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Tolerance Test (tolerance + test)
Kinds of Tolerance Test Selected AbstractsA double-blind, placebo-controlled trial of rosiglitazone for clozapine-induced glucose metabolism impairment in patients with SchizophreniaACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2009D. C. Henderson Objective:, The primary purpose of this 8-week double-blind, placebo-controlled trial of rosiglitazone 4 mg/day was to examine its effect on insulin sensitivity index (SI) and glucose utilization (SG) in clozapine-treated subjects with schizophrenia with insulin resistance. Method:, Eighteen subjects were randomized and accessed with a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) at baseline and at week 8 to estimate SG and SI. Results:, Controlling for the baseline, comparing the rosiglitazone group with placebo group, there was a non-significant improvement in SG (0.016 ± 0.006,0.018 ± 0.008, effect size = 0.23, P = 0.05) with a trend of improvement in SI in the rosiglitazone group (4.6 ± 2.8,7.8 ± 6.7, effect size = 0.18, P = 0.08). There was a significant reduction in small low-density lipoprotein cholesterol (LDL-C) particle number (987 ± 443,694 ± 415, effect size = 0.30, P = 0.04). Conclusion:, Rosiglitazone may have a role in addressing insulin resistance and lipid abnormalities associated with clozapine. [source] (613) Radiculopathy Treatment Assessment Using Pain Tolerance TestPAIN MEDICINE, Issue 2 2000Article first published online: 25 DEC 200 Authors: Y. Eugene Mironer, Carolinas Center for Advanced Management of Pain; Judson J. Somerville, The Pain Management Clinic of Laredo Current measurements of the outcomes of chronic radiculopathy treatment are limited to subjective criteria: level of pain, range of motion, etc. Our previous study showed that nerve conductivity does not correlate well with the intensity of pain after treatment of radiculopathy (1). In the current study we looked at the Pain Tolerance Threshold (PTT) as a possible measurement of the results of radiculopathy treatment. Twenty patients with chronic radiculopathy (13 lumbar and 7 cervical) underwent epidural steroid injections at the level of involvement. Before, and approximately one week after the procedure, we measured PTT in both the involved and contralateral extremity at 3 different frequencies (5Hz, 250Hz, and 2000 Hz) using Neurometer. Level of pain was also assessed using a Visual Analog Scale (VAS). Initial PTT results showed great interpersonal variability. Nearly half of the patients did not show significant differences in PTT between affected and unaffected sides. Of interest, the majority experienced intolerable pain at 2000 Hz stimulation at lower than maximal intensity output, which contradicts previous findings (2). Dynamics of the PTT measurements after treatment did not directly correlate with changes in the level of pain. Nevertheless, in 7 out of 8 patients with low PTT (relative to the unaffected side) it increased significantly, with noticeable decrease of VAS score. Similar results were not found in patients with either normal initial PTT score or minimal improvement of pain. 1. Mironer YE, Somerville JJ The current perception threshold evaluation in radiculopathy: efficacy in diagnosis and assessment of treatment results. Pain Digest 1998;8:37,38. 2. Liu SS, Gerancher JC, Bainton BG, et al. The effects of electrical stimulation at different frequencies on perception and pain in human volunteers: epidural versus intravenous administration of fentanyl. Anesth Analg 1996;82:98,102. [source] Simple Measures to Monitor ,-Cell Mass and Assess Islet Graft DysfunctionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2007R. N. Faradji The aim of this study was to develop a simple test for the assessment of islet graft dysfunction based on measures involving fasting C-peptide. Calculations were made to account for the dependence of C-peptide secretion on glucose concentration (C-peptide/glucose ratio [CP/G]) and adjusted for renal function by calculating the C-peptide/glucose-creatinine ratio (CP/GCr). Values from 22 recipients were analyzed at different times post-last islet infusion. Receiver operating characteristic curves were used to determine which of these measures best predicts high 90-minute glucose (90 min-Glc; >10 mmol/L) after a Mixed Meal Tolerance Test (MMTT). In this initial analysis, CP/G was found to be superior predicting high 90 min-Glc with a larger area under the ROC curve than C-peptide (p = 0.01) and CP/GCr (p = 0.06). We then correlated C-peptide and CP/G with islet equivalents-IEQ/kg infused, 90 min-Glc after MMTT and clinical outcome (,-score). C-peptide and CP/G in the first 3 months post-last islet infusion correlated with IEQ/kg infused. CP/G correlated with 90 min-Glc and ,-score. C-peptide and CP/G are good indicators of islet mass transplanted. CP/G is more indicative of graft dysfunction and clinical outcome than C-peptide alone. The ease of calculation and the good correlation with other tests makes this ratio a practical tool when monitoring and managing islet transplant recipients. [source] Acute exercise reverses TRB3 expression in the skeletal muscle and ameliorates whole body