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Angiopoietin-2 levels in glucose intolerance, hypertension, and metabolic syndrome in Asian Indians (Chennai Urban Rural Epidemiology Study-74).  


The aim of the study was to look at the association of angiopoietin-2 (Ang-2) in Asian Indian subjects with different grades of glucose intolerance and in those with hypertension and metabolic syndrome (MS). Three groups were recruited from the Chennai Urban Rural Epidemiology Study, a population-based study in southern India, as follows: group 1, normal glucose tolerance(n = 45); group 2, impaired glucose tolerance (IGT) (n = 45); and group 3, type 2 diabetes mellitus (T2DM) (n = 40). Angiopoietin-2 was estimated by enzyme-linked immunosorbent assay. Hypertension was diagnosed based on medical history, drug treatment of hypertension, and/or if the subjects had systolic blood pressure at least 130 mm Hg and/or diastolic blood pressure at least 85 mm Hg. Metabolic syndrome was defined using modified National Cholesterol Education Program-Adult Treatment Panel III guidelines. Subjects with T2DM had higher age-adjusted Ang-2 values (3741 +/- 1429 pg/mL) compared with subjects with IGT (1907 +/- 855 pg/mL) and normal glucose tolerance (1462 +/- 856 pg/mL) (P for trend < .001). Regression analysis showed that there was a linear increase in mean Ang-2 values with increasing severity of glucose intolerance, even after adjusting for age, sex, and body mass index. Angiopoietin-2 levels were also elevated in subjects with hypertension (P = .004) and in subjects with MS even in the absence of fasting hyperglycemia (P = .011). There was also a linear increase in the mean values of Ang-2 with increase in number of components of MS (P for trend < .001). This study demonstrates that increased levels of Ang-2 are seen in Asian Indian subjects with IGT, T2DM, and hypertension and in subjects with MS even in the absence of fasting hyperglycemia. PMID:19913849

Anuradha, Sathish; Mohan, Viswanathan; Gokulakrishnan, Kuppan; Dixit, Madhulika



Glucose intolerance in uraemia  

Microsoft Academic Search

Summary  This study confirms our first results showing large and prolonged insulin secretion in patients with azotaemia and glucose intolerance. It shows that the pattern of growth hormone and glucagon secretions was not modified in these well nourished patients with chronic renal diseases and hyperazotaemia : the fasting values were in the normal range and the response during a 5 h

G. Tchobroutsky; G. Rosselin; R. Assan; M. Derot



Comparison between valsartan and amlodipine regarding cardiovascular morbidity and mortality in hypertensive patients with glucose intolerance: NAGOYA HEART Study.  


It has not been fully examined whether angiotensin II receptor blocker is superior to calcium channel blocker to reduce cardiovascular events in hypertensive patients with glucose intolerance. A prospective, open-labeled, randomized, controlled trial was conducted for Japanese hypertensive patients with type 2 diabetes mellitus or impaired glucose tolerance. A total of 1150 patients (women: 34%; mean age: 63 years; diabetes mellitus: 82%) were randomly assigned to receive either valsartan- or amlodipine-based antihypertensive treatment. Primary outcome was a composite of acute myocardial infarction, stroke, coronary revascularization, admission attributed to heart failure, or sudden cardiac death. Blood pressure was 145/82 and 144/81 mm Hg, and glycosylated hemoglobin was 7.0% and 6.9% at baseline in the valsartan group and the amlodipine group, respectively. Both of them were equally controlled between the 2 groups during the study. The median follow-up period was 3.2 years, and primary outcome had occurred in 54 patients in the valsartan group and 56 in the amlodipine group (hazard ratio: 0.97 [95% CI: 0.66-1.40]; P=0.85). Patients in the valsartan group had a significantly lower incidence of heart failure than in the amlodipine group (hazard ratio: 0.20 [95% CI: 0.06-0.69]; P=0.01). Other components and all-cause mortality were not significantly different between the 2 groups. Composite cardiovascular outcomes were comparable between the valsartan- and amlodipine-based treatments in Japanese hypertensive patients with glucose intolerance. Admission because of heart failure was significantly less in the valsartan group. PMID:22232134

Muramatsu, Takashi; Matsushita, Kunihiro; Yamashita, Kentaro; Kondo, Takahisa; Maeda, Kengo; Shintani, Satoshi; Ichimiya, Satoshi; Ohno, Miyoshi; Sone, Takahito; Ikeda, Nobuo; Watarai, Masato; Murohara, Toyoaki



Hypertension in Alaska natives: Association with overweight, glucose intolerance, diet and mechanized activity  

Microsoft Academic Search

Objective. Determine the prevalence of hypertension in Alaska Natives and evaluate risk factors.Design. Population?based univariate and multivariate analysis of blood pressure in 1124 Alaska Natives over 20 years of age.Results. The sample had mean: age 45 years, body mass index 27, systolic pressure 123 mmHg and diastolic pressure 73 mmHg. The age?adjusted rate of hypertension ? 160\\/95 mmHg was 9.1%

Neil J. Murphy; Cynthia D. Schraer; Maureen C. Theile; Edward J. Boyko; Lisa R. Bulkow; Barbara J. Doty; Anne P. Lanier



Hypoxia Causes Glucose Intolerance in Humans  

Microsoft Academic Search

Hypoxic respiratory diseases are frequently accompanied by glucose intolerance. We examined whether hypoxia is a cause of glucose intolerance in healthy subjects. In a double-blind within-subject crossover design, hypoxic versus normoxic conditions were induced in 14 healthy men for 30 minutes by decreasing oxygen saturation to 75% (versus 96% in control subjects) under the conditions of a euglycemic clamp. The

Kerstin M. Oltmanns; Hartmut Gehring; Sebastian Rudolf; Bernd Schultes; Stefanie Rook; Ulrich Schweiger; Jan Born; Horst L. Fehm; Achim Peters



Glucose intolerance in Chinese patients with chronic hepatitis C  

Microsoft Academic Search

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

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


Blood Pressure Is Reduced and Insulin Sensitivity Increased in Glucose-Intolerant, Hypertensive Subjects after 15 Days of Consuming High-Polyphenol Dark Chocolate1-3  

Microsoft Academic Search

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, b-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

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


1) Please comment on the findings of glucose intolerance and ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... 1) Please comment on the findings of glucose intolerance and development of diabetes associated with Egrifta (tesamorelin) therapy and its impact ... More results from


Random Plasma Glucose in Serendipitous Screening for Glucose Intolerance: Screening for Impaired Glucose Tolerance Study 2  

PubMed Central

Background With positive results from diabetes prevention studies, there is interest in convenient ways to incorporate screening for glucose intolerance into routine care and to limit the need for fasting diagnostic tests. Objective The aim of this study is to determine whether random plasma glucose (RPG) could be used to screen for glucose intolerance. Design This is a cross-sectional study. Participants The participants of this study include a voluntary sample of 990 adults not known to have diabetes. Measurements RPG was measured, and each subject had a 75-g oral glucose tolerance test several weeks later. Glucose intolerance targets included diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose110 (IFG110; fasting glucose, 110–125 mg/dl, and 2 h glucose?glucose intolerance (diabetes or IGT or IFG110). The AROC was 0.80 (95% CI 0.74–0.86) for RPG to identify diabetes and 0.72 (0.68–0.75) to identify any glucose intolerance, both highly significant (p?glucose intolerance. Such “serendipitous screening” could help to identify unrecognized diabetes and prediabetes.

Ziemer, David C.; Kolm, Paul; Foster, Jovonne K.; Weintraub, William S.; Vaccarino, Viola; Rhee, Mary K.; Varughese, Rincy M.; Tsui, Circe W.; Koch, David D.; Twombly, Jennifer G.; Venkat Narayan, K. M.



Fat distribution and glucose intolerance among greenland inuit.  


OBJECTIVE A high amount of subcutaneous fat is suggested to explain the observation of lower obesity-associated metabolic risk among Inuit than among Europeans. We examined the association between measures of obesity (visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], BMI, waist circumference [WC], and percentage of body fat) and the indices of glucose metabolism (fasting and 2-h glucose levels, insulin resistance per homeostasis model assessment [HOMA-IR], and the insulin sensitivity index [ISI0,120]) among Greenland Inuit. RESEARCH DESIGN AND METHODS A total of 3,108 adult Inuit participated in a population-based study. The examination included a 75-g oral glucose tolerance test and anthropometric measurements. VAT and SAT were measured by ultrasound according to a validated protocol. Information on sociodemographic characteristics and health behaviors was obtained by interview. RESULTS Mean SATs were 1.8 and 3.5 cm in men and women, respectively. Mean VATs were 7.0 and 6.3 cm in men and women, respectively. The total prevalence of type 2 diabetes was 9%. Percentage of body fat generally was most strongly associated with all outcomes. Both SAT and VAT were significantly associated with glucose intolerance, fasting and 2-h plasma glucose levels, HOMA-IR, and ISI0,120. VAT was more strongly associated with all outcomes than was SAT. After further adjustment for BMI or WC, VAT was associated with glucose intolerance and insulin resistance, whereas there was a trend toward a negative or no association with SAT. CONCLUSIONS High mean values of SAT may to a large extent explain the high WC in Inuit populations, and this is suggested to contribute to the lower observed metabolic risk for a given level of obesity. PMID:23656981

Jørgensen, Marit Eika; Borch-Johnsen, Knut; Stolk, Ronald; Bjerregaard, Peter



Studies of glucose intolerance in cirrhosis of the liver.  


Patients with hepatic cirrhosis often have demonstrable glucose intolerance. We studied 21 patients with cirrhosis of the liver. Oral glucose tolerance tests (OGTT), intravenous arginine stimulation tests (IVAST), and intravenous insulin tolerance tests (IVITT) were performed, and timed blood samples were obtained for the assay of glucose immunoreactive insulin (IRI), C-peptide (C-P), and immunoreactive glucagon (IRG). The 125I-insulin binding to circulating monocytes was studied in some of the patients. All results were compared to those of similar studies performed on healthy controls. During OGTT significant glucose intolerance was demonstrable in the patients with cirrhosis (2 hr plasma glucose 198.8 +/- 14.3 mg/dl in cirrhosis and 116.4 +/- 4.2 in controls; p less than 0.001). Two-hour plasma IRI, C-P, and IRG were significantly higher in the cirrhotic patients than in controls (p less than 0.001; less than 0.001; less than 0.025). In response to IVAST, the patients with cirrhosis showed a greater first-phase insulin secretion and controls had a slightly better second-phase insulin release. Plasma IRG rose from a basal value of 446 pg/ml to 1100 in the patients with cirrhosis and from 171 pg/ml to 494 in controls. After intravenous insulin administration, there was only a 40% decline in plasma glucose concentration from basal values in the patients with cirrhosis whereas the controls showed a 60% decline, demonstrating that the patients with cirrhosis had significant insulin resistance. Moreover, the half-life of insulin was prolonged in the patients with cirrhosis (t 1/2 = 15.5 min in cirrhosis and 10.3 in controls; p less than 0.001); and the ratio of C-P to insulin during OGTT was also reduced, indicating that the patients with cirrhosis have reduced hepatic clearance of insulin. The specific binding of 125I-insulin to circulating monocytes was 2.7% in cirrhosis, 2% in obese controls, and 4% in lean controls. There was a significant negative correlation between the fasting plasma insulin values and the specific binding of insulin. In conclusion, patients with hepatic cirrhosis have significant glucose intolerance characterized by hyperinsulinemia, hyperglucagonemia, insulin resistance, and down-regulation of insulin receptors. Although hyperinsulinemia is probably caused by reduced hepatic clearance of insulin, hyperglucagonemia is primarily due to increased pancreatic secretion. PMID:6352838

Shankar, T P; Solomon, S S; Duckworth, W C; Himmelstein, S; Gray, S; Jerkins, T; Bobal, M A; Iyer, R S



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...


Prevalence of glucose intolerance and associated risk factors in rural and urban populations of different ethnic groups in Kenya  

Microsoft Academic Search

ObjectiveTo assess the prevalence of glucose intolerance in rural and urban Kenyan populations and in different ethnic groups. Further, to identify associations between lifestyle risk factors and glucose intolerance.

D. L. Christensen; H. Friis; D. L. Mwaniki; B. Kilonzo; I. Tetens; M. K. Boit; B. Omondi; L. Kaduka; K. Borch-Johnsen



Dietary Change and Obesity Associated with Glucose Intolerance in Alaska Natives  

Microsoft Academic Search

Objective To investigate frequency of food intake, body weight, and glucose intolerance in Alaska Natives.Design Height, weight, and random blood glucose levels were measured and a frequency-of-food-intake questionnaire was obtained. This questionnaire classified persons as consumers of indigenous foods or nonindigenous foods within three food groups. Those with a random blood glucose measurement ?6.72 mmol\\/L received an oral glucose tolerance




Determinants of Impaired Fasting Glucose Versus Glucose Intolerance in Polycystic Ovary Syndrome  

PubMed Central

OBJECTIVE To determine insulin resistance and response in patients with polycystic ovary syndrome (PCOS) and normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance, and combined glucose intolerance (CGI). RESEARCH DESIGN AND METHODS In this cross-sectional study, 143 patients with PCOS (diagnosed on the basis of National Institutes of Health criteria) underwent oral glucose tolerance testing (OGTT), and 68 patients also had frequently sampled intravenous glucose tolerance tests. Changes in plasma glucose, insulin, cardiovascular risk factors, and androgens were measured. RESULTS Compared with patients with NGT, those with both IFG and CGI were significantly insulin resistant (homeostasis model assessment 3.3 ± 0.2 vs. 6.1 ± 0.9 and 6.4 ± 0.5, P < 0.0001) and hyperinsulinemic (insulin area under the curve for 120 min 973 ± 69 vs. 1,470 ± 197 and 1,461 ± 172 pmol/l, P < 0.0001). Insulin response was delayed in patients with CGI but not in those with IFG (2-h OGTT, insulin 1,001 ± 40 vs. 583 ± 45 pmol/l, P < 0.0001). Compared with the NGT group, the CGI group had a lower disposition index (1,615 ± 236 vs. 987 ± 296, P < 0.0234) and adiponectin level (11.1 ± 1.1 vs. 6.2 ± 0.8 ng/ml, P < 0.0096). Compared with the insulin-resistant tertile of the NGT group, those with IFG had a reduced insulinogenic index (421 ± 130 vs. 268 ± 68, P < 0.05). Compared with the insulin-sensitive tertile of the NGT group, the resistant tertile had higher triglyceride and high-sensitivity C-reactive protein (hs-CRP) and lower HDL cholesterol and sex hormone–binding globulin (SHBG). In the entire population, insulin resistance correlated directly with triglyceride, hs-CRP, and the free androgen index and inversely with SHBG. CONCLUSIONS Patients with PCOS develop IFG and CGI despite having significant hyperinsulinemia. Patients with IFG and CGI exhibit similar insulin resistance but very different insulin response patterns. Increases in cardiac risk factors and free androgen level precede overt glucose intolerance.

Karakas, Sidika E.; Kim, Kyoungmi; Duleba, Antoni J.



Impaired Skeletal Muscle Substrate Oxidation in Glucose-intolerant Men Improves After Weight Loss  

Microsoft Academic Search

Objective:An impaired fatty acid handling in skeletal muscle may be involved in the development of insulin resistance and diabetes mellitus type 2 (DM2). We investigated muscle fatty acid metabolism in glucose-intolerant men (impaired glucose tolerance (IGT)), a prediabetic state, relative to BMI-matched control men (normal glucose tolerance (NGT)) during fasting and after a meal, because most people in the western

Eva Corpeleijn; Marco Mensink; Marianne E. Kooi; Paul M. H. J. Roekaerts; Wim H. M. Saris; Ellen E. Blaak



Combination of Site of Infarct, Unrecognized Glucose Intolerance, and Reinfarction After Acute Myocardial Infarction in Normotensive Subjects Is Determinant of the Development of Subsequent Systemic Hypertension: A Pilot Study  

Microsoft Academic Search

Background: The natural history of hypertension in healthy normotensive subjects has been described in the Framingham population. We aim to study the rate of progression to hypertension in normotensive subjects after acute myocardial infarction (AMI).Methods: One hundred seventy-three consecutive normotensive subjects admitted to the Coronary Care Unit with AMI were studied retrospectively with prospective follow-up 4 years after AMI. All

Abdul-Majeed Salmasi; Layla J. Al-Bahrani; Audrey Alimo; Peter Frost; Mark Dancy



Intracerebroventricular Administration of Bromocriptine Ameliorates the Insulin-Resistant\\/Glucose-Intolerant State in Hamsters  

Microsoft Academic Search

Bromocriptine, a potent dopamine D2 receptor agonist, suppresses lipogenesis and improves glucose intolerance and insulin resistance. Recent evidence suggests that bromocriptine may produce these effects by altering central nervous system (CNS) regulation of metabolism. To determine whether or not the CNS plays a critical role in these bromocriptine-mediated effects on peripheral metabolism, we compared the metabolic responses to bromocriptine when

Shuqin Luo; Yin Liang; Anthony H. Cincotta



Effect of overweight and obesity on glucose intolerance and dyslipidemia in Saudi Arabia, epidemiological study  

Microsoft Academic Search

The aim of this study was to study the effect of overweight and obesity on glucose intolerance and dyslipidemia in Saudi Arabia. A cross-sectional national epidemiological randomized household survey of 2059 Saudi subjects, aged 30–64 years was carried out. The sample was representative and was in accordance with the national population distribution with respect to age, gender, regional and residency,

Abdul Rahman Al-Nuaim



Ocular complications in the old and glucose-intolerant genetically obese (fa\\/fa) rat  

Microsoft Academic Search

Summary  Genetically obese fatty (fa\\/fa) male rats with abnormal oral glucose tolerance associated with initial hyperinsulinaemia as well as control lean (FA\\/FA) rats were investigated for the development of retinal microangiopathies. The animals were kept on a standard or sucrose supplemented diet. When tested at 60 weeks, the glucose intolerance of fa\\/fa rats was accompanied by an insulin response that was

A. Dosso; E. Rungger-Brändle; F. Rohner-Jeanrenaud; E. Ionescu; C. Guillaume-Gentil; B. Jeanrenaud; P. M. Leuenberger



Body Iron Stores and Glucose Intolerance in Premenopausal Women  

PubMed Central

OBJECTIVE Increased serum ferritin levels and iron stores may be involved in the development of abnormal glucose tolerance in women presenting with obesity and/or polycystic ovary syndrome (PCOS). We aimed to study the determinants of serum ferritin levels in premenopausal women among indexes of insulin resistance, adiposity, hyperandrogenism, and genotypes pertaining to inflammation, oxidative stress, and iron metabolism. RESEARCH DESIGN AND METHODS A total of 257 premenopausal women, classified depending on the presence or absence of PCOS, obesity, and/or abnormal glucose tolerance, underwent a complete metabolic evaluation, serum ferritin, haptoglobin, and C-reactive protein (CRP) measurements, and genotyping for proinflammatory and prooxidant variants and mutations in the HFE gene. RESULTS Serum ferritin concentrations were increased in women presenting with PCOS and/or abnormal glucose tolerance, independent of obesity. A stepwise multivariate linear regression analysis (R2 = 0.18, P < 0.0001) retained menstrual dysfunction (? = 0.14, P = 0.035), free testosterone (? = 0.14, P = 0.052), insulin sensitivity index (? = ?0.12, P = 0.012), the His63Asp variant in HFE (? = 0.16, P = 0.008), and abnormal glucose tolerance (? = 0.15, P = 0.015) as significant predictors of the logarithm of ferritin levels, whereas CRP, haptoglobin, waist-to-hip ratio, or variants in the TNF?, TNFRSF1B, IL6, IL6ST, IL6R?, PON1, and HFE Cys282Tyr mutation exerted no influence. CONCLUSIONS Androgen excess (partly because of hyperandrogenemia and partly because of menstrual dysfunction), insulin resistance, abnormal glucose tolerance, and the HFE His63Asp variant correlate with ferritin levels in premenopausal women.

Martinez-Garcia, M. Angeles; Luque-Ramirez, Manuel; San-Millan, Jose L.; Escobar-Morreale, Hector F.



Dietary supplementation with vitamin E and C attenuates dexamethasone-induced glucose intolerance in rats.  


Glucocorticoid excess induces marked insulin resistance and glucose intolerance. A recent study has shown that antioxidants prevent dexamethasone (DEX)-induced insulin resistance in cultured adipocytes. The purpose of this investigation was to examine the effects of dietary vitamin E and C (Vit E/C) supplementation on DEX-induced glucose intolerance in rats. We hypothesized that feeding rats a diet supplemented with Vit E/C would improve glucose tolerance and restore insulin signaling in skeletal muscle, adipose, and liver and prevent alterations in AMPK signaling in these tissues. Male Wistar rats received either a control or Vit E/C-supplemented diet (0.5 g/kg diet each of L-ascorbate and DL-all rac-alpha-tocopherol) for 9 days prior to, and during, 5 days of daily DEX treatment (subcutaneous injections 0.8 mg/g body wt). DEX treatment resulted in increases in the glucose and insulin area under the curve (AUC) during an intraperitoneal glucose tolerance test. The glucose, but not insulin, AUC was lowered with Vit E/C supplementation. Improvements in glucose tolerance occurred independent of a restoration of PKB phosphorylation in tissues of rats stimulated with an intraperitoneal injection of insulin but were associated with increases in AMPK signaling in muscle and reductions in AMPK signaling and the expression of fatty acid oxidation enzymes in liver. There were no differences in mitochondrial enzymes in triceps muscles between groups. This study is the first to report that dietary Vit E/C supplementation can partially prevent DEX-induced glucose intolerance in rats. PMID:22031784

Williams, Deon B; Wan, Zhongxiao; Frier, Bruce C; Bell, Rhonda C; Field, Catherine J; Wright, David C



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

PubMed Central

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.

Ghosh, Payal; Nicholson, Wanda K.



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

PubMed Central

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.

Floras, John; Retnakaran, Ravi



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

Microsoft Academic Search

India is experiencing an epidemic of Type 2 diabetes mellitus (DM) in young adults. This study reports the prevalence of glucose intolerance, and insulin profiles, and their relationship to lifestyle factors in 2218 young adults (aged 26–32 years; 997 urban, 1221 rural) in south India. They were drawn from a cohort of 10,691 individuals born during 1969–1973 in Vellore and

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



Relationship of glucose intolerance and hyperinsulinaemia to body fat pattern in South Asians and Europeans  

Microsoft Academic Search

Summary  Type 2 (non-insulin-dependent) diabetes mellitus and insulin resistance are associated with centrally-distributed obesity. These disturbances are especially prevalent in people of South Asian (Indian, Pakistani and Bangladeshi) descent. We examined the relationship of glucose intolerance to body fat pattern in a population survey of 2936 men and 537 women of South Asian and European origin living in London, UK. In

P. M. McKeigue; T. Pierpoint; J. E. Ferrie; M. G. Marmot



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

PubMed Central

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.



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


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

Latulippe, Marie E; Skoog, Suzanne M



Kinetics of insulin secretion and glucose intolerance in adult patients with cystic fibrosis.  


Disturbance of glucose metabolism and diabetes is an increasing complication in adult patients with cystic fibrosis (CF). The aim of the present study was to evaluate the impact of insulin and glucagon-like peptide-1 (GLP-1) secretion on early disturbance of glucose metabolism and clinical status in an unselected cohort of CF patients. 34 adult CF patients and 10 matched healthy subjects underwent an oral glucose tolerance test. Blood samples were taken to measure indices for insulin secretion and insulin sensitivity. Metabolic parameters were correlated with anthropometric and clinical data. In CF patients, there was a decrease in first phase insulin secretion (FPIR) with progressive delay of insulin peak, which was correlated with worsening glucose tolerance (Stumvoll index: normal glucose tolerance: 450±291; impaired fasting glucose: 252±203; impaired glucose tolerance: 309±254; CF related diabetes: 18±41; controls: 950±388) and high early post-challenge glucose peak (p<0.01 vs. controls). However, total insulin secretory capacity was not decreased in CF patients resulting to low glucose levels in the late phase (120-180 min). We found neither a difference in basal or maximal GLP-1 levels nor in insulin resistance between study groups. Maximum glucose levels correlated with impaired FEV1 (rs=-0.5, p=0.002). Our data demonstrate that alteration of FPIR, but not insulinopenia, insulin resistance, or disturbed GLP-1 secretion is present in the prediabetic state in CF patients. Correlation between high glucose levels and worse clinical status suggest that diabetes treatment should be initiated more early in the state of glucose intolerance. PMID:21448848

Anzeneder, L; Kircher, F; Feghelm, N; Fischer, R; Seissler, J



Glucose Intolerance  

Microsoft Academic Search

Polycystic ovary syndrome (PCOS) affects 5–8% of reproductive-age women. Patients with PCOS present with signs and symptoms\\u000a that are very heterogeneous and variable over time. The symptoms of the PCOS usually begin around menarche, but onset after\\u000a puberty may also occur as a result of environmental modifiers such as weight gain. The consequences of the PCOS, not adequately\\u000a treated, extend

Vincenzo Toscano


Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design  

PubMed Central

Background Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Methods Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-?, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation. Results Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003). Conclusions The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.



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


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 ?-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 ?-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

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



Relationship between renal and cardiovascular changes in a murine model of glucose intolerance  

Microsoft Academic Search

Nutrition is an important variable which may affect the risk for renal disease. We previously showed that a high fructose diet in mice produced hypertension and sympathetic activation [8]. The purpose of this study was to determine if a fructose diet altered renal function. A high fructose diet for 12weeks impaired glucose tolerance, but caused no change in body weight,

Tatiana S. Cunha; Vera Farah; Janaina Paulini; Mariana Pazzine; Khalid M. Elased; Fernanda K. Marcondes; Maria Cláudia Irigoyen; Kátia De Angelis; L. David Mirkin; Mariana Morris



Znt7-null mice are more susceptible to diet-induced glucose intolerance and insulin resistance.  


The Znt7 gene encodes a ubiquitously expressed zinc transporter that is involved in transporting cytoplasmic zinc into the Golgi apparatus and a ZnT7-containing vesicular compartment. Overexpression of ZnT7 in the pancreatic ?-cell stimulates insulin synthesis and secretion through regulation of insulin gene transcription. In this study, we demonstrate that ZnT7 is expressed in the mouse skeletal muscle. The activity of the insulin signaling pathway was down-regulated in myocytes isolated from the femoral muscle of Znt7 knock-out (KO) mice. High fat diet consumption (45% kcal) induced weight gain in male Znt7 KO mice but not female Znt7 KO mice. Male Znt7 KO mice fed the high fat diet at 5 weeks of age for 10 weeks exhibited hyperglycemia in the non-fasting state. Oral glucose tolerance tests revealed that male Znt7 KO mice fed the high fat diet had severe glucose intolerance. Insulin tolerance tests showed that male Znt7 KO mice were insulin-resistant. Diet-induced insulin resistance in male Znt7 KO mice was paralleled by a reduction in mRNA expression of Insr, Irs2, and Akt1 in the primary skeletal myotubes isolated from the KO mice. Overexpression of ZnT7 in a rat skeletal muscle cell line (L6) increased Irs2 mRNA expression, Irs2 and Akt phosphorylation, and glucose uptake. We conclude that a combination of decreased insulin secretion and increased insulin resistance accounts for the glucose intolerance observed in Znt7 KO mice. PMID:22854958

Huang, Liping; Kirschke, Catherine P; Lay, Yu-An E; Levy, Lauren B; Lamirande, Danielle E; Zhang, Patrick H



Znt7-null Mice Are More Susceptible to Diet-induced Glucose Intolerance and Insulin Resistance*  

PubMed Central

The Znt7 gene encodes a ubiquitously expressed zinc transporter that is involved in transporting cytoplasmic zinc into the Golgi apparatus and a ZnT7-containing vesicular compartment. Overexpression of ZnT7 in the pancreatic ?-cell stimulates insulin synthesis and secretion through regulation of insulin gene transcription. In this study, we demonstrate that ZnT7 is expressed in the mouse skeletal muscle. The activity of the insulin signaling pathway was down-regulated in myocytes isolated from the femoral muscle of Znt7 knock-out (KO) mice. High fat diet consumption (45% kcal) induced weight gain in male Znt7 KO mice but not female Znt7 KO mice. Male Znt7 KO mice fed the high fat diet at 5 weeks of age for 10 weeks exhibited hyperglycemia in the non-fasting state. Oral glucose tolerance tests revealed that male Znt7 KO mice fed the high fat diet had severe glucose intolerance. Insulin tolerance tests showed that male Znt7 KO mice were insulin-resistant. Diet-induced insulin resistance in male Znt7 KO mice was paralleled by a reduction in mRNA expression of Insr, Irs2, and Akt1 in the primary skeletal myotubes isolated from the KO mice. Overexpression of ZnT7 in a rat skeletal muscle cell line (L6) increased Irs2 mRNA expression, Irs2 and Akt phosphorylation, and glucose uptake. We conclude that a combination of decreased insulin secretion and increased insulin resistance accounts for the glucose intolerance observed in Znt7 KO mice.

Huang, Liping; Kirschke, Catherine P.; Lay, Yu-An E.; Levy, Lauren B.; Lamirande, Danielle E.; Zhang, Patrick H.



Evaluation of Serum Selenium Levels in Turkish Women with Gestational Diabetes Mellitus, Glucose Intolerants, and Normal Controls  

Microsoft Academic Search

The aim of the study was to investigate the association between serum selenium levels in patients with gestational diabetes\\u000a mellitus (GDM) and glucose intolerants and compare them with those of glucose-tolerant pregnant women. This cross-sectional\\u000a study was prospectively performed in a total of 178 pregnant women undergoing a 50-g oral glucose tolerance test between 24\\u000a and 28 weeks of gestation who

Metin Kilinc; Melih A. Guven; Muhsin Ezer; Ibrahim Egemen Ertas; Ayhan Coskun



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

PubMed Central

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.




Body mass index, waist circumference, waist-hip ratio, and glucose intolerance in Chinese and Europid adults in Newcastle, UK.  

PubMed Central

OBJECTIVE: To compare the prevalence of glucose intolerance (impaired glucose tolerance and diabetes), and its relationship to body mass index (BMI) and waist-hip ratio in Chinese and Europid adults. DESIGN: This was a cross sectional study. SETTING: Newcastle upon Tyne. SUBJECTS: These comprised Chinese and Europid men and women, aged 25-64 years, and resident in Newcastle upon Tyne, UK. MAIN OUTCOME MEASURES: Two hour post load plasma glucose concentration, BMI, waist circumference, and waist-hip ratio. METHODS: Population based samples of Chinese and European adults were recruited. Each subject had a standard WHO oral glucose tolerance test. RESULTS: Complete data were available for 375 Chinese and 610 Europid subjects. The age adjusted prevalences of glucose intolerance in Chinese and Europid men were 13.0% (p = 0.04). Mean BMIs were lower in Chinese men (23.8 v 26.1) and women (23.5 v 26.1) than in the Europids (p values < 0.001), as were waist circumferences (men, 83.3 cm v 90.8, p < 0.001; women, 77.3 cm v 79.2, p < 0.05). Mean waist-hip ratios were lower in Chinese men (0.90 v 0.91, p = 0.02) but higher in Chinese women (0.84 v 0.78, p < 0.001) compared with Europids. In both Chinese and Europid adults, higher BMI, waist circumference, and waist-hip ratio were associated with glucose intolerance. CONCLUSIONS: The prevalence of glucose intolerance in Chinese men and women, despite lower BMIs, is similar to or higher than that in local Europid men and women and intermediate between levels found in China and those in Mauritius. It is suggested that an increase in mean BMI to the levels in the Europid population will be associated with a substantial increase in glucose intolerance in Chinese people.

Unwin, N; Harland, J; White, M; Bhopal, R; Winocour, P; Stephenson, P; Watson, W; Turner, C; Alberti, K G



A1C cut points to define various glucose intolerance groups in Asian Indians.  


OBJECTIVE To determine A1C cut points for glucose intolerance in Asian Indians. RESEARCH DESIGN AND METHODS A total of 2,188 participants without known diabetes were randomly selected from the Chennai Urban Rural Epidemiology Study. All had fasting plasma glucose (FPG) and 2-h postload plasma glucose measurements after a 75-g load and were classified as having impaired fasting glucose (IFG) (American Diabetes Association [ADA] criteria, FPG > or =5.5 and <7 mmol/l, and World Health Organization [WHO] criteria, FPG > or =6.1 and <7 mmol/l), impaired glucose tolerance (IGT) (2-h postload plasma glucose > or =7.8 and <11.1 mmol/l), or diabetes (FPG > or =7 mmol/l and/or 2-h postload plasma glucose > or =11.1 mmol/l). A1C was measured using the Bio-Rad Variant machine. Based on receiver operating characteristic curves, optimum sensitivity and specificity were derived for defining A1C cut points for diabetes, IGT, and IFG. RESULTS Mean +/- SD values of A1C among subjects with normal glucose tolerance, IGT, and diabetes were 5.5 +/- 0.4, 5.9 +/- 0.6, and 8.3 +/- 2.0%, respectively (P(trend) < 0.001) with considerable overlap. To identify diabetes based on 2-h postload plasma glucose, the A1C cut point of 6.1% had an area under the curve (AUC) of 0.941 with 88.0% sensitivity and 87.9% specificity. When diabetes was defined as FPG > or =7.0 mmol/l, the A1C cut point was 6.4% (AUC = 0.966, sensitivity 93.3%, and specificity 92.3%). For IGT, AUC = 0.708; for IFG, AUC = 0.632 (WHO criteria) and 0.708 (ADA criteria), and the A1C cut point was 5.6%. CONCLUSIONS In Asian Indians, A1C cut points of 6.1 and 6.4% defined diabetes by 2-h postload plasma glucose or FPG criteria, respectively. A value of 5.6% optimally identified IGT or IFG but was <70% accurate. PMID:19903752

Mohan, Viswanathan; Vijayachandrika, Venkataraman; Gokulakrishnan, Kuppan; Anjana, Ranjit Mohan; Ganesan, Anbazhagan; Weber, Mary Beth; Narayan, K M Venkat



A1C Cut Points to Define Various Glucose Intolerance Groups in Asian Indians  

PubMed Central

OBJECTIVE To determine A1C cut points for glucose intolerance in Asian Indians. RESEARCH DESIGN AND METHODS A total of 2,188 participants without known diabetes were randomly selected from the Chennai Urban Rural Epidemiology Study. All had fasting plasma glucose (FPG) and 2-h postload plasma glucose measurements after a 75-g load and were classified as having impaired fasting glucose (IFG) (American Diabetes Association [ADA] criteria, FPG ?5.5 and <7 mmol/l, and World Health Organization [WHO] criteria, FPG ?6.1 and <7 mmol/l), impaired glucose tolerance (IGT) (2-h postload plasma glucose ?7.8 and <11.1 mmol/l), or diabetes (FPG ?7 mmol/l and/or 2-h postload plasma glucose ?11.1 mmol/l). A1C was measured using the Bio-Rad Variant machine. Based on receiver operating characteristic curves, optimum sensitivity and specificity were derived for defining A1C cut points for diabetes, IGT, and IFG. RESULTS Mean ± SD values of A1C among subjects with normal glucose tolerance, IGT, and diabetes were 5.5 ± 0.4, 5.9 ± 0.6, and 8.3 ± 2.0%, respectively (Ptrend < 0.001) with considerable overlap. To identify diabetes based on 2-h postload plasma glucose, the A1C cut point of 6.1% had an area under the curve (AUC) of 0.941 with 88.0% sensitivity and 87.9% specificity. When diabetes was defined as FPG ?7.0 mmol/l, the A1C cut point was 6.4% (AUC = 0.966, sensitivity 93.3%, and specificity 92.3%). For IGT, AUC = 0.708; for IFG, AUC = 0.632 (WHO criteria) and 0.708 (ADA criteria), and the A1C cut point was 5.6%. CONCLUSIONS In Asian Indians, A1C cut points of 6.1 and 6.4% defined diabetes by 2-h postload plasma glucose or FPG criteria, respectively. A value of 5.6% optimally identified IGT or IFG but was <70% accurate.

Mohan, Viswanathan; Vijayachandrika, Venkataraman; Gokulakrishnan, Kuppan; Anjana, Ranjit Mohan; Ganesan, Anbazhagan; Weber, Mary Beth; Narayan, K.M. Venkat



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


Fruit juice of Morinda citrifolia (Noni juice) is a well-known health drink and has various pharmacological properties including antioxidant and anti-inflammatory effects. We have hitherto found the protective effect of Noni juice on brain damage caused by ischemic stress in mice. In addition, we also recently reported that regulation of post-ischemic glucose intolerance might be important for good prognosis. Here, we focused on the effect of Noni juice on the development of the post-ischemic glucose intolerance as a cerebral protective mechanism. Noni juice was obtained from the mature fruit grown in Okinawa (about 1.5 L/4 kg of fruit; 100% ONJ). Male ddY mice were given 10% ONJ in drinking water for 7 days. Then, mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Ingestion of 10% ONJ suppressed the development of neuronal damage after MCAO. Interestingly, glucose intolerance observed on the 1st day after MCAO completely disappeared after 10% ONJ administration. Furthermore, ONJ treatment significantly increased serum insulin levels much further than the control group on the 1st day, while serum adiponectin levels were not affected at all. These results suggest that ONJ could facilitate insulin secretion after ischemic stress and may attenuate the development of glucose intolerance. These mechanisms may contribute to the neuronal protective effect of ONJ against ischemic stress. PMID:20574728

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



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

PubMed Central

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

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



Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure  

PubMed Central

The liver plays an important role in insulin-regulated glucose homoeostasis. To study the function of the PDK1 (3-phosphoinositide-dependent protein kinase-1) signalling pathway in mediating insulin's actions in the liver, we employed CRE recombinase/loxP technology to generate L(liver)-PDK1?/? mice, which lack expression of PDK1 in hepatocytes and in which insulin failed to induce activation of PKB in liver. The L-PDK1?/? mice were not insulin-intolerant, possessed normal levels of blood glucose and insulin under normal feeding conditions, but were markedly glucose-intolerant when injected with glucose. The L-PDK1?/? mice also possessed 10-fold lower levels of hepatic glycogen compared with control littermates, and were unable to normalize their blood glucose levels within 2 h after injection of insulin. The glucose intolerance of the L-PDK1?/? mice may be due to an inability of glucose to suppress hepatic glucose output through the gluconeogenic pathway, since the mRNA encoding hepatic PEPCK (phosphoenolpyruvate carboxykinase), G6Pase (glucose-6-phosphatase) and SREBP1 (sterol-regulatory-element-binding protein 1), which regulate gluconeogenesis, are no longer controlled by feeding. Furthermore, three other insulin-controlled genes, namely IGFBP1 (insulin-like-growth-factor-binding protein-1), IRS2 (insulin receptor substrate 2) and glucokinase, were regulated abnormally by feeding in the liver of PDK1-deficient mice. Finally, the L-PDK1?/? mice died between 4–16 weeks of age due to liver failure. These results establish that the PDK1 signalling pathway plays an important role in regulating glucose homoeostasis and controlling expression of insulin-regulated genes. They suggest that a deficiency of the PDK1 pathway in the liver could contribute to development of diabetes, as well as to liver failure.



Glucose intolerance and lipid metabolic adaptations in response to intrauterine and postnatal calorie restriction in male adult rats.  


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

Garg, Meena; Thamotharan, Manikkavasagar; Dai, Yun; Lagishetty, Venu; Matveyenko, Aleksey V; Lee, W N Paul; Devaskar, Sherin U



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

PubMed Central

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

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



Differential Development of Glucose Intolerance and Pancreatic Islet Adaptation in Multiple Diet Induced Obesity Models  

PubMed Central

Background: The C57BL/6 mouse fed a high fat diet is a common and valuable model in experimental studies of obesity and type 2 diabetes (T2D). Different high fat diets are used and in order to determine which diet produces a model most accurately resembling human T2D, they need to be compared head-to-head. Methods: Four different diets, the 60% high fat diet (HFD) and the 58% high fat-high sucrose Surwit diet (HFHS) and their respective controls, were compared in C57BL/6J mice using glucose tolerance tests (IVGTT) and the euglycemic clamp. Results: Mice fed a HFD gained more weight than HFHS fed mice despite having similar energy intake. Both high fat diet models were glucose intolerant after eight weeks. Mice fed the HFD had elevated basal insulin, which was not seen in the HFHS group. The acute insulin response (AIR) was unchanged in the HFD group, but slightly increased in the HFHS diet group. The HFHS diet group had a threefold greater total insulin secretion during the IVGTT compared to its control, while no differences were seen in the HFD group. Insulin sensitivity was decreased fourfold in the HFD group, but not in the HFHS diet group. Conclusion: The HFD and HFHS diet models show differential effects on the development of insulin resistance and beta cell adaptation. These discrepancies are important to acknowledge in order to select the appropriate diet for specific studies.

Omar, Bilal; Pacini, Giovanni; Ahren, Bo



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

PubMed Central

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.

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.



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

PubMed Central

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.

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



Profilin-1 haploinsufficiency protects against obesity-associated glucose intolerance and preserves adipose tissue immune homeostasis.  


Metabolic inflammation may contribute to the pathogenesis of obesity and its comorbidities, including type 2 diabetes and cardiovascular disease. Previously, we showed that the actin-binding protein profilin-1 (pfn) plays a role in atherogenesis because pfn heterozygote mice (PfnHet) exhibited a significant reduction in atherosclerotic lesion burden and vascular inflammation. In the current study, we tested whether pfn haploinsufficiency would also limit diet-induced adipose tissue inflammation and insulin resistance (IR). First, we found that a high-fat diet (HFD) upregulated pfn expression in epididymal and subcutaneous white adipose tissue (WAT) but not in the liver or muscle of C57BL/6 mice compared with normal chow. Pfn expression in WAT correlated with F4/80, an established marker for mature macrophages. Of note, HFD elevated pfn protein levels in both stromal vascular cells and adipocytes of WAT. We also found that PfnHet were significantly protected from HFD-induced glucose intolerance observed in pfn wild-type mice. With HFD, PfnHet displayed blunted expression of systemic and WAT proinflammatory cytokines and decreased accumulation of adipose tissue macrophages, which were also preferentially biased toward an M2-like phenotype; this correlated with preserved frequency of regulatory T cells. Taken together, the findings indicate that pfn haploinsufficiency protects against diet-induced IR and inflammation by modulating WAT immune homeostasis. PMID:23884883

Romeo, Giulio R; Pae, Munkyong; Eberlé, Delphine; Lee, Jongsoon; Shoelson, Steven E



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

PubMed Central

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

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



Glucose intolerance induced by glucocorticoid excess is further impaired by co-administration with ?-hydroxy-?-methylbutyrate in rats.  


