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Impaired Glucose Tolerance (impaired + glucose_tolerance)
Selected AbstractsImpaired 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] Impaired glucose tolerance and incretins in chronic liver diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2008Mark D Gorrell [source] Long-term pancreatic endocrine function following pancreatoduodenectomy with pancreaticogastrostomyJOURNAL OF SURGICAL ONCOLOGY, Issue 6 2008Yoshiaki Murakami MD Abstract Background and Objectives The aim of this study was to evaluate long-term pancreatic endocrine function following pancreatoduodenectomy with pancreaticogastrostomy. Methods Records of 52 patients who had survived for three or more years following pancreatoduodenectomy with pancreaticogastrostomy were studied retrospectively. Serum HbA1c levels had been measured prior to and at 3- to 6-month intervals after surgery. Results Three of 42 patients with normal preoperative serum HbA1c levels (,5.8%), and five of 10 patients with elevated preoperative serum HbA1c levels (>5.8%) showed deterioration of glucose tolerance. Five of these eight patients developed a pancreatic fistula postoperatively. However, the average serum HbA1c levels of patients with normal preoperative serum HbA1c levels have remained within the normal range for 3,10 years after surgery. Conclusions Pancreatic endocrine function was maintained for a long-term period after pancreatoduodenectomy with pancreaticogastrostomy. Impaired glucose tolerance appeared to be associated with postoperative pancreatic fistula formation. J. Surg. Oncol. 2008;97:519,522. © 2008 Wiley-Liss, Inc. [source] Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central ItalyPEDIATRIC DIABETES, Issue 1 2010Claudia Brufani Brufani C, Ciampalini P, Grossi A, Fiori R, Fintini D, Tozzi A, Cappa M, Barbetti F. Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy. Childhood obesity is epidemic in developed countries and is accompanied by an increase in the prevalence of type 2 diabetes (T2DM). Aims: Establish prevalence of glucose metabolism alterations in a large sample of overweight/obese children and adolescents from Central Italy. Methods: The study group included 510 overweight/obese subjects (3,18 yr). Oral glucose tolerance test (OGTT) was performed with glucose and insulin determination. Homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were derived from fasting and OGTT measurements. Beta-cell function was estimated by insulinogenic index. Fat mass was measured by dual-energy x-ray absorptiometry. Results: Glucose metabolism alterations were detected in 12.4% of patients. Impaired glucose tolerance (IGT) was the most frequent alteration (11.2%), with a higher prevalence in adolescents than in children (14.8 vs. 4.1%, p < 0.001); silent T2DM was identified in two adolescents (0.4%). HOMA-IR and glucose-stimulated insulin levels were higher in patients with IGT than individuals with normal glucose tolerance (HOMA-IR = 4.4 ± 2.5 vs. 3.4 ± 2.3, p = 0.001). Fat mass percentage and insulinogenic index were not different between the two groups. In multivariate analysis, age, fasting glucose, and insulin resistance influenced independently plasma glucose at 120 min of OGTT. Individuals with combined impaired fasting glucose/IGT (IFG/IGT) and T2DM were older and had reduced plasma insulin values at OGTT when compared to patients with simple IGT. Conclusions: Glucose metabolism alterations are frequently found among children and adolescents with overweight/obesity from Central Italy. Age, fasting glucose, and insulin resistance are main predictors of IGT. We suggest the use of OGTT as a screening tool in obese European adolescents. [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] 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] 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] 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] 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] Leptin,a predictor of abnormal glucose tolerance and prognosis in patients with myocardial infarction and without previously known Type 2 diabetesDIABETIC MEDICINE, Issue 8 2008M. Wallander Abstract Aims High levels of leptin and low adiponectin are associated with Type 2 diabetes mellitus (T2DM) and cardiovascular (CV) disease. We studied the prognostic implications of leptin and adiponectin in patients with acute myocardial infarction (AMI) without previously