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Glucose Tolerance (glucose + tolerance)
Kinds of Glucose Tolerance Terms modified by Glucose Tolerance Selected AbstractsInadequacies of absolute threshold levels for diagnosing prediabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2010Michael Bergman Abstract Prediabetes comprising Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT) represents an intermediate stage of altered glucose metabolism between normal glucose levels and type 2 diabetes mellitus and is associated with an increased risk for the development of diabetes and cardiovascular disease. There is considerable evidence that glucose levels lower than those meeting the current definition of prediabetes may also be associated with similar risks particularly in high-risk individuals. Prediabetes is often unrecognized and therefore constitutes a major public health concern suggesting the need for earlier intervention than is currently recommended. Copyright © 2010 John Wiley & Sons, Ltd. [source] Chinese Cabbage (Brassica campestris L.) does not Improve Glucose Tolerance, Serum Insulin, or Blood Lipid Profiles in a Rat Model of Type-2 DiabetesJOURNAL OF FOOD SCIENCE, Issue 9 2008M.S. Islam ABSTRACT:, The present study was conducted to investigate the effects of a low (0.5%) and a high (2.0%) dietary dose of freeze-dried Chinese cabbage (CC) (Brassica campestris L.) powder in a type-2 diabetes (T2D) model of rats. Five-week-old male Sprague,Dawley rats were fed a high fat (HF)-containing diet for 2 wk then randomly divided into 4 groups of 8 animals, namely: normal control (NC), diabetic control (DBC), Chinese cabbage low (CCL, 0.5%), and Chinese cabbage high (CCH, 2.0%) groups. Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ; 40 mg/kg body weight) in all groups except the NC group. After 4 wk feeding of experimental diets, although food intake was not different among the DBC, CCL, and CCH groups, body weight gain was significantly (P < 0.05) higher in the CCH group compared to the DBC group. Relatively higher serum insulin concentrations and better glucose tolerance were observed in the CC-fed groups compared to the DBC group; however, the results were not significantly different. Fasting blood glucose, blood glycated hemoglobin (HbA1c), liver weight, and liver glycogen levels were not influenced by the CC-containing diets. Additionally, hypertriglyceridemic tendencies were observed in the CC-fed groups compared to the NC and DBC groups, while difference observed for total-, HDL-, and LDL-cholesterols between the groups were negligible. Results of this study suggest that up to 2% dietary dose of freeze-dried CC is not significantly effective to reduce diabetes-related symptoms in an HF diet-fed STZ-induced T2D model of rats. [source] Impaired Glucose Tolerance in the R6/1 Transgenic Mouse Model of Huntington's DiseaseJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2008K. Josefsen Previous reports have highlighted a possible link between Huntington's disease (HD) and diabetes mellitus (DM), but the association has not been characterised in detail. A transgenic mouse model for HD, the R6/2 mouse, also develops diabetes. In the present study, we examined the R6/1 mouse, which carries a shorter CAG repeat than the R6/2 mouse, and found that, although not diabetic, the mice showed several signs of impaired glucose tolerance. First, following i.p. glucose injection, the blood glucose concentration was approximately 30% higher in young R6/1 mice (10 weeks) compared to wild-type mice (P = 0.004). In older mice (38 weeks), glucose tolerance was further impaired in both R6/1 and wild-type animals. Second, during glucose challenge, the R6/1 mice reached higher plasma insulin levels than wild-type mice, but the peripheral insulin sensitivity was normal as measured by injection of human or mouse insulin or when evaluated by the quantitative insulin sensitivity check index (QUICKI). Third, the beta cell volume was 17% and 39% smaller at 10 and 38 weeks of age, respectively, compared to age-matched wild-type littermates and the reduction was not caused by apoptosis at either age. Finally, we demonstrated the presence of the HD gene product, huntingtin (htt), in both alpha- and beta-cells in R6/1 islets of Langerhans. Since pancreatic beta cells and neurons share several common traits, clarification of the mechanism associating neurodegenerative diseases with diabetes might improve our understanding of the pathogenic events leading to both groups of diseases. [source] Long-term Administration of Rapamycin Reduces Adiposity, but Impairs Glucose Tolerance in High-Fat Diet-fed KK/HlJ MiceBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2009Geng-Ruei Chang In this study, we investigated the metabolic effects of rapamycin in an obese animal model, KK/HlJ mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2 mg/kg or vehicle for 42 days on a high-fat diet. Treated mice lost body weight and adiposity, reduced weight gain and retroperitoneal and epididymal fat pads/body weight, decreased serum leptin and plasma triglyceride levels and had lower liver fat concentration. However, treated mice had higher serum insulin levels and food intake. Dissection of rapamycin-treated mice revealed a marked reduction in fatty liver scores and fat cell size in retroperitoneal and epididymal adipocytes. Moreover, Western blot analysis revealed that rapamycin treatment resulted in decreasing adipophilin expression, as a marker of lipid accumulation, and reducing phosphorylation of mTOR downstream targets S6K1 compared to control group. Unfortunately, rapamycin-treated animals showed a marked decline in glucose tolerance as judged by the 180-min. area under the curve for plasma glucose levels, paralleled by increased generation of plasma reactive oxygen species. These results suggest that continual rapamycin administration may help to prevent diet-induced obesity, while prolonged use of rapamycin may exacerbate glucose intolerance. [source] Increasing prevalence of Type 2 diabetes mellitus in all ethnic groups in MauritiusDIABETIC MEDICINE, Issue 1 2005S. Söderberg Abstract Aims To describe the prevalence of different stages of glucose intolerance in a population from Mauritius followed over 11 years. Methods Population-based surveys were undertaken in