Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects - Implications for preventing coronary heart disease during the prediabetic state

Background-Subjects who convert to type 2 diabetes mellitus have increased cardiovascular risk factors relative to nonconverters, However. it is not k nown whether these atherogenic changes in the prediabetic state are predomi nantly due to insulin resistance, decreased insulin secretion, or both. Methods and Results-We examined this issue in the 7-year follow-up of the S an Antonio Heart Study, in which 195 of 1734 subjects converted to type 2 d iabetes. At baseline, converters had significantly higher body mass index, waist circumference, triglyceride concentration, and blood pressure and low er HDL cholesterol than nonconverters. Atherogenic changes in converters we re markedly attenuated (and no longer significant) after adjustment for the homeostasis model assessment of insulin resistance (HOMA IR, a surrogate f or insulin resistance); in contrast, the differences in risk factors betwee n converters and nonconverters increased after adjustment for the ratio of early insulin increment to early glucose increment (Delta I-30.0/Delta G(30 .0)) during an oral glucose tolerance test (a surrogate for insulin secreti on). We also compared converters who had a predominant insulin resistance ( high HOMA IR and high Delta I-30.0/G(30.0)) (n=56) and converters who had a predominant decrease in insulin secretion (low HOMA IR and low Delta I-30. 0/Delta G(30.0)) (n = 31) with nonconverters (n = 1539). Only the converter s who were insulin resistant had higher blood pressure and triglyceride lev els and lower HDL cholesterol levels than nonconverters. Conclusions-Our data suggest that atherogenic changes in the prediabetic st ate are mainly seen in insulin-resistant subjects and that strategies to pr event type 2 diabetes might focus on insulin-sensitizing interventions rath er than interventions that increase insulin secretion because of potential effects on cardiovascular risk.