose by the colonic microbiota, colonic processing of the fermentation metabolites and how these processes would play a role in the pathophysiology of lactose intolerance. We suggest that the balance between the removal and production rate of osmotic-active components (lactose, and intermediate metabolites, e.g. lactate, succinate, etc.) in the colon is a key factor in the development of symptoms. The involvement of the colon may provide the basis for designing new targeted strategies for dietary and clinical management of lactose intolerance. PMID:18573099

  7. Hypertensive Crisis

    MedlinePLUS

    ... kidney function Aortic dissection Angina (unstable chest pain) Pulmonary edema (fluid backup in the lungs) Eclampsia If you get a blood pressure reading of 180 or higher on top or 110 or higher on the bottom, and are having any ... Hypertension Metabolic Syndrome BP vs. Heart Rate BP ...

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

    PubMed Central

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

    2013-01-01

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

  9. 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

  10. 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

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

    PubMed

    Misselwitz, Benjamin; Pohl, Daniel; Frhauf, 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

  12. 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, 0.130.21) in patients and 0.17 (IQR 0.120.19) in controls (p?>?0.05). Respective levels of GLUT2 mRNA were 0.26 (IQR 0.200.31) and 0.26 (IQR 0.190.31) (p?>?0.05). Median expression levels of GLUT5 protein normalized to alpha-tubulin were 0.95 (IQR 0.521.68) in patients and 0.95 (IQR 0.591.15) in controls (p?>?0.05). Respective protein expression levels for GLUT2 were 1.56 (IQR 1.062.14) and 1.35 (IQR 0.961.79) (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

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

    SciTech Connect

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

    1982-03-01

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

  14. Improvement of diabetes, obesity and hypertension in type 2 diabetic KKA{sup y} mice by bis(allixinato)oxovanadium(IV) complex

    SciTech Connect

    Adachi, Yusuke; Yoshikawa, Yutaka; Yoshida, Jiro; Kodera, Yukihiro . E-mail: kodera_y@wakunaga.co.jp; Katoh, Akira . E-mail: katoh@st.seikei.ac.jp; Takada, Jitsuya . E-mail: takada@hl.rri.kyoto-u.ac.jp; Sakurai, Hiromu . E-mail: sakurai@mb.kyoto-phu.ac.jp

    2006-07-07

    Previously, we found that bis(allixinato)oxovanadium(IV) (VO(alx){sub 2}) exhibits a potent hypoglycemic activity in type 1-like diabetic mice. Since the enhancement of insulin sensitivity is involved in one of the mechanisms by which vanadium exerts its anti-diabetic effects, VO(alx){sub 2} was further tested in type 2 diabetes with low insulin sensitivity. The effect of oral administration of VO(alx){sub 2} was examined in obesity-linked type 2 diabetic KKA{sup y} mice. Treatment of VO(alx){sub 2} for 4 weeks normalized hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia and hypertension in KKA{sup y} mice; however, it had no effect on hypoadiponectinemia. VO(alx){sub 2} also improved hyperleptinemia, following attenuation of obesity in KKA{sup y} mice. This is the first example in which a vanadium compound improved leptin resistance in type 2 diabetes by oral administration. On the basis of these results, VO(alx){sub 2} is proposed to enhance not only insulin sensitivity but also leptin sensitivity, which in turn improves diabetes, obesity and hypertension in an obesity-linked type 2 diabetic animal.

  15. Opportunity of detecting pre-hypertension: worldwide data on blood pressure overswinging

    PubMed Central

    Cornlissen, G.; Delcourt, A.; Toussaint, G.; Otsuka, K.; Watanabe, Y.; Siegelova, J.; Fiser, B.; Dusek, J.; Homolka, P.; Singh, R.B.; Kumar, A.; Singh, R.K.; Sanchez, S.; Gonzalez, C.; Holley, D.; Sundaram, B.; Zhao, Z.; Tomlinson, B.; Fok, B.; Zeman, M.; Dulkova, K.; Halberg, Franz

    2008-01-01

    Overswinging or CHAT (brief for Circadian Hyper-Amplitude-Tension), that is an excessive circadian variation in blood pressure (BP), has been associated with a large increase in cardiovascular disease risk, present even in the absence of an elevated BP itself. This usually asymptomatic condition is usually overlooked by current practice based on spot-checks, because to be diagnosed, measurements need to be taken around-the-clock, preferably for 7 days at the outset. Once diagnosed, however, a usual circadian BP pattern can be restored by means of certain non-pharmacologic or pharmacologic interventions timed appropriately. Thereby, it is possible to reduce the risk of cardiovascular morbidity and mortality, cerebral ischemic events and nephropathy in particular. For the preparation of guidelines regarding the diagnosis of BP disorders and for the institution of primary as well as secondary preventive measures, it is important to know what the incidence of CHAT is on a global basis. We found 191 cases of CHAT among 1602 mostly 7-day/24-h BP profiles, obtained from several centers in different countries participating in an ongoing project on the BIOsphere and the COSmos (BIOCOS). CHAT incidence is about the same between men and women, but it is diagnosed more often among patients with borderline hypertension or with glucose intolerance. It is also more common among MESOR-hypertensive than among MESOR-normotensive individuals. Priority should be given to the development of an unobtrusive and affordable device to automatically monitor BP and to analyze the data as-one-goes, so that cardiovascular disease risk can be prevented. PMID:16275485

  16. Glucose metabolic gene expression in growth hormone transgenic coho salmon.

    PubMed

    Panserat, Stphane; Kamalam, Biju Sam; Fournier, Jeanne; Plagnes-Juan, Elisabeth; Woodward, Krista; Devlin, Robert H

    2014-04-01

    Salmonids are generally known to be glucose intolerant. However, previous studies have shown that growth hormone (GH) transgenic coho salmon display modified nutritional regulation of glycolysis and lipogenesis compared to non-transgenic fish, suggesting the potential for better use of glucose in GH transgenic fish. To examine this in detail, GH transgenic and non-transgenic coho salmon were subjected to glucose tolerance test and subsequent metabolic assessments. After intra-peritoneal injection of 250mg/kg glucose, we analysed post-injection kinetics of glycaemia and expression of several key target genes highly involved in glucose homeostasis in muscle and liver tissues. Our data show no significant differences in plasma glucose levels during peak hyperglycaemia (3-6h after injection), demonstrating a similar glucose tolerance between transgenic and non transgenic. However, and unrelated to the hyperglycaemic episode, GH transgenic fish return to a slightly lower basal glycaemia values 24h after injection. Correspondingly, GH transgenic fish exhibited higher mRNA levels of glucokinase (GK) and glucose-6-phosphate dehydrogenase (G6PDH) in liver, and glucose transporter (GLUT4) in muscle. These data suggest that these metabolic actors may be involved in different glucose use in GH transgenic fish, which would be expected to influence the glucose challenge response. Overall, our data demonstrate that GH transgenic coho salmon may be a pertinent animal model for further study of glucose metabolism in carnivorous fish. PMID:24486143

  17. Osteocalcin as a hormone regulating glucose metabolism.

    PubMed

    Kanazawa, Ippei

    2015-12-25

    The number of patients with osteoporosis and diabetes is rapidly increasing all over the world. Bone is recently recognized as an endocrine organ. Accumulating evidence has shown that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, regulates glucose homeostasis by stimulating insulin expression in pancreas and adiponectin expression in adipocytes, resulting in improving glucose intolerance. On the other hand, insulin and adiponectin stimulate osteocalcin expression in osteoblasts, suggesting that positive feedforward loops exist among bone, pancreas, and adipose tissue. In addition, recent studies have shown that osteocalcin enhances insulin sensitivity and the differentiation in muscle, while secreted factors from muscle, myokines, regulate bone metabolism. These findings suggest that bone metabolism and glucose metabolism are associated with each other through the action of osteocalcin. In this review, I describe the role of osteocalcin in the interaction among bone, pancreas, brain, adipose tissue, and muscle. PMID:26722618

  18. Osteocalcin as a hormone regulating glucose metabolism

    PubMed Central

    Kanazawa, Ippei

    2015-01-01

    The number of patients with osteoporosis and diabetes is rapidly increasing all over the world. Bone is recently recognized as an endocrine organ. Accumulating evidence has shown that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, regulates glucose homeostasis by stimulating insulin expression in pancreas and adiponectin expression in adipocytes, resulting in improving glucose intolerance. On the other hand, insulin and adiponectin stimulate osteocalcin expression in osteoblasts, suggesting that positive feedforward loops exist among bone, pancreas, and adipose tissue. In addition, recent studies have shown that osteocalcin enhances insulin sensitivity and the differentiation in muscle, while secreted factors from muscle, myokines, regulate bone metabolism. These findings suggest that bone metabolism and glucose metabolism are associated with each other through the action of osteocalcin. In this review, I describe the role of osteocalcin in the interaction among bone, pancreas, brain, adipose tissue, and muscle. PMID:26722618

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

    SciTech Connect

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

    1986-01-01

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

  20. Dietary treatment of lactose intolerance in infants and children.

    PubMed

    Sinden, A A; Sutphen, J L

    1991-12-01

    During the past several years there have been many reports of alternative dietary therapies for primary and secondary lactose intolerance. We have learned that it is useful to feed through most episodes of mild diarrhea that previously would have been treated with clear liquid diets. Infant formulas, including both soy-protein and hydrolysate formulas with specially designed carbohydrate, protein, and fat components, are available to treat the infant with diarrheal syndromes and secondary lactase deficiency. Also, the diet can be supplemented with lactase. Specialized lactose-reduced products as well as cultured and fermented dairy products may be used in varying degrees for lactose-intolerant children. The ingestion of milk with food and fiber components in the diet has also been shown to improve symptoms of lactose intolerance. This review summarizes the essentials of diagnosis of and dietary therapy for lactose intolerance. Our findings indicate that a number of specialized formulas and products are available for successful dietary management of lactose intolerance in infants and children. PMID:1960350

  1. Hypertension (High Blood Pressure)

    MedlinePLUS

    ... I Help a Friend Who Cuts? Hypertension (High Blood Pressure) KidsHealth > For Teens > Hypertension (High Blood Pressure) ... Hypertension Treated? Can I Prevent It? What Is Blood Pressure? We all need blood pressure to live. ...

  2. What Causes Pulmonary Hypertension?

    MedlinePLUS

    ... page from the NHLBI on Twitter. What Causes Pulmonary Hypertension? Pulmonary hypertension (PH) begins with inflammation and changes in the ... that can cause them, go to "Types of Pulmonary Hypertension." Rate This Content: NEXT >> Updated: August 2, 2011 ...

  3. Types of Pulmonary Hypertension

    MedlinePLUS

    ... page from the NHLBI on Twitter. Types of Pulmonary Hypertension The World Health Organization divides pulmonary hypertension (PH) ... small blood vessels of the lungs. Group 2 Pulmonary Hypertension Group 2 includes PH with left heart disease. ...

  4. Management of malnourished children with acute diarrhoea and sugar intolerance.

    PubMed

    Beau, J P; Fontaine, O; Garenne, M

    1990-04-01

    A protocol of nutritional rehabilitation using fermented milk, vegetable oil and caster sugar has been tested on 54 Senegalese children, aged 6-36 months, admitted with acute diarrhoea and malnutrition. At the time of admission, 39 per cent of children were dehydrated and 26 per cent had sugar intolerance. In the course of treatment three went home against medical advice and one died from acute pneumonia with respiratory-heart failure. Among the cases of marasmus there were no differences in mean weight gain between children with sugar intolerance and others despite a longer duration of diarrhoea in the first group. Furthermore, the experimental protocol has never been compromised because of worsening diarrhoea or weight loss. These results indicate that a formula based on fermented milk together with oral rehydration can be used to treat malnourished children with acute diarrhoea and sugar intolerance. PMID:2355409

  5. Management of malnourished children with acute diarrhoea and sugar intolerance.

    PubMed

    Beau, J P; Fontaine, O; Garenne, M

    1989-12-01

    A protocol of nutritional rehabilitation using fermented milk, vegetable oil, and castor sugar has been tested on 54 Senegalese children age 6-36 months admitted with acute diarrhoea and malnutrition. At time of admission, 39 per cent of children were dehydrated and 26 per cent had sugar intolerance. In the course of treatment three absconded and one died from acute pneumonia with respiratory and heart failure. Among those with marasmus there were no differences in mean weight gains between children with sugar intolerance and others, despite a longer duration of diarrhoea in the first group. Furthermore, the treatment protocol has never been compromised because of worsening diarrhoea or weight loss. These results indicate that a formula based on fermented milk together with oral rehydration can be used to treat malnourished children with acute diarrhoea and sugar intolerance. PMID:2514280

  6. Recent advances in the management of lactose intolerance.

    PubMed

    Savaiano, D A; Kotz, C

    1989-01-01

    Lactose intolerance is a concern for the majority of the world's population. Persons who experience symptoms following the consumption of milk should consult with their physician. Symptoms may be eliminated or reduced with good dietary management that includes: Limiting milk consumption to one glass at a time. Drinking milk with other foods rather than alone. Eating yogurts instead of fluid milk. Using enzyme tablets to predigest the lactose in milk or to supplement the body's own lactase. Possibly eating small amounts of dairy foods each day to adapt the colonic bacteria. For an additional review of the research findings on lactose intolerance and milk drinking, the reader is directed to reference 4, a very recent and complete review by Scrimshaw and Murray. For information on dietary management of lactose intolerance suitable for the consumer, contact your local affiliate of the National Dairy Council. PMID:2656797

  7. Left atrial volume index is an independent predictor of hypertensive response to exercise in patients with hypertension.

    PubMed

    Lee, Sang-Eun; Youn, Jong-Chan; Lee, Hye Sun; Park, Sungha; Lee, Sang-Hak; Cho, In-Jeong; Shim, Chi Young; Hong, Geu-Ru; Choi, Donghoon; Kang, Seok-Min

    2015-02-01

    A hypertensive response to exercise (HRE) is known to be associated with higher risk of heart failure and future cardiovascular events in patients with hypertension. Left atrial volume index (LAVI) is associated with the diastolic dysfunction, indicating exercise intolerance. Therefore, we investigated whether LAVI is relevant to HRE during cardiopulmonary exercise test (CPET). We studied 118 consecutive hypertensive patients (61 men, 5711 years) and 45 normotensive control subjects (16 men, 548 years). Clinical characteristics, CPET, echocardiographic and laboratory findings were assessed at the time of enrollment. HRE was defined as maximum systolic blood pressure (SBP)?210?mm?Hg in men and ?190?mm?Hg in women. HRE was more prevalent in hypertensive patients compared with normotensive control subjects (50.8% vs. 20.0%, P<0.001). Age and baseline SBP were shown to be associated with HRE in normotensive control subjects, as were baseline SBP and LAVI in hypertensive group. In multivariate analysis, LAVI was found to be an independent predictor of HRE in hypertensive patients (P=0.020) but not in normotensive control subjects (P=0.936) when controlled for age, sex, body mass index and peak oxygen consumption. Higher LAVI, reflecting the duration and severity of increased left atrial pressure is independently associated with HRE in hypertensive patients, but not in normotensive control subjects. PMID:25253581

  8. Dairy Intake, Dietary Adequacy, and Lactose Intolerance12

    PubMed Central

    Heaney, Robert P.

    2013-01-01

    Despite repeated emphasis in the Dietary Guidelines for Americans on the importance of calcium in the adult American diet and the recommendation to consume 3 dairy servings a day, dairy intake remains well below recommendations. Insufficient health professional awareness of the benefits of calcium and concern for lactose intolerance are among several possible reasons, This mini-review highlights both the role of calcium (and of dairy, its principal source in modern diets) in health maintenance and reviews the means for overcoming lactose intolerance (real or perceived). PMID:23493531

  9. [Histamine intolerance syndrome. Its significance for ENT medicine].

    PubMed

    Bttcher, I; Klimek, L

    2008-08-01

    The symptoms of histamine intolerance are similar to those of the IgE-mediated allergic immune response. Patients affected by this disease, mostly middle-aged women, suffer from conditions such as headaches and rhinitis, particularly after consuming histamine-rich foods, indulging in alcoholic beverages, or taking certain pharmaceuticals. Moreover, life-threatening anaphylactic reactions can be observed with this syndrome. This article describes the biochemical processes and cellular background of histamine intolerance syndrome and discusses the diagnostic and therapeutic procedures within otorhinolaryngology. It is our goal to direct attention to this often unrecognized clinical picture and to contribute to increased immunologic knowledge of this disease. PMID:18649066

  10. [Histamine intolerance and pseudoallergy--do they exist?].

    PubMed

    Hannuksela, Matti; Haahtela, Tari

    2012-01-01

    Histamine intolerance (HIT) is a controversial syndrome, in which the body is believed to react to histamine released by certain foodstuffs. Symptoms include among other things headache, urticaria and abdominal discomfort. Several fruits, nuts, spices and food additives have been regarded as pseudoallergens. Since there is no objective investigation to prove HIT, the diagnosis is based on symptoms. On the basis of literature, better clinical studies are needed. Because the phenomenon remains unclear, use of the terms histamine intolerance and pseudoallergens is not recommended. PMID:22667048

  11. When to suspect lactose intolerance. Symptomatic, ethnic, and laboratory clues.

    PubMed

    Srinivasan, R; Minocha, A

    1998-09-01

    Lactose intolerance is widespread, with adult-type hypolactasia being the predominant cause of lactose malabsorption. Daily ingestion of less than 240 mL of milk is well tolerated by most lactose-intolerant adults. Some persons with normal lactase activity may become symptomatic on consumption of products containing lactose. Lactose maldigestion may coexist in adults with irritable bowel syndrome and in children with recurrent abdominal pain. Management consists primarily of dietary changes. People who avoid dairy products should receive calcium supplementation and should be advised to read ingredient labels carefully. Several lactase replacement products are available, but their efficacy varies. PMID:9742907

  12. Essential Hypertension vs. Secondary Hypertension Among Children

    PubMed Central

    Banker, Ashish; Shete, Sanjay; Hashmi, Syed Sharukh; Tyson, John E.; Barratt, Michelle S.; Hecht, Jacqueline T.; Milewicz, Diane M.; Boerwinkle, Eric

    2015-01-01

    BACKGROUND The aim was to determine the proportions and correlates of essential hypertension among children in a tertiary pediatric hypertension clinic. METHODS We evaluated 423 consecutive children and collected demographic and clinical history by retrospective chart review. RESULTS We identified 275 (65%) hypertensive children (blood pressure >95th percentile per the “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents”) from 423 children referred to the clinic for history of elevated blood pressure. The remainder of the patients had normotension (11%), white coat hypertension (11%), prehypertension (10%), and pending diagnosis (3%). Among the 275 hypertensive children, 43% (n = 119; boys = 56%; median age = 12 years; range = 3–17 years) had essential hypertension and 57% (n = 156; boys = 66%; median age = 9 years; range = 0.08–19 years) had secondary hypertension. When compared with those with secondary hypertension, those with essential hypertension had a significantly older age at diagnosis (P = 0.0002), stronger family history of hypertension (94% vs. 68%; P < 0.0001), and lower prevalence of preterm birth (20% vs. 46%; P < 0.001). There was a bimodal distribution of age of diagnosis in those with secondary hypertension. CONCLUSIONS The phenotype of essential hypertension can present as early as 3 years of age and is the predominant form of hypertension in children after age of 6 years. Among children with hypertension, those with essential hypertension present at an older age, have a stronger family history of hypertension, and have lower prevalence of preterm birth. PMID:24842390

  13. 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

  14. How Many People Are Affected or At Risk for Lactose Intolerance?

    MedlinePLUS

    ... Information Clinical Trials Resources and Publications How many people are affected or at risk for lactose intolerance? ... media links Share this: Page Content How many people are lactose intolerant? The true number of people ...