insulin sensitivity in diabetic miceACTA PHYSIOLOGICA, Issue 1 2010A. Matos Abstract Aim:, TRB3 became of major interest in diabetes research when it was shown to interact with and inhibit the activity of Akt. Conversely, physical exercise has been linked to improved glucose homeostasis. Thus, the current study was designed to investigate the effects of acute exercise on TRB3 expression and whole body insulin sensitivity in obese diabetic mice. Methods:, Male leptin-deficient (ob/ob) mice swam for two 3-h-long bouts, separated by a 45-min rest period. After the second bout of exercise, food was withdrawn 6 h before antibody analysis. Eight hours after the exercise protocol, the mice were submitted to an insulin tolerance test (ITT). Gastrocnemius muscle samples were evaluated for insulin receptor (IR) and IRS-1 tyrosine phosphorylation, Akt serine phosphorylation, TRB3/Akt association and membrane GLUT4 expression. Results:, Western blot analysis showed that TRB3 expression was reduced in the gastrocnemius of leptin-deficient (ob/ob) mice submitted to exercise when compared with respective ob/ob mice at rest. In parallel, there was an increase in the insulin-signalling pathway in skeletal muscle from leptin-deficient mice after exercise. Furthermore, the GLUT4 membrane expression was increased in the muscle after the exercise protocol. Finally, a single session of exercise improved the glucose disappearance (KITT) rate in ob/ob mice. Conclusion:, Our results demonstrate that acute exercise reverses TRB3 expression and insulin signalling restoration in muscle. Thus, these results provide new insights into the mechanism by which physical activity ameliorates whole body insulin sensitivity in type 2 diabetes. [source] Antidiabetic and toxicological evaluations of naringenin in normoglycaemic and NIDDM rat models and its implications on extra-pancreatic glucose regulationDIABETES OBESITY & METABOLISM, Issue 11 2008R. R Ortiz-Andrade Aim:, The present investigation was designed to determine the in vivo antidiabetic effect of naringenin (NG) in normoglycaemic and diabetic rat models through blood glucose (GLU) measurements following acute and subchronic time periods. Possible modes of action of NG were investigated and its acute toxicity determined. Methods:, Normoglycaemic and non-insulin-dependent diabetes mellitus (NIDDM) rat models were treated for acute and subchronic (5 days) time periods with 50 mg/kg/day of NG. Blood biochemical profiles were determined after 5 days of the treatment in normoglycaemic and NIDDM rats using commercial kits for GLU, triglycerides (TG), total cholesterol (CHOL) and high-density lipoprotein (HDL). In order to elucidate its antidiabetic mode of action, NG was administered intragastrically and an oral glucose tolerance test performed using GLU and sucrose (2 g/kg) as substrates. The inhibitory effect of a single concentration of NG (10 ,M) on 11,-hydroxysteroid dehydrogenase type 1 (11,-HSD1) activity in vitro was determined. Finally, the preclinical safety and tolerability of NG was determined by toxicological evaluation in mice and rats using Organization for Economic Cooperation and Development (OECD) protocols. Results:, Intragastrically administered NG (50 mg/kg) induced a significant decrease in plasma GLU in normoglycaemic and NIDDM rat models (p < 0.05) following acute and subchronic time periods. After 5 days of administration, NG produced significant diminished blood GLU and TG levels in streptozotocin,nicotinamide,induced diabetic rats. The administration of NG to normal rats significantly increased the levels of TG, CHOL and HDL (p < 0.05). NG (5 and 50 mg/kg) induced a total suppression in the increase of plasma GLU levels after administration of substrates (p < 0.01), but NG did not produce inhibition of ,-glucosidase activity in vitro. However, NG (10 ,M) was shown to inhibit 11,-HSD1 activity by 39.49% in a cellular enzyme assay. Finally, NG showed a Medium Lethal Dose LD50 > 5000 mg/kg and ranking at level five based on OECD protocols. Conclusion:, Our findings suggest that NG may exert its antidiabetic effect by extra-pancreatic action and by suppressing carbohydrate absorption from intestine, thereby reducing the postprandial increase in blood GLU levels. [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] The addition of metformin in type 1 diabetes improves insulin sensitivity, diabetic control, body composition and patient well-beingDIABETES OBESITY & METABOLISM, Issue 1 2007R. J. Moon Aim:, As many overweight people with T1DM are insulin resistant, adjuvant therapy with insulin sensitising agents, such as metformin, may be beneficial. This study evaluated the effect of adjuvant metformin in T1DM on insulin sensitivity, diabetic control, body composition, quality of life (QOL) and treatment satisfaction. Materials and Methods:, A 3-month prospective open-labelled pilot study of 16 patients aged 18-40 with T1DM and body mass index (BMI) >25 kg/m2 was performed. The patients received 500-850 mg metformin twice daily. Insulin sensitivity, assessed by a frequently sampled intravenous glucose tolerance test [n=5], body composition, HbA1c and quality of life (QOL) were measured before and after treatment. A