Glucocorticoid (GC) excess alters glucose homeostasis and promotes modifications in murinometric and anthropometric parameters in rodents and humans, respectively. ?-hydroxy-?-methylbutyrate (HMB), a leucine metabolite, has been proposed as a nutritional strategy for preventing muscle wasting, but few data regarding its effects on glucose homeostasis are available. Here, we analyzed whether the effects of GC excess on glucose homeostasis may be attenuated or exacerbated by the concomitant ingestion of HMB. Adult Wistar rats (90-days-old) were assigned to four groups: (1) vehicle treated (Ctl), (2) dexamethasone (DEX) treated (Dex), (3) HMB treated (Hmb), and (4) DEX plus HMB treated (DexHmb). Dex groups received DEX (1 mg·kg body weight (BW)(-1), intraperitoneal) for 5 consecutive days. HMB groups ingested HMB (320 mg·kg BW(-1), oral gavage) for the same 5 days. HMB ingestion did not attenuate the effects of DEX on food intake and body weight loss, changes in masses of several organs, insulin resistance, and glucose intolerance (p > 0.05). In fact, in DexHmb rats, there was increased fasting glycemia and exacerbated glucose intolerance with the main effect attributed to DEX treatment (p < 0.05). HMB exerted no attenuating effect on plasma triacylglycerol levels from DexHmb rats, but it seems to attenuate the lipolysis induced by ?-adrenergic stimulation (20 ?mol·L(-1) isoproterenol) in fragments of retroperitoneal adipose tissue from DexHmb rats. Therefore, HMB does not attenuate the diabetogenic characteristics of GC excess. In fact, the data suggest that HMB may exacerbate GC-induced glucose intolerance. PMID:24053521

Nunes, Everson A; Gonçalves-Neto, Luiz M; Ferreira, Francielle B D; Dos Santos, Cristiane; Fernandes, Luiz C; Boschero, Antonio C; Calder, Philip C; Rafacho, Alex



Enhanced Lipid Oxidation and Maintenance of Muscle Insulin Sensitivity Despite Glucose Intolerance in a Diet-Induced Obesity Mouse Model  

PubMed Central

Background Diet-induced obesity is a rising health concern which can lead to the development of glucose intolerance and muscle insulin resistance and, ultimately, type II diabetes mellitus. This research investigates the associations between glucose intolerance or muscle insulin resistance and tissue specific changes during the progression of diet-induced obesity. Methodology C57BL/6J mice were fed a normal or high-fat diet (HFD; 60% kcal fat) for 3 or 8 weeks. Disease progression was monitored by measurements of body/tissue mass changes, glucose and insulin tolerance tests, and ex vivo glucose uptake in intact muscles. Lipid metabolism was analyzed using metabolic chambers and ex vivo palmitate assays in intact muscles. Skeletal muscle, liver and adipose tissues were analyzed for changes in inflammatory gene expression. Plasma was analyzed for insulin levels and inflammatory proteins. Histological techniques were used on muscle and liver cryosections to assess metabolic and morphological changes. Principal Findings/Conclusions A rapid shift in whole body metabolism towards lipids was observed with HFD. Following 3 weeks of HFD, elevated total lipid oxidation and an oxidative fiber type shift had occurred in the skeletal muscle, which we propose was responsible for delaying intramyocellular lipid accumulation and maintaining muscle’s insulin sensitivity. Glucose intolerance was present after three weeks of HFD and was associated with an enlarged adipose tissue depot, adipose tissue inflammation and excess hepatic lipids, but not hepatic inflammation. Furthermore, HFD did not significantly increase systemic or muscle inflammation after 3 or 8 weeks of HFD suggesting that early diet-induced obesity does not cause inflammation throughout the whole body. Overall these findings indicate skeletal muscle did not contribute to the development of HFD-induced impairments in whole-body glucose tolerance following 3 weeks of HFD.

Trajcevski, Karin E.; O'Neill, Hayley M.; Wang, David C.; Thomas, Melissa M.; Al-Sajee, Dhuha; Steinberg, Gregory R.; Ceddia, Rolando B.; Hawke, Thomas J.



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

PubMed Central

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

Bertrand, Christelle; Blanchet, Emilie; Pessemesse, Laurence; Annicotte, Jean Sebastien; Feillet-Coudray, Christine; Chabi, Beatrice; Levin, Jonathan; Fajas, Lluis; Cabello, Gerard; Wrutniak-Cabello, Chantal; Casas, Francois



Relationship between renal and cardiovascular changes in a murine model of glucose intolerance.  


Nutrition is an important variable which may affect the risk for renal disease. We previously showed that a high fructose diet in mice produced hypertension and sympathetic activation [8]. The purpose of this study was to determine if a fructose diet altered renal function. A high fructose diet for 12 weeks impaired glucose tolerance, but caused no change in body weight, blood glucose or plasma insulin. Impairment in renal function was documented by the almost two fold increase in urinary protein excretion (Control: 6.6+/-0.6 vs. Fructose: 15.0+/-0.7 mmol protein/mmol creatinine; p<0.05) which was also accompanied by increases in urinary volume. The diet produced little change in renal histology, kidney weight or kidney weight/body weight ratio. Urinary excretion of angiotensin II/creatinine (Control: 78.9+/-16.6 vs. Fructose: 80.5+/-14.2 pg/mmol) and renal angiotensin converting enzyme activity (Control: 9.2+/-1.6 vs. Fructose: 7.6+/-1.0 ACE units) were not different between groups. There was a positive correlation between mean arterial pressure (r=0.7, p=0.01), blood pressure variability (BPV) (r=0.7, p=0.02), low frequency BPV component (r=0.677, p=0.03) and urinary protein excretion. Results show that consumption of a high fructose diet in mice had deleterious effects on renal function, which were correlated with cardiovascular changes. PMID:17207869

Cunha, Tatiana S; Farah, Vera; Paulini, Janaina; Pazzine, Mariana; Elased, Khalid M; Marcondes, Fernanda K; Cláudia Irigoyen, Maria; De Angelis, Kátia; Mirkin, L David; Morris, Mariana



NF-?B-inducing kinase (NIK) promotes hyperglycemia and glucose intolerance in obesity by augmenting glucagon action  

PubMed Central

The canonical IKK?/NF-?B1 pathway has been well documented to promote insulin resistance; however, the noncanonical NIK/NF-?B2 pathway is poorly understood in obesity. Additionally, the contribution of counterregulatory hormones, particularly glucagon, to hyperglycemia in obesity remains 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 NIK decreased glucagon responses and hepatic glucose production (HGP). Obesity is associated with increased glucagon responses, and liver-specific inhibition of NIK decreased glucagon responses and HGP and protected against hyperglycemia and glucose intolerance. Conversely, hepatocyte-specific overexpression of NIK increased glucagon responses and HGP. In isolated livers and primary hepatocytes, NIK also promoted glucagon action and glucose production, at least in part by increasing 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.

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



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

PubMed Central

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.

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



Should we do an oral glucose tolerance test in hypertensive men with normal fasting blood-glucose?  

Microsoft Academic Search

The objective of this study was to examine, using the new WHO criteria for diabetes mellitus, whether insulin and glucose before and after an oral glucose tolerance test would predict cardiovascular mortality in hypertensive men with normal fasting blood glucose. A standard oral glucose challenge was performed after an overnight fast in 113 hypertensive men with either hypercholesterolaemia or smoking.

S Agewall



Deletion of G?Z Protein Protects against Diet-induced Glucose Intolerance via Expansion of ?-Cell Mass*  

PubMed Central

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

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



Hepatocyte-specific deletion of Janus kinase 2 (JAK2) protects against diet-induced steatohepatitis and glucose intolerance.  


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

Shi, Sally Yu; Martin, Rubén García; 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



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

PubMed Central

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.

Shi, Sally Yu; Martin, Ruben Garcia; 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



Improvements in blood pressure, glucose metabolism, and lipoprotein lipids after aerobic exercise plus weight loss in obese, hypertensive middle-aged men  

Microsoft Academic Search

The clustering of metabolic abnormalities often associated with hypertension, including insulin resistance, glucose intolerance, and dyslipidemia, in middle-aged men may be the result of a decrease in cardiovascular fitness (Vo2max) and the accumulation of body fat with aging. This study examines the effects of a 6-month program of aerobic exercise training plus weight loss (AEX + WL) on Vo2max, body

Donald R. Dengel; James M. Hagberg; Richard E. Pratley; Ellen M. Rogus; Andrew P. Goldberg



Prevalence of macro- and microvascular diseases in non-insulin-dependent diabetic and borderline glucose-intolerant subjects with insulin resistance syndrome  

Microsoft Academic Search

This study was undertaken to ascertain whether patients with insulin resistance syndrome, a cluster of risk factors for coronary artery disease (CAD), are really a high risk population for macro- and microvascular diseases in Japanese NIDDM and borderline glucose-intolerant subjects. A diagnosis of insulin resistance syndrome was made if four of the six following criteria are satisfied: glucose disposal rate

Kozo Katsumori; Taro Wasada; Hiroyuki Kuroki; Hiroko Arii; Akiko Saeki; Kaori Aoki; Setsu Saito; Yasue Omori



The importance of glucose for the freezing tolerance/intolerance of the anuran amphibians Rana catesbeiana and Bufo paracnemis.  


Several species of terrestrially hibernating frogs, turtles and insects have developed mechanisms, such as increased plasma glucose, anti-freeze proteins and antioxidant enzymes that resist to freezing, for survival at subzero temperatures. In the present study, we assessed the importance of glucose to cryoresistance of two anuran amphibians: the frog Rana catesbeiana and the toad Bufo paracnemis. Both animals were exposed to -2 degrees C for measurements of plasma glucose levels, liver and muscle glycogen content, haematocrit and red blood cell volume. Frogs survived cold exposure but toads did not. Blood glucose concentration increased from 40.35 +/- 7.25 to 131.87 +/- 20.72 mg/dl (P < 0.01) when the frogs were transferred from 20 to -2 degrees C. Glucose accumulation in response to cold exposition in the frogs was accompanied by a decrease (P < 0.05) in liver glycogen content from 3.94 +/- 0.42 to 1.33 +/- 0.36 mg/100 mg tissue, indicating that liver carbohydrate reserves were probably the primary carbon source of glucose synthesis whereas muscle carbohydrate seems unimportant. In the toads, the cold-induced hyperglycaemia was less (P < 0.05) pronounced (from 27.25 +/- 1.14 to 73.72 +/- 13.50 mg/dl) and no significant change could be measured in liver or muscle glycogen. Cold exposition had no effect on the haematocrit of the frogs but significantly reduced (P < 0.01) the haematocrit of toads from 20.0 +/- 2.1% to 5.8 +/- 1.7% due to a decreased red blood cell volume (from 1532 +/- 63 to 728 +/- 87 mm3). When toads were injected with glucose, blood glucose increased to levels similar to those of frogs and haematocrit did not change, but this failed to make them cryoresistent. In conclusion, the lack of cold-induced glucose catabolism may not be the only mechanism responsible for the freeze intolerance of Bufo paracnemis, a freeze-intolerant species. PMID:10959117

Steiner, A A; Petenusci, S O; Brentegani, L G; Branco, L G



Roles of insulin resistance and beta-cell dysfunction in the pathogenesis of glucose intolerance in cystic fibrosis.  


The roles of insulin deficiency and insulin resistance in the pathogenesis of glucose intolerance in cystic fibrosis (CF) were evaluated in eight patients (aged 16.5 +/- 1.9 yr), four with normal glucose tolerance (NGT) and four with impaired glucose tolerance (IGT), and in seven healthy control (CN) subjects. First and second phase insulin secretions were evaluated during a hyperglycemic clamp. Hepatic glucose production (HGP) and insulin-stimulated glucose disposal were measured using [6,6-2H2]glucose and a stepwise hyperinsulinemic-euglycemic clamp. First and second phase insulin levels were significantly lower in both groups of CF patients compared with control values. There was an inverse relationship between glycohemoglobin level and first phase insulin (r = -0.81; P = 0.015) and second phase insulin (r = -0.97; P < 0.001). During the hyperglycemic clamp, the insulin sensitivity index was lower in CF-IGT, but not CF-NGT, compared with control values (6.66 +/- 1.79, 12.82 +/- 1.61, and 13.02 +/- 1.78 mumol/kg.min/pmol.L, respectively; P < 0.05). Basal HGP and fasting plasma glucose were higher in CF vs. CN [24.8 +/- 2.9 vs. 16.9 +/- 1.4 mumol/kg.min (P = 0.036) and 5.8 +/- 0.2 vs. 5.4 +/- 0.1 mmol/L (P = 0.035), respectively]. During the hyperinsulinemic euglycemic clamp, insulin-stimulated glucose disposal was significantly lower in CF-IGT (45.68 +/- 4.87 mumol/kg.min) vs. CF-NGT (78.99 +/- 1.34 mumol/kg.min) and CN (71.74 +/- 6.88 mumol/kg.min). Insulin sensitivity was lower in CF-IGT vs. CF-NGT (7.04 +/- 0.86 and 14.38 +/- 0.84 mumol/kg.min/pmol.L; P < 0.05). We conclude that 1) glycohemoglobin is a strong correlate of insulin deficiency in CF; and 2) glucose intolerance in this group of CF patients occurred as a consequence of concomitant insulin deficiency and insulin resistance. PMID:8027259

Austin, A; Kalhan, S C; Orenstein, D; Nixon, P; Arslanian, S



Fructose Malabsorption and Intolerance: Effects of Fructose With and Without Simultaneous Glucose Ingestion  

Microsoft Academic Search

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

Marie E. Latulippe; Suzanne Skoog



Gestational diabetes: antepartum characteristics that predict postpartum glucose intolerance and type 2 diabetes in Latino women  

Microsoft Academic Search

We examined antepartum clinical characteristics along with measures of glucose tolerance, insulin sensitivity, pancreatic -cell function, and body composition in Latino women with gestational diabetes mellitus (GDM) for their ability to predict type 2 diabetes or impaired glucose tolerance (IGT) within 6 months after delivery. A total of 122 islet cell antibody-negative women under- went oral and intravenous glucose tolerance

Thomas A. Buchanan; Anny Xiang; Siri L. Kjos; W. P. Lee; Enrique Trigo; Isabel Nader; E. Anne Bergner; Jerry P. Palmer; Ruth K. Peters



Chronic Rapamycin Treatment Causes Glucose Intolerance and Hyperlipidemia by Upregulating Hepatic Gluconeogenesis and Impairing Lipid Deposition in Adipose Tissue  

PubMed Central

OBJECTIVE The mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) pathway is a critical signaling component in the development of obesity-linked insulin resistance and operates a nutrient-sensing negative feedback loop toward the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway. Whereas acute treatment of insulin target cells with the mTOR complex 1 (mTORC1) inhibitor rapamycin prevents nutrient-induced insulin resistance, the chronic effect of rapamycin on insulin sensitivity and glucose metabolism in vivo remains elusive. RESEARCH DESIGN AND METHODS To assess the metabolic effects of chronic inhibition of the mTORC1/S6K1 pathway, rats were treated with rapamycin (2 mg/kg/day) or vehicle for 15 days before metabolic phenotyping. RESULTS Chronic rapamycin treatment reduced adiposity and fat cell number, which was associated with a coordinated downregulation of genes involved in both lipid uptake and output. Rapamycin treatment also promoted insulin resistance, severe glucose intolerance, and increased gluconeogenesis. The latter was associated with elevated expression of hepatic gluconeogenic master genes, PEPCK and G6Pase, and increased expression of the transcriptional coactivator peroxisome proliferator–activated receptor-? coactivator-1? (PGC-1?) as well as enhanced nuclear recruitment of FoxO1, CRTC2, and CREB. These changes were observed despite normal activation of the insulin receptor substrate/PI 3-kinase/Akt axis in liver of rapamycin-treated rats, as expected from the blockade of the mTORC1/S6K1 negative feedback loop. CONCLUSIONS These findings unravel a novel mechanism by which mTORC1/S6K1 controls gluconeogenesis through modulation of several key transcriptional factors. The robust induction of the gluconeogenic program in liver of rapamycin-treated rats underlies the development of severe glucose intolerance even in the face of preserved hepatic insulin signaling to Akt and despite a modest reduction in adiposity.

Houde, Vanessa P.; Brule, Sophie; Festuccia, William T.; Blanchard, Pierre-Gilles; Bellmann, Kerstin; Deshaies, Yves; Marette, Andre



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


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

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



The Usefulness of Homeostatic Measurement Assessment-Insulin Resistance (HOMA-IR) for Detection of Glucose Intolerance in Thai Women of Reproductive Age with Polycystic Ovary Syndrome  

PubMed Central

Objectives. To study the cut-off point of Homeostatic Measurement Assessment-Insulin Resistance (HOMA-IR) as a screening test for detection of glucose intolerance in Thai women with polycystic ovary syndrome (PCOS). Study Design. Cross-sectional study. Setting. Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital. Subject. Two hundred and fifty Thai PCOS women who attended the Gynecologic Endocrinology Unit, during May 2007 to January 2009. Materials and Methods. The paitents were interviewed and examined for weight, height, waist circumference, and blood pressure. Venous blood samples were drawn twice, one at 12-hour fasting and the other at 2 hours after glucose loading. Results. The prevalence of glucose intolerance in Thai PCOS women was 20.0%. The mean of HOMA-IR was 3.53? ± ?7.7. Area under an ROC curve for HOMA-IR for detecting glucose intolerance was 0.82. Using the cut-off value of HOMA-IR >2.0, there was sensitivity at 84.0%, specificity at 61.0%, positive predictive value at 35.0%, negative predictive value at 93.8%, and accuracy at 65.6%. Conclusion. HOMA-IR >2.0 was used for screening test for glucose intolerance in Thai PCOS women. If the result was positive, a specific test should be done to prove the diagnosis.

Wongwananuruk, Thanyarat; Rattanachaiyanont, Manee; Leerasiri, Pichai; Indhavivadhana, Suchada; Techatraisak, Kitirat; Angsuwathana, Surasak; Tanmahasamut, Prasong; Dangrat, Chongdee



Delayed ?-cell response and glucose intolerance in young women with Turner syndrome  

Microsoft Academic Search

Background  To investigate glucose homeostasis in detail in Turner syndrome (TS), where impaired glucose tolerance (IGT) and type 2 diabetes\\u000a are frequent.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Cross sectional study of women with Turner syndrome (TS)(n = 13) and age and body mass index matched controls (C) (n = 13),\\u000a evaluated by glucose tolerance (oral and intravenous glucose tolerance test (OGTT and IVGTT)), insulin sensitivity (hyperinsulinemic,

Britta E Hjerrild; Jens J Holst; Claus B Juhl; Jens S Christiansen; Ole Schmitz; Claus H Gravholt



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


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. PMID:16537411

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



Neuronal overexpression of insulin receptor substrate 2 leads to increased fat mass, insulin resistance, and glucose intolerance during aging.  


The insulin receptor substrates (IRS) are adapter proteins mediating insulin's and IGF1's intracellular effects. Recent data suggest that IRS2 in the central nervous system (CNS) is involved in regulating fuel metabolism as well as memory formation. The present study aims to specifically define the role of chronically increased IRS2-mediated signal transduction in the CNS. We generated transgenic mice overexpressing IRS2 specifically in neurons (nIRS2 (tg)) and analyzed these in respect to energy metabolism, learning, and memory. Western blot (WB) analysis of nIRS2 (tg) brain lysates revealed increased IRS2 downstream signaling. Histopathological investigation of nIRS2 (tg) mice proved unaltered brain development and structure. Interestingly, nIRS2 (tg) mice showed decreased voluntary locomotoric activity during dark phase accompanied with decreased energy expenditure (EE) leading to increased fat mass. Accordingly, nIRS2 (tg) mice develop insulin resistance and glucose intolerance during aging. Exploratory behavior, motor function as well as food and water intake were unchanged in nIRS2 (tg) mice. Surprisingly, increased IRS2-mediated signals did not change spatial working memory in the T-maze task. Since FoxO1 is a key mediator of IRS2-transmitted signals, we additionally generated mice expressing a dominant negative mutant of FoxO1 (FoxO1DN) specifically in neurons. This mutant mimics the effect of increased IRS2 signaling on FoxO-mediated transcription. Interestingly, the phenotype observed in nIRS2 (tg) mice was not present in FoxO1DN mice. Therefore, increased neuronal IRS2 signaling causes decreased locomotoric activity in the presence of unaltered exploratory behavior and motor coordination that might lead to increased fat mass, insulin resistance, and glucose intolerance during aging independent of FoxO1-mediated transcription. PMID:23160735

Zemva, J; Udelhoven, M; Moll, L; Freude, S; Stöhr, O; Brönneke, H S; Drake, R B; Krone, W; Schubert, M



Breast-feeding is associated with reduced postpartum maternal glucose intolerance after gestational diabetes.  


Gestational diabetes mellitus (GDM) is associated with adverse foetal and maternal outcomes, and identifies women at risk of future Type 2 Diabetes Mellitus (T2DM). Breast-feeding may improve postpartum maternal glucose tolerance. We prospectively examined the prevalence of postpartum dysglycaemia after GDM and examined the effect of lactation on postpartum glucose tolerance. We compared postpartum 75g oral glucose tolerance test (OGTT) results from 300 women with GDM and 220 controls with normal gestational glucose tolerance (NGT). Breast-feeding data was collected at time of OGTT. Postpartum OGTT results were classified as normal [fasting plasma glucose (FPG) < 5.6mmol/l, 2-h < 7.8 mmol/l] and abnormal [impaired fasting glucose (IFG), FPG 5.6-6.9 mmol/l; impaired glucose tolerance (IGT), 2-h glucose 7.8-11 mmol/l; IFG+IGT; T2DM, FPG > or = 7 mmol/l +/- 2h glucose > or = 11.1 mmol/l]. 6 (2.7%) with NGT in pregnancy had postpartum dysglycaemia compared to 57 (19%) with GDM in index pregnancy (p < 0.001). Non-European ethnicity (OR 3.40, 95% CI 1.45-8.02, p = 0.005), family history of T2DM (OR 2.14, 95% CI 1.06-4.32, p = 0.034) and gestational insulin use (OR 2.62, 95% CI 1.17-5.87 p = 0.019) were associated with persistent dysglycaemia. The prevalence of persistent hyperglycaemia was significantly lower in women who breast-fed versus bottle-fed postpartum (8.2% v 18.4%, p < 0.001). Breast-feeding may confer beneficial metabolic effects after GDM and should be encouraged. PMID:22838108

O'Reilly, M; Avalos, G; Dennedy, M C; O'Sullivan, E P; Dunne, F P



Nitrendipine improves glucose tolerance and deoxyglucose uptake in hypertensive rats.  


We assessed the effect of the vasodilating calcium channel blocker nitrendipine on glucose tolerance in young spontaneously hypertensive rats (SHR) (n = 15). The nitrendipine group received 1 g/kg chow for 3 weeks. Untreated SHR (n = 14) served as controls. At 3 weeks body weight was comparable, whereas systolic blood pressure was 157 +/- 9 mm Hg in nitrendipine-treated rats versus 191 +/- 10 mm Hg in controls (mean +/- SD, P < .00001). Fasting glucose was 6.8 +/- 2.7 mmol/L in nitrendipine-treated versus 8.9 +/- 1.5 mmol/L in control rats (P < .03). An intravenous glucose tolerance test (300 mg/kg) showed plasma glucose levels at 2, 5, 15, and 30 minutes to be significantly lower in the nitrendipine-treated group versus controls (two-way ANOVA, P < .03). Glucose utilization was estimated by the uptake of [3H]deoxyglucose after its intravenous administration (2 microCi/100 g body wt) to instrumented awake animals. Heart and striated muscle uptake was, respectively, 7983 +/- 5812 and 951 +/- 731 cpm.microL/g.min in the nitrendipine-treated group versus 3532 +/- 2316 and 424 +/- 201 cpm.microL/g.min in controls (P < .02 and P < .04, respectively). [3H]Deoxyglucose plasma half-life and fasting and post-glucose load insulin levels were comparable in the two groups. The results show that nitrendipine improves glucose tolerance by increasing muscle glucose uptake. We suggest that glucose tolerance in SHR is influenced by muscle blood flow and can be improved by vasodilation. PMID:8206592

Bursztyn, M; Raz, I; Mekler, J; Ben-Ishay, D



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

Microsoft Academic Search

OBJECTIVES: South-Asians have lower adiponectin levels compared to Caucasians. It was not clear however, if this intrinsic feature is related to aspects of glucose metabolism. This study aims to determine the relationship between body fat distribution and adipocytokine in South-Asian subjects by measuring serum adipocytokines, adiposity, insulinemia, and glucose tolerance levels. METHODS: In this cross-sectional study, 150 South-Asians (80 males,

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



Hypertension, Insulin, and Proinsulin in Participants With Impaired Glucose Tolerance  

PubMed Central

The association of insulin resistance and hyperinsulinemia to blood pressure has remained controversial. We examined the association of insulinemia to hypertension and blood pressure using baseline measurements for participants of the Diabetes Prevention Program (DPP). The DPP is a multicenter randomized controlled trial of 3819 participants with impaired glucose tolerance, and is designed to evaluate interventions for the delay or prevention of type 2 diabetes. The relationship between hypertension and insulinemia is described overall and by ethnicity. The effects of demographics (age and gender), adiposity, and glucose on the relationship are also presented. Asian Americans and African Americans had a similarly high prevalence of hypertension as did whites; American Indians had a lower prevalence of hypertension. Among participants not on antihypertensive medications, systolic blood pressure was significantly (but weakly) correlated with fasting insulin (r=0.12), homeostasis model assessment of insulin resistance (HOMA IR; r=0.13), and fasting proinsulin (r=0.10) when adjusted for age and gender (all, P<0.001). Systolic blood pressure showed similar correlations to fasting insulin in each ethnic group. After further adjustment for body mass index, the association of fasting insulin to systolic and diastolic blood pressures weakened considerably but remained significant (systolic: r=0.06, P=0.002; DBP: r=0.06, P<0.001). We conclude that a weak but significant association between insulin, (and proinsulin and HOMA IR) and blood pressure exists but is largely explained by overall adiposity. This association is similar among ethnicities, with the possible exception of Hispanics. The relation between insulin concentrations and blood pressure explains relatively little of the ethnic differences in hypertensive prevalence.



Glucose Intolerance and the Amount of Visceral Adipose Tissue Contribute to an Increase in Circulating Triglyceride Concentrations in Caucasian Obese Females  

PubMed Central

Context Lipotoxicity is a risk factor for developing obesity-related metabolic complications, including non-alcoholic fatty liver disease, type 2 diabetes (DM2), cardiovascular disease and stroke. Yet, the mechanisms underlying the development of lipotoxicity itself remain poorly understood. Here, we investigated whether glucose intolerance aggravates lipotoxicity by evaluating the association between triglyceride (TG) concentrations and glucose tolerance status in a cross-sectional study on obese Caucasian women at risk for DM2. Methods 913 obese females unknown to have diabetes were recruited (mean age: 41.2±SD 12.3; median BMI: 36.2, IQR 32.9–40.2). Visceral (VAT) and subcutaneous abdominal adipose tissue volumes were quantified with computed tomography. Glucose, insulin, and triglyceride concentrations were determined in fasting state and following a 75 gram oral glucose tolerance test. Results Based on fasting and 2 h post-load glucose levels, 27% of the women had impaired glucose tolerance (IGT), and 8% had newly diagnosed DM2. Fasting TG concentrations were similar between the IGT- and DM2-groups, and increased as compared to women with normal glucose tolerance (NGT). Even when adjusting for age, hip circumference and VAT, fasting TG concentrations remained elevated as compared to NGT. Mixed modelling analysis of post-load responses showed that TG concentrations declined more slowly in the DM2-group as compared to IGT and NGT. However, when adjusting for VAT the difference in decline between the glucose tolerance groups disappeared. Conclusions Glucose intolerance associates with elevated fasting TG concentrations in obese Caucasian women. We propose that glucose intolerance and increased VAT reduce lipid disposal mechanisms and may accelerate lipotoxicity.

Verrijken, An; Deschepper, Ellen; Mertens, Ilse; Kaufman, Jean-Marc; Van Gaal, Luc F.; Ouwens, D. Margriet; Ruige, Johannes B.



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


Insulin resistance is a key condition in the development of type 2 diabetes. It is well established that exacerbated Jun NH2-terminal kinase (JNK) activity is involved in promoting insulin resistance in peripheral insulin-target tissues; however, this involvement is less documented in pancreatic ?-cells. Using a transgenic mouse model, here we show that JNK activation in ?-cells led to glucose intolerance as a result of impaired capacity to increase insulinemia in response to hyperglycemia. Pancreatic islets from these mice showed no obvious morphostructural abnormalities or decreased insulin content. In contrast, these islets failed to secrete insulin in response to glucose or insulin but were competent in succinate-, ketoisocaproate-, 3-isobutyl-1-methylxanthine (IBMX-), KCl-, and tolbutamide-induced insulin secretion. At the molecular level, JNK activation in ?-cells inhibited insulin-induced Akt phosphorylation, pancreatic and duodenal homeobox 1 nucleocytoplasmic shuttling, and transcription of insulin-target genes. Remarkably, rosiglitazone restored insulin secretion in response to hyperglycemia in mice and insulin-induced insulin secretion and signaling in isolated islets. In conclusion, the mere activation of JNK suffices to induce insulin resistance in pancreatic ?-cells by inhibition of insulin signaling in these cells, but it is not sufficient to elicit ?-cell death. In addition, we provide the first evidence that thiazolidinediones exert insulin-sensitizing action directly on pancreatic ?-cells. PMID:23349497

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



A study on Asian Indian and American vegetarians: indications of a racial predisposition to glucose intolerance.  


Sixty-two Asian Indian and American vegetarians participated in a 3-h glucose tolerance test after an overnight fast to study clinical indices of glucose homeostasis. The Asian Indians had a higher (p less than 0.0035) insulinogenic score than the Americans. The Asian Indians had significantly higher insulin levels than the Americans at every sampling time during the glucose tolerance test except for the 3-h sample. The Indian men had significantly higher (p less than 0.05) plasma glucose than the other three groups at 2 h after the glucose load. American subjects had higher (p less than 0.0008) insulin binding to erythrocytes than the Asian Indian subjects. Scatchard analysis and competition-inhibition plots of the insulin-receptor data indicated that decreased binding in the Indian group results from a lowered number and decreased affinity of erythrocyte receptors. These results suggest that Asian Indians exhibit several clinical indications associated with an increased risk for the development of insulin-independent diabetes. PMID:3318380

Scholfield, D J; Behall, K M; Bhathena, S J; Kelsay, J; Reiser, S; Revett, K R



Early and rapid development of insulin resistance, islet dysfunction and glucose intolerance after high-fat feeding in mice overexpressing phosphodiesterase 3B.  


Inadequate islet adaptation to insulin resistance leads to glucose intolerance and type 2 diabetes. Here we investigate whether beta-cell cAMP is crucial for islet adaptation and prevention of glucose intolerance in mice. Mice with a beta-cell-specific, 2-fold overexpression of the cAMP-degrading enzyme phosphodiesterase 3B (RIP-PDE3B/2 mice) were metabolically challenged with a high-fat diet. We found that RIP-PDE3B/2 mice early and rapidly develop glucose intolerance and insulin resistance, as compared with wild-type littermates, after 2 months of high-fat feeding. This was evident from advanced fasting hyperinsulinemia and early development of hyper-glycemia, in spite of hyperinsulinemia, as well as impaired capacity of insulin to suppress plasma glucose in an insulin tolerance test. In vitro analyses of insulin-stimulated lipogenesis in adipocytes and glucose uptake in skeletal muscle did not reveal reduced insulin sensitivity in these tissues. Significant steatosis was noted in livers from high-fat-fed wild-type and RIP-PDE3B/2 mice and liver triacyl-glycerol content was 3-fold higher than in wild-type mice fed a control diet. Histochemical analysis revealed severe islet perturbations, such as centrally located alpha-cells and reduced immunostaining for insulin and GLUT2 in islets from RIP-PDE3B/2 mice. Additionally, in vitro experiments revealed that the insulin secretory response to glucagon-like peptide-1 stimulation was markedly reduced in islets from high-fat-fed RIP-PDE3B/2 mice. We conclude that accurate regulation of beta-cell cAMP is necessary for adequate islet adaptation to a perturbed metabolic environment and protective for the development of glucose intolerance and insulin resistance. PMID:16731793

Walz, Helena A; Härndahl, Linda; Wierup, Nils; Zmuda-Trzebiatowska, Emilia; Svennelid, Fredrik; Manganiello, Vincent C; Ploug, Thorkil; Sundler, Frank; Degerman, Eva; Ahrén, Bo; Holst, Lena Stenson



Oxidized low-density lipoprotein and intimal medial thickness in subjects with glucose intolerance: the Chennai Urban Rural Epidemiology Study-25.  


The aim of the present study was to assess the association of oxidized low-density lipoprotein (OX-LDL) with carotid intimal medial thickness (IMT) in different grades of glucose intolerance in Asian Indians. Three groups were recruited from the Chennai Urban Rural Epidemiology Study, a population-based study: group 1, normal glucose tolerance (NGT) (n = 175); group 2, impaired glucose tolerance (IGT) (n = 175); and group 3, type 2 diabetes mellitus (n = 175). Oxidized LDL (enzyme-linked immunosorbent assay) and carotid IMT (high-resolution B-mode ultrasonography) were assessed. Subjects with diabetes had higher IMT values (0.85 +/- 0.30 mm) compared with those who have IGT (0.79 +/- 0.16 mm, P < .05) and NGT (0.71 +/- 0.12 mm, P < .001). Subjects with diabetes (40.1 +/- 13.1 U/L) and IGT (34.3 +/- 12.8 U/L) had significantly higher mean OX-LDL values compared with the NGT group (26.2 +/- 16.6 U/L, P < .001). Oxidized LDL showed a correlation with IMT (total population: r = 0.294, P < .001; subjects with NGT: r = 0.444, P < .001; and subjects with IGT: r = 0.481, P < .001). In multiple linear regression analysis, OX-LDL showed a strong association with IMT (beta = .005, P < .001), even after adjusting for age, sex (beta = .003, P < .001), and glucose intolerance (beta = .002, P < .001). In conclusion, OX-LDL levels increase with increasing glucose intolerance. Oxidized LDL is associated with carotid IMT and this is independent of age, sex, and glucose intolerance status. PMID:17224340

Gokulakrishnan, Kuppan; Deepa, Raj; Velmurugan, Kaliyaperumal; Ravikumar, Radhakrishnan; Karkuzhali, Kulasekaran; Mohan, Viswanathan



Overproduction of Angiotensinogen from Adipose Tissue Induces Adipose Inflammation, Glucose Intolerance, and Insulin Resistance  

Microsoft Academic Search

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

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



?-Hydroxybutyrate Is an Early Biomarker of Insulin Resistance and Glucose Intolerance in a Nondiabetic Population  

PubMed Central

Background Insulin resistance is a risk factor for type 2 diabetes and cardiovascular disease progression. Current diagnostic tests, such as glycemic indicators, have limitations in the early detection of insulin resistant individuals. We searched for novel biomarkers identifying these at-risk subjects. Methods Using mass spectrometry, non-targeted biochemical profiling was conducted in a cohort of 399 nondiabetic subjects representing a broad spectrum of insulin sensitivity and glucose tolerance (based on the hyperinsulinemic euglycemic clamp and oral glucose tolerance testing, respectively). Results Random forest statistical analysis selected ?-hydroxybutyrate (?–HB) as the top-ranked biochemical for separating insulin resistant (lower third of the clamp-derived MFFM?=?33 [12] µmol·min?1·kgFFM?1, median [interquartile range], n?=?140) from insulin sensitive subjects (MFFM?=?66 [23] µmol·min?1·kgFFM?1) with a 76% accuracy. By targeted isotope dilution assay, plasma ?–HB concentrations were reciprocally related to MFFM; and by partition analysis, an ?–HB value of 5 µg/ml was found to best separate insulin resistant from insulin sensitive subjects. ?–HB also separated subjects with normal glucose tolerance from those with impaired fasting glycemia or impaired glucose tolerance independently of, and in an additive fashion to, insulin resistance. These associations were also independent of sex, age and BMI. Other metabolites from this global analysis that significantly correlated to insulin sensitivity included certain organic acid, amino acid, lysophospholipid, acylcarnitine and fatty acid species. Several metabolites are intermediates related to ?-HB metabolism and biosynthesis. Conclusions ?–hydroxybutyrate is an early marker for both insulin resistance and impaired glucose regulation. The underlying biochemical mechanisms may involve increased lipid oxidation and oxidative stress.

Gall, Walter E.; Beebe, Kirk; Lawton, Kay A.; Adam, Klaus-Peter; Mitchell, Matthew W.; Nakhle, Pamela J.; Ryals, John A.; Milburn, Michael V.; Nannipieri, Monica; Camastra, Stefania; Natali, Andrea; Ferrannini, Ele



Lactose intolerance  


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


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


High-fat diet (HFD)-induced glucose intolerance and insulin resistance increases the chances of developing type-2 diabetes and cardiovascular disease. To study the mechanism(s) by which a HFD impairs glucose tolerance, we used a quantitative proteomic platform that integrated pI-based OFFGEL fractionation and iTRAQ labeling to profile the temporal changes in adipose membrane protein expression in mice fed a HFD for up to 8 months. Within 2 months of starting the diet, the mice adipose and liver tissues accumulated fat droplets, which contributed to subsequent insulin resistance and glucose intolerance within 6 months. The membrane proteomic delineation of such phenotypic expression resulted in quantification of 1713 proteins with 266, 343, and 125 differentially expressed proteins in 2-, 6-, and 8-month HFD-fed versus control mice, respectively. Pathway analysis of these differentially expressed proteins revealed the interplay between upregulation of fatty acid metabolism and downregulation of glucose metabolism. Substantial upregulation of adipose and liver carnitine palmitoyltransferase (Cpt) 1, the rate-limiting enzyme in the transport of long-chain fatty acids into mitochondria, occurred by 2 months. The increase in hepatic Cpt 1a expression was associated with a progressive decrease in glucose uptake as evidenced by downregulation of the liver glucose transporter protein (Glut) 2. Loss of glycogen storage was found in those hepatocytes full of fat droplets. Intriguingly, skeletal muscle Cpt 1b expression was unaltered by the HFD, whereas skeletal muscle Glut 4 and tyrosine phosphoryated insulin receptor substrate 1 (p-IRS1) were substantially upregulated at the same time as abnormal glucose metabolism developed in adipose and liver tissues. This study defines some of the molecular mechanisms as well as the relationship among adipose tissue, liver and skeletal muscle during development of HFD-induced glucose intolerance in vivo and identifies Cpt 1 as a potential drug target for the control or prevention of diabetes. PMID:23316967

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



Triglyceride and Glucose Intolerance as a Risk Factor for Coronary Heart Disease  

Microsoft Academic Search

The electrophoresis of plasma lipoproteins frequently showed midbands between ?- and pre-?-lipoproteins in survivors of myocardial infarction. There were increases in intermediate-density-lipoprotein (IDL) cholesterol and triglycerides with an increase in IDL cholesterol\\/triglycerides in the very-low-density-lipoprotein fraction, even if the increase in cholesterol was not so significant. Impaired glucose tolerance (IGT) was also frequently found in these patients. Among the patients

Akira Yamamoto; Taku Yamamura; Akito Kawaguchi; Kaoru Kameda; Yuji Matsuzawa



Angiotension converting enzyme inhibition and calcium channel blockage improves cyclosporine induced glucose intolerance in rats  

Microsoft Academic Search

The aim of this study was to evaluate the effects of quinapril, valsartan, and amlodipin on glucose tolerance in cyclosporine (CsA)-toxic rats. Among 40 male Wistar rats 32 were administered cyclosporine (CsA) (15 mg\\/kg) intraperitoneally for 6 weeks. Quinapril (10 mg\\/kg per day) (group Q), valsartan (40 mg\\/kg per day) (group V), and amlodipine (10mg\\/kg per day) (group A) were

D. G Yavuz; S Tu?lular; H Koçak; A Atakan; C ?zener; E Ako?lu; S Akal?n



Beta-glycosphingolipids improve glucose intolerance and hepatic steatosis of the Cohen diabetic rat.  


A link between altered levels of various gangliosides and the development of insulin resistance was described in transgenic mice. Naturally occurring glycosphingolipids were shown to exert immunomodulatory effects in a natural killer T (NKT) cell-dependent manner. This study examined whether glycosphingolipid-induced modulation of the immune system may reduce pancreatic and liver steatosis and stimulate insulin secretion in the Cohen diabetes-sensitive (CDS) rat, a lean model of non-insulin-resistant, nutritionally induced diabetes. Four groups of CDS rats fed a diabetogenic diet were treated with daily intraperitoneal injections of glycosphingolipids beta-glucosylceramide, beta-lactosylceramide, a combination of both (IGL), or vehicle (PBS) for up to 45 days. Immune modulation was assessed by fluorescence-activated cell sorting analysis of intrahepatic and intrasplenic lymphocytes. Steatosis was assessed by MRI imaging and histological examination of liver and pancreas, Blood glucose and plasma insulin concentrations were assessed during an oral glucose tolerance test. Administration of glycosphingolipids, particularly IGL, increased intrahepatic trapping of CD8 T and NKT lymphocytes. Pancreatic and liver histology were markedly improved and steatosis was reduced in all treated groups compared with vehicle-treated rats. Insulin secretion was restored after glycosphingolipid treatment, resulting in improved glucose tolerance. The immunomodulatory effect of beta-glycosphingolipids improved the beta-cell function of the hyperglycemic CDS rat. Thus our results suggest a role for the immune system in the pathogenesis of diabetes in this model. PMID:18940939

Zigmond, Ehud; Zangen, Sarah W; Pappo, Orit; Sklair-Levy, Miriam; Lalazar, Gadi; Zolotaryova, Lydia; Raz, Itamar; Ilan, Yaron



Plasma insulin and blood pressure response to oral glucose tolerance test in young borderline hypertensives.  


In order to evaluate whether borderline hypertension might be associated with hyperinsulinaemia, twenty non-obese borderline hypertensives and twenty matched normotensives underwent a standard oral glucose tolerance test and 24-h ambulatory blood pressure monitoring. Blood pressure, plasma glucose and insulin were measured at fasting and 15, 30, 60, 120 and 180 minutes after glucose load. Fasting plasma insulin was significantly higher in borderline hypertensives in comparison to normotensives (16.6 +/- 6.9 vs 12.4 +/- 4.2 mU/l; P < 0.05). Plasma insulin response estimated by the positive incremental area under the curve did not differ significantly between two groups but borderline hypertensives showed a larger interindividual difference. Decrease of systolic blood pressure after glucose load was significantly greater in borderline hypertensive subjects. Furthermore, blood pressure and plasma insulin relationship was different in borderline hypertensives compared to normotensives. PMID:8412338

Narkiewicz, K; Rynkiewicz, A; Furma?ski, J; Gan, J; Narwojsz, E; Bieniaszewski, L; Krupa-Wojciechowska, B


Maternal Cigarette Smoke Exposure Contributes to Glucose Intolerance and Decreased Brain Insulin Action in Mice Offspring Independent of Maternal Diet  

PubMed Central

Background Maternal smoking leads to intrauterine undernutrition and is associated with low birthweight and higher risk of offspring obesity. Intrauterine smoke exposure (SE) may alter neuroendocrine mediators regulating energy homeostasis as chemicals in cigarette smoke can reach the fetus. Maternal high-fat diet (HFD) consumption causes fetal overnutrition; however, combined effects of HFD and SE are unknown. Thus we investigated the impact of combined maternal HFD and SE on adiposity and energy metabolism in offspring. Method Female Balb/c mice had SE (2 cigarettes/day, 5 days/week) or were sham exposed for 5 weeks before mating. Half of each group was fed HFD (33% fat) versus chow as control. The same treatment continued throughout gestation and lactation. Female offspring were fed chow after weaning and sacrificed at 12 weeks. Results Birthweights were similar across maternal groups. Faster growth was evident in pups from SE and/or HFD dams before weaning. At 12 weeks, offspring from HFD-fed dams were significantly heavier than those from chow-fed dams (chow-sham 17.6±0.3 g; chow-SE 17.8±0.2 g; HFD-sham 18.7±0.3 g; HFD-SE 18.8±0.4 g, P<0.05 maternal diet effect); fat mass was significantly greater in offspring from chow+SE, HFD+SE and HFD+sham dams. Both maternal HFD and SE affected brain lactate transport. Glucose intolerance and impaired brain response to insulin were observed in SE offspring, and this was aggravated by maternal HFD consumption. Conclusion While maternal HFD led to increased body weight in offspring, maternal SE independently programmed adverse health outcomes in offspring. A smoke free environment and healthy diet during pregnancy is desirable to optimize offspring health.

