Premature Birth and Later Insulin Resistance

Paul L. Hofman, M.B., Ch.B., Fiona Regan, M.B., B.S., Wendy E. Jackson, M.B., Ch.B., Craig Jefferies, M.B., Ch.B., David B. Knight, M.B., B.S., Elizabeth M. Robinson, M.Sc., and Wayne S. Cutfield, M.D.

ABSTRACT

Background 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.

Methods 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.

Results 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, 2153 to 2432]; 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).

Conclusions 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.