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

Diabetologia. 1999 Dec;42(12):1433-8. doi: 10.1007/s001250051315.

Abstract

Aims/hypothesis: Inflammation could play a part in insulin resistance. Thiazolidinediones, new antidiabetic drugs, possess anti-inflammatory effects in vitro. We investigated if acute-phase serum proteins are increased in patients with Type II (non-insulin-dependent) diabetes mellitus who had been treated with insulin and whether troglitazone has anti-inflammatory effects in vivo.

Methods: A total of 27 patients (age 63.0+/-1.7 years, HbA1c 8.8+/-0.3%, BMI 32.7+/-0.8 kg/m2, duration 15.2+/-1.4 years, insulin dose 73.3+/-7.0 U/day) participated in the study. The patients received daily either 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 days.

Results: The concentrations of serum amyloid A (6.2+/-1.1 mg/l) and C-reactive protein (6.1+/-1.1 mg/l) were increased (p < 0.001) and complement protein C3 (1.69+/-0.05 g/l) was also above the reference range for healthy subjects. Placebo treatment had no effect on glucose or inflammation, whereas troglitazone reduced fasting glucose (from 10.4+/-0.6 mmol/l to 8.1+/-0.5 mmol/l, p < 0.01), HbA1c (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 haptoglobin 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 reversible action on some acute-phase proteins and C3 but not on others in conjunction with the improvement in glucose metabolism.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / metabolism*
  • Aged
  • Blood Glucose / metabolism*
  • Body Mass Index
  • C-Reactive Protein / metabolism
  • Chromans / pharmacology
  • Chromans / therapeutic use*
  • Complement C3 / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Lipids / blood
  • Male
  • Middle Aged
  • Orosomucoid / metabolism
  • Placebos
  • Serum Amyloid A Protein / metabolism
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use*
  • Thiazolidinediones*
  • Troglitazone

Substances

  • Acute-Phase Proteins
  • Blood Glucose
  • Chromans
  • Complement C3
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Lipids
  • Orosomucoid
  • Placebos
  • Serum Amyloid A Protein
  • Thiazoles
  • Thiazolidinediones
  • C-Reactive Protein
  • Troglitazone