retrospective review of 30 patients with T1DM treated with metformin for at least 4 months was also performed. BMI, HbA1c and insulin requirements during metformin treatment was compared to pre-metformin data, and to patients treated with insulin only. Results:, In the pilot study, insulin sensitivity increased significantly from 0.86 ± 0.33 × 10,4/min/(µU/ml) to 1.17 ± 0.48 × 10,4/min/(µU/ml) after 3 months adjuvant therapy (p = 0.043). This was associated with a decreased insulin requirement and mean daily blood glucose. There were no significant changes in HbA1c or body composition. QOL significantly improved (p < 0.002). The retrospective review revealed an initial reduction in HbA1c (0.8 ± 1.4%, p = 0.001). This effect diminished with prolonged treatment. BMI decreased in patients remaining on metformin for a 2-year period (0.5 ± 0.5kg/m2, p = 0.042). Conclusion:, Adjuvant metformin can improve QOL, insulin sensitivity and glycaemic control in overweight adults with T1DM. [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] 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] Clustering of cardiovascular risk factors with diabetes in Chinese patients: the effects of sex and hyperinsulinaemiaDIABETES OBESITY & METABOLISM, Issue 3 2001Z. -R. SUMMARY Objective This study was designed to investigate factors which affect the clustering of cardiovascular risk factors with diabetes in Chinese patients. Research Design and Methods: Six hundred and fifty-four patients with diabetes were assessed comprehensively for diabetes complications and cardiovascular risk factors in a metropolitan hospital in Beijing, China. Insulin resistance and secretion were also evaluated by measurement of glucose and insulin levels before and after a meal tolerance test. Results were analysed according to patient groups stratified by the number of cardiovascular risk factors coexisting with diabetes. Results Cardiovascular risk factors were common in Chinese diabetic patients. The clustering of three or more of these factors with diabetes occurred more often than by chance alone and was associated with postprandial hyperinsulinaemia. Patients with a high number of risk factors were more prone to macrovascular events but did not have higher albuminuria. Using the commonly adopted lower threshold for diagnosing obesity and central obesity in women, there were more women with multiple risk factors. However, this disappeared if the same criteria were used for men and women. Even in the presence of diabetes, cardiovascular risk factors were inadequately controlled in most patients. Conclusions The concurrence of diabetes and other cardiovascular risk factors which constitute the metabolic syndrome is a common phenomenon in urban Chinese diabetic patients. It is associated with hyperinsulinaemia and possibly the female sex. This study emphasises the importance of public health measures to control cardiovascular risk factors in patients with diabetes. [source] Differential effects of short and long duration insulinotropic agents on meal-related glucose excursionsDIABETES OBESITY & METABOLISM, Issue 2 2001C. J. De Souza SUMMARY Aim Abnormal ,-cell function, characterized as the inability of the ,-cell to mount a rapid secretory response to glucose, is a well-established pathology of type 2 diabetes mellitus. These studies were designed to demonstrate the importance of early insulin release on the control of meal-induced glucose excursions by capitalizing on the significant pharmacodynamic differences between several oral insulin secreting agents. Methods Male Sprague Dawley fitted with indwelling jugular cannulas were used to compare the pharmacodynamic profiles of nateglinide (Nateg), glipizide (Glip) and repaglinide (Repag) through frequent blood samples following the administration of these compounds via oral gavage. In similar animals which were pretrained to consume their daily food intake in two discrete 45-min meals, the effects of compound induced changes in pre-meal, meal and post-meal insulin profiles on glycaemic control were assessed through frequent blood sampling following the administration of these compounds 10 min prior to a 30-min meal. Results There were significant pharmacodynamics differences between the three oral agents tested and the time to elicit peak insulin secretory responses increased from Nateg (4 min) to Repag (10 min) to Glip (45 min). During the meal tolerance test, glibenclamide did not increase pre-meal insulin levels and glucose excursions paralleled those in the control. Conversely, the other three agents, at doses that produced hypoglycaemic responses of similar magnitude, all increased early insulin release (,AUC(-15 to 3 min) = 0.5 ± 0.01, 1.6 ± 0.4, 3.6 ± 0.0, 1.2 ± 0.1 and 1.73 ± 0.4 nmol/min, for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively) and curbed glucose excursions during the meal at varying rates and degrees (,AUC(0,30 min) = 39 ± 6, 8 ± 7, 5 ± 7, ,,1 ± 8 and ,,3 ± 8 mmol/min for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively). However, unlike Nateg, the longer duration of action of Repag and Glip elicited sustained post-meal relative hypoglycaemia. Conclusion These data support the impact of early and rapid insulin