  15. Clinical role of a fixed combination of standardized Berberis aristata and Silybum marianum extracts in diabetic and hypercholesterolemic patients intolerant to statins

    PubMed Central

    Di Pierro, Francesco; Bellone, Iaele; Rapacioli, Giuliana; Putignano, Pietro

    2015-01-01

    Background Statin intolerance is a medical condition often leading patients to nonadherence to the prescribed therapy or to a relevant reduction of the statin dosage. Both situations determine a totally or partially uncontrolled lipid profile, and these conditions unquestionably increase the risk of cardiovascular events. Methods We enrolled hypercholesterolemic, type 2 diabetic patients complaining of intolerance to statins. Some of them had reduced the statin dose ‘until the disappearance of symptoms’; others had opted for treatment with ezetimibe; and yet others were not undergoing any treatment at all. All patients of the three groups were then given a fixed combination of berberine and silymarin (Berberol®), known from previous papers to be able to control both lipidic and glycemic profiles. Results The tested product both as a single therapy and as add-on therapy to low-dose statin or to ezetimibe reduced triglycerides, low-density lipoprotein cholesterol, fasting blood glucose, and glycosylated hemoglobin in a significant manner without inducing toxicity conditions that might be somehow ascribed to a statin-intolerant condition. Conclusion Our study demonstrates that use of Berberol®, administered as a single or add-on therapy in statin-intolerant subjects affected by diabetes and hypercholesterolemia is a safe and effective tool capable of improving the patients’ lipidic and glycemic profiles. PMID:25678808

  16. Are ambiguity aversion and ambiguity intolerance identical? A neuroeconomics investigation.

    PubMed

    Tanaka, Yusuke; Fujino, Junya; Ideno, Takashi; Okubo, Shigetaka; Takemura, Kazuhisa; Miyata, Jun; Kawada, Ryosaku; Fujimoto, Shinsuke; Kubota, Manabu; Sasamoto, Akihiko; Hirose, Kimito; Takeuchi, Hideaki; Fukuyama, Hidenao; Murai, Toshiya; Takahashi, Hidehiko

    2014-01-01

    In recent years, there has been growing interest in understanding a person's reaction to ambiguous situations, and two similar constructs related to ambiguity, "ambiguity aversion" and "ambiguity intolerance," are defined in different disciplines. In the field of economic decision-making research, "ambiguity aversion" represents a preference for known risks relative to unknown risks. On the other hand, in clinical psychology, "ambiguity intolerance" describes the tendency to perceive ambiguous situations as undesirable. However, it remains unclear whether these two notions derived from different disciplines are identical or not. To clarify this issue, we combined an economic task, psychological questionnaires, and voxel-based morphometry (VBM) of structural brain magnetic resonance imaging (MRI) in a sample of healthy volunteers. The individual ambiguity aversion tendency parameter, as measured by our economic task, was negatively correlated with agreeableness scores on the self-reported version of the Revised NEO Personality Inventory. However, it was not correlated with scores of discomfort with ambiguity, one of the subscales of the Need for Closure Scale. Furthermore, the ambiguity aversion tendency parameter was negatively correlated with gray matter (GM) volume of areas in the lateral prefrontal cortex and parietal cortex, whereas ambiguity intolerance was not correlated with GM volume in any region. Our results suggest that ambiguity aversion, described in decision theory, may not necessarily be identical to ambiguity intolerance, referred to in clinical psychology. Cautious applications of decision theory to clinical neuropsychiatry are recommended. PMID:25698984

  17. 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

  18. 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

  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. Lactose intolerance. Recognizing the link between diet and discomfort.

    PubMed

    Aurisicchio, L N; Pitchumoni, C S

    1994-01-01

    Lactose intolerance is a common disorder encountered in clinical practice. Evaluation involves obtaining a thorough nutritional history and recognizing associations between diet and gastrointestinal complaints. Lack of suspicion of the problem can lead to expensive and invasive diagnostic procedures, which may further aggravate patients' anxiety and result in iatrogenic complications. Once the diagnosis is confirmed, simple dietary management may resolve symptoms completely. PMID:8278293

  1. Action of an extract from the seeds of Fraxinus excelsior L. on metabolic disorders in hypertensive and obese animal models.

    PubMed

    Mont, Ferm; Arce, Cristina; Noguera, Maria Antonia; Ivorra, Maria Dolores; Flanagan, John; Roller, Marc; Issaly, Nicolas; D'Ocon, Pilar

    2014-04-01

    Nuzhenide and GI3, the principal secoiridoids of an extract obtained from the seeds of Fraxinus excelsior L. (FXE), are believed to be the active compounds responsible for the previously reported hypoglycemic effects of this extract. In this study, the effects of FXE were studied in two animal models which are representative of metabolic disorders: spontaneously hypertensive rats (SHR) and obese Zucker rats. SHR were acutely treated (oral gavage) with different doses of FXE. In addition, SHR and Zucker rats were chronically fed (20 or 5 weeks, respectively) with standard chow supplemented with FXE. Acute treatment with FXE (200 mg per kg body weight) decreased systolic blood pressure as in the case with captopril (50 mg per kg body weight). Chronic treatment with FXE at 100 mg per kg body weight per day, a dose equivalent to that showing hypoglycemic activity in humans, resulted in a significant decrease in glycemia (-16.3%), triglyceridemia (-33.4%) and body weight (-8.1%) in Zucker rats as well as a significant decrease in SBP in SHR (-6.7%), with a concomitant improvement in endothelial function in both strains. The broad-ranging effects of FXE may be due to a unique compositional profile that could be useful to prevent the metabolic syndrome, characterized by obesity, insulin resistance, glucose intolerance, hypertriglyceridemia and elevated blood pressure. PMID:24573510

  2. 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...

  3. Glucose toxicity.

    PubMed

    Rossetti, L; Giaccari, A; DeFronzo, R A

    1990-06-01

    Glucose toxicity is a well-established entity that has been shown in animal models of diabetes to contribute to development of insulin resistance and impaired insulin secretion. In type II (non-insulin-dependent) diabetes in humans, a considerable body of evidence has accumulated indicating that a chronic physiological increment in the plasma glucose concentration leads to progressive impairment in insulin secretion and may contribute to insulin resistance as well. The precise biochemical mechanism(s) responsible for the hyperglycemia-induced defect in insulin secretion remains to be defined but may be related to a defect in phosphoinositide metabolism. In animal models of diabetes, development of insulin resistance is related to downregulation of the glucose-transport system, and a similar phenomenon is also likely to occur in humans. In addition, hyperglycemia in humans may lead to a defect in glycogen synthesis. In this respect, humans may be different from rats. In type I (insulin-dependent) diabetic patients who are poorly controlled, insulin resistance is a characteristic feature and can be ameliorated by tight glycemic control, suggesting that hyperglycemia is responsible for the insulin resistance. Evidence also has accumulated to implicate glucose toxicity in the functional impairment in insulin secretion that occurs during the initial presentation of patients with type I diabetes, and this may explain the honeymoon period so commonly observed after the institution of insulin therapy. PMID:2192847

  4. Glucose Tests

    MedlinePLUS

    ... services. Advertising & Sponsorship: Policy | Opportunities PLEASE NOTE: Your web browser does not have JavaScript enabled. Unless you enable Javascript , your ability to navigate and access the features of this website will be limited. ... Glucose Tests Share this page: Was this page helpful? Also ...

  5. 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...

  6. Glutathionylation of hepatic and visceral adipose proteins decreases in obese-prone, glucose intolerant rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity and insulin resistance are associated with increases in oxidative stress and lipid peroxidation. On the other hand, adipocytes from obese animals have elevated GSH content, and insulin resistance can be reversed by GSH depletion. Oxidation of active site cysteines of protein tyrosine phospha...

  7. Age- and gender-related changes in glucose homeostasis in glucocorticoid-treated rats.

    PubMed

    dos Santos, Cristiane; Ferreira, Francielle Batista D; Gonalves-Neto, Luiz M; Taboga, Sebastio Roberto; Boschero, Antonio Carlos; Rafacho, Alex

    2014-10-01

    The disruption to glucose homeostasis upon glucocorticoid (GC) treatment in adult male rats has not been fully characterized in older rats or in females. Thus, we evaluated the age- and gender-related changes in glucose homeostasis in GC-treated rats. We injected male and female rats at 3 months and 12 months of age with either dexamethasone (1.0 mg/kg body mass, intraperitoneally) or saline, daily for 5 days. All of the GC-treated rats had decreased body mass and food intake, and adrenal hypotrophy. Increased glycemia was observed in all of the GC-treated groups and only the 3-month-old female rats were not glucose intolerant. Dexamethasone treatment resulted in hyperinsulinemia and hypertriacylglyceridemia in all of the GC-treated rats. The glucose-stimulated insulin secretion (GSIS) was higher in all of the dexamethasone-treated animals, but it was less pronounced in the older animals. The ?-cell mass was increased in the younger male rats treated with dexamethasone. We conclude that dexamethasone treatment induces glucose intolerance in both the 3- and 12-month-old male rats as well as hyperinsulinemia and augmented GSIS. Three-month-old female rats are protected from glucose intolerance caused by GC, whereas 12-month-old female rats developed the same complications that were present in 3- and 12-month-old male rats. PMID:25272090

  8. Effect of a single dose of lactase on symptoms and expired hydrogen after lactose challenge in lactose-intolerant subjects.

    PubMed

    Sanders, S W; Tolman, K G; Reitberg, D P

    1992-06-01

    The effect of a single dose or oral lactase on symptoms, breath hydrogen concentration, and glucose absorption in lactose-intolerant subjects challenged with lactose was studied. Volunteers underwent a lactose challenge test; those whose breath hydrogen concentrations increased 20 ppm or more and who met other criteria were admitted as subjects. After fasting, the subjects were given three chewable lactase tablets (total lactase dose, 9900 FCC units) or placebo tablets in a randomized, double-blind, crossover manner. The subjects also consumed 8 oz of whole milk in which 37.5 g of lactose powder was dissolved (total lactose content, 50 g). The washout period between lactose challenges was at least one week. Breath hydrogen and plasma glucose concentrations were measured before and at intervals after the challenges, and the subjects completed symptom-evaluation questionnaires every eight hours for four days. Twenty-four subjects completed the study. The maximum mean breath hydrogen concentration was significantly lower after lactase treatment than after placebo treatment. In 21 subjects, the area under the hydrogen concentration-time curve (AUC) was lower after lactase than after placebo; three subjects had hydrogen AUCs more than 300 ppm.hr lower. There were no significant differences in plasma glucose levels. Subjective ratings of the severity of abdominal cramping, belching, flatulence, and diarrhea were lower during the first eight hours after challenge in lactase-treated subjects; ratings for bloating were lower during the next eight hours. Single doses of a chewable lactase tablet reduced the concentration of expired hydrogen and symptoms of lactose intolerance after a lactose challenge. PMID:1534729

  9. Low renin hypertension

    PubMed Central

    Sahay, Manisha; Sahay, Rakesh K.

    2012-01-01

    Low renin hypertension is an important and often underdiagnosed cause of hypertension. It may be associated with high aldosterone levels as in Conn's syndrome or low aldosterone levels as in Liddle syndrome, and syndrome of apparent mineralocorticoid excess, glucocorticoid remediable hypertension etc. Some forms of essential hypertension are also associated with low renin levels. Hypokalemia may be an important finding in low renin hypertension. The aldosterone to renin ratio helps in correct diagnosis. The treatment varies with etiology hence an accurate diagnosis is essential. Aldosterone antagonists play an important role in medical management of some varieties of low renin hypertension. PMID:23087856

  10. Oral health in coeliac disease and cow's milk protein intolerance.

    PubMed

    Andersson-Wenckert, I; Blomquist, H K; Fredrikzon, B

    1984-01-01

    The oral health of 24 children and adolescents, 19 with coeliac disease (CD) and 5 with cow's milk protein intolerance (CMPI) were compared with that of 24 randomly selected paired controls. Mineralisation disorders in the form of hypoplasias and/or opacities occurred in 74% of the cases of CD and 68% of their controls. All 5 cases with CMPI had mineralisation disorders, as did 2 of their controls. The disorders usually took the form of opacities, and both these and the hypoplasias were of a mild nature in all the groups. Serious hypoplasias did not occur at all. The caries status was, on average, better in the CD and CMPI groups than in the controls. Recurrent oral lesions occurred with almost the same frequency in the intolerance groups and in the controls. The study, therefore, gave no clear evidence that CD or CMPI involves a significant risk of poorer oral health, provided adequate paediatric and dental care is given. PMID:6585998

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

    PubMed

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

    2015-01-01

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

    PubMed

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

    2011-09-01

    Worry is the inflated concern about potential future threats and is a hallmark feature of generalized anxiety disorder. Previous theoretical work has suggested that worry may be a consequence of intolerance of uncertainty (IU). The current study seeks to explore the behavioral consequences of IU. Specifically, we examine how IU might be associated with aspects of reward-based decision making. We utilized a simple laboratory gambling task in which participants chose between small, low-probability rewards available immediately at the beginning of each trial and large, high-probability rewards only available after some variable delay. Results demonstrate that higher levels of intolerance of uncertainty were associated with a tendency to select the immediately available, but less valuable and less probable rewards. IU also predicted decision-makers' sensitivity to outcomes. We discuss the cognitive and affective mechanisms that are likely to underlie the observed decision-making behavior and the implications for anxiety disorders. PMID:21658521

  13. 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

  14. Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency

    NASA Technical Reports Server (NTRS)

    Shannon, J. R.; Flattem, N. L.; Jordan, J.; Jacob, G.; Black, B. K.; Biaggioni, I.; Blakely, R. D.; Robertson, D.

    2000-01-01

    BACKGROUND: Orthostatic intolerance is a syndrome characterized by lightheadedness, fatigue, altered mentation, and syncope and associated with postural tachycardia and plasma norepinephrine concentrations that are disproportionately high in relation to sympathetic outflow. We tested the hypothesis that impaired functioning of the norepinephrine transporter contributes to the pathophysiologic mechanism of orthostatic intolerance. METHODS: In a patient with orthostatic intolerance and her relatives, we measured postural blood pressure, heart rate, plasma catecholamines, and systemic norepinephrine spillover and clearance, and we sequenced the norepinephrine-transporter gene and evaluated its function. RESULTS: The patient had a high mean plasma norepinephrine concentration while standing, as compared with the mean (+/-SD) concentration in normal subjects (923 vs. 439+/-129 pg per milliliter [5.46 vs. 2.59+/-0.76 nmol per liter]), reduced systemic norepinephrine clearance (1.56 vs. 2.42+/-0.71 liters per minute), impairment in the increase in the plasma norepinephrine concentration after the administration of tyramine (12 vs. 56+/-63 pg per milliliter [0.07 vs. 0.33+/-0.37 pmol per liter]), and a disproportionate increase in the concentration of plasma norepinephrine relative to that of dihydroxyphenylglycol. Analysis of the norepinephrine-transporter gene revealed that the proband was heterozygous for a mutation in exon 9 (encoding a change from guanine to cytosine at position 237) that resulted in more than a 98 percent loss of function as compared with that of the wild-type gene. Impairment of synaptic norepinephrine clearance may result in a syndrome characterized by excessive sympathetic activation in response to physiologic stimuli. The mutant allele in the proband's family segregated with the postural heart rate and abnormal plasma catecholamine homeostasis. CONCLUSIONS: Genetic or acquired deficits in norepinephrine inactivation may underlie hyperadrenergic states that lead to orthostatic intolerance.

  15. Pulmonary Hypertension and Vascular Abnormalities in Bronchopulmonary Dysplasia.

    PubMed

    Mourani, Peter M; Abman, Steven H

    2015-12-01

    Despite advances in the care of preterm infants, these infants remain at risk bronchopulmonary dysplasia (BPD), which results in prolonged need for supplemental oxygen, recurrent respiratory exacerbations, and exercise intolerance. Recent investigations have highlighted the important contribution of the developing pulmonary circulation to lung development, showing that these infants are also at risk for pulmonary vascular disease (PVD), including pulmonary hypertension (PH) and pulmonary vascular abnormalities. Several epidemiologic studies have delineated the incidence of PH in preterm infants and the impact on outcomes. These studies have also highlighted gaps in the understanding of PVD in BPD. PMID:26593082

  16. 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.

  17. 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.

  18. Lactose maldigestion and milk intolerance in healthy Greek schoolchildren.

    PubMed

    Ladas, S D; Katsiyiannaki-Latoufi, E; Raptis, S A

    1991-03-01

    The prevalence of lactose maldigestion in Greek adults is 75% but the age at which the lactase activity starts declining is not known. The prevalences of lactose maldigestion and intolerance were investigated in 150 randomly selected Greek children 5-12 y old by using breath-hydrogen analysis after ingestion of lactose (2 g/kg body wt, maximum 50 g) or 0.240 L of milk. Prevalence of lactose maldigestion increased with age (y = -7.30 + 6.49x, r = 0.88, P = 0.004), being 29.4% and 80.0% at ages 5 and 12 y, respectively. Before testing, the reported prevalences of milk-related symptoms by children with high and low lactose-digestion capacity were 21.1% and 39.7% (chi 2 = 5.96, P = 0.015), respectively. However, the corresponding prevalences of lactose intolerance after ingestion of milk were 7.3% and 8.6% (chi 2 = 0.1, P = 0.72) and only three children had a delta H2 greater than or equal to 20 ppm postprandially. Although intestinal lactase activity declines before age 5 y and many Greek children report milk-related symptoms, true malabsorption and intolerance of lactose after a glass of milk is rarely seen at this age. PMID:2000821

  19. Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3): a parallel-group, double-blind randomised phase 4 trial

    PubMed Central

    Brown, Morris J; Williams, Bryan; Morant, Steve V; Webb, David J; Caulfield, Mark J; Cruickshank, J Kennedy; Ford, Ian; McInnes, Gordon; Sever, Peter; Salsbury, Jackie; Mackenzie, Isla S; Padmanabhan, Sandosh; MacDonald, Thomas M

    2016-01-01

    Summary Background Potassium depletion by thiazide diuretics is associated with a rise in blood glucose. We assessed whether addition or substitution of a potassium-sparing diuretic, amiloride, to treatment with a thiazide can prevent glucose intolerance and improve blood pressure control. Methods We did a parallel-group, randomised, double-blind trial in 11 secondary and two primary care sites in the UK. Eligible patients were aged 18–80 years; had clinic systolic blood pressure of 140 mm Hg or higher and home systolic blood pressure of 130 mmHg or higher on permitted background drugs of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β blockers, calcium-channel blockers, or direct renin inhibitors (previously untreated patients were also eligible in specific circumstances); and had at least one component of the metabolic syndrome in addition to hypertension. Patients with known diabetes were excluded. Patients were randomly assigned (1:1:1) to 24 weeks of daily oral treatment with starting doses of 10 mg amiloride, 25 mg hydrochlorothiazide, or 5 mg amiloride plus 12·5 mg hydrochlorothiazide; all doses were doubled after 12 weeks. Random assignment was done via a central computer system. Both participants and investigators were masked to assignment. Our hierarchical primary endpoints, assessed on a modified intention-to-treat basis at 12 and 24 weeks, were the differences from baseline in blood glucose measured 2 h after a 75 g oral glucose tolerance test (OGTT), compared first between the hydrochlorothiazide and amiloride groups, and then between the hydrochlorothiazide and combination groups. A key secondary endpoint was change in home systolic blood pressure at 12 and 24 weeks. This trial is registered with ClinicalTrials.gov, number NCT00797862, and the MHRA, Eudract number 2009-010068-41, and is now complete. Findings Between Nov 18, 2009, and Dec 15, 2014, 145 patients were randomly assigned to amiloride, 146 to hydrochlorothiazide, and 150 to the combination group. 132 participants in the amiloride group, 134 in the hydrochlorothiazide group, and 133 in the combination group were included in the modified intention-to-treat analysis. 2 h glucose concentrations after OGTT, averaged at 12 and 24 weeks, were significantly lower in the amiloride group than in the hydrochlorothiazide group (mean difference −0·55 mmol/L [95% CI −0·96 to −0·14]; p=0·0093) and in the combination group than in the hydrochlorothiazide group (−0·42 mmol/L [–0·84 to −0·004]; p=0·048). The mean reduction in home systolic blood pressure during 24 weeks did not differ significantly between the amiloride and hydrochlorothiazide groups, but the fall in blood pressure in the combination group was significantly greater than that in the hydrochlorothiazide group (p=0·0068). Hyperkalaemia was reported in seven (4·8%) patients in the amiloride group and three (2·3%) patients in the combination group; the highest recorded potassium concentration was 5·8 mmol/L in a patient in the amiloride group. 13 serious adverse events occurred but the frequency did not differ significantly between groups. Interpretation The combination of amiloride with hydrochlorothiazide, at doses equipotent on blood pressure, prevents glucose intolerance and improves control of blood pressure compared with montherapy with either drug. These findings, together with previous data about morbidity and mortality for the combination, support first-line use of amiloride plus hydrochlorothiazide in hypertensive patients who need treatment with a diuretic. Funding British Heart Foundation and National Institute for Health Research. PMID:26489809

  20. Hypertension and aging.

    PubMed

    Buford, Thomas W

    2016-03-01

    Hypertension is a highly prevalent condition with numerous health risks, and the incidence of hypertension is greatest among older adults. Traditional discussions of hypertension have largely focused on the risks for cardiovascular disease and associated events. However, there are a number of collateral effects, including risks for dementia, physical disability, and falls/fractures which are increasingly garnering attention in the hypertension literature. Several key mechanisms - including inflammation, oxidative stress, and endothelial dysfunction - are common to biologic aging and hypertension development and appear to have key mechanistic roles in the development of the cardiovascular and collateral risks of late-life hypertension. The objective of the present review is to highlight the multi-dimensional risks of hypertension among older adults and discuss potential strategies for treatment and future areas of research for improving overall care for older adults with hypertension. PMID:26835847

  1. Cirrhosis and Portal Hypertension

    MedlinePLUS

    MENU Return to Web version Cirrhosis and Portal Hypertension Overview What is cirrhosis? In people who have ... lead to coma and death. What is portal hypertension? Normally, blood is carried to the liver by ...