known Type 2 DM. Methods One hundred and eighty-one patients were included. Based on an oral glucose tolerance test at hospital discharge (day 4,5), 168 (67% men) had normal or abnormal glucose tolerance (AGT), defined as impaired glucose tolerance or T2DM. Sex- and age-matched healthy persons served as control subjects (n = 185). The associations between fasting serum leptin and adiponectin (day 2) and newly discovered AGT and CV events (CV mortality, non-fatal stroke, reinfarction or severe heart failure) during a median follow-up of 34 months were investigated. Results Compared with control subjects, patients of both genders had significantly higher levels of leptin 2 days after an AMI. These levels were higher than those obtained at hospital discharge and 3 months later. Circulating levels of (ln) leptin 2 days after the AMI predicted AGT at discharge (odds ratio 2.03, P = 0.042). Ln leptin at day 2 was the only biochemical variable that significantly predicted CV events both on univariate [hazard ratio (HR) 1.60, P = 0.018] and on multivariate analysis (HR 1.75, P = 0.045). Adiponectin levels did not differ between patients and control subjects and did not relate to AGT or CV events. Conclusions Elevated circulating levels of leptin on the first morning after an AMI are associated with the presence of AGT at discharge and with a poorer long-term prognosis. [source] HbA1c as a screening tool for detection of Type 2 diabetes: a systematic reviewDIABETIC MEDICINE, Issue 4 2007C. M. Bennett Abstract Aim To assess the validity of glycated haemoglobin A1c (HbA1c) as a screening tool for early detection of Type 2 diabetes. Methods Systematic review of primary cross-sectional studies of the accuracy of HbA1c for the detection of Type 2 diabetes using the oral glucose tolerance test as the reference standard and fasting plasma glucose as a comparison. Results Nine studies met the inclusion criteria. At certain cut-off points, HbA1c has slightly lower sensitivity than fasting plasma glucose (FPG) in detecting diabetes, but slightly higher specificity. For HbA1c at a Diabetes Control and Complications Trial and UK Prospective Diabetes Study comparable cut-off point of , 6.1%, the sensitivity ranged from 78 to 81% and specificity 79 to 84%. For FPG at a cut-off point of , 6.1 mmol/l, the sensitivity ranged from 48 to 64% and specificity from 94 to 98%. Both HbA1c and FPG have low sensitivity for the detection of impaired glucose tolerance (around 50%). Conclusions HbA1c and FPG are equally effective screening tools for the detection of Type 2 diabetes. The HbA1c cut-off point of > 6.1% was the recommended optimum cut-off point for HbA1c in most reviewed studies; however, there is an argument for population-specific cut-off points as optimum cut-offs vary by ethnic group, age, gender and population prevalence of diabetes. Previous studies have demonstrated that HbA1c has less intra-individual variation and better predicts both micro- and macrovascular complications. Although the current cost of HbA1c is higher than FPG, the additional benefits in predicting costly preventable clinical complications may make this a cost-effective choice. [source] Association between MspI polymorphism of the APO AI gene and Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 6 2005S. Morcillo Abstract Aims Genes of the Apo AI/CIII/AIV cluster on chromosome 11 have been related to plasma lipid patterns. The close relationship between carbohydrate metabolism and lipid metabolism warrants investigation of the association between this cluster and Type 2 diabetes mellitus. We therefore examined the possible association between polymorphisms of this cluster and Type 2 diabetes mellitus as part of a study of the prevalence of diabetes and the metabolic syndrome in southern Spain. Methods A total of 1224 persons were selected randomly from the town of Pizarra in the province of Malaga, southern Spain. The sample errors for the prevalence of Type 2 diabetes mellitus and the three polymorphisms studied were all , 4%. All subjects underwent phenotyping after an oral glucose tolerance test (75 g) (WHO 1998 criteria) and the XmnI and MspI polymorphisms of Apo AI and the SstI polymorphism of Apo CIII were genotyped. Results Those subjects with the mutated AA genotype of the MspI polymorphism (,75 G,A) of Apo AI had a greater risk of impaired glucose tolerance [odds ratio (OR) = 1.95, CI = 1.02,3.8, P = 0.05], Type 2 diabetes