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The Effects of the ACE Gene Insertion/Deletion Polymorphism on Glucose Tolerance and Insulin Secretion in Elderly People Are Modified by Birth Weight

National Public Health Institute (E.K., H.Y., T.F., J.E.), 00300 Helsinki, Finland; Hospital for Children and Adolescents (E.K., S.A.), Helsinki University Central Hospital, 00029 HUS, Helsinki, Finland; Finnish Genome Centre (A.R., J.K.), University of Helsinki, Helsinki, Finland; Department of Biosciences at Novum and Clinical Research Centre (J.K.), Karolinska Institute, 141 86 Stockholm, Sweden; and Medical Research Council Environmental Epidemiology Unit (E.K., C.O., D.J.P.B.), Southampton General Hospital, Southampton SO16 6YD, United Kingdom

Address all correspondence and requests for reprints to: Dr. Eero Kajantie, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland. E-mail: eero.kajantie{at}helsinki.fi.

The I allele of an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) appears to be protective against the complications of type 2 diabetes. Low birth weight, a marker of an adverse intrauterine environment, is associated with higher rates of type 2 diabetes. We examined whether the ACE I/D polymorphism could explain or modify the association between low birth weight and adulthood glucose tolerance.

We measured plasma glucose and insulin concentrations after an oral glucose challenge in a group of 423 men and women, ages 65–75 yr, with measurements at birth recorded. The presence of the I allele was associated with shorter duration of gestation (P = 0.006) and, relative to gestational age, higher birth weight (P = 0.008) and length (P = 0.02). The I allele was associated with lower glucose at 120 min (P = 0.04) and a greater insulin response (P = 0.03 for insulin at 30 min and P = 0.06 for insulin area under the curve) to a standard oral glucose tolerance test. However, the associations between the ACE genotype and adulthood insulin secretion were only present in people with low birth weight (P for interaction birth weight _* ACE genotype on insulin at 30 min = 0.003 and on insulin area under the curve = 0.05).

The ACE I allele is associated with shorter duration of gestation and higher birth weight. The association between the presence of the ACE I allele and increased indices of adult insulin secretion is confined to subjects with low birth weight. We suggest that these findings reflect interactions between genotype and intrauterine environment with resulting changes in gene expression.

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