  2. Hypertension in women

    PubMed Central

    Hage, Fadi G; Mansur, Sulaf J; Xing, Dongqi; Oparil, Suzanne

    2013-01-01

    Hypertension is the most common modifiable risk factor for cardiovascular disease, the leading cause of death in both men and women. The prevalence and severity of hypertension rise markedly with age, and blood pressure control becomes more difficult with aging in both genders, particularly in women. In addition, there are forms of hypertension that occur exclusively in women, e.g., hypertension related to menopause, oral contraceptive use, or pregnancy (e.g., chronic hypertension, gestational hypertension, pre-eclampsia or eclampsia). Randomized controlled trials show that antihypertensive therapy provides similar reductions in major cardiovascular events in men and women. Therefore, gender should not influence decisions on selection of blood pressure lowering therapies, except for consideration of gender-specific side effects or contraindications for use in women who are or may become pregnant. This article reviews the prevalence, awareness, treatment, and control of hypertension in women, as well as recent guidelines for management of hypertension in women. PMID:25028640

  3. Pulmonary hypertension - at home

    MedlinePLUS

    Pulmonary hypertension (PAH) is abnormally high blood pressure in the arteries of the lungs. With PAH, the right ... Chin K, Channick RN. Pulmonary hypertension. In: Broaddus VC, ... Nadel's Textbook of Respiratory Medicine . 6th ed. Philadelphia, ...

  4. 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

  5. Depression in hypertensive subjects.

    PubMed

    Ramachandran, V; Parikh, G J; Srinivasan, V

    1983-10-01

    168 patients attending hypertension clinic were randomly selected for the study. They were thoroughly investigated using E.C.G., X-ray chest, Urine analysis, Blood sugar, Blood urea, Serum cholesterol, Serum K, Serum Na, Scrum creatinine and Uric acid level. Detailed psychiatric case history and mental examination was carried out. Beck Rating Scale was used to measure the depression. 25% of hypertensive subjects exhibited depressive features and their mean score in Beck Rating scale is 21.76. The mean score of non-depressives is 4.46. All patients were receiving methyl dopa.25 mg. twice or thrice daily with thiazide diuretic. No significant difference in the incidence of depression with the duration of medication was observed.The hypertension was classified into mild, moderate and severe depending on the diastolic pressure. Depression was more frequent in severe hypertensives but not to the statistically significant level.Further hypertensives were classified into:1. Hypertension without organ involvement2. Hypertension with LVH only3. Hypertension with additional organ involvement4. Malignant hypertensionDepression was significantly more frequent in hypertensives with complications and also hypertensives in whom the B.P. remained uncontrolled. As all the patients were on the same drug, the drug effect is common to all; hence, the higher incidence of depression in hypertensives with complications is due to the limitation and distress caused by the illness. PMID:21847301

  6. 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.

  7. Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain.

    PubMed

    Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L; Kanekiyo, Takahisa; Bu, Guojun

    2015-04-01

    Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-? (A?) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of A? in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor ? in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. PMID:25855193

  8. Neuronal LRP1 Regulates Glucose Metabolism and Insulin Signaling in the Brain

    PubMed Central

    Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L.; Kanekiyo, Takahisa

    2015-01-01

    Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-? (A?) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of A? in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor ? in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. PMID:25855193

  9. Energy Excess, Glucose Utilization, and Skeletal Remodeling: New Insights.

    PubMed

    Lecka-Czernik, Beata; Rosen, Clifford J

    2015-08-01

    Skeletal complications have recently been recognized as another of the several comorbidities associated with diabetes. Clinical studies suggest that disordered glucose and lipid metabolism have a profound effect on bone. Diabetes-related changes in skeletal homeostasis result in a significant increased risk of fractures, although the pathophysiology may differ from postmenopausal osteoporosis. Efforts to understand the underlying mechanisms of diabetic bone disease have focused on the direct interaction of adipose tissue with skeletal remodeling and the potential influence of glucose utilization and energy uptake on these processes. One aspect that has emerged recently is the major role of the central nervous system in whole-body metabolism, bone turnover, adipose tissue remodeling, and beta cell secretion of insulin. Importantly, the skeleton contributes to the metabolic balance inherent in physiologic states. New animal models have provided the insights necessary to begin to dissect the effects of obesity and insulin resistance on the acquisition and maintenance of bone mass. In this Perspective, we focus on potential mechanisms that underlie the complex interactions between adipose tissue and skeletal turnover by focusing on the clinical evidence and on preclinical studies indicating that glucose intolerance may have a significant impact on the skeleton. In addition, we raise fundamental questions that need to be addressed in future studies to resolve the conundrum associated with glucose intolerance, obesity, and osteoporosis. PMID:26094610

  10. Insulin resistance in liver cirrhosis. Positron-emission tomography scan analysis of skeletal muscle glucose metabolism.

    PubMed Central

    Selberg, O; Burchert, W; vd Hoff, J; Meyer, G J; Hundeshagen, H; Radoch, E; Balks, H J; Mller, M J

    1993-01-01

    BACKGROUND. Insulin resistance and glucose intolerance are a major feature of patients with liver cirrhosis. However, site and mechanism of insulin resistance in cirrhosis are unknown. We investigated insulin-induced glucose metabolism of skeletal muscle by positron-emission tomography to identify possible defects of muscle glucose metabolism in these patients. METHODS. Whole body glucose disposal and oxidation were determined by the combined use of the euglycemic-hyperinsulinemic clamp technique (insulin infusion rate: 1 mU/kg body wt per min) and indirect calorimetry in seven patients with biopsy-proven liver cirrhosis (Child: 1A, 5B, and 1C) and five healthy volunteers. Muscle glucose uptake of the thighs was measured simultaneously by dynamic [18F]fluorodeoxyglucose positron-emission tomography scan. RESULTS. Both whole body and nonoxidative glucose disposal were significantly reduced in patients with liver cirrhosis (by 48%, P < 0.001, and 79%, P < 0.0001, respectively), whereas glucose oxidation and the increase in plasma lactate were normal. Concomitantly, skeletal muscle glucose uptake was reduced by 69% in liver cirrhosis (P < 0.003) and explained 55 or 92% of whole body glucose disposal in cirrhotics and controls, respectively. Analysis of kinetic constants using a three-compartment model further indicated reduced glucose transport (P < 0.05) but unchanged phosphorylation of glucose in patients with liver cirrhosis. CONCLUSIONS. Patients with liver cirrhosis show significant insulin resistance that is characterized by both decreased glucose transport and decreased nonoxidative glucose metabolism in skeletal muscle. Images PMID:8486761

  11. Synthetic Oligodeoxynucleotides Containing Multiple Telemeric TTAGGG Motifs Suppress Inflammasome Activity in Macrophages Subjected to Oxygen and Glucose Deprivation and Reduce Ischemic Brain Injury in Stroke-Prone Spontaneously Hypertensive Rats.

    PubMed

    Zhao, Jing; Mou, Yongshan; Bernstock, Joshua D; Klimanis, Dace; Wang, Sixian; Spatz, Maria; Maric, Dragan; Johnson, Kory; Klinman, Dennis M; Li, Xiaohong; Li, Xinhui; Hallenbeck, John M

    2015-01-01

    The immune system plays a fundamental role in both the development and pathobiology of stroke. Inflammasomes are multiprotein complexes that have come to be recognized as critical players in the inflammation that ultimately contributes to stroke severity. Inflammasomes recognize microbial and host-derived danger signals and activate caspase-1, which in turn controls the production of the pro-inflammatory cytokine IL-1?. We have shown that A151, a synthetic oligodeoxynucleotide containing multiple telemeric TTAGGG motifs, reduces IL-1? production by activated bone marrow derived macrophages that have been subjected to oxygen-glucose deprivation and LPS stimulation. Further, we demonstrate that A151 reduces the maturation of caspase-1 and IL-1?, the levels of both the iNOS and NLRP3 proteins, and the depolarization of mitochondrial membrane potential within such cells. In addition, we have demonstrated that A151 reduces ischemic brain damage and NLRP3 mRNA levels in SHR-SP rats that have undergone permanent middle cerebral artery occlusion. These findings clearly suggest that the modulation of inflammasome activity via A151 may contribute to a reduction in pro-inflammatory cytokine production by macrophages subjected to conditions that model brain ischemia and modulate ischemic brain damage in an animal model of stroke. Therefore, modulation of ischemic pathobiology by A151 may have a role in the development of novel stroke prevention and therapeutic strategies. PMID:26473731

  12. Synthetic Oligodeoxynucleotides Containing Multiple Telemeric TTAGGG Motifs Suppress Inflammasome Activity in Macrophages Subjected to Oxygen and Glucose Deprivation and Reduce Ischemic Brain Injury in Stroke-Prone Spontaneously Hypertensive Rats

    PubMed Central

    Bernstock, Joshua D.; Klimanis, Dace; Wang, Sixian; Spatz, Maria; Maric, Dragan; Johnson, Kory; Klinman, Dennis M.; Li, Xiaohong; Li, Xinhui; Hallenbeck, John M.

    2015-01-01

    The immune system plays a fundamental role in both the development and pathobiology of stroke. Inflammasomes are multiprotein complexes that have come to be recognized as critical players in the inflammation that ultimately contributes to stroke severity. Inflammasomes recognize microbial and host-derived danger signals and activate caspase-1, which in turn controls the production of the pro-inflammatory cytokine IL-1?. We have shown that A151, a synthetic oligodeoxynucleotide containing multiple telemeric TTAGGG motifs, reduces IL-1? production by activated bone marrow derived macrophages that have been subjected to oxygen-glucose deprivation and LPS stimulation. Further, we demonstrate that A151 reduces the maturation of caspase-1 and IL-1?, the levels of both the iNOS and NLRP3 proteins, and the depolarization of mitochondrial membrane potential within such cells. In addition, we have demonstrated that A151 reduces ischemic brain damage and NLRP3 mRNA levels in SHR-SP rats that have undergone permanent middle cerebral artery occlusion. These findings clearly suggest that the modulation of inflammasome activity via A151 may contribute to a reduction in pro-inflammatory cytokine production by macrophages subjected to conditions that model brain ischemia and modulate ischemic brain damage in an animal model of stroke. Therefore, modulation of ischemic pathobiology by A151 may have a role in the development of novel stroke prevention and therapeutic strategies. PMID:26473731

  13. Prevalence and Characteristics of Chemical Intolerance: A Japanese Population-Based Study.

    PubMed

    Azuma, Kenichi; Uchiyama, Iwao; Katoh, Takahiko; Ogata, Hiromitsu; Arashidani, Keiichi; Kunugita, Naoki

    2015-11-01

    Population-based cross-sectional study was performed to estimate the prevalence of chemical intolerance and to examine the characteristics of the sample. A Web-based survey was conducted that included 7,245 adults in Japan. The criteria for chemical intolerance proposed by Skovbjerg yielded a prevalence of 7.5% that was approximately consistent with that reported from a Danish population-based survey. Female gender, older age, and renovation in the house during the past 7years were positively associated with chemical intolerance. Improvements in the condition were observed with daily ventilation habits. Medical history of atopic dermatitis, allergic rhinitis, food allergy, multiple chemical sensitivity, and depression were associated with chemical intolerance. Fatigue, depressed mood, and somatic symptoms were also positively correlated with chemical intolerance. Better elucidation of the causes, comorbidities, concomitants, and consequences of chemical intolerance has the potential to provide effective solutions for its prevention and treatment. PMID:25137616

  14. Understanding and treating hypertension in diabetic populations

    PubMed Central

    Battistoni, Allegra; Savoia, Carmine; Tocci, Giuliano

    2015-01-01

    Hypertension and diabetes frequently occurs in the same individuals in clinical practice. Moreover, the presence of hypertension does increase the risk of new-onset diabetes, as well as diabetes does promote development of hypertension. Whatever the case, the concomitant presence of these conditions confers a high risk of major cardiovascular complications and promotes the use integrated pharmacological interventions, aimed at achieving the recommended therapeutic targets. While the benefits of lowering abnormal fasting glucose levels in patients with hypertension and diabetes have been consistently demonstrated, the blood pressure (BP) targets to be achieved to get a benefit in patients with diabetes have been recently reconsidered. In the past, randomized clinical trials have, indeed, demonstrated that lowering BP levels to less than 140/90 mmHg was associated to a substantial reduction of the risk of developing macrovascular and microvascular complications in hypertensive patients with diabetes. In addition, epidemiological and clinical reports suggested that “the lower, the better” for BP in diabetes, so that levels of BP even lower than 130/80 mmHg have been recommended. Recent randomized clinical trials, however, designed to evaluate the potential benefits obtained with an intensive antihypertensive therapy, aimed at achieving a target systolic BP level below 120 mmHg as compared to those obtained with less stringent therapy, have challenged the previous recommendations from international guidelines. In fact, detailed analyses of these trials showed a paradoxically increased risk of coronary events, mostly myocardial infarction, in those patients who achieved the lowest BP levels, particularly in the high-risk subsets of hypertensive populations with diabetes. In the light of these considerations, the present article will briefly review the common pathophysiological mechanisms, the potential sites of therapeutic interactions and the currently recommended BP targets to be achieved under pharmacological treatment in hypertension and diabetes. PMID:26543822

  15. Understanding and treating hypertension in diabetic populations.

    PubMed

    Volpe, Massimo; Battistoni, Allegra; Savoia, Carmine; Tocci, Giuliano

    2015-10-01

    Hypertension and diabetes frequently occurs in the same individuals in clinical practice. Moreover, the presence of hypertension does increase the risk of new-onset diabetes, as well as diabetes does promote development of hypertension. Whatever the case, the concomitant presence of these conditions confers a high risk of major cardiovascular complications and promotes the use integrated pharmacological interventions, aimed at achieving the recommended therapeutic targets. While the benefits of lowering abnormal fasting glucose levels in patients with hypertension and diabetes have been consistently demonstrated, the blood pressure (BP) targets to be achieved to get a benefit in patients with diabetes have been recently reconsidered. In the past, randomized clinical trials have, indeed, demonstrated that lowering BP levels to less than 140/90 mmHg was associated to a substantial reduction of the risk of developing macrovascular and microvascular complications in hypertensive patients with diabetes. In addition, epidemiological and clinical reports suggested that "the lower, the better" for BP in diabetes, so that levels of BP even lower than 130/80 mmHg have been recommended. Recent randomized clinical trials, however, designed to evaluate the potential benefits obtained with an intensive antihypertensive therapy, aimed at achieving a target systolic BP level below 120 mmHg as compared to those obtained with less stringent therapy, have challenged the previous recommendations from international guidelines. In fact, detailed analyses of these trials showed a paradoxically increased risk of coronary events, mostly myocardial infarction, in those patients who achieved the lowest BP levels, particularly in the high-risk subsets of hypertensive populations with diabetes. In the light of these considerations, the present article will briefly review the common pathophysiological mechanisms, the potential sites of therapeutic interactions and the currently recommended BP targets to be achieved under pharmacological treatment in hypertension and diabetes. PMID:26543822

  16. Use of octreotide in the treatment of refractory orthostatic intolerance.

    PubMed

    Kanjwal, Khalil; Saeed, Bilal; Karabin, Beverly; Kanjwal, Yousuf; Grubb, Blair P

    2012-01-01

    There have been reports on the use of octreotide in patients with orthostatic hypotension, postural tachycardia syndrome, and orthostatic syncope. However, there are little if any data on the use of octreotide in patients who have failed multiple other medications. This study was a retrospective chart analysis and was approved by our Institutional Review Board. A total of 12 patients were identified for inclusion in this study. The diagnosis of orthostatic intolerance was based on patient history, physical examination, and response to Head Up Tilt Table testing. These patients had failed multiple medications and were ultimately treated with octreotide. In a retrospective chart review, we collected data, including demographic information, presenting symptoms, laboratory data, tilt-table response, standing heart rate, standing blood pressure before and after treatment (wherever available), and treatment outcomes. Twelve patients aged 33 18 years, eight (66.7%) females, were found to have symptoms of refractory orthostatic intolerance and failed multiple regimens of medication and were ultimately treated with octreotide administration. Five patients (41.7%) had demonstrated a postural tachycardia syndrome pattern, five (41.7%) a neurocardiogenic, and two (16.6%) a dysautonomic response on a Head Up Tilt Table. Symptoms of syncope and orthostatic palpitations improved in six (50%) of the patients. Standing heart rate was significantly reduced after octreotide administration (80 8 versus 108 13; P < 0.05). The standing systolic blood pressure was increased after octreotide administration (107 26 versus 116 22). Three patients (25%) reported complete elimination of syncope, whereas another three had reduction in the frequency of their syncope. However, symptoms of fatigue improved only in two (29%) of the seven patients. Octreotide may improve symptoms in some patients with refractory orthostatic intolerance. PMID:20535001

  17. Down on heights? One in three has visual height intolerance.

    PubMed

    Huppert, Doreen; Grill, Eva; Brandt, Thomas

    2013-02-01

    The distressing phenomenon of visual height intolerance (vHI) occurs when a visual stimulus causes apprehension of losing control of balance and falling from some height. Epidemiological data of this condition in the general population are lacking. Assignment of prevalence, determinants, and compensation of vHI was performed in a cross-sectional epidemiological study of 3,517 individuals representing the German population. Life-time prevalence of vHI is 28 % (females 32 %). A higher prevalence is associated independently with a family history of vHI, anxiety disorders, migraine, or motion sickness susceptibility. Women aged 50-59 have a higher prevalence than younger women or men of all ages. Initial attacks occur most often (30 %) in the second decade; however, attacks can manifest throughout life. The main symptoms are fearfulness, inner agitation, a queasy-stomach feeling, subjective postural instability with to-and-fro vertigo, and weakness in the knees. Climbing a tower is the first most common precipitating stimulus; the spectrum of such stimuli widens with time in more than 50 % of afflicted individuals. The most frequent reaction to vHI is to avoid the triggering stimuli (>50 %); 11 % of susceptible individuals consult a doctor, most often a general practitioner, neurologist, ENT doctor, or psychiatrist. In brief, visual height intolerance affects one-third of the general population, considerably restricting the majority of these individuals in their daily activities. The data show that the two terms do not indicate a categorical distinction but rather a continuum from slight forms of visual height intolerance to the specific phobia of fear of heights. PMID:23070463

  18. Orthostatic intolerance without postural tachycardia: how much dysautonomia?

    PubMed Central

    Parsaik, Ajay K.; Singer, Wolfgang; Allison, Thomas G.; Sletten, David M.; Joyner, Michael J.; Benarroch, Eduardo E.; Low, Phillip A.

