Evidence of left atrial remodeling and left ventricular diastolic dysfunction in type 2 diabetes mellitus with preserved systolic function.

BACKGROUND AND AIMS: Prognosis of type 2 diabetes is associated with the occurrence of cardiovascular diseases. Left atrial (LA) size is a predictor of outcome in several diseases, including diabetes. Long duration of diabetes is an established risk factor of poor prognosis. No data are available on the relationship between LA size and duration of diabetes. The present study was aimed to investigate the relationship between LA volume index (LAVI) and the duration of diabetes to test the hypothesis that LA volume will increase as a function of diabetes duration. METHODS AND RESULTS: Forty-four male patients with newly diagnosed and 172 male patients with established type 2 diabetes were recruited for this cross-sectional study. All patients were evaluated with a transthoracic echocardiographic Doppler. About 28.2% of patients had increased LAVI. Indices of both diastolic and systolic function were significantly lower in patients with larger left atrium. The values of LAVI increased across classes of duration of diabetes. In multivariable analysis, longer duration was a predictor of LAVI ≥34 ml/m2 (odds ratio 1.65, 95% CI 1.11-2.46, p = 0.014) after adjusting for age, hemoglobin A1c, hypertension, microvascular complication status, and relevant echocardiographic parameters of systolic and diastolic function. CONCLUSIONS: These results indicate that duration of diabetes is strongly and positively associated with larger LAVI in type 2 diabetic men with preserved systolic function. Future studies are needed to better elucidate the biological mechanisms underlying linking type 2 diabetes with abnormally increased LAVI in subjects with type 2 diabetes.

What are the preferred strategies for control of glycaemic variability in patients with type 2 diabetes mellitus?

The aim of therapy in type 2 diabetes in terms of blood glucose control is to reduce to target levels HbA1c and to reduce glycaemic variability in order to avoid both hypoglycaemia and wide excursions of postprandial glucose. The first approach to reduce glycaemic variability should consider a dietary and behavioural approach aiming to limit the glycaemic index and the glycaemic load of food and the prescription and implementation of a physical activity plan appropriate for the subject. From the pharmacological point of view, the diabetes specialist has now a much richer therapeutic armamentarium. The therapeutic algorithms can help the physician to choose the most appropriate drug. The traditional approach involves: i) metformin, acting mainly on fasting blood glucose; ii) sulphonylureas, that have shown a number of drawbacks, including the high risk of hypoglycemia; iii) pioglitazone, with a substantial effect on fasting and postprandial glucose and a low risk of hypoglycaemia; iv) insulin, that can be utilized with the basal or prandial approach. The new drugs belonging to the class of dipeptidyl peptidase-4 inhibitors have shown the reduction of postprandial glucose, a neutral effect on weight increase, a good safety profile and preliminary positive cardiovascular effects. When excess weight prevails, the glucagon-like peptide-1 agonists may be the preferred choice for their effect on weight reduction, reduction of hyperinsulinism and glycaemic variability.

Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and retinopathy in type 1 diabetic patients.

AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) is associated with an increased prevalence of chronic kidney disease (CKD) and retinopathy in patients with type 2 diabetes. Information on this issue is lacking for type 1 diabetes. We evaluated whether NAFLD is associated with increased prevalence of retinopathy and CKD in type 1 diabetic patients. METHODS: All type 1 diabetic patients (n = 202) who regularly attended our diabetes clinic and did not have any clinical evidence of cirrhosis or other secondary causes of chronic liver disease were studied. Main study measures were detection of NAFLD (by patient history and liver ultrasound), diabetic retinopathy (diagnosed by ophthalmoscopy) and CKD (defined as abnormal albuminuria or estimated GFR of < or =60 ml min(-1) 1.73 m(-2)). RESULTS: The age- and sex-adjusted prevalence of diabetic retinopathy (53.2 vs 19.8%) and CKD (37.8 vs 9.9%) was markedly higher in patients with NAFLD than in those without (p < 0.0001). In multivariate logistic regression analysis, NAFLD was associated with prevalent retinopathy (adjusted OR 3.31, 95% CI 1.4-7.6, p = 0.005) or CKD (adjusted OR 3.90, 95% CI 1.5-10.1, p = 0.005). These associations were independent of age, sex, diabetes duration, HbA(1c), medication use and presence of the metabolic syndrome. CONCLUSIONS/INTERPRETATION: Our findings suggest that ultrasound-diagnosed NAFLD is associated, independently of several confounding factors, with a higher prevalence of CKD and retinopathy in type 1 diabetic individuals.