the multiethnic nation of Mauritius in 1987, 1992 and 1998, with 5083, 6616, and 6291 participants, respectively. Questionnaires, anthropometric measurements, and a 2-h 75-g oral glucose tolerance test were included. Subjects aged between 25 and 75 years with classifiable data were identified; 4991, 6463 and 5392 from 1987, 1992 and 1998, respectively. Glucose tolerance was classified according to WHO 1999 criteria. Results The prevalence of Type 2 diabetes increased significantly during the period studied, from 12.8% in 1987, to 15.2% in 1992, and 17.9% in 1998. The increasing prevalence was seen in both men and women, and in all age groups. The prevalence of known diabetes (KDM) increased progressively, and more markedly than the increase in newly diagnosed diabetes (NDM). A diagnosis of impaired glucose tolerance (IGT) was more prevalent amongst women whereas impaired fasting glucose (IFG) was more common amongst men. The prevalences of IGT and IFG did not change markedly during the period. The prevalence of diabetes and IGT was similar for participants of Indian, Creole and Chinese background in each survey, and the increasing prevalence of diabetes was seen in all ethnic groups. Conclusion In this study, we report an increasing prevalence of diabetes over an 11-year period in Mauritius. This increase was seen in both sexes, and in all age and ethnic groups, and was mainly due to an increase in the numbers of those with known diabetes. [source] No effect of 8-week time in bed restriction on glucose tolerance in older long sleepersJOURNAL OF SLEEP RESEARCH, Issue 4 2008MARK R. ZIELINSKI Summary The aim of this study was to investigate the effects of 8 weeks of moderate restriction of time in bed (TIB) on glucose tolerance and insulin sensitivity in healthy older self-reported long sleepers. Forty-two older adults (ages 50,70 years) who reported average sleep durations of ,8.5 h per night were assessed. Following a 2-week baseline, participants were randomly assigned to two 8-week treatments: either (i) TIB restriction (n = 22), which involved following a fixed sleep schedule in which time in bed was reduced by 90 min compared with baseline; (ii) a control (n = 18), which involved following a fixed sleep schedule but no imposed change of TIB. Sleep was monitored continuously via wrist actigraphy recordings, supplemented with a daily diary. Glucose tolerance and insulin sensitivity were assessed before and following the treatments. Compared with the control treatment, TIB restriction resulted in a significantly greater reduction of nocturnal TIB (1.39 ± 0.40 h versus 0.14 ± 0.26 h), nocturnal total sleep time (TST) (1.03 ± 0.53 h versus 0.40 ± 0.42 h), and 24-h TST (1.03 ± 0.53 h versus 0.33 ± 0.43 h) from baseline values. However, no significant effect of TIB restriction was found for glucose tolerance or insulin sensitivity. These results suggest that healthy older long sleepers can tolerate 8 weeks of moderate TIB restriction without impairments in glucose tolerance or insulin sensitivity. [source] Antihyperglycaemic and protective effects of flavonoids on streptozotocin,induced diabetic ratsPHYTOTHERAPY RESEARCH, Issue S2 2010Amélia P. Rauter Abstract The antihyperglycaemic effect of eight standard flavonoids, previously identified in the ethanol extract of the claimed antidiabetic plant Genista tenera, was evaluated on streptozotocin (STZ)-induced diabetic Wistar rats. The aglycones apigenin, chrysoeriol and genistein, the monoglucosides apigenin 7- O -glucoside, luteolin 7- O -glucoside and genistein 7- O -glucoside and the diglycosides rutin and luteolin 7,3,-di- O -glucoside were administered i.p. for 7 days (4,mg/kg b.w./day). The protective effect of these compounds over liver and kidneys of STZ,diabetic models was also evaluated by the determination of seric AST, ALT and urea levels. After 7 days of treatment, apigenin, chrysoeriol and genistein significantly lowered the blood glucose levels of diabetic animals; this effect was more pronounced (P < 0.01) in the oral glucose tolerance test. Glucose tolerance was also significantly improved in the rutin (P < 0.01) and in the genistein 7,O,glucoside (P < 0.05) treated groups. In addition, almost all the tested compounds effectively protected the liver and kidneys against STZ-induced damage in rats. Copyright © 2010 John Wiley & Sons, Ltd. [source] Pregnancy and lactation have anti-obesity and anti-diabetic effects in Ay/a miceACTA PHYSIOLOGICA, Issue 2 2010E. N. Makarova Abstract Aim:, Dominant ,yellow' mutation at the mouse agouti locus (Ay) results in obesity. Pregnancy and lactation are characterized by large energy demand. The aim of this study was to investigate whether obesity would develop in pregnant and suckling Ay mice. Methods:, Body weight and food intake in pregnancy, lactation, and after weaning, plasma leptin, insulin, corticosterone and blood glucose concentrations on days 7, 13 and 18 of pregnancy, days 1, 10, 21 and 80 postpartum, glucose and insulin tolerance on pregnancy days 7 and 18 were measured in C57Bl/6J mice of a/a (normal metabolism) and Ay/a genotypes. The same parameters were also measured in age-matched virgin females. Results:, Virgin Ay/a females exhibited hyperphagia, enhanced body weight, glucose intolerance and normal blood parameters at the mating age. With age, they developed obesity, hyperleptinaemia, hyperinsulinaemia and hyperglycaemia. Obesity did not develop in mated Ay/a mice; during suckling, they had equal food intake and body weight as a/a mice. During pregnancy, glucose tolerance was enhanced in Ay/a mice and became equal in both genotypes. In both genotypes, concentrations of hormones increased, and glucose decreased from pregnancy day 7 to day 18 and returned to normal values after parturition. Ay/a mice did not differ from a/a in corticosterone, insulin and glucose levels during pregnancy and lactation, in leptin levels during suckling; however, Ay/a mice had two times higher leptin levels than a/a during pregnancy. After weaning, Ay/a mice began to eat and weigh more than a/a exhibiting normal metabolic parameters for 50 days. Conclusion:, Pregnancy and lactation retard obesity and diabetes development in Ay mice. [source] Effects of physical exercise versus rosiglitazone on endothelial function in coronary artery disease patients with