    2014-01-01

    Background Chronic symptoms of orthostatic intolerance occur in postural tachycardia syndrome (POTS) and patients with orthostatic intolerance (OI) without tachycardia. We recently reported that deconditioning is almost universal in both patient groups. In this study, we focussed on the question of how much dysautonomia, besides orthostatic tachycardia, is there in POTS vs. OI, and how the two groups compare in regards to clinical, autonomic, laboratory, and exercise variables. Methods We retrospectively studied all patients referred for orthostatic intolerance at Mayo Clinic between January 2006 and June 2011, who underwent standardized autonomic and exercise testing. Results Eighty-four POTS and 100 OI fulfilled inclusion criteria, 89 % were females. The mean age was 25 and 32 years, respectively. Clinical presentation, autonomic parameters, laboratory findings, and degree of deconditioning were overall similar between the two groups, except for the excessive orthostatic heart rate (HR) rise and mild vasomotor findings observed in POTS but not in OI (slightly larger Valsalva ratio and incomplete blood pressure recovery during Valsalva). Both groups responded poorly to various medications. Severely deconditioned patients were similar to non-deconditioned patients, except for 24 h urine volume (1,555 vs. 2,417 ml), sweat loss on thermoregulatory sweat test (1.5 vs. 0.5 %), and few respiratory parameters during exercise, which are likely clinically insignificant. Conclusion Though similar in clinical presentation, POTS and OI are different entities with greater, albeit still mild, dysautonomia in POTS. The clinical and pathophysiological relevance of minimal dysautonomia in the absence of orthostatic tachycardia as seen in OI remain uncertain. PMID:23729158

  19. 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.

  20. Blood Glucose Log

    MedlinePLUS

    ... Of ThiS page. If you have high blood glucose , make notes in your log and talk with ... physical activity, or diabetes medicines. Having low blood glucose means that your blood glucose level is too ...

  1. Effects of Estrogen on Glucose Uptake by Rat Muscle 1

    PubMed Central

    Shamoon, Harry; Felig, Philip

    1974-01-01

    The isolated rat diaphragm was used to study the effects of 17β-estradiol on basal and insulin-mediated glucose uptake. Rats were injected with estradiol for 2 wk in daily doses of 10 μg/100 g of body weight and were compared to untreated control animals. Estrogen treatment resulted in a 16% decrease in basal glucose uptake by diaphragm muscle as compared to controls. In contrast, in the presence of insulin, glucose uptake by muscle increased 103% above basal in estradiol-treated animals as compared to a 38% rise in the control group. The absolute rate of glucose uptake induced by insulin in the estradiol treated animals (5.8 mg/g/hr) was 22% higher than in controls. These findings were not accompanied by changes in weight gain, plasma glucose and plasma immunoreactive insulin concentrations in the treated animals. In vitro incubation of diaphragm muscle with estradiol did not have an effect on basal or insulin-mediated glucose uptake. The data indicate that treatment with naturally occurring estrogens increases muscle sensitivity to insulin-stimulated glucose uptake. These findings suggest that the carbohydrate intolerance associated with the administration of oral contraceptives may be related to the use of synthetic rather than natural estrogens and/or progestins in such preparations. PMID:4456835

  2. Efficacy of Garcinia Cambogia on Body Weight, Inflammation and Glucose Tolerance in High Fat Fed Male Wistar Rats

    PubMed Central

    Sripradha, Ramalingam

    2015-01-01

    Introduction: Obesity leads to derangements in lipid and glucose homeostasis resulting in various metabolic complications. Plants containing vital phytochemicals are known to posses anti obesity properties and have proved to exert beneficial effects in obesity. Objectives: The present study was aimed to investigate the effects of Garcinia Cambogia on body weight, glucose tolerance and inflammation in high fat diet fed male Wistar rats. Materials and Methods: Five month old male wistar rats (n=40) were divided into four groups. Two groups were fed with standard rodent diet and the remaining two with 30% high fat diet. One group in each of the two sets received the crude ethanolic extract of Garcinia Cambogia at a dose of 400mg/kg body weight/day for ten weeks. Body weight, intraperitoneal glucose tolerance test, leptin, tumour necrosis factor-? (TNF-?) and renal function (urea, creatinine, uric acid) were studied. Results: High fat diet fed rats showed increased body weight gain, glucose intolerance, elevated levels of plasma leptin and TNF-?. Supplementation of Garcinia Cambogia extract (GE) along with high fat diet significantly decreased body weight gain, glucose intolerance, plasma leptin and TNF-? level. No significant changes were observed in the renal function parameters in any of the groups. Conclusion: Supplementation of the Garcinia Cambogia extract with high fat diet reduced body weight gain, inflammation and glucose intolerance. PMID:25859449

  3. Histamine regulation in glucose and lipid metabolism via histamine receptors: model for nonalcoholic steatohepatitis in mice.

    PubMed

    Wang, Ke-Yong; Tanimoto, Akihide; Yamada, Sohsuke; Guo, Xin; Ding, Yan; Watanabe, Teruo; Watanabe, Takeshi; Kohno, Kimitoshi; Hirano, Ken-Ichi; Tsukada, Hideo; Sasaguri, Yasuyuki

    2010-08-01

    Histamine has been proposed to be an important regulator of energy intake and expenditure. The aim of this study was to evaluate histamine regulation of glucose and lipid metabolism and development of nonalcoholic steatohepatitis (NASH) with a hyperlipidemic diet. Histamine regulation of glucose and lipid metabolism, adipocytokine production, and development of hyperlipidemia-induced hepatic injury were studied in histamine H1 (H1R(-/-)) and H2 (H2R(-/-)) receptor knockout and wild-type mice. H1R(-/-) mice showed mildly increased insulin resistance. In contrast, H2R(-/-) mice manifested profound insulin resistance and glucose intolerance. High-fat/high-cholesterol feeding enhanced insulin resistance and glucose intolerance. Studies with two-deoxy-2-[(18)F]-fluoro-d-glucose and positron emission tomography showed a brain glucose allocation in H1R(-/-) mice. In addition, severe NASH with hypoadiponectinemia as well as hepatic triglyceride and free cholesterol accumulation and increased blood hepatic enzymes were observed in H2R(-/-) mice. H1R(-/-) mice showed an obese phenotype with visceral adiposity, hyperleptinemia, and less severe hepatic steatosis and inflammation with increased hepatic triglyceride. These data suggest that H1R and H2R signaling may regulate glucose and lipid metabolism and development of hyperlipidemia-induced NASH. PMID:20566747

  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. Variability of gluten intolerance in treated childhood coeliac disease.

    PubMed Central

    McNicholl, B; Egan-Mitchell, B; Fottrell, P F

    1979-01-01

    Fifty children consecutively attending a clinic for coeliac disease co-operated in a trial; 10 found to have flat mucosa were excluded. Forty children of mean age 9.8 years, whose duodenal or jejunal mucosa had returned to normal or near normal appearance after a mean of 5.8 years on gluten-free diets, were put back on normal diets. In 37, mucosal occurred in a mean of 16.9 months (four to 74 months). Four of the 37 had serial biopsies, in which mucosal enzymes (particularly lactase) fell and interepithelial lymphocyte counts rose before the mucosal morphology was regarded as definitely 'coeliac'. Three children had normal mucosal appearance after 58 to 73 months on normal diets, one of whom showed temporary mucosal abnormalities, another having occasionally low enzymes, in both suggesting underlying gluten sensitivity. Lactase suppression and raised IEL counts appear to be sensitive indicators of gluten intolerance. In our experience, a diagnosis of coeliac disease based on severe mucosal damage and a satisfactory response to a gluten-free but milk-containing diet implies a very strong likelihood of permanent or prolonged gluten intolerance, but with a striking variability in its expression. Images Figure PMID:428824

  6. 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

  7. Intergenerational transmission of prejudice, sex role stereotyping, and intolerance.

    PubMed

    O'Bryan, Megan; Fishbein, Harold D; Ritchey, P Neal

    2004-01-01

    The attitudes of 111 ninth and eleventh graders and both of their biological parents were independently assessed for prejudice against people with HIV/ AIDS, homosexuals, Blacks, and fat people, as well as for male and female sex role stereotyping. This study corrected for two shortcomings in previous research: neglecting to assess both parents and assessing only a single domain of prejudice. We addressed the intergenerational transmission of prejudice and stereotyping using three competing models: same-sex, parent equivalent, and differential effects. Using multiple regressions in which parents' scores were entered separately, along with control variables, different maternal and paternal influences were detected. Mothers were the primary influence for prejudice regarding HIV/AIDS, fatness, and race, and fathers were the primary influence for male and female stereotyping and prejudice against homosexuals, supporting the differential effects model. We also established that prejudice and stereotyping in specific domains reflected a more general proclivity to be intolerant. In contrast to prejudice and stereotyping in specific domains, fathers and mothers about equally shaped the adolescents' intolerance, supporting the parent equivalent model. PMID:15673220

  8. Hypertension in young adults.

    PubMed

    De Venecia, Toni; Lu, Marvin; Figueredo, Vincent M

    2016-03-01

    Hypertension remains a major societal problem affecting 76 million, or approximately one third, of US adults. While more prevalent in the older population, an increasing incidence in the younger population, including athletes, is being observed. Active individuals, like the young and athletes, are viewed as free of diseases such as hypertension. However, the increased prevalence of traditional risk factors in the young, including obesity, diabetes mellitus, and renal disease, increase the risk of developing hypertension in younger adults. Psychosocial factors may also be contributing factors to the increasing incidence of hypertension in the younger population. Increased left ventricular wall thickness and mass are increasingly found in young adults on routine echocardiograms and predict future cardiovascular events. This increasing incidence of hypertension in the young calls for early surveillance and prompt treatment to prevent future cardiac events. In this review we present the current epidemiological data, potential mechanisms, clinical implications, and treatment of hypertension in young patients and athletes. PMID:26821528

  9. A glucose-centric perspective of hyperglycemia.

    PubMed

    Ramasarma, T; Rafi, M

    2016-02-01

    Digestion of food in the intestines converts the compacted storage carbohydrates, starch and glycogen, to glucose. After each meal, a flux of glucose (> 200 g) passes through the blood pool (4-6 g) in a short period of 2 h, keeping its concentration ideally in the range of 80-120 mg/100 mL. Tissue-specific glucose transporters (GLUTs) aid in the distribution of glucose to all tissues. The balance glucose after meeting the immediate energy needs is converted into glycogen and stored in liver (up to 100 g) and skeletal muscle (up to 300 g) for later use. High blood glucose gives the signal for increased release of insulin from pancreas. Insulin binds to insulin receptor on the plasma membrane and activates its autophosphorylation. This initiates the post-insulin-receptor signal cascade that accelerates synthesis of glycogen and triglyceride. Parallel control by phos-dephos and redox regulation of proteins exists for some of these steps. A major action of insulin is to inhibit gluconeogensis in the liver decreasing glucose output into blood. Cases with failed control of blood glucose have alarmingly increased since 1960 coinciding with changed life-styles and large scale food processing. Many of these turned out to be resistant to insulin, usually accompanied by dysfunctional glycogen storage. Glucose has an extended stay in blood at 8 mM and above and then indiscriminately adds on to surface protein-amino groups. Fructose in common sugar is 10-fold more active. This random glycation process interferes with the functions of many proteins (e.g., hemoglobin, eye lens proteins) and causes progressive damage to heart, kidneys, eyes and nerves. Some compounds are known to act as insulin mimics. Vanadium-peroxide complexes act at post-receptor level but are toxic. The fungus-derived 2,5-dihydroxybenzoquinone derivative is the first one known to act on the insulin receptor. The safe herbal products in use for centuries for glucose control have multiple active principles and 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

  10. Risks for arterial hypertension.

    PubMed

    Schmieder, R E; Messerli, F H; Ruddel, H

    1986-02-01

    In this article, the most important risk factors that may predict the transition from borderline to established hypertension are reviewed. Primary prevention has to focus on identifying individuals who are at highest risk and delaying or reversing further elevation of arterial pressure levels. A review of the literature indicates that several environmental and congenital factors can be identified as risk factors for the development of hypertension, including family history of essential hypertension, age, race, obesity, alcohol consumption, salt intake, hormonal status, and some stress factors. Of all diagnostic approaches to predict the development of hypertension, measurements of resting heart rate and responses to dynamic exercise have some predictive value. PMID:3518934

  11. Pulmonary Hypertension in Sarcoidosis.

    PubMed

    Baughman, Robert P; Engel, Peter J; Nathan, Steven

    2015-12-01

    Pulmonary hypertension is a complication of sarcoidosis leading to dyspnea and associated with increased morbidity and mortality. Sarcoidosis-associated pulmonary hypertension (SAPH) can be due to several factors, including vascular involvement by the granulomatous inflammation, compression of the pulmonary arteries by adenopathy, fibrotic changes within the lung, and left ventricular diastolic dysfunction. Several case series have suggested that some patients with SAPH benefit from specific therapy for pulmonary hypertension. A randomized, placebo-controlled trial found 16weeks' bosentan therapy to be associated with significant improvement in pulmonary artery pressure. Future studies may better define who would respond to treatment of pulmonary hypertension. PMID:26593143

  12. Hypertension and adrenal disorders.

    PubMed

    Chemaitilly, Wassim; Wilson, Robert C; New, Maria I

    2003-12-01

    Adrenal disorders causing hypertension can be related to the dysfunction of either the adrenal cortex or the adrenal medulla. These disorders, including congenital adrenal hyperplasia (CAH), owing to 11B-hydroxylase deficiency and to 17alpha-hydroxylase deficiency; apparent mineralocorticoid excess; familial hyperaldosteronism type I; primary aldosteronism; Cushing's syndrome; and familial glucocorticoid resistance, primarily affect the adrenal cortex and cause low-renin hypertension. The classic disorder of the adrenal medulla resulting in hypertension is pheochromocytoma, although hypertension in obesity might also be associated with catecholamine secretion. In this review, we discuss these etiologies and the most recent advances in our knowledge of their pathophysiology, diagnosis, and treatment. PMID:14594571

  13. Pediatric endocrine hypertension.

    PubMed

    Bhavani, Nisha

    2011-10-01

    Endocrine causes of hypertension are rare in children and screening for endocrine hypertension in children should be carried out only after ruling out renal and renovascular causes. Excess levels and/or action of mineralocorticoids associated with low renin levels lead to childhood hypertension and this can be caused by various conditions which are discussed in detail in the article. Childhood pheochromocytomas are being increasingly diagnosed because of the improved application of genetic testing for familial syndromes associated with pheochromocytomas. Adolescents with polycystic ovarian syndrome (PCOS) can also have hypertension associated with their obese phenotype. PMID:22145140

  14. Endothelin: role in hypertension.

    PubMed

    Schiffrin, E L

    1998-01-01

    Endothelins (ET) are 21-aminoacid peptides produced ubiquitously, which were discovered originally as endothelial products. These peptides may play important roles in cardiovascular physiology and pathophysiology. As the pathophysiologic roles of endothelins in cardiovascular disease become increasingly apparent, the potential therapeutic use of endothelin antagonists or endothelin converting enzyme inhibitors is recognized. The main endothelin produced by the endothelium is ET-1. Endothelin-1 is overexpressed in the vascular wall of salt-dependent models of hypertension, such as DOCA-salt hypertensive rats, DOCA-salt-treated spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats, and in stroke-prone SHR, angiotensin II-infused rats and 1-kidney 1 clip Goldblatt hypertensive rats, but not in SHR, 2-K 1C hypertensive rats or L-NAME-treated rats. The vasoconstrictor effect of ET-1 may contribute to blood pressure elevation and its growth-promoting action to vascular hypertrophy in the hypertensive models which overexpress ET-1 in blood vessels. In rats without generalized activation of the endothelin system, expression of ET-1 is often enhanced in coronary arteries, which suggests a role for ET-1 in myocardial ischemia in hypertension. In rats overexpressing ET-1, ETA/B and ETA-selective antagonists lowered blood pressure slightly, and significantly reduced vascular growth, particularly of small arteries, suggesting that ET-1 has a direct effect on growth. Protection from renal injury and from stroke has also been demonstrated in hypertensive rats treated with endothelin antagonists. In normotensive human subjects endothelin-dependent tone can be shown in the forearm. In a study of mild hypertensive patients, the ETA/B antagonist bosentan reduced blood pressure similarly to an ACE inhibitor. Moderate to severe hypertensive patients presented enhanced expression of ET-1 mRNA in the endothelium of subcutaneous resistance arteries. In blacks with familial hypertension increased plasma levels of endothelin have been found. Thus, ET-1 may play a role in some experimental hypertensive models and in human hypertension. In summary, endothelial ET-1 may be overexpressed in the more severe forms of hypertension, and in certain special populations which may respond particularly well to endothelin antagonism. Endothelin antagonists may prove to be effective disease-modifying agents if in future clinical trials they are shown clinically to blunt vascular growth and endothelial dysfunction, reduce stroke and exert the cardioprotective and renal protective effects already reported in experimental hypertension. These agents could contribute to reduce the long-term complications of hypertension, which remains to be demonstrated in humans. PMID:9830507

  15. Mild fasting hyperglycemia shifts fuel reliance toward fat during exercise in adults with impaired glucose tolerance

    PubMed Central

    Malin, Steven K.; Viskochil, Richard; Oliver, Corianne

    2013-01-01

    Impaired glucose tolerance (IGT) is characterized by decreased oxidative capacity and reduced carbohydrate utilization during exercise. However, it is unclear if the presence of impaired fasting glucose (IFG) affects fuel utilization during exercise in adults with IGT. We tested the hypothesis that the presence of IFG in adults with IGT decreases reliance on carbohydrate during exercise. Middle-aged, obese, sedentary individuals (n = 6, IGT and n = 6, IFG+IGT) were compared during exercise at 60% peak O2 consumption for 45 min on a cycle ergometer. Glucose rates of appearance and disposal and muscle glycogen were assessed by stable isotope dilution methods, and fat utilization was estimated via indirect calorimetry. A 75-g oral glucose tolerance test was used to determine fasting and 2-h glucose concentrations. A glucose intolerance severity z-score was calculated from the oral glucose tolerance test. Glucose flux (i.e., rates of appearance and disposal) was not different between groups. However, individuals with IFG+IGT had lower muscle glycogen use (P < 0.05) and elevated fat oxidation (P < 0.01) during exercise compared with those with isolated IGT. Plasma nonesterified fatty acids and glucose were significantly higher during exercise in subjects with IFG+IGT vs. IGT alone (P < 0.05). Fat utilization during exercise correlated with fasting glucose (r = 0.57, P = 0.05), glucose intolerance severity z-score (r = 0.66, P = 0.01), and nonesterified fatty acids (trend; r = 0.55, P = 0.08). The presence of IFG shifts fuel selection toward increased fat oxidation and decreased muscle glycogen utilization during exercise in adults with IGT. Whether these differences in substrate use contribute to, or are the result of, movement along the continuum from prediabetes to type 2 diabetes awaits further work. PMID:23599396

  16. How Is Pulmonary Hypertension Diagnosed?

    MedlinePLUS

    ... page from the NHLBI on Twitter. How Is Pulmonary Hypertension Diagnosed? Your doctor will diagnose pulmonary hypertension (PH) ... Tests To Look for the Underlying Cause of Pulmonary Hypertension PH has many causes, so many tests may ...

