No acute effect of nateglinide on postprandial lipid and lipoprotein responses in subjects at risk for type 2 diabetes.
BACKGROUND
To study the acute effect of nateglinide, an insulinotropic agent, on the postprandial triglyceride and lipoprotein responses in subjects at risk for type 2 diabetes.


METHODS
Six women and 10 men, with at least one first-degree relative with type 2 diabetes were included (Age: 48 +/- 7 years, BMI: 27.5 +/- 2.8 kg m(-2), P-triglycerides: 1.3 +/- 0.4 mmol L(-1), P-cholesterol: 5.4 +/- 0.6 mmol L(-1), B-glucose: 4.6 +/- 0.3 mmol L(-1)). They each had two 8-h meal tolerance tests with either nateglinide or placebo given 10 min prior to the meals in randomized order. Lipoprotein fractions were separated by density gradient ultracentrifugation. First-phase insulin secretion was assessed by an intravenous glucose tolerance test (300 mg kg(-1) body weight) and insulin sensitivity by a hyperinsulinaemic euglycaemic clamp (40 mU m(-2) min(-1)).


RESULTS
The 1-h insulin levels during the meal tolerance test were significantly higher with nateglinide (577 +/- 81 vs 376 +/- 58 pmol L(-1), p < 0.001), as well as the response during the first two hours (IAUC: 41 243 +/- 5844 vs 29 956 +/- 4662 pmol L(-1) min, p < 0.01). Accordingly, nateglinide lowered the 8-h postprandial glucose response by around 60% compared to placebo (p < 0.001). In contrast, no significant lowering was seen in the excursion of postprandial triglycerides in total plasma or lipoprotein fractions. Consistently, the concentration of exogenous (apoB-48) and endogenous (apoB-100) lipoproteins was not reduced by nateglinide.


CONCLUSIONS
Acute administration of nateglinide reduces, as expected, the postprandial glucose concentration, but no reduction in triglyceride or lipoprotein responses are seen in subjects at risk for type 2 diabetes.
Johanson
E H
EH
The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden. else@medic.gu.se
Jansson
P-A
PA
Gustafson
B
B
Sandqvist
M
M
Taskinen
M-R
MR
Smith
U
U
Axelsen
M
M
D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D003510:Cyclohexanes / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019518:Postprandial Period; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D008055:Lipids; D008074:Lipoproteins; D014280:Triglycerides; D000077715:Nateglinide; D010649:Phenylalanine; D002784:Cholesterol