prediabetesDIABETES OBESITY & METABOLISM, Issue 9 2010S. Desch We conducted a three-arm, parallel-group, randomized, controlled trial to compare the effects of rosiglitazone and physical exercise on endothelial function in patients with coronary artery disease and impaired fasting glucose or impaired glucose tolerance over a 6-month period. Group A received rosiglitazone tablets 8 mg daily (n = 16), group B underwent a structured physical exercise programme (n = 15) and group C served as a control group (n = 12). At baseline and after 6 months, brachial artery ultrasound imaging was performed to assess reactive flow-mediated dilation (FMD). Rosiglitazone treatment and exercise both led to significant improvements in insulin resistance at 6 months, whereas no change was observed in control patients. FMD improved significantly in physical exercise patients, whereas no change could be observed in patients receiving rosiglitazone or in the control group. Between-group comparisons also showed a significant relative improvement in FMD in exercise patients compared with rosiglitazone. [source] Balancing needs and means: the dilemma of the ,-cell in the modern worldDIABETES OBESITY & METABOLISM, Issue 2009G. Leibowitz The insulin resistance of type 2 diabetes mellitus (T2DM), although important for its pathophysiology, is not sufficient to establish the disease unless major deficiency of ,-cell function coexists. This is demonstrated by the fact that near-physiological administration of insulin (CSII) achieved excellent blood glucose control with doses similar to those used in insulin-deficient type 1 diabetics. The normal ,-cell adapts well to the demands of insulin resistance. Also in hyperglycaemic states some degree of adaptation does exist and helps limit the severity of disease. We demonstrate here that the mammalian target of rapamycin (mTOR) system might play an important role in this adaptation, because blocking mTORC1 (complex 1) by rapamycin in the nutritional diabetes model Psammomys obesus caused severe impairment of ,-cell function, increased ,-cell apoptosis and progression of diabetes. On the other hand, under exposure to high glucose and FFA (gluco-lipotoxicity), blocking mTORC1 in vitro reduced endoplasmic reticulum (ER) stress and ,-cell death. Thus, according to the conditions of stress, mTOR may have beneficial or deleterious effects on the ,-cell. ,-Cell function in man can be reduced without T2DM/impaired glucose tolerance (IGT). Prospective studies have shown subjects with reduced insulin response to present, several decades later, an increased incidence of IGT/T2DM. From these and other studies we conclude that T2DM develops on the grounds of ,-cells whose adaptation capacity to increased nutrient intake and/or insulin resistance is in the lower end of the normal variation. Inborn and acquired factors that limit ,-cell function are diabetogenic only in a nutritional/metabolic environment that requires high functional capabilities from the ,-cell. [source] Effects of cevoglitazar, a dual PPAR,/, agonist, on ectopic fat deposition in fatty Zucker ratsDIABETES OBESITY & METABOLISM, Issue 6 2009D. Laurent Aim:, By acting as both insulin sensitizers and lipid-lowering agents, dual-acting peroxisome proliferator-activated receptors ,/, (PPAR,/,) agonists may be used to improve glucose tolerance in type 2 diabetic patients without inducing adiposity and body weight gain. Here, in an animal model of obesity and insulin resistance, the metabolic response to cevoglitazar, a dual PPAR,/,, was characterized using a combination of in vivo and ex vivo magnetic resonance methodologies and compared to treatment effects of fenofibrate, a PPAR, agonist, and pioglitazone, a PPAR, agonist. Methods:, Four groups of fatty Zucker rats: (i) Vehicle; (ii) fenofibrate 150 mg/kg; (iii) pioglitazone 30 mg/kg; and (iv) cevoglitazar 5 mg/kg were investigated before and after treatment. Animals were fed a fat-enriched (54% kcal fat) diet for 6 weeks, 2 weeks high of fat,exposure alone followed by a 4-week dosing period. Results and conclusions:, Cevoglitazar was as effective as pioglitazone at improving glucose tolerance. However, unlike pioglitazone, both fenofibrate and cevoglitazar reduced BW gain and adiposity, independent of food intake. All three treatment regimens normalized intramyocellular lipids. Metabolic profiling showed that in the muscle cevoglitazar improves the lipid profile via both PPAR,- and PPAR,-mediated mechanisms. Pioglitazone reduced hepatic lipid accumulation, while cevoglitazar and fenofibrate reduced hepatic lipid concentration below baseline levels (p < 0.05). Metabolic profiling showed that in the liver, cevoglitazar functions largely through PPAR, agonism resulting in increased ,-oxidation. Cevoglitazar only induced small changes to the lipid composition of visceral fat. In subcutaneous fat, however, cevoglitazar induced changes similar to those observed with fenofibrate suggesting export of fatty acids from this depot. [source] Exenatide prevents fat-induced insulin resistance and raises adiponectin expression and plasma levelsDIABETES OBESITY & METABOLISM, Issue 10 2008L. Li Background:, Exenatide (exendin-4) can reduce blood glucose levels, increase insulin secretion and improve insulin sensitivity through mechanisms that are not completely understood. Methods:, In the present study, we examined the effects of exenatide treatment on glucose tolerance (intravenous glucose tolerance test), insulin sensitivity (euglycaemic,hyperinsulinaemic clamps), insulin signalling (insulin receptor substrate 1 tyrosine phosphorylation) and adipocytokine levels (visfatin and adiponectin) in high fat,fed rats. Results:, Administration of exenatide (0.5 or 2.0 ,g/kg twice daily × 6 weeks) prevented high-fat diet (HFD),induced increases in body weight, plasma free fatty acids, triglycerides and total cholesterol. Exenatide also prevented HFD-induced deterioration in peripheral and hepatic insulin sensitivity, insulin clearance, glucose tolerance and decreased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in fat and skeletal muscles. Interestingly, plasma visfatin levels decreased in exenatide-treated rats, whereas expression and plasma levels of adiponectin increased. Conclusions:, These results indicate that chronic exenatide treatment enhances