  17. How Is Pulmonary Hypertension Treated?

    MedlinePLUS

    ... page from the NHLBI on Twitter. How Is Pulmonary Hypertension Treated? Pulmonary hypertension (PH) has no cure. However, ... healthy organs from a deceased donor. Group 2 Pulmonary Hypertension Conditions that affect the left side of the ...

  18. 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

  19. 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

  20. 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…

  1. 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

  2. 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…

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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...

  8. Stress and hypertension.

    PubMed

    Kulkarni, S; O'Farrell, I; Erasi, M; Kochar, M S

    1998-12-01

    Stress can cause hypertension through repeated blood pressure elevations as well as by stimulation of the nervous system to produce large amounts of vasoconstricting hormones that increase blood pressure. Factors affecting blood pressure through stress include white coat hypertension, job strain, race, social environment, and emotional distress. Furthermore, when one risk factor is coupled with other stress producing factors, the effect on blood pressure is multiplied. Overall, studies show that stress does not directly cause hypertension, but can have an effect on its development. A variety of non-pharmacologic treatments to manage stress have been found effective in reducing blood pressure and development of hypertension, examples of which are meditation, acupressure, biofeedback and music therapy. Recent results from the National Health and Nutrition Examination Survey indicate that 50 million American adults have hypertension (defined to be a systolic blood pressure of greater than 139 mm Hg or a diastolic blood pressure of greater than 89 mm Hg). In 95% of these cases, the cause of hypertension is unknown and they are categorized as "essential" hypertension. Although a single cause may not be identified, the general consensus is that various factors contribute to blood pressure elevation in essential hypertension. In these days of 70 hour work weeks, pagers, fax machines, and endless committee meetings, stress has become a prevalent part of people's lives; therefore the effect of stress on blood pressure is of increasing relevance and importance. Although stress may not directly cause hypertension, it can lead to repeated blood pressure elevations, which eventually may lead to hypertension. In this article we explore how stress can cause hypertension and what can be done about it. PMID:9894438

  9. Hypertension (High Blood Pressure)

    MedlinePLUS

    ... due to hypertension. The NIH is working with scientific and medical communities to update hypertension management guidelines (JNC-8), including integrating them with updated guidelines on management of cholesterol and obesity. For additional information please contact: Carl ... | RePORT Office of Science Policy Analysis | Office of Science Policy | Office of ...

  10. Misconceptions of hypertension.

    PubMed Central

    Oke, David Adewale; Bandele, Emmanuel Olarenwaju

    2004-01-01

    A prospective questionnaire study of the misconceptions of hypertension by hypertensive patients was carried out in 1365 male and female hypertensive patients aged between 21-80 years. About 40% of the study population could not define hypertension, but even those who did appeared to be in denial of the disease. About 24% were unaware of the causes of hypertension; the most common cause mentioned was psychosocial stress. Between 0.6% and 14% of subjects were unaware of the effect of risk factors, like obesity, cigarette smoking, exercise, excessive alcohol and salt consumption, or hypertension. Interestingly, some feel that regular sexual intercourse worsens hypertension. Eight percent of subjects had no fear of the effect of poor compliance to antihypertensive medication, while 10% were anxious about the heavy financial burden imposed by hypertension management, Sixty-five percent of subjects feel that they will require no more medication once they achieve control of their blood pressure. Twenty-one percent of respondents are of the opinion that they will achieve a permanent cure only from alternative medical practitioners and will consider using alternative medicine in future. The study confirms the importance of medical education for patients irrespective of their level of education, as many of these patients still entertain that gross misconceptions may have negative impact on outcome. Images Figure 1 Figure 2 Figure 3 PMID:15481752

  11. Pulmonary Arterial Hypertension

    MedlinePLUS

    ... also decrease the amount of oxygen getting to your brain. What are the Symptoms of Pulmonary Arterial Hypertension? ... hypertension are treated differently, it is important that your health care provider takes the time and orders the necessary tests to nd out what kind of pulmonary ...

  12. Noncirrhotic Portal Hypertension

    PubMed Central

    Rajekar, Harshal; Vasishta, Rakesh K; Chawla, Yogesh K; Dhiman, Radha K

    2011-01-01

    Portal hypertension is characterized by an increase in portal pressure (> 10 mmHg) and could be a result of cirrhosis of the liver or of noncirrhotic diseases. When portal hypertension occurs in the absence of liver cirrhosis, noncirrhotic portal hypertension (NCPH) must be considered. The prognosis of this disease is much better than that of cirrhosis. Noncirrhotic diseases are the common cause of portal hypertension in developing countries, especially in Asia. NCPH is a heterogeneous group of diseases that is due to intrahepatic or extrahepatic etiologies. In general, the lesions in NCPH are vascular in nature and can be classified based on the site of resistance to blood flow. In most cases, these disorders can be explained by endothelial cell lesions, intimal thickening, thrombotic obliterations, or scarring of the intrahepatic portal or hepatic venous circulation. Many different conditions can determine NCPH through the association of these various lesions in various degrees. Many clinical manifestations of NCPH result from the secondary effects of portal hypertension. Patients with NCPH present with upper gastrointestinal bleeding, splenomegaly, ascites after gastrointestinal bleeding, features of hypersplenism, growth retardation, and jaundice due to portal hypertensive biliopathy. Other sequelae include hyperdynamic circulation, pulmonary complications, and other effects of portosystemic collateral circulation like portosystemic encephalopathy. At present, pharmacologic and endoscopic treatments are the treatments of choice for portal hypertension. The therapy of all disorders causing NCPH involves the reduction of portal pressure by pharmacotherapy or portosystemic shunting, apart from prevention and treatment of complications of portal hypertension. PMID:25755321

  13. 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.

  14. Vascular responsiveness to norepinephrine in sympathicotonic orthostatic intolerance.

    PubMed

    Miller, J W; Streeten, D H

    1990-05-01

    Sympathicotonic orthostatic intolerance (hypotension, tachycardia, or both) is associated with normal or excessive orthostatic increases in plasma norepinephrine concentration and is reversible by the inflation of a military anti-shock trouser suit enveloping the lower limbs and abdomen. These facts suggest that one possible mechanism of the disorder might be a defect in alpha-adrenergic receptor or postreceptor responsiveness of the veins or arterioles. We have investigated in 11 patients and 15 healthy controls the blood pressure and heart rate responses to increasing rates of intravenous norepinephrine infusion (1 to 16 micrograms/min), the dorsal hand vein contractile responses to increasing rates of norepinephrine infusion (1 to 256 ng/min) with a linear variable differential transformer, and the platelet alpha 2-adrenergic receptor densities and dissociation constants. No statistically significant difference in any of these parameters was found between the normal subjects and nine of the 11 patients with orthostatic intolerance. The venous contractile response to norepinephrine was excessive in one patient and was virtually absent in another. Because supersensitivity of the hand veins to norepinephrine suggests up-regulation of alpha 2-receptors resulting from postganglionic autonomic insufficiency, this finding in one patient with sympathicotonic orthostatic hypotension might have been caused by venous denervation. The venous unresponsiveness to norepinephrine in the other patient presumably resulted from a defect in the venous receptors or smooth muscle function. It is evident that norepinephrine responsiveness and the innervation of the arterioles and hand veins was normal in the other nine patients, in whom the defect must have been mediated by some other mechanism. PMID:2160509

  15. Hypertension in the elderly

    PubMed Central

    Lionakis, Nikolaos; Mendrinos, Dimitrios; Sanidas, Elias; Favatas, Georgios; Georgopoulou, Maria

    2012-01-01

    The elderly are the most rapidly growing population group in the world. Data collected over a 30-year period have demonstrated the increasing prevalence of hypertension with age. The risk of coronary artery disease, stroke, congestive heart disease, chronic kidney insufficiency and dementia is also increased in this subgroup of hypertensives. Hypertension in the elderly patients represents a management dilemma to cardiovascular specialists and other practioners. During the last years and before the findings of the Systolic Hypertension in Europe Trial were published, the general medical opinion considered not to decrease blood pressure values similarly to other younger patients, in order to avoid possible ischemic events and poor oxygenation of the organs (brain, heart, kidney). The aim of this review article is to highlight the importance of treating hypertension in aged population in order to improve their quality of life and lower the incidence of the cardiovascular complications. PMID:22655162

  16. Hypertension management: an update.

    PubMed

    Nguyen, Quang; Dominguez, Joann; Nguyen, Loida; Gullapalli, Nageshwara

    2010-01-01

    Hypertension is a significant and costly public health problem. It is a major, but modifiable contributor for the development of cardiovascular disease. Randomized controlled trials have shown that controlling hypertension reduces the risk of stroke, coronary artery disease, congestive heart failure, end-stage renal disease, peripheral vascular disease, as well as overall mortality. The risk of developing these hypertension-related complications is continuous, starting at a blood pressure level as low as 115/75 mm Hg. Despite the inherent health risks associated with uncontrolled hypertension, elevated blood pressure remains inadequately treated in the majority of patients. This article reviews guidelines for optimal evaluation of hypertension and current therapeutic options available to combat this common yet pervasive disease. PMID:25126308

  17. Hypertension Management: An Update

    PubMed Central

    Nguyen, Quang; Dominguez, Joann; Nguyen, Loida; Gullapalli, Nageshwara

    2010-01-01

    Hypertension is a significant and costly public health problem. It is a major, but modifiable contributor for the development of cardiovascular disease. Randomized controlled trials have shown that controlling hypertension reduces the risk of stroke, coronary artery disease, congestive heart failure, end-stage renal disease, peripheral vascular disease, as well as overall mortality. The risk of developing these hypertension-related complications is continuous, starting at a blood pressure level as low as 115/75 mm Hg. Despite the inherent health risks associated with uncontrolled hypertension, elevated blood pressure remains inadequately treated in the majority of patients. This article reviews guidelines for optimal evaluation of hypertension and current therapeutic options available to combat this common yet pervasive disease. PMID:25126308

  18. [Psychological factors in hypertension].

    PubMed

    Manuck, S; Morrison, R; Bellack, A

    1986-01-01

    We briefly overview behavioral factors of possible relevance to essential hypertension. We examine, in particular, dimensions of individual differences relating to: (a) problems of anger and assertion; and (b) cardiovascular responsivity to behavioral stressors. Hypertensive patients do show larger cardiovascular reactions to common laboratory stressors than normotensive, controls, and similar differences emerge in comparisons of normotensive individuals with and without a family history of hypertension. Concerning the purported dispositional attributes of hypertensives, we also propose re-examining psychodynamic notions regarding the suppression or denial of anger within a more objective, behavioral framework-specifically, as measurable deficits in assertive skill. Preliminary observations point to the presence of lower assertiveness in some hypertensive patients and increased hostility among others. These behavioral characteristics also appear to be associated with different patterns of cardiovascular reactivity, as recorded during interpersonal encounters that call for assertive responding. PMID:3512899

  19. Predictors of Hypertension Among Filipino Immigrants in the Northeast US

    PubMed Central

    Islam, Nadia Shilpi; Aguilar, David E.; Wyatt, Laura C.; Tandon, S. Darius; Abesamis-Mendoza, Noilyn; Nur, Potri Ranka Manis Queano; Rago-Adia, Josephine; Ileto, Benjamin; Rey, Mariano J.; Trinh-Shevrin, Chau

    2013-01-01

    Hypertension remains disproportionately high among Filipinos compared to other racial and ethnic minority populations, and little research on cardiovascular disease risk factors has been conducted among Filipino immigrants in the Northeastern part of the United States. To determine hypertension prevalence and risk factors among Filipino Americans in the New York City area, blood pressure and other clinical measurements were taken from a sample of Filipino Americans during 119 community health screenings conducted between 2006 and 2010. Additional socio-demographic and health-related characteristics were also collected via a cross-sectional survey. A total of 1,028 Filipino immigrants completed the survey and had clinical readings collected. Bivariate analyses and logistic regression were performed in order to predict and assess risk factors for hypertension among our sample. Fifty-three percent of individuals were hypertensive, and half of hypertensive individuals were uninsured. Logistic regression indicated that older age, male gender, living in the United States for over 5 years, a BMI greater than 23.0 kg/m2, an elevated glucose reading, a family history of hypertension, and fair or poor self-reported health status were predictors of hypertension. There is a great need to develop more effective community-based interventions in the Filipino community to address cardiovascular health disparities. PMID:23553685

  20. Four faces of baroreflex failure: hypertensive crisis, volatile hypertension, orthostatic tachycardia, and malignant vagotonia

    NASA Technical Reports Server (NTRS)

    Ketch, Terry; Biaggioni, Italo; Robertson, RoseMarie; Robertson, David

    2002-01-01

    BACKGROUND: The baroreflex normally serves to buffer blood pressure against excessive rise or fall. Baroreflex failure occurs when afferent baroreceptive nerves or their central connections become impaired. In baroreflex failure, there is loss of buffering ability, and wide excursions of pressure and heart rate occur. Such excursions may derive from endogenous factors such as stress or drowsiness, which result in quite high and quite low pressures, respectively. They may also derive from exogenous factors such as drugs or environmental influences. METHODS AND RESULTS: Impairment of the baroreflex may produce an unusually broad spectrum of clinical presentations; with acute baroreflex failure, a hypertensive crisis is the most common presentation. Over succeeding days to weeks, or in the absence of an acute event, volatile hypertension with periods of hypotension occurs and may continue for many years, usually with some attenuation of pressor surges and greater prominence of depressor valleys during long-term follow-up. With incomplete loss of baroreflex afferents, a mild syndrome of orthostatic tachycardia or orthostatic intolerance may appear. Finally, if the baroreflex failure occurs without concomitant destruction of the parasympathetic efferent vagal fibers, a resting state may lead to malignant vagotonia with severe bradycardia and hypotension and episodes of sinus arrest. CONCLUSIONS: Although baroreflex failure is not the most common cause of the above conditions, correct differentiation from other cardiovascular disorders is important, because therapy of baroreflex failure requires specific strategies, which may lead to successful control.

  1. Comparison of impedance to insulin-mediated glucose uptake in normal subjects and in subjects with latent diabetes

    PubMed Central

    Shen, Shiao-Wei; Reaven, Gerald M.; Farquhar, John W.

    1970-01-01

    A technique was devised for a more accurate measurement than has been heretofore possible of one of the factors responsible for hyperglycemia in the complex syndrome of diabetes. This factor is termed impedance and represents the tissues' insensitivity or resistance to insulin-mediated glucose uptake. It was measured by use of steady-state exogenous insulin and glucose infusions during a period of pharmacological suppression of endogenous insulin secretion. Endogenous new glucose production was also inhibited. Impedance as calculated is a direct function of steady-state glucose concentrations, since exogenous insulin concentrations were similar in all studies. Two groups of normal weight subjects were studied. One had maturity onset latent diabetes, and the other (matched for age, weight, and per cent adiposity) was normal. Impedance was closely reproducible in the same individual and remained relatively constant during prolonged infusions. The diabetics had average infusion glucose concentrations (and thus impedance) 68% higher than the normal group, and it is of note that their previously measured glucose intolerance differed by a similar degree; that is, the diabetic's intolerance (as defined by mean weighted plasma glucose response after oral glucose) was 52% greater than that of the normal individuals. PMID:5480843

  2. Determination of fructose metabolic pathways in normal and fructose-intolerant children: a 13C NMR study using [U-13C]fructose.

    PubMed

    Gopher, A; Vaisman, N; Mandel, H; Lapidot, A

    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-13C]fructose was given nasogastrically to control and to HFI children. Hepatic fructose conversion to glucose was estimated by examination of 13C NMR spectra of plasma glucose. The conversion parameters in the control and HFI children were estimated on the basis of doublet/singlet values of the plasma beta-glucose C-1 splitting pattern as a function of the rate of fructose infusion (0.26-0.5 mg/kg per min). Significantly lower values (approximately 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 13C NMR measurement of plasma [13C]glucose isotopomer populations. The finding of isotopomer populations of three adjacent 13C atoms at glucose C-4 (13C3-13C4-13C5) 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 approximately 50% of the total amount of hepatic fructose conversion to glucose. It is suggested that phosphorylation of fructose 1-phosphate to fructose 1,6-bisphosphate by 1-phosphofructokinase occurs in human liver (and intestine) when fructose is administered nasogastrically; 47% and 27% of the total fructose conversion to glucose in controls and in HFI children, respectively, takes place by way of this pathway. In view of the marked decline by 67% in synthesis of glucose from fructose in HFI subjects found in this study, the extent of [13C]glucose formation from a "trace" amount (approximately 20 mg/kg) of [U-13C]fructose infused into the patient can be used as a safe and noninvasive diagnostic test for inherent faulty fructose metabolism. PMID:2371280

  3. Determination of fructose metabolic pathways in normal and fructose-intolerant children: a 13C NMR study using [U-13C]fructose.

    PubMed Central

    Gopher, A; Vaisman, N; Mandel, H; Lapidot, A

    1990-01-01

    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-13C]fructose was given nasogastrically to control and to HFI children. Hepatic fructose conversion to glucose was estimated by examination of 13C NMR spectra of plasma glucose. The conversion parameters in the control and HFI children were estimated on the basis of doublet/singlet values of the plasma beta-glucose C-1 splitting pattern as a function of the rate of fructose infusion (0.26-0.5 mg/kg per min). Significantly lower values (approximately 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 13C NMR measurement of plasma [13C]glucose isotopomer populations. The finding of isotopomer populations of three adjacent 13C atoms at glucose C-4 (13C3-13C4-13C5) 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 approximately 50% of the total amount of hepatic fructose conversion to glucose. It is suggested that phosphorylation of fructose 1-phosphate to fructose 1,6-bisphosphate by 1-phosphofructokinase occurs in human liver (and intestine) when fructose is administered nasogastrically; 47% and 27% of the total fructose conversion to glucose in controls and in HFI children, respectively, takes place by way of this pathway. In view of the marked decline by 67% in synthesis of glucose from fructose in HFI subjects found in this study, the extent of [13C]glucose formation from a "trace" amount (approximately 20 mg/kg) of [U-13C]fructose infused into the patient can be used as a safe and noninvasive diagnostic test for inherent faulty fructose metabolism. Images PMID:2371280

  4. Hypertension in Malaysia

    PubMed Central

    Naing, Cho; Yeoh, Peng Nam; Wai, Victor Nyunt; Win, Ni Ni; Kuan, Lai Pei; Aung, Kyan

    2016-01-01

    Abstract This study aimed to determine trends in prevalence, awareness, and control of hypertension in Malaysia and to assess the relationship between socioeconomic determinants and prevalence of hypertension in Malaysia. The distribution of hypertension in Malaysia was assessed based on available data in 3 National Health and Morbidity Surveys (NHMSs) and 1 large scale non-NHMS during the period of 1996 to 2011. Summary statistics was used to characterize the included surveys. Differences in prevalence, awareness, and control of hypertension between any 2 surveys were expressed as ratios. To assess the independent associations between the predictors and the outcome variables, regression analyses were employed with prevalence of hypertension as an outcome variable. Overall, there was a rising trend in the prevalence of hypertension in adults ≥30 years: 32.9% (30%–35.8%) in 1996, 42.6% (37.5%–43.5%) in 2006, and 43.5% (40.4%–46.6%) in 2011. There were significant increase of 32% from 1996 to 2011 (P < 0.001) and of 29% from 1996 to 2006 (P < 0.05), but only a small change of 1% from 2006 to 2011 (P = 0.6). For population ≥18 years, only a 1% increase in prevalence of hypertension occurred from the 2006 NHMS (32.2%) to the 2011 NHMS (32.7%) (P = 0.25). A relative increase of 13% occurred in those with primary education (P < 0.001) and a 15% increase was seen in those with secondary education (P < 0.001). The rate of increase in the prevalence of hypertension in the population with income level RM 3000–3999 was the highest (18%) during this period. In general, the older age group had higher prevalence of hypertension in the 2006 and 2011 NHMSs. The prevalence peaked at 74.1% among population aged 65 to 69 years in the 2011 NHMS. Both the proportion of awareness and the control of hypertension in Malaysia improved from 1996 to 2006. A change in the control of hypertension was 13% higher in women than in men. The findings suggest that the magnitude of hypertension in Malaysia needs additional attention. Strengthening the screening for hypertension in primary health-care settings in the high-risk groups and frequent health promotion to the community to enhance individual awareness and commitment to healthy living would be of immense value. PMID:26765422

  5. Lifelong Obesity in a Polygenic Mouse Model Prevents Age- and Diet-Induced Glucose Intolerance– Obesity Is No Road to Late-Onset Diabetes in Mice

    PubMed Central

    Brenmoehl, Julia; Walz, Christina; Zeissler, Anja; Tuchscherer, Armin; Piechotta, Marion; Wiesner, Rudolf J.; Bielohuby, Maximilian; Hoeflich, Andreas

    2013-01-01

    Aims/Hypothesis Visceral obesity holds a central position in the concept of the metabolic syndrome characterized by glucose intolerance in humans. However, until now it is unclear if obesity by itself is responsible for the development of glucose intolerance. Methods We have used a novel polygenic mouse model characterized by genetically fixed obesity (DU6) and addressed age- and high fat diet-dependent glucose tolerance. Results Phenotype selection over 146 generations increased body weight by about 2.7-fold in male 12-week DU6 mice (P<0.0001) if compared to unselected controls (Fzt:DU). Absolute epididymal fat mass was particularly responsive to weight selection and increased by more than 5-fold (P<0.0001) in male DU6 mice. At an age of 6 weeks DU6 mice consumed about twice as much food if compared to unselected controls (P<0.001). Absolute food consumption was higher at all time points measured in DU6 mice than in Fzt:DU mice. Between 6 and 12 weeks of age, absolute food intake was reduced by 15% in DU6 mice (P<0.001) but not in Fzt:DU mice. In both mouse lines feeding of the high fat diet elevated body mass if compared to the control diet (P<0.05). In contrast to controls, DU6 mice did not display high fat diet-induced increases of epididymal and renal fat. Control mice progressively developed glucose intolerance with advancing age and even more in response to the high fat diet. In contrast, obese DU6 mice did neither develop a glucose intolerant phenotype with progressive age nor when challenged with a high fat diet. Conclusions/Interpretation Our results from a polygenic mouse model demonstrate that genetically pre-determined and life-long obesity is no precondition of glucose intolerance later in life. PMID:24236159

  6. Lactose intolerance and African Americans: implications for the consumption of appropriate intake levels of key nutrients.

