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Impaired Insulin Action in Puberty

List of authors.
  • Stephanie A. Amiel, M.B., M.R.C.P. (U.K.),
  • Robert S. Sherwin, M.D.,
  • Donald C. Simonson, M.D.,
  • Albert A. Lauritano, M.S.,
  • and William V. Tamborlane, M.D.

Abstract

Patients with insulin-dependent diabetes mellitus often have poor metabolic control during puberty. To determine whether puberty is associated with decreased insulin-stimulated glucose metabolism, we compared the results of euglycemic insulin-clamp studies in adults and prepubertal and pubertal children with and without insulin-dependent diabetes. In nondiabetic pubertal children, insulin-stimulated glucose metabolism (201±12 mg per square meter of body surface area per minute) was sharply reduced, as compared with that of prepubertal children and adults (316±34 and 290±21 mg per square meter, respectively; P<0.01), despite comparable hyperinsulinemia (insulin levels of 80 to 90 μU per milliliter). Similarly, the response to insulin was 25 to 30 percent lower in the diabetic pubertal children than in the diabetic prepubertal children (P<0.05) and adults (P = 0.07). At each stage of development, the stimulating effect of insulin on glucose metabolism was decreased by 33 to 42 percent in the children with diabetes (P<0.01). In all the groups of children studied, the response to insulin was inversely correlated with mean 24-hour levels of growth hormone (r = -0.52, P = 0.01). Among the diabetic children, the glycosylated hemoglobin levels were substantially higher in the pubertal children than in the prepubertal children (P<0.02), although the daily insulin doses tended to be higher.

These data suggest that insulin resistance occurs during puberty in both normal children and children with diabetes. The combined adverse effects of puberty and diabetes on insulin action may help explain why control of glycemia is so difficult to achieve in adolescent patients. (N Engl J Med 1986; 315:215–9.)

Funding and Disclosures

Supported by grants (AM 20495 and RR 00125) from the National Institutes of Health. Dr. Amiel is the recipient of a Postdoctoral Fellowship from the Juvenile Diabetes Foundation International, and Dr. Simonson is a recipient of a Special Emphasis Research Career Award (AG 00233) from the National Institutes of Health.

We are indebted to the nursing staff of the Children's Clinical Research Center for the excellent care given to the children participating in the study, to the staff of the Core Laboratory of the Clinical Research Centers for their expert technical assistance, and to Sonja Kornienko for preparation of the manuscript.

Author Affiliations

From the Departments of Pediatrics and Medicine and the Clinical Research Centers, Yale University School of Medicine, New Haven, Conn., and Squibb–Novo, Inc., Princeton, N.J. Address reprint requests to Dr. Amiel at the Department of Pediatrics, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06510.

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