Influence of the ACE Gene Insertion/Deletion Polymorphism on Insulin Sensitivity and Impaired Glucose Tolerance in Healthy Subjects

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 Ϯ 1.7; ID: 5.7 Ϯ 1.5; II: 5.6 Ϯ 1.5 mmol/l) (P ϭ 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 ϭ 0.02). Insulin sensitivity was lower in participants with the DD genotype than in those with the II genotype (136 Ϯ 63 vs. 147 Ϯ 65 mol ⅐ min Ϫ1 ⅐ kg ffm Ϫ1 ⅐ mmol Ϫ1 ⅐ l Ϫ1 ; P ϭ 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 ϭ 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. Diabetes Care 31:789-794, 2008

Association of angiotensin-converting enzyme (ACE) and fatty acid binding protein 2 (FABP2) genes polymorphism with type 2 diabetes mellitus in Northern India

“…24 On the other hand, D allele was associated with a reduction in insulin secretion. 24,25 (2002) reported a strong association of the I/I genotype with insulin resistance in T2DM patients. 35 Our data also showed a stronger association of the I/I genotype in T2DM patients.…”

“…Bonnet (2008) reported in healthy subjects that the D allele conferred an increased risk of having glucose tolerance by decreasing insulin sensitivity. 24 On the other hand, D allele was associated with a reduction in insulin secretion. 24,25 (2002) reported a strong association of the I/I genotype with insulin resistance in T2DM patients.…”

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“…A common variant of the ACE (kininase II), gene associated with high ACE levels and presumably reduced concentrations of kinins, has been linked to the risk of insulin resistance in a large cohort, but angiotensin may be also involved in this effect (Bonnet et al 2008). Promoter variations in the B2 receptor gene have been linked to risk of insulin resistance or diabetes in smaller populations (Fallo et al 2004, Alvim Rde et al 2012.…”