Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Diabetologia
Published in: Diabetologia 5/2005

01-05-2005 | Article

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

Authors: F. Vasseur, N. Helbecque, S. Lobbens, V. Vasseur-Delannoy, C. Dina, K. Clément, P. Boutin, T. Kadowaki, P. E. Scherer, P. Froguel

Published in: Diabetologia | Issue 5/2005

Login to get access

Abstract

Aims/hypothesis

Morbid obesity (BMI>40 kg/m2) affecting 0.5–5% of the adult population worldwide is a major risk factor for type 2 diabetes. We aimed to elucidate the genetic bases of diabetes associated with obesity (diabesity), and to analyse the impact of corpulence on the effects of diabetes susceptibility genes.

Methods

We genotyped known single nucleotide polymorphisms (SNPs) in the adiponectin-encoding adipocyte C1q and collagen-domain-containing (ACDC) gene (−11,391G>A, −11,377C>G, +45T>G and +276G>T), the peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala SNP and ACDC exon 3 variants in 703 French morbidly obese subjects (BMI 47.6±7.4 kg/m2), 808 non-obese subjects (BMI<30 kg/m2) and 493 obese subjects (30≤BMI<40 kg/m2).

Results

Two 5′-ACDC SNPs −11,391G>A, −11,377C>G were associated with adiponectin levels (p=0.0003, p=0.008) and defined a ‘low-level’ haplotype associated with decreased adiponectin levels (p=0.0002) and insulin sensitivity (p=0.01) and with a risk of type 2 diabetes that was twice as high (p=0.002). In contrast, the prevalence of the PPARG Pro12Ala was identical in diabetic and normoglycaemic morbidly obese subjects. The PPARG Pro12 allele only displayed a trend of association with type 2 diabetes in the non-obese group. ACDC exon 3 variants were associated with type 2 diabetes in the non-obese group only (odds ratio 7.85, p<0.0001). In contrast, the 5′-ACDC ‘low-level’ haplotype was associated with type 2 diabetes in obese and morbidly obese subjects (odds ratio 1.73 and 1.92) but not in non-obese individuals.