Diabetic retinopathy is associated with an increased incidence of cardiovascular events in Type 2 diabetic patients.

AIMS: We investigated the association of diabetic retinopathy with the risk of incident cardiovascular disease (CVD) events in a large cohort of Type 2 diabetic adults. METHODS: Our study cohort comprised 2103 Type 2 diabetic outpatients who were free of diagnosed CVD at baseline. Retinal findings were classified based on fundoscopy (by a single ophthalmologist) to categories of no retinopathy, non-proliferative retinopathy and proliferative/laser-treated retinopathy. Outcomes measures were incident CVD events (i.e. non-fatal myocardial infarction, non-fatal ischaemic stroke, coronary revascularization procedures or cardiovascular death). RESULTS: During approximately 7 years of follow-up, 406 participants subsequently developed incident CVD events, whereas 1697 participants remained free of diagnosed CVD. After adjustment for age, body mass index, waist circumference, smoking, lipids, glycated haemoglobin, diabetes duration and medications use, patients with non-proliferative or proliferative/laser-treated retinopathy had a greater risk (P < 0.001 for all) of incident CVD events than those without retinopathy [hazard ratio 1.61 (95% confidence interval 1.2-2.6) and 3.75 (2.0-7.4) for men, and 1.67 (1.3-2.8) and 3.81 (2.2-7.3) for women, respectively]. After additional adjustment for hypertension and advanced nephropathy (defined as overt proteinuria and/or estimated glomerular filtration rate < or = 60 ml/min/1.73 m(2)), the risk of incident CVD remained markedly increased in those with proliferative/laser-treated retinopathy [hazard ratio 2.08 (1.02-3.7) for men and 2.41 (1.05-3.9) for women], but not in those with non-proliferative retinopathy. CONCLUSIONS: Diabetic retinopathy (especially in its more advanced stages) is associated with an increased CVD incidence independent of other known cardiovascular risk factors.

Cigarette smoking and plasma total homocysteine levels in young adults with type 1 diabetes.

OBJECTIVE: The purposes of this study were to compare plasma total homocysteine (tHcy) levels, a recognized cardiovascular risk factor, in nondiabetic subjects and type 1 diabetic patients, and to evaluate whether chronic cigarette smoking had a deleterious effect on plasma tHcy levels in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Plasma tHcy concentrations were measured in 60 young type 1 diabetic patients without clinical evidence of macroangiopathy and in 30 healthy control subjects who were matched for age, sex, BMI, and smoking habit. RESULTS: Plasma tHcy levels were significantly higher in type 1 diabetic patients than in control subjects (12.5 +/- 4.8 vs. 10.3 +/- 2.2 micromol/l, P = 0.01). After stratification by smoking status, diabetic smokers had values for age, sex, BMI, lipids, creatinine, blood pressure, glycometabolic control, diabetes duration, and microvascular complications that were superimposable on their nonsmoking counterparts. Nevertheless, plasma tHcy levels were markedly elevated in diabetic smokers versus nonsmokers (15.5 +/- 5.7 vs. 10.6 +/- 3 pmol/l, P < 0.0001) in a dose-dependent fashion (P < 0.0001, by analysis of variance when subjects were categorized for the number of cigarettes smoked daily). CONCLUSIONS: Chronic cigarette smoking seems to adversely affect plasma tHcy levels in young adults with type 1 diabetes.

Elevated plasma levels of soluble receptors of TNF-alpha and their association with smoking and microvascular complications in young adults with type 1 diabetes.

