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The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity

Nature Genetics volume 26, pages 444–446 (2000)Cite this article

A Correction to this article was published on 01 May 2001

Abstract

In millions of people, obesity leads to type 2 diabetes (T2D; also known as non-insulin-dependent diabetes mellitus1). During the early stages of juvenile obesity, the increase of insulin secretion in proportion to accumulated fat balances insulin resistance and protects patients from hyperglycaemia2. After several decades, however, β-cell function deteriorates and T2D develops in approximately 20% of obese patients3,4. In modern societies, obesity has thus become the leading risk factor for T2D (ref. 5). The factors that predispose obese patients to alteration of insulin secretion upon gaining weight remain unknown. To determine which genetic factors predispose obese patients to β-cell dysfunction, and possibly T2D, we studied single-nucleotide polymorphisms (SNPs) in the region of the insulin gene (INS) among 615 obese children. We found that, in the early phase of obesity, alleles of the INS variable number of tandem repeat (VNTR) locus are associated with different effects of body fatness on insulin secretion. Young obese patients homozygous for class I VNTR alleles secrete more insulin than those with other genotypes.

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Figure 1: Genotypic variations in the relationship between fasting insulin levels and BMI in obese children.
Figure 2: The Hph1 T/T obese patients showed a more rapid weight gain in late childhood and adolescence.

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Acknowledgements

We thank A. Dermane for clinical assistance; M. Delpech, F. Amalric, C. Julier and B. Bihain for discussions; Y. Lefourn and N. Lahlou for insulin measurements; and C. Dos Santos for genotyping.

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Authors and Affiliations

  1. Department of Pediatric Endocrinology, Hôpital St Vincent de Paul, Paris, France

    Catherine Le Stunff & Pierre Bougnères

  2. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA

    Daniele Fallin & Nicholas J. Schork

  3. Harvard University School of Public Health, Boston, Massachusetts, USA

    Nicholas J. Schork

  4. Genset Corp., La Jolla, California, USA

    Catherine Le Stunff, Nicholas J. Schork & Pierre Bougnères

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  1. Catherine Le Stunff
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  2. Daniele Fallin
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  4. Pierre Bougnères
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Correspondence to Pierre Bougnères.

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Le Stunff, C., Fallin, D., Schork, N. et al. The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity. Nat Genet 26, 444–446 (2000). https://doi.org/10.1038/82579

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