Influence of the ACE Gene Insertion/Deletion Polymorphism on Insulin Sensitivity and Impaired Glucose Tolerance in Healthy Subjects
- Fabrice Bonnet, MD, PHD12,
- Sheila Patel, PHD3,
- Martine Laville, MD, PHD2,
- Beverley Balkau, PHD45,
- Angela Favuzzi, MD6,
- Lucilla D. Monti, MD7,
- Nebojsa Lalic, MD8,
- Mark Walker, MD, PHD9 and
- on behalf of the European Group for the Study of Insulin Resistance Relationship Between Insulin Sensitivity and Cardiovascular Disease Risk Study Group
- 1Department of Medicine, Endocrinology Unit, Centre Hospitalier Universitaire (CHU), Université Rennes, Rennes, France
- 2Centre de Recherche en Nutrition Humaine Rhône-Alpes, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de la Recherche Agronomique, Université Lyon, Hospices Civils de Lyon, Lyon, France
- 3Cardiovascular Endocrine Group, Department of Medicine, University of Melbourne, Melbourne, Australia
- 4INSERM U780, Villejuif, France
- 5Universitaire Paris-Sud, Orsay, France
- 6Department of Internal Medicine, Catholic University, “S. Cuore,” Rome, Italy
- 7Diabetology, Endocrinology, and Metabolic Disease Unit, Fondazione Centro San Raffaele del Monte Tabor, Milan, Italy
- 8Institute for Endocrinology, Diabetes, and Metabolic Diseases, University of Belgrade, Belgrade, Serbia
- 9Department of Diabetes, School of Clinical Medical Sciences, University of Newcastle, Newcastle, U.K
- Address correspondence and reprint requests to Dr. Fabrice Bonnet, Department of Endocrinology, CHU Rennes, University of Rennes 1, 35002 Rennes, France. E-mail: fabrice.bonnet{at}chu-rennes.fr
Abstract
OBJECTIVE—Recent studies suggested that the blockade of the renin-angiotensin system (RAS) may be associated with metabolic benefits. However, data about the potential influence of the ACE insertion/deletion (I/D) genotype on insulin resistance have been contradictory with studies of limited sample sizes. The purpose of this study was to investigate the relationship between the ACE gene I/D polymorphism and both insulin sensitivity and glucose intolerance in a large cohort of healthy subjects.
RESEARCH DESIGN AND METHODS—A total of 1,286 participants in the Relationship Between Insulin Sensitivity and Cardiovascular Disease Risk Study had a 75-g oral glucose tolerance test and a hyperinsulinemic-euglycemic clamp to assess whole-body insulin sensitivity.
RESULTS—Age, BMI, waist, fat-free mass (ffm), and physical activity did not differ by ACE genotype. Fasting glucose and insulin were similar among genotypes, but 2-h glucose levels were higher in DD than in ID and II subjects (DD: 5.9 ± 1.7; ID: 5.7 ± 1.5; II: 5.6 ± 1.5 mmol/l) (P = 0.004). Participants with the DD genotype were more likely to have impaired glucose tolerance than those with the ID and II genotypes (13.1 vs. 8.7%; P = 0.02). Insulin sensitivity was lower in participants with the DD genotype than in those with the II genotype (136 ± 63 vs. 147 ± 65 μmol · min−1· kg ffm−1 · mmol−1 · l−1; P = 0.02). The presence of the D allele was associated with a trend, albeit not significant, for reduced insulin secretion during the oral glucose tolerance test (P = 0.07).
CONCLUSIONS—The ACE I/D polymorphism is associated with whole-body insulin sensitivity and with impaired glucose tolerance in our healthy population. These findings confirm potential interactions between the RAS and glucose metabolism.
- I/D, insertion/deletion
- IGT, impaired glucose tolerance
- OGTT, oral glucose tolerance test
- RAS, renin-angiotensin system
- RISC, Relationship Between Insulin Sensitivity and Cardiovascular Disease Risk
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 30 January 2008. DOI: 10.2337/dc07-1788.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
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- Accepted January 4, 2008.
- Received September 12, 2007.
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