mellitus, both known (OR = 7.38, CI = 1.3,39.7, P = 0.02) and unknown (OR = 3.7, CI = 1.4,9.9, P = 0.009). This risk was independent of age, sex, obesity, triglyceride level, HDL cholesterol and pattern of insulin resistance. Conclusions Pending confirmation in prospective studies, the AA genotype of the MspI polymorphism of the Apo AI gene, within the Apo A-I/C-III/A-IV cluster, seems to be a risk factor for Type 2 diabetes mellitus. [source] A multivariate logistic regression equation to screen for dysglycaemia: development and validationDIABETIC MEDICINE, Issue 5 2005B. P. Tabaei Abstract Aims To develop and validate an empirical equation to screen for dysglycaemia [impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and undiagnosed diabetes]. Methods A predictive equation was developed using multiple logistic regression analysis and data collected from 1032 Egyptian subjects with no history of diabetes. The equation incorporated age, sex, body mass index (BMI), post-prandial time (self-reported number of hours since last food or drink other than water), systolic blood pressure, high-density lipoprotein (HDL) cholesterol and random capillary plasma glucose as independent covariates for prediction of dysglycaemia based on fasting plasma glucose (FPG) , 6.1 mmol/l and/or plasma glucose 2 h after a 75-g oral glucose load (2-h PG) , 7.8 mmol/l. The equation was validated using a cross-validation procedure. Its performance was also compared with static plasma glucose cut-points for dysglycaemia screening. Results The predictive equation was calculated with the following logistic regression parameters: P = 1 + 1/(1 + e,X) = where X = ,8.3390 + 0.0214 (age in years) + 0.6764 (if female) + 0.0335 (BMI in kg/m2) + 0.0934 (post-prandial time in hours) + 0.0141 (systolic blood pressure in mmHg) , 0.0110 (HDL in mmol/l) + 0.0243 (random capillary plasma glucose in mmol/l). The cut-point for the prediction of dysglycaemia was defined as a probability , 0.38. The equation's sensitivity was 55%, specificity 90% and positive predictive value (PPV) 65%. When applied to a new sample, the equation's sensitivity was 53%, specificity 89% and PPV 63%. Conclusions This multivariate logistic equation improves on currently recommended methods of screening for dysglycaemia and can be easily implemented in a clinical setting using readily available clinical and non-fasting laboratory data and an inexpensive hand-held programmable calculator. [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] Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose toleranceDIABETIC MEDICINE, Issue 5 2004S. M. A. Bennett Abstract Aims To determine the effects of rosiglitazone on insulin sensitivity, glucose tolerance and ambulatory blood pressure when administered to subjects with persistent impaired glucose tolerance (IGT). Methods Eighteen subjects with persistent IGT were randomized to receive rosiglitazone 4 mg twice daily or matching placebo for 12 weeks. Evaluation at baseline and at the end of treatment included measurement of whole body insulin sensitivity during a euglycaemic hyperinsulinaemic clamp and deriving an insulin sensitivity index. Changes in glucose and insulin concentration were determined after oral glucose tolerance test (OGTT) and mixed meal tolerance tests, and 24-h ambulatory blood pressure was monitored. Results Rosiglitazone significantly improved the insulin sensitivity index by 2.26 µg/kg per min per pmol/l relative to placebo (P = 0.0003). Four of nine subjects receiving rosiglitazone reverted to normal glucose tolerance and 5/9 remained IGT, although four of these had improved 2-h glucose values. In the placebo group, 1/9 subjects progressed to Type 2 diabetes and 8/9 remained IGT. Following OGTT and meal tolerance test, glucose and insulin area under curve were reduced over 3 and 4 h, respectively. Compared with placebo, ambulatory blood pressure decreased significantly in the rosiglitazone group by 10 mmHg systolic (P = 0.0066) and 8 mmHg diastolic (P = 0.0126). Conclusions Consistent with its effects in patients with Type 2 diabetes, rosiglitazone substantially improved whole body insulin sensitivity and the glycaemic and insulinaemic responses to an OGTT and meal tolerance test in subjects with persistent IGT. Furthermore, rosiglitazone reduced systolic and diastolic ambulatory blood pressure in these subjects. [source] What does postprandial hyperglycaemia mean?DIABETIC MEDICINE, Issue 