Association of the insulin-receptor variant Met-985 with hyperglycemia and non-insulin-dependent diabetes mellitus in the Netherlands: A population-based study

LM tHart, RP Stolk, RJ Heine, DE Grobbee, FEE vanderDoes, JA Maassen

OnderzoeksoutputAcademicpeer review

32 Citaten (Scopus)


One of the characteristics of non-insulin-dependent diabetes mellitus (NIDDM) is the presence of insulin resistance. Most NIDDM patients have a normal sequence of the insulin receptor, indicating that, if insulin-receptor mutations contribute to the development of NIDDM, they will be present only in a minor fraction of the NlDDM population. The goal of the present study was to examine whether insulin-receptor mutations contribute to the development of NIDDM. We examined 161 individuals with NIDDM and 538 healthy controls from the population-based Rotterdam study for the presence of mutations in the insulin-receptor gene by SSCP. A heterozygous mutation changing valine-985 into methionine was detected in 5.6% of diabetic subjects and in 1.3% of individuals with normal oral glucose tolerance test. Adjusted for age, gender, and body-mass index, this revealed a relative risk for diabetes of 4.49 (95% confidence interval 1.59-12.25) for Met-985 carriers. When the total study group was analyzed, the prevalence of the mutation increased with increasing serum glucose levels (test for trend P <.005). We conclude that the Met-985 insulin-receptor variant associates with hyperglycemia and represents a risk factor for NIDDM.

Originele taal-2English
Pagina's (van-tot)1119-1125
Aantal pagina's7
TijdschriftAmerican Journal of Human Genetics
Nummer van het tijdschrift5
StatusPublished - nov.-1996

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