Fasting Intact Proinsulin Is a Highly Specific Predictor of Insulin Resistance in Type 2 Diabetes

OBJECTIVE: In later stages of type 2 diabetes, proinsulin and proinsulin-like molecules are secreted in increasing amounts with insulin. A recently introduced chemiluminescence assay is able to detect the uncleaved "intact" proinsulin and differentiate it from proinsulin-like molecules. This investigation explored the predictive value of intact proinsulin as an insulin resistance marker. RESEARCH DESIGN AND METHODS: In total, 48 patients with type 2 diabetes (20 women and 28 men, aged 60 +/- 9 years means +/- SD, diabetes duration 5.1 +/- 3.8 years, BMI 31.2 +/- 4.8 kg/m2, and HbA1c 6.9 +/- 1.2%) were studied by means of an intravenous glucose tolerance test and determination of fasting values of intact proinsulin, insulin, resistin, adiponectin, and glucose. Insulin resistance was determined by means of minimal model analysis (MMA) (as the gold standard) and homeostatis model assessment (HOMA). RESULTS: There was a significant correlation between intact proinsulin values and insulin resistance (MMA P10 pmol/l) showed a very high specificity (MMA 100% and HOMA 92.9%) and a moderate sensitivity (MMA 48.6% and HOMA 47.1%) as marker for insulin resistance. Adiponectin values were slightly lower in the insulin resistant group, but no correlation to insulin resistance could be detected for resistin in the cross-sectional design. CONCLUSIONS: Elevated intact proinsulin seems to indicate an advanced stage of beta-cell exhaustion and is a highly specific marker for insulin resistance. It might be used as arbitrary marker for the therapeutic decision between secretagogue, sensitizer, or insulin therapy in type 2 diabetes.