Chen, Hui; Iglesias, Miguel A.; Caruso, Vanni; Morris, Margaret J.



Lactose intolerance among Mexican Americans.  


Thirty-three Mexican Americans between the ages of 9 and 60 were interviewed and tested for lactose intolerance. The participants of the study included 16 children and 17 persons not related by birth, including the parents of the children. Determination of lactose intolerance was based on a rise of less than 25mg/100 ml of blood glucose as measured by an Ames Dextrostix/Reflectance Meter following consumption of a lactose load. Forty-seven percent of the 17 nonrelated Mexican Americans were lactose intolerant. There was a marked relationship between low rise in blood glucose and symptoms of diarrhea, flatulence, and distention. Sixteen children from four families had an incidence of 50 per cent intolerance. The findings of intolerance in two successive generations of three families and in both sexes of the families adds support to the contention that lactose intolerance has a genetic basis, without sex predilection. PMID:1146721

Sowers, M F; Winterfeldt, E



Adenoviral leptin as gene therapy for obesity related hypertension  

Microsoft Academic Search

Leptin has been postulated as an important hormone linking obesity with sympathetic activation and hypertension. In a rat model of dietary obesity moderate hyperleptinemia by adenoviral gene transfer has been shown to reverse all the other features of the metabolic syndrome including insulin resistance and glucose intolerance. To determine if leptin improves or worsens hypertension in this model, we measured

Weiguo Zhang; Sabine Telemaque-Potts; Paul R. Anderson; Zhongyun Wang; Jie An; Chris B. Newgard; Ronald G. Victor



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


The evolutionarily conserved kinase PIKfyve that synthesizes PtdIns5P and PtdIns(3,5)P? 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 10-11 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

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



Long-term exposure to a high-fat diet results in the development of glucose intolerance and insulin resistance in interleukin-1 receptor I-deficient mice.  


Emerging evidence has demonstrated that saturated fatty acids prime pro-IL-1? production and inflammasome-mediated IL-1? activation is critical in obesity-associated insulin resistance (IR). Nonetheless, IL-1 receptor I-deficient (IL-1RI(-/-)) mice develop mature-onset obesity despite consuming a low-fat diet (LFD). With this apparent contradiction, the present study evaluated whether IL-1RI(-/-) mice were protected against long-term (6 mo) high-fat diet (HFD)-induced IR. Male wild-type and IL-1RI(-/-) mice were fed LFD or HFD for 3 or 6 mo, and glucose and insulin tolerance tests were performed. Adipose insulin sensitivity, cytokine profiles, and adipocyte morphology were assessed. The adipogenic potential of stromal vascular fraction was determined. Hepatic lipid accumulation and insulin sensitivity were characterized. IL-1RI(-/-) mice developed glucose intolerance and IR after 6 mo HFD compared with 3 mo HFD, coincident with enhanced weight gain, hyperinsulinemia, and hyperleptinemia. The aggravated IR phenotype was associated with loss of adipose functionality, switch from adipocyte hyperplasia to hypertrophy and hepatosteatosis. Induction of adipogenic genes was reduced in IL-1RI(-/-) preadipocytes after 6 mo HFD compared with 3 mo HFD. Obese LFD-IL-1RI(-/-) mice exhibited preserved metabolic health. IL-1RI(-/-) mice develop glucose intolerance and IR after 6 mo HFD intervention. While mature-onset obesity is evident in LFD-IL-1RI(-/-) mice, the additional metabolic insult of HFD was required to drive adipose inflammation and systemic IR. These findings indicate an important interaction between dietary fat and IL-1, relevant to optimal metabolic health. PMID:23921145

McGillicuddy, Fiona C; Reynolds, Clare M; Finucane, Orla; Coleman, Eilish; Harford, Karen A; Grant, Christine; Sergi, Domenico; Williams, Lynda M; Mills, Kingston H G; Roche, Helen M



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


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

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



Exercise intolerance.  


Patients with heart failure and normal EF have severe chronic exercise intolerance. The pathophysiology of exercise intolerance in this syndrome is incompletely understood, but as in systolic heart failure, it is likely multifactorial. Current data suggest that important contributors include decreased LV diastolic compliance, decreased aortic distensibility, exaggerated exercise systolic blood pressure, relative chronotropic incompetence, and possibly anemia and skeletal muscle remodeling. Because it is a primary determinant of quality of life, can be quantified objectively, is reproducible, and is modifiable, exercise intolerance is an attractive therapeutic target. PMID:16115516

Kitzman, Dalane W


Lactose Intolerance  


... as a result of intestinal diseases, such as celiac disease, gastroenteritis and an inflammatory bowel disease like Crohn's ... that can cause lactose intolerance include bacterial overgrowth, celiac disease and Crohn's disease. Certain cancer treatments. If you ...


Is adequate the current definition for impaired fasting plasma glucose in hypertensive patients?  

Microsoft Academic Search

Patients with impaired fasting plasma glucose (IFPG) (110-126 mg\\/dl) have an increased cardiovascular risk and greater risk of developing diabetes.Our objective was to evaluate the association between IFPG and early target organ damage in hypertensive patients, and to assess the impact of different IFPG thresholds.We designed a cross-sectional study including 75 non-diabetic essential hypertensive patients, aged 58 ± 12 years,

Carlos Campo; Julian Segura; Cecilia Roldan; Luis Vigil; Jose L Rodicio; Luis M Ruilope



The relationship between abnormal glucose tolerance and hypertensive disorders of pregnancy in healthy nulliparous women  

Microsoft Academic Search

Objective: The study’s aim was to determine whether healthy nulliparous women with abnormal glucose tolerance during pregnancy are at increased risk for development of pregnancy-associated hypertension or preeclampsia. Study Design: A series of 4589 healthy nulliparous women from 5 university centers were evaluated prospectively to determine whether calcium supplementation would prevent preeclampsia. Pregnancy-associated hypertension was a diastolic blood pressure ?90

Gary M. Joffe; Joy R. Esterlitz; Richard J. Levine; John D. Clemens; Marian G. Ewell; Baha M. Sibai; Patrick M. Catalano



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


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

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



A study on Asian Indian and American vegetarians: indications of a racial predisposition to glucose intolerance13  

Microsoft Academic Search

Sixty-two Asian Indian and American vegetarians participated in a 3-h glucose tolerance test after an overnight fast to study clinical indices ofglucose homeostasis. The Asian Indians had a higher (p < 0.0035) insulinogenic score than the Americans. The Asian Indians had significantly higher insulin levels than the Americans at every sampling time during the glucose tolerance test except for the

Daniel J Scholfield; Kay M Behall; Sam J Bhathena; June Kelsay; Sheldon Reiser; Kenneth R Revett


Voluntary running improves glucose tolerance and insulin resistance in female spontaneously hypertensive rats  

Microsoft Academic Search

We evaluated the effects of voluntary exercise training on glucose metabolism and measures of insulin sensitivity in female spontaneously hypertensive rats (SHR). Age-matched Wistar-Kyoto rats (WKY) were used as normotensive controls. Exercising SHR were housed in running wheels for 8 weeks (SHRx8) or 16 weeks (SHRx16). At 22 weeks of age, we measured systolic blood pressure, performed oral glucose tolerance

Tanya L. Kinney LaPier; Arthur L. M. Swislocki; Raymond J. Clark; Kenneth J. Rodnick



The glucose intolerance induced by caffeinated coffee ingestion is less pronounced than that due to alkaloid caffeine in men.  


Although acute alkaloid caffeine (CAF) ingestion results in an impaired glucose tolerance, chronic coffee (RCOF) ingestion decreases the risk of developing type 2 diabetes. This study examines the hypothesis that CAF ingestion impairs glucose tolerance to a greater extent than RCOF and that the ingestion of decaffeinated coffee (DECAF) results in a positive effect. Eleven healthy males underwent 4 double-blinded randomized trials. Each trial included the ingestion of either: 1) CAF in capsule form (4.45 mg/kg body weight), 2) RCOF (4.45 mg/kg body weight caffeine), 3) dextrose (placebo, PL) in capsule form, or 4) DECAF (equal in volume to the RCOF trial), followed 1-h later by a 2-h oral glucose tolerance test. Blood samples were collected at baseline (-30), 0 (time of treatment ingestion), 60 (initiation of oral glucose tolerance test), 75, 90, 120, 150, and 180 min. Area under the curve for glucose and insulin were higher (P < or = 0.05) following CAF than both PL and DECAF and, although a similar trend (P = 0.07) was observed following RCOF compared with DECAF, the effect was less pronounced. Interestingly, DECAF resulted in a 50% lower glucose response (P < or = 0.05) than PL, suggesting that the effects of PL and DECAF on glucose tolerance are not the same. These findings suggest that the effects of CAF and RCOF are not identical and may provide a partial explanation as to why acute CAF ingestion impairs glucose tolerance while chronic RCOF ingestion protects against type 2 diabetes. PMID:16614416

Battram, Danielle S; Arthur, Rebecca; Weekes, Andrew; Graham, Terry E



Overexpression of Kinase-Negative Protein Kinase C? in Pancreatic ?-Cells Protects Mice From Diet-Induced Glucose Intolerance and ?-Cell Dysfunction  

PubMed Central

OBJECTIVE In vitro models suggest that free fatty acid–induced apoptotic ?-cell death is mediated through protein kinase C (PKC)?. To examine the role of PKC? signaling in vivo, transgenic mice overexpressing a kinase-negative PKC? (PKC?KN) selectively in ?-cells were generated and analyzed for glucose homeostasis and ?-cell survival. RESEARCH DESIGN AND METHODS Mice were fed a standard or high-fat diet (HFD). Blood glucose and insulin levels were determined after glucose loads. Islet size, cleaved caspase-3, and PKC? expression were estimated by immunohistochemistry. In isolated islet cells apoptosis was assessed with TUNEL/TO-PRO3 DNA staining and the mitochondrial potential by rhodamine-123 staining. Changes in phosphorylation and subcellular distribution of forkhead box class O1 (FOXO1) were analyzed by Western blotting and immunohistochemistry. RESULTS PKC?KN mice were protected from HFD-induced glucose intolerance. This was accompanied by increased insulin levels in vivo, by an increased islet size, and by a reduced staining of ?-cells for cleaved caspase-3 compared with wild-type littermates. In accordance, long-term treatment with palmitate increased apoptotic cell death of isolated islet cells from wild-type but not from PKC?KN mice. PKC?KN overexpression protected islet cells from palmitate-induced mitochondrial dysfunction and inhibited nuclear accumulation of FOXO1 in mouse islet and INS-1E cells. The inhibition of nuclear accumulation of FOXO1 by PKC?KN was accompanied by an increased phosphorylation of FOXO1 at Ser256 and a significant reduction of FOXO1 protein. CONCLUSIONS Overexpression of PKC?KN in ?-cells protects from HFD-induced ?-cell failure in vivo by a mechanism that involves inhibition of fatty acid–mediated apoptosis, inhibition of mitochondrial dysfunction, and inhibition of FOXO1 activation.

Hennige, Anita M.; Ranta, Felicia; Heinzelmann, Isabel; Dufer, Martina; Michael, Diana; Braumuller, Heidi; Lutz, Stefan Z.; Lammers, Reiner; Drews, Gisela; Bosch, Fatima; Haring, Hans-Ulrich; Ullrich, Susanne



Prevention mechanisms of glucose intolerance and obesity by cacao liquor procyanidin extract in high-fat diet-fed C57BL/6 mice.  


In this study, we investigated whether cacao liquor procyanidin (CLPr) extract, which consists of 4.3% catechin, 6.1% epicatechin, 39.4% procyanidins and others, ameliorated hyperglycemia and obesity in C57BL/6 mice fed a control or high-fat diet for 13 weeks. CLPr suppressed high-fat diet-induced hyperglycemia, glucose intolerance and fat accumulation in white adipose tissue. CLPr also promoted translocation of glucose transporter 4 (GLUT4) and phosphorylation of AMP-activated protein kinase ? (AMPK?) in the plasma membrane of skeletal muscle and brown adipose tissue. Phosphorylation of AMPK? was also enhanced in the liver and white adipose tissue. CLPr up-regulated the gene and protein expression levels of uncoupling protein (UCP)-1 in brown adipose tissue and UCP-3 in skeletal muscle. These results indicate that CLPr is a beneficial food material for the prevention of hyperglycemia and obesity. Activation of AMPK?, translocation of GLUT4 and up-regulation of UCP expression in skeletal muscle and adipose tissue are involved in the molecular mechanisms by which CLPr prevents hyperglycemia and obesity. PMID:22465028

Yamashita, Yoko; Okabe, Masaaki; Natsume, Midori; Ashida, Hitoshi



Oral salmon calcitonin protects against impaired fasting glycemia, glucose intolerance, and obesity induced by high-fat diet and ovariectomy in rats.  


OBJECTIVE: Oral salmon calcitonin (sCT) has demonstrated clinical efficacy in treating osteoporosis in postmenopausal women. The postmenopausal state is also associated with obesity-related insulin resistance (IR) and type 2 diabetes. The aim of this study was to investigate the preventive effects of oral sCT on energy and glucose homeostasis in high-fat diet (HFD)- and ovariectomy (OVX)-induced obese rats. Furthermore, the weight-regulatory and gluco-regulatory effects of short-term oral sCT intervention on HFD-induced obese rats were explored. METHODS: For prevention, female rats exposed to HFD with or without OVX were treated with oral sCT for 5 weeks. As intervention, HFD-induced obese male rats were treated with oral sCT for 4 days. Body weight, food intake, and plasma glucose, insulin, and leptin levels were measured, and the clinical homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated. In addition, oral glucose tolerance was evaluated in the systemic and portal circulations. RESULTS: For prevention, oral sCT reduced body weight by ?16% to 19% (P < 0.001), reduced plasma insulin and leptin by ?50%, and improved impaired fasting glycemia (P < 0.05) concomitantly with amelioration of IR (HOMA-IR; P < 0.01) in HFD- and OVX-induced obesity. Furthermore, oral sCT significantly reduced the incremental area under the curve for plasma glucose and insulin by ?40% and ?70%, respectively, during glucose tolerance testing. As intervention in HFD-induced obese rats, oral sCT reduced body weight, fasting glycemia, and insulinemia in conjunction with HOMA-IR (P < 0.001). Finally, oral sCT alleviated glucose intolerance predominantly in the portal circulation. CONCLUSIONS: Oral sCT treatment displays weight-regulatory and glucoregulatory efficacy in HFD- and OVX-induced obese rats, indicating the clinical usefulness of oral sCT in postmenopausal obesity-related IR and type 2 diabetes. PMID:23385715

Feigh, Michael; Andreassen, Kim V; Hjuler, Sara T; Nielsen, Rasmus H; Christiansen, Claus; Henriksen, Kim; Karsdal, Morten A



Cold Intolerance  


... Professionals Excerpt from the Handbook on the Late Effects of Poliomyelitis for Physicians and Survivors © Cold Intolerance Many polio survivors report that their feet have always been cold to the touch, their skin a purplish color. As they age, their limbs become more sensitive ...


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

PubMed Central

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.

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



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


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

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



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


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

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



The once-daily human GLP-1 analog, liraglutide, reduces olanzapine-induced weight gain and glucose intolerance  

Microsoft Academic Search

Therapeutic use of atypical antipsychotic agents is often associated with weight gain and impaired glucose tolerance. The once-daily human GLP-1 analog liraglutide improves glycemic control and reduces body weight. We have investigated the ability of liraglutide to improve olanzapine-induced metabolic effects in female rats.Female Sprague–Dawley rats were implanted with subcutaneous osmotic mini pumps for delivery of olanzapine (1.75 mg\\/24 h) or vehicle

Kirsten Lykkegaard; Philip J. Larsen; Niels Vrang; Camilla Bock; Troels Bock; Lotte Bjerre Knudsen



The application of glucose biosensor in studying the effects of insulin and anti-hypertensive drugs towards glucose level in brain striatum.  


The mechanisms involving insulin and anti-hypertensive drugs regulation for in vivo cerebral glucose metabolism are not well-understood. This might be due to lack of direct means of measuring cerebral glucose. It is known that the continuous delivery of glucose to the brain is critical for its normal metabolic function. In this study, we report the effect of insulin and anti-hypertensive drugs on glucose level in the striatum of rats. The rats were divided into two groups, i.e. hyperglycemia (14.8+/-0.3mM plasma glucose) and diabetic (10.8+/-0.2mM plasma glucose). A custom-built glucose microsensor was implanted at coordinates A/P 1.0 from bregma, M/L +2.5 and D/V -5.0 (from dura) in the striatum. The amperometric response obtained at +0.23 V vs. Ag|AgCl corresponded to the glucose level in striatum. By varying the concentrations of protaminc zinc insulin infused into the rats, striatum glucose level was found to remain constant throughout, i.e. 9.8+/-0.1 and 4.7+/-0.1mM for hyperglycemic rats and for diabetic rats, respectively. However, infusion of valsartan and felodipine has lowered the striatum glucose level significantly. These findings agreed with the hypothesis that suggested striatum glucose uptake do not depend on insulin but is clearly dependant on anti-hypertensive drugs administration. PMID:18440218

Ahmad, Farook; Yusof, Ahmad Pauzi Md; Bainbridge, Martina; Ab Ghani, Sulaiman



30 days of continuous olanzapine infusion determines energy imbalance, glucose intolerance, insulin resistance, and dyslipidemia in mice.  


The aim of this study was to model in mice the association between metabolic syndrome and the administration of atypical antipsychotic (AAP). Two dosages (4 and 8 mg/kg per day) of olanzapine (OL) were infused in 36 female mice for 30 days by osmotic mini-pumps. This study was also designed to further extend the implications raised in other experiments by our model of AAP-induced metabolic dysregulation. Through the use of the osmotic mini-pumps, this model is aimed to circumvent the shorter (than in humans) half-life of AAPs in rodents and to chronically administer OL by a reliable and less disturbing method. Indirect calorimetry was used to evaluate metabolic rate (MR) and respiratory exchange ratio together with weight and caloric intake. Serum insulin, leptin, and glucose tolerance (oral glucose tolerance test) were assessed. Pancreatic beta cells insulin levels, periuterine and liver fat content were also analyzed. Olanzapine-infused mice exhibited a reduction of overall MR (kilojoule per hour) and resting MR and respiratory exchange ratio, with periuterine fat significantly enlarged. All metabolic alterations were detected at the highest dose, with major effects found on weight gain and hyperphagia. Impaired glucose metabolism, associated with hyperinsulinemia and hyperleptinemia were found. Insulin resistance was evidenced by the raise of HOMA-IR index. Increased insulin and lipid storage were detected at pancreatic and hepatic levels respectively. These findings illustrate the development of a cluster of risk factors (metabolic syndrome) and, for the first time, a decrease of energy expenditure (MR) due to chronic OL infusion. PMID:19910724

Coccurello, Roberto; Brina, Daniela; Caprioli, Antonio; Conti, Roberto; Ghirardi, Orlando; Schepis, Filippo; Moles, Anna



Skeletal myoblast transplantation for attenuation of hyperglycaemia, hyperinsulinaemia and glucose intolerance in a mouse model of type 2 diabetes mellitus  

Microsoft Academic Search

Aims\\/hypothesis  We aimed to demonstrate the feasibility and efficacy of intra-muscular transplantation of human skeletal myoblasts (hSkMs)\\u000a for attenuation of hyperglycaemia and improvement of insulin sensitivity using a mouse model of type 2 diabetes mellitus.\\u000a \\u000a \\u000a \\u000a Methods  KK Cg-Ay\\/J mice, aged 12 to 14 weeks, underwent an initial intraperitoneal glucose tolerance test (GTT) and were divided into\\u000a the following groups: KK control group, basal

L. Ye; K. O. Lee; L. P. Su; W. C. Toh; H. K. Haider; P. K. Law; W. Zhang; S. P. Chan; E. K. W. Sim



Intolerant tolerance.  


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

Khushf, G



Disrupted daily light-dark cycle induces the expression of hepatic gluconeogenic regulatory genes and hyperglycemia with glucose intolerance in mice.  


We elucidated associations between metabolic disorders and the environmental light-dark (LD) cycle that entrains the circadian clock located in the suprachiasmatic nucleus of mammals. Mice were fed with a high-fat/high-sucrose diet for eight weeks under a normal 12h light-12h dark cycle (LD 12:12) or an ultradian 3h light-3h dark cycle (LD 3:3) that might perturb the central clock. The circadian behavioral rhythms were gradually disturbed under LD 3:3. Hyperglycemia with glucose intolerance and increases in diabetic markers, glycated albumin and hemoglobin A1c, were significantly induced without affecting body weight gain and food consumption in LD 3:3. Expression levels of hepatic gluconeogenic regulatory genes such as Pck1, G6pc, Hnf4a, and Foxo1/3/4 genes were increased under LD 3:3. Hypercholesterolemia with hepatic cholesterol accumulation was also induced in LD 3:3. Ultradian LD 3:3 cycles did not affect the adipose inflammation that is considered a major player in obesity-associated metabolic disorders. Our findings provide a link between metabolic disorders and environmental photoperiodic cycles in genetically normal animals. PMID:23376072

Oishi, Katsutaka; Itoh, Nanako



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

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-?-D-glucoside (0.9%), ononin (1.2%), calycosin (4.53%) and formononetin (1.1%), significantly reduced the secretion of pro-inflammatory cytokines (TNF-?, IL-6 and MCP-1) in human THP-1 macrophages and lipopolysaccharide (LPS)-induced activation of NF-?B 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-? 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.



One-Hour Postload Plasma Glucose Levels and Diastolic Function in Hypertensive Patients  

PubMed Central

OBJECTIVE To address whether glucose tolerance status, and in particular 1-h postload plasma glucose levels, may affect diastolic function in 161 never-treated hypertensive white subjects. Impaired left ventricular relaxation, an early sign of diastolic dysfunction, represents the first manifestation of myocardial involvement in diabetic cardiomyopathy. A plasma glucose value ?155 mg/dL for the 1-h postload 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. RESEARCH DESIGN AND METHODS Subjects underwent OGTT and standard echocardiography. Diastolic function was assessed by pulsed Doppler transmitral flow velocity and tissue Doppler imaging. Insulin sensitivity was assessed by Matsuda index. RESULTS Among the participants, 120 had NGT, 26 had impaired glucose tolerance (IGT), and 15 had type 2 diabetes. According to the 1-h postload plasma glucose cutoff point of 155 mg/dL, we divided NGT subjects as follows: NGT <155 mg/dL (n = 90) and NGT ?155 mg/dL (n = 30). Those with NGT ?155 mg/dL had higher left atrium dimensions (P < 0.0001) and isovolumetric relaxation time (IVRT) (P = 0.037) than those with NGT <155 mg/dL. By contrast, early/late transmitral flow velocity and all tissue Doppler parameters were significantly lower in those with NGT ?155 mg/dL than in those with NGT<155 mg/dL. At multiple regression analysis, 1-h glucose was the major determinant of left atrium area, IVRT, septal e?, septal e?-to-a? ratio, lateral e?, and lateral e?-to-a? ratio. CONCLUSIONS The main finding of this study is that 1-h postload plasma glucose is associated with left ventricular diastolic dysfunction. Subjects with NGT ?155 mg/dL had significantly worse diastolic function than those with NGT<155 mg/dL.

Sciacqua, Angela; Miceli, Sofia; Greco, Laura; Arturi, Franco; Naccarato, Paola; Mazzaferro, Deborah; Tassone, Eliezer J.; Turano, Laura; Martino, Francesco; Sesti, Giorgio; Perticone, Francesco



One-Hour Postload Plasma Glucose Levels and Left Ventricular Mass in Hypertensive Patients  

PubMed Central

OBJECTIVE Left ventricular hypertrophy (LVH), an independent risk factor for cardiovascular (CV) morbidity and mortality, recognizes a multifactorial pathogenesis. A plasma glucose value ?155 mg/dL for the 1-h postload plasma glucose during an oral glucose tolerance test (OGTT) identifies subjects with normal glucose tolerance (NGT) at high risk for type 2 diabetes. We addressed the question if glucose tolerance status, particularly 1-h postload plasma glucose levels, affects left ventricular mass (LVM) and cardiac geometry in essential hypertension. RESEARCH DESIGN AND METHODS We enrolled 767 never-treated hypertensive subjects, 393 women and 374 men (mean age 49.6 ± 8.5 years). All patients underwent an OGTT for the evaluation of glucose tolerance and standard echocardiography. LVM was calculated using the Devereux formula and normalized by body surface area (LVM index [LVMI]). Insulin sensitivity was assessed by the Matsuda index. Among all participants, 514 had NGT, 168 had impaired glucose tolerance (IGT), and 85 had type 2 diabetes. According to the 1-h postload plasma glucose cutoff point of 155 mg/dL, we divided normotolerant subjects into two groups: NGT <155 mg/dL (n = 356) and NGT ?155 mg/dL (n = 158). RESULTS Subjects in the NGT ?155 mg/dL group had worse insulin sensitivity than subjects in the NGT <155 mg/dL group (Matsuda index 63.9 vs. 88.8; P < 0.0001). Men with NGT ?155 mg/dL had a higher LVMI than men with NGT <155 mg/dL (126.6 vs. 114.3 g/m2; P = 0.002) and a different LVH prevalence (41.1 vs. 25.8%; P < 0.0001). At multiple regression analysis, 1-h glucose resulted in the major determinant of LVMI in normotolerant, IGT, and diabetic groups. CONCLUSIONS These data show that NGT ?155 mg/dL subjects, compared with NGT <155 mg/dL subjects, have a higher LVMI and a greater prevalence of LVH similar to that of IGT and diabetic patients.

Sciacqua, Angela; Miceli, Sofia; Carullo, Giuseppe; Greco, Laura; Succurro, Elena; Arturi, Franco; Sesti, Giorgio; Perticone, Francesco



Changes in plasma, erythrocyte, and platelet magnesium levels in normotensive and hypertensive obese subjects during oral glucose tolerance test  

Microsoft Academic Search

We evaluated the 75-g oral glucose tolerance test (OGTT)-induced modifications in glucose, insulin, and norepinephrine plasma concentrations, and in plasma, erythrocyte, and platelet magnesium levels in two groups of obese subjects (normotensive obese, NT-Ob, N = 19; hypertensive obese, HT-Ob, N = 15), and in a group of healthy control subjects (N = 12). During OGTT we detected a reduction

Francesco Corica; Alessandro Allegra; Riccardo Ientile; Michele Buemi; Andrea Corsonello; Salvatore Bonanzinga; Salvatore Macaione; Domenico Ceruso



Hyperuricemia and Incidence of Hypertension Among Men Without Metabolic Syndrome  

Microsoft Academic Search

The aim of this project was to study the risk of developing hypertension over a 6-year follow-up in normotensive men with baseline hyperuricemia (serum uric acid 7.0 mg\\/dL) but without diabetes\\/glucose intolerance or metabolic syndrome. We analyzed the data on men without metabolic syndrome or hypertension at baseline from the Multiple Risk Factor Intervention Trial. These men (n3073; age: 35

Eswar Krishnan; C. Kent Kwoh; H. Ralph Schumacher; Lewis Kuller



[Hypertension and diabetes mellitus].  


Numerous surveys have shown that in industrial countries diabetic subjects develop hypertension more frequently than non-diabetic persons. In fact, three typical hypertension forms in these patients can be discerned: essential, renal, and isolated systolic hypertension. In type 2-diabetes (NIDDM) hypertension can be seen in close association with obesity, glucose intolerance, lipid changes, and insulin resistance within the framework of the metabolic syndrome. The increased incidence of hypertension in type 1-diabetes (IDDM) is a result of development of diabetic nephropathy. In the elderly type 2-diabetics particularly frequently isolated systolic hypertension is present which reflects increased arterial stiffness and loss of vascular distensibility. In hypertension progression of both macrovascular disease and microangiopathy is increased whereby interaction of hyperglycemia and hypertension seems to be the main risk factor. In most hypertensive diabetic patients drugs will be necessary to lower blood pressure in a therapeutical range. There are several effective substances available which should be prescribed individually according to the needs and accompanying conditions in these patients. PMID:8475640

Janka, H U



[Primary hemostasis activity in patients with arterial hypertension and impaired glucose tolerance treated with trandolapril].  


The study was designed to evaluate effect of trandolapril, an ACE inhibitor, on platelet aggregation in patients with arterial hypertension and impaired glucose tolerance. The drug was given to 38 patients for 12 weeks. The key end points were dynamics of the blood lipid spectrum, lipid peroxidation in plasma and platelets, antioxidative protection of the blood's liquid medium and platelets, platelet aggregation. The data obtained were treated using Student's t-test. They show that trandolapril exerts positive effect on peroxidation syndrome and reduces platelet aggregation. PMID:21574438

Simonenko, V B; Medvedev, I N; Gamolina, O V



White-Coat Hypertension.  


AIM: A number of studies have examined if WCHT is associated with increased cardiovascular risk but with definitions of WCHT that were not sufficiently robust, and results have been inconsistent. This review aims to standardise the evidence by only including studies which used a definition of WCHT consistent with international guidelines. METHOD: Published studies were reviewed for data on vascular dysfunction, target organ damage, risk of future sustained hypertension and cardiovascular events. FINDINGS: WCHT has a population prevalence of approximately 15% and is associated with non-smoking and slightly elevated clinic blood pressure. Compared to normotensives, subjects with WCHT are at increased cardiovascular risk due to a higher prevalence of glucose dysregulation, increased left ventricular mass index and increased risk of future diabetes and hypertension. CONCLUSION: Management of a subject with WCHT should focus on cardiovascular risk factors, particularly glucose intolerance, not blood pressure alone. This article is protected by copyright. All rights reserved. PMID:23682974

Martin, Catherine A; McGrath, Barry P



Effect of metformin on the vascular and glucose metabolic actions of insulin in hypertensive rats.  


We investigated the long-term effect of metformin treatment on blood pressure, insulin sensitivity, and vascular responses to insulin in conscious spontaneously hypertensive rats (SHR). The rats were instrumented with intravascular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and blood flow. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp technique. Two groups of SHR received metformin (100 or 300 mg x kg(-1) x day(-1)) for 3 wk while another group of SHR and a group of Wistar Kyoto (WKY) rats were left untreated. We found that vasodilation of skeletal muscle and renal vasculatures by insulin is impaired in SHR. Moreover, a reduced insulin sensitivity was detected in vivo and in vitro in isolated soleus and extensor digitorum longus muscles from SHR compared with WKY rats. Three weeks of treatment with metformin improves the whole-body insulin-mediated glucose disposal in SHR but has no blood pressure-lowering effect and no influence on vascular responses to insulin (4 mU x kg(-1) x min(-1)). An improvement in insulin-mediated glucose transport activity was detected in isolated muscles from metformin-treated SHR, but in the absence of insulin no changes in basal glucose transport activity were observed. It is suggested that part of the beneficial effect of metformin on insulin resistance results from a potentiation of the hormone-stimulating effect on glucose transport in peripheral tissues (mainly skeletal muscle). The results argue against a significant antihypertensive or vascular effect of metformin in SHR. PMID:10801260

Santuré, M; Pitre, M; Gaudreault, N; Marette, A; Nadeau, A; Bachelard, H



Insulin Resistance in Hypertension Is Associated With Body Fat Rather Than Blood Pressure  

Microsoft Academic Search

Abstract—The insulin resistance syndrome has been characterized by hypertension, upper body obesity, insulin resistance, hyperinsulinemia, glucose intolerance, and hypertriglyceridemia. Previous studies are inconsistent regarding the relationship between,blood pressure and insulin resistance. We therefore compared,the metabolic profile in 60 hypertensive subjects (mean6SD arterial pressure, 11667 mm Hg) and 60 normotensive subjects (mean arterial pressure, 8865 mm Hg) matched for age, gender,

Ingrid Toft; Kaare H. Bønaa; Trond Jenssen


Orthostatic Intolerance: Potential Pathophysiology and Therapy  

Microsoft Academic Search

Orthostatic intolerance affects an estimated 1 in 500 persons and causes a wide range of disabilities. After essential hypertension, it is the most frequently encountered dysautonomia, accounting for the majority of patients referred to centers specializing in autonomic disorders. Patients are typically young females with symptoms such as dizziness, visual changes, head and neck discomfort, poor concentration, fatigue, palpitations, tremulousness,

Chih-Cherng Lu; Ching-Jiunn Tseng; Hung-Shang Tang; Che-Se Tung



Glucose tolerance test  


Factors that may affect the test results: Acute stress (for example, from surgery or an infection) Vigorous exercise Several drugs may cause glucose intolerance, including: Atypical antipsychotic medications, ...


Two-hour insulinemia after oral glucose overload and women at risk of pregnancy-induced hypertensive disorders.  


Objective: Pregnant women with impaired insulin sensitivity are at risk for developing pregnancy-induced hypertensive disorders (PIHD). We analyzed glucose and insulin circulating levels throughout a 2-h oral 75?g glucose tolerance test in pregnant women, and related the 2-h insulinemias to PIHD prevalence. Methods: Pregnant women (gestational week 24-28) were submitted to a glucose overload, and glucose and insulin plasma concentrations were measured throughout the test. These peripheral metabolite levels, the homeostasis model assessment (HOMA) values and the glucose to insulin ratio (G:Ir) were analyzed. Anthropometric parameters and pregnancy outcome were recorded. Results: Women with normal fasting glycemia, insulinemia and HOMA values, G:Ir and 2?h-glycemia but whose 2?h-insulinemia was higher than 215.25?pM were at greater risk for developing late pregnancy hypertension and preeclampsia compared to women of similar characteristics but whose 2?h-insulinemias were lower than 215.25?pM. Conclusion: 2-h insulinemias higher than 215.25?pM after a 75?g glucose overload could be highly indicative of women at increased risk of developing PIHD. PMID:23844648

Romero, José; Spinedi, Eduardo



Association between One-Hour Post-Load Plasma Glucose Levels and Vascular Stiffness in Essential Hypertension  

PubMed Central

Objectives Pulse wave velocity (PWV) is a surrogate end-point for cardiovascular morbidity and mortality. A plasma glucose value ?155 mg/dl for the 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 (T2D) and for subclinical organ damage. Thus, we addressed the question if 1-hour post-load plasma glucose levels, affects PWV and its central hemodynamic correlates, as augmentation pressure (AP) and augmentation index (AI). Methods We enrolled 584 newly diagnosed hypertensives. All patients underwent OGTT and measurements of PWV, AP and AI. Insulin sensitivity was assessed by Matsuda-index. Results Among participants, 424 were NGT and 160 had impaired glucose tolerance (IGT). Of 424 NGT, 278 had 1-h post-load plasma glucose <155 mg/dl (NGT<155) and 146 had 1-h post-load plasma glucose ?155 mg/dl (NGT?155). NGT?155 had a worse insulin sensitivity and higher hs-CRP than NGT<155, similar to IGT subjects. In addition, NGT ?155 in comparison with NGT<155 had higher central systolic blood pressure (134±12 vs 131±10 mmHg), as well as PWV (8.4±3.7 vs 6.7±1.7 m/s), AP (12.5±7.1 vs 9.8±5.7 mmHg) and AI (29.4±11.9 vs 25.1±12.4%), and similar to IGT. At multiple regression analysis, 1-h post-load plasma glucose resulted the major determinant of all indices of vascular stiffness. Conclusion Hypertensive NGT?155 subjects, compared with NGT<155, have higher PWV and its hemodynamic correlates that increase their cardiovascular risk profile.

Sciacqua, Angela; Maio, Raffaele; Miceli, Sofia; Pascale, Alessandra; Carullo, Giuseppe; Grillo, Nadia; Arturi, Franco; Sesti, Giorgio; Perticone, Francesco



The Glucose Intolerance Induced by Caffeinated Coffee Ingestion Is Less Pronounced than That Due to Alkaloid Caffeine in Men1,2  

Microsoft Academic Search

Although acute alkaloid caffeine (CAF) ingestion results in an impaired glucose tolerance, chronic coffee (RCOF) ingestion decreases the risk of developing type 2 diabetes. This study examines the hypothesis that CAF ingestion impairs glucose tolerance to a greater extent than RCOF and that the ingestion of decaffeinated coffee (DECAF) results in a positive effect. Eleven healthy males underwent 4 double-blinded

Danielle S. Battram; Rebecca Arthur; Andrew Weekes; Terry E. Graham


Glucose intolerance caused by a defect in the entero-insular axis: A study in gastric inhibitory polypeptide receptor knockout mice  

PubMed Central

Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic ? cells. GIPR?/? mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR?/? mice because of the lack of such enhancement. Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes.

Miyawaki, Kazumasa; Yamada, Yuichiro; Yano, Hideki; Niwa, Hitoshi; Ban, Nobuhiro; Ihara, Yu; Kubota, Akira; Fujimoto, Shinpei; Kajikawa, Mariko; Kuroe, Akira; Tsuda, Kinsuke; Hashimoto, Hiroyuki; Yamashita, Tokuyuki; Jomori, Takahito; Tashiro, Fumi; Miyazaki, Jun-ichi; Seino, Yutaka



Assessment of hepatic insulin degradation, in normoglycemic hypertensive patients, by minimal modelling of standard intravenous glucose tolerance test data.  


Role of hepatic insulin degradation in modulating insulin delivery to peripheral circulation, in insulin-resistant hypertensive patients, is not yet fully understood. This issue was investigated here by a novel application to hypertension of a previously proposed minimal modelling of insulin and C-peptide data, using population values for insulin and C-peptide kinetics parameters. Data, from frequently sampled intravenous glucose tolerance test (FSIGTT), were analysed in ten normoglycemic, hypertensive patients (H-group), compared with eight normoglycemic, normotensive subjects (N-group), matched for age, gender and body mass index. Minimal modelling of C-peptide and insulin data provided beta-cell responsiveness to glucose perturbation (first, Phi(1), second, Phi(2), and basal, Phi(b), phase), insulin secretion rate, ISR(t) and total pre-hepatic insulin secretion, TIS, as well as insulin delivery rate, IDR(t), and total insulin delivery, TID, into plasma, over 5-h test. Instantaneous normalized hepatic insulin degradation rate was computed as HIDR(t)=1-[IDR(t)/ISR(t)]. In our H-group, insulin sensitivity, S(I), assessed by minimal model of glucose kinetics, showed a 56% reduction, which confirmed deterioration of insulin action in hypertension. This was associated with significant increase in Phi(1) (105%), TIS (55%) and TID (62%). No significant alterations were observed in other characteristic parameters of secretion and hepatic degradation of insulin, such that no significant difference was observed in HIDR(t) between our H and N groups. In conclusion, an increase of first phase and total insulin secretion occurring, in our H-group, in the presence of no alteration of hepatic insulin degradation, resulted in up-regulation of total insulin delivered to plasma (TID) for insulin-resistance compensation. PMID:19767120

Di Nardo, Francesco; Boemi, Massimo; Burattini, Roberto



Novel effect of adenosine 5'-monophosphate on ameliorating hypertension and the metabolism of lipids and glucose in stroke-prone spontaneously hypertensive rats.  


The aim of the study was to investigate the effects of adenosine 5'-monophosphate (AMP) in stroke-prone spontaneously hypertensive rats (SHRSP). Male rats (10 weeks old) were divided into three groups: a control group fed an AIN-93 M diet and two others fed supplemental AMP (17.5 and 87.5 mg/kg diet) for 3 weeks. AMP effectively improved hypertension, plasma triglyceride, and HDL-cholesterol, glucose, kidney function parameters, hepatic lipid, enhances plasma nitric oxide, and plasma adiponectin accompanied by the up-regulation of mRNA expression levels of the hepatic adiponectin receptor 2. Single and chronic oral administration of AMP affected the hepatic mRNA expression levels of genes involved in ?-oxidation, fatty acid synthesis, and AMP-activated protein kinase. Furthermore, a single oral dose of AMP (40 mg/kg body weight) improved hypertension and hyperglycemia in SHRSP. In conclusion, AMP displays a novel effect in ameliorating metabolic-related diseases in SHRSP and could be beneficial as a functional food. PMID:22103713

Ardiansyah; Shirakawa, Hitoshi; Koseki, Takuya; Hiwatashi, Kazuyuki; Takahasi, Saori; Akiyama, Yoshinobu; Komai, Michio



Impaired glucose homeostasis in non-diabetic Greek hypertensives with diabetes family history. Effect of the obesity status.  


Arterial hypertension (AH) and diabetes mellitus (DM) are established cardiovascular risk factors. Impaired glucose homeostasis (IGH; impaired fasting glucose or/and impaired glucose tolerance) or pre-diabetes, obesity, and DM family history identify individuals at risk for type 2 DM in whom preventive interventions are necessary. The aim of this study was to determine the glycemic profile in non-diabetic Greek adult hypertensive men and women according to DM family history and the obesity status. Diabetes family history, obesity markers (waist-to-hip ratio, WHR; body mass index, BMI), glycemic parameters (fasting and 2-hour post-load plasma glucose, if necessary; glycated hemoglobin, HbA1c; fasting insulin), insulin resistance indices (homeostasis model assessment, HOMA; quantitative insulin sensitivity check index, QUICKI; Bennett; McAuley), and IGH prevalence were determined in a large cohort of 11,540 Greek hypertensives referred to our institutions. Positive DM family history was associated with elevated fasting glucose (98.6 ± 13.1 vs 96.5 ± 12.3 mg/dL), HbA1c (5.58% ± 0.49% vs 5.50% ± 0.46%), fasting insulin (9.74 ± 4.20 vs 9.21 ± 3.63 ?U/mL) and HOMA (2.43 ± 1.19 vs 2.24 ± 1.01) values, lower QUICKI (0.342 ± 0.025 vs 0.345 ± 0.023), Bennett (0.285 ± 0.081 vs 0.292 ± 0.078) and McAuley (6.73 ± 3.43 vs 6.95 ± 3.44) values, and higher IGH prevalence (45.3% vs 38.7%); P < .01 for all comparisons. The difference in the prevalence of IGH according to DM family history was significant (P < .01) in both genders and every WHR and BMI subgroup (except for women with BMI <20 kg/m(2)). Non-diabetic hypertensives with positive DM family history present with higher IGH prevalence and worse glycemic indices levels compared with those with negative family history, especially in the higher WHR/BMI subgroups. PMID:23562108

Vyssoulis, Gregory P; Liakos, Charalampos I; Karpanou, Eva A; Triantafyllou, Athanasios I; Michaelides, Andreas P; Tzamou, Vanessa E; Markou, Maria I; Stefanadis, Christodoulos I



Time course of high-fat diet-induced reductions in adipose tissue mitochondrial proteins: potential mechanisms and the relationship to glucose intolerance.  


