Insulin resistance is a key determinant of progression from impaired glucose tolerance (IGT) to type 2 diabetes mellitus, but not all individuals with IGT appear insulin resistant. An analysis from the STOP DIABETES trial published in Diabetes, Obesity and Metabolism found that nearly one-third of participants with IGT had preserved insulin sensitivity and a distinct metabolic phenotype.

The analysis evaluated two groups with IGT using the Matsuda index: insulin-sensitive IGT (IS-IGT; n=107), defined above the 25th percentile of individuals with normal glucose tolerance, and insulin-resistant IGT (IR-IGT; n=222), defined at or below the 25th percentile. IS-IGT participants were also compared with insulin-sensitive normal glucose tolerance (IS-NGT) participants with 1-hour plasma glucose below 155 mg/dL (n=574).

Compared with the IR-IGT group, IS-IGT participants had higher high-density lipoprotein cholesterol (HDL-C), lower body mass index (BMI), lower triglycerides, lower triglyceride-to-HDL ratio, lower high-sensitivity C-reactive protein (hs-CRP), and more normal blood pressure status (all p<0.01 to p<0.001).

Although the IS-IGT group had a higher disposition index than the IR-IGT group (p<0.0001), the early insulinogenic index was lower at 10.5 ± 0.4 versus 21.4 ± 0.5 (p<0.0001). Compared with IS-NGT participants, those with IS-IGT showed reduced beta-cell function and increased insulin clearance.

These findings indicate that a substantial subgroup with IGT develops dysglycemia despite preserved whole-body insulin sensitivity. In this population, impaired beta-cell response and higher insulin clearance may represent important metabolic features.