release in the control of prandial and post-meal glycaemia and demonstrate that a short anticipatory burst of insulin, restricted to the beginning of a meal, provides a clear metabolic advantage and prevents post-meal hypoglycaemic episodes when compared to a greater but reactive insulin exposure that follows a meal-induced increase in glucose excursion. [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 prevalence of depressive symptoms in a white European and South Asian population with impaired glucose regulation and screen-detected Type 2 diabetes mellitus: a comparison of two screening toolsDIABETIC MEDICINE, Issue 8 2010N. Aujla Diabet. Med. 27, 896,905 (2010) Abstract Aims, To compare the identification of prevalent depressive symptoms by the World Health Organization-5 Wellbeing Index (WHO-5) and Centre for Epidemiological Studies Depression Scale (CES-D) for South Asian and white European people, male and female, attending a diabetes screening programme, and to explore the adequacy of the screening tools for this population. An additional aim was to further explore associations of depressive symptoms with impaired glucose regulation (IGR) and Type 2 diabetes mellitus (Type2 DM). Methods, Eight hundred and sixty-four white European (40,75 years old) and 290 South Asian people (25,75 years old) underwent an oral glucose tolerance test (OGTT), detailed history and anthropometric measurements and completed the WHO-5 and CES-D. Depressive symptoms were defined by a WHO-5 score , 13, and CES-D score , 16. Results, Unadjusted prevalence of depressive symptoms with the WHO-5, for people with Type2 DM was 42.3% (47.4% in white European; 28.6% in South Asian) and for IGR 30.7% (26% in white European; 45.8% in South Asian). With the CES-D, the prevalence in Type2 DM was 27.2% (25.4% in white European; 31.8% in South Asian) and for IGR 30.7% (27.8% in white European; 40.7% in South Asian). Statistically significant differences in the prevalence of depressive symptoms for sex or ethnicity were not identified. Odds ratios adjusted for age, sex and ethnicity showed no significant association of depression with Type2 DM or IGR, with either WHO-5 or CES-D. Agreement was moderate (, = 0.48, 95% confidence intervals 0.42,0.54), and reduced when identifying depressive symptoms in people with Type2 DM. For this group, a WHO-5 cut-point of , 10 was optimal. Conclusions, Depressive symptoms, identified by WHO-5 or CES-D, were not significantly more prevalent in people with Type2 DM or IGR. The WHO-5 and CES-D differed in their identification of depressive symptoms in people with Type2 DM, though discrepancies between sex and ethnicity were not identified. [source] Comparing risk profiles of individuals diagnosed with diabetes by OGTT and HbA1cThe Danish Inter99 studyDIABETIC MEDICINE, Issue 8 2010R. Borg Diabet. Med. 27, 906,910 (2010) Abstract Aims, Glycated haemoglobin (HbA1c) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods. Methods, We assessed the prevalence of cardiovascular risk factors in individuals with undiagnosed diabetes according to the World Health Organization classification or by the newly proposed HbA1c level , 6.5% among 6258 participants of the Danish Inter99 study. Receiver operating curve analysis assessed the ability of fasting: 2-h plasma glucose and HbA1c to distinguish between individuals at high and low risk of ischemic heart disease, predicted by the PRECARD program. Results, Prevalence of undiagnosed diabetes was 4.1% [95% confidence interval (CI) 3.7,4.7%] by the current oral glucose tolerance test definition, whereas 6.6% (95% CI 6.0,7.2%) had diabetes by HbA1c levels. HbA1c -defined individuals were relatively older with higher proportions of men, smokers, lipid abnormalities and macro-albuminuria, but they were leaner and had lower blood pressure. HbA1c was better than fasting- and 2-h plasma glucose at distinguishing between individuals of high and low predicted risk of ischaemic heart disease; however, the difference between HbA1c and fasting- and 2-h plasma glucose was not statistically significant. Conclusions, Compared with the current oral glucose tolerance test definition, more individuals were classified as having diabetes based on the HbA1c criteria. This group had as unfavourable a risk profile as those identified by the oral glucose tolerance test. [source] Type 2 diabetes and cardiovascular disease in polycystic ovary syndrome: what are the risks and can they be reduced?DIABETIC MEDICINE, Issue 5 2010J. Tomlinson Diabet. Med. 27, 498,515 (2010) Abstract Polycystic ovary syndrome (PCOS) is a risk factor for Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), but these risks are poorly defined. This study aimed to evaluate the evidence for these risks and whether screening and risk reduction are feasible. Medline reviews and data quality analysis were used using standard tools. Results showed that (i) polycystic ovary syndrome is a risk factor forT2DM but the magnitude of risk is uncertain, (ii) fasting plasma glucose is an inadequate screening test forT2DM in this population and the oral glucose tolerance test is superior, (iii) the identification of women with PCOS for diabetes screening is constrained by current