Increasing evidence suggests that reduced adipose tissue mitochondrial content is associated with the pathogenesis of type 2 diabetes. These investigations have utilized severely insulin-resistant rodent models. Thus, it is difficult to ascertain the potential mechanisms that initiate these changes and whether reductions in adipose mitochondria are an initiating event in the development of impaired glucose homeostasis. Thus, we sought to determine the time course of high-fat diet-induced reductions of mitochondrial content in epididymal adipose tissue in relation to changes in purported mediators of mitochondrial biogenesis and the development of impaired glucose homeostasis. Male Wistar rats were fed a high-fat diet ( approximately 59% of kcals from fat) for 2, 4, or 6 wk. Six weeks of high-fat feeding resulted in reductions in CORE I, COX IV, cytochrome c, HSP60, relative mtDNA copy number, and PGC-1alpha expression. These changes were not associated with decreases in eNOS and AMPK or increases in markers of oxidative stress. Interestingly, ex vivo treatment of adipose tissue cultures with palmitate led to decreases in PGC-1alpha expression and COX IV and CORE I protein content as observed in vivo. Thus, the high-fat diet-induced reductions in adipose tissue mitochondrial proteins may be mediated by increases in plasma fatty acids. Importantly, reductions in adipose tissue mitochondrial content occurred after the development of impaired glucose homeostasis. Thus, reductions in adipose tissue mitochondrial proteins are most likely not a causal event in the development of impaired glucose homeostasis. PMID:18780775

Sutherland, Lindsey N; Capozzi, Lauren C; Turchinsky, N Joan; Bell, Rhonda C; Wright, David C



Angiotensin-Converting Enzyme 2 Deficiency Aggravates Glucose Intolerance via Impairment of Islet Microvascular Density in Mice with High-Fat Diet.  


The aim of this study was to evaluate the effects of angiotensin-converting enzyme 2 (ACE2) on glucose homeostasis and islet function in mice. Male wildtype (WT) and ACE2 knockout (ACE2 KO) mice were divided into chow diet group and long-term high-fat diet (HFD) group. After 16 weeks of feeding, the islet function of the animals was evaluated by intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin releasing test (IPIRT). The pancreas was immunohistochemically stained to analyze the relative content of insulin (IRC), vascular endothelial growth factor (VEGF), and microvessel density (MVD) in islets. There was no difference of body weight, area under curve of glucose (AUCG), area under curve of insulin from 0 to 5?min (AUGI0-5), MVD, and RVC (relative content of VEGF) between WT and ACE2 KO mice with regular chow diet. Under the condition of long-term HFD, the AUCG of ACE2 KO mice was increased obviously in comparison with the WT mice, with decreased IRC, MVD, AUGI0-5, AUCI0-30, and RVC (all P < 0.05). In conclusion, these results show that ACE2 deficiency deteriorates islet function of mice with long-term HFD via impairment of islet microvasculature. PMID:23671869

Yuan, Li; Wang, Ying; Lu, Chunli; Li, Xiaoya



Angiotensin-Converting Enzyme 2 Deficiency Aggravates Glucose Intolerance via Impairment of Islet Microvascular Density in Mice with High-Fat Diet  

PubMed Central

The aim of this study was to evaluate the effects of angiotensin-converting enzyme 2 (ACE2) on glucose homeostasis and islet function in mice. Male wildtype (WT) and ACE2 knockout (ACE2 KO) mice were divided into chow diet group and long-term high-fat diet (HFD) group. After 16 weeks of feeding, the islet function of the animals was evaluated by intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin releasing test (IPIRT). The pancreas was immunohistochemically stained to analyze the relative content of insulin (IRC), vascular endothelial growth factor (VEGF), and microvessel density (MVD) in islets. There was no difference of body weight, area under curve of glucose (AUCG), area under curve of insulin from 0 to 5?min (AUGI0–5), MVD, and RVC (relative content of VEGF) between WT and ACE2 KO mice with regular chow diet. Under the condition of long-term HFD, the AUCG of ACE2 KO mice was increased obviously in comparison with the WT mice, with decreased IRC, MVD, AUGI0–5, AUCI0–30, and RVC (all P < 0.05). In conclusion, these results show that ACE2 deficiency deteriorates islet function of mice with long-term HFD via impairment of islet microvasculature.

Yuan, Li; Wang, Ying; Lu, Chunli; Li, Xiaoya



Chemical gastric inhibitory polypeptide receptor antagonism protects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat and cafeteria diets  

Microsoft Academic Search

Aims\\/hypothesis  Gastric inhibitory polypeptide (GIP) receptor antagonism with (Pro3)GIP improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure\\/function in ob\\/ob mice. This study examined the ability of (Pro3)GIP to counter the development of obesity, insulin resistance and diabetes in mice fed high-fat and cafeteria diets.\\u000a \\u000a \\u000a \\u000a Materials and methods  Young Swiss TO mice on standard chow or high-fat, cafeteria or

V. A. Gault; P. L. McClean; R. S. Cassidy; N. Irwin; P. R. Flatt





... hypertension: Treatment. 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 ...




An estimated 58 million Americans are at increased risk of morbidity and premature death due to high blood pressure (BP) and require some type of therapy or systematic monitoring. This article focuses on recent advances in our understanding of the pathogenesis of hypertension, new approaches to the diagnosis and treatment of secondary hypertension, and current views of the most appropriate nonpharmacologic and pharmacologic therapy for essential hypertension. In view of the extremely high prevalence of the disorder, emphasis is placed on efficient and cost-effective strategies for diagnosing and managing the hypertensive patient. Recent evidence indicates that nonpharmacologic therapy, including dietary potassium and calcium supplements, reduction of salt intake, weight loss for the obese patient, regular exercise, a diet high in fiber and low in cholesterol and saturated fats, smoking cessation, and moderation of alcohol consumption produces significant sustained reductions in BP while reducing overall cardiovascular risk. Accordingly, nonpharmacologic antihypertensive therapy should be included in the treatment of all hypertensive patients. In persons with mild hypertension, nonpharmacologic approaches may adequately reduce BP, thereby avoiding the expense and potential side effects of drug therapy. In patients with more severe hypertension, nonpharmacologic therapy, used in conjunction with pharmacologic therapy, can reduce the dosage of antihypertensive medications necessary for BP control. Patients treated with nonpharmacologic therapy only should be followed closely, and if BP control is not satisfactory, drug therapy should be added. The large number of drugs available for use in hypertension treatment, coupled with our rapidly expanding knowledge of the pathophysiology of hypertension and of the adverse effects of these drugs in individual patient groups, make it possible to individualize antihypertensive treatment. When used as monotherapy, most agents effectively lower BP in the majority of patients with mild or moderate essential hypertension. Thus, a single agent from one of four classes: diuretics, angiotensin-converting enzyme inhibitors, calcium channel blockers, and beta-adrenergic blockers, usually provides effective BP control with minimal side effects in most patients. Therapy should be initiated with the agent most likely to be effective in BP lowering and best tolerated. If the initial agent is ineffective at maximal recommended therapeutic doses or has undue side effects, an alternative agent from another class should be tried. When monotherapy is unsuccessful, a second agent, usually of a different mechanism of action, should be PMID:2565199

Oparil, S; Calhoun, D A



Maternal diabetes programs hypertension and kidney injury in offspring.  


We investigated whether maternal diabetes programs the offspring to develop hypertension and kidney injury in adulthood and examined potential underlying mechanisms. In a murine model we studied the offspring of three groups of dams (non-diabetic, diabetic, and diabetic treated with insulin). Mean systolic blood pressure in the offspring was monitored from 8 to 20 weeks. Body and kidney weights in the offspring of diabetic mothers were significantly lower than in offspring of non-diabetic mothers. Offspring of diabetic mothers developed hypertension, microalbuminuria, and glucose intolerance. Increased accumulation of extracellular matrix proteins in the glomeruli and marked upregulation of angiotensinogen, angiotensin II type 1 receptor, angiotensin-converting enzyme, transforming growth factor beta-1 (TGF-beta1), and plasminogen activator inhibitor-1 (PAI-1) gene expression were evident in the renal cortex of hypertensive offspring of diabetic mothers. By contrast, angiotensin-converting enzyme-2 (ACE2) gene expression was lower in the hypertensive offspring of diabetic mothers than in that of non-diabetic mothers. These changes were prevented in the offspring of insulin-treated diabetic mothers. These data indicate that maternal diabetes induces perinatal programming of hypertension, renal injury, and glucose intolerance in the offspring and suggest a central role for the activation of the intrarenal renin-angiotensin system and TGF-beta1 gene expression in this process. PMID:20422227

Chen, Yun-Wen; Chenier, Isabelle; Tran, Stella; Scotcher, Michael; Chang, Shiao-Ying; Zhang, Shao-Ling



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


Women, but not men, show an association between fructose consumption and an increased risk of Type 2 diabetes mellitus. As rats are considered a model for human fructose metabolism, we sought to determine whether such a gender-related difference is present in Sprague-Dawley rats and to analyze the molecular mechanism behind. Male and female Sprague-Dawley rats had free access to water or to a 10% w/v fructose solution for 14 days. Plasma analytes, liver triglycerides and enzyme activities and the expression of enzymes and transcription factors related to fatty acid metabolism, insulin signaling and glucose tolerance were determined. Fructose-fed rats had hypertriglyceridemia, steatosis and reduced fatty acid oxidation activity, although the metabolic pattern of fructose-fed female rats was different to that observed for male rats. Fructose-fed female, but not male rats, showed no change in plasma leptin; they had hyperinsulinemia, an altered glucose tolerance test and less liver insulin receptor substrate-2. Further, only fructose-fed female rats had increased adenosine 5'-monophosphate (AMP)-activated protein kinase activity, resulting in a decreased expression of hepatic nuclear factor 4 and sterol response element binding protein 1. These differences were related to the fact that liver expression of the enzyme fructokinase, controlling fructose metabolism, was markedly induced by fructose ingestion in female, but not in male rats, resulting in a significant increase in the AMP/adenosine 5'-triphosphate (ATP) ratio and, thus, AMP-activated protein kinase activation, in female rats only. The difference in fructokinase induction could explain the higher metabolic burden produced by fructose ingestion in the livers of female Sprague-Dawley rats. PMID:21115336

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



Regulation of blood pressure and glucose metabolism induced by L-tryptophan in stroke-prone spontaneously hypertensive rats  

PubMed Central

Background Amino acids have been reported to act as modulators of various regulatory processes and to provide new therapeutic applications for either the prevention or treatment of metabolic disorders. The purpose of the present study is to investigate the effects of single oral dose administration and a continuous treatment of L-tryptophan (L-Trp) on the regulation of blood pressure and glucose metabolism in stroke-prone spontaneously hypertensive rats (SHRSP). Methods First, male 9-week-old SHRSP were administered 100 mg L-Trp·kg-1 body weight in saline to the L-Trp group and 0.9% saline to the control group via a gastric tube as a single oral dose of L-Trp. Second, three groups of SHRSP were fed an AIN-93M-based diet supplemented with L-tryptophan (L-Trp) (0, 200, or 1000 mg·kg-1 diet) for 3 weeks as continuous treatment of L-Trp. Results Single oral dose administration of L-Trp improved blood pressure, blood glucose, and insulin levels. Blood pressure, blood glucose, and insulin levels improved significantly in the L-Trp treatment groups. The administration of L-Trp also significantly increased plasma nitric oxide and serotonin levels. Conclusion L-Trp by both single oral dose administration and continuous treatment improves glucose metabolism and blood pressure in SHRSP.



Association of Dopamine ?-Hydroxylase Polymorphism with Hypertension through Interaction with Fasting Plasma Glucose in Japanese  

Microsoft Academic Search

Dopamine-?-hydroxylase (DBH) catalyzes the conversion of dopamine to norepinephrine and is released from sympathetic neurons into the circulation. Several lines of evidence, including the finding of elevated plasma DBH activity in essential hypertension, suggest an important role of DBH in hypertension. Recently, a novel polymorphism (-1021C\\/T) in the 5? flanking region of the DBH gene has been shown to account

Michiko Abe; Zhihong Wu; Miyuki Yamamoto; Jing Ji Jin; Yasuharu Tabara; Masaki Mogi; Katsuhiko Kohara; Tetsuro Miki; Jun Nakura



Dietary Intake and Serum and Hair Concentrations of Minerals and their Relationship with Serum Lipids and Glucose Levels in Hypertensive and Obese Patients with Insulin Resistance  

Microsoft Academic Search

Inadequate minerals intake, as well as disruption of some metabolic processes in which microelements are cofactors, are suggested\\u000a to lead to the development of hypertension. The role of minerals in the pathogenesis of hypertension still remains to be explained.\\u000a In the present study, we sought to determine associations between serum and hair mineral concentrations and serum lipids and\\u000a glucose levels.

Joanna Suliburska; Pawe? Bogda?ski; Danuta Pupek-Musialik; Zbigniew Krejpcio



Rosuvastatin does not affect fasting glucose, insulin resistance, or adiponectin in patients with mild to moderate hypertension.  


The effects of statins on insulin resistance and new-onset diabetes are unclear. The purpose of this study was to evaluate the effects of rosuvastatin on insulin resistance and adiponectin in patients with mild to moderate hypertension. In a randomized, prospective, single-blind study, 53 hypertensive patients were randomly assigned to the control group (n=26) or the rosuvastatin (20 mg once daily) group (n=27) during an 8-week treatment period. Both groups showed significant improvements in systolic blood pressure and flow-mediated dilation (FMD) after 8 weeks of treatment. Rosuvastatin treatment improved total cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels. The control and rosuvastatin treatment groups did not differ significantly in the change in HbA1c (3.0±10.1% vs. -1.3±12.7%; p=0.33), fasting glucose (-1.3±18.0% vs. 2.5±24.1%; p=0.69), or fasting insulin levels (5.2±70.5% vs. 22.6±133.2%; p=0.27) from baseline. Furthermore, the control and rosuvastatin treatment groups did not differ significantly in the change in the QUICKI insulin sensitivity index (mean change, 2.2±11.6% vs. 3.6±11.9%; p=0.64) or the HOMA index (11.6±94.9% vs. 32.4±176.7%; p=0.44). The plasma adiponectin level increased significantly in the rosuvastatin treatment group (p=0.046), but did not differ significantly from that in the control group (mean change, 23.2±28.4% vs. 23.1±27.6%; p=0.36). Eight weeks of rosuvastatin (20 mg) therapy resulted in no significant improvement or deterioration in fasting glucose levels, insulin resistance, or adiponectin levels in patients with mild to moderate hypertension. PMID:23678475

Kim, Weon; Hong, Myong Joo; Woo, Jong Shin; Kang, Won Yu; Hwang, Sun Ho; Kim, Wan



Prevalence and Associated Factors of Diabetes and Impaired Fasting Glucose in Chinese Hypertensive Adults Aged 45 to 75 Years  

PubMed Central

Objective This study examined the prevalence of impaired fasting glucose (IFG) and diabetes and their associated factors in 17,184 Chinese hypertensive adults aged 45–75 years. Methods A cross-sectional investigation was carried out in a rural area of Lianyungang, China. Previously undiagnosed diabetes [fasting plasma glucose (FPG) ?7.0mmol/l] and IFG (6.1–6.9mmol/l) were defined based on FPG concentration. Previously diagnosed diabetes was determined on the basis of self-report. Total diabetes included both previously diagnosed diabetes and previously undiagnosed diabetes. Results The prevalence of previously diagnosed diabetes, undiagnosed diabetes, and IFG were 3.4%, 9.8%, and 14.1%, respectively. About 74.2% of the participants with diabetes had not previously been diagnosed. In the multivariable logistic-regression model, older age, men, antihypertensive treatment, obesity (BMI ?25kg/m2), abdominal obesity (waist circumference ?90cm for men and ?80cm for women), non-current smoking, a family history of diabetes, higher heart rate, lower physical activity levels, and inland residence (versus coastal) were significantly associated with both total diabetes and previously undiagnosed diabetes. Furthermore, methylene- tetrahydrofolate reductase (MTHFR) 677 TT genotype was an independent associated factor for total diabetes, and current alcohol drinking was an independent associated factor for previously undiagnosed diabetes. At the same time, older age, men, abdominal obesity, non-current smoking, current alcohol drinking, a family history of diabetes, higher heart rate, and inland residence (versus coastal) were important independent associated factors for IFG. Conclusion In conclusion, we found a high prevalence of diabetes in Chinese hypertensive adults. Furthermore, about three out of every four diabetic adults were undiagnosed. Our results suggest that population-level measures aimed at the prevention, identification (even if only based on the FPG evaluation), and treatment of diabetes should be urgently taken to overcome the diabetes epidemic in Chinese hypertensive adults.

Zhang, Yan; Ma, Wei; Fan, Fangfang; Wang, Binyan; Xing, Houxun; Tang, Genfu; Wang, Xiaobin; Xu, Xin; Xu, Xiping; Huo, Yong




Microsoft Academic Search

Hypertension is a forum for the presentation of scientific investigation of the highest quality in the broad field of cardiovascular regulation as it may affect high blood pressure research. The editors are interested in receiving original articles that deal with either basic or clinical research in the fields of biochemistry, cellular and molecular biology, immunology, physiology, pharmacology, and epidemiology. In

Allyn L. Mark; Francois M. Abboud; Gerald F. DiBona; Donald D. Heistad; Larry S. Tobacman; Victor J. Dzau; Carlos Ferrario; Eduardo Marban; Suzanne Oparil; Henry W. Overbeck; Stephen M. Schwartz; Karen Potvin Klein; Connie J. Nelson; John D. Baxter; Kathleen H. Berecek; Edward H. Blaine; Mordecai P. Blaustein; Barry M. Brenner; Michael J. Brody; Hans R. Brunner; Aram V. Chobanian; Robert J. Cody; Allen W. Cowley Jr.; Michael J. Dunn; Alvan R. Feinstein; D. Fink; S. Floras; Ronald H. Freeman; Edward D. Frohlich; Detlev Ganten; Haralambos P. Gavras; Celso E. Gomez-Sanchez; W. Gross; Oregon Willa Hsueh; Tadashi Inagami; I. Johnston; Stevo Julius; Norman M. Kaplan; Paul I. Korner; Theodore A. Kotchen; Eduardo M. Krieger; Brazil Kai Lau; Ronald M. Lauer; Jean-Francois Liard; Marshall D. Lindheimer; Friedrich C. Luft; Giuseppe Mancia; Harry S. Margolius; David A. McCarron; Oregon John; C. McGiff; Trefor O. Morgan; Michael J. Mulvany; Kazuo Murakami; Gary Nicholls; Michael J. Peach; Marc A. Pfeffer; V. Postnov; Morton P. Printz; John P. Rapp; John L. Reid; Donald J. Reis; J. Carlos Romero; E. Safar; A. Guillermo Scicli; T. Shepherd; Thomas Unger; Paul M. Vanhoutte; Stephen F. Vatner; Ronald G. Victor; B. Gunnar Wallin; Gordon H. Williams; Roger R. Williams; Vermont Margaret Foti; Mary Jane Jesse; Clyde E. Johnson; Ben G. Zimmerman



Effect of chronic treatment with enalapril on glucose tolerance and serum insulin in non-insulin-resistant Japanese patients with essential hypertension  

Microsoft Academic Search

The effect of enalapril, an angiotensin converting enzyme inhibitor, on glucose tolerance and serum insulin response to a glucose load has been evaluated in 8 non-obese patients (3 women and 5 men) with untreated essential hypertension (WHO Stage I or II) and without insulin resistance. Following a 2-month run-in control period, each patient received oral enalapril 10 mg once daily

T. Baba; T. Kodama; T. Ishizaki



Prophylactic treatment with telmisartan induces tissue-specific gene modulation favoring normal glucose homeostasis in Cohen-Rosenthal diabetic hypertensive rats.  


The objectives were to assess the potential of long-term prophylactic administration of telmisartan, an angiotensin II receptor antagonist and a partial peroxisome proliferator activator receptor (PPAR)? agonist, in preventing the development of hypertension and hyperglycemia and to demonstrate the alteration in gene expression associated with the development of hyperglycemia and insulin resistance in Cohen-Rosenthal diabetic hypertensive rat, a unique model of hypertension and type 2 diabetes mellitus comorbidity. Cohen-Rosenthal diabetic hypertensive rats were continuously treated with telmisartan (3 mg/[kg d]) starting at age 6 to 8 weeks before developing hypertension or diabetes. Weight changes, blood pressure, blood insulin, adiponectin, glucose tolerance, and insulin sensitivity were monitored. Fat, liver, and muscle messenger RNAs were examined for the expression of genes potentially involved in the onset of insulin resistance. In addition to the expected antihypertensive effect of prophylactic telmisartan, diabetes was blunted, evidenced at the end of the study by a significantly lower glucose level. This was accompanied by improved glucose tolerance, increased sensitivity to insulin, reduction in fasting insulin levels and homeostasis model assessment index, as well as an increase in serum adiponectin. Telmisartan also prevented the increase in serum triglycerides and the associated appearance of lipid droplets in the liver. Diabetes induced tissue-specific changes in messenger RNAs expression of the following selected genes, which were restored by telmisartan treatment: PPAR?, PPAR?, PPAR? coactivator 1?, adiponectin, adiponectin receptor 1, adiponectin receptor 2, phosphotyrosine binding domain and a pleckstrin homology domain-containing adaptor protein, adenosine monophosphate kinase, and glucose translocator 4. Telmisartan blunted the development of hypertension, insulin resistance, and diabetes in prediabetic Cohen-Rosenthal diabetic hypertensive rats through pleiotropic activity, involving specific gene regulation of target organs. PMID:21820685

Younis, Firas; Oron, Yoram; Limor, Rona; Stern, Naftali; Rosenthal, Talma



Lack of interaction of beta-cell function-associated variants with hypertension on change in fasting glucose and diabetes risk: the Framingham Offspring Study  

PubMed Central

Objective To test if pancreatic beta-cell genetic frailty and hypertension interact in their associations with change over time in fasting glucose (?FG) or type-2 diabetes (T2D) risk. Methods and results We pooled data from 3,471 Framingham Offspring Study participants into 6 ~4-yr periods (15,852 person-exams; mean age 52; 54% women). We defined two genetic exposures reflecting beta-cell genetic risk burden: single nucleotide polymorphism (SNP) score counts of FG- and T2D–associated risk alleles at 16 and 33 putative beta-cell loci, respectively; and three hypertension exposures: 1)hypertension vs. no-hypertension; 2)treated vs. untreated-hypertension; and 3)five mutually-exclusive anti-hypertensive categories (beta-blockers, thiazides, renin-angiotensin system agents, combinations, others) vs. untreated-hypertension. We tested ~4-year mean ?FG or odds of T2D by per-risk allele score change and hypertension category, seeking genetic score-by-hypertension interaction. Genetic scores increased ~4-yr ?FG (0.6 mg/dl per-risk allele; p=8.9×10?16) and T2D–risk (~17% per-risk allele; p=2.1×10?7). Versus no-hypertension, hypertension conferred higher ?FG (2.6 vs. 1.7 mg/dl; p<0.0001) and T2D–risk (OR=2.9, 95% CI [2.8–3.0]; p<0.0001). Versus untreated-hypertension, treated hypertension conferred higher ?FG (3.4 vs. 3.0 mg/dl; p<0.0001) and T2D–risk (OR=1.4 [1.3–1.5]; p=0.02). Beta-blockers (OR=1.6 [1.1–2.4]), combinations (OR=1.6 [1.1–2.5]) and others (OR=2.0 [1.4–2.9]) increased T2D–risk (all p<0.02). In joint models including interaction terms, all genetic score-by-hypertension interaction terms were p>0.05. In joint models without interaction, FG-SNP or T2D–SNP genetic scores (both p<0.001) and hypertension (p<0.0001) independently increased ?FG or T2D–risk. Conclusion Hypertension, hypertension treatment and common FG-/T2D–SNP genetic scores independently predicted ?FG and T2D incidence, but did not modify each other’s association with ?FG or T2D risk.

de Miguel-Yanes, JM; Porneala, B; Pencina, MJ; Fox, CS; Florez, JC; Siscovick, DS; Dupuis, J; Meigs, JB



An argument for intolerance.  


"Multiculturalism", "pluralism" and "tolerance" have become buzz words in applied ethics. While serious and well thought out work is going on in these areas, a misunderstanding of the importance of tolerance, and the difficulties raised by multicultural moral conflict seems common. In this paper I argue that intolerance of some cultural traditions is morally required, and suggest that the forging of a moral mono-culture is preferable to pluralism. PMID:11129841

Catherwood, J F



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)

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.

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



Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between Azelnidipine and amlodipine on glucose tolerance and endothelial function - a crossover trial (AGENT)  

PubMed Central

Background Hypertension is associated with impaired glucose tolerance and insulin resistance. Medical treatment that interferes with various steps in the renin-angiotensin system improves glucose tolerance and insulin resistance. However, it remains unclear if long-acting calcium channel blockers (CCBs) such as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in clinical practice. Methods Seventeen non-diabetic patients with essential hypertension who had controlled blood pressure levels using amlodipine (5 mg/day) were enrolled in this study. After randomization, either azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At baseline and the end of each CCB therapy, samples of blood and urine were collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition, hematopoietic progenitor cells (HPCs) were measured at each point by flow cytometry and endothelial functions were measured by fingertip pulse amplitude tonometry using EndoPAT. Results Although blood pressure levels were identical after each CCB treatment, the heart rate significantly decreased after azelnidipine administration than that after amlodipine administration (P < 0.005). Compared with amlodipine administration, azelnidipine significantly decreased levels of glucose and insulin 120 min after the 75 g OGTT (both P < 0.05). Serum levels of high-sensitivity C-reactive protein (P = 0.067) and interleukin-6 (P = 0.035) were decreased. Although endothelial functions were not different between the two medication groups, the number of circulating HPCs was significantly increased after azelnidipine administration (P = 0.016). Conclusions These results suggest that azelnidipine treatment may have beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory state, and number of circulating progenitor cells in non-diabetic patients with essential hypertension.



Lactose Intolerance in Children  


... Healthy Children Radio: Summer Camp (Audio) Substantial Fraction of American Youth Arrested By Age 23 Hypertension in the Child Athlete Pediatric First Aid for Caregivers and Teachers (PedFACTs) ...


The Driselase-treated fraction of rice bran is a more effective dietary factor to improve hypertension, glucose and lipid metabolism in stroke-prone spontaneously hypertensive rats compared to ferulic acid.  


The aim of this study is to investigate the effects of dietary supplementation with the Driselase-treated fraction (DF) of rice bran and ferulic acid (FA) on hypertension and glucose and lipid metabolism in stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP at 4 weeks of age were divided into three groups, and for 8 weeks were fed (1) a control diet based on AIN-93M, (2) a DF of rice bran-supplemented diet at 60 g/kg and (3) an FA-supplemented diet at 0.01 g/kg. Means and standard errors were calculated and the data were tested by one-way ANOVA followed by a least significance difference test. The results showed that both the DF and FA diets significantly improved hypertension as well as glucose tolerance, plasma nitric oxide (NOx), urinary 8-hydroxy-2'-deoxyguanosine and other parameters. In particular, compared to the FA diet, the DF diet produced a significant improvement in urinary NOx, hepatic triacylglycerol and several mRNA expressions of metabolic parameters involved in glucose and lipid metabolisms. The results of the metabolic syndrome-related parameters obtained from this study suggest that the DF diet is more effective than the FA diet. PMID:17217561

Ardiansyah; Shirakawa, Hitoshi; Koseki, Takuya; Hashizume, Katsumi; Komai, Michio



Beneficial effects of L- and N-type calcium channel blocker on glucose and lipid metabolism and renal function in patients with hypertension and type II diabetes mellitus.  


It has been proved that cilnidipine has N-type calcium channels inhibitory activity as well as L-type calcium channels and inhibits excessive release of norepinephrine from the sympathetic nerve ending. This study was undertaken to compare the efficacy of amlodipine (an inhibitor of L-type calcium channels) and cilnidipine (an inhibitor of both L-type and N-type calcium channels) in patients with hypertension and type II diabetes mellitus. Seventy-seven hypertensive patients were divided into two groups according to presence/absence of type II diabetes mellitus. In these two groups of patients, the effects of amlodipine and cilnidipine on glucose and lipid metabolism and renal function were compared. As for glucose and lipid metabolism, homeostasis model assessment insulin resistance (HOMA-R) level in the non-diabetic group and triglyceride in the diabetes group were significantly lower with cilnidipine than with amlodipine. As regards renal function in the diabetic group, estimated glomerular filtration rate (eGFR) was significantly higher and urinary albumin/creatinine ratio was significantly lower with cilnidipine than with amlodipine. Cilnidipine which inhibits N-type calcium channels is more useful for patients with hypertension and diabetes mellitus from its effects on glucose and lipid metabolism and renal function. PMID:20337636

Masuda, Takashi; Ogura, Misao N; Moriya, Tatsumi; Takahira, Naonobu; Matsumoto, Takuya; Kutsuna, Toshiki; Hara, Miyako; Aiba, Naoko; Noda, Chiharu; Izumi, Tohru



[Orthostatic intolerance syndromes].  


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

Gónzalez-Hermosillo, J A


Achievement of recommended glucose and blood pressure targets in patients with type 2 diabetes and hypertension in clinical practice - study rationale and protocol of DIALOGUE  

PubMed Central

Background Patients with type 2 diabetes have 2–4 times greater risk for cardiovascular morbidity and mortality than those without, and this is even further aggravated if they also suffer from hypertension. Unfortunately, less than one third of hypertensive diabetic patients meet blood pressure targets, and more than half fail to achieve target HbA1c values. Thus, appropriate blood pressure and glucose control are of utmost importance. Since treatment sometimes fails in clinical practice while clinical trials generally suggest good efficacy, data from daily clinical practice, especially with regard to the use of newly developed anti-diabetic and anti-hypertensive compounds in unselected patient populations, are essential. The DIALOGUE registry aims to close this important gap by evaluating different treatment approaches in hypertensive type 2 diabetic patients with respect to their effectiveness and tolerability and their impact on outcomes. In addition, DIALOGUE is the first registry to determine treatment success based on the new individualized treatment targets recommended by the ADA and the EASD. Methods DIALOGUE is a prospective observational German multicentre registry and will enrol 10,000 patients with both diabetes and hypertension in up to 700 sites. After a baseline visit, further documentations are scheduled at 6, 12 and 24 months. There are two co-primary objectives referring to the most recent guidelines for the treatment of diabetes and hypertension: 1) individual HbA1c goal achievement with respect to anti-diabetic pharmacotherapy and 2) individual blood pressure goal achievement with different antihypertensive treatments. Among the secondary objectives the rate of major cardio-vascular and cerebro-vascular events (MACCE) and the rate of hospitalizations are the most important. Conclusion The registry will be able to gain insights into the reasons for the obvious gap between the demonstrated efficacy and safety of anti-diabetic and anti-hypertensive drugs in clinical trials and their real world balance of effectiveness and safety.



Applying the correlation between glycosylated haemoglobin and plasma glucose levels  

Microsoft Academic Search

the classification of its results. In brief, it suggested restricting the diagnosis diabetes mellitus to degrees of glucose intolerance clearly associated with increased risk of later development of the specific complications of diabetes. For lesser degrees of glucose intolerance, previously called diabetes by some and normal by others, it proposed the new class of 'impaired glucose tolerance'. This 'at-risk' category

T. A. Welborn; M. Knuiman; R. E. Davis; K. Stanton; V. McCann; I. Constable



Hereditary fructose intolerance.  

PubMed Central

Hereditary fructose intolerance (HFI, OMIM 22960), caused by catalytic deficiency of aldolase B (fructose-1,6-bisphosphate aldolase, EC, 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

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



Impact of increasing carbohydrate intolerance on maternal-fetal outcomes in 3637 women without gestational diabetes  

Microsoft Academic Search

OBJECTIVE: Our purpose was to assess maternal-fetal outcomes in patients with increasing carbohydrate intolerance not meeting the current criteria for the diagnosis of gestational diabetes.STUDY DESIGN: We conducted a prospective analytic cohort study in which nondiabetic women aged ?24 years, receiving prenatal care in three Toronto teaching hospitals, were eligible for enrollment. A glucose challenge test and an oral glucose

Mathew Sermer; C. David Naylor; Douglas J. Gare; Anne B. Kenshole; J. W. K. Ritchie; Dan Farine; Howard R. Cohen; Karen McArthur; Stephen Holzapfel; Anne Biringer; Erluo Chen



An observational study comparing 2-hour 75-g oral glucose tolerance with fasting plasma glucose in pregnant women: both poorly predictive of birth weight  

Microsoft Academic Search

Background: The definition and treatment of glucose intolerance during pregnancy are matters of intense controversy. Our goal was to examine the value of the 75-g oral glucose tolerance test (OGTT) in terms of its ability to predict birth weight per- centile in a group of women with singleton pregnancies who received minimal treatment for their glucose intolerance. Methods: We reviewed

Christian Ouzilleau; Marie-Andrée Roy; Louiselle Leblanc; André Carpentier; Pierre Maheux



Hypertension, Diabetes and Overweight: Looming Legacies of the Biafran Famine  

PubMed Central

Background Sub-Saharan Africa is facing rapidly increasing prevalences of cardiovascular disease, obesity, diabetes and hypertension. Previous and ongoing undernutrition among pregnant women may contribute to this development as suggested by epidemiological studies from high income countries linking undernutrition in fetal life with increased burden of non-communicable diseases in later life. We undertook to study the risks for hypertension, glucose intolerance and overweight forty years after fetal exposure to famine afflicted Biafra during the Nigerian civil war (1967–1970). Methods and Findings Cohort study performed in June 27–July 31, 2009 in Enugu, Nigeria. Adults (n?=?1,339) born before (1965–67), during (1968–January 1970), or after (1971–73) the years of famine were included. Blood pressure (BP), random plasma glucose (p-glucose) and anthropometrics, as well as prevalence of hypertension (BP>140/90 mmHg), impaired glucose tolerance (IGT; p-glucose 7.8–11.0 mmol/l), diabetes (DM; p-glucose ?11.1 mmol/l), or overweight (BMI>25 kg/m2) were compared between the three groups. Fetal-infant exposure to famine was associated with elevated systolic (+7 mmHg; p<0.001) and diastolic (+5 mmHg; p<0.001) BP, increased p-glucose (+0.3 mmol/L; p<0.05) and waist circumference (+3cm, p<0.001), increased risk of systolic hypertension (adjusted OR 2.87; 95% CI 1.90–4.34), IGT (OR 1.65; 95% CI 1.02–2.69) and overweight (OR 1.41; 95% CI 1.03–1.93) as compared to people born after the famine. Limitations of this study include the lack of birth weight data and the inability to separate effects of fetal and infant famine. Conclusions Fetal and infant undernutrition is associated with significantly increased risk of hypertension and impaired glucose tolerance in 40-year-old Nigerians. Prevention of undernutrition during pregnancy and in infancy should therefore be given high priority in health, education, and economic agendas.

Chima, Charles; Edstedt Bonamy, Anna-Karin; Ozumba, Benjamin; Norman, Mikael



Lactose Intolerance and the Irritable Colon  

PubMed Central

Symptoms of lactase deficiency include nausea, abdominal pain, distension, bloating and diarrhea after ingesting foods which contain lactose. Lactose intolerance and bowel motility disorders have similar symptoms, and people with irritable bowel syndrome and unexplained abdominal pain may have lactose intolerance. A definite diagnosis can be made by detecting hydrogen in the breath after a lactose load, by lactase assay from a small bowel biopsy specimen or by lactose intolerance testing. Lactose intolerance is more likely in blacks, Asians and South Americans. If lactose intolerance is present without concomitant bowel motility disorder, the response to a lactose free diet is excellent.

McSherry, J. A.



Insulin sensitivity, glucose effectiveness, and ?-cell function in obese males with essential hypertension: Investigation of the effects of treatment with a calcium channel blocker (diltiazem) or an angiotensin-converting enzyme inhibitor (quinapril)  

Microsoft Academic Search

It has been suggested that hyperinsulinemia secondary to insulin resistance may be a pathogenetic factor common to obesity, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. Furthermore, ?-blockers and thiazide diuretics have been shown to be capable of increasing insulin resistance and thus of inducing NIDDM in predisposed individuals. We used the minimal model approach (MMA) to glucose metabolism and insulin kinetics

José Cabezas-Cerrato; Daniel A. Garcia-Estevez; David Araújo; Manuel Iglesias



Favourable effects of the Dietary Approaches to Stop Hypertension diet on glucose tolerance and lipid profiles in gestational diabetes: a randomised clinical trial.  


Although gestational diabetes mellitus (GDM) is associated with an increased risk of maternal and neonatal morbidity, there is no consensus as to the optimal approach of nutritional management in these patients. The present study was designed to assess the effect of the Dietary Approaches to Stop Hypertension (DASH) eating plan on glucose tolerance and lipid profiles of pregnant women with GDM. The present randomised controlled clinical trial was performed among thirty-four women diagnosed with GDM at 24-28 weeks of gestation. Subjects were randomly assigned to consume either the control diet (n 17) or the DASH eating pattern (n 17) for 4 weeks. The control diet was designed to contain 45-55% carbohydrates, 15-20% protein and 25-30% total fat. The macronutrient composition of the DASH diet was similar to the control diet; however, the DASH diet was rich in fruits, vegetables, whole grains and low-fat dairy products, and contained lower amounts of saturated fats, cholesterol and refined grains with a total of 2400 mg Na/d. Fasting blood samples were taken at baseline and after 4 weeks of intervention to measure fasting plasma glucose, glycated Hb (HbA1c) and lipid profiles. Participants underwent a 3 h oral glucose tolerance tests and blood samples were collected at 60, 120 and 180 min to measure plasma glucose levels. Adherence to the DASH eating pattern, compared with the control diet, resulted in improved glucose tolerance such that plasma glucose levels reduced at 60 (21·86 v. 20·45 mmol/l, Pgroup = 0·02), 120 (22·3 v. 0·2 mmol/l, Pgroup = 0·001) and 180 min (21·7 v. 0·22 mmol/l, Pgroup = 0·002) after the glucose load. Decreased HbA1c levels (20·2 v. 0·05 %, Pgroup = 0·001) was also seen in the DASH group compared with the control group. Mean changes for serum total (20·42 v. 0·31 mmol/l, Pgroup = 0·01) and LDL-cholesterol (20·47 v. 0·22 mmol/l, Pgroup = 0·005), TAG (20·17 v. 0·34 mmol/l, Pgroup = 0·01) and total:HDL-cholesterol ratio (20·6 (SD 0·9) v. 0·3 (SD 0·8), Pgroup = 0·008) were significantly different between the two diets. Additionally, consumption of the DASH diet favourably influenced systolic blood pressure (22·6 v. 1·7 mmHg, Pgroup = 0·001). Mean changes of fasting plasma glucose (20·29 v. 0·15 mmol/l, Pgroup = 0·09) were nonsignificant comparing the DASH diet with the control diet. In conclusion, consumption of the DASH eating pattern for 4 weeks among pregnant women with GDM resulted in beneficial effects on glucose tolerance and lipid profiles compared with the control diet. PMID:23148885

Asemi, Zatollah; Tabassi, Zohreh; Samimi, Mansooreh; Fahiminejad, Taherh; Esmaillzadeh, Ahmad



Lactose intolerance and health disparities among African Americans and Hispanic Americans: an updated consensus statement.  


Dairy foods contribute nine essential nutrients to the diet including calcium, potassium and vitamin D; nutrients identified by the 2010 Dietary Guidelines for Americans as being "of public health concern" within the U.S. population. Milk and milk product intake is associated with better diet quality and has been associated with a reduced risk of chronic diseases or conditions including hypertension, cardiovascular disease, metabolic syndrome, Type 2 Diabetes and osteoporosis. Some research also indicates dairy food intake may be linked to reduced body fat, when accompanied by energy-restriction. On average, both African Americans and Hispanic Americans consume less than the recommended levels of dairy foods, and perceived or actual lactose intolerance can be a primary reason for limiting or avoiding dairy intake. True lactose intolerance prevalence is not known because healthcare providers do not routinely measure for it, and no standardized assessment method exists. Avoiding dairy may lead to shortfalls of essential nutrients and increased susceptibility to chronic disease. This updated Consensus Statement aims to provide the most current information about lactose intolerance and health, with specific relevance to the African American and Hispanic American communities. Topics covered include diagnostic considerations, actual and recommended dairy food intake and levels of consumption of key dairy nutrients among African Americans and Hispanic Americans; prevalence of self-reported lactose intolerance among various racial/ethnic groups; the association between dairy food intake, lactose intolerance and chronic disease; and research-based management recommendations for those with lactose intolerance. PMID:24079212

Bailey, Rahn K; Fileti, Cecelia Pozo; Keith, Jeanette; Tropez-Sims, Susanne; Price, Winston; Allison-Ottey, Sharon Denise



Fructose Intolerance: An Under-Recognized Problem  

Microsoft Academic Search

OBJECTIVES:Although the role of lactose intolerance in the pathogenesis of abdominal symptoms is well known, the role of fructose intolerance is unclear. Our aims were 1) to examine the prevalence of fructose intolerance in patients with unexplained abdominal symptoms, and 2) to explore whether fructose concentration influences fructose breath test.METHODS:Over 2 yr, patients with unexplained symptoms answered questionnaires and underwent

Young K. Choi; Fredrick C. Johlin; Robert W. Summers; Michelle Jackson; Satish S. C. Rao



The concentration of oxygen, lactate and glucose in the central veins, right heart, and pulmonary artery: a study in patients with pulmonary hypertension  

PubMed Central

Introduction Decreases in oxygen saturation (SO2) and lactate concentration [Lac] from superior vena cava (SVC) to pulmonary artery have been reported. These gradients (?SO2 and ?[Lac]) are probably created by diluting SVC blood with blood of lower SO2 and [Lac]. We tested the hypothesis that ?SO2 and ?[Lac] result from mixing SVC and inferior vena cava (IVC) blood streams. Methods This was a prospective, sequential, observational study of hemodynamically stable individuals with pulmonary artery hypertension (n = 9) who were about to undergo right heart catheterization. Catheters were advanced under fluoroscopic guidance into the IVC, SVC, right atrium, right ventricle, and pulmonary artery. Samples were obtained at each site and analyzed for SO2, [Lac], and glucose concentration ([Glu]). Analysis of variance with Tukey HSD test was used to compare metabolite concentrations at each site. Results There were no differences in SO2 or [Lac] between IVC and SVC, both being greater than their respective pulmonary artery measurements (P < 0.01 for SO2 and P < 0.05 for [Lac]). SO2 and [Lac] in right atrium, right ventricle, and pulmonary artery were similar. ?SO2 was 4.4 ± 1.4% (mean ± standard deviation) and ?[Lac] was 0.16 ± 0.11 mmol/l (both > 0; P < 0.001). ?[Glu] was -0.19 ± 0.31 mmol/l, which was not significantly different from zero, with SVC [Glu] being less than IVC [Glu]. Conclusion Mixing of SVC with IVC blood does not account for the development of ?SO2 and ?[Lac] in hemodynamically stable individuals with pulmonary artery hypertension. An alternate mechanism is mixing with coronary sinus blood, implying that ?SO2 and ?[Lac] may reflect changes in coronary sinus SO2 and [Lac] in this patient population.

Gutierrez, Guillermo; Venbrux, Anthony; Ignacio, Elizabeth; Reiner, Jonathan; Chawla, Lakhmir; Desai, Anish



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


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

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



Insulin secretion capacity in the development from normal glucose tolerance to type 2 diabetes  

Microsoft Academic Search

We have examined the contribution of insulin secretion and insulin resistance to glucose intolerance in Japanese. Some indices of insulin secretion and insulin sensitivity based on the results of OGTT were used. The decline of insulin secretion capacity was significant throughout the development of glucose intolerance from NGT via IGT to DM. Decreased insulinogenic indices were conspicuous when it is

Mitsuo Fukushima; Haruhiko Suzuki; Yutaka Seino



Common syndromes of orthostatic intolerance.  