    PubMed

    2009-10-01

    Lactose intolerance is a complex condition that is complicated by cultural beliefs and perceptions about the consumption of dairy products. These attitudes about dairy may contribute to inadequate intake of key nutrients that may impact conditions that contribute to health disparities in African Americans. While a complex health problem, lactose intolerance is easy to treat. However, no treatment can improve the body's ability to produce lactase. Yet, symptoms can be controlled through dietary strategies. This position paper emphasizes the importance of using patient and provider-level strategies in order to reduce the risks to the health of African Americans that may accrue as a result of dairy nutrient deficiency. Evaluation and assessment of interventions tested is critical so that evidence-based approaches to addressing dairy nutrient deficiency and lactose Intolerance can be created. Lastly, it is essential for physicians to communicate key messages to their patients. Since dairy nutrients address important health concerns, the amelioration of lactose intolerance is an investment in health. Lactose intolerance is common, is easy to treat, and can be managed. It is possible to consume dairy even in the face of a history of maldigestion or lactose intolerant issues. Gradually increasing lactose in the diet--drinking small milk portions with food, eating yogurt, and consuming cheese--are effective strategies for managing lactose intolerance and meeting optimal dairy needs. PMID:19899495

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

    PubMed Central

    Boi?evi?, Sandra; Pape-Medvidovi?, Edita; Ljubi?, 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

  8. Hypertension Risk Subsequent to Gestational Dysglycemia Is Modified by Race/Ethnicity.

    PubMed

    Bentley-Lewis, Rhonda; Huynh, Jennifer; Li, Sylvia; Wenger, Julia; Thadhani, Ravi

    2016-01-01

    Gestational diabetes mellitus is associated with an increased risk of type 2 diabetes mellitus and hypertension. Additionally, gestational dysglycemia has been associated with an increased risk of type 2 diabetes mellitus but not yet associated with hypertension subsequent to pregnancy in long-term follow-up. Therefore, we set out to examine this relationship as well as the role of race/ethnicity in modifying this relationship. We analyzed a prospective observational cohort followed between 1998 and 2007. There were 17 655 women with self-reported race/ethnicity and full-term, live births. A 1-hour 50 g oral glucose-load test and a 3-hour 100 g oral glucose-tolerance test enabled third trimester stratification of women into 1 of 4 glucose-tolerance groups: (1) normal (n=15 056); (2) abnormal glucose-load test (n=1558); (3) abnormal glucose-load and -tolerance tests (n=520); and (4) gestational diabetes mellitus (n=521). Women were then followed for a meanstandard deviation of 4.12.9 years after delivery for the development of hypertension. Although gestational diabetes mellitus was associated with an increased risk of hypertension after pregnancy (odds ratio [95% confidence interval]: 1.58 [1.02, 2.45]; P=0.04), dysglycemia defined by an abnormal glucose-load test predicted hypertension only among black women (4.52 [1.24, 16.52]; P=0.02). The risk of hypertension after pregnancy among dysglycemia groups not meeting criteria for gestational diabetes mellitus varied based on the race/ethnicity of the population. Further research on the implications of the intersection of race/ethnicity and gestational dysglycemia on subsequent hypertension is warranted. PMID:26573715

  9. Perioperative hypertension management

    PubMed Central

    Varon, Joseph; Marik, Paul E

    2008-01-01

    Perioperative hypertension is commonly encountered in patients that undergo surgery. While attempts have been made to standardize the method to characterize the intraoperative hemodynamics, these methods still vary widely. In addition, there is a lack of consensus concerning treatment thresholds and appropriate therapeutic targets, making absolute recommendations about treatment difficult. Nevertheless, perioperative hypertension requires careful management. When treatment is necessary, therapy should be individualized for the patient. This paper reviews the pharmacologic agents and strategies commonly used in the management of perioperative hypertension. PMID:18827911

  10. Lung Disease and Hypertension

    PubMed Central

    Imaizumi, Yuki; Eguchi, Kazuo; Kario, Kazuomi

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) patients are at a high risk of developing cardiovascular diseases. Airflow limitation is a predictor of future risks of hypertension and cardiovascular events. COPD is now understood as a systemic inflammatory disease, with the focus on inflammation of the lungs. An association between inflammation and sympathetic overactivity has also been reported. In this article, we review the association between chronic lung disease and the risks of hypertension, cardiovascular morbidity, the underlying mechanisms, and the therapeutic approach to hypertension and cardiovascular diseases in patients with lung diseases. PMID:26587450

  11. Management of Intracranial Hypertension

    PubMed Central

    Rangel-Castillo, Leonardo; Gopinath, Shankar; Robertson, Claudia S.

    2008-01-01

    Effective management of intracranial hypertension involves meticulous avoidance of factors that precipitate or aggravate increased intracranial pressure. When intracranial pressure becomes elevated, it is important to rule out new mass lesions that should be surgically evacuated. Medical management of increased intracranial pressure should include sedation, drainage of cerebrospinal fluid, and osmotherapy with either mannitol or hypertonic saline. For intracranial hypertension refractory to initial medical management, barbiturate coma, hypothermia, or decompressive craniectomy should be considered. Steroids are not indicated and may be harmful in the treatment of intracranial hypertension resulting from traumatic brain injury. PMID:18514825

  12. Three 15-min bouts of moderate postmeal walking significantly improves 24-h glycemic control in older people at risk for impaired glucose tolerance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to compare the effectiveness of three 15-min bouts of postmeal walking with 45 min of sustained walking on 24-h glycemic control in older persons at risk for glucose intolerance. Inactive older (=60 years of age) participants (N = 10) were recruited from the community a...

  13. Comparative uptake of calcium from milk and a calcium-rich mineral water in lactose intolerant adults: implications for treatment of osteoporosis.

    PubMed

    Halpern, G M; Van de Water, J; Delabroise, A M; Keen, C L; Gershwin, M E

    1991-01-01

    Despite the links between low calcium (Ca) intake and age-related bone loss, hypertension, and colon cancer, the majority of Western populations have average daily Ca intakes substantially below recommended daily allowances. Although dietary products are widely known as a rich and valuable source of Ca in the diet, consumption of diary products is low and has been decreasing because of perceptions of excess calories and fat in the diet, as well as taste aversions. During the last decade, a marked increase in the consumption of bottled waters has occurred. Since some of these waters are characterized by high concentrations of Ca, we have studied Ca bioavailability from a Ca-rich water, using 15 lactose intolerant male individuals as subjects, and compared such bioavailability to that from milk. We report herein that the bioavailability of Ca from the water was generally as good as or better than that from milk, a food product well known for its very high Ca bioavailability. Indeed, in eight of 15 subjects, there was a higher level of Ca absorption from mineral water than from milk; bioavailability was equal in five of 15 subjects; in contrast, in two of 15 subjects, the bioavailability of Ca absorption from milk was greater than that from the mineral water. The potential implications of this observation for the prevention and management of age-related bone loss are important for preventive medicine and indicate a new, important source of dietary Ca for lactose intolerant individuals. PMID:1790046

  14. Blood Glucose Monitoring Devices

    MedlinePLUS

    ... the Bar for Blood Glucose Meter Performance Recalls & Alerts Shasta Technologies GenStrip Blood Glucose Test Strips May ... Latest Recalls Report an Adverse Event MedWatch Safety Alerts News Releases Consumer Updates About FDA Contact FDA ...

  15. Hyperglycemia (High Blood Glucose)

    MedlinePLUS Videos and Cool Tools

    ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

  16. Continuous Glucose Monitoring

    MedlinePLUS

    ... glucose levels. What are the prospects for an artificial pancreas? To overcome the limitations of current insu ... glucose monitoring and insulin delivery by developing an artificial pancreas. An artificial pancreas is a system that ...

  17. GLP-2 as Beneficial Factor in the Glucose Homeostasis in Mice Fed a High Fat Diet.

    PubMed

    Baldassano, Sara; Rappa, Francesca; Amato, Antonella; Cappello, Francesco; Mulè, Flavia

    2015-12-01

    Glucagon like peptide-2 (GLP-2) is a gastrointestinal hormone released in response to dietary nutrients, which acts through a specific receptor, the GLP-2 receptor (GLP-2R). The physiological effects of GLP-2 are multiple, involving also the intestinal adaptation to high fat diet (HFD). In consideration of the well-known relationship between chronic HFD and impaired glucose metabolism, in the present study we examined if the blocking of the GLP-2 signaling by chronic treatment with the GLP-2R antagonist, GLP-2 (3-33), leads to functional consequences in the regulation of glucose metabolism in HFD-fed mice. Compared with animals fed standard diet (STD), mice at the 10th week of HFD showed hyperglycaemia, glucose intolerance, high plasma insulin level after glucose load, increased pancreas weight and β cell expansion, but not insulin resistance. In HFD fed mice, GLP-2 (3-33) treatment for 4 weeks (from the 6th to the 10th week of diet) did not affect fasting glycaemia, but it significantly increased the glucose intolerance, both fasting and glucose-induced insulin levels, and reduced the sensitivity to insulin leading to insulin-resistance. In GLP-2 (3-33)-treated HFD mice pancreas was significantly heavier and displayed a significant increase in β-cell mass in comparison with vehicle-treated HFD mice. In STD mice, the GLP-2 (3-33) treatment did not affect fasted or glucose-stimulated glycemia, insulin, insulin sensitivity, pancreas weight and beta cell mass. The present study suggests that endogenous GLP-2 may act as a protective factor against the dysregulation of the glucose metabolism that occurs in HFD mice, because GLP-2 (3-33) worsens glucose metabolism disorders. PMID:25967277

  18. Hypertensive heart disease

    MedlinePLUS

    ... failure: pathophysiology and diagnosis. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ... Victor RG. Arterial hypertension. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ...

  19. Pathophysiology of Portal Hypertension

    PubMed Central

    Iwakiri, Yasuko

    2014-01-01

    Portal hypertension is a major complication of liver disease, which results from a variety of pathological conditions that increase the resistance to the portal blood flow into the liver. The primary cause of portal hypertension in cirrhosis is an increase in intrahepatic vascular resistance due to massive structural changes associated with fibrosis and increased vascular tone in the hepatic microcirculation. As portal hypertension develops, the formation of collateral vessels and arterial vasodilation progress, which results in increased blood flow to the portal circulation. Eventually the hyperdynamic circulatory syndrome develops, leading to esophageal varices or ascites. This review article will summarize the factors that increase 1) intrahepatic vascular resistance and 2) the blood flow in the splanchnic and systemic circulations in liver cirrhosis. Finally, the future directions of basic/clinical research in portal hypertension will be discussed. PMID:24679494

  20. All about Blood Glucose

    MedlinePLUS

    Toolkit No. 15 All About Blood Glucose Keeping your blood glucose (sugar)in your target range can prevent or delay the health problems ... Diabetes Association, Inc. 2/14 Toolkit No.15: All About Blood Glucose continued team about when and ...

  1. Overview of glucose regulation.

    PubMed

    Tirone, T A; Brunicardi, F C

    2001-04-01

    Glucose homeokinesis is a remarkable process that provides glucose to the body for energy and a constant source of glucose to the brain while preventing hyperglycemia. The latter leads to excessive glycosylation of proteins, changing their structure and function and eventually affecting every organ system in the body. Despite a variable diet of feast and famine throughout the day, the body maintains strict blood glucose levels through a remarkable network between the pancreas, liver, adipose tissue, muscle, and brain. These interactions and both glucose production and utilization are discussed. Glucose production is governed by the liver, which can generate free glucose from hepatic glycogen stores and de novo through gluconeogenesis. Specific glucose transporters found on every cell of the body administer glucose utilization. Each transporter works with a different serum glucose level. The mechanism of these transporters and the specific glucose cycles are discussed. The purpose of this article is to review glucose regulation; it serves as a reference for the other presentations of this symposium. PMID:11344399

  2. 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 ...

  3. Ghrelin signalling in ?-cells regulates insulin secretion and blood glucose.

    PubMed

    Yada, T; Damdindorj, B; Rita, R S; Kurashina, T; Ando, A; Taguchi, M; Koizumi, M; Sone, H; Nakata, M; Kakei, M; Dezaki, K

    2014-09-01

    Insulin secretion from pancreatic islet ?-cells is stimulated by glucose. Glucose-induced insulin release is potentiated or suppressed by hormones and neural substances. Ghrelin, an acylated 28-amino acid peptide, was isolated from the stomach in 1999 as the endogenous ligand for the growth hormone (GH) secretagogue-receptor (GHS-R). Circulating ghrelin is produced predominantly in the stomach and to a lesser extent in the intestine, pancreas and brain. Ghrelin, initially identified as a potent stimulator of GH release and feeding, has been shown to suppress glucose-induced insulin release. This insulinostatic action is mediated by G?(i2) subtype of GTP-binding proteins and delayed outward K? (Kv) channels. Interestingly, ghrelin is produced in pancreatic islets. The ghrelin originating from islets restricts insulin release and thereby upwardly regulates the systemic glucose level. Furthermore, blockade or elimination of ghrelin enhances insulin release, which can ameliorate glucose intolerance in high-fat diet fed mice and ob/ob mice. This review focuses on the insulinostatic action of ghrelin, its signal transduction mechanisms in islet ?-cells, ghrelin's status as an islet hormone, physiological roles of ghrelin in regulating systemic insulin levels and glycaemia, and therapeutic potential of the ghrelin-GHS-R system as the target to treat type 2 diabetes. PMID:25200304

  4. Glucose Metabolism and Pancreatic Defects in Spinal Muscular Atrophy

    PubMed Central

    Bowerman, Melissa; Swoboda, Kathryn J.; Michalski, John-Paul; Wang, Gen-Sheng; Reeks, Courtney; Beauvais, Ariane; Murphy, Kelley; Woulfe, John; Screaton, Robert A.; Scott, Fraser W.; Kothary, Rashmi

    2014-01-01

    Objective Spinal muscular atrophy (SMA) is the number 1 genetic killer of young children. It is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Although SMA is primarily a motor neuron disease, metabolism abnormalities such as metabolic acidosis, abnormal fatty acid metabolism, hyperlipidemia, and hyperglycemia have been reported in SMA patients. We thus initiated an in-depth analysis of glucose metabolism in SMA. Methods Glucose metabolism and pancreas development were investigated in the Smn2B/− intermediate SMA mouse model and type I SMA patients. Results Here, we demonstrate in an SMA mouse model a dramatic cell fate imbalance within pancreatic islets, with a predominance of glucagon-producing α cells at the expense of insulin-producing β cells. These SMA mice display fasting hyperglycemia, hyperglucagonemia, and glucose resistance. We demonstrate similar abnormalities in pancreatic islets from deceased children with the severe infantile form of SMA in association with supportive evidence of glucose intolerance in at least a subset of such children. Interpretation Our results indicate that defects in glucose metabolism may play an important contributory role in SMA pathogenesis. PMID:22926856

  5. Resistant Hypertension and Chronotherapy

    PubMed Central

    Prkacin, Ingrid; Balenovic, Diana; Djermanovic-Dobrota, Vesna; Lukac, Iva; Drazic, Petra; Pranjic, Iva-Klara

    2015-01-01

    Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the continuous use of three antihypertensive agents in optimal dose, including diuretic, and lifestyle changes. According to data from United States of America and Europe, the prevalence ranges from 10 up to 30% in patients with hypertension. Numerous biological and lifestyle factors can contribute to the development of resistant hypertension: medications, volume overload, obesity, diabetes mellitus, older age, renal parenchymal and renovascular disease, primary aldosteronism, obstructive sleep apnea, pheochormocytoma, Cushings syndrome, thyroid diseases, aortic coarctation. For diagnosing patients history is important, assessing compliance, regular blood pressure measurement, physical examination, biochemical evaluation and noninvasive imaging. The evaluation including 24h ambulatory monitoring of blood pressure (ABPM) in the identification of non-dipper hypertension. Non-dipper has particular importance and the prevalence of abnormally high sleep blood pressure is very often in chronic kidney patients. Therapeutic restoration of normal physiologic blood pressure reduction during night-time sleep (circadial variation) is the most significant independent predictor of decreased risk and the basis for the chronotherapy. The resistant hypertension treatment is achieved with nonpharmacological and pharmacological approach, treating secondary hypertension causes and invasive procedures. PMID:26005390

  6. Resistant hypertension and chronotherapy.

    PubMed

    Prkacin, Ingrid; Balenovic, Diana; Djermanovic-Dobrota, Vesna; Lukac, Iva; Drazic, Petra; Pranjic, Iva-Klara

    2015-04-01

    Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the continuous use of three antihypertensive agents in optimal dose, including diuretic, and lifestyle changes. According to data from United States of America and Europe, the prevalence ranges from 10 up to 30% in patients with hypertension. Numerous biological and lifestyle factors can contribute to the development of resistant hypertension: medications, volume overload, obesity, diabetes mellitus, older age, renal parenchymal and renovascular disease, primary aldosteronism, obstructive sleep apnea, pheochormocytoma, Cushing's syndrome, thyroid diseases, aortic coarctation. For diagnosing patient's history is important, assessing compliance, regular blood pressure measurement, physical examination, biochemical evaluation and noninvasive imaging. The evaluation including 24h ambulatory monitoring of blood pressure (ABPM) in the identification of "non-dipper" hypertension. Non-dipper has particular importance and the prevalence of abnormally high sleep blood pressure is very often in chronic kidney patients. Therapeutic restoration of normal physiologic blood pressure reduction during night-time sleep (circadial variation) is the most significant independent predictor of decreased risk and the basis for the chronotherapy. The resistant hypertension treatment is achieved with nonpharmacological and pharmacological approach, treating secondary hypertension causes and invasive procedures. PMID:26005390

  7. [Management of arterial hypertension].