insulin sensitivity and protects against high fat,induced insulin resistance. [source] Cardiovascular drugs as antidiabetic agents: evidence for the prevention of type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 7 2008D. P. Macfarlane Given the long-term health consequences and increasing incidence of type 2 diabetes, there is great interest to potentially prevent or delay its onset. Primary prevention studies have demonstrated that intensive exercise and weight reduction, and to a lesser extent certain antidiabetic agents, can reduce new onset diabetes in at-risk individuals. Results from post hoc analyses and secondary end-point outcomes of large randomized controlled trials of cardiovascular drugs suggest that these may also have beneficial effects, reducing the incidence of new onset diabetes in addition to their proven cardiovascular benefits. Multiple meta-analyses confirm that drugs primarily acting on the renin,angiotensin system (RAS) reduce the incidence of diabetes in the populations studied, perhaps via improved insulin sensitivity and/or effects on pancreatic beta cells. However, results from the recent Diabetes REduction Approaches with Medication study specifically failed to show a significant reduction in the incidence of diabetes with ramipril in individuals with abnormal glucose tolerance at baseline. There is only limited evidence that statins improve glucose tolerance, and although beta-blockers tend to have detrimental effects on glucose tolerance, newer agents with vasodilatory properties may confer benefits. With current guidelines, the use of cardiovascular drugs modifying the RAS will increase in at-risk individuals, but at present, they cannot be recommended to prevent diabetes. [source] Rosiglitazone is more effective than metformin in improving fasting indexes of glucose metabolism in severely obese, non-diabetic patientsDIABETES OBESITY & METABOLISM, Issue 6 2008A. Brunani Aim:, In obese patients, the diet-induced weight loss markedly improves glucose tolerance with an increase in insulin sensitivity and a partial reduction of insulin secretion. The association with metformin treatment might potentiate the effect of diet alone. Methods:, From patients admitted to our Nutritional Division for diet programme, we selected obese, non-diabetic, uncomplicated patients with age 18,65 years and body mass index 35,50 kg/m2 and studied the effects of a 6-month pharmacological treatment with either metformin (850 mg twice daily) or rosiglitazone (4 mg twice daily) on possible changes in body weight, fat mass, glucose and lipids metabolism. Results:, A significant weight loss and reduction of fat mass was demonstrated with metformin (,9.7 ± 1.8 kg and ,6.6 ± 1.1 kg) and also with rosiglitazone (,11.0 ± 1.9 kg and ,7.2 ± 1.8 kg), without fluid retention in either treatment group. Rosiglitazone administration induced a significant decrease in glucose concentration (4.7 ± 0.1 vs. 4.4 ± 0.1 mmol/l, p < 0.005) and insulin-circulating level (13.6 ± 1.5 vs. 8.0 ± 0.,7 ,U/ml, p < 0.005), an increase in insulin sensitivity as measured by homeostatic model assessment (HOMA) of insulin sensitivity (68.9 ± 8.8 vs. 109.9 ± 10.3, p < 0.005) with a concomitant decrease in ,-cell function as measured by HOMA of ,-cell function (163.2 ± 16.1 vs. 127.4 ± 8.4, p < 0.005). In contrast, metformin did not produce any significant effect on blood glucose concentration, insulin level and HOMA2 indexes. No adverse events were registered with pharmacological treatments. Conclusion:, Our study shows that in severely obese, non-diabetic, hyperinsulinaemic patients undergoing a nutritional programme, rosiglitazone is more effective than metformin in producing favourable changes in fasting-based indexes of glucose metabolism, with a reduction of both insulin resistance and hyperinsulinaemia. In spite of previous studies reporting rosiglitazone-induced body weight gain, in our study the joint treatment with diet and rosiglitazone was accompanied by weight loss and fat mass reduction. [source] Effects of short-term cinnamon ingestion on in vivo glucose toleranceDIABETES OBESITY & METABOLISM, Issue 6 2007T. P. J. Solomon Aims:, Various spices display insulin-potentiating activity in vitro, and in particular, cinnamon spice and its phenolic extracts have been shown to exhibit these capabilities. In vivo study shows that cinnamon may have beneficial effects on glucose homeostasis; therefore the aim of this study was to further investigate this phenomenon in humans. Methods:, Seven lean healthy male volunteers, aged 26 ± 1 years, body mass index 24.5 ± 0.3 kg/m2 (mean ± s.e.m.), underwent three oral glucose tolerance tests (OGTT) supplemented with either a 5 g placebo (OGTTcontrol), 5 g of cinnamon (OGTTcin), or 5 g of cinnamon taken 12 h before (OGTTcin12hpre) in a randomized-crossover design. Results:, Cinnamon ingestion reduced total plasma glucose responses (AUC) to oral glucose ingestion [,13% and ,10% for OGTTcin (p < 0.05) and OGTTcin12hpre (p < 0.05), respectively], as well as improving insulin sensitivity as assessed by insulin sensitivity index measures based on Matsuda's model in both OGTTcin (p < 0.05) and OGTTcin12hpre (p < 0.05) trials compared with OGTTcontrol. Conclusions:, These data illustrate that cinnamon spice supplementation may be important to in vivo glycaemic control and insulin sensitivity in humans, and not only are its effects immediate, they also appear to be sustained for 12 h. [source] Reflecting on Type 2 Diabetes Prevention: More Questions than Answers!DIABETES OBESITY & METABOLISM, Issue 2007J. Rosenstock Given the enormous public health and economic burden posed by the global epidemic of type 2 diabetes mellitus (T2DM), intervention in the prediabetes stage of disease to prevent progression to T2DM and its vascular complications seems the most sensible approach. Precisely how best to intervene remains the subject of much debate. Prudent lifestyle changes have been shown to significantly reduce the risk of progression in individuals with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Although lifestyle modifications are notoriously difficult to maintain, there is evidence that intensive intervention results in continued preventive benefit after the stopping of structured counselling. A number of drug therapies, including