The purposes of this study were 1) to compare soluble tumor necrosis factor-alpha receptors, which are thought to reflect the degree of TNF-alpha activation, in nondiabetic subjects and type 1 diabetic patients, and 2) to evaluate the effects of smoking and microvascular complications on soluble tumor necrosis factor-alpha receptor levels in type 1 diabetic individuals. Plasma soluble tumor necrosis factor-alpha receptor levels (R1 and R2) were measured in 50 young type 1 diabetic patients without clinical macroangiopathy and in a matched group of 20 healthy volunteers. When diabetic patients were grouped according to smoking and microvascular complication status, the groups of patients had similar values of age, sex, body mass index, blood pressure, lipids, creatinine, and glycometabolic control. Nevertheless, soluble tumor necrosis factor-alpha receptor-R1 levels but not R2 levels, were markedly elevated (P < 0.05 or less) in complicated vs. uncomplicated (2.40 +/- 0.3 vs. 1.80 +/- 0.1 ng/ml) patients and in smokers vs. nonsmokers (2.66 +/- 0.4 vs. 1.76 +/- 0.1 ng/ml). In a two-factor ANOVA, both smoking (P < 0.01) and microvascular complications (P < 0.05) were independent predictors of soluble tumor necrosis factor-alpha receptor-R1. Soluble tumor necrosis factor-alpha receptor levels of diabetic patients who did not smoke or without complications were similar to those of healthy controls. In conclusion, smoking and microvascular complications seem to exert an additive and deleterious impact on TNF-alpha activation, as reflected by levels of soluble tumor necrosis factor-alpha receptors, in young adults with type 1 diabetes.

Serum selenium in liver cirrhosis: correlation with markers of fibrosis.

In 55 patients with alcoholic cirrhosis and in 47 healthy individuals we assayed the concentration of selenium in serum (S-Se) by proton induced X-ray emission, the aminoterminal peptide of type III procollagen (NPIIIP) by RIA and the plasma fibronectin (FN) by immuno-nephelometry, together with routine biochemical tests. S-Se was lower in cirrhosis than in controls (0.57, SD 0.20 vs 0.92, SD 0.16 mumol/l; p less than 0.001) and was more reduced in ascitic than in compensated patients (0.50, SD 0.19 vs 0.66, SD 0.17 mumol/l; p less than 0.001). Regression analysis showed a positive correlation of S-Se with serum albumin and FN, whereas necrotic or inflammatory activity seems unrelated to S-Se; a negative correlation was found between S-Se and NPIIIP, suggesting a protective role of selenium against fibrosis.

Measurement of microvolt T-wave alternans, a new arrhythmic risk stratification test, in Type 2 diabetic patients without clinical cardiovascular disease.

AIMS: Patients with a positive microvolt T-wave alternans (TWA) are at increased risk of ventricular arrhythmias and sudden cardiac death. Although Type 2 diabetes is associated with an increased risk of these events, there is a dearth of available data on measurements of TWA in people with Type 2 diabetes. METHODS: We studied 43 Type 2 diabetic volunteers who were free of diagnosed cardiovascular disease (CVD). Microvolt TWA analysis was performed non-invasively using the CH 2000 system during submaximal exercise with the patients sitting on a bicycle ergometer. RESULTS: TWA analysis was positive in 9 (21%) patients, negative in 32 (74.4%) and indeterminate in 2 (4.6%) subjects. TWA positive patients had significantly higher HbA(1c) levels than those with TWA negativity (8.1 +/- 0.9 vs. 7.2 +/- 0.8%, P < 0.01). Age, sex, BMI, blood pressure, lipids, 24-h heart rate variability, QTc interval duration, smoking history, diabetes duration and treatment, and microvascular complication status did not differ between the groups. In regression logistic analysis, HbA(1c) was the only significant predictor of TWA positivity (odds ratio 5.7, 95% CI 1.3-26, P = 0.023) after controlling for potential confounders. CONCLUSIONS: These results suggest that in Type 2 diabetic patients without clinically manifest CVD, TWA positivity is common (approximately 20%) and is closely correlated with glycaemic control.

Increased prevalence of cardiovascular disease in Type 2 diabetic patients with non-alcoholic fatty liver disease.

AIMS: To estimate the prevalence of cardiovascular disease (CVD) in Type 2 diabetic patients with and without non-alcoholic fatty liver disease (NAFLD), and to assess whether NAFLD is independently related to prevalent CVD. METHODS: We studied 400 Type 2 diabetic patients with NAFLD and 400 diabetic patients without NAFLD who were matched for age and sex. Main outcome measures were prevalent CVD (as ascertained by medical history, physical examination, electrocardiogram and echo-Doppler scanning of carotid and lower limb arteries), NAFLD (by ultrasonography) and presence of the metabolic syndrome (MetS) as defined by the World Health Organization or Adult Treatment Panel III criteria. RESULTS: The prevalences of coronary (23.0 vs. 15.5%), cerebrovascular (17.2 vs. 10.2%) and peripheral (12.8 vs. 7.0%) vascular disease were significantly increased in those with NAFLD as compared with those without NAFLD (P < 0.001), with no differences between sexes. The MetS (by any criteria) and all its individual components were more frequent in NAFLD patients (P < 0.001). In logistic regression analysis, male sex, age, smoking history and MetS were independently related to prevalent CVD, whereas NAFLD was not. CONCLUSIONS: The prevalence of CVD is increased in patients with Type 2 diabetes and NAFLD in association with an increased prevalence of MetS as compared with diabetic patients without NAFLD. Follow-up studies are necessary to determine whether this higher prevalence of CVD among diabetic patients with NAFLD affects long-term mortality.

