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


CONCLUSIONS
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.
Ebeling
P
P
Department of Medicine, Helsinki University Central Hospital, Finland.
Teppo
A M
AM
Koistinen
H A
HA
Viikari
J
J
Rönnemaa
T
T
Nissén
M
M
Bergkulla
S
S
Salmela
P
P
Saltevo
J
J
Koivisto
V A
VA
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology / Q000627:therapeutic use*; D003176:Complement C3 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000378:metabolism; D010919:Placebos; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone
D000209:Acute-Phase Proteins; D001786:Blood Glucose; D002097:C-Reactive Protein; D002839:Chromans; D003176:Complement C3; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D009961:Orosomucoid; D010919:Placebos; D000685:Serum Amyloid A Protein; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone