A single dose of nateglinide improves post-challenge glucose metabolism and endothelial dysfunction in Type 2 diabetic patients.
OBJECTIVE
This randomized crossover placebo-controlled study aimed to assess the efficacy of nateglinide, a phenylalanine-derived insulin secretagogue, on forearm endothelial function in diabetic subjects before and after an oral glucose load.


METHODS
Forearm blood flow (FBF) was measured using strain-gauge plethysmography during reactive hyperaemia before and after an oral glucose load (75 g) with a prior use of placebo or nateglinide (90 mg) in 15 diet-treated Type 2 diabetic patients or age-matched controls with normal glucose tolerance.


RESULTS
The peak FBF response and total reactive hyperaemic flow (flow debt repayment: FDR), indices of resistance artery endothelial function, were decreased after an oral glucose load in diabetic patients, but unchanged in controls. Nateglinide administered to diabetic patients accelerated insulin secretion and reduced post-challenge plasma glucose, and also abolished the post-challenge impairment of endothelial function. The peak FBF and FDR were well correlated with 120-min glucose levels and 30-min insulinogenic index.


CONCLUSIONS
A single challenge of glucose was shown to impair endothelial function in diabetic patients, and the post-challenge endothelial dysfunction was improved by a prior use of nateglinide. Long-term effects of nateglinide on endothelial function in Type 2 diabetic patients need to be clarified in future studies.
Second Department of Internal Medicine, Faculty of Medicine, University of Ryukus, Okinawa, Japan. mshimabukuro-ur@umin.ac.jp
M
M
Shimabukuro
N
N
Higa
N
N
Takasu
T
T
Tagawa
S
S
Ueda
D000284:Administration, Oral; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D003510:Cyclohexanes / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D004311:Double-Blind Method; D004727:Endothelium / Q000098:blood supply; D005260:Female; D005542:Forearm / Q000098:blood supply; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D012039:Regional Blood Flow / Q000502:physiology
D001786:Blood Glucose; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D007328:Insulin; D000077715:Nateglinide; D010649:Phenylalanine; D005947:Glucose