metformin, acarbose, orlistat and rosiglitazone, have also been proven effective in preventing progression from IFG/IGT, but unresolved issues still remain. Specifically, whether large numbers of individuals with glucose dysregulation who may never progress to T2DM should be exposed to the risk of pharmacological adverse effects is a topic of discussion and debate. Furthermore, there are limited data on the effectiveness of implementing interventions during the prediabetic state to prevent cardiovascular complications that may be hyperglycaemia related. A recent American Diabetes Association (ADA) consensus statement on IFG/IGT recommends lifestyle modification for individuals with IFG or IGT. Of note, the ADA consensus statement introduces the option of adding metformin treatment to lifestyle changes in those individuals who have combined IFG/IGT plus an additional risk factor for progression and who also have some features that increase the likelihood of benefiting from metformin treatment. The dipeptidyl peptidase-4 inhibitors are a new class of oral antidiabetic agents that, in addition to being effective in improving glycaemic control, may exert beneficial effects in preserving ,-cell function. These characteristics, combined with a low risk of hypoglycaemia, weight neutrality and what appears , so far , to be a relatively benign tolerability profile, make these agents intriguing candidates for preventive treatment. [source] Screening and diagnosis of prediabetes: where are we headed?DIABETES OBESITY & METABOLISM, Issue 2007K. G. M. M. Alberti It is currently estimated that more than 300 million people have impaired glucose tolerance (IGT), putting them at increased risk for type 2 diabetes mellitus (T2DM) and its adverse consequences. In addition, many others are at risk on the basis of a family history of T2DM, obesity, dyslipidaemia and hypertension. Screening for risk should include both blood glucose testing in high-risk populations and prescreening (e.g. by questionnaire, waist circumference measurement) to identify high-risk individuals in overall low-risk populations; these individuals should then undergo glucose testing. Fasting plasma glucose measurement cannot diagnose IGT; the preferred definite test for diagnosis is oral glucose tolerance testing. [source] Oral antidiabetic agents as cardiovascular drugsDIABETES OBESITY & METABOLISM, Issue 1 2007D. P. Macfarlane The increased risk of cardiovascular disease associated with type 2 diabetes is well documented. Lesser degrees of abnormal glucose metabolism including impaired fasting glycaemia and impaired glucose tolerance are also associated with increased cardiovascular risk. Studies showing improved cardiovascular outcomes with oral antidiabetic agents are limited, with the UKPDS demonstrating improved macrovascular outcomes only in a subgroup of obese patients with type 2 diabetes treated with metformin, and the heavily criticized STOP NIDDM trial showing a reduction in the number of cardiovascular events with the alpha glucosidase inhibitor acarbose. In recent years there has been an increase in the number of oral antidiabetic drugs available to treat the hyperglycaemia of diabetes. Some of these drugs have complex metabolic properties, additional to their antihyperglycaemic effect, improving endothelial function and markers of atherogenesis, with the potential to reduce cardiovascular morbidity and mortality, as supported by the recently published results of the PROACTIVE study. The results of further long-term cardiovascular outcome studies with these newer agents are awaited. [source] Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metforminDIABETES OBESITY & METABOLISM, Issue 4 2006Irina Chazova Aim:, To compare the effects of moxonidine and metformin on glycaemic control in patients with impaired glucose tolerance and signs of the metabolic syndrome. Methods:, A multicentre, prospective, randomized, open-label study design was adopted with blinded endpoint evaluation. Patients ,40 years old, with impaired glucose tolerance (or diabetes mellitus treated with diet alone) and a body mass index (BMI) of at least 27 kg/m2 were treated twice daily with moxonidine 0.2 mg or metformin 500 mg for 16 weeks. Oral glucose tolerance test (OGTT) was performed at baseline and end-of-study; plasma insulin and plasma glucose levels were measured at 0, 60, 120 and 180 min after administration. Results:, With regard to effects on insulin [mean area under the curve (AUC) for insulin], the primary efficacy endpoint of the study, both drugs did not show equivalence. On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1,35.0). The change in mean insulin AUC was most marked in the subgroup of patients with higher sympathetic activity (heart rate >80 bpm). Mean fasting plasma glucose (FPG) levels and HbA1c levels were largely unchanged by moxonidine treatment but significantly decreased by metformin treatment. The difference between the groups was 14.7% (p = 0.0523) in the intent-to-treat (ITT) sample. By study end, both treatments had significantly increased the Matsuda Insulin Sensitivity Index (ISI) from baseline to a comparable extent: moxonidine by reducing plasma insulin after a glucose challenge, metformin by reducing FPG. BMI fell significantly in both groups and blood pressure normalized; both drugs were well tolerated. Conclusions:, Moxonidine improved insulin sensitivity in response to glucose challenge in patients with evidence of metabolic syndrome. This improvement resulted from a reduction in plasma insulin levels and was most marked in patients with high sympathetic drive at baseline. By enhancing insulin sensitivity, moxonidine treatment may help prevent the development of diabetes and thereby ameliorate the risk for cardiovascular disease. [source] Insulin resistance , a common link between type 2 diabetes and cardiovascular diseaseDIABETES OBESITY & METABOLISM, Issue 3 2006Harold E. Lebovitz Evidence suggests that diabetes and cardiovascular disease (CVD) may share an underlying cause(s), a theory known as the ,common soil' hypothesis. Insulin resistance is central both to the progression from normal glucose tolerance to type 2 diabetes and to a constellation of cardiovascular risk factors known as the metabolic syndrome. These risk factors include visceral obesity and