TY - JOUR

T1 - The Ala/Va198 polymorphism of the hepatocyte nuclear factor-1α gene contributes to the interindividual variation in serum C-peptide response during an oral glucose tolerance test

T2 - Evidence from studies of 231 glucose- tolerant first degree relatives of type 2 diabetic probands

AU - Urhammer, Søren A.

AU - Hansen, Torben

AU - Ekstrøm, Claus T.

AU - Eiberg, Hans

AU - Pedersen, Oluf

PY - 1998/12/1

Y1 - 1998/12/1

N2 - The third form of maturity-onset diabetes of the young is caused by mutations in the hepatocyte nuclear factor-1α gene. Recently, we demonstrated an association between a prevalent polymorphism at codon 98, Ala/Val98, of this gene and a 20% decreased insulin release during an oral glucose tolerance test (OGTT) in middle-aged glucose-tolerant Danish Caucasian subjects. The major objective of the present study was to replicate this finding among glucose-tolerant first degree relatives of type 2 diabetic patients of the same ethnic origin. All participants, 231 glucose-tolerant offspring of 62 type 2 diabetic probands, underwent an OGTT with measurements of plasma glucose, serum insulin, and serum C peptide during the test. Thirty-three heterozygous carriers of the Ala/Val variant were identified, whereas no subjects had the variant in its homozygous form. Ala/Val carriers had a 20% reduction in serum C peptide at 30 min during the OGTT (1225 ± 636 vs. 1507 ± 624 pmol/L; P = 0.02) compared to wild-type carriers. No significant differences in serum insulin levels during the OGTT were observed between carriers of the variant and Ala/Ala homozygotes. In conclusion, among Danish glucose-tolerant first degree relatives of type 2 diabetic patents the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1α gene is associated with a decreased serum C-peptide secretion during an OGTT. This finding confirms our previously reported observation of the functional importance of the variant to insulin secretion during an OGTT among middle- aged healthy subjects.

AB - The third form of maturity-onset diabetes of the young is caused by mutations in the hepatocyte nuclear factor-1α gene. Recently, we demonstrated an association between a prevalent polymorphism at codon 98, Ala/Val98, of this gene and a 20% decreased insulin release during an oral glucose tolerance test (OGTT) in middle-aged glucose-tolerant Danish Caucasian subjects. The major objective of the present study was to replicate this finding among glucose-tolerant first degree relatives of type 2 diabetic patients of the same ethnic origin. All participants, 231 glucose-tolerant offspring of 62 type 2 diabetic probands, underwent an OGTT with measurements of plasma glucose, serum insulin, and serum C peptide during the test. Thirty-three heterozygous carriers of the Ala/Val variant were identified, whereas no subjects had the variant in its homozygous form. Ala/Val carriers had a 20% reduction in serum C peptide at 30 min during the OGTT (1225 ± 636 vs. 1507 ± 624 pmol/L; P = 0.02) compared to wild-type carriers. No significant differences in serum insulin levels during the OGTT were observed between carriers of the variant and Ala/Ala homozygotes. In conclusion, among Danish glucose-tolerant first degree relatives of type 2 diabetic patents the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1α gene is associated with a decreased serum C-peptide secretion during an OGTT. This finding confirms our previously reported observation of the functional importance of the variant to insulin secretion during an OGTT among middle- aged healthy subjects.

UR - http://www.scopus.com/inward/record.url?scp=0032217152&partnerID=8YFLogxK

M3 - Journal article

C2 - 9851800

AN - SCOPUS:0032217152

VL - 83

SP - 4506

EP - 4509

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -