Plasma glucose, insulin, and glucagon before and after long-term overfeeding in identical twins

Plasma glucose, insulin, and glucagon levels were measured before and after long-term overfeeding (4.2 MJ/d during a 100-day period) in 24 lean adults (12 pairs of monozygotic twins). Fasting plasma glucose, insulin, and glucagon were significantly increased by overfeeding. During a 75-g oral glucose tolerance test (OGTT), no major alteration in glucose tolerance was observed and insulin area under the curve was increased. During a meal test, insulin and glucagon areas under the curve were increased. The pre-overfeeding values for glucose, insulin, and glucagon (fasting and areas) were not correlated with the gains in body weight and in fat mass. However, fasting glucagon before overfeeding was positively correlated with the gains in abdominal visceral fat and in femoral fat. The changes with overfeeding in insulin area during the OGTT were positively correlated with the changes in total subcutaneous fat, even after adjustment for total body fat gain. Significant twin intrapair similarity was observed for fasting plasma glucagon before overfeeding and for the changes in fasting insulin and glucagon with overfeeding. These results indicate that (1) in response to long-term overfeeding, both fasting insulin and glucagon are increased; (2) initial levels of glucose, insulin, and glucagon do not predict the gains in body weight and total body fat during overfeeding, but are related to changes in indicators of fat topography; (3) the changes in total subcutaneous fat represent an important correlate of insulin changes with overfeeding; and (4) the genotype could be an important determinant of insulin and glucagon responses to a prolonged positive-energy-balance period.