diagnostic criteria for PCOS; however, women with oligomenorrhoea and those with diagnosed PCOS and obesity or a family history of T2DM are at highest risk, (iv) risk factors for T2DM are improved by weight loss interventions and by metformin. However, no studies have determined whether T2DM incidence is reduced, (v) polycystic ovary syndrome is associated with cardiovascular disease (CVD) risk factors but data on CVD incidence are weak, (vi) risk factors for CVD are improved by the same interventions and statins and (vi) no studies have evaluated whether CVD incidence is reduced. While PCOS has important metabolic associations, and short-term interventions reduce risk factors for T2DM and CVD, data on prevalence and incidence of T2DM and particularly CVD are poor. There is a need for a clear definition of PCOS, for diabetes screening protocols and for long-term studies to determine whether risks can be reduced. [source] Maternal and neonatal outcomes and time trends of gestational diabetes mellitus in Sweden from 1991 to 2003DIABETIC MEDICINE, Issue 4 2010H. E. Fadl Diabet. Med. 27, 436,441 (2010) Abstract Aims, To determine maternal and neonatal outcomes for women with gestational diabetes mellitus (GDM) in Sweden during 1991,2003, and to compare the outcomes in the two time periods. Methods, This is a population-based cohort study using the Swedish Medical Birth Register data for the period 1991,2003. There were 1 260 297 women with singleton pregnancies registered during this time, of whom 10 525 were diagnosed with GDM, based on a 75 g oral glucose tolerance test. The main diagnostic criteria were fasting capillary whole blood glucose , 6.1 mmol/l and 2 h blood glucose , 9.0 mmol/l. Results, Maternal characteristics differed significantly between the GDM and non-GDM group. Adjusted odds ratios (OR) were as follows: for pre-eclampsia, 1.81 (95% confidence interval (CI) 1.64,2.00); for shoulder dystocia, 2.74 (2.04,3.68); and for Caesarean section, 1.46 (1.38,1.54). No difference was seen in perinatal mortality, stillbirth rates, Apgar scores, fetal distress or transient tachypnoea. There was a markedly higher risk of large for gestational age, OR 3.43 (3.21,3.67), and Erb's palsy, OR 2.56 (1.96,3.32), in the GDM group, and statistically significant differences in prematurity < 37 weeks, birth weight > 4.5 kg, and major malformation, OR 1.19,1.71. No statistically significant improvement in outcomes was seen between the two study periods. Conclusions, Women with GDM have higher risks of pre-eclampsia, shoulder dystocia and Caesarean section. Their infants are often large for gestational age and have higher risks of prematurity, Erb's palsy and major malformations. These outcomes did not improve over time. [source] Gestational diabetes: fasting capillary glucose as a screening test in a multi-ethnic, high-risk populationDIABETIC MEDICINE, Issue 8 2009M. M. Agarwal Abstract Aims, In populations at high risk of gestational diabetes mellitus (GDM), screening every pregnant woman by an oral glucose tolerance test (OGTT) is very demanding. The aim of this study was to determine the value of the fasting capillary glucose (FCG) as a screening test for GDM. Methods, FCG was measured by a plasma-correlated glucometer in 1465 pregnant women who underwent a one-step diagnostic 75-g OGTT for universal screening of GDM. Results, One hundred and ninety-six (13.4%) women had GDM as defined by the criteria of the American Diabetes Association. The area under the receiver operating characteristic curve (AUC) of the FCG was 0.83 (95% confidence interval 0.80,0.86). A FCG threshold of 4.7 mmol/l (at an acceptable sensitivity of 86.0%) independently could rule-out GDM in 731 (49.9%) women, while the FCG could rule-in GDM (100% specificity) in 16 (1.1%) additional women; therefore, approximately half of the women would not need to continue with the cumbersome OGTT. Conclusions, Screening using a FCG significantly reduces the number of OGTTs needed for the diagnosis of GDM. Wider assessment, particularly in low-risk populations, would confirm the potential value of the FCG as a screening test for GDM. [source] The relationship between depression and diabetes mellitus: findings from the Hertfordshire Cohort StudyDIABETIC MEDICINE, Issue 6 2009R. I. G. Holt Abstract Aims, To assess the relationship between depression scores and diabetes, glucose and insulin in a cross-sectional population-based study. Methods, One thousand, five hundred and seventy-nine men and 1418 women from the Hertfordshire Cohort Study were assessed for diabetes. Plasma glucose and insulin concentrations were measured at 0, 30 and 120 min during a standard 75-g oral glucose tolerance test. Depressive and anxiety symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). Results, Overall, 431 (14.6%) were diagnosed with diabetes [232 men (14.9%) and 199 women (14.3%)]. One hundred and eight (47%) men and 74 (37%) women had known diabetes. The remainder were previously undiagnosed. Fifty-nine (3.7%) men and 65 (4.6%) women had possible depression (HAD-D scores 8,10) and 17 (1.1%) men and 20 (1.4%) women had probable depression (HAD-D scores , 11). Probable depression was associated with an adjusted odds ratio for