RESEARCH DESIGN AND METHODS -In the present study, we compared insulin sensitivity as assessed by a 4-h euglycemic ( 5 mmol/l) hyperinsulinemic ( 300 pmol/l) clamp with HOMA in 115 subjects with various degrees of glucose tolerance and insulin sensitivity.R E S U LT S -We found a strong correlation between clamp-measured total glucose disposal and HOMA-estimated insulin sensitivity (r = 0.820, P 0.0001), with no substantial diff e rences between men (r = 0.800) and women (r = 0.796), younger (aged 50 years, r = 0.832) and older (r = 0.800) subjects, nonobese (BMI 27 kg/m 2 , r = 0.800) and obese (r = 0.765) subjects, nondiabetic (r = 0.754) and diabetic (r = 0.695) subjects, and normotensive ( r = 0.786) and hypertensive (r = 0.762) subjects. Also, we found good agre ement between the two methods in the categorization of subjects according to insulin sensitivity (weighted k = 0.63).C O N C L U S I O N S -We conclude that the HOMA can be reliably used in large-scale or epidemiological studies in which only a fasting blood sample is available to assess insulin sensitivity. r g i n g T r e a t m e n t s a n d T e c h n o l o g i e s Diabetes Care

The prevalence of insulin resistance in the most common metabolic disorders is still an undefined issue. We assessed the prevalence rates of insulin resistance in subjects with impaired glucose tolerance (IGT), NIDDM, dyslipidemia, hyperuricemia, and hypertension as identified within the frame of the Bruneck Study. The study comprised an age- and sex-stratified random sample of the general population (n = 888; aged 40-79 years). Insulin resistance was estimated by homeostasis model assessment (HOMA(IR)), preliminarily validated against a euglycemic-hyperinsulinemic clamp in 85 subjects. The lower limit of the top quintile of HOMA(IR) distribution (i.e., 2.77) in nonobese subjects with no metabolic disorders (n = 225) was chosen as the threshold for insulin resistance. The prevalence of insulin resistance was 65.9% in IGT subjects, 83.9% in NIDDM subjects, 53.5% in hypercholesterolemia subjects, 84.2% in hypertriglyceridemia subjects, 88.1% in subjects with low HDL cholesterol, 62.8% in hyperuricemia subjects, and 58.0% in hypertension subjects. The prevalence of insulin resistance in subjects with the combination of glucose intolerance (IGT or NIDDM), dyslipidemia (hypercholesterolemia and/or hypertriglyceridemia and/or low HDL cholesterol), hyperuricemia, and hypertension (n = 21) was 95.2%. In isolated hypercholesterolemia, hypertension, or hyperuricemia, prevalence rates of insulin resistance were not higher than that in nonobese normal subjects. An appreciable number of subjects (n = 85, 9.6% of the whole population) was insulin resistant but free of IGT, NIDDM, dyslipidemia, hyperuricemia, and hypertension. These results from a population-based study documented that 1) in hypertriglyceridemia and a low HDL cholesterol state, insulin resistance is as common as in NIDDM, whereas it is less frequent in hypercholesterolemia, hyperuricemia, and hypertension; 2) the vast majority of subjects with multiple metabolic disorders are insulin resistant; 3) in isolated hypercholesterolemia, hyperuricemia, or hypertension, insulin resistance is not more frequent than can be expected by chance alone; and 4) in the general population, insulin resistance can be found even in the absence of any major metabolic disorders.