3 2004R. J. Heine Abstract Aims The potential importance of postprandial glucose (PPG) control in the development of complications in Type 2 diabetes is much debated. The recent American Diabetes Association (ADA) consensus statement discussed the role of postprandial hyperglycaemia in the pathogenesis of diabetic complications and concluded that the relationship between PPG excursions and the well-established risk factors for cardiovascular disease (CVD) should be further examined. Using the ADA statement as a starting point and including the more recent American College of Endocrinology guidelines on glycaemic control, a panel of experts in diabetes met to review the role of PPG within the context of the overall metabolic syndrome, in the development of complications in Type 2 diabetes. Results Post-prandial hyperglycaemia is a risk indicator for micro- and macrovascular complications, not only in patients with Type 2 diabetes but also in those with impaired glucose tolerance. In addition, the metabolic syndrome confers an increased risk of CVD morbidity and mortality. The debate focused on the relative contributions of postprandial hyperglycaemia, the metabolic syndrome and, in particular, raised triglyceride levels in the postprandial state, to the development of cardiovascular complications of diabetes. Conclusions The panel recommended that in the prevention and management of microvascular complications of Type 2 diabetes, targeting both chronic and acute glucose fluctuations is necessary. Lowering the macrovascular risk also requires control of (postprandial) triglyceride levels and other components of the metabolic syndrome. [source] Epidemiology of gestational diabetes mellitus and its association with Type 2 diabetesDIABETIC MEDICINE, Issue 2 2004A. Ben-Haroush Abstract Gestational diabetes (GDM) is defined as carbohydrate intolerance that begins or is first recognized during pregnancy. Although it is a well-known cause of pregnancy complications, its epidemiology has not been studied systematically. Our aim was to review the recent data on the epidemiology of GDM, and to describe the close relationship of GDM to prediabetic states, in addition to the risk of future deterioration in insulin resistance and development of overt Type 2 diabetes. We found that differences in screening programmes and diagnostic criteria make it difficult to compare frequencies of GDM among various populations. Nevertheless, ethnicity has been proven to be an independent risk factor for GDM, which varies in prevalence in direct proportion to the prevalence of Type 2 diabetes in a given population or ethnic group. There are several identifiable predisposing factors for GDM, and in the absence of risk factors, the incidence of GDM is low. Therefore, some authors suggest that selective screening may be cost-effective. Importantly, women with an early diagnosis of GDM, in the first half of pregnancy, represent a high-risk subgroup, with an increased incidence of obstetric complications, recurrent GDM in subsequent pregnancies, and future development of Type 2 diabetes. Other factors that place women with GDM at increased risk of Type 2 diabetes are obesity and need for insulin for glycaemic control. Furthermore, hypertensive disorders in pregnancy and afterwards may be more prevalent in women with GDM. We conclude that the epidemiological data suggest an association between several high-risk prediabetic states, GDM, and Type 2 diabetes. Insulin resistance is suggested as a pathogenic linkage. It is possible that improving insulin sensitivity with diet, exercise and drugs such as metformin may reduce the risk of diabetes in individuals at high risk, such as women with polycystic ovary syndrome, impaired glucose tolerance, and a history of GDM. Large controlled studies are needed to clarify this issue and to develop appropriate diabetic prevention strategies that address the potentially modifiable risk factors. Diabet. Med. 20, ***,*** (2003) [source] Progression to clinically diagnosed and treated diabetes from impaired glucose tolerance and impaired fasting glycaemiaDIABETIC MEDICINE, Issue 12 2003Q. Qiao Abstract Aims To evaluate the risk of diabetes in subjects with impaired fasting glycemia (IFG) as compared with impaired glucose tolerance (IGT) and normal glucose tolerance. Methods Men (1223) and women (1370) aged 45,64 years and free of diabetes at baseline were followed-up for 10 years, with 26 737 