diabetes of 3.89 [95% confidence interval (CI) 1.28,11.88] in men and 1.51 (95% CI 0.47,4.84) in women. In men without previously diagnosed diabetes, fasting insulin (P = 0.035), 2-h glucose concentrations (P = 0.028) and insulin resistance (P = 0.032) were significantly associated with HAD-D scores. With the exception of 2-h glucose concentrations (P = 0.034), the associations were not significant in women. Conclusions, These data support the hypothesis that depression may increase the risk for diabetes. The relationship between depression score and metabolic variables extends across the whole population and is not confined to those with either diagnosed depression or diabetes. This relationship should lead clinicians to consider screening for diabetes in those with depression and vice versa. [source] Validation of an algorithm combining haemoglobin A1c and fasting plasma glucose for diagnosis of diabetes mellitus in UK and Australian populationsDIABETIC MEDICINE, Issue 2 2009S. E. Manley Abstract Aim, To determine whether glycated haemoglobin (HbA1c) can be used in combination with fasting plasma glucose (FPG) for the diagnosis of diabetes in patients with impaired fasting glucose (IFG) and in a broader spectrum of patients. Methods, An algorithm was derived from oral glucose tolerance test (OGTT) capillary samples in 500 consecutive UK patients with IFG by World Health Organization criteria. It was validated in a further 500 UK patients and, with venous specimens, in 1175 unselected Australian patients. Results, The derivation cohort was aged 61 years (50,69 years) (median IQ range) with 52% male and 12% South Asian. Diabetes Control and Complications Trial-aligned HbA1c was 6.2% (5.8,6.6%) (reference interval < 6.0%) and FPG 6.7 mmol/l (6.3,7.2 mmol/l). FPG was in the diabetes range in 36% of patients, with an OGTT identifying a further 12% with diabetes. The derived algorithm, (HbA1c , 6.0% with FPG < 7.0 mmol/l) identified those patients requiring an OGTT to diagnose diabetes. When applied to the UK validation cohort, sensitivity was 97% and specificity 100%. The algorithm was equally effective in the unselected group, aged 59 years (49,68 years) and 54% male, with sensitivity 93% and specificity 100%. HbA1c was 6.0% (5.6,6.6%) and FPG 6.0 mmol/l (5.3,6.8 mmol/l), with 26% having IFG. Use of the algorithm would reduce the number of OGTTs performed in the UK validation cohort by 33% and by 66% in the Australian patients studied. Conclusions, Use of this algorithm would simplify procedures for diagnosis of diabetes and could also be used for monitoring pre-diabetes. Validation is now required in other populations and patient groups. [source] Differences in height explain gender differences in the response to the oral glucose tolerance testDIABETIC MEDICINE, Issue 11 2008W. Rathmann No abstract is available for this article. [source] Psychosocial factors are independent risk factors for the development of Type 2 diabetes in Japanese workers with impaired fasting glucose and/or impaired glucose tolerance,DIABETIC MEDICINE, Issue 10 2008M. Toshihiro Abstract Aims, We prospectively studied Japanese workers with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and analysed possible risk factors for diabetes, including psychosocial factors such as stress. Methods, The participants were 128 male Japanese company employees (mean age, 49.3 ± 5.9 years) with IFG and/or IGT diagnosed by oral glucose tolerance test (OGTT). Participants were prospectively studied for 5 years with annual OGTTs. The Kaplan,Meier method and Cox's proportional hazard model were used to analyse the incidence of diabetes and the factors affecting glucose tolerance, including anthropometric, biochemical and social,psychological factors. Results, Of 128 participants, 36 (28.1%) developed diabetes and 39 (30.5%) returned to normal glucose tolerance (NGT) during a mean follow-up of 3.2 years. Independent risk factors for diabetes were night duty [hazard ratio (HR) = 5.48, P = 0.002], higher fasting plasma glucose (FPG) levels within 6.1,6.9 mmol/l (HR = 1.05, P = 0.031), stress (HR = 3.81, P = 0.037) and administrative position (HR = 12.70, P = 0.045), while independent factors associated with recovery were lower FPG levels (HR = 0.94, P = 0.017), being a white-collar worker (HR = 0.34, P = 0.033), non-smoking (HR = 0.31, P = 0.040) and lower serum alanine aminotransferase (ALT) levels (HR = 0.97, P = 0.042). Conclusions, In addition to FPG levels at baseline, psychosocial factors (night duty, stress and administrative position) are risk factors for Type 2 diabetes, while being a white-collar worker, a non-smoker and lower serum ALT levels are factors associated with return to NGT in Japanese workers with IFG and/or IGT. [source] Prevalence and projections of diabetes and pre-diabetes in adults in Sri Lanka,Sri Lanka Diabetes, Cardiovascular Study (SLDCS)DIABETIC MEDICINE, Issue 9 2008P. Katulanda Abstract Aims To determine the prevalence of diabetes mellitus and pre-diabetes (impaired fasting glucose and impaired glucose tolerance) in adults in Sri Lanka. Projections for the year 2030 and factors associated with diabetes and pre-diabetes are also presented. Methods This cross-sectional study