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As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema. (Funded by Takeda Pharmaceuticals and others; ClinicalTrials.gov number, NCT00220961.).

OBJECTIVE -The oral glucose tolerance test identifies high-risk subjects for diabetes, but it is costly and inconvenient. To find better predictors of type 2 diabetes, we evaluated two different definitions of the metabolic syndrome because insulin resistance, which is commonly associated with this clustering of metabolic factors, frequently precedes the onset of type 2 diabetes. RESEARCH DESIGN AND METHODS-We compared the ability of the National Cholesterol Education Program (NCEP) definition, a modified version of the 1999 World Health Organization (WHO) definition that excludes the 2-h glucose requirement, and impaired glucose tolerance (IGT) to predict incident type 2 diabetes. In the San Antonio Heart Study, 1,734 participants completed a 7-to 8-year follow-up examination.RESULTS -IGT and the NCEP definition had higher sensitivity than the modified WHO definition (51.9, 52.8, and 42.8%, respectively). IGT had a higher positive predictive value than the NCEP and modified WHO definitions (43.0, 30.8, and 30.4%, respectively). The combination of the IGT and NCEP definitions increased the sensitivity to 70.8% with an acceptable positive predictive value of 29.7%. Risk for incidence of type 2 diabetes using the NCEP definition was independent of other risk factors, including IGT and fasting insulin (odds ratio 3.30, 95% CI 2.27-4.80). The NCEP definition performed better with fasting glucose Ն5.4 mmol/l (sensitivity 62.0% and positive predictive value 30.9%). The OGTT is the standard method for identifying subjects at increased risk for developing type 2 diabetes in clinical research. However, OGTT is not widely used in clinical practice because it is inconvenient and costly. Identifying subjects at risk for diabetes has become more relevant because of the positive results seen with lifestyle modification and medication in the prevention (or delay) of type 2 diabetes (5-9). CONCLUSIONSIn seeking better predictors of type 2 diabetes, we evaluated two different definitions of the metabolic syndrome because insulin resistance, which is commonly associated with this clustering of metabolic factors, frequently precedes the onset of type 2 diabetes. We compared the ability of the NCEP definition, a modified version of the 1999 WHO definition of the metabolic syndrome, and IGT to predict the incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS SubjectsThe San Antonio Heart Study (SAHS) is a population-based, epidemiological study of type 2 diabetes and cardiovascular disease (initial response rate 65.3%). A total of 2,941 Mexican Americans and nonHispanic whites aged 25-68 years were enrolled in phase 2 (10,11). We excluded participants in phase 1 (waist circumference was not measured) and those in phase 2 with diabetes at baseline (baseline prevalence of type 2 diabetes 10.6%). From a total of 2,569 eligible participants, 1,734 subjects completed a 7-to 8-year follow-up examination. Survey protocols at baseline and follow-up were identical and were approved by the Institutional Review Board of the University of T...

OBJECTIVE:To study the relation of fibrinogen and C-reactive protein (CRP) to various measures of body fat and body fat distribution and to investigate whether these relations were explained by differences in insulin sensitivity. DESIGN AND SUBJECTS: Cross-sectional analysis of the IRAS (Insulin Resistance Atherosclerosis Study), a large (n ¼ 1559) triethnic population (non-Hispanic whites, African-Americans and Mexican-Americans) across different states of glucose tolerance. MEASUREMENTS: Glucose tolerance (oral glucose tolerance test), insulin sensitivity (frequently sampled intravenous glucose tolerance test and minimal model analysis), assessment of body fat mass and distribution (weight, girths, bioelectrical impedance), subclinical atherosclerosis (B-mode ultrasonography of carotid artery intima-media thickness, IMT), CRP (highly sensitive immunoassay), fibrinogen (standard assay). RESULTS: Both CRP and fibrinogen were related to all measures of body fat. Strong correlations (correlation coefficient r ! 0.35) were found between CRP and body mass index (BMI), waist circumference and adipose body mass, respectively. The associations were consistent in non-diabetic and type-2 diabetic subjects, were generally stronger in women, and were only moderately attenuated by the prevailing insulin sensitivity (S I ). In a multivariate linear regression model waist circumference explained 14.5% of the variability of circulating CRP levels (P ¼ 0.0001), BMI 0.4% (P ¼ 0.0067), and S I 1.7% (P ¼ 0.0001). Common carotid artery IMT was related to CRP and fibrinogen in men, but not in women, and was attenuated after adjusting for BMI or waist. CONCLUSION: Our findings show that measures of body fat are strongly associated with circulating levels of CRP and fibrinogen. These associations were not explained by lower S I in obese subjects. Chronic, subclinical inflammation may be one pathophysiological mechanism explaining the increased risk of atherosclerotic disease associated with adiposity.