dyslipidaemia characterized by low levels of high-density lipoprotein cholesterol, hypertriglyceridaemia and raised small dense low-density lipoprotein particle levels. Changes in adipose tissue mass and metabolism may link insulin resistance and visceral obesity, a condition that is common in type 2 diabetes. Furthermore, weight reduction, increased physical activity, metformin and acarbose have been shown to reduce the development of type 2 diabetes in genetically predisposed subjects and may decrease the high cardiovascular risk of patients with diabetes. Some fatty acid derivatives can affect energy metabolism by activating peroxisome proliferator-activated receptors (PPARs), nuclear receptors that play a key role in energy homeostasis. These receptors represent an ideal therapeutic target for reducing cardiovascular risk, because they are involved in the regulation of both insulin action and lipid metabolism. In addition to lifestyle changes, PPAR, agonists such as thiazolidinediones are frequently beneficial and have been shown to ameliorate insulin resistance, while activation of PPAR, (e.g. by fibrates) can lead to improvements in free fatty acid oxidation and lipid profile, and a reduction in cardiovascular events. The development of agents with both PPAR, and PPAR, activity promises added benefits with amelioration of insulin resistance, delayed progression to and of type 2 diabetes and a reduction of CVD. [source] Effects of short-term metformin treatment on insulin sensitivity of blood glucose and free fatty acidsDIABETES OBESITY & METABOLISM, Issue 1 2004S. Iannello Aim:, Based on the known effect of metformin (MET) in improving insulin sensitivity in type 2 diabetes, with the scope to focus the effects on glycaemic and free fatty acids (FFA) levels, we studied the effects of a short-term treatment with this drug in obese subjects and obese patients with diabetes or family history of diabetes (FHD). We used a method to allow us to evaluate the possible difference of insulin sensibility with regard to the insulin action on glycaemia and blood FFA, both in the basal state and during oral glucose tolerance test (OGTT). Methods:, Insulin sensitivity was investigated before and after MET treatment (850 mg bid for 10 days) in seven obese subjects with normal glucose tolerance and without FHD and 13 obese patients with diabetes (n = 7) or FHD (n = 6). By using specifically designed formulae, we calculated four insulin-sensitivity indices (ISI) from basal level (b) and area values (a) (during OGTT) of insulinaemia, glycaemia (gly) or FFA (ffa), namely: ISI (gly)-b, ISI (gly)-a, ISI (ffa)-b and ISI (ffa)-a. Results:, In patients with diabetes or FHD, MET improved ISI (gly)-b (0.79 ± 0.06 vs. 0.59 ± 0.07, p < 0.001) and ISI (gly)-a (0.69 ± 0.09 vs. 0.51 ± 0.07, p < 0.05), whereas only minor changes occurred for ISI (ffa)-b and ISI (ffa)-a. In contrast, in simple obese subjects, MET induced further deterioration of both ISI (gly)-a (0.47 ± 0.07 vs. 0.64 ± 0.10, p < 0.01) and ISI (ffa)-a (0.43 ± 0.07 vs. 0.55 ± 0.08, p < 0.05). Fasting level and total area of lactate were high in the obese patients and were not affected by MET. A statistically significant increase (p < 0.01), however, was observed for the ,decremental' area of lactate in obese subjects with diabetes or FHD, which might probably contribute to the reduction of insulin resistance induced by the drug in these patients. Conclusions:, Although the low number of subjects studied precludes absolute conclusions, data would suggest that MET improved ISI towards glucose but not towards FFA, in the diabetic and ,prediabetic' obese patients, whereas worsened it in the obese subjects without FHD. Therefore, the effects of MET would not be secondary to changes of FFA but rather to a primary action of MET on glucose metabolism. Thus, utilization of MET to treat the insulin resistance in obesity is indicated only in the presence of alterations of glucose metabolism or FHD. [source] Minor long-term changes in weight have beneficial effects on insulin sensitivity and ,-cell function in obese subjectsDIABETES OBESITY & METABOLISM, Issue 1 2002A. M. Rosenfalck SUMMARY Aim To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG) and ,-cell function. Design Glucose metabolism was evaluated before and after participation in a two-year weight loss trial of Orlistat vs. placebo, combined with an energy and fat restricted diet. Subjects Twelve obese patients (11 women, 1 man), age 45.8 ± 10.5 years, body weight (BW) 99.7 ± 13.3 kg, BMI 35.3 ± 2.8 kg/m2. Measurements At inclusion and 2 years later an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test (FSIGT) were performed. Body composition was estimated by a dual-energy X-ray absorptiometry (DXA) whole body scanning. Results The patients obtained varying changes in BW ranging from a weight loss of 17.8 kg to a weight gain of 6.0 kg. Corresponding changes in fat mass (FM) varied from a 40% reduction to a 19% increase. A significant decrease in both fasting (p =,0.038) and 2 h (p =,0.047) blood glucose at OGTT was found. The improvement in insulin sensitivity (SI) estimated by means of Bergmans Minimal Model, was significantly and linearly correlated to change in total FM (r = , 0.83, p =,0.0026). A multiple regression analysis showed that changes in truncal FM was the strongest predictor of change in SI explaining 67% of the variation. First phase insulin response (AIRg) remained unchanged whereas insulin disposition index increased significantly (p =,0.044). At inclusion five patients had impaired glucose tolerance of which four, who lost weight, were normalized at the retest 2 years later. Conclusion In obese subjects long-term minimal or moderate changes in weight were found to be linearly associated with changes in insulin sensitivity. In obese subjects with impaired glucose tolerance even a minor weight loss was able to normalize glucose tolerance. [source] Glucometabolic state of in-hospital primary hypertension patients with normal fasting blood glucose in a sub-population of ChinaDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2009Yang-Xin Chen Abstract Background There is a high prevalence of abnormal glucometabolism (AGM) in patients with coronary heart disease (CHD) and primary hypertension (PH). However, little is known about the