was conducted between 2005 and 2006. A nationally representative sample of 5000 adults aged , 18 years was selected by a multi-stage random cluster sampling technique. Fasting plasma glucose was tested in all participants and a 75-g oral glucose tolerance test was performed in non-diabetic subjects. Prevalence was estimated for those > 20 years of age. Results Response rate was 91% (n = 4532), males 40%, age 46.1 ± 15.1 years (mean ± standard deviation). The age,sex standardized prevalence (95% confidence interval) of diabetes for Sri Lankans aged , 20 years was 10.3% (9.4,11.2%) [males 9.8% (8.4,11.2%), females 10.9% (9.7,12.1%), P = 0.129). Thirty-six per cent (31.9,40.1%) of all diabetic subjects were previously undiagnosed. Diabetes prevalence was higher in the urban population compared with rural [16.4% (13.8,19.0%) vs. 8.7% (7.8,9.6%); P < 0.001]. The prevalence of overall, urban and rural pre-diabetes was 11.5% (10.5,12.5%), 13.6% (11.2,16.0%) and 11.0% (10.0,12.0%), respectively. Overall, 21.8% (20.5,23.1%) had some form of dysglycaemia. The projected diabetes prevalence for the year 2030 is 13.9%. Those with diabetes and pre-diabetes compared with normal glucose tolerance were older, physically inactive, frequently lived in urban areas and had a family history of diabetes. They had higher body mass index, waist circumference, waist,hip ratio, systolic/diastolic blood pressure, low-density lipoprotein cholesterol and triglycerides. Insulin was prescribed to 4.4% (2.7,6.1%) of all diabetic subjects. Conclusions One in five adults in Sri Lanka has either diabetes or pre-diabetes and one-third of those with diabetes are undiagnosed. [source] Plasma triglycerides and LDL cholesterol are related in a parabolic fashion in the general population and patients with Type 2 diabetes mellitus: long-term follow-up results from the Hoorn studyDIABETIC MEDICINE, Issue 9 2008M. C. G. J. Brouwers Abstract Aims Low-density lipoprotein cholesterol (LDL-C) levels are often fairly normal in Type 2 diabetes mellitus (DM). We anticipated that a parabolic relation between plasma triglycerides and LDL-C, as previously demonstrated in familial combined hyperlipidaemia (FCHL), might account for this phenomenon. Methods Our hypothesis was tested in 1343 subjects derived from the general population who were studied on two occasions 6 years apart (the Hoorn study). Three groups were constructed depending on plasma triglycerides: group A (individuals with both measurements below 1.5 mmol/l), group B (one measurement below and one above 1.5 mmol/l) and group C (both measurements above 1.5 mmol/l). Diabetes status was ascertained by an oral glucose tolerance test. Results In a mixed linear model, a significant, positive relation between triglycerides and LDL-C was observed for males in group A (,a = 0.5, P < 0.001) and group B (,b = 0.2, P < 0.001), whereas a significant negative relation was found for males in group C (,c = ,0.2, P = 0.003). The regression slopes did not differ between diabetic and non-diabetic subjects. Similar results were obtained for women, with the exception that the relation was not significantly negative in group C (,c = ,0.1, P = 0.4). Conclusion Plasma triglcyerides and LDL-C are related in a parabolic fashion, not only in FCHL, but also in the general population and Type 2 DM. These findings aid our interpretation of typical dyslipidaemia and the effects of treatment that are frequently observed in hypertriglyceridaemic states. [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] Effect of RBP4 gene variants on circulating RBP4 concentration and Type 2 diabetes in a Chinese populationDIABETIC MEDICINE, Issue 1 2008C. Hu Abstract Aims Retinol binding protein 4 (RBP4) is a newly discovered adipokine, which plays a role in insulin resistance and obesity. The aim of this study was to determine the relationship between genetic variants of the RBP4 gene, circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism in the Chinese population. Methods We sequenced exons and the putative promoter region to identify single nucleotide polymorphisms (SNPs) in the RBP4 gene in 32 Chinese subjects. Additional SNPs were selected from a public database to increase marker density. Taking account of the pairwise linkage disequilibrium and minor allele frequencies, a subset of SNPs was further genotyped in 255 Type 2 diabetic patients and 372 normal control subjects. Circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism were measured. Results Ten SNPs were identified and five were further genotyped in the full sample. No individual SNP was significantly associated with Type 2 diabetes, but a rare haplotype CAA formed by +5388 C>T, +8201 T>A and +8204 T>A was more frequent in diabetic patients (P = 0.0343, empirical P = 0.0659 on 10 000 permutations). In both groups, non-coding SNPs were associated with circulating RBP4 concentrations (P < 0.05). In the normal control subjects, the SNP +5388 C>T was associated with serum C-peptide levels both fasting and 2 h after an oral glucose tolerance test (P = 0.0162 and P = 0.0075, respectively). Conclusion Our findings suggest that genetic variants in the RBP4 gene may be associated with circulating RBP4 concentration and phenotypes related to glucose metabolism. [source] Oestradiol replacement treatment and glucose homeostasis in two men with congenital aromatase deficiency: evidence for a role of oestradiol and sex steroids imbalance on insulin sensitivity in menDIABETIC MEDICINE, Issue 12 2007V. Rochira Abstract Aims The role of sex steroids in glucose and insulin metabolism in men remains unclear. To investigate the effects of sex steroids and oestrogen on insulin sensitivity in men, we studied two male adults with aromatase deficiency (subject 1 and subject 2). Methods The effects of transdermal oestradiol (tE2) treatment at different dosages on insulin sensitivity were studied before tE2 treatment (phase 1), and after 6 months (phase 2) and 12 months of tE2 treatment (phase 3) by means of homeostasis model assessment,insulin resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI), insulin tolerance test (ITT), and oral glucose tolerance test (OGTT). The latter was performed only in subject 1, as subject 2 suffered from Type 2 diabetes. Results The restoration of normal serum oestradiol led to improved insulin sensitivity, as shown by changes in HOMA-IR and QUICKI. The ITT provided evidence of improved insulin sensitivity during tE2 treatment. Insulin secretion after OGTT was reduced during tE2 treatment in subject 1. After 12 months of tE2 treatment, insulin sensitivity was improved compared with in phases 1 and 2. Conclusions The study suggests a direct involvement of oestrogens in insulin sensitivity, and supports a possible role of oestradiol : testosterone ratio, which may be as influencial as the separate actions of each sex steroid on glucose homeostasis. [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] Long-term effects of leisure time physical activity on risk of insulin resistance and impaired glucose tolerance, allowing for body weight history, in Danish menDIABETIC MEDICINE, Issue 1 2007T. Berentzen Abstract Aims To determine if the level of leisure time physical activity (LTPA) in young adulthood in obese and non-obese men reduces the risk of insulin resistance (IR) and impaired glucose tolerance (IGT) in middle age, and if such an effect is explained by the current level of LTPA, or by the body mass index (BMI) history preceding and subsequent to the assessment of LTPA. Methods Longitudinal study of groups of obese and randomly selected non-obese men identified at around age 19, and re-examined at mean ages of 32, 44 and 51. BMI was measured at all four examinations. LTPA was assessed by self-administrated questionnaires at the last three examinations. IR and the presence of IGT was determined by an oral glucose tolerance test at the last examination. Results LTPA in young adulthood reduced the risk of IR and IGT in middle age throughout the range of BMI. Adjustment for the BMI history preceding and subsequent to the assessment of LTPA attenuated the association with IR and IGT, but active men remained at low risk of IR and IGT. Adjustment for subsequent and current levels of LTPA, smoking habits, alcohol intake, educational level and family history of diabetes had no notable influence on the results. Conclusion LTPA appears to reduce the risk of IR and IGT, an effect which is not explained by the current level of physical activity, and only partially explained by the BMI history preceding and subsequent to the assessment of LTPA. [source] Reduced insulin secretion in normoglycaemic patients with ,-thalassaemia majorDIABETIC MEDICINE, Issue 12 2006N. G. Angelopoulos Abstract Aims To assess insulin sensitivity and secretion in the fasting state in regularly transfused patients with ,-thalassaemia major with normal glucose response during an oral glucose tolerance test and to estimate its possible relation to iron overload. Methods We measured fasting glucose, insulin and C-peptide levels in 24 patients with ,-thalassaemia major and 18 control subjects matched for age and body mass index. Insulin sensitivity and insulin release index were calculated according to the homeostasis model assessment (HOMA). Correlations with age, body mass index and serum ferritin were also calculated. Results Fasting glucose levels in patients were increased compared with control subjects (5.5 ± 0.12 vs. 4.7 ± 0.13 mmol/l, mean ± sem, P < 0.001). Pancreatic B-cell insulin secretion in the fasting state (estimated by SCHOMA) was lower in thalassaemic patients (SCHOMA 88.5 ± 11.11 vs. 184.3 ± 23.72 in control subjects, P < 0.001). Patients were then divided into those with impaired (IFG) and normal (NFG) fasting glucose. SCHOMA was higher in the patients with NFG compared with those with IFG patients (110.6 ± 17.63 vs. 66.3 ± 10.88, respectively, P < 0.05) but estimated insulin sensitivity (ISIHOMA) was similar. Plasma values of C-peptide correlated positively with ferritin (r = 0.42, P = 0.04) and SCHOMA (r = 0.45, P = 0.02) and negatively with ISIHOMA (r = ,0.43, P = 0.03). Conclusions These results support the concept that impaired B-cell function, as reflected by a reduction in the insulin secretion index, is present in ,-thalassaemic patients with normoglycaemia before changes in oral glucose tolerance tests are apparent. [source] | ||||||||||||||||||||||||||||||||||||||||