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

Stewart, Julian M




Technology Transfer Automated Retrieval System (TEKTRAN)

There is an increased requirement for selenium during pregnancy, presumably for fetal growth, which manifests as decreasing maternal blood and tissue selenium concentrations. These decreases are greater in pregnant women with gestational or pre-existing diabetes. We measured selenium status and gluc...


Management of portal hypertension  

PubMed Central

Treatment of portal hypertension is evolving based on randomised controlled trials. In acute variceal bleeding, prophylactic antibiotics are mandatory, reducing mortality as well as preventing infections. Terlipressin or somatostatin combined with endoscopic ligation or sclerotherapy is the best strategy for control of bleeding but there is no added effect of vasoactive drugs on mortality. Non-selective ß-blockers are the first choice therapy for both secondary and primary prevention; if contraindications or intolerance to ß-blockers are present then band ligation should be used. Novel therapies target the increased intrahepatic resistance caused by microcirculatory intrahepatic deficiency of nitric oxide and contraction of activated intrahepatic stellate cells.

Samonakis, D; Triantos, C; Thalheimer, U; Patch, D; Burroughs, A



Deconditioning in patients with orthostatic intolerance  

PubMed Central

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] 22–37 years). Symptom duration was 4 years (IQR 2–7.8). 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.

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



Freezing tolerance\\/intolerance and cryoprotectant synthesis in terrestrially overwintering anurans in the Great Plains, USA  

Microsoft Academic Search

Mechanistic bases for freezing tolerance in anurans have been well-studied only in wood frogs, Rana sylvatica, so comprehensive explanations for the mechanisms and evolution of freezing tolerance in anurans are lacking. We measured crystallization temperatures, freezing tolerance\\/intolerance, and tissue glucose and glycogen phosphorylase activities in frozen and unfrozen winter-acclimated Pseudacris triseriata, Bufo cognatus and B. woodhousei. Freezing occurred at higher

D. L. Swanson; B. M. Graves; K. L. Koster



Dairy intake, dietary adequacy, and lactose intolerance.  


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

Heaney, Robert P



Management of diabetic hypertensives  

PubMed Central

Hypertension occurs twice as commonly in diabetics than in comparable nondiabetics. Patients with both disorders have a markedly higher risk for premature microvascular and macrovascular complications. Aggressive control of blood pressure (BP) reduces both micro- and macrovascular complications. In diabetic hypertensives, angiotensin converting enzyme inhibitors (ACEIs) are the first line in management of hypertension, and can be replaced by angiotensin II receptor blockers (ARBs) if patients are intolerant of them. Recent studies suggest ARBs to be on par with ACEI in reducing both macro- and microvascular risks. Adding both these agents may have a beneficial effect on proteinuria, but no extra macrovascular risk reduction. Thiazides can also be used as first line drugs, but are better used along with ACEI/ARBs. Beta-blockers [especially if the patient has coronary artery disease] and calcium channel blockers are used as second line add-on drugs. Multidrug regimens are commonly needed in diabetic hypertensives. Achieving the target BP of <130/80 is the priority rather than the drug combination used in order to arrest and prevent the progression of macro- and microvascular complications in diabetic hypertensives.

Ganesh, Jai; Viswanathan, Vijay



Hypertension in rats deficient in copper  

SciTech Connect

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 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.

Klevay, L.M.



Toward universal criteria for gestational diabetes: The 75-gram glucose tolerance test in pregnancy  

Microsoft Academic Search

OBJECTIVES: The purpose of this study was to determine the distribution of values for the 75 gm glucose tolerance test in pregnancy and to define glucose intolerance by the relationship between maternal glucose values and neonatal macrosomia.STUDY DESIGN: A total 3505 unselected pregnant women were given a 75 gm, 2-hour glucose tolerance test. Diet or insulin therapy was offered only

David A. Sacks; Jeffrey S. Greenspoon; Salim Abu-Fadil; Harold M. Henry; Girma Wolde-Tsadik; Janis F. F. Yao



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)

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.

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



Heat Intolerance, Heat Exhaustion Monitored: A Case Report.  

National Technical Information Service (NTIS)

A 32 year-old male (S.H.) monitored during an 8-day heat acclimation (HA) investigation, unexpectedly exhibited heat intolerance and heat exhaustion. Thirteen other males completed HA without indications of either heat intolerance or heat exhaustion. Beca...

L. E. Armstrong R. W. Hubbard P. C. Szlyk I. V. Sils W. J. Kraemer



Orthostatic intolerance in the chronic fatigue syndrome  

Microsoft Academic Search

This study aims to investigate the prevalence and pathophysiology of orthostatic intolerance (OI) and its potential contribution to symptoms of a group of unselected patients with chronic fatigue syndrome (CFS). Seventy five patients (65 women, 10 men) with CFS were evaluated. During an initial visit, a clinical suspicion as to the likelihood of observing laboratory evidence of OI was assigned.

Ronald Schondorf; Julie Benoit; Theodore Wein; Denis Phaneuf



Food intolerance and the irritable bowel syndrome  

Microsoft Academic Search

Two hundred patients (156 women) with the irritable bowel syndrome were treated with dietary exclusion for three weeks. Of the 189 who completed this study, 91 (48.2%) showed symptomatic improvement. Subsequent challenge with individual foods showed that 73 of these 91 responders were able to identify one or more food intolerances and 72 remained well on a modified diet during

R Nanda; R James; H Smith; C R Dudley; D P Jewell



High liver glycogen in hereditary fructose intolerance  

Microsoft Academic Search

A case of hereditary fructose intolerance is reported in a girl aged 2 years at the time of her death. She had apparently progressed normally until the age of 14 months. At 19 months she was admitted to hospital with failure to thrive, hepatomegaly, and superficial infections. Investigations revealed hypoglycaemia, persistent acidosis, aminoaciduria, and a high liver glycogen level which

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



Dermatitis herpetiformis intolerant to dapsone in Aids.  


A 35-year-old man with AIDS and pulmonary tuberculosis presented with lesions suggestive of dermatitis herpetiformis and intolerance to dapsone. He was managed successfully with a combination of nicotinamide 200 mg/day and indomethacin 75 mg/day, topical steroids and gluten free diet. PMID:20885054

Krishna, K; Kavitha, K


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


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 glucose·g(-1)·2 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

Pravenec, Michal; Zídek, Václav; Landa, Vladimír; Simáková, Miroslava; Mlejnek, Petr; Silhavy, Jan; Maxová, Martina; Kazdová, Ludmila; Seidman, Jonathan G; Seidman, Christine E; Eminaga, Seda; Gorham, Joshua; Wang, Jiaming; Kurtz, Theodore W



It’s too difficult! Frustration intolerance beliefs and procrastination  

Microsoft Academic Search

Beliefs regarding intolerance of frustration are central to the theory of Rational Emotive Behaviour Therapy (REBT) and are hypothesised as playing an important role in procrastination. However, there is evidence that frustration intolerance may involve several dimensions. To investigate the relative contribution of these dimensions, a multidimensional measure of frustration intolerance beliefs was employed in a student sample (n=86). The

Neil Harrington



Diabetic population mortality and cardiovascular risk attributable to hypertension: A decade follow-up from the Tehran Lipid and Glucose Study.  


Abstract To determine the extent to which burden of cardiovascular disease (CVD) outcomes among diabetic population is attributable to hypertension. Nine-year follow-up data were secured for 7068 participants aged ? 20 years old, free from CVD at baseline. Cox proportional hazards regression was implemented to estimate hazard ratios (HRs) of hypertension. Population-attributable hazard fraction (PAHF) was used to assess proportion of diabetic population hazard of CVD events and mortality attributable to hypertension. In the whole population, irrespective of diabetes or hypertension status, incidence rate (95% CI) of CVD, coronary heart disease (CHD), as well as CVD and all-cause mortality per 1000 person-year were 8.3 (7.6-9.0), 7.1 (6.5-7.8), 1.8 (1.5-2.1) and 3.9 (3.5-4.5), respectively. Among diabetes participants, hypertension was a risk factor for CHD (HR = 1.63, 95% CI 1.15-2.03), CVD (HR = 1.74, 95% CI 1.50-2.41), CVD mortality (HR = 1.65, 95% CI 0.87-3.12) and all-cause mortality (HR = 1.53, 95% CI 0.97-2.42). HRs, however, were not statistically significant for all-cause or CVD mortality. PAHFs (%) of hypertension was 27.5 (95% CI 8.3-42.6) for CHD, 29.6 (95% CI 10.6-44.4) for CVD, 27.9 (95% CI - 17.2 to 55.7) for CVD mortality and 22.6 (95% CI - 5.9 to 43.4) for all-cause mortality. Our study shows that there is an excess risk of CVD in hypertensive patients with diabetes related to inadequate control of blood pressure. PMID:23458066

Bozorgmanesh, Mohammadreza; Hadaegh, Farzad; Mohebi, Reza; Ghanbarian, Arash; Eskandari, Fatemeh; Azizi, Fereidoun



High prevalence of undiagnosed diabetes and abnormal glucose tolerance in the Iranian urban population: Tehran Lipid and Glucose Study  

Microsoft Academic Search

BACKGROUND: To estimate the prevalence of diagnosed and undiagnosed diabetes mellitus, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG\\/IGT in a large urban Iranian population aged ? 20 years. METHODS: The study population included 9,489 participants of the Tehran Lipid and Glucose Study with full relevant clinical data. Age-standardized prevalence of diabetes and glucose intolerance categories were

Farzad Hadaegh; Mohammad Reza Bozorgmanesh; Asghar Ghasemi; Hadi Harati; Navid Saadat; Fereidoun Azizi



Prevalence and Predictors of Risk for Type 2 Diabetes Mellitus and Impaired Glucose Tolerance in Polycystic Ovary Syndrome: A Prospective, Controlled Study in 254 Affected Women  

Microsoft Academic Search

Women with polycystic ovary syndrome (PCOS) are insulin resis- tant, have insulin secretory defects, and are at high risk for glucose intolerance. We performed this study to determine the prevalence of glucose intolerance and parameters associated with risk for this in PCOS women. Two-hundred and fifty-four PCOS women, aged 14 - 44 yr, were prospectively evaluated at 2 centers, 1



Syndromes of orthostatic intolerance: a hidden danger.  


Orthostatic hypotension (OH) is a relatively common heterogenous and multifactorial disorder, traditionally classified as neurogenic (less common but often more severe) or nonneurogenic (more common, with no direct signs of autonomic nervous system disease). The different clinical variants of orthostatic intolerance include initial, classical and delayed OH as well as postural tachycardia syndrome. Orthostatic instability may induce syncopal attacks either alone or in combination with other mechanisms, and is often dismissed as a precipitating factor. Moreover, prevalent OH is an independent risk factor for all-cause mortality and cardiovascular morbidity, and the majority of patients with OH are asymptomatic or have few nonspecific symptoms. Management of symptomatic orthostatic intolerance includes both nonpharmacological and pharmacological methods, but it is not always successful and may lead to complications. Future studies of OH should focus on mechanisms that lead to neurogenic and nonneurogenic OH, novel diagnostic methods and more effective therapeutic modalities. PMID:23216860

Fedorowski, A; Melander, O



Galactose intolerance and the risk of cataract.  

PubMed Central

Cataracts may arise in association with various major and minor disorders restricting galactose metabolism, and the risk is broadly associated with the degree of galactose intolerance. A family is described in which a girl presented at the age of 7 3/4 years with cataracts, galactosuria, and partial deficiencies of the enzymes galactokinase and galactose-1-phosphate uridyl transferase. Galactose intolerance as determined by an oral test was impaired and fluctuated with variation in activity of the above galactose enzymes. Minor defects were also present in the parents and a maternal half-brother. The child has a compound disorder of galactose metabolism differing from those previously described. Assessment of galactose tolerance may be useful in the investigation of families with an incidence of cataract. Images

Winder, A. F.; Fells, P.; Jones, R. B.; Kissun, R. D.; Menzies, I. S.; Mount, J. N.



Lactose intolerance: diagnosis, genetic, and clinical factors  

PubMed Central

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.

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



Management of the Patient with Statin Intolerance  

Microsoft Academic Search

Current guidelines recommend statins as first-line therapy for reducing low-density lipoprotein cholesterol (LDL-C) and preventing\\u000a cardiovascular events. Patients taking statins frequently experience adverse effects during therapy. The first step is to\\u000a determine whether the adverse effects are indeed related to statin therapy by statin dechallenge and rechallenge. Strategies\\u000a for managing statin intolerance include changing statins, intermittent dosing, intensification of lifestyle

Byron F. Vandenberg; Jennifer Robinson



Evaluating the glucose tolerance test in mice.  


The objective of this study was to determine the optimal conditions under which to assess glucose tolerance in chow- and high-fat-fed C57BL/6J mice. Mice were fed either chow or high-fat diet for 8 wk. Variables tested were fasting duration (0-, 3-, 6-, and 24-h and overnight fasting), route of administration (intraperitoneal vs. oral) load of glucose given (2, 1, or 0.5 g/kg and fixed 50-mg dose), and state of consciousness. Basal glucose concentrations were increased in high-fat- compared with chow-fed mice following 6 h of fasting (9.1 +/- 0.3 vs. 7.9 +/- 0.4 mmol/l P = 0.01). Glucose tolerance was most different and therefore significant (P = 0.001) in high-fat-fed mice after 6 h of fasting (1,973 +/- 96 vs. 1,248 +/- 83 mmol.l(-1).120 min(-1)). The difference in glucose tolerance was greater following an OGTT (142%), in contrast to an IPGTT, with a 127% difference between high fat and chow. We also found that administering 2 g/kg of glucose resulted in a greater level of significance (P = 0.0008) in glucose intolerance in high-fat- compared with chow-fed mice. A fixed dose of 50 mg glucose regardless of body weight was enough to show glucose intolerance in high-fat- vs. chow-fed mice. Finally, high-fat-fed mice showed glucose intolerance compared with their chow-fed counterparts whether they were tested under conscious or anesthetized conditions. We conclude that 2 g/kg glucose administered orally following 6 h of fasting is best to assess glucose tolerance in mice under these conditions. PMID:18812462

Andrikopoulos, Sofianos; Blair, Amy R; Deluca, Nadia; Fam, Barbara C; Proietto, Joseph



Statin intolerance: now a solved problem.  


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

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


Obesity hypertension  

Microsoft Academic Search

The association between obesity and hypertension is well recognized. However, the exact mechanisms whereby obesity causes hypertension are complex and multifactorial. The current article summarizes some of the known mechanisms responsible for obesity hypertension.

Albert P. Rocchini



Obesity hypertension.  


The association between obesity and hypertension is well recognized. However, the exact mechanisms whereby obesity causes hypertension are complex and multifactorial. The current article summarizes some of the known mechanisms responsible for obesity hypertension. PMID:11866230

Rocchini, Albert P



Glycogen synthase kinase 3 inhibition improves insulin-stimulated glucose metabolism but not hypertension in high-fat-fed C57BL\\/6J mice  

Microsoft Academic Search

Aims\\/hypothesis  In the current study, the effect of a highly specific peptide inhibitor of glycogen synthase kinase 3 (GSK3) (L803-mts) on\\u000a glucose metabolism and BP was examined in a high-fat (HF) fed mouse model of diabetes.\\u000a \\u000a \\u000a \\u000a Methods  C57\\/BL6J mice were placed on an HF diet for 3 months and treated with L803-mts for 20 days, following which glucose metabolism\\u000a was examined by euglycaemic–hyperinsulinaemic clamp

R. Rao; C.-M. Hao; R. Redha; D. H. Wasserman; O. P. McGuinness; M. D. Breyer



Glucose Homeostasis of Man in Helium-Oxygen at 1-50 Atmospheres Absolute.  

National Technical Information Service (NTIS)

Divers who inhabit hyperbaric, hyperoxic atmospheres of helium-oxygen (He-O2) are said to exhibit hypoglycemia, rather than the glucose intolerance observed in men exposed to hypobaric hyperoxia, simulated weightlessness, or other environmental stresses. ...

L. W. Raymond J. Sode W. P. Spaur D. E. Uddin R. Johnsonbaugh



The compelling anomaly of chemical intolerance.  


In science, anomalies expose the limitations of existing paradigms and drive the search for new ones. In the late 1800s, physicians observed that certain illnesses spread from sick, feverish individuals to those contacting them, paving the way for the germ theory of disease. The germ theory served as a crude, but elegant formulation that explained dozens of seemingly unrelated illnesses affecting literally every organ system. Today, we are witnessing another medical anomaly-a unique pattern of illness involving chemically exposed groups in more than a dozen countries, who subsequently report multisystem symptoms and new-onset chemical, food, and drug intolerances. These intolerances may be the hallmark for a new disease process or paradigm, just as fever is a hallmark for infection. The fact that diverse demographic groups, sharing little in common except some initial chemical exposure event, develop these intolerances is a compelling anomaly pointing to a possible new theory of disease, one that has been referred to as "Toxicant-Induced Loss of Tolerance" ("TILT"). TILT has the potential to explain certain cases of asthma, migraine headaches, and depression, as well as chronic fatigue, fibromyalgia, and "Gulf War syndrome". It appears to evolve in two stages: (1) initiation, characterized by a profound breakdown in prior, natural tolerance resulting from either acute or chronic exposure to chemicals (pesticides, solvents, indoor air contaminants, etc.), followed by (2) triggering of symptoms by small quantities of previously tolerated chemicals (traffic exhaust, fragrances, gasoline), foods, drugs, and food/drug combinations (alcohol, caffeine). While the underlying dynamic remains an enigma, observations indicating that affected individuals respond to structurally unrelated drugs and experience cravings and withdrawal-like symptoms, paralleling drug addiction, suggest that multiple neurotransmitter pathways may be involved. PMID:12000012

Miller, C S



Severity of HCV-Induced Liver Damage Alters Glucose Homeostasis in Noncirrhotic Patients with Chronic HCV Infection  

Microsoft Academic Search

Background\\/Aims: To investigate the link between hepatitis C infection and glucose intolerance, we measured insulin sensitivity, glucose effectiveness and ?-cell secretion in noncirrhotic HCV-infected patients with normal glucose tolerance according to WHO criteria as assessed by oral glucose tolerance tests. Methods: Glucose, insulin and C-peptide data from frequently sampled intravenous glucose tolerance tests were analyzed using the minimal modeling technique

T. Konrad; S. Zeuzem; G. Toffolo; P. Vicini; G. Teuber; D. Briem; J. Lormann; T. Lenz; G. Herrmann; A. Berger; C. Cobelli; K.-H. Usadel



Clinical impact of mild carbohydrate intolerance in pregnancy: A study of 2904 nondiabetic Danish women with risk factors for gestational diabetes mellitus  

Microsoft Academic Search

Objective: The objective was to study the clinical impact of mild carbohydrate intolerance in pregnant women with risk factors for gestational diabetes mellitus. Study Design: This was a historical cohort study of 2904 pregnant women examined for gestational diabetes on the basis of risk factors. Information on oral glucose tolerance test results and clinical outcomes was collected from laboratory charts

Dorte M. Jensen; Peter Damm; Bente Sørensen; Lars Mølsted-Pedersen; Jes G. Westergaard; Joachim Klebe; Henning Beck-Nielsen



Dietary fructose intolerance: diet modification can impact self-rated health and symptom control.  


Carbohydrate intolerance to lactose is widely accepted as a cause of gastrointestinal symptoms, but controversy persists on how important dietary fructose intolerance (DFI) is in causing gastrointestinal pain and suffering and if an elimination diet can control the presenting complaints. The objective of this study was to identify a group of well-defined DFI patients and explore whether dietary education followed by dietary compliance could control symptoms and improve quality of life. During a 5-year period, patients referred to a pancreato-biliary clinic were evaluated for dietary carbohydrate intolerances if they presented with gastrointestinal pain and/or gas and/or bloating and/or diarrhea. Patients were tested with a standardized mixture of glucose, fructose, and lactose diluted in sterile water. End-expiratory breath samples were collected for hydrogen and methane measurement. Symptoms were scored using a 9-point symptom questionnaire. The patients underwent in-depth education by a dietician, and were provided with access to a cookbook, a newsletter, and a support group. A dietary questionnaire was used to evaluate compliance with the fructose-restricted diet. DFI can cause significant gastrointestinal symptoms that may not respond to medications or surgical interventions. Symptoms can improve and self-rated health does improve in DFI patients willing to adhere to a low fructose diet. PMID:15624540

Johlin, Frederick C; Panther, Mary; Kraft, Nancy


Redox status and lipid peroxidation in alcoholic hypertensive patients and alcoholic hypertensive patients with diabetes  

Microsoft Academic Search

Background: Free radical-mediated oxidative stress has been implicated in the progression of alcoholic hypertension and diabetic hypertension. Methods: The lipid peroxides and antioxidant status of plasma and erythrocytes were investigated in alcoholic hypertensive patients and alcoholic hypertensive patients with diabetes and compared with normal subjects. Results: A significant increase is observed in the levels of glucose, lipid peroxidation (P<0.05) in

R. M. Veerappan; S. Senthil; M. Ramakrishna Rao; R. Ravikumar; K. V. Pugalendi



Nutritional regulation of hepatic glucose metabolism in fish  

Microsoft Academic Search

Glucose plays a key role as energy source in the majority of mammals, but its importance in fish appears limited. Until now,\\u000a the physiological basis for such apparent glucose intolerance in fish has not been fully understood. A distinct regulation\\u000a of hepatic glucose utilization (glycolysis) and production (gluconeogenesis) may be advanced to explain the relative inability\\u000a of fish to efficiently

P. Enes; S. Panserat; S. Kaushik; A. Oliva-Teles



Refining the Measurement of Distress Intolerance  

PubMed Central

Distress intolerance is an important transdiagnostic variable that has long been implicated in the development and maintenance of psychological disorders. Self-report measurement strategies for distress intolerance have emerged from several different models of psychopathology and these measures have been applied inconsistently in the literature in the absence of a clear gold standard. The absence of a consistent assessment strategy has limited the ability to compare across studies and samples, thus hampering the advancement of this research agenda. This study evaluated the latent factor structure of existing measures of DI to examine the degree to which they are capturing the same construct. Results of confirmatory factor analysis in 3 samples totaling 400 participants provided support for a single factor latent structure. Individual items of these four scales were then correlated with this factor to identify those that best capture the core construct. Results provided consistent supported for 10 items that demonstrated the strongest concordance with this factor. The use of these 10 items as a unifying measure in the study of DI and future directions for the evaluation of its utility are discussed.

McHugh, R. Kathryn; Otto, Michael W.



Refining the measurement of distress intolerance.  


Distress intolerance is an important transdiagnostic variable that has long been implicated in the development and maintenance of psychological disorders. Self-report measurement strategies for distress intolerance (DI) have emerged from several different models of psychopathology and these measures have been applied inconsistently in the literature in the absence of a clear gold standard. The absence of a consistent assessment strategy has limited the ability to compare across studies and samples, thus hampering the advancement of this research agenda. This study evaluated the latent factor structure of existing measures of DI to examine the degree to which they are capturing the same construct. Results of confirmatory factor analysis in three samples totaling 400 participants provided support for a single-factor latent structure. Individual items of these four scales were then correlated with this factor to identify those that best capture the core construct. Results provided consistent support for 10 items that demonstrated the strongest concordance with this factor. The use of these 10 items as a unifying measure in the study of DI and future directions for the evaluation of its utility are discussed. PMID:22697451

McHugh, R Kathryn; Otto, Michael W



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

PubMed Central

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 Dartmouth–Northern 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 non–chemically 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.

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



Gestational diabetes, pregnancy hypertension, and late vascular disease.  


The complexity of the several pathogenic pathways that cause hypertension and vascular disease and the prolonged interval that appears to predate clinical morbidity have hindered inquiry into the association between GDM and vascular disorders. As a forme fruste of later type 2 diabetes, GDM-affected gravidas are identified as at risk of diabetes-related atherosclerosis, glomerular disruption, and pathogenic retinal angio-genesis. That GDM is evidence for underlying chronic conditions such as dysregulation of innate immune response that, independent of the diabetic state, produces vascular disease is difficult state, produces vascular disease is difficult to assert with the present published literature. Cross-sectional studies of patients with established gestational hypertension or preeclampsia are ambiguous as to the possible pathogenic effect of insulin resistance. Cohort studies initiated in early and mid-pregnancy show evidence that both gestational hypertension and preeclampsia may be more prevalent in gravidas with greater insulin resistance. The association of gestational glucose intolerance with gestational hypertension appears to be independent of obesity and ambient glycemia but explained in part by insulin resistance. Late pregnancy preeclampsia is associated with elevated mid-pregnancy BMI, blood pressure, fasting glucose and insulin, urate, and C-reactive protein, suggestive of metabolic and immune dysregulation. GDM appears to be associated with overexpressed innate immune response, which, in turn, is associated with vascular dysfunction and vascular disease. Among women with GDM, markers of insulin resistance do not appear to correlate with hypertension in short-term cohort studies. However, when non-GDM subjects are compared with subjects with GDM, postpregnancy studies do show an associated with vascular dysfunction and vascular disease. Among women with GDM, markers of insulin resistance do not appear to correlate with hypertension in short-term cohort studies. However, when non-GDM subjects are compared with subjects with GDM, postpregnancy studies do show an association of insulin resistance with both inflammatory dysregulation and vascular dysfunction. Cohort studies that have used population-based pregnancy databases consistently identify a clinically significant association of both gestational hypertension and preeclampsia with later hypertensive disorders. Associations with coronary artery disease or stroke are less consistent, requiring further investigation. Preventing the evolution of diabetes and lipid and immune dysregulation of the metabolic syndrome has become a silent public health issue because of the epidemic of childhood and early adulthood obesity and the opportunity at hand to treat insulin resistance by behavioral and pharmacological interventions. However, limited available literature highlights the need for long-term cohort studies of women with well-characterized metabolic and vascular profiles during pregnancy and decades later. Our present knowledge suggests that screening for GDM provides an opportunity of pregnancy outcome improvement. Limited studies of diabetes prevention in at-risk patient groups suggest that we may have the opportunity to reduce the risk of later diabetes. Additional investigation is required to determine if interventions that prevent or postpone diabetes also delay the onset of vascular disease. PMID:17596480

Carpenter, Marshall W



High Prevalence of Celiac Disease in Patients with Lactose Intolerance  

Microsoft Academic Search

Background\\/Aims: Acquired lactase deficiency is a common cause of gastrointestinal symptoms but its etiology remains unclear. Celiac disease could lead to lactase deficiency and is much more common than previously suspected. Several studies have highlighted the prevalence of lactose intolerance in celiac disease, but studies assessing the prevalence of celiac disease in lactose intolerance are lacking. We evaluated the prevalence

Veronica Ojetti; Gabriella Nucera; Alessio Migneco; Maurizio Gabrielli; Cristiano Lauritano; Silvio Danese; Maria Assunta Zocco; Enrico Celestino Nista; Giovanni Cammarota; Antonino De Lorenzo; Giovanni Gasbarrini; Antonio Gasbarrini



Intolerance and tolerance in the Jewish tradition and contemporary Israel  

Microsoft Academic Search

In this paper the author relates Jewish cultural resources to the structuring of intolerance and tolerance in the Jewish tradition. The role of collectivist and primordial orientations are highlighted not only in the definition of intolerance but in the construction of patterns of tolerance as well. Because of the decisive role of these orientations, the distinction between public and private

Shlomo Fischer



Intolerance of Uncertainty, Fear of Anxiety, and Adolescent Worry  

ERIC Educational Resources Information Center

|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…

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



[Value of prokinetics in enteral nutrition intolerance].  


Malnutrition is associated with an increase in morbidity and mortality and therefore a raise in hospitalization's costs. Nevertheless, an early nutritional support can reverse this trend. Gastrointestinal dysfunctions (gastroparesis, abdominal distension, high gastric residues) in patient on enteral nutrition, may appear and very likely generate an increasing risk of regurgitations, pulmonary aspiration and infection. These symptoms represent the main factors limiting dosage in administering enteral nutrition. Prokinectics agents (metoclopramid, cisaprid and erythromycin) which improve gastric motility are often used in order to maintain enteral nutrition and to cover the energetic needs of patients. This revenue shows some way of using prokinectics in case of enteral nutrition intolerance and propose a step-by-step guideline on how to start and increase progressively enteral nutrition. PMID:11723704

Maisonneuve, N; Karsegard, V L; Genton, L; Pichard, C



Hyperdibasicaminoaciduria and hyperammonemia in familial protein intolerance.  


A 3-year-old boy with hyperdibasicaminoaciduria and hyperammonemia showed characteristics of familial protein intolerance (FPI). Oral loading tests of lysine and arginine disclosed a remarkably reduced capability for intestinal absorption of these amino acids. Because urinary excretion and renal clearance of dibasic amino acids were only moderately elevated in the patient, the conspicuously decreased serum concentration of lysine, arginine, and ornithine was attributed to the defect in internal absorption. A possible explanation for elevated blood ammonia levels in FPI is that it is due to a deficiency of arginine and ornithine in the urea cycle that in turn results from a severe impairment in absorption of the amino acids by the gut mucosa. PMID:998577

Kato, T; Tanaka, E; Horisawa, S



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.  


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

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



Normalization effect of preceding protein meals on "diabetic" oral glucose tolerance in Eskimos  

PubMed Central

Routine testing of 76 clinically non-diabetic Eskimos showed marked impairment of oral glucose tolerance in 54% but normal intravenous glucose tolerance in most of these. Total insulin output following the glucose drink was not found different in Eskimos with normal and abnormal glucose tolerance nor did lean meat meals given 60 minutes before the glucose significantly increase it. Intolerance to oral glucose loads appeared significantly related to a delay of insulin release and both timing of insulin response and shape of blood glucose curve normalized in the meat-preceded tests.

Schaefer, Otto; Crockford, Peter M.; Romanowski, Barbara



Food Intolerance vs. Food Allergy: What's the Difference?  


... com /health /food-allergy /AN01109 ">Food allergy vs. food intolerance: What's the difference? Guidelines for sites linking to Advertisement Mayo Clinic Store Check out these best-sellers ...


The Cost-Effectiveness of Second-Level Drugs in the Treatment of Essential Hypertension  

PubMed Central

Using the computerized record system at the Hypertension Clinic, Naval Regional Medical Center, Oakland, Caliornia, the authors compared the cost, efficacy, and incidence of intolerable side effect among four second-level antihypertensive agents: methyldopa (Aldomet), clonidine (Catapres), propranolol (Inderal), and prazosin (Minipress). In the population studied, there was no significant difference in efficacy among the drugs. The incidence of intolerable side effect was comparable with the exception of a higher incidence in women receiving methyldopa. Clonidine or propranolol plus a diuretic was found to be the least expensive regimen. The impact of drug cost in the context of treating 23 million hypertensive Americans is discussed.

Lombardo, Joseph V.; Paul, Bertha M.; Baer, Robert; Lewis, Stephen B.



[Case in point: allergy, intolerance or pseudoallergy to chocolate?].  


Chocolate is traditionally considered as allergenic for predisposed subjects although many immunologic reactions are erroneously evaluated as allergic, due to misleading procedures. Therefore the term intolerance has been more properly employed. After summarizing the negative effects of chocolate, especially in children, we stress that the diagnosis of chocolate intolerance should be based upon reliable studies, including elimination/provocation tests in a double-blind fashion. PMID:2701027

Cantani, A; Ferrara, M; Vazzoler, C



Lactose Intolerance in Pregnant African-American Women  

Microsoft Academic Search

LEARNING OUTCOME: To state the prevalence and effects of lactose intolerance in pregnant African-American womenObjective: To determine the prevalence of lactose intolerance in pregnant African-American women, any change in tolerance that may occur and reported symptoms after consuming 240 ml of 1% milk.Design: This longitudinal study compared lactose status: 1) prior to 16 weeks gestation, 2) between the 30th and

D. M. Paige; F. R. Witter; J. A. Perman; Y. Bronner; L. A. Kessler



PPAR regulates glucose metabolism and insulin sensitivity  

Microsoft Academic Search

The metabolic syndrome is a collection of obesity-related disorders. The peroxisome proliferator-activated receptors (PPARs) regulate transcription in response to fatty acids and, as such, are potential therapeutic targets for these diseases. We show that PPAR (NR1C2) knockout mice are metabolically less active and glucose-intolerant, whereas receptor activation in db\\/db mice improves insulin sensitivity. Euglycemic-hyperinsulinemic-clamp experiments further demonstrate that a PPAR-specific

Chih-Hao Lee; Peter Olson; Andrea Hevener; Isaac Mehl; Ling-Wa Chong; Jerrold M. Olefsky; Frank J. Gonzalez; Jungyeob Ham; Heonjoong Kang; Jeffrey M. Peters; Ronald M. Evans



Gallstones, serum lipids, and glucose tolerance among male officials of Self-Defense Forces in Japan  

Microsoft Academic Search

The relationships of gallstones and the postcholecystectomy state with serum total cholesterol, serum triglycerides, glucose tolerance, and obesity were examined in male officials of the Self-Defense Forces in northern Kyushu, Japan. The study population had rather low rates of gallstones (2%) and prior cholecystectomy (3%). A strong relationship between obesity and gallstones was confirmed. Glucose intolerance was associated with the

Suminori Kono; Seishi Kochi; Shiro Ohyama; Aijiro Wakisaka



Acute effects of fructose and glucose ingestion with and without caffeine in young and old humans  

Microsoft Academic Search

Aging is associated with a decline in energy expenditure (EE), glucose intolerance, and a reduction in body nitrogen content. In addition, a reduction in the thermic response to glucose but not to fructose or protein has been reported in the elderly. The present study was conducted to further examine nutrient-induced thermogenesis and the effects of specific sugars on amino acid

Naomi K. Fukagawa; Helen Veirs; Gail Langeloh



Hyperinsulinemia in glucose-tolerant women with preeclampsia A controlled study  

Microsoft Academic Search

Essential hypertension is associated with insulin resistance and hyperinsulinemia. To assess whether hyperinsulinemia is also present in hypertensive disease induced by pregnancy, we studied the plasma glucose and insulin responses to 50 g of oral glucose in 10 women with definite, severe preeclampsia but normal glucose tolerance, and compared them with the responses observed in a well-matched control group of

Esperanza Martinez Abundis; Manuel Gonzalez Ortiz; Alfredo Quiñones Galvan; Ele Ferrannini



Resistant hypertension  

Microsoft Academic Search

Recent clinical trials suggest that resistant hypertension is increasingly common. In the majority of patients, uncontrolled\\u000a hypertension is due to persistent elevation of the systolic blood pressure. Older age and obesity are associated with poor\\u000a blood pressure control. Other contributing factors include severity of the underlying hypertension and renal insufficiency.\\u000a Poor patient adherence is thought be a common cause of

David A. Calhoun; Mohammad A. Zaman; Mari K. Nishizaka



Portal Hypertension  

Microsoft Academic Search

The term portal hypertension or, more strictly, portal venous hypertension, refers explicitly to a pathologic elevation of pressure in the veins that carry blood from the splanchnic organs (including\\u000a the spleen) to the liver. Implicit in the working definition of portal hypertension is the necessary condition that the rise\\u000a in portal pressure is not simply a consequence of an increase

Adrian Reuben; Roberto J. Groszmann


Fetal Programming of Adult Glucose Homeostasis in Mice  

Microsoft Academic Search

BackgroundEmerging 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.ObjectivesThe purpose of this study was to identify

Christopher R. Cederroth; Serge Nef



Mineralocorticoid hypertension  

PubMed Central

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.

Gupta, Vishal



Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats.  


The effect of dietary chromium supplementation on glucose and insulin metabolism in healthy, non-obese cats was evaluated. Thirty-two cats were randomly divided into four groups and fed experimental diets consisting of a standard diet with 0 ppb (control), 150 ppb, 300 ppb, or 600 ppb added chromium as chromium tripicolinate. Intravenous glucose tolerance, insulin tolerance and insulin sensitivity tests with minimal model analysis were performed before and after 6 weeks of feeding the test diets. During the glucose tolerance test, glucose concentrations, area under the glucose concentration-time curve, and glucose half-life (300 ppb only), were significantly lower after the trial in cats supplemented with 300 ppb and 600 ppb chromium, compared with values before the trial. Fasting glucose concentrations measured on a different day in the biochemistry profile were also significantly lower after supplementation with 600 ppb chromium. There were no significant differences in insulin concentrations or indices in either the glucose or insulin tolerance tests following chromium supplementation, nor were there any differences between groups before or after the dietary trial.Importantly, this study has shown a small but significant, dose-dependent improvement in glucose tolerance in healthy, non-obese cats supplemented with dietary chromium. Further long-term studies are warranted to determine if the addition of chromium to feline diets is advantageous. Cats most likely to benefit are those with glucose intolerance and insulin resistance from lack of exercise, obesity and old age. Healthy cats at risk of glucose intolerance and diabetes from underlying low insulin sensitivity or genetic factors may also benefit from long-term chromium supplementation. PMID:11869052

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



[Hypertensive nephrosclerosis].  


Hypertensive nephrosclerosis is the leading cause of end stage renal disease (ESRD) in France, however, in prospective clinical trials of hypertension, ESRD accounts only for a small fraction of all events (incidence rate 0.2 to 0.4% by year). Hypertensive nephrosclerosis is characterized histologically by a series of vascular injury, none of which is truly specific and that can be observed also in obesity or normal aging. Hypertensive nephrosclerosis is mildly symptomatic, but the prognosis is never benign, due to cardiovascular and renal burden. This unspecific presentation may explain why the diagnosis of hypertensive nephrosclerosis is easily carried by excess, the main differential diagnoses are atherosclerotic ischemic renal disease, poorly symptomatic primitive nephropathies or the sequelae of unnoticed malignant hypertensive nephrosclerosis. The very high prevalence of hypertensive nephrosclerosis in populations from African ancestry has suggested a genetic predisposition. MYH9/APOL1 gene variants have recently been identified and are strongly associated with hypertensive nephrosclerosis, however the pathophysiological link between these variants and renal disease is still unclear. The treatment is mainly based on blocking the renin angiotensin system, especially when proteinuria is present. The target blood pressure is less firmly established, the latest data from the AASK study, however, do suggest a benefit on progression of lower values < 135/80 or even < 130/80 mmHg, especially in patients with proteinuria. PMID:21641755

Krummel, Thierry; Bazin, Dorothée; Faller, Anne-Laure; Hannedouche, Thierry



Portal Hypertension  

PubMed Central

Portal hypertension is an increase in pressure in the portal vein and its tributaries. It is defined as a portal pressure gradient (the difference in pressure between the portal vein and the hepatic veins) greater than 5 mm Hg. Although this gradient defines portal hypertension, a gradient of 10 mm Hg or greater defines clinically significant portal hypertension, because this pressure gradient predicts the development of varices,1 decompensation of cirrhosis,2,3 and hepatocellular carcinoma.4 The most direct consequence of portal hypertension is the development of gastroesophageal varices that may rupture and lead to the development of variceal hemorrhage. This article reviews the pathophysiologic bases of the different pharmacologic treatments for portal hypertension in patients with cirrhosis and places them in the context of the natural history of varices and variceal hemorrhage.

Minano, Cecilia; Garcia-Tsao, Guadalupe



[The importance of glycosylated plasma protein determination in the diagnosis of carbohydrate intolerance in obesity].  


To evaluate the possible interest of the dosage of glycated plasma proteins in the diagnosis of glucidic intolerance, OGTT with determination of glycaemia and insulinaemia, HbA1c and fructosamine was determined in 6 normal and 35 obese subjects. On the basis of OGTT the subjects were subdivided into 20 obese with normal glucose tolerance, 7 with IGT and 8 with DM. In the comparison between all the subjects there was a significantly higher plasma fructosamine concentration in the obese with DM (p less than 0.001). No difference was noticed between the normal subjects and the other two classes of obese patients. This suggests that the evaluation of glycated plasma proteins is scarcely sure in a screening plan. PMID:2255412

Ardizzi, A; Grugni, G; Moreni, G; Sartorio, A; Conti, A; Morabito, F



Chronic sulforaphane oral treatment accentuates blood glucose impairment and may affect GLUT3 expression in the cerebral cortex and hypothalamus of rats fed with a highly palatable diet.  


Obesity and insulin resistance are the key factors underlying the etiology of major health problems such as hypertension, diabetes and stroke. These important health issues lead researchers to investigate new approaches to prevent and treat obesity and insulin resistance. Good candidates are the phytochemical compounds that have been extensively studied in the field. Therefore, the aim of this study was to test whether sulforaphane (SFN, 1 mg kg?¹, 4 months treatment), a potent inducer of antioxidant enzymes present in cruciferous vegetables, had some beneficial effects on obesity and insulin resistance induced by a highly palatable (HP) diet in male Wistar rats. Glucose tolerance, serum and hepatic lipid levels, lipid profile, ALT, AST, urea and creatinine, GLUT1 and GLUT3 levels in the cerebral cortex, hippocampus and hypothalamus were analyzed. Glucose tolerance was lower in the HP diet groups, especially in the HP group treated with SFN. Except for the liver triacylglycerols, no differences were found in serum lipids, hepatic and kidney markers of the HP diet groups. Although expression of GLUT1 was similar between groups for all three brain structures analyzed, expression of GLUT3 in the cortex and hypothalamus had a tendency to decrease in the HP diet group treated with SFN. In conclusion, SFN at the specific dose was able to accentuate glucose intolerance and may affect GLUT3 expression in the cerebral cortex and hypothalamus. PMID:23797263

Souza, C G; Riboldi, B P; Hansen, F; Moreira, J D; Souza, D G; de Assis, A M; Brum, L M; Perry, M L S; Souza, D O



Sodium Oxybate Intolerance Associated with Familial Serum Acylcarnitine Elevation  

PubMed Central

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

Berner, Jon



Repressive coping and alexithymia in idiopathic environmental intolerance  

Microsoft Academic Search

Objective  To examine if the non-expression of negative emotions (i.e., repressive coping) and differences in the ability to process\\u000a and regulate emotions (i.e., alexithymia) is associated with idiopathic environmental intolerance (IEI).\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The study included participants who had previously participated in a general population-based study and reported symptoms\\u000a of environmental intolerance (n = 787) and patients with IEI (n = 237). The participants completed questionnaires assessing

Sine Skovbjerg; Robert Zachariae; Alice Rasmussen; Jeanne Duus Johansen; Jesper Elberling



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

SciTech Connect

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.

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



Arterial Hypertension  

Microsoft Academic Search

\\u000a High blood pressure (BP) is a very important cardiovascular (CV) risk factor and is often labeled the “silent killer” because\\u000a arterial hypertension will lead to serious CV events such as ischemic heart disease, stroke, and heart failure. Moreover,\\u000a uncontrolled essential hypertension also leads to renal insufficiency, which accelerates the process of blood pressure elevation\\u000a (1, 2). There is a shift

Daniel A. Duprez


Metabolic handling of orally administered glucose in cirrhosis.  