Non-alcoholic fatty liver disease is associated with carotid artery wall thickness in diet-controlled type 2 diabetic patients.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with several metabolic syndrome (MetS) features. We assessed whether NAFLD is significantly associated with carotid artery intima-media thickness (IMT), as a marker of subclinical atherosclerosis, and whether such association is independent of classical cardiovascular risk factors and MetS features. We studied 100 diet-controlled Type 2 diabetic patients with ultrasonographically diagnosed NAFLD and 100 diabetic patients without NAFLD who were comparable for age and sex. Main outcome measures were carotid IMT (by ultrasonography), classical risk factors, insulin resistance [as estimated by homeostasis model assessment (HOMA)-IR] and MetS (as defined by the Adult Treatment Panel III criteria). NAFLD patients had a markedly greater carotid IMT (1.24 +/- 0.13 vs 0.95 +/- 0.11 mm; p < 0.001) than those without the condition. The MetS and all its clinical traits were more highly prevalent in those with NAFLD (p < 0.001). Adjustment for age, sex, smoking history, diabetes duration, glycosylated hemoglobin, LDL cholesterol, liver enzymes and microalbuminuria did not really affect the significant differences in carotid IMT that were observed between the groups. Further adjustment for the MetS also had little impact, but additional adjustment for HOMA-IR score consistently attenuated any statistical significance (p = 0.28). In multivariate regression analysis, HOMA-IR score along with age and MetS (principally raised blood pressure values) were independently related to carotid IMT, whereas NAFLD was not. In conclusion, these results suggest that among diet-controlled Type 2 diabetic individuals the significant increase of carotid IMT in the presence of NAFLD is largely explained by HOMA-estimated insulin resistance.

Relationship of non-alcoholic hepatic steatosis to cortisol secretion in diet-controlled Type 2 diabetic patients.

AIMS: To examine the association of non-alcoholic hepatic steatosis (HS) with the activity of the hypothalamo-pituitary-adrenal (HPA) axis in Type 2 diabetic individuals. METHODS: The activity of the HPA axis, as measured by 24-h urinary free cortisol (UFC) excretion and serum cortisol levels after 1.0 mg dexamethasone, was measured in 40 diet-controlled, predominantly overweight, Type 2 diabetic patients with non-alcoholic HS and in 40 diabetic patients without HS who were comparable for age, sex and body mass index (BMI). RESULTS: Subjects with non-alcoholic HS had significantly higher 24-h UFC excretion (191 +/- 4 vs. 102 +/- 3 nmol/24 h; P < 0.001) and post-dexamethasone cortisol concentrations (29.1 +/- 2 vs. 14.4 +/- 1 nmol/l; P < 0.001) than those without HS. Patients with HS had significantly higher values for HOMA insulin resistance score, plasma triglycerides and liver enzymes. Age, sex, BMI, waist-hip ratio (WHR), diabetes duration, HbA1c, LDL-cholesterol and blood pressure values were not different between the groups. The differences in urinary and serum cortisol concentrations between the groups remained significant after adjustment for age, sex, BMI, WHR, HOMA insulin resistance score, plasma triglycerides, HbA1c and liver enzymes. In multiple logistic regression analyses, 24-h UFC or serum cortisol concentrations (P < 0.05 and P = 0.02, respectively), along with age and HOMA insulin resistance, predicted the presence of HS, independently of potential confounders. CONCLUSIONS: These results demonstrate that non-alcoholic HS is closely associated with a subtle, chronic overactivity of the HPA axis in diet-controlled Type 2 diabetic individuals.

Non-alcoholic hepatic steatosis and its relation to increased plasma biomarkers of inflammation and endothelial dysfunction in non-diabetic men. Role of visceral adipose tissue.

