Term infants who are small for gestational age appear prone to the development of insulin resistance during childhood. We hypothesized that insulin resistance, a marker of type 2 diabetes mellitus, would be prevalent among children who had been born prematurely, irrespective of whether they were appropriate for gestational age or small for gestational age. Seventy-two healthy prepubertal children 4 to 10 years of age were studied: 50 who had been born prematurely (32 weeks' gestation or less), including 38 with a birth weight that was appropriate for gestational age (above the 10th percentile) and 12 with a birth weight that was low (i.e., who were small) for gestational age, and 22 control subjects (at least 37 weeks' gestation, with a birth weight above the 10th percentile). Insulin sensitivity was measured with the use of paired insulin and glucose data obtained by frequent measurements during intravenous glucose-tolerance tests. Children who had been born prematurely, whether their weight was appropriate or low for gestational age, had an isolated reduction in insulin sensitivity as compared with controls (appropriate-for-gestational-age group, 14.2x10(-4) per minute per milliunit per liter [95 percent confidence interval, 11.5 to 16.2]; small-for-gestational-age group, 12.9x10(-4) per minute per milliunit per liter [95 percent confidence interval, 9.7 to 17.4]; and control group, 21.6x10(-4) per minute per milliunit per liter [95 percent confidence interval, 17.1 to 27.4]; P=0.002). There were no significant differences in insulin sensitivity between the two premature groups (P=0.80). As compared with controls, both groups of premature children had a compensatory increase in acute insulin release (appropriate-for-gestational-age group, 2002 pmol per liter [95 percent confidence interval, 1434 to 2432] [corrected]; small-for-gestational-age group, 2253 pmol per liter [95 percent confidence interval, 1622 to 3128]; and control group, 1148 pmol per liter [95 percent confidence interval, 875 to 1500]; P<0.001). Like children who were born at term but who were small for gestational age, children who were born prematurely have an isolated reduction in insulin sensitivity, which may be a risk factor for type 2 diabetes mellitus. Copyright 2004 Massachusetts Medical Society.