PubMed Central

We used a dual-isotope method (oral [1-14C]glucose and intravenous [6-3H]glucose) to examine whether the oral glucose intolerance of cirrhosis is due to (a) a greater input of glucose into the systemic circulation (owing to a lower first-pass hepatic uptake of ingested glucose, or to impaired inhibition of hepatic glucose output), (b) a lower rate of glucose removal, or (c) a combination of these mechanisms. Indirect calorimetry was used to measure oxidative and nonoxidative metabolism. Basal plasma glucose levels (cirrhotics, 5.6 +/- 0.4[SE], controls, 5.1 +/- 0.2 mmol/liter), and rates of glucose appearance (Ra) and disappearance (Rd) were similar in the two groups. After 75 g of oral glucose, plasma glucose levels were higher in cirrhotics than controls, the curves diverging for 80 min despite markedly higher insulin levels in cirrhotics. During the first 20 min, there was very little change in glucose Rd and the greater initial increase in plasma glucose in cirrhotics resulted from a higher Ra of ingested [1-14C]glucose into the systemic circulation, suggesting a reduced first-pass hepatic uptake of portal venous glucose. The continuing divergence of the plasma glucose curves was due to a lower glucose Rd between 30 and 80 min (cirrhotics 236 +/- 17 mg/kg in 50 min, controls 280 +/- 17 mg/kg in 50 min, P < 0.05, one-tailed test). Glucose metabolic clearance rate rose more slowly in cirrhotics and was significantly lower than in controls during the first 2 h after glucose ingestion (2.24 +/- 0.17 vs 3.30 +/- 0.23 ml/kg per min, P < 0.005), in keeping with their known insulin insensitivity. Despite the higher initial glucose Ra in cirrhotics, during the entire 4-h period the quantity of total glucose and of ingested glucose (cirrhotics 54 +/- 2 g [72% of oral load], controls 54 +/- 3 g) appearing in the systemic circulation were similar. Overall glucose Rd (cirrhotics 72.5 +/- 3.8 g/4 h, controls 77.2 +/- 2.2 g/4h) and percent suppression of hepatic glucose output over 4 h (cirrhotics, 53 +/- 10%, controls 49 +/- 8%) were also similar. After glucose ingestion much of the extra glucose utilized was oxidized to provide energy that in the basal state was derived from lipid fuels. Glucose oxidation after glucose ingestion was similar in both groups and accounted for approximately two-thirds of glucose Rd. The reduction in overall nonoxidative glucose disposal did not reach significance (21 +/- 5 vs. 29 +/- 3 g/4 h, 0.05 < P < 0.1). Although our data would be compatible with an impairment of tissue glycogen deposition after oral glucose, glucose storage as glycogen probably plays a small part part in overall glucose disposal. Our results suggest that the higher glucose levels seen in cirrhotics after oral glucose are due initially to an increase in the amount of ingested glucose appearing in the systemic circulation, and subsequently to an impairment in glucose uptake by tissues due to insulin insensitivity. Impaired suppression of hepatic glucose output does not contribute to oral glucose intolerance.

Kruszynska, Y T; Meyer-Alber, A; Darakhshan, F; Home, P D; McIntyre, N



Tolerance of Intolerance: Values and Virtues at Stake in Education  

ERIC Educational Resources Information Center

The article addresses the issue of the tolerance of intolerance in an educational context. It concerns a real case in a Swedish upper secondary school some years ago, when a student was suspended from school owing to his sympathies with Nazi ideas. One hundred and twenty student teachers' responses to this decision were analysed in respect of the…

Orlenius, Kennert



Tolerance of intolerance: values and virtues at stake in education  

Microsoft Academic Search

The article addresses the issue of the tolerance of intolerance in an educational context. It concerns a real case in a Swedish upper secondary school some years ago, when a student was suspended from school owing to his sympathies with Nazi ideas. One hundred and twenty student teachers' responses to this decision were analysed in respect of the idea of

Kennert Orlenius



Preliminary Investigation of Intolerance of Uncertainty Treatment for Anxiety Disorders  

ERIC Educational Resources Information Center

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…

Hewitt, Sarah N.; Egan, Sarah; Rees, Clare



Calcium, dairy products, and osteoporosis: Implications of lactose intolerance  

Microsoft Academic Search

A high calcium intake reduces the severity of osteoporosis. Although dairy products are rich and inexpensive sources of calcium, these products contain large quantities of lactose, a sugar that is digested with difficulty by an appreciable fraction of the population. The resultant malabsorption of lactose may produce abdominal symptoms, a condition known as lactose intolerance. To prevent these symptoms, many

Patricia M. Bannan; Michael D. Levitt



Assessment of food chemical intolerance in adult asthmatic subjects  

Microsoft Academic Search

BACKGROUND: Identification of food chemical intolerance in asthmatic subjects can be reliably assessed by changes in the forced expiratory volume in one second (FEV1) in response to double blind, placebo controlled challenges on a strict elimination diet. However, this method is cumbersome and time consuming. A study was undertaken to determine whether changes in bronchial responsiveness to histamine following food

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



A case of galactosemia misdiagnosed as cow's milk intolerance.  


We report on a female patient affected by galactosemia in whom the diagnosis was obscured by the concomitant presence of manifestations suggesting a cow's milk intolerance. This case exemplifies the problems in reaching a correct diagnosis in patients with metabolic diseases. PMID:22992216

Della Casa, Roberto; Ungaro, Carla; Acampora, Emma; Pignata, Claudio; Vajro, Pietro; Salerno, Mariacarolina; Santamaria, Francesca; Parenti, Giancarlo



A case of galactosemia misdiagnosed as cow's milk intolerance  

PubMed Central

We report on a female patient affected by galactosemia in whom the diagnosis was obscured by the concomitant presence of manifestations suggesting a cow’s milk intolerance. This case exemplifies the problems in reaching a correct diagnosis in patients with metabolic diseases.



Intolerance of Ambiguity and Political Orientation among Israeli University Students.  

ERIC Educational Resources Information Center

|Explores relations between political orientation and cognitive style among Israeli university students. Finds that intolerance of ambiguity contributed significantly to political orientation and that the political Left showed more complex cognitive styles than the Right. Notes implications for testing competing hypotheses about cognitive style…

Fibert, Zigi; Ressler, William Harris



Construct Validity of the Korean Women's Abuse Intolerance Scale  

Microsoft Academic Search

b Background: Domestic violence against married women has persisted throughout Korean history. However, very little empirical research has been conducted in Korea about domestic violence, its causes, or women's responses. b Objective: To develop and test psychometrically the Korean Women's Abuse Intolerance Scale (KWAIS) to measure women's propensity or desire to leave abusive husbands in Korea. b Methods: The first

Myunghan Choi; Linda R. Phillips; Aurelio José Figueredo; Katheleen Insel; Sung-Kil Min



Psychological features of subjects with idiopathic environmental intolerance  

Microsoft Academic Search

Objectives: Idiopathic environmental intolerance (IEI) is associated with unexplained symptoms attributed to nonnoxious levels of environmental substances. Clinically, some of the symptoms of IEI overlap with those of panic disorder (PD). We have recently reported a link between IEI and panic responses to a single inhalation of 35% carbon dioxide (CO2), a reliable panic induction challenge. This study assessed depression,

Naveen P Poonai; Martin M Antony; Karen E Binkley; Peter Stenn; Richard P Swinson; Paul Corey; Frances S Silverman; Susan M Tarlo



[Monogenic hypertension].  


Four types of monogenic hypertension belong to the group of mineralocorticoid hypertension, which are characterized by high renal water and sodium retention and resulting suppression of plasma renin activity (PRA), high urinary potassium secretion and consecutive low plasma potassium:1. increased production of the hormone aldosterone: glucocorticoid-remediable aldosteronism (GRH), 2. prereceptor disorder with loss of selectivity of the mineralocorticoid receptor: apparent mineralocorticoid excess (AME), 3. receptor disorder with constitutive activation of the mineralocorticoid receptor: "Geller syndrome", 4. postreceptor disorder with enhanced function of the epithelial sodium channel: Liddle's syndrome. While in GRH high synthesis of aldosterone results in high plasma aldosterone and low PRA, in the primary renal malfunctions of the AME, constitutive activation of the mineralocorticoid receptor and the Liddle's syndrome both plasma aldosterone and PRA are low. These forms of hypertension are rather rare in their complete expression, but they point to candidate genes whose mutations may predispose to hypertension. A point mutation of the ENaC beta-subunit (T594M) occurs rather frequent in people of African origin, with 5%. Therefore it is suggested to analyze the genotype of black hypertensive patients as a prerequisite for a rational amiloride therapy. Contrarily, the rather frequent (A[2139]G) polymorphism of the promoter of the alpha-subunit is supposed to mark a lower risk of hypertension. Mutations in the serine-threonine kinases WNK1 or WNK4 cause pseudohypoaldosteronism type II. WNK1 and WNK4 are expressed in the distal part of the nephron. Stimulation of sodium reabsorption by aldosterone is normal but without influence on hyperkalemia. An extrarenal disorder is suggested to be the cause of autosomal-dominant hypertension with brachydactyly: the patients react with a severely impaired baroreflex und show neurovascular contact. The mutation causing this syndrome is not known. PMID:12715144

Bähr, Volker; Oelkers, Wolfgang; Diederich, Sven



Histamine Regulation in Glucose and Lipid Metabolism via Histamine Receptors  

PubMed Central

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-[18F]-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.

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



Glucose tolerance and resistance to insulin-stimulated glucose uptake in men aged 70 years in relation to size at birth  

Microsoft Academic Search

Summary   Although several studies have shown that reduced size at birth predicts glucose intolerance and insulin resistance in adult\\u000a life, the relation has been inconsistent and usually stronger for ponderal index than for birthweight. We examined glucose\\u000a tolerance and insulin sensitivity (by the euglycaemic clamp method) in relation to size at birth in 709 men aged 69–73 years\\u000a in Uppsala,

P. M. McKeigue; H. O. Lithell; D. A. Leon



Hypertensive Crisis  


... considered a hypertensive crisis. To reduce morbidity and mortality in this situation, early evaluation of organ function ... not wait to see if your pressure comes down on its own. Seek emergency medical ... away. This content was last reviewed on 04/04/2012.


Alpha-sarcoglycan deficiency featuring exercise intolerance and myoglobinuria.  


An 8-year-old boy was referred for recent onset of easy fatigue. He showed hyperCKemia and mild scapular winging. Muscle biopsy on the quadriceps muscle demonstrated slight fibre size variability. Dystrophin was normally distributed, carnitine palmitoyl transferase and glycolytic enzymes had normal activities. In the following years the patient developed exercise intolerance and myoglobinuria. Immunohistochemistry showed marked reduction of alpha-sarcoglycan, confirmed by Western blotting. Molecular analysis revealed compound heterozygosity with Arg284Cys and Glu137Lys substitutions, corresponding to nucleotide changes C850 T and G409 A in the gene. At present the patient, 20 years old, shows mild proximal weakness with prominent involvement of the paraspinal muscles, dorsal kyphosis and lumbar hyperlordosis. Exercise intolerance and myoglobinuria, already described in Becker muscular dystrophy, should be also considered among the possible presentations of sarcoglycan deficiencies. PMID:12075495

Mongini, T; Doriguzzi, C; Bosone, I; Chiadò-Piat, L; Hoffman, E P; Palmucci, L



Is fatigue in Marfan syndrome related to orthostatic intolerance?  

Microsoft Academic Search

Patients with Marfan syndrome have a tall stature, which could be associated with low orthostatic tolerance. Fatigue, a common\\u000a complaint of these patients, is also related to orthostatic intolerance. Treatment with beta-blockers, to prevent aortic complications,\\u000a could be a reinforcing factor of both. This study aimed to investigate (1) the relationship between symptoms of orthostatic\\u000a tolerance and in patients with

Nynke van Dijk; Mardi C. Boer; Barbara J. M. Mulder; Gert A. van Montfrans; Wouter Wieling



Varicella and varicella immunity in patients with lysinuric protein intolerance  

Microsoft Academic Search

Two patients with lysinuric protein intolerance (LPI) had near-fatal generalized varicella infection with severe interstitial pneumonitis, hepatitis, decreased platelet count, bleeding and hypoalbuminaemia. Active haemolysis resulted in anaemia and massive haemoglobinuria. Serum lactate dehydrogenase activity and ferritin concentration, which in patients with LPI in normal circumstances exceed the upper reference values 3-fold to 10-fold, increased to >10 000U\\/L and >10

M. Lukkarinen; K. Näntö-Salonen; O. Ruuskanen; T. Lauteala; S. Säkö; M. Nuutinen; O. Simell



Carbon dioxide inhalation challenges in idiopathic environmental intolerance  

Microsoft Academic Search

Background: Idiopathic environmental intolerance (IEI) is associated with unexplained physical symptoms, which overlap considerably with those of panic disorder (PD).Objective: This study tested the hypothesis that patients with symptoms to suggest IEI exhibit features of PD in response to nonnoxious environmental stimuli.Methods: A single-blind, case-control 35% carbon dioxide inhalation challenge was conducted at a university-based occupational health unit with the

Naveen Poonai; Martin M. Antony; Karen E. Binkley; Peter Stenn; Richard P. Swinson; Paul Corey; Frances S. Silverman; Susan M. Tarlo



Repetitive Hemodilution in Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension: Effects on Pulmonary Hemodynamics, Gas Exchange, and Exercise Capacity  

Microsoft Academic Search

Background: In cor pulmonale associated with severe chronic obstructive pulmonary disease (COPD), disturbances of pulmonary microcirculation may contribute significantly to hypoxemia, pulmonary hypertension, and exercise intolerance. Objective: It was tested whether reduction of blood viscosity induced by repetitive hemodilution might improve pulmonary hemodynamics and oxygen uptake. Methods: Seven patients with stable COPD (forced expiratory volume in 1 s 33 ±

Mathias M. Borst; Matthias Leschke; Ursula König; Heinrich Worth



Glucose allostasis.  


In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy individuals with normal glucose tolerance, normoglycemia can always be maintained by compensatorily increasing AIR in response to decreasing M (and vice versa). This has been mathematically described by the hyperbolic relationship between AIR and M and referred to as glucose homeostasis, with glucose concentration assumed to remain constant along the hyperbola. Conceivably, glucose is one of the signals stimulating AIR in response to decreasing M. Hypothetically, as with any normally functioning feed-forward system, AIR should not fully compensate for worsening M, since this would remove the stimulus for the compensation. We provide evidence from cross-sectional, longitudinal, and prospective data from Pima Indians (n = 413) and Caucasians (n = 60) that fasting and postprandial glucose concentrations increase with decreasing M despite normal compensation of AIR. For this physiologic adaptation to chronic stress (insulin resistance), we propose to use the term "glucose allostasis." Allostasis (stability through change) ensures the continued homeostatic response (stability through staying the same) to acute stress at some cumulative costs to the system. With increasing severity and over time, the allostatic load (increase in glycemia) may have pathological consequences, such as the development of type 2 diabetes. PMID:12663459

Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert; Vozarova, Barbora; Bogardus, Clifton



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


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

Nielsen, J; Christensen, D L



How can we block sympathetic overactivity? Effects of rilmenidine and atenolol in overweight hypertensive patients  

Microsoft Academic Search

The aim of the present study was to evaluate effects of long-term treatment with rilmenidine compared with atenolol on lipid and glucose metabolism and cardiovascular remodelling in hypertension. In total, 37 patients with hypertension were randomised to rilmenidine 1–2 mg\\/day or atenolol 50–100 mg\\/day for 26 weeks. Standard oral glucose tolerance test with a parallel measurement of insulin and glucose

A O Konrady; Y R Kasherininov; A A Shavarov; E K Shavarova; N V Vachrameeva; A N Krutikov; E V Smirnova; E V Shlyakhto



The Relationship between Impaired Glucose Tolerance, Type 2 Diabetes, and Cognitive Function  

Microsoft Academic Search

The present review integrates findings of published studies that have evaluated the cognitive function of treated and untreated type 2 diabetic patients and provides a detailed overview of the neuropsychological assessments conducted. Cognitive deficits are observed in older people with glucose intolerance or untreated diabetes but these deficits appear to be attenuated by treatments that improve glycemic control. Cognitive decrements

Nesrine Awad; Michèle Gagnon; Claude Messier



Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers  

Microsoft Academic Search

Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity

Julia Sacher; Nilufar Mossaheb; Christoph Spindelegger; Nikolas Klein; Thomas Geiss-Granadia; Robert Sauermann; Edith Lackner; Christian Joukhadar; Markus Müller; Siegfried Kasper



Hypertension in Women  

Microsoft Academic Search

Hypertension is the most common cause of increased risk for heart and vascular disease in the adult population. Both men and women are at risk for hypertension and both benefit from antihypertensive therapy. However, hypertension tends to be less prevalent in women and is better tolerated; hypertensive women have fewer strokes and hean attacks than do hypertensive men. Women may

Lawrence R. Krakoff



Plasma nonesterified Fatty Acid intolerance and hyperglycemia are associated with intravenous lipid-induced impairment of insulin sensitivity and disposition index.  


Context: It is currently unclear why susceptibility to lipid-induced impairment of beta-cell function varies in different populations. Objective: The aim of the study was to determine whether mild hyperglycemia may be associated with nonesterified fatty acid (NEFA) intolerance and increased iv lipid-induced lipotoxic effect on the beta-cell. Design and Setting: The study consisted of an experimental design with control group conducted at an academic clinical research center. Participants: Twenty-six overweight or obese individuals (12 with normal glucose tolerance, nine with impaired glucose tolerance or type 2 diabetes, and five subjects who previously had impaired glucose tolerance or type 2 diabetes but at the time of study had normal glucose tolerance after biliopancreatic diversion). Interventions: We assessed insulin sensitivity (S(I)) and beta-cell function [insulin disposition index (DI)] after an overnight iv infusion of heparin + Intralipid (HI) vs. normal saline for 16 h using a stepwise, incremental iv glucose infusion followed by a hyperglycemic clamp. Main Outcome Measures: We measured S(I), DI, HI-induced change in plasma NEFA, and its association with HI-induced change in S(I) and DI. Results: HI resulted in significant reduction in S(I) and DI across the three groups of participants. HI-induced elevation of plasma NEFA was higher in hyperglycemic vs. normoglycemic groups. Both fasting glucose level and the magnitude of HI-induced NEFA elevation were associated with the reduction in S(I) (P = 0.007 and P = 0.01, respectively) and DI (P = 0.001 and P = 0.007, respectively). Conclusion: Mild hyperglycemia and NEFA intolerance to iv lipid are associated with susceptibility to lipid-induced reduction in S(I) and DI. PMID:20097711

Carpentier, André C; Bourbonnais, Annie; Frisch, Frédérique; Giacca, Adria; Lewis, Gary F



[Insulin resistance--a physiopathological condition with numerous sequelae: non-insulin-dependent diabetes mellitus (NIDDM), android obesity, essential hypertension, dyslipidemia and atherosclerosis].  


Recent research has demonstrated that reduced insulin-stimulated glucose metabolism in skeletal muscle (insulin resistance) and hyperinsulinism are common features in widespread diseases such as essential hypertension, android obesity, non-insulin dependent diabetes mellitus, dyslipidemia (in the form of raised serum triglyceride and reduced serum high-density lipoprotein (HDL) cholesterol) and arteriosclerosis. Simultaneously, investigations in a comprehensive group of healthy middle-aged men have revealed insulin resistance in one fourth. On the basis of these observations, a working hypothesis is suggested which postulates that genetic abnormalities in one or more of the candidate genes in the modes of action of insulin occur in a great proportion of the population. These may result in insulin resistance (primary genetic insulin resistance). Primary insulin resistance may be potentiated by a series of circumstances such as ageing, high-fat diet, lack of physical activity, hormonal and metabolic abnormalities or drugs (secondary insulin resistance). As a consequence of the reduced effect of insulin on muscle tissue, compensatory hyperinsulinism develops. Depending on the remaining vulnerability of the individual the hyperinsulinism is presumed to result in development of one or more phenotypes. For example if the beta-cells of the pancreas are unable to secrete sufficient insulin to compensate the insulin resistance on account of genetic defects, glucose intolerance will develop. In a similar manner, hyperinsulinism in insulin-resistant individuals who are predisposed to essential hypertension is presumed to reveal genetic defects in the blood pressure regulating mechanisms and thus contribute to development of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1631967

Pedersen, O



Specific food intolerance: its place as a cause of gastrointestinal symptoms.  

PubMed Central

Thirteen out of 49 patients suspected of having specific food intolerance after withdrawal and reintroduction of specific foods, were further subjected to double blind placebo controlled food challenges. Only three of these subjects were thus shown to have proven specific food intolerance. Of the remaining 10, nine were strong 'placebo reactors'. The study suggests that a small number of patients with gastrointestinal symptoms have verifiable specific food intolerance but that a greater number have symptoms attributable to psychogenic causes.

Farah, D A; Calder, I; Benson, L; MacKenzie, J F



Allergy \\/Intolerance to Buckwheat and Other Food Products among Swedish Subjects with Celiac Disease  

Microsoft Academic Search

Buckwheat can be used to produce a gluten free flour valuable for persons with gluten intolerance (celiac disease). Celiac disease is affecting about 0.2% of adults in Sweden. The aim of the current study is to investigate the prevalence of buckwheat allergy\\/intolerance, as well as other types of food allergies\\/intolerance, among members of a society for celiac disease patients in

Jeong-Lim Kim; Gunilla Wieslander; Dan Norblck



Perceived food intolerance in subjects with irritable bowel syndrome – etiology, prevalence and consequences  

Microsoft Academic Search

Objectives:This study estimates the prevalence of perceived food intolerance and its consequences in subjects with irritable bowel syndrome (IBS), evaluates the utility of common tests for food intolerance, studies the relation between perceived food intolerance and other disorders, and discusses the etiology.Design:Cross-sectional study.Setting:National health survey.Subjects:A selection of the population (n=11078) in Oppland county, Norway, was invited to a health screening,

K W Monsbakken; P O Vandvik; P G Farup



Oxidative metabolism of neutrophils in vitro and human mercury intolerance.  


Neutrophils from 22 patients and 15 healthy controls were exposed in vitro to mercuric chloride and phenyl mercuric acetate in increasing doses and the superoxide anion production of the isolated cells was measured using the NBT (nitroblue tetrazolium) test. The patients were chosen for the study on the basis of their history following exposure to amalgam dust during dental treatment. Based on their psychosomatic response to challenge with percutaneously administered low doses (i.e. patch test doses) of metallic mercury and phenyl mercuric acetate, they were subdivided into two groups: 12 patients with a high score on the psychometric test (positive or mercury-intolerant patients) and 10 with a negative or low score (negative or mercury-tolerant patients). A significant difference in the NBT reduction of unstimulated neutrophils and one concentration of mercuric chloride was found between the tolerant and intolerant patients. Neutrophils from tolerant patients showed a peak NBT value at lower concentrations of mercuric chloride than did cells from the healthy controls and the intolerant patients. When the cells were exposed to increasing amounts of phenyl mercuric acetate, the positive and negative patients differed significantly. Furthermore, an inhibition was noted of the NBT response. Thus, the in vitro oxidative response pattern of neutrophils differs in subjects who do or do not react psychosomatically when exposed to in vivo provocations with low doses of mercury. The findings may be relevant for those complaining of subjective symptoms related to mercury released from dental amalgam and could provide some understanding of the pathogenetic mechanisms. PMID:20654420

Marcusson, J A; Jarstrand, C



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


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

Huppert, Doreen; Grill, Eva; Brandt, Thomas



Hypertensive Disorders of Pregnancy  

PubMed Central

Hypertension is the most common medical problem encountered during pregnancy, complicating 2-3% of pregnancies. Hypertensive disorders during pregnancy are classified into 4 categories, as recommended by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy: 1) chronic hypertension, 2) preeclampsia-eclampsia, 3) preeclampsia superimposed on chronic hypertension, and 4) gestational hypertension (transient hypertension of pregnancy or chronic hypertension identified in the latter half of pregnancy) (1). This terminology is preferred over the older but widely used term pregnancy-induced hypertension (PIH) because it is more precise.

Mammaro, Alessia; Carrara, Sabina; Cavaliere, Alessandro; Ermito, Santina; Dinatale, Angela; Pappalardo, Elisa Maria; Militello, Mariapia; Pedata, Rosa



Refeeding hypertension in obese spontaneously hypertensive rats  

Microsoft Academic Search

Abstract,Very-low-calorie diets ,lower,blood ,pressure acutely in obese humans and rats. However, refeeding after dietary restriction produces,mild hypertension in rats. Refeed- ing hypertension was characterized in genetically obese spon- taneously hypertensive rats (obese SHR, Koletsky rat), a model of genetic obesity and hypertension. Obese SHR were,fed a restricted diet (Optifast) for 12 days, refed ad libitum for 28 days, dieted again

P Ernsberger; RJ Koletsky; JS Baskin; M Foley



Portal hypertension.  


The treatment of portal hypertensive gastrointestinal hemorrhage has seen many new and innovative advances in the past 15 years, including pharmocotherapy, sclerotherapy, transjugular intrahepatic portacaval shunt, partial portacaval shunt, and hepatic transplantation. Such an array of therapeutic options provides great flexibility for the physicians managing this complex disorder. The less invasive procedures tend to be associated with higher rates of rebleeding from esophageal varices. However, these procedures serve as excellent bridges to hepatic transplantation in poor-risk patients. Surgical portasystemic shunts offer a permanent solution to portal hypertensive bleeding but also have several drawbacks. Standard (end-to-side or side-to-side) portacaval shunts are associated with unacceptably high rates of p4rtasystemic encephalopathy because of complete diversion of portal flow away from the liver. Selective shunts, such as the distal splenorenal shunt, result in maintenance of portal perfusion, but this is not lasting in alcoholic cirrhotics. Partial shunting (small-diameter portacaval H-graft with collateral ligation) is the most recent addition to the surgical armamentarium. This allows for hepatic portal perfusion, thus minimizing encephalopathy rates, but it violates the right upper quadrant if the patient is a candidate for hepatic transplantation. This large array of treatment options, each with its own advantages and disadvantages, permits for careful selection of the best modality based on several influencing factors. These include the underlying liver disease, the prognosis, the health team's experience, the resources available to the patient and the community, and the cost-effectiveness of each treatment. PMID:7583983

Rhee, P; Sarfeh, I J



Resistant hypertension.  


Resistant hypertension (RH) is defined as blood pressure above a goal despite adherence to at least 3 optimally dosed antihypertensive medications of different classes, one of which is a diuretic. Evaluation of possible RH begins with an assessment of adherence to medications. The white-coat effect should be ruled out by out-of-office blood pressure monitoring. Obesity, heavy alcohol intake, and interfering substances all contribute to RH. Dietary sodium restriction is an important part of management. RH may be secondary to problems such as renal disease, obstructive sleep apnea, or aldosteronism, and testing for these conditions should be considered. Adequate diuretic treatment is a key part of therapy. Chlorthalidone is more effective than hydrochlorothiazide in reducing blood pressure because it is more potent and lasts longer. In addition, it may reduce cardiovascular events to a greater extent than hydrochlorothiazide. When glomerular filtration rate is <30 mL/min, a loop diuretic usually is needed. The addition of spironolactone, with careful attention to potassium levels, is an evidence-based strategy for the treatment of RH. Other strategies include use of a vasodilating ?-blocker, adding a long-acting nondihydropyridine calcium channel blocker, or adding clonidine. When blood pressure is not coming under control despite 4 or 5 agents, referral to a hypertension specialist may be warranted. PMID:22773717

Viera, Anthony J


Intolerance of sexy peers: intrasexual competition among women.  


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

Vaillancourt, Tracy; Sharma, Aanchal



The Intolerance of Uncertainty Scale for Children: A Psychometric Evaluation  

PubMed Central

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 Uncertainty Scale (IUS) and examined the internal consistency, convergent validity, and classification properties of these forms in youth aged 7–17 (M = 11.6 years, SD = 2.6). Participating youth (N = 197; 100 females) either met diagnostic criteria for an anxiety disorder (N = 73) or were non-referred community participants (N = 124). The child-report form (i.e., IUS for Children, or IUSC), and to a lesser extent the parent-report form, demonstrated strong internal consistency and convergent validity, evidenced by significant associations with anxiety and worry (and reassurance-seeking in the case of the child-report form). Children diagnosed with anxiety disorders scored higher than non-referred community youth on both forms. ROC analysis demonstrated acceptable overall utility in distinguishing the two groups of youth. Findings provide preliminary support for use of the IUSC for continuous measurement of children’s ability to tolerate uncertainty.

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



Acute caffeine ingestion does not impair glucose tolerance in persons with tetraplegia.  


Acute caffeine (Caf) ingestion impairs glucose tolerance in able-bodied humans during an oral glucose tolerance test (OGTT). The mechanism responsible for this effect remains unclear, however, it is suggested to be due to the accompanying increase in epinephrine concentration. We examined whether or not Caf would elicit a glucose intolerance in persons with tetraplegia (TP) who do not exhibit an increased epinephrine response following Caf ingestion. All TP [n = 14; 9 incomplete (Inc) lesion, 5 complete (Com) lesion] completed two OGTT 1 h after consuming either gelatin (Pl) or Caf capsules (dose = 4 mg/kg). Blood samples were collected at baseline (time = 0 min), 1 h after capsule ingestion (time = 60 min), and every 30 min during the OGTT (time = 90-180 min). Glucose, insulin, proinsulin, and C-peptide responses were similar (P > 0.05) between treatments, demonstrating no effect of Caf on glucose tolerance. This lack of a Caf effect may be due to the low epinephrine concentration that remained unchanged (P > 0.05) throughout all experiments. Interestingly, the Com exhibited a 50% higher glucose response (P 0.05) lower insulin response (vs. Inc), suggesting a more pronounced glucose intolerance within this subgroup. Furthermore, nine TP (5 Com, 4 Inc) had glucose levels of >or= 7.8 mM at the end of the OGTT (time = 180 min), classifying them as glucose intolerant. In summary, acute Caf ingestion does not increase epinephrine concentration or impair glucose tolerance in TP. PMID:17068214

Battram, D S; Bugaresti, J; Gusba, J; Graham, T E



Endothelin antagonism in patients with resistant hypertension and hypertension nephropathy.  


Resistant hypertension is a failure to achieve a blood pressure (BP) goal of < 140/90 mm Hg despite treatment with at least three different antihypertensive medications classes at a maximally tolerated dose and including a diuretic. The most important systems that require alteration include the renin-angiotensin-aldosterone system, sympathetic nervous system, and (more recently) the endothelin (ET) system. To date, several clinical trials have assessed the effects of ET antagonism, both selective and nonselective, on BP control in humans. The nonselective ET antagonist bosentan was evaluated in patients with mild-to-moderate hypertension. Bosentan was able to lower diastolic BP when compared to placebo and, similarly, to enalapril. Similar findings have been published for darusentan, an ET receptor antagonist with higher affinity for the type A receptor. More recent research has focused on the impact of ET in the setting of resistant hypertension. Studies with darusentan as an add-on therapy in patients with resistant hypertension found a significant BP-lowering effect of 17/10 mm Hg compared to placebo. This BP-lowering effect was similar at higher doses. In a similar patient cohort, darusentan also lowered mean 24-hour BP to a greater extent than the central ??-agonist guanfacine. Another selective ET(A) antagonist, atrasentan, provided other benefits on metabolism in addition to its antihypertensive effect. Atrasentan significantly decreased glucose in diabetes and improved lipid profiles while slowing coronary artery disease progression. Selective ET receptor blockade also has dose-dependent side effects. In a large number of trials, almost one third of the patients suffered excessive fluid retention and edema that was significantly higher than in the placebo groups. One trial, ASCEND, was terminated early due to an increased incidence of fluid retention and increased episodes of heart failure. Thus, this class of agents is effective in resistant hypertension, but lower doses with fewer side effects need to be developed. PMID:21894002

Lazich, Ivana; Bakris, George L



Glucose Sensing  

NASA Astrophysics Data System (ADS)

In the last decade concepts in fluorescence sensing have emerged as powerful techniques with an increasing number of applications in the fields of biology, chemistry, physics, and medicine. The increasing importance of these techniques is typified in one emerging area by developing non-invasive and continuous approaches for physiological glucose monitoring.

Geddes, Chris D.; Lakowicz, Joseph R.


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

Microsoft Academic Search

PURPOSE: Patients with idiopathic orthostatic intolerance often have debilitating symptoms on standing that are suggestive of cerebral hypoperfusion despite the absence of orthostatic hypotension.SUBJECTS AND METHODS: We evaluated the effects of graded head-up tilt on cerebral blood flow as determined by transcranial Doppler measurements in 10 patients with idiopathic orthostatic intolerance (nine women, one man, 22 to 47 years) and

Giris Jacob; Denis Atkinson; Jens Jordan; John R Shannon; Raffaello Furlan; Bonnie K Black; David Robertson



An exploration of food intolerance in the primary care setting: The general practitioner's experience  

Microsoft Academic Search

Food intolerance is one of medicine's modern enigmas. Its etiology and mechanism are unclear and the subject of constant debate, while estimates of its prevalence vary widely from 2% to over 20% of the population. Using interpretive phenomenonological analysis, this study explored the phenomenon of food intolerance in primary care from the general practitioner's (GP) perspective. Semi-structured interviews were carried

Mia Nelson; Jane Ogden



Lactose Intolerance: Exploring Reaction Kinetics Governing Lactose Conversion of Dairy Products within the Undergraduate Laboratory  

ERIC Educational Resources Information Center

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…

Smart, Jimmy L.



HRQoL questionnaire evaluation in lactose intolerant patients with adverse reactions to foods.  


The occurrence of patients with gastrointestinal symptoms attributed either to food allergy or intolerance has significantly increased. Nevertheless, an accurate and detailed case history, a systematic evaluation and the outcomes of specific allergy tests to identify the offending foods, including "in vivo" and "in vitro" allergy tests, are often negative for food allergy and may indicate a lactose intolerance, which is a recurrent condition affecting about 50% of adults. The aims of our study were the following: (1) What is the real incidence of the food hypersensitivity and the primary lactose intolerance in patients with gastrointestinal symptoms, initially referred to allergy or food intolerance? (2) Does lactose intolerance affect the quality of life and compliance to the therapy program? We investigated 262 consecutive patients, 72 men and 190 women. An accurate and detailed history and clinical examination were completed to investigate the offending foods. The evaluation in each patient included: allergy tests, lactose H2 breath test (LHBT) and the HRQoL questionnaire. Five years after the diagnosis of lactose intolerance, a questionnaire on the persistence of gastrointestinal symptoms after lactose ingestion and the diet compliance was distributed. Our results demonstrate an high prevalence of lactose intolerance, more frequent in women; in these patients, bloating and diarrhea are the most reported symptoms. We observe only a significant positive correlation between adverse drug reaction (ADR) and LHBT+ patients, but not an augmented prevalence of food allergy and a negative impact on the HRQoL questionnaire of lactose intolerance. PMID:21614464

Erminia, Ridolo; Ilaria, Baiardini; Tiziana, Meschi; Silvia, Peveri; Antonio, Nouvenne; Pierpaolo, Dall'Aglio; Loris, Borghi



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

Microsoft Academic Search

BACKGROUND: Upon return from space many astronauts experience symptoms of orthostatic intolerance. Research has implicated altered autonomic cardiovascular regulation due to spaceflight with further evidence to suggest that there might be pre-flight autonomic indicators of post-flight orthostatic intolerance. We used heart rate variability (HRV) to determine whether autonomic regulation of the heart in astronauts who did or did not experience

Andrew P Blaber; Roberta L Bondar; Mahmood S Kassam



Consequences of perceived food intolerance for welfare, lifestyle and food choice practices, in a community sample  

Microsoft Academic Search

The objective of this study was to investigate the consequences for lifestyle, welfare and dietary practices of perceiving food intolerance, in a community sample. Questionnaires enquiring about adverse symptoms attributed to foods and other agents were sent to randomly identified householders in diverse electoral wards in the Birmingham area. A total of 300 respondents with perceived food intolerance (PFI) were

R. C. Knibb; D. A. Booth; R. Platts; A. Armstrong; I. W. Booth; A. MacDonald



A Pilot Study Exploring the Effects of Reflexology on Cold Intolerance  

Microsoft Academic Search

Cold intolerance is an inability to tolerate cold temperatures and is accompanied by symptoms including headache, shoulder discomfort, dizziness and palpitations. The current study was performed to examine whether reflexology therapy affected cold intolerance in human subjects and whether the treatment was systemically effective. Ten female volunteer examinees with subjective feelings of cold were examined. After a 5-minute foot bath,

Wenping Zhang; Shougo Takahashi; Takashi Miki; Hisayo Fujieda; Torao Ishida



Relationships among Perceived Racial Stress, Intolerance of Uncertainty, and Worry in a Black Sample  

ERIC Educational Resources Information Center

|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…

Rucker, LaTanya S.; West, Lindsey M.; Roemer, Lizabeth



The Intolerance of Uncertainty Index: Replication and Extension with an English Sample  

ERIC Educational Resources Information Center

|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…

Carleton, R. Nicholas; Gosselin, Patrick; Asmundson, Gordon J. G.



Lactose Intolerance: Exploring Reaction Kinetics Governing Lactose Conversion of Dairy Products within the Undergraduate Laboratory  

ERIC Educational Resources Information Center

|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…

Smart, Jimmy L.



Pediatric hypertension 2001.  


During the past decade, there has been a surge of interest in childhood and adolescent hypertension. The current review summarizes work published during the past year in the following areas: prenatal and early postnatal causes of hypertension; new information on the genetics of childhood hypertension; the relation of obesity, insulin resistance, and diabetes to hypertension; the use of ambulatory blood pressure monitoring to evaluate childhood hypertension; and advances in drug therapy for children with hypertension. The information obtained during the past year has improved our understanding of the pathogenesis, diagnosis, and treatment of childhood hypertension. PMID:12151874

Rocchini, Albert P



Risk of Orthostatic Intolerance During Re-Exposure to Gravity: Record 11 (MRL No. 02, Orthostatic)-BASELINE.  

National Technical Information Service (NTIS)

Post-flight orthostatic intolerance, the inability to maintain blood pressure while in an upright position, is an established, space-related medical problem. Orthostatic intolerance has been shown to progress to presyncope (inability to maintain standing ...

A. Lee S. Platts



Pesticide-initiated idiopathic environmental intolerance in South Korean farmers.  


This study was designed to study patients with intolerance to pesticide smells. Ten subjects chosen were complaining of vague symptoms such as headache, dizziness, fatigue, nausea, vomiting, abdominal pain, myalgia, flu-like symptoms, etc., whenever exposed to the pesticide smells even at low intensity. To determine whether the etiology of this kind of pesticide hypersensitivity was of organic or psychiatric nature, all the subjects underwent tests as follows: complete blood cell count, urinalysis, and blood chemistry as routine tests; esophogastroduodenoscopy and abdomen ultrasonography for the gastrointestinal symptoms; chest x-ray, pulmonary function tests, and electrocardiography for the respiratory and/or cardiac symptoms; nerve conduction velocity and brain magnetic resonance imaging (MRI) for peripheral and central nerve system symptoms; and K-WAIS, Rey-Kim memory test, Rorschach, Mini Mental State Examination (MMSE), and Minnesota Multiphasic Personality Inventory (MMPI) for psychoanalysis. Of the 10 cases in which the chief complaint was headache, symptoms of two cases were caused by maxillary sinusitis. Another two showed typical multiple chemical sensitivity (MCS) or idiopathic environmental intolerance (IEI). Six out of the 10 cases, whose symptoms closely resembled the others, did not conclusively meet the criteria of classic MCS or IEI. The subjects of this case shared vague fears, both fear of pesticides and hypochondriasis. Some subjects faced financial insecurity and social uncertainty; others felt uneasy about the future of their farming life. Thus, to help verify the causes of MCS or IEI, which is strongly suggestive of pesticide smells, diagnosis needs a dual approach: on the anima and soma. Psychoanalysis can delve into the mental status of the patients to see whether the patients are aware of their symptoms. Clinical tests can see through the physical structure and functions of the organs on which patients' complaints are centered. PMID:17497536

Lee, Hae-Sung; Hong, So-Yong; Hong, Zoong-Rock; Gil, Hyo-Ook; Yang, Jong-Oh; Lee, Eun-Young; Han, Mi-Jung; Jang, Nam-Woon; Hong, Sae-Yong



[Hypertension in obese children and adolescents].  


Obesity, especially upper body fat distribution, has become an increasingly important medical problem in children and adolescents. Outcomes related to childhood obesity include, as in adult population, hypertension, type 2 diabetes mellitus, dyslipidemia, left ventricular hypertrophy, obstructive sleep apnea, orthopedic and socio-psychological problems. Obese children are at approximately 3-fold higher risk for hypertension from non-obese ones. Obesity-hypertension appears to be characterized by a preponderance of isolated systolic hypertension, increased heart rate and blood pressure variability, increased levels of plasma catecholamine and aldosterone, and salt-sensitivity. Lifestyle changes of weight loss, healthier diet and regular physical exercise are effective in obesity-hypertension control, though pharmacological treatment is frequently necessary. Screening for dyslipidemia and impaired glucose tolerance should be performed in paediatric patients with obese hypertension on regular basis, at least once annually or semiannually to discover metabolic syndrome and to prevent its increased cardiovascular risk. Of course, prevention of obesity is the primary goal. PMID:19370974

Peco-Anti?, Amira


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

PubMed Central

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

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



Visceral Adiposity and the Prevalence of Hypertension in Japanese Americans  

Microsoft Academic Search

Background—Visceral adiposity is generally considered to play a key role in the metabolic syndrome, including hypertension. The purpose of this study was to evaluate cross-sectionally whether visceral adiposity is associated with prevalence of hypertension independent of other adipose depots and fasting plasma insulin. Methods and Results—Study subjects included 563 Japanese Americans with normal or impaired glucose tolerance or diabetes but

Tomoshige Hayashi; Edward J. Boyko; Donna L. Leonetti; Marguerite J. McNeely; Laura Newell-Morris; Steven E. Kahn; Wilfred Y. Fujimoto



Maternal Glucose Tolerance in Pregnancy Affects Fetal Insulin Sensitivity  

PubMed Central

OBJECTIVE Offspring of mothers with impaired glucose tolerance are far more likely to develop type 2 diabetes. We tested the hypothesis that maternal glucose tolerance in pregnancy affects fetal insulin sensitivity or ?-cell function. RESEARCH DESIGN AND METHODS In a prospective singleton pregnancy cohort study, we analyzed glucose, insulin, and proinsulin concentrations in maternal blood at the 50-g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation and in venous cord blood (n = 248). The cord blood glucose-to-insulin ratio and proinsulin concentration were used as indicators of fetal insulin sensitivity and the proinsulin-to-insulin ratio was used as an indicator of fetal ?-cell function. RESULTS Higher OGTT blood glucose levels were associated with significantly lower cord plasma glucose-to-insulin ratios (r = ?0.31, P < 0.001) and higher proinsulin concentrations (r = 0.31, P < 0.001) but not with proinsulin-to-insulin ratios. In a comparison of gestational diabetic (n = 26) versus euglycemic pregnancy, cord blood glucose-to-insulin ratios were substantially lower (geometric mean 10.1 vs. 20.0 mg/dl/?U/ml; P < 0.001), whereas proinsulin concentrations were much higher (24.4 vs. 13.8 pmol/l; P < 0.001), despite similar cord blood glucose concentrations indicating adequate management of diabetes. The differences remained significant after controlling for prepregnancy and fetal adiposity, family history of diabetes, gestational age, and other potential confounders. Significant changes in the glucose-to-insulin ratio and proinsulin concentration were also observed in obese (n = 31) mothers, but the differences became not statistically significant after adjustment for maternal glucose tolerance and fetal adiposity. CONCLUSIONS Maternal glucose intolerance may impair fetal insulin sensitivity (but not ?-cell function) and consequently “program” the susceptibility to type 2 diabetes.

Luo, Zhong-Cheng; Delvin, Edgard; Fraser, William D.; Audibert, Francois; Deal, Cheri I.; Julien, Pierre; Girard, Isabelle; Shear, Roberta; Levy, Emile; Nuyt, Anne-Monique



Comparison of the effects of captopril and nicardipine on insulin sensitivity and thrombotic profile in patients with hypertension and android obesity. CaptISM Study Group. Captopril Insulin Sensitivity Multicenter Study Group.  