OBJECTIVE -To assess the cardiovascular risk profile, the degree of insulin resistance, and ␤-cell secretion in a cohort of subjects with different categories of impaired glucose regulation (IGR): impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/ IGT.RESEARCH DESIGN AND METHODS -We studied 902 nondiabetic subjects between 30 and 80 years of age, recruited from a cross-sectional population-based study in Telde, Gran Canaria Island, Spain. Categories of glucose tolerance were defined according to 2003 modified American Diabetes Association criteria. Risk factors for cardiovascular disease, the presence of the metabolic syndrome, and indirect measures of both insulin resistance and ␤-cell function were analyzed.RESULTS -A total of 132 (14.6%) participants had isolated IFG, 59 (6.5%) isolated IGT, and 48 (5.3%) combined IFG/IGT. Groups with normal glucose tolerance (NGT) and combined IFG/IGT had, respectively, the most favorable and unfavorable levels of cardiovascular risk factors, metabolic syndrome rates, and measures of insulin resistance. Subjects with IFG and IGT showed an intermediate profile between NGT and IFG/IGT categories. We found no significant differences between IFG and IGT in cardiovascular risk factors, metabolic syndrome prevalence, or insulin resistance. The IFG group exhibited a more impaired insulin secretion than those with IGT or IFG/IGT. I n 1997, the American Diabetes Association (ADA) issued new diagnostic criteria for diabetes and established a new category of impaired glucose regulation (IGR) called impaired fasting glucose (IFG), a fasting category analogous to impaired glucose tolerance (IGT) and defined as a fasting plasma glucose (FPG) between 6.1 and 6.9 mmol/l (1). In 2003, based on epidemiological predictive data from different populations showing that decreasing the lower limit of IFG would optimize its sensitivity and specificity for predicting future diabetes, the ADA established a new cutoff point of 5.6 mmol/l (2). CONCLUSIONSAlthough both IFG and IGT are risk factors for diabetes and cardiovascular disease (CVD) (3), IGT is more consistently associated with an increase in cardiovascular-related and all-cause mortality (4 -9). Moreover, evidence that interventions may reduce progression to diabetes is limited to IGT (10 -12).To explain a different prognostic value of IFG and IGT on the risk of diabetes and CVD, different studies have analyzed the prevalence of cardiovascular risk factors, insulin sensitivity, and ␤-cell function among subjects with different categories of IGR (13-22). However, results have been discordant, and most studies were performed before the introduction of the 2003 ADA criteria.Here, we have compared the cardiovascular risk profile (traditional and new risk factors), the prevalence of the metabolic syndrome, as well as different indexes for the assessment of insulinglucose homeostasis in subjects with normal glucose tolerance (NGT) and IGR that participated in the Telde Study, a population-based survey performed in Gr...

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.

OBJECTIVE -The purpose of this study was to explore the relation between insulin resistance and plasma levels of soluble adhesion molecules and to examine the effects of acute hyperinsulinemia on these molecules in type 2 diabetic individuals.RESEARCH DESIGN AND METHODS -Intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-and P-selectin plasma concentrations were measured in 36 nonobese type 2 diabetic patients without cardiovascular disease and in 7 healthy subjects. Insulin sensitivity was assessed by a 4-h euglycemic (ϳ5 mmol/l)-hyperinsulinemic (ϳ300 pmol/l) clamp performed in combination with [ RESULTS -Diabetic subjects were insulin resistant but did not show plasma concentrations of adhesion molecules that were significantly higher than control subjects. In diabetic subjects, plasma ICAM-1 and E-selectin were negatively correlated with total glucose disposal during the insulin clamp (r ϭ Ϫ0.432, P Ͻ 0.01; and r ϭ Ϫ0.375, P Ͻ 0.05, respectively), whereas plasma VCAM-1 and P-selectin were not. Plasma ICAM-1 as well as E-and P-selectin were positively correlated with BMI, total body fat (TBF), and waist girth (P Ͻ 0.05-0.001). In multiple regression analyses, the relation of plasma ICAM-1 and E-selectin with insulin sensitivity was lost after adjustment for potential confounders, including HbA 1c , blood pressure, and/or LDL cholesterol. In these analyses, BMI was the only independent predictor of plasma ICAM-1 (R 2 ϭ 0.244, P Ͻ 0.002), whereas TBF was the only independent predictor of plasma E-selectin (R 2 ϭ 0.202, P ϭ 0.01). The 4-h insulin infusion during the glucose clamp did not significantly change plasma levels of adhesion molecules.CONCLUSIONS -Overall adiposity, rather than insulin resistance, may be a determinant of plasma levels of ICAM-1 and E-selectin in type 2 diabetic individuals. In these patients, acute hyperinsulinemia does not exert any significant effect on plasma adhesion molecules. These findings support the possibility that adipose tissue releases one or more factors that may adversely affect endothelial function on one hand and insulin sensitivity on the other. Diabetes Care