person years accumulated. The incident diabetic cases were identified through the national Drug Register and the Hospital Discharge Register. Results During the 10 years of follow-up, 53 (4.3%) men and 47 (3.4%) women developed diabetes. IFG alone defined 22 (15.5/1000 person years) diabetic cases, which was higher than for subjects with normal fasting glucose. Subjects with isolated IGT identified an additional 34 cases (155% more) which could not be defined by IFG alone. The area under the ROC curve was larger for 2-h glucose (0.77, 95% CI 0.72,0.82) than for fasting glucose (0.65, 0.58,0.71). The multivariate adjusted Cox hazard ratio was higher for isolated IGT (3.9, 95% CI 2.4,6.2) than for isolated IFG (2.3, 0.9,5.7) as compared with subjects with neither IFG nor IGT. Conclusion Both IFG and IGT are risk predictors for diabetes, but IGT defines a much larger target population for prevention. [source] Preventing Type 2 diabetes and the dysmetabolic syndrome in the real world: a realistic viewDIABETIC MEDICINE, Issue 9 2003P. Zimmet The last two decades have seen an explosive increase in the number of people with diabetes globally. There is now an urgent need for strategies to prevent the emerging global epidemic. Several recent successful intervention studies, both lifestyle and pharmacological, targeting subjects with impaired glucose tolerance (IGT) have stimulated enthusiasm for prevention of Type 2 diabetes. Lifestyle interventions reduced the incidence of diabetes by over 50% in the Finnish Diabetes Prevention Study and the Diabetes Prevention Program. Can the findings of these two studies be applied globally? Underpinning the enthusiasm, there needs to be a realistic approach to interventions in both developed and developing nations, and in ethnic groups where a better understanding of the socio-economic, cultural and demographic issues and perceptions surrounding chronic diseases such as diabetes is required. Whether the strategies used in these two studies can be translated into a ,real world' scenario is doubtful. In practice, it is more than likely that a number of strategies will be needed to compliment the lifestyle approach. These will include pharmacological approaches with metformin, acarbose and other agents used to treat diabetes and its complications, currently under investigation. Longer-term follow-up studies will also clarify whether both lifestyle and pharmacological interventions actually prevent Type 2 diabetes, or merely delay its onset. [source] Comparison of ADA and WHO criteria for the diagnosis of diabetes in elderly KoreansDIABETIC MEDICINE, Issue 10 2002K. M. Choi Abstract Aims This study was conducted to compare the prevalence and cardiovascular risk factors of different categories of glucose tolerance in the elderly Korean population using World Health Organization (WHO) and American Diabetes Association (ADA) criteria. Methods This study included 1456 non-diabetic subjects over the age of 60 years, selected from a cross-sectional study, which was conducted in 1999 in Seoul, Korea. Fasting and post-challenge 2-h plasma glucose, insulin levels, body mass index (BMI), waist,hip ratio (WHR), blood pressure, and lipid profiles were examined. Prevalence of glucose tolerance categories and the level of agreement (, statistics) were obtained using WHO 2-h criteria and ADA fasting criteria. Comparison of cardiovascular risk factors among several concordant and discordant glucose intolerance groups was done. Results The prevalence rates of newly diagnosed diabetes of elderly men defined by WHO 2-h criteria and ADA fasting criteria were 11.8% and 4.8%, respectively. That of elderly women was 8.1% by WHO 2-h criteria and 3.1% by ADA fasting criteria. The prevalence of impaired glucose tolerance (IGT) by WHO criteria was also higher than that of impaired fasting glucose (IFG) by ADA criteria (23.5% vs. 10.0% men, 23.7% vs. 7.5% women). The level of agreement between ADA fasting criteria and WHO 2-h criteria was low (weighted , = 0.228 men, weighted , = 0.301 women). The concordant diabetic women by both ADA fasting criteria and WHO 2-h criteria showed higher BMI, WHR, diastolic blood pressure, total cholesterol and triglyceride levels than concordant normal subjects. However, the isolated post-challenge hyperglycaemia (IPH) women group was not different significantly from the concordant normal women group except in BMI. Conclusions Our results clearly show that