Hyperglycaemia increases dipeptidyl peptidase IV activity in diabetes mellitus

Aims/hypothesis: Chronic hyperglycaemia increases dipeptidyl peptidase IV (DPP-IV) activity in endothelial cells in vitro. The present study was designed to assess the effect of high glucose on circulating DPP-IV activity in patients with type 1 and type 2 diabetes. Methods: Plasma DPP-IV activity was measured in 29 patients with type 1 diabetes and 29 age-, sex- and BMI-matched control subjects. We also assessed DPP-IV activity in 31 type 2 diabetic patients with HbA(1)c > 8.5% and in plasma from matched groups of 31 newly diagnosed diabetic subjects with HbA(1)c < 7.5%, 31 subjects with IGT and 62 subjects with NGT. In a further sample of 66 type 2 diabetic patients, a longitudinal study was also performed to evaluate variations in DPP-IV activity and HbA(1)c over 3 months. Results: DPP-IV activity in type 1 diabetic patients was not significantly different from that in control subjects; however, a significant correlation between DPP-IV and HbA(1)c was observed in diabetic subjects (r=0.47; p < 0.01). Type 2 diabetic patients with HbA(1)c > 8.5% showed significantly (p < 0.05) higher DPP-IV activity (mean +/- SD 27.7 +/- 7.1 U/l) than newly diagnosed diabetic patients and subjects with IGT (22.1 +/- 6.0 and 18.8 +/- 8.8 U/l, respectively). Variations in DPP-IV activity over 3 months in type 2 diabetic patients showed a significant positive correlation with variations in HbA(1)c (r=0.26; p < 0.05). Conclusions/interpretations: Chronic hyperglycaemia induces a significant increase in DPP-IV activity in type 1 and type 2 diabetes. This phenomenon could contribute to the reduction in circulating active glucagon-like peptide-1 and to the consequent postprandial hyperglycaemia in type 2 diabetic patients with poor metabolic control.