    PubMed

    Groha, P; Schunkert, H

    2015-09-01

    Arterial hypertension is one of the most frequent diseases in the western world and is one of the three most important risk factors for heart diseases. The 2013 guidelines of the European Societies of Hypertension and Cardiology (ESH/ESC) provide a clear action plan for evidence-based diagnostics and therapeutic measures in hypertensive subjects and simplify target blood pressures across various patient groups. Non-pharmacological options play a central role in the treatment of arterial hypertension. The indications for drug therapy arise from three criteria including the level of hypertension, risk profile of the patient, as well as response to non-pharmacological therapy. For the first choice monotherapy five substance groups are available: diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin (AT) 1 receptor antagonists and calcium antagonists. By combination therapy, the responder rate can be significantly increased with respect to a normalization of blood pressure. A true treatment resistance, in which the therapeutic goal is not reached in spite of a triple combination with maximum dosage, is extremely rare. Further treatment options are combinations of four drug classes and changes of medication. Hypertensive emergencies require a rapid intervention; nevertheless, the magnitude of blood pressure lowering can greatly vary depending on the individual clinical picture. PMID:26303172

  8. Hypertension and diabetes mellitus.

    PubMed

    Marre, M; Berrut, G; Bouhanick, B

    1993-01-01

    The association of arterial hypertension and diabetes mellitus is frequent: one third of patients attending a diabetic clinic. Excess hypertension frequency is marked in type II, non insulin-dependent diabetes, a condition often associated with other vascular risk factors such as obesity and lipid disorders. Insulin resistance is a common feature between type II diabetes, hypertension and other risk factors. In type I, insulin-dependent diabetes, hypertension is often linked to diabetic nephropathy. There is a genetic basis for diabetic nephropathy, which may share a common background with familial hypertension. Apart from possible genetic predispositions to hypertension diabetes association, chronic hyperglycaemia can lead to alteration in functional and structural properties of blood and vessels, which both contribute to elevated vascular resistance and blood pressure. From a therapeutic viewpoint, blood pressure values above 140/90 mmHg are not tolerable in diabetic subjects under 40 years of age. Due to their renal haemodynamic effects, angiotensin I converting enzyme inhibitors may be of special interest to protect kidney function in diabetic subjects. PMID:8218950

  9. Hypertension: quo vadis?

    PubMed

    Borghi, Claudio

    2012-11-01

    High blood pressure (BP) along with smoking habit and lipid disorders are the most important and modifiable risk factors for cardiovascular diseases. However, the prevalence of high BP has grown progressively over time with a progressive increase not only in the absolute number of patients but in the proportion of those showing BP values out of control. The increasing world-wide prevalence of hypertension and the related increase in burden of the disease due to diagnosis, treatment and management of the complications mandates both Health Authorities and research institutions to find out new strategies to improve the BP control. So, one of the main questions is which are the possible perspectives for the future of high BP management, and in particular how can we face the problem of hypertension in the near future? Four main points will be shortly discussed: the genetic contribution to hypertension development and control, the availability of effective preventive strategies, the improvement of disease management, and the role of extensive control of concomitant risk factors. It is relatively easy to suppose that the integration of the best available knowledge with the more recent diagnostic and therapeutic achievements will improve the management of hypertension through a more effective detection of subjects at risk who will undergo an earlier diagnosis leading to a more tailored, tolerated and effective treatment of the hypertensive disease. This means that the future direction of the hypertension management is the simpler: the patient instead of the disease. PMID:23259570

  10. Glucose Homeostasis in Mice Is Transglutaminase 2 Independent

    PubMed Central

    Iismaa, Siiri E.; Aplin, Mark; Holman, Sara; Yiu, Ting W.; Jackson, Kristy; Burchfield, James G.; Mitchell, Christopher J.; OReilly, Liam; Davenport, Aimee; Cantley, James; Schmitz-Peiffer, Carsten; Biden, Trevor J.; Cooney, Gregory J.; Graham, Robert M.

    2013-01-01

    Transglutaminase type 2 (TG2) has been reported to be a candidate gene for maturity onset diabetes of the young (MODY) because three different mutations that impair TG2 transamidase activity have been found in 3 families with MODY. TG2 null (TG2?/?) mice have been reported to be glucose intolerant and have impaired glucose-stimulated insulin secretion (GSIS). Here we rigorously evaluated the role of TG2 in glucose metabolism using independently generated murine models of genetic TG2 disruption, which show no compensatory enhanced expression of other TGs in pancreatic islets or other tissues. First, we subjected chow- or fat-fed congenic SV129 or C57BL/6 wild type (WT) and TG2?/? littermates, to oral glucose gavage. Blood glucose and serum insulin levels were similar for both genotypes. Pancreatic islets isolated from these animals and analysed in vitro for GSIS and cholinergic potentiation of GSIS, showed no significant difference between genotypes. Results from intraperitoneal glucose tolerance tests (GTTs) and insulin tolerance tests (ITTs) were similar for both genotypes. Second, we directly investigated the role of TG2 transamidase activity in insulin secretion using a coisogenic model that expresses a mutant form of TG2 (TG2R579A), which is constitutively active for transamidase activity. Intraperitoneal GTTs and ITTs revealed no significant differences between WT and TG2R579A/R579A mice. Given that neither deletion nor constitutive activation of TG2 transamidase activity altered basal responses, or responses to a glucose or insulin challenge, our data indicate that glucose homeostasis in mice is TG2 independent, and question a link between TG2 and diabetes. PMID:23717413

  11. Orthostatic Intolerance Ambulation in Patients Using Patient Controlled Analgesia

    PubMed Central

    Park, Kwang Ok

    2013-01-01

    Background Opioid analgesics are widely used to reduce postoperative pain and to enhance post-operative recovery. However, orthostatic intolerance (OI) induced by opioid containing intravenous patient controlled analgesia (IPCA) may hinder postoperative recovery. This study investigated factors that affect OI in patients receiving IPCA for postoperative pain control. Methods OI was instantly evaluated at the time of first ambulation in 175 patients taking opioid containing IPCA after open and laparoscopic subtotal gastrectomies. Patients were classified as having OI if they experienced dizziness, nausea/vomiting, blurred vision, headache, somnolence and syncope. Factors contributing to OI were assessed with logistic regression analysis. Results Out of 175 patients, 61 (52.6%) male and 44 (74.6%) female patients experienced OI at the time of first ambulation. The frequency of OI related symptoms were dizziness (97, 55.4%), nausea (46, 26.3%), headache (9, 5.1%), blurred vision (3, 1.7%) and vomiting (2, 1.1%). Significant risk factors for OI were gender (P=0.002) and total amount of opioids administered (P=0.033). Conclusions The incidence of OI is significantly higher in male than in female patients and is influenced by the opioid dose. PMID:23862002

  12. 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

  13. 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

  14. Genes and exercise intolerance: insights from McArdle disease.

    PubMed

    Nogales-Gadea, Gisela; Godfrey, Richard; Santalla, Alfredo; Coll-Cant, Jaume; Pintos-Morell, Guillem; Pins, Toms; Arenas, Joaqun; Martn, Miguel Angel; Lucia, Alejandro

    2016-02-01

    McArdle disease (glycogen storage disease type V) is caused by inherited deficiency of a key enzyme in muscle metabolism, the skeletal muscle-specific isoform of glycogen phosphorylase, "myophosphorylase," which is encoded by the PYGM gene. Here we review the main pathophysiological, genotypic, and phenotypic features of McArdle disease and their interactions. To date, moderate-intensity exercise (together with pre-exercise carbohydrate ingestion) is the only treatment option that has proven useful for these patients. Furthermore, regular physical activity attenuates the clinical severity of McArdle disease. This is quite remarkable for a monogenic disorder that consistently leads to the same metabolic defect at the muscle tissue level, that is, complete inability to use muscle glycogen stores. Further knowledge of this disorder would help patients and enhance understanding of exercise metabolism as well as exercise genomics. Indeed, McArdle disease is a paradigm of human exercise intolerance and PYGM genotyping should be included in the genetic analyses that might be applied in the coming personalized exercise medicine as well as in future research on genetics and exercise-related phenotypes. PMID:26465709

  15. Managing the patient with episodic sinus tachycardia and orthostatic intolerance.

    PubMed

    Narichania, Aalap D; Schleifer, J William; Shen, Win-Kuang

    2014-01-01

    Patients with episodic sinus tachycardia and associated orthostatic intolerance present a diagnostic and management dilemma to the clinician. We define this group of disorders to include sinus node reentrant tachycardia (SNRT), inappropriate sinus tachycardia (IAST), and postural orthostatic tachycardia syndrome (POTS). After a brief review of the current understanding of the pathophysiology and epidemiology of this group of disorders, we focus on the diagnosis and management of IAST and POTS. Our approach attempts to recognize the considerable overlap in pathophysiology and clinical presentation between these two heterogeneous conditions. Thus, we focus on a mechanism-based workup and therapeutic approach. Sinus tachycardia related to identifiable causes should first be ruled out in these patients. Next, a basic cardiovascular and autonomic workup is suggested to exclude structural heart disease, identify a putative diagnosis, and guide therapy. We review both nonpharmacologic and pharmacologic therapy, with a focus on recent advances. Larger randomized control trials and further mechanistic studies will help refine management in the future. PMID:25524735

  16. 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.

  17. Novel Epoxy Activated Hydrogels for Solving Lactose Intolerance

    PubMed Central

    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 510%?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, Km and Vmax, 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

  18. 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

  19. Excessive insulin secretion in Japanese schizophrenic patients treated with antipsychotics despite normal fasting glucose levels.

    PubMed

    Sugai, Takuro; Suzuki, Yutaro; Fukui, Naoki; Watanabe, Junzo; Ono, Shin; Tsuneyama, Nobuto; Someya, Toshiyuki

    2012-12-01

    The development of impaired glucose tolerance induced by antipsychotics (APs) is of concern as a serious adverse effect of psychiatric drug therapy. However, the mechanism by which APs cause dysfunction of the glucose-insulin response is not fully understood. Recent studies have shown that patients treated with APs for schizophrenia were more likely to exhibit impaired glucose tolerance after a glucose load compared with healthy control subjects, even if fasting glucose levels were within the reference range. To explain these findings, we hypothesized that insulin secretion is increased in schizophrenic patients treated with AP, even those normal fasting glucose (NFG) levels. Therefore, oral glucose tolerance tests were conducted in 159 Japanese inpatients with AP-treated schizophrenia and in 90 healthy subjects without schizophrenia. Plasma glucose and serum insulin concentrations were measured before (0 minute) and at 30, 60, 90, and 120 minutes after the oral glucose load. Although insulin levels at 0 minute were similar in both groups of subjects, insulin levels were significantly higher in the patients treated with AP at all times after the glucose load than in the healthy subjects. In analyses of NFG subjects, insulin levels were significantly higher in the patients treated with AP compared with the healthy subjects at all times after glucose loading. Overall, we found that insulin secretion in response to a glucose load was significantly higher in the patients treated with AP, irrespective of NFG. These results suggest that APs affect the glucose-insulin response, which may lead to subclinical insulin resistance before the onset of overt glucose intolerance. PMID:23131894

  20. Improving hypertension self-management with community health coaches.

    PubMed

    Dye, Cheryl J; Williams, Joel E; Evatt, Janet Hoffman

    2015-03-01

    Approximately two thirds of those older than 60 years have a hypertension diagnosis. The aim of our program, Health Coaches for Hypertension Control, is to improve hypertension self-management among rural residents older than 60 years through education and support offered by trained community volunteers called Health Coaches. Participants received baseline and follow-up health risk appraisals with blood work, educational materials, and items such as blood pressure monitors and pedometers. Data were collected at baseline, 8 weeks, and 16 weeks on 146 participants who demonstrated statistically significant increases in hypertension-related knowledge from baseline to 8 weeks that persisted at 16 weeks, as well as significant improvements in stage of readiness to change behaviors and in actual behaviors. Furthermore, clinically significant decreases in all outcome measures were observed, with statistically significant changes in systolic blood pressure (-5.781 mmHg; p = .001), weight (-2.475 lb; p < .001), and glucose (-5.096 mg/dl; p = .004) after adjusting for multiple comparisons. Although 40.4% of participants met the Healthy People 2020 definition of controlled hypertension at baseline, the proportion of participants meeting this definition at 16 weeks postintervention increased to 51.0%. This article describes a university-community-hospital system model that effectively promotes hypertension self-management in a rural Appalachian community. PMID:24837989

  1. Familial hypertension and albuminuria in normotensive type I diabetic patients.

    PubMed

    Freire, M B; Ferreira, S R; Vivolo, M A; Oliveira, J M; Zanella, M T

    1994-01-01

    An inherited predisposition to hypertension may increase susceptibility to nephropathy in type I diabetes. We evaluated the influence of a family history of essential hypertension on albuminuria in normotensive, normoalbuminuric type I diabetic patients. Forty-two diabetics (12.9 +/- 2.04 years) were divided into three groups according to tertiles of albumin excretion rate (group 1, 1.27 +/- 0.35; group 2, 2.43 +/- 0.49; group 3, 6.37 +/- 3.43 micrograms/min; P < .001). Familial hypertension was considered to be present if the patient had one parent or grandparent on antihypertensive therapy. The three groups did not differ concerning age, diabetes duration, insulin requirement, body mass index, blood pressure, and urinary glucose excretion. Albumin excretion rate did not correlate with any parameter studied. The frequency of hypertension was significantly lower among the relatives of the patients from group 1 compared with those from groups 2 and 3 (28.6% versus 64.3% versus 78.6%, P < .03). Our data suggest that a familial antecedent of hypertension in normoalbuminuric type I diabetic patients is associated with a high normal albumin excretion rate not related to increases in blood pressure. Early changes in renal hemodynamics, seen in patients with a predisposition to hypertension, may contribute to increments in albuminuria even within the normal range. PMID:8282370

  2. [Lactase deficiency and lactose intolerance-related symptoms in adult healthy subjects from western France].

    PubMed

    Cloarec, D; Gouilloud, S; Bornet, F; Bruley des Varannes, S; Bizais, Y; Galmiche, J P

    1991-01-01

    The prevalence of lactase deficiency (LD) and lactose intolerance is not well known in France. Using breath hydrogen and methane analysis after 50 g oral lactose load, we investigated the prevalences of LD, lactose intolerance, and methane producer status in 102 healthy adults born in western France, and we examined the relationships between these parameters and the daily milk consumption. In 10 subjects with LD and lactose intolerance, we studied the reproducibility of the lactose hydrogen breath test results for the diagnosis of LD and lactose intolerance and estimated the quantity of lactose malabsorbed in comparison with the lactulose hydrogen breath test. The prevalence of LD was 23.4 percent and symptoms of lactose intolerance were observed in 50 percent of the 24 subjects with LD. The daily milk consumption was not significantly different in the 24 subjects with LD and in the 78 subjects without LD (281 +/- 197 vs 303 +/- 217 ml/24 h). The prevalence of methane producer status was 42.1 percent. The symptomatic group of lactose malabsorbers (n = 12) was characterized by a shorter lactose mouth to caecum transit time (39 +/- 20 vs 88 +/- 48 min; P less than 0.05), and more marked hydrogen production (6.1 +/- 2.3 vs 3.4 +/- 2.4 10(3) ppm.min; P less than 0.04). In the 10 subjects with LD and lactose intolerance, the hydrogen breath test was reproducible for diagnosis of LD and lactose intolerance, and for hydrogen production. The quantity of lactose malabsorbed was 60 percent. In France, symptoms of lactose intolerance are not severe and do not affect the daily consumption of milk and dairy products. PMID:1752368

  3. Fructose and lactose intolerance and malabsorption testing: the relationship with symptoms in functional gastrointestinal disorders

    PubMed Central

    Wilder-Smith, C H; Materna, A; Wermelinger, C; Schuler, J

    2013-01-01

    Background The association of fructose and lactose intolerance and malabsorption with the symptoms of different functional gastrointestinal disorders (FGID) remains unclear. Aim To investigate the prevalence of fructose and lactose intolerance (symptom induction) and malabsorption and their association with clinical gastrointestinal (GI) as well as non-GI symptoms in FGID and the outcome of dietary intervention. Methods Fructose and lactose intolerance (defined by positive symptom index) and malabsorption (defined by increased hydrogen/methane) were determined in 1372 FGID patients in a single centre using breath testing. Results were correlated with clinical symptoms in different FGID Rome III subgroups. The effectiveness of a targeted saccharide-reduced diet was assessed after 68 weeks. Results Intolerance prevalence across all FGIDs was 60% to fructose, 51% to lactose and 33% to both. Malabsorption occurred in 45%, 32% and 16% respectively. There were no differences in intolerance or malabsorption prevalence between FGID subgroups. FGID symptoms correlated with symptoms evoked during testing (r = 0.350.61. P < 0.0001), but not with malabsorption. Non-GI symptoms occurred more commonly in patients with intolerances. Methane breath levels were not associated with constipation using several cut-off thresholds. Adequate symptom relief was achieved in >80% of intolerant patients, irrespective of malabsorption. Conclusions Fructose and lactose intolerances are common in FGID and associated with increased non-GI symptoms, but not with specific FGID subtypes. Symptoms experienced during breath testing, but not malabsorption, correlate with FGID symptoms. Effective symptom relief with dietary adaptation is not associated with malabsorption. Mechanisms relating to the generation of GI and non-GI symptoms due to lactose and fructose in FGID need to be explored further. PMID:23574302

  4. Histamine 50-Skin-Prick Test: A Tool to Diagnose Histamine Intolerance

    PubMed Central

    Kofler, Lukas; Ulmer, Hanno; Kofler, Heinz

    2011-01-01

    Background. Histamine intolerance results from an imbalance between histamine intake and degradation. In healthy persons, dietary histamine can be sufficiently metabolized by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the key enzyme in degradation. Histamine elicits a wide range of effects. Histamine intolerance displays symptoms, such as rhinitis, headache, gastrointestinal symptoms, palpitations, urticaria and pruritus. Objective. Diagnosis of histamine intolerance until now is based on case history; neither a validated questionnaire nor a routine test is available. It was the aim of this trial to evaluate the usefullness of a prick-test for the diagnosis of histamine intolerance. Methods. Prick-testing with 1% histamine solution and wheal size-measurement to assess the relation between the wheal in prick-test, read after 20 to 50 minutes, as sign of slowed histamine degradation as well as history and symptoms of histamine intolerance. Results. Besides a pretest with 17 patients with HIT we investigated 156 persons (81 with HIT, 75 controls): 64 out of 81 with histamine intolerance(HIT), but only 14 out of 75 persons from the control-group presented with a histamine wheal ?3?mm after 50 minutes (P < .0001). Conclusion and Clinical Relevance. Histamine-50 skin-prickt-test offers a simple tool with relevance. PMID:23724226

  5. Histamine 50-skin-prick test: a tool to diagnose histamine intolerance.

    PubMed

    Kofler, Lukas; Ulmer, Hanno; Kofler, Heinz

    2011-01-01

    Background. Histamine intolerance results from an imbalance between histamine intake and degradation. In healthy persons, dietary histamine can be sufficiently metabolized by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the key enzyme in degradation. Histamine elicits a wide range of effects. Histamine intolerance displays symptoms, such as rhinitis, headache, gastrointestinal symptoms, palpitations, urticaria and pruritus. Objective. Diagnosis of histamine intolerance until now is based on case history; neither a validated questionnaire nor a routine test is available. It was the aim of this trial to evaluate the usefullness of a prick-test for the diagnosis of histamine intolerance. Methods. Prick-testing with 1% histamine solution and wheal size-measurement to assess the relation between the wheal in prick-test, read after 20 to 50 minutes, as sign of slowed histamine degradation as well as history and symptoms of histamine intolerance. Results. Besides a pretest with 17 patients with HIT we investigated 156 persons (81 with HIT, 75 controls): 64 out of 81 with histamine intolerance(HIT), but only 14 out of 75 persons from the control-group presented with a histamine wheal ?3?mm after 50 minutes (P < .0001). Conclusion and Clinical Relevance. Histamine-50 skin-prickt-test offers a simple tool with relevance. PMID:23724226

