Adiponectin Gene Polymorphisms and Adiponectin Levels Are Independently Associated With the Development of Hyperglycemia During a 3-Year Period

The Epidemiologic Data on the Insulin Resistance Syndrome Prospective Study

  1. Frédéric Fumeron1,
  2. Roberte Aubert1,
  3. Afshan Siddiq2,
  4. Dina Betoulle1,
  5. Frank Péan1,
  6. Samy Hadjadj1,
  7. Jean Tichet3,
  8. Elsie Wilpart4,
  9. Marie-Claude Chesnier5,
  10. Beverley Balkau6,
  11. Philippe Froguel27,
  12. Michel Marre1 and
  13. for the Epidemiologic Data on the Insulin Resistance Syndrome (DESIR) Study Group
  1. 1EA 3516, Interactions Gènes-Environnement dans les Pathologies Métaboliques à Risque Cardiovasculaire, Faculté Xavier Bichat, Paris, France
  2. 2Hammersmith Genome Centre and Genomic Medicine, Imperial College, London, U.K
  3. 3Institut Régional Pour la Santé, Tours, France
  4. 4Centre d’Examens de Santé, Orléans, France
  5. 5Institut Régional Pour la Santé, Alençon, France
  6. 6INSERM U258-IFR69, Villejuif, France
  7. 7CNRS 8090, Institut de Biologie de Lille, Institut Pasteur, Lille, France
  1. Address correspondence and reprint requests to Frédéric Fumeron, EA 3516, Xavier Bichat Medical School, BP 416, 16 rue Henri Huchard, 75870 Paris Cedex 18, France. E-mail: fumeron{at}bichat.inserm.fr

Abstract

The plasma concentration of the adipocyte-derived peptide adiponectin is decreased in patients with obesity and type 2 diabetes. The adiponectin gene is located on chromosome 3q27, where a diabetes susceptibility locus has been mapped. Adiponectin gene polymorphisms (single nucleotide polymorphisms [SNPs]) have been associated with BMI, insulin sensitivity, and type 2 diabetes in some cross-sectional studies. Our aim was to assess the contribution of these SNPs in the development of features of the insulin resistance syndrome in a 3-year prospective study in ∼4,500 French Caucasian subjects from the Epidemiologic Data on the Insulin Resistance Syndrome (DESIR) cohort. For subjects who were normoglycemic at baseline, the 3-year risk of becoming hyperglycemic (diabetes or impaired fasting glucose) was affected by two SNPs: G-11391A and T45G. For G-11391A, the risk was increased in GA carriers (odds ratio [OR] adjusted for sex [versus GG] = 1.60 [95% CI 1.16–2.20]; P = 0.004). For T45G, it was increased in GG carriers (OR [versus TT] = 2.71 [1.31–5.60]; P = 0.007). After 3 years, GG subjects had a greater increase in BMI (P = 0.009) and waist-to-hip ratio (P = 0.007). Adiponectin levels at baseline were associated with the development of hyperglycemia (P = 0.005), but the predictive effects on the risk for hyperglycemia were independent of adiponectin genotypes. In conclusion, in the DESIR study, variations at the adiponectin locus affect body weight gain, body fat distribution, and onset of hyperglycemia, as well as adiponectin levels. Adiponectin gene SNPs may have several phenotypic effects that co-occur with the development of the metabolic syndrome.

Footnotes

  • R.A. and A.S. contributed equally to this study.

    A complete list of DESIR Study Group members can be found in the appendix.

    Additional information for this article can be found in two online appendixes at http://diabetes.diabetesjournals.org.

    • Accepted December 23, 2003.
    • Received August 6, 2002.
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