Background—Subjects who convert to type 2 diabetes mellitus have increased cardiovascular risk factors relative to nonconverters. However, it is not known whether these atherogenic changes in the prediabetic state are predominantly due to insulin resistance, decreased insulin secretion, or both.

Methods and Results—We examined this issue in the 7-year follow-up of the San Antonio Heart Study, in which 195 of 1734 subjects converted to type 2 diabetes. At baseline, converters had significantly higher body mass index, waist circumference, triglyceride concentration, and blood pressure and lower HDL cholesterol than nonconverters. Atherogenic changes in converters were markedly attenuated (and no longer significant) after adjustment for the homeostasis model assessment of insulin resistance (HOMA IR, a surrogate for insulin resistance); in contrast, the differences in risk factors between converters and nonconverters increased after adjustment for the ratio of early insulin increment to early glucose increment (ΔI_30-0/ΔG_30-0) during an oral glucose tolerance test (a surrogate for insulin secretion). We also compared converters who had a predominant insulin resistance (high HOMA IR and high ΔI_30-0/ΔG_30-0) (n=56) and converters who had a predominant decrease in insulin secretion (low HOMA IR and low ΔI_30-0/ΔG_30-0) (n=31) with nonconverters (n=1539). Only the converters who were insulin resistant had higher blood pressure and triglyceride levels and lower HDL cholesterol levels than nonconverters.

Conclusions—Our data suggest that atherogenic changes in the prediabetic state are mainly seen in insulin-resistant subjects and that strategies to prevent type 2 diabetes might focus on insulin-sensitizing interventions rather than interventions that increase insulin secretion because of potential effects on cardiovascular risk.