Conclusions/interpretation

These data clarify the contribution of the 5′-ACDC SNPs to the risk of diabesity. Their interaction with corpulence suggests for the first time a different genetic profile of type 2 diabetes in morbidly obese patients compared with in less obese individuals.
Literature
1.
Garaulet M, Viguerie N, Porubsky S et al (2004) Adiponectin gene expression and plasma values in obese women during very-low-calorie diet: relationship with cardiovascular risk factors and insulin resistance. J Clin Endocrinol Metab 89:756–760
2.
Liu YM, Lacorte JM, Viguerie N et al (2003) Adiponectin gene expression in subcutaneous adipose tissue of obese women in response to short-term very low calorie diet and refeeding. J Clin Endocrinol Metab 88:5881–5886
3.
Weyer C, Funahashi T, Tanaka S et al (2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935CrossRefPubMed
4.
Yamauchi T, Kamon J, Waki H et al (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946CrossRefPubMed
5.
Ouchi N, Kihara S, Arita Y et al (2001) Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 103:1057–1063
6.
Spranger J, Kroke A, Mohlig M et al (2003) Adiponectin and protection against type 2 diabetes mellitus. Lancet 361:226–228CrossRefPubMed
7.
Lindsay RS, Funahashi T, Hanson RL et al (2002) Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 360:57–58CrossRefPubMed
8.
Comuzzie AG, Funahashi T, Sonnenberg G et al (2001) The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab 86:4321–4325CrossRefPubMed
9.
Vasseur F, Helbecque N, Dina C et al (2002) Single-nucleotide polymorphism haplotypes in both the 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. Hum Mol Genet 11:2607–2614CrossRefPubMed
10.
Hara K, Boutin P, Mori Y et al (2002) Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 51:536–540PubMed
11.
Menzaghi C, Ercolino T, Di Paola R et al (2002) A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 51:2306–2312PubMed
12.
Fumeron F, Aubert R, Siddiq A et al (2004) 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. Diabetes 53:1150–1157
13.
Maeda N, Takahashi M, Funahashi T et al (2001) PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50:2094–2099
14.
Altshuler D, Hirschhorn JN, Klannemark M et al (2000) The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 26:76–80CrossRefPubMed
15.
Yang WS, Hsiung CA, Ho LT et al (2003) Genetic epistasis of adiponectin and PPARgamma2 genotypes in modulation of insulin sensitivity: a family-based association study. Diabetologia 46:977–983
16.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMed
17.
Zhao JH, Curtis D, Sham PC (2000) Model-free analysis and permutation tests for allelic associations. Hum Hered 50:133–139CrossRefPubMed
18.
Barrett JC, Fry B, Maller J, Daly MJ (2004) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265
19.
Tregouet DA, Barbaux S, Escolano S et al (2002) Specific haplotypes of the P-selectin gene are associated with myocardial infarction. Hum Mol Genet 11:2015–2023CrossRefPubMed
20.
Tregouet DA, Escolano S, Tiret L, Mallet A, Golmard JL (2004) A new algorithm for haplotype-based association analysis: the Stochastic-EM algorithm. Ann Hum Genet 68:165–177
21.
Zaykin DV, Westfall PH, Young SS, Karnoub MA, Wagner MJ, Ehm MG (2002) Testing association of statistically inferred haplotypes with discrete and continuous traits in samples of unrelated individuals. Hum Hered 53:79–91CrossRefPubMed
22.
Excoffier L, Slatkin M (1995) Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population. Mol Biol Evol 12:921–927PubMed
23.
Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68:978–989CrossRefPubMed
24.
Zhao JH, Lissarrague S, Essioux L, Sham PC (2002) Genecounting: haplotype analysis with missing genotypes. Bioinformatics 18:1694–1695
25.
Paul SR, Donner A (1989) A comparison of tests of homogeneity of odds ratios in K 2×2 tables. Stat Med 8:1455–1468
26.
Greenland S (1983) Tests for interaction in epidemiologic studies: a review and a study of power. Stat Med 2:243–251
27.
Jones MP, O’Gorman TW, Lemke JH, Woolson RF (1989) A Monte Carlo investigation of homogeneity tests of the odds ratio under various sample size configurations. Biometrics 45:171–181
28.
Kondo H, Shimomura I, Matsukawa Y et al (2002) Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes 51:2325–2328PubMed
29.
Waki H, Yamauchi T, Kamon J et al (2003) Impaired multimerization of human adiponectin mutants associated with diabetes: molecular structure and multimer formation of adiponectin. J Biol Chem 278:40352–40363CrossRefPubMed
30.
Patel S, Unwin NC, Vasseur F, Froguel P, Walker M (2002) Investigation of the role of the T to G SNP in the adiponectin (APM1) gene in abdominal obesity using parent–offspring trios. Abstract of 38th annual meeting of the EASD. Diabetologia 45:413
31.
Clement K, Hercberg S, Passinge B et al (2000) The Pro115Gln and Pro12Ala PPAR gamma gene mutations in obesity and type 2 diabetes. Int J Obes Relat Metab Disord 24:391–393
32.
Yamamoto Y, Hirose H, Miyashita K et al (2002) PPAR(gamma)2 gene Pro12Ala polymorphism may influence serum level of an adipocyte-derived protein, adiponectin, in the Japanese population. Metabolism 51:1407–1409
33.
Thamer C, Machicao F, Fritsche A, Stumvoll M, Haring H (2003) No influence of the PPARgamma2 Pro12Ala genotype on serum adiponectin concentrations in healthy Europeans. Metabolism 52:798; author reply 798–799
34.
Flegal KM, Carroll MD, Ogden CL, Johnson CL (2002) Prevalence and trends in obesity among US adults, 1999–2000. JAMA 288:1723–1727CrossRefPubMed
Metadata
Title
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
Authors
F. Vasseur
N. Helbecque
S. Lobbens
V. Vasseur-Delannoy
C. Dina
K. Clément
P. Boutin
T. Kadowaki
P. E. Scherer
P. Froguel
Publication date
01-05-2005
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 5/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-005-1729-z

Other articles of this Issue 5/2005

Diabetologia 5/2005 Go to the issue

Article

Insulin sensitivity, proinsulin and insulin as predictors of coronary heart disease. A population-based 10-year, follow-up study in 70-year old men using the euglycaemic insulin clamp

Article

Small intestinal enteropathy in non-obese diabetic mice fed a diet containing wheat

Article

Dynamic change in adiposity from fetal to postnatal life is involved in the metabolic syndrome associated with reduced fetal growth

Article

Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects

Erratum

Comparison of high-fat and high-protein diets with a high-carbohydrate diet in insulin-resistant obese women

Article

Sex differences in cardiovascular and total mortality among diabetic and non-diabetic individuals with or without history of myocardial infarction
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits