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


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 micromol x min(-1)x kg ffm(-1) x mmol(-1) x 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.
Bonnet
Fabrice
F
Department of Medicine, Endocrinology Unit, Centre Hospitalier Universitaire, Université Rennes, Rennes, France. fabrice.bonnet@chu-rennes.fr
Patel
Sheila
S
Laville
Martine
M
Balkau
Beverley
B
Favuzzi
Angela
A
Monti
Lucilla D
LD
Lalic
Nebojsa
N
Walker
Mark
M
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D004251:DNA Transposable Elements; D005260:Female; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics*; D008019:Life Style; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012016:Reference Values; D017384:Sequence Deletion
D001786:Blood Glucose; D004251:DNA Transposable Elements; D007328:Insulin; D007703:Peptidyl-Dipeptidase A