the 1997 ADA fasting criteria are less sensitive for diagnosing diabetes than oral glucose tolerance test (OGTT)-based WHO criteria in elderly Koreans. Also, there is a poor agreement of different categories of glucose tolerance between ADA and WHO criteria; therefore, the OGTT remains a valuable test in diagnosing diabetes and classifying various categories of glucose intolerance, especially in elderly Koreans. [source] Metabolic effects of metformin in patients with impaired glucose toleranceDIABETIC MEDICINE, Issue 7 2001M. Lehtovirta Abstract Aims To assess the effect of metformin on insulin sensitivity, glucose tolerance and components of the metabolic syndrome in patients with impaired glucose tolerance (IGT). Methods Forty first-degree relatives of patients with Type 2 diabetes fulfilling WHO criteria for IGT and participating in the Botnia study in Finland were randomized to treatment with either metformin 500 mg b.i.d. or placebo for 6 months. An oral glucose tolerance test (OGTT) and a euglycaemic hyperinsulinaemic clamp in combination with indirect calorimetry was performed at 0 and 6 months. The patients were followed after stopping treatment for another 6 months in an open trial and a repeat OGTT was performed at 12 months. Results Metformin treatment resulted in a 20% improvement in insulin-stimulated glucose metabolism (from 28.7 ± 13 to 34.4 ± 10.7 µmol/kg fat-free mass (FFM)/min) compared with placebo (P = 0.01), which was primarily due to an increase in glucose oxidation (from 16.6 ± 3.6 to 19.1 ± 4.4 µmol/kg FFM; P = 0.03) These changes were associated with a minimal improvement in glucose tolerance, which was maintained after 12 months. Conclusions Metformin improves insulin sensitivity in subjects with IGT primarily by reversal of the glucose fatty acid cycle. Obviously large multicentre studies are needed to establish whether these effects are sufficient to prevent progression to manifest Type 2 diabetes and associated cardiovascular morbidity and mortality. Diabet. Med. 18, 578,583 (2001) [source] Type 2 diabetes mellitus, impaired glucose tolerance and associated factors in a rural Palestinian villageDIABETIC MEDICINE, Issue 10 2000A. Husseini SUMMARY Aims To investigate the prevalence of Type 2 diabetes mellitus and impaired glucose tolerance (IGT) and to identify risk factors associated with diabetes in a rural Palestinian village. Methods A cross-sectional, population-based study investigating 500 adults aged 30,65 years (response rate 85%) determined the diabetes status using the oral glucose tolerance test (OGTT). A standard questionnaire, a simple clinical examination and laboratory tests assessed blood lipids, blood pressure, waist-to-hip ratio (WHR), body mass index (BMI) and other risk factors for diabetes Results The prevalence of Type 2 diabetes was 9.8% (95% confidence interval 7.3,12.3) and IGT 8.6% (6.1,11.1), while the prevalence standardized to the European population was 11.6% (8.8,14.4) for Type 2 diabetes and 10.3% (7.6,13.0) for IGT. Age, positive family history, high triglycerides level, and high WHR were significantly associated with Type 2 diabetes. Conclusions Of the factors associated with diabetes, WHR and triglycerides levels are potentially modifiable, and should be addressed by preventive health activities. The high prevalence of Type 2 diabetes mellitus and its potential increase as a result of the ageing of the Palestinian population constitutes a major public health problem. [source] Lifestyle intervention in individuals with normal versus impaired glucose toleranceEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2007S. Schäfer Abstract Background, Lifestyle intervention is effective in the prevention of type 2 diabetes in individuals with impaired glucose tolerance (IGT). It is currently unknown whether it has beneficial effects on metabolism to a similar extent, in individuals with normal glucose tolerance (NGT) compared to individuals with IGT. Materials and methods, Data from 181 subjects (133 with NGT and at risk for type 2 diabetes and 48 with IGT) who participated in the Tuebingen Lifestyle Intervention Program with increase in physical activity and decrease in caloric intake were included into this study. Body fat distribution was quantified by whole-body magnetic resonance (MR) tomography and liver fat and intramyocellular fat by 1H-MR spectroscopy. Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT). Results, After 9 ± 2 months of follow-up, the diagnosis of IGT was reversed in 24 out of 48 individuals. Only 14 out of 133 participants with NGT developed IGT. Body weight decreased in both groups by 3% (both P < 0·0001). Two-hour glucose concentrations during an OGTT decreased in individuals with IGT (,14%, P < 0·0001) but not with NGT (+2%, P = 0·66). Insulin sensitivity increased both in individuals with IGT (+9%, P = 0·04) and NGT (+17%, P < 0·0001). Visceral fat (,8%, P = 0·006), liver fat (,28%, P < 0·0001) and intramyocellular fat (,15%, P = 0·006) decreased in participants with IGT. In participants with NGT these changes were significant for visceral fat (,16%, P < 0·0001) and liver fat (,35%, P < 0·0001). Conclusions, Moderate weight loss under a lifestyle intervention with reduction in total, visceral and ectopic fat and increase in insulin sensitivity improves glucose tolerance in individuals with IGT but not with NGT. In individuals with NGT, the beneficial effects of a lifestyle intervention on fat distribution and insulin sensitivity possibly prevent future deterioration in glucose tolerance. [source] Idiopathic polyneuropathy and impaired glucose metabolism in a Norwegian patient seriesEUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2008M. Nebuchennykh Background and purpose:, North American studies have indicated a high prevalence of impaired glucose tolerance (IGT) in patients with sensory polyneuropathy. We searched for the occurrence of IGT in a Norwegian patient material with polyneuropathy. Methods:, Seventy patients with symptoms and signs of sensory polyneuropathy were included. Cases with known causes of neuropathy were excluded. All patients underwent a 2 h oral glucose tolerance test (OGTT). Nerve conduction studies (NCS), quantitative sensory testing (QST) and skin biopsy with assessment of intra-epidermal nerve fibre (IENF) density were performed. Results:, Sixteen patients (23%) had impaired glucose metabolism (IGM): 2 (3%) were found to have diabetes, 9 (13%) had IGT, 3 (4%) had impaired fasting glucose (IFG) and 2 (3%) both IFG and IGT. About 62% of the patients with IGM and polyneuropathy and 50% of those with chronic idiopathic axonal polyneuropathy (CIAP) had abnormalities on NCS. Reduction of IENF occurred in 37% of the patients with IGM and 43% of those with CIAP. Conclusions:, Patients with polyneuropathy and IGM had essentially the same degree of involvement of small and large nerve fibres as patients with CIAP. IGT seems less frequent in Norwegian patients with polyneuropathy than reported in North American populations. [source] The value of a specialist lipid clinicINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2008S. C. Martin Summary Aims:, To establish the value of the first 3 years of a cardiovascular risk factor clinic in tackling the major risk factors for cardiovascular disease (CVD). Methods:, A database review of all 339 patients referred to the clinic. Results:, Blood pressure levels in the hypertensive patients were significantly reduced and 9% of the smokers managed to quit for 12 months, half of them subsequently relapsing. Ninety-eight oral glucose tolerance tests were performed and 40% were abnormal yielding 10 patients with hitherto unsuspected diabetes and 29 with impaired glucose tolerance. Sixty-four of the 97 referrals of patients in the primary prevention group (no evidence of CVD) were found to have calculated Framingham coronary heart disease risk estimates of < 15% per decade, the lowest being 0.3%. Lipid levels were significantly reduced in both the hypercholesterolaemic (n = 290) and hypertriglyceridaemic (n = 49) patient groups through the use of more potent statins, extensive use of combination therapy and appropriate use of fibrates and omega-3 fish oil supplements. The annual drug cost per patient treated only increased from £310.72 to £398.08, yet there was a 3.5-fold increase in the number of patients achieving the General Medical Services 2 target of a total cholesterol < 5 mmol/l and a 4.5-fold increase in patients achieving the Joint British Societies 2 target of a low-density lipoprotein (LDL) cholesterol < 2 mmol/l. Conclusion:, The need for a specialist clinic was demonstrated by the 66% of primary prevention referrals who did not meet the current NICE treatment threshold. Additionally, the clinic was able to diagnose and treat 39 patients with undiagnosed diabetes mellitus/impaired glucose tolerance and 12 with