  6. PROX1 GENE VARIANT IS ASSOCIATED WITH FASTING GLUCOSE CHANGE AFTER ANTIHYPERTENSIVE TREATMENT

    PubMed Central

    Gong, Yan; McDonough, Caitrin W; Beitelshees, Amber L; Karnes, Jason H; OConnell, Jeffrey R.; Turner, Stephen T; Chapman, Arlene B; Gums, John G; Bailey, Kent R; Boerwinkle, Eric; Johnson, Julie A; Cooper-DeHoff, Rhonda M

    2013-01-01

    Study Objective To assess the relationship of the 33 single nucleotide polymorphisms (SNPs) previously associated with fasting glucose in Caucasians in genome-wide association studies (GWAS) with glucose response to antihypertensive drugs shown to increase risk for hyperglycemia and diabetes. Design Randomized, multicenter clinical trial. Subjects A total of 456 Caucasian men and women with uncomplicated hypertension Measurements and Main Results The Pharmacogenomic Evaluation of Antihypertensives Responses study evaluated blood pressure and glucose response in uncomplicated hypertensive patients randomized to either atenolol or hydrochlorothiazide (HCTZ) monotherapy, followed by combination therapy with both agents. Association of these SNPs with atenolol- or HCTZ-induced glucose response was evaluated in 456 Caucasian patients using linear regression adjusting for age, gender, body mass index, baseline glucose, baseline insulin, and principal component for ancestry. SNP rs340874 in the 5 region of PROX1 gene was significantly associated with atenolol-induced glucose change (p=0.0013). Participants harboring the C allele of this SNP had greater glucose elevation after approximately 9 weeks of atenolol monotherapy (beta = +2.39 mg/dL per C allele), consistent with the direction of effect in fasting glucose GWAS that C allele is associated with higher fasting glucose. Conclusion These data suggest that PROX1 SNP rs340874 discovered in fasting glucose GWAS may also be a pharmacogenetic risk factor for antihypertensive - induced hyperglycemia. ?-blockers and thiazides may interact with genetic risk factors to increase risk for dysglycemia and diabetes. PMID:24122840

  7. Sensitivity to para-phenylenediamine and intolerance to hydrochlorothiazide.

    PubMed

    Jacob, Sharon E; Zapolanski, Tamar; Chayavichitsilp, Pamela

    2008-01-01

    para-Phenylenediamine (PPD) is a contact allergen that cross-reacts with a variety of medications, including thiazide diuretics and sulfonamides. We present the case of a 52-year-old African American atopic woman who came for evaluation of a severe eyelid dermatitis and recurrent outbreaks of acneiform (follicular-based) pruritic papules on her face, chest, and back. These symptoms presented after the patient was started on hydrochlorothiazide for hypertension. The patient also reported a history of eyelid dermatitis associated with "black hair dye." Patch testing revealed a positive reaction to para-phenylenediamine (1+) and Disperse Blue 106 (1+). It was suspected that the patient might be demonstrating cross-reactivity to hydrochlorothiazide and a flare-up reaction of the eyelid dermatitis. After her cardiologist changed her blood pressure medication, the patient's eyelid dermatitis and eruption cleared. This case highlights the impact of PPD sensitization on the medical care of a patient with hypertension and the importance of choosing safer PPD-free alternatives and minimizing PPD exposures. PMID:19134428

  8. Hypertensive Disorders of Pregnancy.

    PubMed

    Leeman, Lawrence; Dresang, Lee T; Fontaine, Patricia

    2016-01-15

    Elevated blood pressure in pregnancy may represent chronic hypertension (occurring before 20 weeks' gestation or persisting longer than 12 weeks after delivery), gestational hypertension (occurring after 20 weeks' gestation), preeclampsia, or preeclampsia superimposed on chronic hypertension. Preeclampsia is defined as hypertension and either proteinuria or thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or cerebral or visual symptoms. Proteinuria is not essential for the diagnosis and does not correlate with outcomes. Severe features of preeclampsia include a systolic blood pressure of at least 160 mm Hg or a diastolic blood pressure of at least 110 mm Hg, platelet count less than 100 103 per L, liver transaminase levels two times the upper limit of normal, a doubling of the serum creatinine level or level greater than 1.1 mg per dL, severe persistent right upper-quadrant pain, pulmonary edema, or new-onset cerebral or visual disturbances. Preeclampsia without severe features can be managed with twice-weekly blood pressure monitoring, antenatal testing for fetal well-being and disease progression, and delivery by 37 weeks' gestation. Preeclampsia with any severe feature requires immediate stabilization and inpatient treatment with magnesium sulfate, antihypertensive drugs, corticosteroids for fetal lung maturity if less than 34 weeks' gestation, and delivery plans. Preeclampsia can worsen or initially present after delivery. Women with hypertensive disorders should be monitored as inpatients or closely at home for 72 hours postpartum. PMID:26926408

  9. Endocrine causes of hypertension.

    PubMed

    Gomez-Sanchez, C E; Gomez-Sanchez, E P; Yamakita, N

    1995-03-01

    Hypertension is a prominent feature of various endocrine diseases including primary aldosteronism, pheochromocytoma (considered separately in this issue), Cushing's syndrome, adrenal enzymatic deficiencies like 11 beta-hydroxylase, 17 alpha-hydroxylase deficiencies, and congenital or acquired 11 beta-hydroxysteroid dehydrogenase deficiencies. Patients with 11 beta-hydroxylase deficiency cannot convert 11-deoxycortisol or deoxycorticosterone into the active glucocorticoids cortisol and corticosterone, respectively. The increase in the powerful mineralocorticoid deoxycorticosterone, resulting from the enzymatic block, promotes sodium retention, hypertension, and hypokalemia. Females who have the deficiency also show signs of virilization due to the shunting of the precursors to the synthesis of adrenal androgens. Patients with 17 alpha-hydroxylase deficiency present with hypertension and/or hypokalemia, and male members exhibit pseudohermaphroditism with no development of male sexual characteristics. The defect is due to the lack of 17-hydroxylated steroids, which are necessary precursors in the synthesis of androgens and estrogens. The hypertension is due to the accumulation of the mineralocorticoid deoxycorticosterone. The mineralocorticoid receptor derives its specificity from the co-expression of the 11 beta-hydroxysteroid dehydrogenase, which converts the active steroids corticosterone and cortisol to the inactive 11-dehydrocorticosterone and cortisone, preventing their interaction with the receptor. Congenital absence of the 11 beta-hydroxysteroid dehydrogenase or acquired deficiency induced by consuming licorice or its derivatives result in occupancy of the mineralocorticoid receptor by cortisol and corticosterone, and production of mineralocorticoid-type hypertension. PMID:7777721

  10. Sleep and Hypertension

    PubMed Central

    Harding, Susan M.

    2010-01-01

    Ambulatory BP studies indicate that even small increases in BP, particularly nighttime BP levels, are associated with significant increases in cardiovascular morbidity and mortality. Accordingly, sleep-related diseases that induce increases in BP would be anticipated to substantially affect cardiovascular risk. Both sleep deprivation and insomnia have been linked to increases in incidence and prevalence of hypertension. Likewise, sleep disruption attributable to restless legs syndrome increases the likelihood of having hypertension. Observational studies demonstrate a strong correlation between the severity of obstructive sleep apnea (OSA) and the risk and severity of hypertension, whereas prospective studies of patients with OSA demonstrate a positive relationship between OSA and risk of incident hypertension. Intervention trials with continuous positive airway pressure (CPAP) indicate a modest, but inconsistent effect on BP in patients with severe OSA and a greater likelihood of benefit in patients with most CPAP adherence. Additional prospective studies are needed to reconcile observational studies suggesting that OSA is a strong risk factor for hypertension with the modest antihypertensive effects of CPAP observed in intervention studies. PMID:20682533

  11. Novel treatment approaches in hypertensive type 2 diabetic patients

    PubMed Central

    Castro Torres, Yaniel; Katholi, Richard E

    2014-01-01

    Type 2 diabetes mellitus (T2DM) and hypertension represent two common conditions worldwide. Their frequent association with cardiovascular diseases makes management of hypertensive patients with T2DM an important clinical priority. Carvedilol and renal denervation are two promising choices to reduce plasma glucose levels and blood pressure in hypertensive patients with T2DM to reduce future complications and improve clinical outcomes and prognosis. Pathophysiological mechanisms of both options are under investigation, but one of the most accepted is an attenuation in sympathetic nervous system activity which lowers blood pressure and improves insulin sensitivity. Choice of these therapeutic approaches should be individualized based on specific characteristics of each patient. Further investigations are needed to determine when to consider their use in clinical practice. PMID:25126399

  12. 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).

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

    PubMed

    Strhle, 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

  14. 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

  15. 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 (448.833.6 msec), QTc dispersion (59.530.3 msec) and the lowest values in heart rate response to deep breathing (HRDB) (10.36.0 beats/min) and Valsalva ratio (1.30.2). Patients with POTS showed the shortest QTc interval (421.728.6 msec), the highest HRDB values (24.59.2 beats/min), Valsalva ratio (1.80.3), 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

  16. Utility of corrected QT interval in orthostatic intolerance.

    PubMed

    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 (448.833.6 msec), QTc dispersion (59.530.3 msec) and the lowest values in heart rate response to deep breathing (HRDB) (10.36.0 beats/min) and Valsalva ratio (1.30.2). Patients with POTS showed the shortest QTc interval (421.728.6 msec), the highest HRDB values (24.59.2 beats/min), Valsalva ratio (1.80.3), 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

  17. 48-h Glucose infusion in humans: effect on hormonal responses, hunger and food intake

    PubMed Central

    Teff, Karen L.; Petrova, Maja; Havel, Peter J.; Townsend, Raymond R.

    2009-01-01

    Experimentally-induced hyperglycemia by prolonged glucose infusion allows investigation of the effects of sustained stimulation of the pancreatic ?-cell on insulin secretion and sensitivity. Hormonal responses to a meal following prolonged glucose infusions have not been investigated. To determine if a 48-h glucose infusion alters hormonal responses to a test meal as well as food intake and hunger in normal weight individuals, 16 subjects (8 men, 8 women, age 1830 y, mean BMI=21.71.6 kg/m2) were infused for 48-h with either saline (50 ml/h) or 15% glucose (200 mg/m2/min). Subjects ingested a 600 kcal mixed nutrient meal 3-h after infusion termination. Blood samples were taken during the 48-h and for 4 hours following food ingestion. The 48-h glucose infusion elicited a metabolic profile of a glucose intolerant obese subjects, with increased plasma glucose, insulin and leptin (all P<0.01) and increased HOMA-IR (P<0.001). During meal ingestion, early insulin secretion was increased (P<0.05) but postprandial glucose (P<0.01) and insulin (P<0.01) excursions were lower following the glucose infusion. Postprandial plasma triglyceride concentrations were increased after glucose compared with saline. Food intake and hunger ratings were not different between the two conditions. Plasma leptin levels were inversely correlated with hunger (P<0.03) in both conditions and with food intake (P<0.003) during the glucose condition only. Thus, a 48-h glucose infusion does not impair postprandial hormonal responses, alter food intake or hunger in normal weight subjects. The glucose-induced increases in plasma leptin result in a stronger inverse relationship between plasma leptin and hunger as well as food intake. These data are the first to demonstrate a relationship between leptin and hunger in normal weight, non-calorically restricted human subjects. PMID:17275862

  18. 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

  19. Knowledge and awareness of hypertension among patients with systemic hypertension.

    PubMed Central

    Familoni, B. Oluranti; Ogun, S. Abayomi; Aina, A. Olutoyin

    2004-01-01

    BACKGROUND: In Nigeria, systemic hypertension is the commonest noncommunicable disease, and public awareness about hypertension and its determinants is poor. This study aims to assess the knowledge and level of awareness of the disease among hypertensive patients attending the medical outpatient clinic of Olabisi Onabanjo University Teaching Hospital (OOUTH). METHODOLOGY: Hypertensive patients who attended the medical outpatient clinic during the one-year study period and gave their consent were recruited into the study. Response to a questionnaire on various aspects of hypertension was analyzed using the STATA for Windows software. RESULTS: There were 254 hypertensive patients, of which 111 were males and 143 were females, giving a male: female ratio of 1:1.3. The mean age (SD) of the patients was 51 years +/- 12.2; 52.4% of the participants were aware that hypertension was the commonest noncommunicable disease in Nigeria. About one in 10 patients (11.4%) was aware that "nil symptom" is the commonest symptom of hypertension, while 37% were not aware that hypertension could cause renal failure. Only about one-third (35.4%) of the patients knew that hypertension should ideally be treated for life, while 58.3% believed that antihypertensive drugs should be used only when there are symptoms. The remaining 6.3% believed that the treatment of hypertension should be for periods ranging from two weeks to five years but not for life. CONCLUSION: This study has demonstrated inadequate knowledge of hypertension in patients with hypertension in our study population. Conscious efforts should be made and time set aside to health educate hypertensive patients. Organization of "hypertensive club or society" could be encouraged. These will reduce dissemination of false or inaccurate information by hypertensive patients to the public and its attendant dangers. PMID:15160976

  20. Fetal Programming of Adult Glucose Homeostasis in Mice

    PubMed Central

    Cederroth, Christopher R.; Nef, Serge

    2009-01-01

    Background Emerging evidence suggests that dietary soy and phytoestrogens can have beneficial effects on lipid and glucose metabolism. We have previously shown that male mice fed from conception to adulthood with a high soy-containing diet had reduced body weight, adiposity and a decrease in glucose intolerance, an early marker of insulin resistance and diabetes. Objectives The purpose of this study was to identify the precise periods of exposure during which phytoestrogens and dietary soy improve lipid and glucose metabolism. Since intrauterine position (IUP) has been shown to alter sensitivity to endocrine disruptors, we also investigated whether the combination of IUP and fetal exposure to dietary phytoestrogens could potentially affect adult metabolic parameters. Methods Male outbred mice (CD-1) were allowed ad libitum access to either a high soy-containing diet or a soy-free diet either during gestation, lactation or after weaning. Adiposity and bone mass density was assessed by dual x-ray absorptiometry. Glucose tolerance was assessed by a glucose tolerance test. Blood pressure was examined by the tail-cuff system. Results Here we show that metabolic improvements are dependent on precise windows of exposure during life. The beneficial effects of dietary soy and phytoestrogens on adiposity were apparent only in animals fed post-natally, while the improvements in glucose tolerance are restricted to animals with fetal exposure to soy. Interestingly, we observed that IUP influenced adult glucose tolerance, but not adiposity. Similar IUP trends were observed for other estrogen-related metabolic parameters such as blood pressure and bone mass density. Conclusion Our results suggest that IUP and fetal exposure to estrogenic environmental disrupting compounds, such as dietary phytoestrogens, could alter metabolic and cardiovascular parameters in adult individuals independently of adipose gain. PMID:19789640

  1. Renal specific secondary hypertension.

    PubMed

    Kalra, P A

    2007-01-01

    Chronic kidney disease (CKD) is now understood to affect over 5% of all adult patients and it conveys a risk of reduced survival in those affected. At least 80% of those patients with stages 3-5 CKD (i.e. GFR <60 ml/min) suffer with hypertension, and in most the major cause is due to pertubation of an important renal endocrine system, the renin-angiotensin-aldosterone (RAA) axis. In this article the epidemiology of renal-related hypertension and its importance in pre-disposing to the increased cardiovascular risk in renal disease are discussed. Hypertension is known to be a major cause of progressive loss of renal function in CKD, particularly because of activation of the RAA, and hence the case for blockade of this system with ACE inhibitors and Angiotensin receptor blockers is highlighted. PMID:17695554

  2. Stress and hypertension.

    PubMed Central

    Mustacchi, P.

    1990-01-01

    In susceptible persons emotional stress results in immediate sympathetic stimulation, with a vasomotor response that results in a high-output state and elevated blood pressure; the vasopressor response seems to be transient. There seems to be no longitudinal epidemiologic validation of the attractive hypothesis that transiently elevated blood pressures are the prelude to fixed hypertension, however. The acquisition of hypertension by populations abandoning their traditional mode of living has been attributed to the sociocultural stress inherent in westernization, but these studies usually have not taken into account concomitants of this type of acculturation, such as dietary changes and increased body weight. The inverse relationship of blood pressure levels to education could explain the development of hypertension when aspiration to upward mobility is thwarted. The severity of perceived occupational stress relates inversely to blood pressure, suggesting that familiarity with a job renders the demands made by the work environment more predictable and less threatening in terms of vasopressor response. PMID:2219875

  3. Methamphetamine Use and Pulmonary Hypertension

    MedlinePLUS

    Methamphetamine Use Pulmonary & PH Hypertension Did you know that if you have used methamphetamines you are at risk for Pulmonary Hypertension? www. ... are made every year. PH in Association with Methamphetamine Use My doctor recently told me that I ...

  4. Valsartan use in pediatric hypertension.

    PubMed

    Meyers, Kevin E C; Behar, Brittany

    2011-03-01

    Hypertension affects up to 5% of school-aged children and is defined by an average systolic or diastolic blood pressure greater than the 95th percentile for age, sex and height. In prepubertal children a secondary cause for hypertension including renal disease, coarctation of the aorta or endocrine disease should be excluded by appropriate evaluation. The incidence and prevalence of essential hypertension in adolescents has increased together with the increase in obesity and now accounts for at least 50% of hypertension in this age group. Many children with primary hypertension and most children with secondary causes for hypertension require drug therapy. There are numerous drug classes that are presently used to treat hypertensive pediatric patients, which include β-blockers, peripheral α-blockers, direct vasodilators, ACE inhibitors, calcium channel blockers, diuretics and ARBs. This article will review the pharmacology of the ARB valsartan with respect to its efficacy, tolerability and safe use in hypertensive pediatric patients. PMID:21453020

  5. Chronic thromboembolic pulmonary hypertension.

    PubMed

    O'Connell, Caroline; Montani, David; Savale, Laurent; Sitbon, Olivier; Parent, Florence; Seferian, Andrei; Bulifon, Sophie; Fadel, Elie; Mercier, Olaf; Mussot, Sacha; Fabre, Dominique; Dartevelle, Philippe; Humbert, Marc; Simonneau, Grald; Jas, Xavier

    2015-12-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension (PH) characterized by the persistence of thromboembolic obstructing the pulmonary arteries as an organized tissue and the presence of a variable small vessel arteriopathy. The consequence is an increase in pulmonary vascular resistance resulting in progressive right heart failure. CTEPH is classified as group IV pulmonary hypertension according to the WHO classification of pulmonary hypertension. CTEPH is defined as precapillary pulmonary hypertension (mean pulmonary artery pressure?25mmHg with a pulmonary capillary wedge pressure?15mmHg) associated with mismatched perfusion defects on ventilation-perfusion lung scan and signs of chronic thromboembolic disease on computed tomography pulmonary angiogram and/or conventional pulmonary angiography, in a patient who received at least 3 months of therapeutic anticoagulation. CTEPH as a direct consequence of symptomatic pulmonary embolism (PE) is rare, and a significant number of CTEPH cases develop in the absence of history of PE. Thus, CTEPH should be considered in any patient with unexplained PH. Splenectomy, chronic inflammatory conditions such as inflammatory bowel disease, indwelling catheters and cardiac pacemakers have been identified as associated conditions increasing the risk of CTEPH. Ventilation-perfusion scan (V/Q) is the best test available for establishing the thromboembolic nature of PH. When CTEPH is suspected, patients should be referred to expert centres where pulmonary angiography, right heart catheterization and high-resolution CT scan will be performed to confirm the diagnosis and to assess the operability. Pulmonary endarterectomy (PEA) remains the gold standard treatment for CTEPH when organized thrombi involve the main, lobar or segmental arteries. This