glucometabolic state of PH patients with normal fasting blood glucose (FBG). Methods Oral glucose tolerance test (OGTT) was performed for 445 in-hospital PH patients with normal FBG and re-performed for those patients with impaired glucose tolerance (IGT) during the follow-up period. Results Diabetes mellitus (DM), IGT, and AGM (including IGT and DM) accounted for 4.4, 24.5, and 28.9% of patients, respectively. Prevalence of AGM in patients with higher haemoglobin A1c (HbA1c) (,6.0%), risk factors (CHD, overweight, hyperlipidaemia, proteinuria) was significantly higher than that in patients without these factors. Regression analysis showed that age, overweight, proteinuria, HbA1c, and CRP were the independent risk factors of AGM. Follow-up data in 98 IGT patients showed that no improvement of glucometabolism was found, but contrarily, a significant increase of new onset of impaired fasting glucose (IFG) and DM was found after 9 months (P < 0.05), even if diet control and moderate exercise were adopted. Conclusions AGM is prevalent and underestimated in PH patients with normal FBG, and it will develop even if therapeutic life-style changes are adopted. Except for FBG, more attention should be paid to postprandial blood glucose. OGTT should be a routine procedure for PH patients, especially in-hospital PH patients, regardless of normal FBG, and active drug intervention for IGT patients with PH may be recommended. Copyright © 2009 John Wiley & Sons, Ltd. [source] The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2009Swapnil N. Rajpathak Abstract This review addresses the possible role of the insulin-like growth factor (IGF)-axis in normal glucose homoeostasis and in the etiopathogenesis of type 2 diabetes. IGF-I, a peptide hormone, shares amino acid sequence homology with insulin and has insulin-like activity; most notably, the promotion of glucose uptake by peripheral tissues. Type 2 diabetes as well as pre-diabetic states, including impaired fasting glucose and impaired glucose tolerance, are associated cross-sectionally with altered circulating levels of IGF-I and its binding proteins (IGFBPs). Administration of recombinant human IGF-I has been reported to improve insulin sensitivity in healthy individuals as well as in patients with insulin resistance and type 2 diabetes. Further, IGF-I may have beneficial effects on systemic inflammation, a risk factor for type 2 diabetes, and on pancreatic ,-cell mass and function. There is considerable inter-individual heterogeneity in endogenous levels of IGF-I and its binding proteins; however, the relationship between these variations and the risk of developing type 2 diabetes has not been extensively investigated. Large prospective studies are required to evaluate this association. Copyright © 2009 John Wiley & Sons, Ltd. [source] C-peptide constricts pancreatic islet arterioles in diabetic, but not normoglycaemic miceDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2008Lina Nordquist Abstract Background Pancreatic islet blood flow is regulated separately from that of the exocrine pancreas, and a consistent finding during impaired glucose tolerance is an increased blood perfusion. The aim of the present study was to investigate whether C-peptide affects pancreatic islet arterioles in normal and diabetic mice. Materials and Methods Control and diabetic C57-Bl mice were studied after 2 weeks of alloxan-induced diabetes. Islet arterioles were dissected and microperfused with Dulbecco's modified Eagle medium (DMEM) solution. The effect of luminal application of mouse C-peptide was investigated. Results C-peptide reduced the diameter of islet arterioles from diabetic mice (,10 ± 4%, P < 0.05) compared to base-line values, whilst arterioles from normoglycaemic animals did not respond to C-peptide (P = 0.2). Conclusion These findings suggest a role for C-peptide in the regulation of islet blood flow, especially during conditions with impaired glucose tolerance. Copyright © 2007 John Wiley & Sons, Ltd. [source] The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF ratsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2007Sung Hee Choi Abstract Objective To investigate the effects of pioglitazone and metformin treatment during pre-diabetic period for the prevention of diabetes in a rat model. Methods OLETF rats aged 18-weeks, were treated with pioglitazone (10 mg/kg/day) and metformin (300 mg/kg/day) for 10 weeks from their pre-diabetic period. We measured weight, lipid profiles, fat distribution, glucose tolerance, and pancreatic insulin content. Results Prominent weight gain (mostly subcutaneous fat area) was observed in the pioglitazone-treated OLETF (O-P) rats versus significant weight loss was observed in the metformin-treated OLETF (O-M) rats. Pioglitazone reversed the serum triglyceride (TG) and FFAs levels to normal (TG 0.46 ± 0.04 vs 0.88 ± 0.05 mmol/l in LETO). At the age of 28 weeks, the O-P rats showed completely normal glucose tolerance, and the glucose disposal rate (GDR) was markedly improved (25.6 ± 0.4 vs 20.6 ± 0.5 mg/min/kg in O-C, p < 0.05). The O-M rats also showed an improved fasting glucose and GDR level, but not as much as those with O-P rats. The pancreas insulin contents were much improved in the O-P rats (22.9 ± 1.2 vs 18.8 ± 1.3 nmol/pancreas in O-M rats, p < 0.05) with histological improvement. Conclusion The pre-diabetic treatment with pioglitazone, despite significant weight gain, completely prevents to develop diabetes and enhances beta cell function with preservation of islet cell changes. Metformin treatment was also effective, but mainly by ameliorating the insulin resistance with marked reduction in body weight. The reversal of dyslipidaemia and the fat redistribution might contribute to the greater improvement of pioglitazone treatment compared to metformin in OLETF rats. Copyright © 2007 John Wiley & Sons, Ltd. [source] Inflammation and the etiology of type 2 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2006Åke Sjöholm Type 2 diabetes is increasingly common worldwide and is beginning to strike younger age groups. Almost 90% of all patients with diabetes show insulin resistance, which also precedes the first symptoms of diabetes. The mechanisms underlying the development of insulin resistance are not well understood. