Influence of the ACE gene insertion/deletion polymorphism on insulin sensitivity and impaired glucose tolerance in healthy subjects

Fabrice Bonnet, Sheila Patel, Martine Laville, Beverley Balkau, Angela Favuzzi, Lucilla D. Monti, Nebojsa Lalic, Mark Walker

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 [xmol · 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.

Original languageEnglish
Pages (from-to)789-794
Number of pages6
JournalDiabetes Care
Volume31
Issue number4
DOIs
Publication statusPublished - Apr 2008

Fingerprint

Glucose Intolerance
Insertional Mutagenesis
Gene Deletion
Insulin Resistance
Healthy Volunteers
Genotype
Renin-Angiotensin System
Glucose Tolerance Test
Glucose
Fats
Insulin
Glucose Clamp Technique
Sample Size
Fasting
Research Design
Cardiovascular Diseases
Alleles
Exercise
Population

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing

Cite this

Influence of the ACE gene insertion/deletion polymorphism on insulin sensitivity and impaired glucose tolerance in healthy subjects. / Bonnet, Fabrice; Patel, Sheila; Laville, Martine; Balkau, Beverley; Favuzzi, Angela; Monti, Lucilla D.; Lalic, Nebojsa; Walker, Mark.

In: Diabetes Care, Vol. 31, No. 4, 04.2008, p. 789-794.

Research output: Contribution to journalArticle

Bonnet, Fabrice ; Patel, Sheila ; Laville, Martine ; Balkau, Beverley ; Favuzzi, Angela ; Monti, Lucilla D. ; Lalic, Nebojsa ; Walker, Mark. / Influence of the ACE gene insertion/deletion polymorphism on insulin sensitivity and impaired glucose tolerance in healthy subjects. In: Diabetes Care. 2008 ; Vol. 31, No. 4. pp. 789-794.
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N2 - 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 [xmol · 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.

AB - 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 [xmol · 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.

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