Acute nateglinide administration in subjects with type 2 diabetes: effects on postprandial metabolism, coagulation, and fibrinolysis.
OBJECTIVE
Postprandial glycaemia and lipaemia are known risk factors for atherosclerosis in type 2 diabetes. Coagulation activation in the postprandial state also contributes to acceleration of atherosclerosis. Nateglinide is effective in reducing postprandial glycaemia. Its effect on glycaemia may also be beneficial in postprandial lipaemia and coagulation. The aim of this study was to examine the potential effect of a single dose of nateglinide on postprandial triglyceridaemia, coagulation, and fibrinolysis in patients with type 2 diabetes.


RESULTS
Ten subjects with type 2 diabetes, treated with diet alone were recruited in a crossover randomized study. In the morning, after a 12- to 14-h fast, each subject received a standard mixed meal (total energy 783 kcal), preceded by one tablet of 120 mg nateglinide or placebo. Venous blood samples were drawn prior to meal consumption and 6h afterwards for the measurement of plasma glucose, insulin, and C-peptide, lipids, coagulation, and fibrinolysis factors. As expected, there was a significant reduction in postprandial glycaemia after nateglinide administration compared to placebo (P<0.001). Plasma insulin levels were significantly higher after nateglinide than after placebo (P=0.002). Nateglinide administration resulted in a lower overall postprandial reduction of tissue-plasminogen activator than placebo (-2.9+/-1.3 vs. -8.3+/-3.7 ng/ml h, P=0.003). In addition, a significant reduction of postprandial plasminogen activator inhibitor-1 was observed in comparison with the baseline values after nateglinide (P=0.001), although the overall response was not significantly different after nateglinide and placebo (P=0.31). Plasma concentrations of C-peptide, lipids and the remaining coagulation parameters studied were not different between nateglinide and placebo.


CONCLUSIONS
Acute nateglinide administration improves postprandial glycaemia and fibrinolytic activity in patients with type 2 diabetes. This combined effect, if confirmed by a long-treatment study, might reduce cardiovascular risk in type 2 diabetes.
Tentolouris
N
N
First Department of Propaedeutic Medicine, Laiko Hospital, Athens University Medical School, Athens, Greece.
Boutati
E
E
Karambakalis
N
N
Perrea
D
D
Perea
D
D
Tselepis
A D
AD
Tsoukala
C
C
Kyriaki
D
D
Lourida
E
E
Anastasopoulou
I
I
Karafoullidou
A
A
Raptis
S A
SA
Katsilambros
N
N
D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D018592:Cross-Over Studies; D003510:Cyclohexanes / Q000494:pharmacology* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008055:Lipids / Q000097:blood*; D008297:Male; D008660:Metabolism / Q000187:drug effects; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019518:Postprandial Period / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D008055:Lipids; D000077715:Nateglinide; D010649:Phenylalanine