Hypertension is often related to metabolic disorders, such as android obesity, glucose intolerance, dyslipidemia, and hyperinsulinism (X syndrome). Insulin resistance (IR), described as the common link among these disorders, could contribute to an increase in coronary risk. The euglycemic insulin clamp technique has been used to show that different classes of antihypertensive agents have different effects on IR. The purpose of this multicenter study was to compare the effects of captopril to those of nicardipine on insulin profile using the oral glucose tolerance test (OGTT), a routine-feasible test. After a 1-month single-blind placebo period, 154 patients with hypertension and android obesity were randomized to 3 months of double-blind therapy with either 50 mg captopril twice daily (n = 77) or 50 mg nicardipine twice daily n = 77). An OGTT with an assay of insulin was performed before and after active treatment. Lipid parameters, Factor VII (F VII), fibrinogen, plasminogen activator inhibitor 1 (PAI-1), and insulin-like growth factor I (IGF-I) were measured at the same time. After 3 months of treatment, the changes from baseline in mean +/- SD values for the insulin area under the curve (AUC) were -24.8 +/- 107.4 microIU x h/mL (-15.2%) for captopril v 6.1 +/- 98.6 microIU x h/mL (4.8%) for nicardipine (P = .072). Changes in peak insulin values were -18.3 +/- 86.2 microIU/mL (-14%) for captopril v 6.7 +/- 79.4 microIU/mL (6.6%) for nicardipine (P = .070).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7986464

Raccah, D; Pettenuzzo-Mollo, M; Provendier, O; Boucher, L; Cozic, J A; Gorlier, R; Huin, P; Sicard, J; Vague, P



Retrospective analysis of cetuximab monotherapy for patients with irinotecan-intolerant metastatic colorectal cancer  

Microsoft Academic Search

Background  The efficacy and safety of cetuximab for irinotecan-intolerant patients has not yet been evaluated in detail.\\u000a \\u000a \\u000a \\u000a Methods  We retrospectively analyzed the efficacy and safety of cetuximab monotherapy for patients with metastatic colorectal cancer\\u000a (MCRC) that was intolerant to irinotecan.\\u000a \\u000a \\u000a \\u000a \\u000a Results  Among 105 patients who received cetuximab-containing chemotherapy until March 2010, 22 patients were treated with cetuximab\\u000a monotherapy due to irinotecan intolerance. Cetuximab

Ayako MizotaKohei; Kohei Shitara; Chihiro Kondo; Motoo Nomura; Tomoya Yokota; Daisuke Takahari; Takashi Ura; Yoshitaka Inaba; Hidekazu Yamaura; Yozo Sato; Mina Kato; Kei Muro



PubMed Central

Background Endothelin-1 (ET-1) is implicated in the pathogenesis of hypertension. In vitro studies demonstrate that ET-1 is up-regulated by insulin and glucose. The purpose of this study was to determine the effects of insulin and glucose upon ET-1 levels in young adult African Americans, a population with a high burden of hypertension and diabetes. Methods Plasma and urine ET-1 levels were measured before and after an oral glucose tolerance test (OGTT) and insulin clamp procedure in 288 participants. Subjects were classified according to glucose tolerance and blood pressure (BP) status. Results Plasma and urine ET-1 were not significantly different among the glucose tolerance groups. There was a trend toward increased plasma ET-1 among DM compared to IGT and NGT, however this was not statistically significant (p=0.085). According to BP status, plasma ET-1 was highest among the high BP group compared to the normal BP group (p=0.01). Following glucose challenge, plasma ET-1 levels decreased and urine ET-1 increased in all three BP groups (p=0.037). Conclusions Our data show that plasma ET-1 is higher among young adult Black Americans with hypertension compared to normotension. Urine ET-1 levels increased in response to glucose challenge possibly indicating early renal injury.

DeLoach, Stephanie; Huan, Yonghong; Daskalakis, Constantine; Falkner, Bonita



Telomerase deficiency impairs glucose metabolism and insulin secretion  

PubMed Central

Reduced telomere length and impaired telomerase activity have been linked to several diseases associated with senescence and aging. However, a causal link to metabolic disorders and in particular diabetes mellitus is pending. We here show that young adult mice which are deficient for the Terc subunit of telomerase exhibit impaired glucose tolerance. This is caused by impaired glucose-stimulated insulin secretion (GSIS) from pancreatic islets, while body fat content, energy expenditure and insulin sensitivity were found to be unaltered. The impaired secretion capacity for insulin is due to reduced islet size which is linked to an impaired replication capacity of insulin-producing beta-cells in Terc-deficient mice. Taken together, telomerase deficiency and hence short telomeres impair replicative capacity of pancreatic beta-cells to cause impaired insulin secretion and glucose intolerance, mechanistically defining diabetes mellitus as an aging-associated disorder.

Kuhlow, Doreen; Florian, Simone; von Figura, Guido; Weimer, Sandra; Schulz, Nadja; Petzke, Klaus J.; Zarse, Kim; Pfeiffer, Andreas F.H; Rudolph, K. Lenhard; Ristow, Michael



HIV and Pulmonary Hypertension  


... lead to PH. A direct cause and effect relation between HIV infection and pulmonary hypertension has not ... in bringing pulmonary hypertension into the national and international consciousness. PHA is constantly increasing its services to ...


[Hypertension and hyperhidrosis. Pheochromocytoma].  


A 39-year-old woman was referred to our hypertension clinic with refractory hypertension. The patient history gave certain clues for pheochromocytoma. The diagnosis was proven with elevated metanephrines and computer tomography. The tumor was surgically removed. PMID:18303664

Mettler, J; Battegay, E; Egelhof, T; Oertli, D; Zimmerli, L; Bilz, S



Hypertension in women.  


One in 4 adults has hypertension worldwide, which equates to approximately 1 billion individuals. Hypertension is a leading cause of death, and lowering blood pressure prevents mortality and morbidity in women and men. Although men have higher blood pressures compared with women at all ages, older women have a slightly higher prevalence of hypertension, and hypertension is more often uncontrolled in women. Hypertension associated with pregnancy and polycystic ovary syndrome is unique to women. Exogenous hormone administration in the form of oral contraceptives, and rarely postmenopausal hormone replacement, contributes to the burden of hypertension in women. Renovascular hypertension due to fibromuscular dysplasia is more common in women. Hypertension treatment should focus on lowering blood pressure and treating additional cardiovascular risk factors, and there is no evidence to support gender-specific approaches to lowering blood pressure and modifying cardiovascular risk. PMID:23978544

August, Phyllis



Secondary hypertension: Evaluation and treatment  

Microsoft Academic Search

Most patients with hypertension in the United States have essential (primary) hypertension (95 %), the cause of which is unknown. The remaining 5 % of adults with hypertension have the secondary form of hypertension, the cause and pathophysiologic process of which are known. Internists and other primary care physicians refer to this as treatable or curable hypertension, because the hypertension

Basil E. Akpunonu; Patrick J. Mulrow; Elizabeth A. Hoffman



Hypertension in pregnancy  

Microsoft Academic Search

Hypertension in pregnancy contributes significantly to both maternal and neonatal morbidity and mortality. Among different\\u000a forms of pregnancy-associated hypertension, preeclampsia-eclampsia has the highest impact on morbidity and mortality. Chronic\\u000a hypertension may result in preterm and small for gestational age infants, even when it is mild-to-moderate. Chronic hypertension\\u000a is a risk factor for superimposed preeclampsia and results in higher rates of

Maryann Mugo; Gurushankar Govindarajan; L. Romayne Kurukulasuriya; James R. Sowers; Samy I. McFarlane



Hypertensive crisis in children  

Microsoft Academic Search

Hypertensive crisis is rare in children and is usually secondary to an underlying disease. There is strong evidence that the\\u000a renin-angiotensin system plays an important role in the genesis of hypertensive crisis. An important principle in the management\\u000a of children with hypertensive crisis is to determine if severe hypertension is chronic, acute, or acute-on-chronic. When it\\u000a is associated with signs

Jayanthi Chandar; Gastón Zilleruelo


Low ethanol intake prevents salt-induced hypertension in WKY rats  

Microsoft Academic Search

Low alcohol intake in humans lowers the risk of coronary heart disease and may lower blood pressure. In hypertension, insulin resistance with altered glucose metabolism leads to increased formation of aldehydes. We have shown that chronic low alcohol intake decreased systolic blood pressure (SBP) and tissue aldehyde conjugates in spontaneously hypertensive rats and demonstrated a strong link between elevated tissue

Sudesh Vasdev; Vicki Gill; Sushil Parai; Veeresh Gadag



Cognitive function and hypertension  

Microsoft Academic Search

The importance of lowering blood pressure (BP) in hypertensive subjects is well known but the relationship between hypertension and cognitive function is controversial. This article reviews the role of hypertension in the aetiology of cognitive impairment and the relationships between BP, cerebral perfusion and cognition. It also summarizes findings of studies addressing the effect of antihypertensive therapy and cognition. An

J Birns; L Kalra



Depression in hypertensive subjects.  


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

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



Adrenocortical Causes of Hypertension  

PubMed Central

Primary aldosteronism is the most common cause of secondary hypertension. In the past, screening for primary aldosteronism was offered only in patients with hypertension associated with hypokalemia. Recent studies showed that hypokalemia is seen in only 25% of the patients with primary aldosteronism, which has increased the prevalence of primary aldosteronism to 10–15% of all cases with new onset hypertension.

Moraitis, Andreas; Stratakis, Constantine



Genetics of Hypertensive Syndrome  

Microsoft Academic Search

The knowledge of the genetic bases of hypertension has improved over the last decade; this area of research has high priority due to the high incidence of hypertension and its impact on public health. Monogenetic mineralocorticoid hypertension syndromes are associated with suppressed plasma renin activity due to excessive activation of the mineralocorticoid pathway. We review the pathophysiology, phenotype, and method

Alejandro Martinez-Aguayo; Carlos Fardella



Sympathetic Overactivity in Hypertension  

Microsoft Academic Search

Considerable progress has been made in our understanding of the role of the nervous system in human hypertension. The evidence for a widespread autonomic abnormality in the early phases of hypertension is overwhelming and excessive sympathetic activity is consistently present in such patients since their childhood. The enhanced sympathetic tone in hypertension is associated with the metabolic syndrome of insulin

Stevo Julius; Shawna Nesbitt



Effects of candesartan cilexetil on glucose homeostasis  

Microsoft Academic Search

In a multicenter, randomized, double-blind, placebo-controlled clinical trial the effects of candesartan cilexetil (cand.cil.), a novel angiotensin II antagonist selective for the AT1 receptor with long-lasting antihypertensive activity, on glucose homeostasis - and the serum lipid profile - were assessed in patients with mild hypertension and stable type II diabetes mellitus. A total of 161 men and women, 30-75 years

P. Trenkwalder



Physiologic Basis of Muscular Fatigue, Pathophysiology of Exercise Intolerance, and Enhancing Exercise Tolerance in Health.  

National Technical Information Service (NTIS)

The Final Proceedings for The Physiology and Pathophysiology of Exercise Tolerance, 21 September 1994 - 24 September 1994. The Topics covered include: the physiologic basis of muscular fatigue, pathophysiology of exercise intolerance, and enhancing exerci...

J. M. Steinacker S. A. Ward



Domain-General and Domain-Specific Strategies for the Assessment of Distress Intolerance  

PubMed Central

Recent research has provided evidence that distress intolerance—the perceived inability to tolerate distressing states—varies based on the domain of distress (e.g., pain, anxiety). Although domain-specific assessment strategies may provide information targeted to specific disorders or maladaptive behaviors, domain-general measures have the potential to facilitate comparisons across studies, disorders, and populations. The current study evaluated the utilization of self-report measures of distress intolerance as domain-general measures by examining their association with indices of behavioral avoidance and substance craving. Two groups of participants (N = 55) were recruited including a substance-dependent group and a comparison group equated based on the presence of an affective disorder. Results provided support for the validity of domain-general measures for assessing distress intolerance across varied domains. The importance of both domain-general and domain-specific measurement of distress intolerance is discussed.

McHugh, R. Kathryn; Otto, Michael W.



Domain-general and domain-specific strategies for the assessment of distress intolerance.  


Recent research has provided evidence that distress intolerance-the perceived inability to tolerate distressing states-varies based on the domain of distress (e.g., pain, anxiety). Although domain-specific assessment strategies may provide information targeted to specific disorders or maladaptive behaviors, domain-general measures have the potential to facilitate comparisons across studies, disorders, and populations. The current study evaluated the utilization of self-report measures of distress intolerance as domain-general measures by examining their association with indices of behavioral avoidance and substance craving. Two groups of participants (N = 55) were recruited including a substance-dependent group and a comparison group equated based on the presence of an affective disorder. Results provided support for the validity of domain-general measures for assessing distress intolerance across varied domains. The importance of both domain-general and domain-specific measurement of distress intolerance is discussed. PMID:21823763

McHugh, R Kathryn; Otto, Michael W



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

PubMed Central

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.

Gibson, Peter R.



Orthostatic Intolerance Ambulation in Patients Using Patient Controlled Analgesia  

PubMed Central

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.

Park, Kwang Ok



Salicylate intolerance: a masquerader of multiple adverse drug reactions  

PubMed Central

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

Fernando, Suran Loshana; Clarke, Lesley R



Cryopreservation of spermatozoa from freeze-tolerant and -intolerant anurans.  


Spermatozoa of the freeze-tolerant wood frog (Rana sylvatica) were used to develop a general protocol for the frozen storage of amphibian spermatozoa. Tolerance of spermatozoa to cryoprotective agents and freezing in suspension (-80 degrees C) was determined from rates of sperm lysis and dual-fluorochrome vital dye assays. We tested the efficacy of four cryoprotectants (Me2SO, methanol, glycerol, and ethylene glycol), two supplements (fetal bovine serum or glutathione), and combinations of these cryoprotectants and supplements. Me2SO and fetal bovine serum were the most effective cryoprotectant and supplement, respectively, in reducing sperm lysis. Vital dye assays showed that viability was greatest for spermatozoa treated with both Me2SO and fetal bovine serum. Thus, this combination was used to cryopreserve spermatozoa from the freeze-intolerant anurans, Rana pipiens and Bufo americanus. Recovery of viable spermatozoa was significantly greater for R. sylvatica (mean +/- SE = 81.2 +/- 9.6%) than for R. pipiens (59.0 +/- 2.8%) and B. americanus (47.8 +/- 4.1%), perhaps owing to inherent factors promoting its freeze tolerance. Nonetheless, our results support the feasibility of using gamete cryopreservation techniques in programs aimed at the captive propagation of amphibians. PMID:9769166

Beesley, S G; Costanzo, J P; Lee, R E



Glucose Tolerance and Weight Loss in Obese Women with Obstructive Sleep Apnea  

PubMed Central

Background The association of obstructive sleep apnea (OSA) with glucose intolerance and the beneficial effect of lifestyle intervention have been poorly investigated in women particularly before menopausal status. The study explored 1) whether OSA is associated with impaired glucose homeostasis in obese non diabetic premenopausal and menopausal women and 2) the effects of a 3- month lifestyle intervention on glucose homeostasis in OSA women. Design and Methods We consecutively recruited 98 obese women (39 premenopausal) from those referred for a weight loss intervention. Ambulatory nocturnal polysomnography, body composition, oral glucose tolerance test, insulin sensitivity and ? cell function were assessed before and after intervention. Results 41% of premenopausal and 64% of menopausal women had OSA which was associated with worse glucose homeostasis before menopausal status. Mean and minimal nocturnal oxygen saturation (SaO2) was associated with neck/height ratio (NHR), independently of total and central obesity. Mean and minimal nocturnal SaO2 and NHR were correlated with insulin sensitivity and fasting glucose. In multivariate analyses, nocturnal mean SaO2 was negatively and independently correlated with fasting glucose (p<0.0001) and NHR with insulin sensitivity (p<0.0001). In OSA women, the intervention induced a 5% weight reduction and a significant increase in minimal nocturnal SaO2, insulin sensitivity and ? cell function. Changes in fasting glucose and insulin sensitivity were associated with those in minimal nocturnal SaO2 (p<0.05) and not with weight loss. Conclusions In obese women, glucose homeostasis worsens due to nocturnal hypoxia and increased neck circumference through mechanisms partially independent of obesity. OSA is more clearly associated with glucose intolerance in premenopausal than in menopausal women. In OSA women, the improvement of nocturnal hypoxia induced by lifestyle modifications is associated with that of glucose homeostasis.

Gilardini, Luisa; Lombardi, Carolina; Redaelli, Gabriella; Vallone, Luciana; Faini, Andrea; Mattaliano, Paola; Parati, Gianfranco; Invitti, Cecilia



Self-Reported Symptoms of Cold Intolerance in Workers with Injuries of the Hand  

Microsoft Academic Search

Cold intolerance is a well-recognized complication of crushing injuries and amputations in the hand. These symptoms are usually\\u000a thought to resolve within 2 years of injury. The objectives of our study were to determine the prevalence and course over\\u000a time of self-reported symptoms of cold intolerance in workers with hand injuries. Files from a large worker’s compensation\\u000a carrier were randomly selected

Brent Graham; Michel Schofield



Intolerance to nonsteroidal antiinflammatory drugs: Results of controlled drug challenges in 98 patients  

Microsoft Academic Search

BACKGROUND: Controlled oral challenge is the only definitive way to detect the different clinical manifestations of intolerance to nonsteroidal antiinflammatory drugs (NSAIDs). OBJECTIVE: This study was carried out to describe the clinical manifestations of drug challenges in a population with histories of intolerance to NSAIDs. METHODS: Two-hundred forty subjects were included in a single-blind, placebo-controlled drug challenge protocol. RESULTS: Eighty

Joaquín Quiralte; Carlos Blanco; Rodolfo Castillo; Julio Delgado; Teresa Carrillo



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

PubMed Central

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 6–8 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 = 0.35–0.61. 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.

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



Adult Human Milk Intolerance and Intestinal Lactase Deficiency: A Review.  

National Technical Information Service (NTIS)

In man, the dietary milk sugar, lactose, is hydrolyzed to glucose and galactose by the small intestinal enzyme, lactase. This enzyme is located in the brush border of the small intestinal epithelial cell. Recent studies have called attention to the associ...

N. S. Rosenweig



Intolerance to tyrosine kinase inhibitors in chronic myeloid leukemia: Definitions and clinical implications.  


Tyrosine kinase inhibitor (TKI) treatment targeting breakpoint cluster region-Abelson murine leukemia virus, the cause of chronic myeloid leukemia (CML), has revolutionized therapy for patients with this disease. The majority of patients with CML maintain favorable responses with long-term imatinib therapy; however, the availability of the second-generation TKIs nilotinib and dasatinib limits the need for patients intolerant to imatinib to continue with therapy. Unfortunately, there is currently no standard definition of intolerance to imatinib. Common Toxicity Criteria for grading adverse events, designed to identify acute toxicities, are often used to determine intolerance. However, because CML therapies are long-term, patient quality of life may provide a better measure of true intolerance. Several general methods of quantifying patient quality of life are in use for patients with CML, and a CML-specific variant of the M. D. Anderson Symptom Inventory is in development. An appropriate and consistent definition of intolerance will provide clinicians with an algorithm for managing their patients with severe or chronic adverse events during treatment with imatinib. As more long-term data become available for newer TKIs, the definition of intolerance in the context of CML treatment will continue to evolve to maximize the likelihood of durable responses and superior quality of life for patients. PMID:20922786

Pinilla-Ibarz, Javier; Cortes, Jorge; Mauro, Michael J



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

PubMed Central

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.

Kofler, Lukas; Ulmer, Hanno; Kofler, Heinz



Clarithromycin treatment in preterm infants: a pilot study for prevention of feeding intolerance.  


Abstract Objective: To compare the effectiveness of oral clarithromycin versus placebo treatment in preventing feeding intolerance in very low birth weight (VLBW) infants. Study Design: A prospective, randomised controlled trial in which two groups of preterm infants (birth weight <1500?g) were randomised to clarithromycin (7.5?mg/kg/dose every 12?h) or placebo treatment. During the period, 38 infants, whose parents accepted participation, were enrolled in the study. Feeding intolerance and time to achieve full enteral feeding were considered as primary outcome measures. Results: Feeding intolerance was significantly longer in placebo than clarithromycin (p?=?0.031). Time to achieve full feeding after beginning the treatment was equal among the groups. Conclusion: This is the first randomised controlled study of clarithromycin and placebo treatment that compares the improvement of feeding intolerance in VLBW infants. Our findings indicate a dramatic improvement in feeding intolerance after oral clarithromycin treatment. But according to our results, clarithromycin-treated infants were not able to attain full enteral feeding more quickly than placebo. This may be due to prophylactic usage of clarithromycin. Significant differences might have resulted if only infants who had feeding intolerance were recruited. PMID:23570248

Gokmen, Tulin; Ozdemir, Ramazan; Bozdag, Senol; Oguz, Serife Suna; Erdeve, Omer; Uras, Nurdan; Dilmen, Ugur



Shared Variance among Self-Report and Behavioral Measures of Distress Intolerance  

PubMed Central

Distress intolerance may be an important individual difference variable in understanding maladaptive coping responses across diagnostic categories. However, the measurement of distress intolerance remains inconsistent across studies and little evidence for convergent validity among existing measures is available. This study evaluated the overlap among self-report and behavioral measures of distress intolerance in four samples, including an unselected sample, a sample of patients with drug dependence, and two samples of cigarette smokers. Results suggested that the self-report measures were highly correlated, as were the behavioral measures; however, behavioral and self-report measures did not exhibit significant associations with each other. There was some evidence of domain specificity, with anxiety sensitivity demonstrating strong associations with somatic distress intolerance, and a lack of association between behavioral measures that elicit affective distress and those that elicit somatic distress. These findings highlight a potential divergence in the literature relative to the conceptualization of distress intolerance as either sensitivity to distress or as the inability to persist at a task when distressed. Further research is needed to elucidate the conceptualization and measurement of distress intolerance to facilitate future clinical and research applications of this construct.

McHugh, R. Kathryn; Daughters, Stacey B.; Lejuez, Carl W.; Murray, Heather W.; Hearon, Bridget A.; Gorka, Stephanie M.; Otto, Michael W.



Predictors of Beta-Blocker Intolerance and Mortality in Patients After Acute Coronary Syndrome  

PubMed Central

Purpose To investigate the predictors of intolerance to beta-blockers treatment and the 6-month mortality in hospitalized patients with acute coronary syndrome (ACS). Methods This was a single-center, prospective, and longitudinal study including 370 consecutive ACS patients in Killip class I or II. BBs were prescribed according to international guidelines and withdrawn if intolerance occurred. The study was approved by the institutional ethics committee of our university. Statistics: the clinical parameters evaluated at admission, and the related intolerance to BBs and death at 6 months were analyzed using logistic regression (p<0.05)in PATIENTS. Results BB intolerance was observed in 84 patients and was associated with no prior use of statins (OR: 2.16, 95%CI: 1.26–3.69, p= 0.005) and Killip class II (OR: 2.5, 95%CI: 1.30-4.75, p=0.004) in the model adjusted for age, sex, blood pressure, and renal function. There was no association with ST-segment alteration or left anterior descending coronary artery plaque. Intolerance to BB was associated with the greatest risk of death (OR: 4.5, 95%CI: 2.15–9.40, p<0.001). Conclusions After ACS, intolerance to BBs in the first 48 h of admission was associated to non previous use of statin and Killip class II and had a high risk of death within 6 months.

De Stefano, Laercio Martins; Ferraz, Alex Lombardi Barbosa; Ferreira, Ana Lucia dos Anjos; Gut, Ana Lucia; Cogni, Ana Lucia; Farah, Elaine; Matsubara, Beatriz Bojikian



Hypertension and renal function.  


The presence of hypertension in domestic animals is poorly described. Values for hypertension were established in dogs using a direct blood pressure measurement. A protocol was devised to recognize and characterize primary (essential) and secondary hypertension. Essential hypertension was associated with marked elevations in blood pressure and can be shown to be a hereditary disease in dogs. Secondary hypertension is more common and most frequently associated with Cushing's disease and renal failure. Treatment to reduce blood pressure in both groups can be achieved using pharmacologic agents which are more effective than sodium restriction alone. Hypertension appears to be an underdiagnosed disease in dogs. The significance of chronic hypertension in dogs in terms of vascular pathology is not yet clear. PMID:3576594

Bovee, K C; Littman, M P



Hypoglycemia (Low Blood Glucose)  


... Treatment & Care > Blood Glucose Control Hypoglycemia (Low blood glucose) Listen Hypoglycemia is a condition characterized by abnormally ... an emergency. How Can I Prevent Low Blood Glucose? Your best bet is to practice good diabetes ...


CSF glucose test  


Glucose test - CSF; Cerebrospinal fluid glucose test ... The glucose level in the CSF should be 50 - 80 mg/100 mL (or greater than 2/3 of the blood sugar level). Note: Normal value ranges may vary slightly ...


Glucose test (image)  


... person with diabetes constantly manages their blood's sugar (glucose) levels. After a blood sample is taken and tested, it is determined whether the glucose levels are low or high. If glucose levels ...


The role of milk and lactose intolerance in Ethiopian patients with non-ulcer dyspepsia: a case control study.  


Milk intolerance, lactose intolerance and non-ulcer dyspepsia are common among Ethiopians. This study, therefore, was designed to find out if milk intolerance associated with lactase deficiency account for non-ulcer dyspepsia. Ninety-eight patients with non-ulcer dyspepsia and 95 controls were examined and interviewed for demographic data and milk drinking habits. Then each had a lactose tolerance test (LTT), stool examination for pH, ova and parasites. The demographic characteristics and the number of milk drinkers were comparable in the 2 groups. However, milk intolerance and lactose intolerance were significantly higher among the patients with non-ulcer dyspepsia than among the control group (p less than 0.01, p less than 0.05 respectively). The combination of milk intolerance, lactose intolerance and LTT was also significantly different (p less than 0.01). The mean stool pH was markedly reduced after lactose ingestion and there were more ova and parasites in the stools of the control group. These observations suggest that milk intolerance and/or lactose intolerance account significantly for the symptoms of the patients with non-ulcer dyspepsia. However, since lactose intolerance and abnormal LTT are very common among adult Ethiopians symptoms related to the drinking of milk should be interpreted with caution vis-a-vis the results of the lactose loading test. PMID:2787744

Tsega, E; Endeshaw, Y; Mengesha, B; Tedla, B



Dephosphorylation of Translation Initiation Factor 2? Enhances Glucose Tolerance and Attenuates Hepatosteatosis in Mice  

Microsoft Academic Search

SUMMARY The molecular mechanisms linking the stress of un- folded proteins in the endoplasmic reticulum (ER stress) to glucose intolerance in obese animals are poorly understood. In this study, enforced expres- sion of a translation initiation factor 2a (eIF2a)-spe- cific phosphatase, GADD34, was used to selectively compromise signaling in the eIF2(aP)-dependent arm of the ER unfolded protein response in liver

Seiichi Oyadomari; Heather P. Harding; Yuhong Zhang; Miho Oyadomari; David Ron



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


Inherited or acquired impairment of xenobiotics metabolism is a postulated mechanism underlying environment-associated pathologies such as multiple chemical sensitivity, fibromyalgia, chronic fatigue syndrome, dental amalgam disease, and others, also collectively named idiopathic environmental intolerances (IEI). In view of the poor current knowledge of their etiology and pathogenesis, and the absence of recognised genetic and metabolic markers of the diseases. They are often considered "medically unexplained syndromes",. These disabling conditions share the features of polysymptomatic multi-organ syndromes, considered by part of the medical community to be aberrant responses triggered by exposure to low-dose organic and inorganic chemicals and metals, in concentrations far below average reference levels admitted for environmental toxicants. A genetic predisposition to altered biotransformation of environmental chemicals, drugs, and metals, and of endogenous low-molecular weight metabolites, caused by polymorphisms of genes coding for xenobiotic metabolizing enzymes, their receptors and transcription factors appears to be involved in the susceptibility to these environment-associated pathologies, along with epigenetic factors. Free radical/antioxidant homeostasis may also be heavily implicated, indirectly by affecting the regulation of xenobiotic metabolizing enzymes, and directly by causing increased levels of oxidative products, implicated in the chronic damage of cells and tissues, which is in part correlated with clinical symptoms. More systematic studies of molecular epidemiology, toxico- and pharmaco-genomics, elucidating the mechanisms of regulation, expression, induction, and activity of antioxidant/detoxifying enzymes, and the possible role of inflammatory mediators, promise a better understanding of this pathologically increased sensitivity to low-level chemical stimuli, and a solid basis for effective individualized antioxidant- and/or chelator-based treatments. PMID:20929047

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



Internalized racism, body fat distribution, and abnormal fasting glucose among African-Caribbean women in Dominica, West Indies.  

PubMed Central

The current study examined the relationship of internalized racism to glucose intolerance in a population of Afro-Caribbean women aged 18 to 55. Also of interest was whether this relationship would be differentially influenced by the type of body fat distribution or confounded by the level of hostility. A total of 244 women were selected from a systematic sample of households on the island of Dominica, West Indies. Demographic data together with information on internalized racism were collected by questionnaire. Anthropometric information and fasting blood glucose were also measured. Women with high levels of internalized racism exhibited an increased risk of elevated fasting glucose compared to those with low levels of internalized racism (odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.1-5.5). There was no difference in mean body mass index (BMI) by level of internalized racism. However those with high internalized racism had a significantly larger waist circumference after adjusting for age, education, hostility, and elevated fasting glucose status. In multivariate analyses controlling for age, education, hostility, and either weight or BMI, internalized racism remained independently associated with elevated fasting glucose. However, once waist circumference was included in the model, the relationship of internalized racism to elevated fasting glucose was not statistically significant. This study demonstrates a significant relationship between internalized racism and abnormal levels of fasting glucose which may be mediated through abdominal fat. The exact nature of the relationship of internalized racism to glucose intolerance may be an important area of future study.

Butler, Cleve; Tull, Eugene S.; Chambers, Earle C.; Taylor, Jerome



Internalized racism, body fat distribution, and abnormal fasting glucose among African-Caribbean women in Dominica, West Indies.  


The current study examined the relationship of internalized racism to glucose intolerance in a population of Afro-Caribbean women aged 18 to 55. Also of interest was whether this relationship would be differentially influenced by the type of body fat distribution or confounded by the level of hostility. A total of 244 women were selected from a systematic sample of households on the island of Dominica, West Indies. Demographic data together with information on internalized racism were collected by questionnaire. Anthropometric information and fasting blood glucose were also measured. Women with high levels of internalized racism exhibited an increased risk of elevated fasting glucose compared to those with low levels of internalized racism (odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.1-5.5). There was no difference in mean body mass index (BMI) by level of internalized racism. However those with high internalized racism had a significantly larger waist circumference after adjusting for age, education, hostility, and elevated fasting glucose status. In multivariate analyses controlling for age, education, hostility, and either weight or BMI, internalized racism remained independently associated with elevated fasting glucose. However, once waist circumference was included in the model, the relationship of internalized racism to elevated fasting glucose was not statistically significant. This study demonstrates a significant relationship between internalized racism and abnormal levels of fasting glucose which may be mediated through abdominal fat. The exact nature of the relationship of internalized racism to glucose intolerance may be an important area of future study. PMID:11918383

Butler, Cleve; Tull, Eugene S; Chambers, Earle C; Taylor, Jerome



Insulin Therapy, Hyperglycemia, and Hypertension in Type 1 Diabetes Mellitus  

PubMed Central

Background Diabetes mellitus and hypertension are closely linked, but the long-term blood pressure effects of glucose-lowering therapy and hyperglycemia are not clear. Methods We examined the effects of intensive insulin therapy and hyperglycemia on the development of hypertension in the Diabetes Control and Complications Trial (DCCT) and its observational follow-up, the Epidemiology of Diabetes Intervention and Complications (EDIC) study. Incident hypertension was defined as 2 consecutive study visits with a systolic blood pressure of 140 mmHg or higher, a diastolic blood pressure of 90mmHg or higher, or use of antihypertensive medications to treat high blood pressure. Results Participants were enrolled from August 23, 1983, through June 30, 1989. During a 15.8-year median follow-up, 630 of 1441 participants developed hypertension. During the DCCT, the incidence of hypertension was similar comparing participants assigned to intensive vs conventional therapy. However, intensive therapy during the DCCT reduced the risk of incident hypertension by 24% during EDIC study follow-up (hazard ratio, 0.76; 95% confidence interval [CI], 0.64–0.92). A higher hemoglobin A1c level, measured at baseline or throughout follow-up, was associated with increased risk for incident hypertension (adjusted hazard ratios, 1.11 [95% CI, 1.06–1.17] and 1.25 [95% CI, 1.14–1.37], respectively, for each 1% higher hemoglobin A1c level), and glycemic control appeared to mediate the antihypertensive benefit of intensive therapy. Older age, male sex, family history of hypertension, greater baseline body mass index, weight gain, and greater albumin excretion rate were independently associated with increased risk of hypertension. Conclusions Hyperglycemia is a risk factor for incident hypertension in type 1 diabetes, and intensive insulin therapy reduces the long-term risk of developing hypertension.

de Boer, Ian H.; Kestenbaum, Bryan; Rue, Tessa C.; Steffes, Michael W.; Cleary, Patricia A.; Molitch, Mark E.; Lachin, John M.; Weiss, Noel S.; Brunzell, John D.



Orthostatic intolerance in 6 degrees head-down tilt and lower body negative pressure loading  

NASA Astrophysics Data System (ADS)

6 degrees head-down tilt bed rest experiment for 6 days was conducted at Nihon University Itabashi Hospital for 10 male athletes. In order to observe the orthostatic intolerance due to six days head-down tilt bed rest, 70 degrees head up tilt tests were performed before and after the head-down tilt. Two types of orthostatic intolerance were distinguished by the time course of their cardiovascular responses. One was vagotonia type and the other was brain anemia type. The latter type was commonly seen among astronauts after space flight due to the lack of plasma volume. As this volume change is considered to be initiated by some fluid loss from the lower extremities, analysis was made to clarify the relation between the leg volume change and the types of orthostatic intolerance. Nakayama proposed a Heart Rate Controllability Index, which is calculated from the initiate leg volume change and heart rate increase in head up tilt, for an indicator of the orthostatic intolerability. The index was applied to the subjects of six days head-down tilt above mentioned. For the subjects who showed a sign of presyncopy, the index values were higher or lower than that of the rest subjects who showed no sign of presyncopy. In order to evaluate the validity of the index, another experiment was conducted to induce an orthostatic intolerance by a different way of loading. The same types of orthostatic intolerance were observed and the index value hit high in the brain anemia type of orthostatic intolerance, while the vagotonia type showed relatively lower values than the normal group.

Yajima, Kazuyoshi; Miyamoto, Akira; Ito, Masao; Mano, Takaichi; Nakayama, Kiyoshi


[The treatment of hypertension in patients with a metabolic disorder].  


Life expectancy has increased significantly in the last decades in many Western populations, due to the fall of total and cardiovascular death rates. However, morbidity for cardiovascular diseases has decreased to a smaller extent due to the still unsatisfactory improvement in the overall population risk profile. This is true for blood pressure control (with only 20% of hypertensive patients achieving normotension with antihypertensive drugs), hypercholesterolemia (with borderline-high serum cholesterol levels in 50% of the population), and smoking habits. Since hypertension, hypercholesterolemia, hyperglycemia and insulin resistance are frequently associated, further improvement in cardiovascular risk can be obtained only with a comprehensive approach to the hypertensive patients, including dietary and life style modifications and the use of antihypertensive drugs with beneficial effects on lipid and glucose metabolism. It has to be noted in fact that some antihypertensive drugs have divergent effects on lipid and glucose metabolism. Long-term diuretic administration may reduce glucose tolerance, increase serum glucose and cholesterol. Beta-adrenergic blockers with no sympathomimetic activity raise triglycerides and decrease HDL cholesterol. ACE-inhibitors improve insulin sensitivity, while calcium entry blockers are neutral on both glucose and lipid metabolism. Recent reports suggest that alpha-1 adrenoceptor blockers may reduce total and LDL cholesterol while alleviating insulin resistance and increasing HDL cholesterol. PMID:8562259

Dal Palù, C; Semplicini, A



[Endocrine hypertension in pregnancy].  


Hypertension is a frequent complication of pregnancy and may compromise fetal and maternal outcome. Hypertension may be pregnancy-induced, essential or secondary to endocrine disorders. Most cases of endocrine hypertension are the consequence of adrenal diseases. Pheochromocytoma, hypercorticism, primary aldosteronism or glucocorticoid-remediable aldosteronism can be present or diagnosed at any term and may cause severe hypertension. The most hazardous form of endocrine hypertension during pregnancy is pheochromocytoma because it may involve paroxysmal arrhythmia and/or hypertension during labor. Clinical clues and biological tests are similar to those used in non-pregnant subjects. Tests for tumor location are limited to ultrasound and magnetic resonance scans in order to avoid maternal and fetal irradiation. Medication to prepare for pheochromocytoma surgery uses alpha- and beta-blockers. The timing of surgery depends on the term of pregnancy at the diagnosis of the tumor. PMID:12442092

Launay-Mignot, P; Roueff, S; Tropeano, A-I; Thaunat, O; Plouin, P F



Pathophysiology of obesity hypertension  

Microsoft Academic Search

Excess weight gain is a major cause of essential hypertension, and abnormal kidney function appears to be a cause as well\\u000a as a consequence of obesity hypertension. Excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis\\u000a play a major role in mediating increased blood pressure associated with weight gain. Activation of the renin-angiotensin and\\u000a sympathetic nervous systems and

John E. Hall



FGF19 action in the brain induces insulin-independent glucose lowering  

PubMed Central

Insulin-independent glucose disposal (referred to as glucose effectiveness [GE]) is crucial for glucose homeostasis and, until recently, was thought to be invariable. However, GE is reduced in type 2 diabetes and markedly decreased in leptin-deficient ob/ob mice. Strategies aimed at increasing GE should therefore be capable of improving glucose tolerance in these animals. The gut-derived hormone FGF19 has previously been shown to exert potent antidiabetic effects in ob/ob mice. In ob/ob mice, we found that systemic FGF19 administration improved glucose tolerance through its action in the brain and that a single, low-dose i.c.v. injection of FGF19 dramatically improved glucose intolerance within 2 hours. Minimal model analysis of glucose and insulin data obtained during a frequently sampled i.v. glucose tolerance test showed that the antidiabetic effect of i.c.v. FGF19 was solely due to increased GE and not to changes of either insulin secretion or insulin sensitivity. The mechanism underlying this effect appears to involve increased metabolism of glucose to lactate. Together, these findings implicate the brain in the antidiabetic action of systemic FGF19 and establish the brain’s capacity to rapidly, potently, and selectively increase insulin-independent glucose disposal.

Morton, Gregory J.; Matsen, Miles E.; Bracy, Deanna P.; Meek, Thomas H.; Nguyen, Hong T.; Stefanovski, Darko; Bergman, Richard N.; Wasserman, David H.; Schwartz, Michael W.



The new hypertension guidelines.  


The Canadian Hypertension Education Program (CHEP) has published guidelines annually since 2000. The CHEP guidelines are a model of concise, comprehensive, up-to-date, evidence-rated guidelines for physicians who diagnose and treat hypertension. The guidelines address measurement of blood pressure and the definition of hypertension, secondary hypertension evaluation and treatment, and blood pressure targets and medication choices in patients with and without compelling indications. This review describes CHEP's process for developing guidelines and provides an overview of the 2013 recommendations. PMID:24088284

H Stern, Ralph



Pediatric endocrine hypertension  

PubMed Central

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.

Bhavani, Nisha



Genic intolerance to functional variation and the interpretation of personal genomes.  


A central challenge in interpreting personal genomes is determining which mutations most likely influence disease. Although progress has been made in scoring the functional impact of individual mutations, the characteristics of the genes in which those mutations are found remain largely unexplored. For example, genes known to carry few common functional variants in healthy individuals may be judged more likely to cause certain kinds of disease than genes known to carry many such variants. Until now, however, it has not been possible to develop a quantitative assessment of how well genes tolerate functional genetic variation on a genome-wide scale. Here we describe an effort that uses sequence data from 6503 whole exome sequences made available by the NHLBI Exome Sequencing Project (ESP). Specifically, we develop an intolerance scoring system that assesses whether genes have relatively more or less functional genetic variation than expected based on the apparently neutral variation found in the gene. To illustrate the utility of this intolerance score, we show that genes responsible for Mendelian diseases are significantly more intolerant to functional genetic variation than genes that do not cause any known disease, but with striking variation in intolerance among genes causing different classes of genetic disease. We conclude by showing that use of an intolerance ranking system can aid in interpreting personal genomes and identifying pathogenic mutations. PMID:23990802

Petrovski, Slavé; Wang, Quanli; Heinzen, Erin L; Allen, Andrew S; Goldstein, David B



A New Thiopurine S-Methyltransferase Haplotype Associated With Intolerance to Azathioprine.  


The authors have analyzed single nucleotide polymorphisms in the thiopurine S-methyltransferase (TPMT) gene in the context of efficacy and toxicity of azathioprine (AZA) to determine possible genotype-phenotype correlations between TPMT allelic variants and response to AZA treatment in 76 Italian patients with myasthenia gravis. They confirm known intronic and exonic TPMT polymorphisms that do not correlate with AZA responses and demonstrate a novel intronic polymorphism in a patient intolerant to AZA. Most importantly, they show that of the 22 AZA-intolerant patients, all 5 who carried mutations of the intolerance-linked haplotype TPMT(?)3A also carried the intronic T140+114A (rs3931660), all 3 mutations being part of a new haplotype designated TMPT(?)3E. TPMT(?)3E was not observed in unresponsive or responsive patients. The association of TPMT(?)3E with AZA intolerance and its frequency must be ascertained in larger, ethnically different cohorts. Nevertheless, in view of the highly significant association (Psim = 0.0026) between TPMT(?)3E and AZA intolerance in the study, this new haplotype should be taken into consideration in pharmacogenetic profiling for AZA. PMID:22308273

Colleoni, Lara; Kapetis, Dimos; Maggi, Lorenzo; Camera, Giorgia; Canioni, Eleonora; Cavalcante, Paola; Kerlero de Rosbo, Nicole; Baggi, Fulvio; Antozzi, Carlo; Confalonieri, Paolo; Mantegazza, Renato; Bernasconi, Pia



A new thiopurine s-methyltransferase haplotype associated with intolerance to azathioprine.  


The authors have analyzed single nucleotide polymorphisms in the thiopurine S-methyltransferase (TPMT) gene in the context of efficacy and toxicity of azathioprine (AZA) to determine possible genotype-phenotype correlations between TPMT allelic variants and response to AZA treatment in 76 Italian patients with myasthenia gravis. They confirm known intronic and exonic TPMT polymorphisms that do not correlate with AZA responses and demonstrate a novel intronic polymorphism in a patient intolerant to AZA. Most importantly, they show that of the 22 AZA-intolerant patients, all 5 who carried mutations of the intolerance-linked haplotype TPMT*3A also carried the intronic T140+114A (rs3931660), all 3 mutations being part of a new haplotype designated TMPT*3E. TPMT*3E was not observed in unresponsive or responsive patients. The association of TPMT*3E with AZA intolerance and its frequency must be ascertained in larger, ethnically different cohorts. Nevertheless, in view of the highly significant association (Psim = 0.0026) between TPMT*3E and AZA intolerance in the study, this new haplotype should be taken into consideration in pharmacogenetic profiling for AZA. PMID:23400745

Colleoni, Lara; Kapetis, Dimos; Maggi, Lorenzo; Camera, Giorgia; Canioni, Eleonora; Cavalcante, Paola; Kerlero de Rosbo, Nicole; Baggi, Fulvio; Antozzi, Carlo; Confalonieri, Paolo; Mantegazza, Renato; Bernasconi, Pia



Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes  

PubMed Central

A central challenge in interpreting personal genomes is determining which mutations most likely influence disease. Although progress has been made in scoring the functional impact of individual mutations, the characteristics of the genes in which those mutations are found remain largely unexplored. For example, genes known to carry few common functional variants in healthy individuals may be judged more likely to cause certain kinds of disease than genes known to carry many such variants. Until now, however, it has not been possible to develop a quantitative assessment of how well genes tolerate functional genetic variation on a genome-wide scale. Here we describe an effort that uses sequence data from 6503 whole exome sequences made available by the NHLBI Exome Sequencing Project (ESP). Specifically, we develop an intolerance scoring system that assesses whether genes have relatively more or less functional genetic variation than expected based on the apparently neutral variation found in the gene. To illustrate the utility of this intolerance score, we show that genes responsible for Mendelian diseases are significantly more intolerant to functional genetic variation than genes that do not cause any known disease, but with striking variation in intolerance among genes causing different classes of genetic disease. We conclude by showing that use of an intolerance ranking system can aid in interpreting personal genomes and identifying pathogenic mutations.

Petrovski, Slave; Wang, Quanli; Heinzen, Erin L.; Allen, Andrew S.; Goldstein, David B.



Effect of acacia polyphenol on glucose homeostasis in subjects with impaired glucose tolerance: A randomized multicenter feeding trial  

PubMed Central

Numerous in vitro and animal studies, as well as clinical trials have indicated that plant-derived polyphenols exert beneficial effects on glucose intolerance or type 2 diabetes. This clinical study aimed to investigate the effects of acacia polyphenol (AP) on glucose and insulin responses to an oral glucose tolerance test (OGTT) in non-diabetic subjects with impaired glucose tolerance (IGT). A randomized, double-blind, placebo-controlled trial was conducted in a total of 34 enrolled subjects. The subjects were randomly assigned to the AP-containing dietary supplement (AP supplement; in a daily dose of 250 mg as AP; n=17) or placebo (n=17) and the intervention was continued for 8 weeks. Prior to the start of the intervention (baseline) and after 4 and 8 weeks of intervention, plasma glucose and insulin were measured during a two-hour OGTT. Compared with the baseline, plasma glucose and insulin levels at 90 and/or 120 min, as well as the total area under the curve values during the OGTT (AUC0?2h) for glucose and insulin, were significantly reduced in the AP group, but not in the placebo group after intervention for 8 weeks. The decline from baseline in plasma glucose and insulin at 90 or 120 min of the OGTT for the AP group was significantly greater compared with that of the placebo group after 8 weeks of intervention. No AP supplement-related adverse side-effects nor any abnormal changes in routine laboratory tests and anthropometric parameters were observed throughout the study period. The AP supplement may have the potential to improve glucose homeostasis in subjects with IGT.




Analysis for hypertension and related risk factors of physical examination population  

PubMed Central

Background and Objectives: Essential hypertension is the most common chronic disease. To provide a basis for developing the prevention and control strategies of hypertension by epidemiological investigation on factors related to hypertension in health examination population. Methods: Data of health examination population from Jilin municipal enterprise and public institutions during January 2011 and July 2012 were randomly selected, and statistical analysis was performed for the age, gender, body mass index, blood lipids, blood uric acid, serum creatinine, blood glucose and hypertension classification indexes. Results: 1859 patients were diagnosed as hypertension. The detection rate of hypertension, awareness rate, new discovery rate, treatment rate, control rate and rate of the patients with family history of hypertension were 21.0%, 27.5%, 72.5%, 19.1%, 6.0% and 26.7%, respectively. A statistically significant difference was found in serum creatinine, blood glucose, serum cholesterol, L-DLC, coronary disease, stroke and diabetes mellitus by the comparison among the different blood pressure grades. There was a difference in blood pressure, blood uric acid, blood creatinine, glucose, total cholesterol, triglycerides, H-DLC, L-DLC and other indexes between female and male. No difference was found in the family history of hypertension, renal damage, blood uric acid, triglycerides and H-DLC among the different blood pressure levels. Conclusions: The hypertension in health examination population has the features of high new discovery rate, low awareness rate and low treatment rate. The factors of age, gender, body mass index, serum creatinine, blood glucose, blood cholesterol, L-DLC, coronary heart disease, stroke and diabetes are associated closely with hypertension.

Qiao, Sen; Ye, Qing; Dou, Yue; Li, Mingzi; Kou, Yuhong; Qian, Dawei; Li, Mingcheng; Wang, Gang



Metabolic Effects of Long-term Treatments With Nifedipine-Retard and Captopril in Young Hypertensive Patients  

Microsoft Academic Search

The objective of this study was to clarify potential differences in the metabolism of glucose and lipids in a long-term treatment (for 5 years) for hypertension among nifedipine-retard and captopril in young, nonobese hypertensive men (HT). In 78 previously untreated HT who were given nifedipine-retard and in 81 HT given captopril, blood pressure (BP), pulse rate, blood glucose, and plasma

Kazuko Masuo; Hiroshi Mikami; Toshio Ogihara; Michael L. Tuck



Managing chronic myeloid leukemia patients intolerant to tyrosine kinase inhibitor therapy  

PubMed Central

The outcomes for patients with chronic myeloid leukemia have improved dramatically with the development and availability of BCR–ABL1 tyrosine kinase inhibitors (TKIs) over the past decade. TKI therapy has a superior safety profile compared with the previous standard of care, interferon-?, and most adverse events (AEs) observed with front-line and second-line TKI treatment are managed with supportive care. However, some patients are intolerant to TKI therapy and experience AEs that cannot be managed through dose reduction or symptomatic treatment. Careful management of AEs helps patients to remain adherent with treatment and increases their chances for successful outcomes. Proactive vigilance for potential AEs and treatment strategies that reduce symptom burden will help to minimize patient intolerance. This review discusses the most common AEs associated with intolerance to TKI therapy and treatment strategies to help manage patients at risk for or experiencing these events.

DeAngelo, D J



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

SciTech Connect

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

Schrander, J.J.; Unsalan-Hooyen, R.W.; Forget, P.P.; Jansen, J. (Academic Hospital Maastricht (Netherlands))



Effects of regional intravenous guanethidine block in posttraumatic cold intolerance in hand amputees.  


In twenty-four patients with intolerance to cold after partial or complete finger amputations, lower skin temperature together with cold and vibration allodynia (allodynia = pain due to a non-noxious stimulus to neural skin) were found in the cold intolerant area compared with the corresponding area in the uninjured hand. When treated with regional intravenous guanethidine block nine patients became free from symptoms for up to twelve weeks, which is longer than would be expected from the duration of the known pharmacological effects of guanethidine. The patients had several features in common with reflex sympathetic dystrophies, and we suggest that neurogenic rather than vascular disturbances are mainly involved in the post-traumatic cold intolerance syndrome. PMID:4031591

Engkvist, O; Wahren, L K; Wallin, G; Torebjrk, E; Nystrom, B



Predictors of Hypertension Among Filipino Immigrants in the Northeast US.  


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/m(2), 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

Ursua, Rhodora A; 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



Lifestyle and hypertension  

Microsoft Academic Search

Lifestyle factors are critical determinants of blood pressure levels operating against a background of genetic susceptibility. Excess body fat is a predominant cause of hypertension with additive effects of dietary salt, alcohol, and physical inactivity. Controlled trials in hypertensives show blood pressure lowering effects of supplemental potassium, fibre, n-3 fatty acids, and diets rich in fruit and vegetables and low

L. J. Beilin; I. B. Puddey; V. Burke



Retinoids and Pulmonary Hypertension  

Microsoft Academic Search

Background—Retinoic acid has antimitogenic effects on smooth muscle cells. Studies on the systemic circulation suggest that it may reduce vascular thickening. Relationships between retinoids and pulmonary hypertension\\/pulmonary vascular remodeling, however, have not been explored. Thus, the present study examined retinoid levels in plasma of patients with idiopathic pulmonary arterial hypertension and the effects of retinoic acid on human pulmonary artery

Ioana R. Preston; Guangwen Tang; Jason U. Tilan; Nicholas S. Hill; Yuichiro J. Suzuki



Obesity and hypertension  

Microsoft Academic Search

Substantial evidence from epidemiological data supports a link between obesity and hypertension. However, the relationship between the two disorders is not straightforward and most likely represents an interaction of demographic, genetic, hormonal, renal, and hemodynamic factors. Age, race, and sex also modulate the strength of the association between obesity and hypertension. Hyperinsulinemia, which is characteristic of obesity, can contribute to

Nasser Mikhail; Michael S. Golub; Michael L. Tuck



Hypertension after renal transplant.  


Hypertension is common after renal transplant and is associated with adverse graft and patient outcomes. A thorough understanding of the unique factors that operate in renal transplant recipients is essential for the proper evaluation and management of this disorder. In this review, the authors outline the pathogenesis, diagnostic workup, and treatment of hypertension after renal transplant. PMID:17617764

Tedla, Fasika; Hayashi, Rick; McFarlane, Samy I; Salifu, Moro O



Tff3, as a Novel Peptide, Regulates Hepatic Glucose Metabolism  

PubMed Central

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder strongly associated with hepatic glucose intolerance and insulin resistance. The trefoil peptides are a family of small regulatory proteins and Tff3 is widely expressed in multiple tissues including liver. But the roles of Tff3 in regulation of glucose metabolism and insulin sensitivity in liver remain unclear. Here we show that the hepatic Tff3 expression levels were decreased in ob/ob and high-fat diet-induced obese mice. Overexpression of Tff3 in primary mouse hepatocytes inhibited the expression of gluconeogenic genes, including G6pc, PEPCK and PGC-1?, subsequently decreasing cellular glucose output. GTT and ITT experiments revealed that adenovirus-mediated overexpression of Tff3 in diabetic or obese mice improved glucose tolerance and insulin sensitivity. Collectively, our results indicated that Tff3 peptides are involved in glucose homeostasis and insulin sensitivity, providing a promising peptide on new therapies against the metabolic disorders associated with T2DM.

Xue, Yuan; Shen, Lian; Cui, Ying; Zhang, Huabing; Chen, Qi; Cui, Anfang; Fang, Fude; Chang, Yongsheng



A neuroendocrine model of obesity worsen insulin resistance of spontaneously hypertensive rats: a new model of type 2 diabetes  

Microsoft Academic Search

Obesity is frequently associated with hypertension and type 2 diabetes caracterized by an insulin resistance state, but in general models of inducible obesity in rats do not show an elevated blood pressure (BP).Aim: to evaluate the effects of an neuroendocrine model of obesity, eg neonatal monosodium glutamate (MSG) administration, on BP and glucose metabolism of spontaneously hypertensive rats (SHR).Methods: SHR

Carolina B. N. Ferreira; Andrea P. Pastore; Mario L. R. Cesaretti; Milton Ginoza; Maria Tereza Zanella; Artur B. Ribeiro; Osvaldo Kohlmann



Hypertension in the elderly.  


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

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



[Hypertension in pregnancy].  


Hypertension in pregnancy is one of the main causes of maternal, fetal and newborn morbidity and mortality in civilised countries. Current recommendations of the European Society for Hypertension prefer definition of hypertension in pregnancy based on absolute values of blood pressure, i.e. systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg. The most important task of classification of hypertension in pregnancy is to distinguish whether hypertension comes before pregnancy (the so called pre-existing hypertension) or whether it is a pregnancy-induced condition (the so called gestational hypertension). Pre-existing hypertension is diagnosed either before pregnancy or within the first 20 weeks of pregnancy. Gestational hypertension is characterised with poor blood circulation in many body organs, higher value of blood pressure usually being just one of the characteristic features. Non-pharmacological treatment of hypertension must be considered in pregnant women with systolic blood pressure 140-150 mm Hg or diastolic blood pressure 90-99 mm Hg. Salt restriction is not recommended, as well as weight reduction in obese women. Systolic blood pressure > or = 170 mm Hg or diastolic blood pressure > or = 110 mm Hg in pregnant women must be considered serious condition necessitating hospitalisation. Pharmacological therapy should include labetalol i.v. or metyldopa or nifedipin administered orally. Intravenous administration of dihydralazine is no longer a therapy of choice, for its use is connected with increased occurrence of adverse effects. The threshold values for commencement of anti-hypertension therapy are systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg in females with gestational hypertension without proteinuria or with pre-existing hypertension before commencement of 28th week of pregnancy. Drug administration to reduce hypertension is instituted after reaching the same threshold values in females with gestational hypertension and proteinuria or after occurrence of the symptoms any time during pregnancy, with the same threshold values of blood pressure in the case of pre-existing hypertension at the presence of accompanying diseases or organ malfunction and further in the case of pre-existing hypertension and gestational hypertension. In other cases drug treatment of hypertension is recommended at systolic blood pressure values of 150 mm Hg or diastolic blood pressure values of 95 mm Hg. Unless serious hypertension is involved, the drugs of choice include metyldope, labetalol, calcium channel blockers and beta-blockers. Calcium channel blockers are considered safe, unless administered concurrently with magnesium sulphate (risk of hypotension in the case of potential synergism). ACE inhibitors and angiotensine blockers II (AT1-blockers) are contraindicated in pregnancy. Treatment with diuretics is not substantiated, unless oliguria is present. I.v. magnesium sulphate is recommended for prevention of eclampsia and spasm treatment. PMID:16722158

Cífková, R



Epigenomics of hypertension.  


Multiple genes and pathways are involved in the pathogenesis of hypertension. Epigenomic studies of hypertension are beginning to emerge and hold great promise of providing novel insights into the mechanisms underlying hypertension. Epigenetic marks or mediators including DNA methylation, histone modifications, and noncoding RNA can be studied at a genome or near-genome scale using epigenomic approaches. At the single gene level, several studies have identified changes in epigenetic modifications in genes expressed in the kidney that correlate with the development of hypertension. Systematic analysis and integration of epigenetic marks at the genome-wide scale, demonstration of cellular and physiological roles of specific epigenetic modifications, and investigation of inheritance are among the major challenges and opportunities for future epigenomic and epigenetic studies of hypertension. PMID:24011581

Liang, Mingyu; Cowley, Allen W; Mattson, David L; Kotchen, Theodore A; Liu, Yong



Hypertension in the elderly  

PubMed Central

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.

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



Maternal intolerance of uncertainty, anxiety, and adherence with food challenge referrals.  


Anxiety regarding food challenges may serve an important role in parents' decisions to adhere to their child's food challenge referrals. This study examined the role of intolerance of uncertainty in food challenge referral adherence by assessing state/trait anxiety among mothers whose children were referred for a food challenge. Mothers whose children passed a food challenge reported significant decreases in anxiety regarding allergic reactions, but intolerance of uncertainty did not predict adherence. Trust in the physician was a primary reason mothers attended the food challenge, suggesting that physicians should consider the impact of the physician-patient relationship when treating these families. PMID:23129828

Herbert, Linda J; Dahlquist, Lynnda M; Bollinger, Mary E



Glucose homeostasis in mice is transglutaminase 2 independent.  


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 (TG2(R579A)), which is constitutively active for transamidase activity. Intraperitoneal GTTs and ITTs revealed no significant differences between WT and TG2(R579A/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

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



Natural sweetening of food products by engineering Lactococcus lactis for glucose production.  


We show that sweetening of food products by natural fermentation can be achieved by a combined metabolic engineering and transcriptome analysis approach. A Lactococcus lactis ssp. cremoris strain was constructed in which glucose metabolism was completely disrupted by deletion of the genes coding for glucokinase (glk), EII(man/glc) (ptnABCD), and the newly discovered glucose-PTS EII(cel) (ptcBAC). After introducing the lactose metabolic genes, the deletion strain could solely ferment the galactose moiety of lactose, while the glucose moiety accumulated extracellularly. Additionally, less lactose remained in the medium after fermentation. The resulting strain can be used for in situ production of glucose, circumventing the need to add sweeteners as additional ingredients to dairy products. Moreover, the enhanced removal of lactose achieved by this strain could be very useful in the manufacture of products for lactose intolerant individuals. PMID:16844396

Pool, Wietske A; Neves, Ana Rute; Kok, Jan; Santos, Helena; Kuipers, Oscar P



Endocrine arterial hypertension: therapeutic approach in clinical practice.  


This review describes the therapeutic approach of endocrine arterial hypertension in clinical practice. In mineralocorticoid-related hypertension, adrenalectomy is the treatment of choice for aldosterone-producing adenomas and monolateral primary aldosteronism, whereas pharmacologic blood pressure (BP) control is indicated for the other forms of primary aldosteronism such as bilateral adrenal hyperplasia. Spironolactone is the drug of choice, but intolerable side effects limit its use; amiloride or eplerenone are a valid alternative. If BP remains uncontrolled, angiotensin converting enzyme inhibitors (ACE-I), angiotensin II receptor antagonists (AII-RA) and calcium channel blockers (CCB) may be added. Hypertension accompanying Cushing's syndrome can be approached with surgery, but antihypertensive treatment both pre- and postoperative is required as well. Eplerenone, AII-RA and ACE-I are indicated, while peroxisome proliferator activated receptor upsilon agonists may help for the insulin resistance syndrome. Drugs that suppress steroidogenesis should be used with care because of their serious side effects. Subjects with catecholamine-dependent hypertension due to a neuroendocrine neoplasm need to undergo preoperative alpha-adrenergic blockade with phenoxybenzamine or doxazozine. When adequate alpha-adrenergic blockade is achieved, beta-adrenergic blockade with low dose propranolol may be added. If target BP is not achieved, CCB and/or metyrosine are indicated. Laparoscopic adrenalectomy is the procedure of choice for solitary intra-adrenal neoplasms <8 cm. Acute hypertensive crises that may occur before or during surgery should be treated intravenously with sodium nitroprusside, phentolamine, nicardipine or labetalol. For malignant neoplasms, chemo- and radiopharmaceutical therapy may be considered. PMID:18923367

Mazza, A; Armigliato, M; Zamboni, S; Rempelou, P; Rubello, D; Pessina, A C; Casiglia, E



Thiazolidinedione derivative improves fat distribution and multiple risk factors in subjects with visceral fat accumulation—double-blind placebo-controlled trial  

Microsoft Academic Search

Background: It has been clarified that visceral fat accumulation leads to atherosclerosis through multiple risk factors such as insulin resistance, glucose intolerance, hyperlipidemia and hypertension. So far, it has been reported that a thaizolidinedione derivative, troglitazone, improves the insulin resistance in subjects with diabetes, glucose intolerance and obesity. However, it has not been reported yet that troglitazone affects fat distribution

Tadashi Nakamura; Tohru Funahashi; Shizuya Yamashita; Makoto Nishida; Yoshiharu Nishida; Masahiko Takahashi; Kikuko Hotta; Hiroshi Kuriyama; Shinji Kihara; Noriyuki Ohuchi; Takamichi Nishimura; Bun-ichiro Kishino; Katsunori Ishikawa; Toshiharu Kawamoto; Katsuto Tokunaga; Chisa Nakagawa; Ikuo Mineo; Fumiko Watanabe; Seiichiro Tarui; Yuji Matsuzawa



The negative influence of high-glucose ambience on neurogenesis in developing quail embryos.  


Gestational diabetes is defined as glucose intolerance during pregnancy and it is presented as high blood glucose levels during the onset pregnancy. This condition has an adverse impact on fetal development but the mechanism involved is still not fully understood. In this study, we investigated the effects of high glucose on the developing quail embryo, especially its impact on the development of the nervous system. We established that high glucose altered the central nervous system mophologically, such that neural tube defects (NTDs) developed. In addition, we found that high glucose impaired nerve differentiation at dorsal root ganglia and in the developing limb buds, as revealed by neurofilament (NF) immunofluorescent staining. The dorsal root ganglia are normally derived from neural crest cells (NCCs), so we examine the delamination of NCCs from dorsal side of the neural tube. We established that high glucose was detrimental to the NCCs, in vivo and in vitro. High glucose also negatively affected neural differentiation by reducing the number and length of neurites emanating from neurons in culture. We established that high glucose exposure caused an increase in reactive oxidative species (ROS) generation by primary cultured neurons. We hypothesized that excess ROS was the factor responsible for impairing neuron development and differentiation. We provided evidence for our hypothesis by showing that the addition of vitamin C (a powerful antioxidant) could rescue the damaging effects of high glucose on cultured neurons. PMID:23818954

Chen, Yao; Fan, Jian-xia; Zhang, Zhao-long; Wang, Guang; Cheng, Xin; Chuai, Manli; Lee, Kenneth Ka Ho; Yang, Xuesong



Inositol 1,4,5-trisphosphate receptor 1 mutation perturbs glucose homeostasis and enhances susceptibility to diet-induced diabetes.  


The inositol 1,4,5-trisphosphate receptors (IP3Rs) as ligand-gated Ca(2)(+) channels are key modulators of cellular processes. Despite advances in understanding their critical role in regulating neuronal function and cell death, how this family of proteins impact cell metabolism is just emerging. Unexpectedly, a transgenic mouse line (D2D) exhibited progressive glucose intolerance as a result of transgene insertion. Inverse PCR was used to identify the gene disruption in the D2D mice. This led to the discovery that Itpr1 is among the ten loci disrupted in chromosome 6. Itpr1 encodes for IP3R1, the most abundant IP3R isoform in mouse brain and also highly expressed in pancreatic ?-cells. To study IP3R1 function in glucose metabolism, we used the Itpr1 heterozygous mutant mice, opt/+. Glucose homeostasis in male mice cohorts was examined by multiple approaches of metabolic phenotyping. Under regular diet, the opt/+ mice developed glucose intolerance but no insulin resistance. Decrease in second-phase glucose-stimulated blood insulin level was observed in opt/+ mice, accompanied by reduced ?-cell mass and insulin content. Strikingly, when fed with high-fat diet, the opt/+ mice were more susceptible to the development of hyperglycemia, glucose intolerance, and insulin resistance. Collectively, our studies identify the gene Itpr1 being interrupted in the D2D mice and uncover a novel role of IP3R1 in regulation of in vivo glucose homeostasis and development of diet-induced diabetes. PMID:21565852

Ye, Risheng; Ni, Min; Wang, Miao; Luo, Shengzhan; Zhu, Genyuan; Chow, Robert H; Lee, Amy S



Independent and opposite associations of waist and hip circumferences with diabetes, hypertension and dyslipidemia: the AusDiab Study  

Microsoft Academic Search

OBJECTIVE: Fat distribution as measured by waist-to-hip ratio has been shown to be an important independent predictor of glucose intolerance. Few studies, however, have considered the contributions of the waist and hip circumferences independently. The aim of this study was to investigate the independent associations of waist and hip circumference with diabetes in a large population-based study, and to investigate

M. B. Snijder; P. Z. Zimmet; M. Visser; J. M. Dekker; J. C. Seidell; J. E. Shaw



Sacral neuromodulation outcomes for the treatment of refractory idiopathic detrusor overactivity stratified by indication: Lack of anticholinergic efficacy versus intolerability  

PubMed Central

Introduction: Patients may fail oral overactive bladder therapies due to either poor drug efficacy or intolerability. We determined if the success of sacral neuromodulation varies if performed secondary to lack of anticholinergic efficacy versus drug intolerability. Methods: A retrospective review was performed on 152 patients undergoing staged sacral neuromodulation from 2004 to 2010 for refractory idiopathic detrusor overactivity with or without urge incontinence. Outcomes following sacral neuromodulation trials were compared based on the primary indication for anticholinergic failure: lack of drug efficacy versus intolerable side effects. Results: Overall, successful sacral neuromodulation trials were reported in 70% (106/152) of patients. Successful outcomes were noted in 70% (89/128) and 71% (17/24) of patients with poor anti-cholinergic efficacy and drug intolerability, respectively (p = NS). Conclusions: We found no significant difference in outcome success in patients undergoing sacral neuromodulation trials for refractory detrusor overactivity due to lack of anticholinergic efficacy versus intolerability.

Davis, Tanya; Makovey, Iryna; Guralnick, Michael L.; O'Connor, R. Corey



The 2009 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 - therapy  

PubMed Central

OBJECTIVE: To update the evidence-based recommendations for the prevention and management of hypertension in adults for 2009. OPTIONS AND OUTCOMES: For lifestyle and pharmacological interventions, evidence from randomized controlled trials and systematic reviews of trials was preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. Progression of kidney dysfunction was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease. EVIDENCE: A Cochrane collaboration librarian conducted an independent MEDLINE search from 2007 to August 2008 to update the 2008 recommendations. To identify additional published studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence. RECOMMENDATIONS: For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to less than 2300 mg (100 mmol)/day (and 1500 mg to 2300 mg [65 mmol to 100 mmol]/day in hypertensive patients); perform 30 min to 60 min of aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index 18.5 kg/m2 to 24.9 kg/m2) and waist circumference (smaller than 102 cm for men and smaller than 88 cm for women); limit alcohol consumption to no more than 14 units per week in men or nine units per week in women; follow a diet that is reduced in saturated fat and cholesterol, and that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and consider stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on by the patient’s global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to lower than 140/90 mmHg in all patients, and to lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor antagonists (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as the initial treatment of hypertension if the systolic blood pressure is 20 mmHg above the target or if the diastolic blood pressure is 10 mmHg above the target. The combination of ACE inhibitors and ARBs should not be used. Other agents appropriate for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine CCBs or ARBs. In patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with proteinuric nondiabetic chronic kidney disease, ACE inhibitors or ARBs (if intolerant to ACE inhibitors) are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position

Khan, Nadia A; Hemmelgarn, Brenda; Herman, Robert J; Bell, Chaim M; Mahon, Jeff L; Leiter, Lawrence A; Rabkin, Simon W; Hill, Michael D; Padwal, Raj; Touyz, Rhian M; Larochelle, Pierre; Feldman, Ross D; Schiffrin, Ernesto L; Campbell, Norman RC; Moe, Gordon; Prasad, Ramesh; Arnold, Malcolm O; Campbell, Tavis S; Milot, Alain; Stone, James A; Jones, Charlotte; Ogilvie, Richard I; Hamet, Pavel; Fodor, George; Carruthers, George; Burns, Kevin D; Ruzicka, Marcel; deChamplain, Jacques; Pylypchuk, George; Petrella, Robert; Boulanger, Jean-Martin; Trudeau, Luc; Hegele, Robert A; Woo, Vincent; McFarlane, Phil; Vallee, Michel; Howlett, Jonathan; Bacon, Simon L; Lindsay, Patrice; Gilbert, Richard E; Lewanczuk, Richard Z; Tobe, Sheldon



[Management of resistant hypertension].  


High blood pressure is one of the leading factors influencing the cardiovascular risk. Despite current knowledge on the management of hypertension and the numerous antihypertensive drugs available, hypertension remains insufficiently controlled and part of these "uncontrolled" patients meet the definition of resistant hypertension. Resistant hypertension is defined by the failure of lowering blood pressure values to blood pressure target (office blood pressure < 140/90 or 130/80 mmHg in patients with diabetes or chronic kidney disease) despite appropriate treatment with optimal doses of three antihypertensive drugs from three different classes, one of which is a diuretic. Pseudoresistance should be excluded by using 24h ambulatory blood pressure or home blood pressure. The management of resistant hypertension includes the screening of secondary forms of hypertension and the identification of life style factors such as obesity, excessive alcohol and dietary sodium intake, volume overload, drug-induced hypertension. The treatment associates lifestyle changes, discontinuation of interfering substances, association of antihypertensive drugs on top of the initial triple therapy (including diuretic, blockers of the renin-angiotensin system and calcium channel blockers) ie aldosterone antagonists as fourth line treatment. New device-based approaches aiming to decrease the sympathetic tone including renal denervation and baroreceptor stimulation are under development. PMID:23789498

Briet, Marie; Bobrie, Guillaume; Azizi, Michel



Pathogenesis of the essential hypertensions  

Microsoft Academic Search

The pathogenesis of essential hypertension (EH) is reviewed with a special focus on the development phase or the pre-hypertensive period. Three animal models are presented: the spontaneously hypertensive rat, the Dahl's salt-sensitive rat, and the Milan hypertensive rat. Some of the findings in animal models have ispired new fields and technical approaches for studying EH in man. From the original

Jean-Guy Mongeau



Molecular Structure of Glucose  

NSDL National Science Digital Library

Glucose is named after a Greek word meaning sugar or sweet. One of the most important compounds to life, glucose was first discovered by Andreas Marggraf in 1747. The structure for glucose was first discovered by Emil Fischer during the late 19th century and early 20th century. Glucose is found in all life forms and is used as a means of storing energy. When it polymerizes, it forms cellulose, which comprises plant structures.



A cross-sectional study of the association between persistent organic pollutants and glucose intolerance among Greenland Inuit  

Microsoft Academic Search

Aims\\/hypothesis  Some evidence supports the hypothesis that persistent organic pollutants (POPs) may increase the risk of type 2 diabetes.\\u000a The Inuit population in Greenland, which is highly exposed to POPs due to a high intake of marine mammals, has experienced\\u000a a rapid increase in diabetes prevalence over the last 30 years. Thus the aim was to study the association between POPs and

M. E. Jørgensen; K. Borch-Johnsen; P. Bjerregaard



High-fat hypercaloric diet induces obesity, glucose intolerance and hyperlipidemia in normal adult male Wistar rat  

Microsoft Academic Search

There is strong evidence that genetic factors contribute to the development of obesity in humans as well as laboratory animals. Another important factor leading to obesity is an increase in energy intake. However, it is difficult to make normal rats obese by controlling daily food intake. There is no report of normal adult male Wistar rats becoming obese and diabetic

Toshiharu Akiyama; Issei Tachibana; Hisashi Shirohara; Nobuaki Watanabe; Makoto Otsuki



Reductions in caloric intake and early postnatal growth prevent glucose intolerance and obesity associated with low birthweight  

Microsoft Academic Search

Aims\\/hypothesis  Low birthweight (LBW) and rapid postnatal weight gain, or catch-up growth, are independent risk factors for the development of obesity and diabetes during adult life. Individuals who are both small at birth and have postnatal catch-up growth are at the highest risk. We hypothesised that dietary interventions designed to attenuate catch-up growth in LBW subjects may have long-term beneficial consequences.Materials

J. C. Jimenez-Chillaron; M. Hernandez-Valencia; A. Lightner; R. R. Faucette; C. Reamer; R. Przybyla; S. Ruest; K. Barry; J. P. Otis; M. E. Patti



Chronic Phase Shifts of the Photoperiod throughout Pregnancy Programs Glucose Intolerance and Insulin Resistance in the Rat  

Microsoft Academic Search

Shift work during pregnancy is associated with an increased risk for preterm birth and low birth weight. However, the impact upon the long term health of the children is currently unknown. In this study, we used an animal model to determine the consequences of maternal shift work exposure on the health of the adult offspring. Pregnant rats were exposed to

Tamara J. Varcoe; Nicole Wight; Athena Voultsios; Mark D. Salkeld; David J. Kennaway; Shin Yamazaki



Abnormal Norepinephrine Clearance and Adrenergic Receptor Sensitivity in Idiopathic Orthostatic Intolerance  

Microsoft Academic Search

Background—Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of $30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. Methods

Giris Jacob; John R. Shannon; Fernando Costa; Raffaello Furlan; Italo Biaggioni; Rogelio Mosqueda-Garcia; Rose Marie Robertson; David Robertson


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

ERIC Educational Resources Information Center

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

Karabin, Beverly Lynn



Selective Attention, Memory Bias, and Symptom Perception in Idiopathic Environmental Intolerance and Somatoform Disorders  

Microsoft Academic Search

Idiopathic environmental intolerance (IEI) refers to a polysymptomatic condition, similar to somatoform disorders. Various processes seem to contribute to its yet unknown etiology. Attention and memory for somatic symptom and IEI-trigger words was compared among participants with IEI (n = 54), somatoform disorders (SFD; n = 44) and control participants (n = 54). Groups did not differ in a dot-probe

Michael Witthöft; Alexander L. Gerlach; Josef Bailer



Discrepancies between reported food intolerance and sensitization test findings in irritable bowel syndrome patients  

Microsoft Academic Search

OBJECTIVE: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with clinical signs typical of “intestinal” food allergies or intolerance. The aim of this study was to characterize the clinical features of IBS patients suspected of suffering from adverse reactions to food.METHODS: The study involved 128 consecutive IBS patients divided into four groups according to their main symptom on presentation

Raffaella Dainese; Ermenegildo A Galliani; Franca De Lazzari; Vincenza Di Leo; Remo Naccarato



Chiropractic Management of Cow's Milk Protein Intolerance in Infants With Sleep Dysfunction Syndrome: A Therapeutic Trial  

Microsoft Academic Search

ObjectiveIn addition to the more usual cutaneous, gastrointestinal, and respiratory problems, infants with cow's milk intolerance (CMI) may present with a disturbed sleep pattern. Frustrated mothers may turn to their doctor of chiropractic for assistance. This pilot study shows how a therapeutic trial may offer a realistic, noninvasive approach to the chiropractic management of infants with this clinical problem.

Jennifer R. Jamison; Neil J. Davies



Lactose intolerance among severely malnourished children with diarrhoea admitted to the nutrition unit, Mulago hospital, Uganda  

Microsoft Academic Search

BACKGROUND: Lactose intolerance is a common complication of diarrhoea in infants with malnutrition and a cause of treatment failure. A combination of nutritional injury and infectious insults in severe protein energy malnutrition reduces the capacity of the intestinal mucosa to produce lactase enzyme necessary for the digestion of lactose. The standard management of severe malnutrition involves nutritional rehabilitation with lactose-based

Richard Nyeko; Israel Kalyesubula; Edison Mworozi; Hanifa Bachou



What is lactose tolerance / intolerance?, 2D animationSite: DNA Interactive (  

NSDL National Science Digital Library

This gene on chromosome 2 codes for the enzyme lactase. This enzyme enables infants to break down lactose, the main sugar in milk. In people who are lactose tolerant, the gene remains active throughout their lives. In most people who are lactose intolerant, the gene is turned off after infancy, making the digestion of dairy products difficult and painful.



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

PubMed Central

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 18–30 y, mean BMI=21.7±1.6 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.

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



Hypertension in Iranian Urban Population, Epidemiology, Awareness, Treatment and Control  

PubMed Central

Background: To assess the epidemiological characteristics of hypertensive patients in urban population of Yazd, A central city in Iran. Methods: This cross sectional study was conducted from 2005–2006 and carried out on population aging 20–74 years. It is a part of the phase I of Yazd healthy heart program that it is a community interventional study for prevention of cardiovascular disease. Data obtained from questionnaires were analyzed by SPSS version 13. P value less than 0.05 were considered significant level. Results: This study comprised of 2000 participants that 847 (42.5%) were diagnosed as being hypertensive. After age adjustment, prevalence of hypertension was 25.6% (23.3% for women and 27.5% for men (P< 0.001). Age, Total cholesterol, LDL-cholesterol, triglyceride, fasting blood glucose, impaired glucose tolerance test, body mass index and waist were significantly higher in the hypertensive groups. 53.7% of hypertensive cases were aware of own condition, 45% were treated, and 33.9% of treated were controlled (30.7% and 35.4% in men and women respectively). In other word, 24% of all hypertensives (aware or unaware about own blood pressure condition) were treated and only 8% of them were controlled. Men significantly had less awareness (P< 0.001), lower tendency to take medication (P< 0.001), and less were controlled (P= 0.046). Conclusion: We understand high prevalence, low awareness, treatment, and control of hypertension and higher prevalence of other traditional metabolic risk factors in these cases. It seems that urgent preventional studies should be conducted in this population.

Namayandeh, SM; Sadr, SM; Rafiei, M; Modares-Mosadegh, M; Rajaefard, M



The association of brain natriuretic peptide and insulin resistance in obesity-related hypertension.  


Hypertension is frequently associated with obesity and natriuretic peptide levels are reported to decrease in obese subjects. Both the lower brain natriuretic peptide (BNP) concentration and insulin resistance are suggested to be associated with hypertension. However, their involvement in obesity-related hypertension has not been clearly defined. Forty-four obese women (21 normotensive and 23 hypertensive) and 25 healthy women matched for age were included in the study. Anthropometrical parameters were determined. Serum BNP, fasting insulin and glucose concentrations, and lipid parameters were evaluated. Insulin resistance was calculated using Homeostasis Model Assessment (HOMA) and Quantative Insulin Sensitivity Check Index (QUICKI) formulations. Within the obese groups, HOMA and QUICKI reflected the increased insulin resistance in hypertensive obese subjects with a significant correlation to blood pressure. The decrease in BNP in the obese groups was in favour of the hypertensive obese subjects (31.43+/-6.43; 26.36+/-4.29; and 17.51+/-3.08 pg/ml, respectively) with a fractional statistical significance between the hypertensive obese group and the controls (P=0.047). Only for the obese hypertensive group, fasting glucose, HOMA and QUICKI were significantly correlated with BNP. Moreover, fasting plasma glucose (R(2)=0.22, P=0.007) and fasting plasma insulin (R(2)=0.39, P=0.03) were independently correlated with BNP only for the obese hypertensive group. It can be concluded that the decrease in BNP concentrations in the obese hypertensive subjects seem to be well correlated with the insulin resistance. PMID:17392814

Tekes, S; Cikim, A S



Clinical Manifestations of Portal Hypertension  

PubMed Central

The portal hypertension is responsible for many of the manifestations of liver cirrhosis. Some of these complications are the direct consequences of portal hypertension, such as gastrointestinal bleeding from ruptured gastroesophageal varices and from portal hypertensive gastropathy and colopathy, ascites and hepatorenal syndrome, and hypersplenism. In other complications, portal hypertension plays a key role, although it is not the only pathophysiological factor in their development. These include spontaneous bacterial peritonitis, hepatic encephalopathy, cirrhotic cardiomyopathy, hepatopulmonary syndrome, and portopulmonary hypertension.

Al-Busafi, Said A.; McNabb-Baltar, Julia; Farag, Amanda; Hilzenrat, Nir



Increased Cardiopulmonary Disease Risk in a Community-Based Sample With Chemical Odor Intolerance: Implications for Women's Health and HealthCare Utilization  

Microsoft Academic Search

Chemical intolerance, or reported illness from odors of common environmental chemicals (e.g., car exhaust, pesticides), is emerging as an important environmental and public health-care issue. Epidemiologic methods provide relevant heuristic devices for studies of complex disorders, such as chemical intolerance. The authors examined personal and reported parental cardiopulmonary disease prevalence rates in a community sample of chemically intolerant and control

Carol M. Baldwin; Iris R. Bell



Fetal Programming of Adult Glucose Homeostasis in Mice  

PubMed Central

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.

Cederroth, Christopher R.; Nef, Serge



Redox-sensitive endoplasmic reticulum stress and autophagy at rostral ventrolateral medulla contribute to hypertension in spontaneously hypertensive rats.  


Perturbations of proper functions of the endoplasmic reticulum (ER) cause accumulation of misfolded or unfolded proteins in the cell, creating a condition known as ER stress. Prolonged ER stress has been implicated in hypertension. Oxidative stress in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons for the maintenance of vasomotor tone reside, plays a pivotal role in neurogenic hypertension. This study aimed to evaluate the contribution of ER stress in RVLM to oxidative stress-associated hypertension and delineate the underlying molecular mechanisms. The expression of glucose-regulated protein 78 kDa and the phosphorylation of protein kinase RNA-like ER kinase-translation initiation factor ?, 2 major protein markers of ER stress, were augmented in RVLM and preceded the development of hypertensive phenotype in spontaneously hypertensive rats. In RVLM of spontaneously hypertensive rats, stabilizing ER stress by salubrinal promoted antihypertension, and scavenging the reactive oxygen species by tempol reduced the augmented ER stress. Furthermore, induction of oxidative stress by angiotensin II induced ER stress in RVLM, and induction of ER stress by tunicamycin in RVLM induced pressor response in normotensive Wistar-Kyoto rats. Autophagy, as reflected by the expression of lysosome-associated membrane protein-2 and microtubule-associated protein 1 light chain 3-II (LC3-II), was significantly increased in RVLM of spontaneously hypertensive rats and was abrogated by salubrinal. In addition, inhibition of autophagy or silencing LC3-II gene in RVLM resulted in antihypertension in spontaneously hypertensive rats. These results suggest that redox-sensitive induction of ER stress and activation of autophagy in RVLM contribute to oxidative stress-associated neurogenic hypertension. PMID:23608659

Chao, Yung-Mei; Lai, Ming-Derg; Chan, Julie Y H



Intolerable human suffering and the role of the ancestor: literary criticism as a means of analysis.  


Intolerable human suffering and the role of the ancestor: literary criticism as a means of analysis This essay explores the experience of intolerable human suffering in Toni Cade Bambara's novel, The Salt Eaters. The method of analysis is literary criticism, a technique that shares many of the same goals as other types of inquiry. It employs close reading to illuminate the novel's meaning(s), thereby revealing information about the nature of intolerable human suffering. Morrison's characteristics of black art is the literary and cultural framework that guides the analysis of Bambara's novel. The paradigm has broad application for nursing. The purpose of this analysis was to describe the role of the ancestral system as a predictor of the trajectory of suffering. The results extend Morrison's paradigm and her notion of ancestor to include traditions and other non-corporeal factors that are essential for well-being and survival. The protagonist in Bambara's novel, Velma Henry, is the patient and exemplar who does not succumb to intolerable suffering because of its cumulative weight, but because she has lost touch with the traditions of her people, an essential component of her ancestral system. The ancestral system is a rich and complex network of individuals, groups, customs and beliefs that are instructive, protective and benevolent. Ancestors are also timeless and provide wisdom, but when the ancestral system is weak or absent, the trajectory of suffering is not favourable. Nurses must learn to recognize intolerable human suffering, to identify the patient's ancestral system, and to work within that system to keep suffering patients from harm. PMID:11012813

Harrison, E



Integrating anxiety sensitivity, distress tolerance, and discomfort intolerance: a hierarchical model of affect sensitivity and tolerance.  


The purpose of the present investigation was to concurrently examine the latent dimensional and hierarchical structure of anxiety sensitivity (AS) and two key theoretically relevant and related affect (in)tolerance and sensitivity constructs: distress tolerance and discomfort intolerance. These constructs were measured using the Anxiety Sensitivity Index (Reiss, Peterson, Gursky, & McNally, 1986), the Distress Tolerance Scale (Simons & Gaher, 2005), and the Discomfort Intolerance Scale (Schmidt, Richey, & Fitzpatrick, 2006). A total of 229 individuals (124 females; M(age)=21.0 years, SD=7.5) without current Axis I psychopathology participated by completing a battery of self-report questionnaires. A two-stage exploratory factor analysis was conducted to examine the lower- and higher-order latent structural relations among the variables. The factor solution was subsequently evaluated in relation to negative affectivity, anxious arousal, and anhedonic depression. AS and distress tolerance appeared to be related to one another as distinct lower-order facets of a common higher-order affect tolerance and sensitivity factor, whereas discomfort intolerance did not appear to demonstrate similar relations with either AS or distress tolerance at the lower-order or higher-order levels. A unique pattern of association with theoretically-relevant criterion variables was observed between the affect tolerance and sensitivity higher-order factor, the AS and distress tolerance lower-order factors, and the discomfor