Cited by 371Adipokines, Inflammation, and Metabolic DiseasesGenetic Associations and EpidemiologyAdipose Tissue and Metabolism

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Association of the T-G Polymorphism in Adiponectin (Exon 2) With Obesity and Insulin Sensitivity

Stumvoll, Michael, Tschritter, Otto, Fritsche, Andreas, Staiger, Harald, Renn, Walter, Weisser, Melanie, Machicao, Fausto, Häring, Hans·2002·Diabetes

DOI 10.2337/diabetes.51.1.37

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Abstract

The adipocyte-derived hormone adiponectin seems to protect from insulin resistance, a key factor in the pathogenesis of type 2 diabetes. Genome-wide scans have mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. A common silent T-G exchange in nucleotide 94 (exon 2) of the adiponectin gene has been associated with increased circulating adiponectin levels. Metabolic abnormalities associated with the G allele have not been reported. We therefore assessed whether this polymorphism alters insulin sensitivity and/or measures of obesity using the Tübingen Family Study database (prevalence of the G allele, 28%). In 371 nondiabetic individuals, we found a significantly greater BMI in GG + GT (25.5 ± 0.7 kg/m2) compared with TT (24.1 ± 0.3 kg/m2; P = 0.02). Insulin sensitivity (determined by euglycemic clamp, n = 209) was significantly lower in GG + GT (0.089 ± 0.007 units) compared with TT (0.112 ± 0.005 units; P = 0.02). This difference disappeared completely on adjustment for BMI. Because our population contains a relatively high proportion of first-degree relatives of patients with type 2 diabetes, we stratified by family history (FHD). Much to our surprise, the genotype differences in BMI and insulin sensitivity in the whole population were attributable entirely to differences in the subgroup without FHD, whereas in the subgroup with FHD, the G allele had absolutely no effect. Moreover, individuals without FHD had a significantly lower BMI than individuals with FHD (25.2 ± 0.4 vs. 26.2 ± 0.5 kg/m2; P = 0.01), which was not the case for the GG + GT subgroup without FHD (27.0 ± 0.9 kg/m2; NS). This suggests that in individuals without familial predisposition for type 2 diabetes, the adiponectin polymorphism may mildly increase the obesity risk (and secondarily insulin resistance). In contrast, in individuals who are already burdened by other genetic factors, this small effect may be very hard to detect.

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Association of Adiponectin Level and Variants in the Adiponectin Gene with Glucose Metabolism, Energy Expenditure, and Cytokines in Offspring of Type 2 Diabetic Patients
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Authors: Stumvoll, M., Tschritter, O., Fritsche, A., Staiger, H., Renn, W., Weisser, M., Machicao, F., & Häring, H.
Affiliations: Medizinische Klinik, Abteilung für Endokrinologie, Stoffwechsel und Pathobiochemie, Eberhard-Karls-Universität, Tübingen, Germany
University of Tübingen (DE)
ORCID: Fritsche, Andreas
Staiger, Harald
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2002-01-01
Volume: 51
Issue: 1
Pages: 37-41
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.51.1.37
OpenAlex: W2106550052
Cited by: 371
References: 16
Citations by year: 2026: 2 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 9 · 2020: 6 · 2019: 8 · 2018: 8 · 2017: 11 · 2016: 14 · 2015: 14 · 2014: 18 · 2013: 17 · 2012: 14
FWCI: 24.00
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords: adiponectin, exon 2, obesity, insulin sensitivity, insulin resistance, type 2 diabetes risk, family history of diabetes, body mass index, chromosome 3q27, genetic association
MeSH terms: Adult, Alleles, Blood Glucose, Body Composition, Chromosome Mapping, Chromosomes, Human, Pair 3, Diabetes Mellitus, Type 2, Exons, Female, Glucose Tolerance Test, Humans, Insulin, Male, Obesity, Polymorphism, Genetic, Proteins, Reference Values, Body Mass Index, Adipocytes, Intercellular Signaling Peptides and Proteins, Adiponectin

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Association of the T-G Polymorphism in Adiponectin (Exon 2) With Obesity and Insulin Sensitivity

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