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.

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 approximately 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.

[1]  P. Froguel,et al.  Impaired Multimerization of Human Adiponectin Mutants Associated with Diabetes , 2003, Journal of Biological Chemistry.

[2]  J. Engel,et al.  Structure-Function Studies of the Adipocyte-secreted Hormone Acrp30/Adiponectin , 2003, The Journal of Biological Chemistry.

[3]  C. Dina,et al.  Does the −11377 promoter variant of APM1 gene contribute to the genetic risk for Type 2 diabetes mellitus in Japanese families? , 2003, Diabetologia.

[4]  H. Boeing,et al.  Adiponectin and protection against type 2 diabetes mellitus , 2003, The Lancet.

[5]  B. Khoo,et al.  A tumour that secretes glucagon-like peptide-1 and somatostatin in a patient with reactive hypoglycaemia and diabetes , 2003, The Lancet.

[6]  K. Clément,et al.  Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. , 2002, Human molecular genetics.

[7]  Jonathan Krakoff,et al.  Adiponectin and development of type 2 diabetes in the Pima Indian population , 2002, The Lancet.

[8]  P. Scherer,et al.  A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. , 2002, Diabetes.

[9]  C. Bogardus,et al.  Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. , 2002, Diabetes.

[10]  H. Lodish,et al.  ACRP30, a new hormone controlling fat and glucose metabolism. , 2002, European journal of pharmacology.

[11]  P. Scherer,et al.  ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism , 2002, Trends in Endocrinology & Metabolism.

[12]  C. Dina,et al.  Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. , 2002, Diabetes.

[13]  P. Scherer,et al.  The adipocyte-secreted protein Acrp30 enhances hepatic insulin action , 2001, Nature Medicine.

[14]  T. Funahashi,et al.  Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. , 2001, Diabetes.

[15]  H. Lodish,et al.  Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Weber,et al.  Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[17]  C. Dina,et al.  Genomewide search for type 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21-q24. , 2000, American journal of human genetics.

[18]  J. Schölmerich,et al.  Mutation analysis of the human adipocyte‐specific apM‐1 gene , 2000, European journal of clinical investigation.

[19]  S. Kihara,et al.  Genomic structure and mutations in adipose-specific gene, adiponectin , 2000, International Journal of Obesity.

[20]  B. Balkau,et al.  Relationships between abdominal body fat distribution and cardiovascular risk factors: an explanation for women’s healthier cardiovascular risk profile. The D.E.S.I.R. Study , 1999, International Journal of Obesity.

[21]  P. Raskin,et al.  Report of the expert committee on the diagnosis and classification of diabetes mellitus. , 1999, Diabetes care.

[22]  B. Balkau,et al.  Distribution of fasting serum insulin measured by enzyme immunoassay in an unselected population of 4,032 individuals. Reference values according to age and sex. D.E.S.I.R. Study Group. Données Epidémiologiques sur le Syndrome d'Insulino-Résistance. , 1996, Diabetes & metabolism.

[23]  B. Balkau,et al.  [An epidemiologic survey from a network of French Health Examination Centres, (D.E.S.I.R.): epidemiologic data on the insulin resistance syndrome]. , 1996, Revue d'epidemiologie et de sante publique.

[24]  M. Stumvoll,et al.  Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. , 2002, Diabetes.