AIMS: To compare plasma biomarkers of inflammation and endothelial dysfunction in individuals with and without non-alcoholic hepatic steatosis (HS), and to evaluate whether such differences were mediated by the adverse metabolic pattern, typically found in these subjects. METHODS: HS (by ultrasound and computed tomography), visceral fat (by computed tomography), insulin resistance (by homeostasis model assessment-HOMA), plasma biomarkers of inflammation and endothelial dysfunction (hs-C reactive protein, fibrinogen, von Willebrand factor, plasminogen activator inhibitor-1 activity) were measured in 100 non-smoking, healthy, male volunteers. RESULTS: Plasma hs-CRP, fibrinogen, v-WF and plasminogen activator inhibitor-1 (PAI-1) activity levels were markedly higher (P < 0.01 or less) in subjects with non-alcoholic HS (n = 35) than in those without HS (n = 65). The former also had significantly higher values for body mass index (BMI), visceral fat, diastolic blood pressure, HOMA insulin resistance score, plasma insulin (both fasting and after glucose load), triglycerides, liver enzymes, and lower high-density lipoprotein (HDL)-cholesterol concentration. While the marked differences in these pro-inflammatory biomarkers observed between the groups were little affected by adjustment for age, BMI, blood pressure values, HOMA insulin resistance score, plasma triglyceride and liver enzyme concentrations, they were completely abolished after controlling for visceral fat. Similarly, in multivariate regression analyses, increased visceral fat significantly predicted the pro-inflammatory biomarkers, independently of HS and other potential confounders. CONCLUSIONS: These results indicate that, in non-smoking, non-diabetic men, the significant increase of plasma biomarkers of inflammation and endothelial dysfunction in the presence of non-alcoholic HS is largely mediated by abdominal visceral fat accumulation.

Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in Type 1 diabetic patients without clinically manifest macroangiopathy.

AIMS: To evaluate whether plasma biomarkers of inflammation and endothelial dysfunction differed in Type 1 diabetic patients as compared with those in non-diabetic subjects, and to examine the association of these biomarkers with early stages of microvascular complications. METHODS: Plasma biomarkers of inflammation [fibrinogen, hs-C-reactive protein (hs-CRP)] and endothelial dysfunction [von Willebrand factor (v-WF), intercellular adhesion molecule-1, plasminogen activator inhibitor-1 (PAI-1) activity] were measured in 88 non-smoking young patients with Type 1 diabetes without clinical macrovascular disease and in 40 healthy controls. RESULTS: Plasma levels of hs-CRP, fibrinogen, v-WF, soluble intracellular adhesion molecule-1 (sICAM-1) and PAI-1 activity were markedly higher (P < 0.01 or less) in Type 1 diabetic patients than in healthy controls; these results were essentially unchanged when healthy controls were compared with patients without complications. After stratification by microvascular complication status, plasma biomarkers of inflammation and endothelial dysfunction were significantly increased in those with more advanced disease compared with those with early complications or without complications, respectively. However, while the significant differences in these biomarkers were little affected by adjustment for sex, age, BMI and blood pressure values, they were totally abolished after additional adjustment for diabetes duration and glycaemic control. CONCLUSIONS: These results indicate that in Type 1 diabetes there is a subclinical, chronic inflammation which is, at least partly, independent of clinically manifest macro- and microvascular complications, smoking or other traditional cardiovascular risk factors; this subclinical inflammation is closely correlated to the magnitude and duration of hyperglycaemia.

Effects of short-term treatment with coenzyme A or sulodexide on plasma lipids in patients with hypertriglyceridemia (type IV) or mixed hyperlipemia (type IIb).

Twenty-seven inpatients suffering from type II and IV dyslipidemia, randomly divided into two groups of 14 and 13 subjects, were treated with coenzyme A (2,000 Lipmann U daily) and sulodexide (300 Lipasemic U daily), respectively, in both cases administered intravenously for 20 days. The principial plasma lipid parameters (total and HDL-cholesterol, LDL-cholesterol in subjects with triglyceridemia less than 400 mg/dl, triglycerides, apoproteins and lipoproteins) were recorded before and after treatment. Tests on patients included an assessment, on a semiquantitative scale, of symptoms arising from modifications of blood flow to the various organs. Statistical analysis of data demonstrated that coenzyme A has a significant cholesterol-lowering action (with an increase in HDL-cholesterol) and a more pronounced hypotriglyceridemic effect in both types of dyslipidemia considered, results on both variables proving more satisfactory than with the control drug.

The Metabolic Syndrome is an independent predictor of cardiovascular disease in Type 2 diabetic subjects. Prospective data from the Verona Diabetes Complications Study.

AIMS: To evaluate the cardiovascular risk associated with the presence of the Metabolic Syndrome in Type 2 diabetic subjects. METHODS: Subjects with the Metabolic Syndrome, defined by WHO criteria, were identified in a large sample of non-insulin-treated Type 2 diabetic patients examined within the Verona Diabetes Complications Study (n = 946). At baseline and after a mean of 4.5 years follow-up, cardiovascular disease (CVD) was assessed by medical history, physical examination, electrocardiogram (ECG) and echo-duplex of carotid and lower limb arteries. Death certificates and medical records of subjects who died during the follow-up were scrutinized in order to identify CVD deaths. In statistical analyses, CVD was considered as an aggregate end-point, including fatal and non-fatal coronary, cerebrovascular and peripheral vascular disease as well as ischaemic ECG abnormalities and vascular lesions at the echo-duplex. RESULTS: The proportion of subjects with the Metabolic Syndrome was very high (92.3%). At the baseline, 31.7% of subjects were coded positive for CVD, which was more prevalent in subjects with the Metabolic Syndrome (32.9 vs. 17.8%, P = 0.005). Among subjects free of CVD at the baseline (n = 559), CVD events during the follow-up were significantly increased in patients with the Metabolic Syndrome as compared with those without it (19.9% vs. 3.9%, P < 0.001). Multiple logistic regression analysis showed that, along with sex, age, smoking and HbA1c, the presence of the Metabolic Syndrome independently predicted prevalent (OR 2.01, P = 0.045) and incident CVD (OR 4.89, P = 0.031). CONCLUSIONS: In Type 2 diabetes, the presence of the Metabolic Syndrome is associated with an almost 5-fold increase in CVD risk.

Predictors of insulin sensitivity in Type 2 diabetes mellitus.

AIMS: To identify the independent predictors of insulin sensitivity in Type 2 diabetes, and to establish whether isolated Type 2 diabetes (i.e. diabetes without overweight, dyslipidaemia and hypertension) is a condition of insulin resistance. METHODS: We examined 45 patients with non-insulin-treated Type 2 diabetes undergoing a 4-h euglycaemic hyperinsulinaemic clamp (20 mU/m2 per min) combined with 3H-3-D-glucose and 14C-U-glucose infusions and indirect calorimetry. We also examined 1366 patients with non-insulin-treated Type 2 diabetes randomly selected among those attending the Diabetes Clinic and in whom insulin resistance was estimated by Homeostasis Model Assessment (HOMA-IR). RESULTS: In the 45 patients undergoing glucose clamp studies, insulin-mediated total glucose disposal (TGD) was independently and negatively associated with systolic blood pressure (standardized beta coefficient = -0.407, P = 0.003), plasma triglycerides (beta= -0.355, P = 0.007), and HbA1c (beta= -0.350, P = 0.008). The overall variability of TGD explained by these variables was 53%. Overweight diabetic subjects with central fat distribution, hypertension, hypertriglyceridaemia and poor glycometabolic control had insulin-mediated TGD values markedly lower than their lean counterparts without hypertension, with normal triglycerides, and with good glycometabolic control (16 +/- 5 vs. 31 +/- 10 micromol/min per kg lean body mass, P < 0.01). Nevertheless, the latter still were markedly insulin-resistant when compared with sex- and age-matched non-diabetic control subjects (31 +/- 10 vs. 54 +/- 13 micromol/min per kg lean body mass, P < 0.01). In the 1366 Type 2 diabetic patients of the epidemiological study, HOMA-IR value was independently associated with HbA1c (beta = 0.283, P < 0.0001), plasma triglycerides (beta = 0.246, P < 0.0001), body mass index (beta = 0.139, P < 0.001), waist girth (beta = 0.124, P < 0.001) and hypertension (beta = 0.066, P = 0.006). CONCLUSION: Overweight, central fat distribution, dyslipidaemia, hypertension and poor glycometabolic control are strong independent predictors of insulin resistance in Type 2 diabetes. However, reduced insulin sensitivity can be found even when Type 2 diabetes is isolated and well controlled.