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

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 ϳ4,500 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. T he role of the newly described adipocyte-derived peptide adiponectin is still poorly understood. Nevertheless, its plasma concentration is decreased in patients with obesity, type 2 diabetes, or coronary artery disease (1,2). The treatment of diabetic animals with adiponectin has been shown (3,4) to improve insulin sensitivity. The adiponectin gene consists of three exons and two introns located on chromosome 3q27, where a diabetes susceptibility locus has been mapped (5,6). Single nucleotide polymorphisms (SNPs) of the adiponectin gene have been associated with BMI, insulin sensitivity, and type 2 diabetes in some cross-sectional studies (7-9), but these associations have not been seen in all studies (10,11). The aim of our study was to assess the effects of these polymorphisms on the 3-year evolution of features of the insulin resistance syndrome in a large Caucasian population of men and women, aged 30 -64 years, known as the Epidemiologic Data on the Insulin Resistance Syndrome (DESIR) cohort. The influence of baseline plasma adiponectin levels on the 3-year risk of developing hyperglycemia (impaired fasting glycemia or type 2 diabetes) was also estimated. RESEARCH DESIGN AND METHODSThe study population consisted of men and women, aged 30 -64 years, who participated in DESIR, a 9-year follow-up study that aims to clarify the Additional information for this article can be found in two online appendixes at http://diabetes.diabetesjournals.org. DESIR, Epidemiologic Data on the Insulin Resistance Syndrome; IFG, impaired fasting glucose; SNP, single nucleotide polymorphism; WHR, waistto-hip ratio.

Promoter adiponectin polymorphisms and waist/hip ratio variation in a prospective French adults study

“…The present association study suggests that À11391A and À11377C carriers of 5 0 ADIPOQ gene variants could be prone to a higher regional fat increase over time in a general population. In contrast, Fumeron et al 22 found no association between the Adiponectin gene and weight gain G Dolley et al À11391G4A SNP and WHR at baseline and during the 3-year follow-up in their study in a population survey.…”

Hypoadiponectinaemia and high risk of type 2 diabetes are associated with adiponectin-encoding (ACDC) gene promoter variants in morbid obesity: evidence for a role of ACDC in diabesity

“…Heritability of adiponectin levels is 40-70% [8,9], and single nucleotide polymorphisms (SNPs) in the coding and 5′ sequences of the gene [9,10] define haplotypes at risk of type 2 diabetes that reduce adiponectin levels in diabetic and normoglycaemic populations [9,11]. These data show that low adiponectin level might be one of the primary determinants of type 2 diabetes, which is in part genetically determined, a hypothesis that we recently evidenced further in the prospectively followed French Caucasian DESIR population [12]. The PPARG agonists, glitazones, increase adiponectin levels, suggesting that part of their hypoglycaemic action is mediated by the hormone release [13].…”

“…These data corroborate those obtained in less obese subjects from different ethnic groups [9][10][11] and provide further evidence for the association of ACDC promoter SNP with the genetic modulation of adiponectinaemia and insulin sensitivity. Moreover, a prospective study in a general Caucasian population reported that genetic variations at the ACDC gene (including SNP −11,391) modulated adiponectin levels and increased the risk of becoming diabetic [12]. Although we could not detect an impact of ACDC promoter genetic variants on type 2 diabetes in non-obese subjects, they were closely associated with type 2 diabetes in obese (OR 1.73) and morbidly obese (OR 1.92) subjects, confirming the physiological role of adiponectin in the protection against the deleterious metabolic effects of an excess in corpulence.…”

Metabolic profiles in patients with chronic hepatitis C: a case–control study

“…Adiponectin, an adipokine, has been implicated in the pathogenesis of type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD), and appears to have many favorable effects on glucose and lipid metabolism [20,21]. It is positively correlated with insulin sensitivity and is decreased in obese and type 2 diabetic patients [22].…”