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Age-Dependent Nongenetic Influences of Birth Weight and Adult Body Fat on Insulin Sensitivity in Twins

Steno Diabetes Center (R.N.M., L.G.G., E.L.R., C.M., A.V., P.P.), DK-2820 Gentofte, Denmark; and Department of International Health (L.G.G.), University of Copenhagen, DK-2200 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Pernille Poulsen, Steno Diabetes Center, Niels Steensens Vej 1, DK-2820 Gentofte, Denmark. E-mail: pepn{at}novonordisk.com.

Objective: We hypothesized a nongenetic influence of birth weight (BW) and twin and zygosity status on dual-energy x-ray absorptiometry determined adult total and regional body composition and a quantitative equal, although independent, importance of adult body composition and BW for insulin sensitivity.

Design and Methods: This was a clinical study of 110 young (aged 22–31 yr) and 86 elderly twins (aged 57–66 yr) and 32 age-matched controls with measures of BW, adult body composition, and insulin sensitivity.

Results: BW was nongenetically, positively associated with height, weight, and total and regional (trunk, arm, and leg) fat mass and percentages in the young twins. In the elderly twins, BW was persistently nongenetically related to height as well as leg fat mass and percentage. Insulin sensitivity was nongenetically influenced by total fat percentage as well as arm and trunk fat percentages, all leading to a decrease in insulin sensitivity by 20% per SD increase in the elderly twins. Conversely, a SD increase in BW led to an increase of 16% in insulin sensitivity. Total body fat and regional fat was similarly associated with insulin sensitivity in the younger twins, whereas no influence of BW was seen.

Conclusion: BW was nongenetically, positively associated with adult height and total and regional fat mass in an age-dependent manner. BW and total and regional body fat percentages were nongenetically associated with insulin sensitivity in the elderly subjects, supporting an influence of the fetal environment on insulin sensitivity that is quantitatively similar to and independent of the effect of adult adiposity.