Effects of nateglinide on the secretion of glycated insulin and glucose tolerance in type 2 diabetes.
OBJECTIVE
Glycation of insulin has been demonstrated within pancreatic beta-cells and the resulting impaired bioactivity may contribute to insulin resistance in diabetes. We used a novel radioimmunoassay to evaluate the effect of nateglinide on plasma concentrations of glycated insulin and glucose tolerance in type 2 diabetes.


METHODS
Ten patients (5 M/5 F, age 57.8+/-1.9 years, HbA(1c) 7.6+/-0.5%, fasting plasma glucose 9.4+/-1.2 mmol/l, creatinine 81.6+/-4.5 microM/l) received oral nateglinide 120 mg or placebo, 10 min prior to 75 g oral glucose in a random, single blind, crossover design, 1 week apart. Blood samples were taken for glycated insulin, glucose, insulin and C-peptide over 225 min.


RESULTS
Plasma glucose and glycated insulin responses were reduced by 9% (P=0.005) and 38% (P=0.047), respectively, following nateglinide compared with placebo. Corresponding AUC measures for insulin and C-peptide were enhanced by 36% (P=0.005) and 25% (P=0.007) by nateglinide.


CONCLUSIONS
Glycated insulin in type 2 diabetes is reduced in response to the insulin secretagogue nateglinide, resulting in preferential release of native insulin. Since glycated insulin exhibits impaired biological activity, reduced glycated insulin release may contribute to the antihyperglycaemic action of nateglinide.
Lindsay
J R
JR
Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, BT12 6BA Belfast, UK.
McKillop
A M
AM
Mooney
M H
MH
O'Harte
F P M
FP
Flatt
P R
PR
Bell
P M
PM
D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D003510:Cyclohexanes / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test; D006031:Glycosylation; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000008:administration & dosage* / Q000031:analogs & derivatives; D016037:Single-Blind Method
D001786:Blood Glucose; D002096:C-Peptide; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D007328:Insulin; D000077715:Nateglinide; D010649:Phenylalanine