Low Insulin Sensitivity (Si = 0) in Diabetic and Nondiabetic Subjects in the Insulin Resistance Atherosclerosis Study

Abstract

OBJECTIVE -To determine the meaning of S i ϭ 0 derived from the frequently sampled intravenous glucose tolerance test.RESEARCH DESIGN AND METHODS -The issue of assessing insulin resistance in large studies is important because the most definitive method ("gold standard"), the hyperinsulinemic-euglycemic clamp, is expensive and invasive. The frequently sampled intravenous glucose tolerance test (FSIGTT) has been widely used, but in insulin-resistant subjects (especially diabetic subjects), it yields considerable numbers of subjects whose S i is zero. The interpretation of an S i equaling zero is unknown.RESULTS -To address this issue, we examined 1,482 subjects from the Insulin Resistance Atherosclerosis Study (IRAS) using an insulin-modified FSIGTT and minimal model calculation of S i . The proportion of insulin-resistant subjects (S i Ͻ 1.61 ϫ 10 Ϫ4 [min Ϫ1 ⅐ U Ϫ1 ⅐ ml Ϫ1 ] based on the median of the nondiabetic population) was 38.6% in subjects with normal glucose tolerance (NGT), 74% in subjects with impaired glucose tolerance (IGT), and 92% in subjects with type 2 diabetes. The proportion of subjects with S i ϭ 0 was 2.2% in subjects with NGT, 13.2% in subjects with IGT, and 35.7% in subjects with type 2 diabetes. In subjects with IGT, those with S i ϭ 0 had significantly lower HDL cholesterol levels and higher BMI, waist circumference, fibrinogen, plasminogen-activator inhibitor 1 (PAI-1), C-reactive protein (CRP), and 2-h insulin levels than insulin-resistant subjects with S i Ͼ 0. In type 2 diabetes, subjects with S i ϭ 0 had significantly greater BMI and waist circumference and higher triglyceride, PAI-1, CRP, fibrinogen, and fasting and 2-h insulin levels than insulin-resistant subjects with S i Ͼ 0. In addition, diabetic subjects with S i ϭ 0 had more metabolic disorders related to the insulin resistance syndrome than diabetic insulin-resistant subjects with S i Ͼ 0.CONCLUSIONS -We found very few subjects with S i ϭ 0 among subjects with NGT and few subjects with S i ϭ 0 among subjects with IGT. In contrast, S i ϭ 0 was common in subjects with diabetes. Subjects with S i ϭ 0 tended to have more features of the insulin resistance syndrome than other insulin-resistant subjects with S i Ͼ 0, as would be expected of subjects with almost no insulin-mediated glucose disposal, thus suggesting that subjects with S i ϭ 0 are correctly classified as being very insulin resistant rather than having failed the minimal model program. Diabetes Care 26:2796 -2803, 2003H yperinsulinemia and insulin resistance have been related to the development of type 2 diabetes (1-7) and cross-sectionally and prospectively with cardiovascular risk factors and atherosclerosis (8 -17). Most studies (especially large population-based studies) use surrogates for insulin resistance such as fasting insulin (18) because of the expense and difficulty of direct measures of insulin resistance. In populations in which both insulin levels and insulin resistance have been measured, the latter often has been more closely associated with important...

Improved fibrinolysis by an intensive lifestyle intervention in subjects with impaired glucose tolerance. The Finnish Diabetes Prevention Study

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An empirical index of insulin sensitivity from short IVGTT: validation against the minimal model and glucose clamp indices in patients with different clinical characteristics

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