Troglitazone reduces hyperglycaemia and selectively acute-phase serum proteins in patients with Type II diabetes

Aims/hypothesis. Inflammation could play a part in insulin resistance. Thia zolidinediones, new antidiabetic drugs, possess anti-inflammatory effects i n vitro. We investigated if acute-phase serum proteins are increased in pat ients with Type II (non-insulin-dependent) diabetes mellitus who had been t reated with insulin and whether troglitazone has anti-inflammatory effects in vivo. Methods. A total of 27 patients (age 63.0 +/- 1.7 years, HbA(1c) 8.8 +/- 0. 3 %, BMI 32.7 +/- 0.8 kg/m(2), duration 15.2 +/- 1.4 years, insulin dose 73 .3 +/- 7.0 U/day) participated in the study. The patients received daily ei ther 400 mg troglitazone or placebo for 16 weeks. Blood samples were taken at baseline, at the end of therapy and after a follow-up time of 23 +/- 4 d ays. Results. The concentrations of serum amyloid A (6.2 +/- 1.1 mg/l) and C-rea ctive protein (6.1 +/- 1.1 mg/l 1) were increased (p < 0.001) and complemen t protein C3 (1.69 +/- 0.05 g/l) was also above the reference range for hea lthy subjects. Placebo treatment had no effect on glucose or inflammation, whereas troglitaz-one reduced fasting glucose (from 10.4 +/- 0.6 mmol/l to 8.1 +/- 0.5 mmol/l, p < 0.01), HbA(1c) (from 8.7 +/- 0.3 % to 7.5 +/- 0.3 % , p < 0.01), insulin requirements (from 75 +/- 10 U/day to 63 +/- 10 U/day, p < 0.05), serum amyloid A (from 6.3 +/- 1.5 mg/l to 4.0 +/- 1.3 mg/l, p = 0.001), alpha-1-acid glycoprotein (from 906 +/- 51 mg/l to 729 +/- 52 mg/l , p = 0.001) and C3 (from 1.72 +/- 0.07 g/l to 1.66 +/- 0.06 g/l, p < 0.05) but not alpha-1-antitrypsin, ceruloplasmin, C-reactive protein or haptoglo bin significantly. Concentrations of glucose and acute-phase reactants had returned to those before treatment at the follow-up visit. Conclusion/interpretation. In Type II diabetic patients serum amyloid A and complement protein C3 are raised. Troglitazone exerts a selective reversib le action on some acute-phase proteins and C3 but not on others in conjunct ion with the improvement in glucose metabolism.