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Glucose Metabolism in Identical Twins Discordant for Obesity. The Critical Role of Visceral Fat¹

Departments of Medicine (T.R.), Public Health (Ma.K.), and Diagnostic Radiology (T.K.), University of Turku, FIN-20520 Turku, Finland; Research and Development Centre (J.M., Me.K.), Social Insurance Institution, FIN-20720, Turku, Finland; Department of Human Molecular Genetics (A.J.), National Public Health Institute and Department of Forensic Medicine, University of Helsinki, FIN-00300 Helsinki, Finland; Department of Psychiatry, Helsinki University Central Hospital (A.R.), FIN-00180 Helsinki, Finland; Physical Activity Sciences Laboratory (C.B.), Laval University, Quebec G1K 7PH, Canada; and Department of Public Health (J.K.), University of Helsinki, FIN-00014 Helsinki, Finland

Address all correspondence and requests for reprints to: Dr. Tapani Rönnemaa, Department of Medicine, University of Turku, FIN-20520 Turku, Finland.

Obesity, especially intraabdominally deposited fatness, is associated with reduced insulin sensitivity. However, it is not well established whether this association is confounded by genetic factors. We studied 23 monozygous twin pairs (14 female, 9 male), 33–59 yr old, who had, on the average, 18 kg intrapair difference in body weight. A 75-g oral glucose tolerance test with glucose and insulin measurements at 30-min intervals was performed, and fat distribution was determined with magnetic resonance imaging. The pairs were divided into two groups by the gender-specific median of the abdominal visceral fat area (AVF) in the obese co-twins. In the high-AVF pairs, the mean area under curve (AUC) for glucose (mmol x min/L) was 758 vs. 968 (P = 0.001), AUC for insulin (mU x min/L) was 4320 vs. 8741 (P = 0.001), and insulin sensitivity index (mg x L x L/mmol x mU x min) was 71.5 vs. 45.9 (P < 0.001) in the lean and obese co-twins, respectively. In the low AVF pairs, the mean AUC for glucose was 669 vs. 706 (not significant), AUC for insulin was 3323 vs. 4241 (not significant), and the sensitivity index was 85.2 vs. 73.7 (P = 0.04) in the lean and obese co-twins, respectively. In subjects who are genetically identical but who are discordant for body mass, only those who differ most in visceral fat level are characterized by major alterations in insulin sensitivity and glucose tolerance.

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