Insulin resistance and beta-cell dysfunction in newly diagnosed type 2 diabetes: Expression, aggregation and predominance. Verona Newly Diagnosed Type 2 Diabetes Study 10

Abstract

Aims: We investigated quantitative expression, mutual aggregation and relation with hyperglycemia of insulin resistance (IR) and beta-cell dysfunction (BCD) in newly diagnosed type 2 diabetes.

Methods: We assessed IR with euglycemic hyperinsulinemic clamp and BCD with modelled glucose/C-peptide response to oral glucose in 729 mostly drug-naïve patients. We measured glycated hemoglobin, pre-prandial, post-prandial and meal-related excursion of blood glucose.

Results: IR was found in 87.8% [95% confidence intervals 85.4-90.2] and BCD in 90.0% [87.8-92.2] of subjects, ranging from mild to moderate or severe. Approximately 20% of subjects had solely one defect: BCD 10.8% [8.6-13.1] or IR 8.6% [6.6-10.7]. Insulin resistance and BCD aggregated in most subjects (79.1% [76.2-82.1]). We arbitrarily set nine possible combinations of mild, moderate or severe IR and mild, moderate or severe BCD, finding that each had a similar frequency (∼10%). In multiple regression analyses parameters of glucose control were related more strongly with BCD than with IR.

Conclusions: In newly-diagnosed type 2 diabetes, IR and BCD are very common with a wide range of expression but no specific pattern of aggregation. Beta-cell dysfunction is likely to play a greater quantitative role than IR in causing/sustaining hyperglycemia in newly-diagnosed type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT01526720.

Keywords: beta-cell dysfunction; hyperglycemia; insulin resistance; newly diagnosed; type 2 diabetes mellitus.