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenetic factor in the development of insulin resistance and type 2 diabetes. This opens new perspectives for diagnosis and treatment of early insulin resistance and incipient glucose intolerance. Surrogate markers for this low-grade chronic inflammation include CRP, IL-6 and TNF-,. Some antidiabetic agents, for example, glitazones that reduce insulin resistance, and insulin itself, reduce inflammation. Conversely, antiinflammatory drugs (ASA/NSAID) may improve glucose tolerance. Vasoactive drugs that are often prescribed to people with diabetes, for example, statins and ACE inhibitors/angiotensin receptor antagonists, also counteract inflammation and reduce the risk of type 2 diabetes. More specific and sensitive biomarkers should be identified, which may predict early disturbances in insulin sensitivity and cardiovascular risk. Also, inflammatory signalling pathways need to be explored in greater detail, and may form the basis of drugable targets against the epidemic of insulin resistance and atherosclerosis. Copyright © 2005 John Wiley & Sons, Ltd. [source] Following in mother's footsteps?DIABETIC MEDICINE, Issue 3 2010Mother, cardiovascular disease 15 years after gestational diabetes, daughter risks for insulin resistance Diabet. Med. 27, 257,265 (2010) Abstract Aims, To determine effects on mothers and daughters of gestational diabetes mellitus/gestational impaired glucose tolerance (GDM/GIGT) on their future metabolic and cardiovascular risks. Methods, Case mothers who had GDM/GIGT in pregnancy (cases; n = 90) and normoglycaemic control women (n = 99) and their daughters underwent lifestyle assessment and metabolic tests 15-years post-partum. Results, Prevalence of glucose intolerance (GI) in daughters was 1.1%. Maternal prevalence was 44.4% in cases compared to 13.1% in controls, with conversion best predicted by weight gain. Case daughters had higher insulin resistance (IR) and greater waist circumference (WC) (51.2%) relative to control daughters (36.4%, p < 0.05) made worse if case mothers became GI at follow-up (65%) (relative risk =1.8; 95% confidence interval 1.2,2.9). In multivariable linear regression analyses adjusting for daughters' birthweight, maternal obesity (> 30.0 kg/m2) at 15years and mothers' case-control status were strong predictors of daughters' WC (p < 0.01; P < 0.01, respectively). For daughters' body mass index (BMI) percentile and percentage of body fat, maternal obesity was a stronger predictor (p < 0.01; p < 0.001)) than mothers' case-control status (p < 0.01; P = 0.09). Conclusions, GDM/GIGT pregnancies led to increased conversion to GI in mothers, minimal in daughters. Case daughters have increased risk of central adiposity and insulin resistance, whereas maternal obesity strongly predicted daughters' BMI percentile and per cent of body fat. Controlling hyperglycaemia in pregnancy and family weight management may provide the key to preventing offspring obesity and glucose intolerance post GDM/GIGT. [source] Role of glucotoxicity and lipotoxicity in the pathophysiology of Type 2 diabetes mellitus and emerging treatment strategiesDIABETIC MEDICINE, Issue 12 2009S. Del Prato Abstract Type 2 diabetes mellitus is a disease characterized by persistent and progressive deterioration of glucose tolerance. Both insulin resistance and impaired insulin secretion contribute to development of Type 2 diabetes. However, whilst insulin resistance is fully apparent in the pre-diabetic condition, impairment of insulin secretion worsens over the time, being paralleled by a progressive decline in both pancreatic B-cell function and B-cell mass. Intense research has identified a number of genetic variants that may predispose to impaired B-cell function, but such predisposition can be precipitated and worsened by toxic effects of hyperglycaemia (glucotoxicity) and elevated levels of free fatty acids (lipotoxicity). All these aspects of the pathogenesis of Type 2 diabetes are discussed in this review. Moreover, treatments that target reduction in glucotoxicity or lipotoxicity are outlined, including emerging strategies that target the role of glucagon-like peptide 1 and sodium glucose co-transporter 2. [source] Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidismDIABETIC MEDICINE, Issue 10 2009F. Tassone Abstract Aims, An increased frequency of both impaired glucose tolerance and Type 2 diabetes mellitus (DM) has been reported in primary hyperparathyroidism (pHPT), thus we sought to investigate insulin sensitivity and insulin secretion in a large series of pHPT patients. Subjects and methods, One hundred and twenty-two consecutive pHPT patients without known DM were investigated [age (mean ± sd) 59.3 ± 13.6 years, body mass index (BMI) 25.7 ± 4.2 kg/m2; serum calcium 2.8 ± 0.25 mmol/l; PTH 203.2 ± 145.4 ng/l]. Sixty-one control subjects were matched, according to the degree of glucose tolerance, in a 2 : 1 patient:control ratio. Fasting- and oral glucose tolerance test-derived estimates of insulin sensitivity and secretion were determined by means of the quantitative insulin sensitivity check index (QUICKI) and the insulin sensitivity index (ISI) composite. Results, Both the QUICKI and ISI composite were lower in pHPT patients than control subjects (P < 0.03 and P < 0.05, respectively) after adjusting for age, systolic blood pressure and BMI. Conversely, all insulin secretion estimates were significantly increased in pHPT patients than in control subjects (P < 0.04 and P < 0.03, respectively) and after adjusting for age, systolic blood pressure and BMI. Log serum calcium levels were negatively associated with the QUICKI and log ISI composite (R = ,0.30, P = 0.001; R = ,0.23, P = 0.020, respectively) in pHPT patients. Serum calcium levels significantly and independently contributed to impaired insulin sensitivity in multivariate analysis (QUICKI as dependent variable: , = ,0.31, P = 0.004, R2 = 0.15; log ISI composite as dependent variable: , = ,0.29, P = 0.005, R2 = 0.16). Conclusions, Our study confirms a reduction in both basal and stimulated insulin sensitivity in primary hyperparathyroidism, in spite of increased insulin secretion. Moreover, our data show for the first time a significant relationship between hypercalcaemia and insulin sensitivity in this condition. [source] | ||||||||||||||||||||||||||||||||||||||||