hypothyroidism. LDL cholesterol was reduced overall by 36% implying a greater than one-third reduction in future cardiovascular events before the improvements in blood pressure control and smoking cessation are included and this was achieved at marginal extra cost to the mean drug bill at referral. [source] CpG oligodeoxynucleotides accelerate reovirus type 2-triggered insulitis in DBA/1 suckling miceINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2002T. Hayashi Summary. We reported previously that reovirus type-2 (Reo-2) triggers T-helper (Th) 1-mediated autoimmune insulitis resulting in temporal impaired glucose tolerance (IGT) approximately 10 days post infection (d.p.i) in suckling DBA/1 mice. We hypothesized that CpG motifs in bacteria may enhance virus-induced insulitis through its content of unmethylated CpG motifs. In the infected mice, the intraperitoneal treatment of synthetic 20-base oligodeoxynucleotides with CpG motifs (CpG ODN) caused increase in cumulative incidence of insulitis with IGT, increased serum interferon (IFN)-, concentration, and high frequency of autoantibody against pancreatic islet cells, compared to the infected mice without CpG ODN at 17 d.p.i. Also CD4+ and CD8+ lymphocytes infiltrated in and/or around pancreatic islets in the CpG ODN-treated mice. This evidence suggests that CpG ODN may contribute to accelerate Reo-2-induced autoimmune reaction against pancreatic islet cells via additional effects of Th1 cytokines especially IFN-,. [source] Cigarette smoking, oral moist snuff use and glucose intoleranceJOURNAL OF INTERNAL MEDICINE, Issue 2 2000P.-G. Persson Abstract. Persson P-G, Carlsson S, Svanström L, Östenson C-G, Efendic S, Grill V (Karolinska Hospital and Karolinska Institutet, Stockholm, Sweden). Cigarette smoking, oral moist snuff use and glucose intolerance. J Intern Med 2000; 248: 103,110. Objective. To investigate the association between cigarette smoking and use of oral moist snuff and impaired glucose tolerance and type 2 diabetes. Design. We performed a population-based cross-sectional study of glucose intolerance and tobacco use in Stockholm during 1992,94. The sample consisted of 3128 men, aged 35,56 years, of whom 52% had a family history of diabetes. In an oral glucose tolerance test, we detected 55 men with type 2 diabetes and 172 with impaired glucose tolerance. Information on cigarette smoking and oral moist snuff use was collected by a questionnaire. Results. The odds ratio of type 2 diabetes was increased for smokers of 25+ cigarettes day,1 (odds ratio = 2.6, 95% confidence interval = 1.1,5.9) as well as for moist snuff dippers of 3+ boxes week,1 (odds ratio = 2.7, 95% confidence interval = 1.3,5.5). The odds ratio of relatively high (highest tertile) fasting insulin levels in subjects with impaired glucose tolerance associated with cigarette smoking of 25+ cigarettes day,1 was 1.5 (95% confidence interval = 0.7,3.6). The corresponding estimate of a relatively low (lowest tertile) 2 h insulin response was 2.5 (95% confidence interval = 0.9,7.1). Conclusions. These results indicate that heavy users of cigarettes or moist snuff have an increased risk of type 2 diabetes. The results could suggest that tobacco use is associated with a low insulin response. [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] Obesity in Youth: Implications for the Advanced Practice Nurse in Primary CareJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 8 2004C-ANP, Diane Berry PhD Purpose To discuss the advanced practice nurse's diagnosis and management of obesity in youth in primary care. Data Sources Review of current scientific literature, practice guidelines, and a case study. Conclusions Obesity in youth is difficult to manage. Recent research suggests a genetic and environmental etiology associated with impaired glucose tolerance, type 2 diabetes, hypertension, hyperlipidemia, and hypertriglyceridemia. Nutrition education, increasing physical activity, decreasing sedentary behaviors, and behavioral modification have been used with varying success. Management is directed at healthy lifestyle behavior change for youth and their families. Implications for Practice If obesity, impaired glucose tolerance, hypertension, hypercholesterolemia, and hypertriglyceridemia are left untreated, youth may develop type 2 diabetes and coronary artery disease later in life and suffer early morbidity and mortality. [source] | |||||||||||||||||||||||||||||||