Impaired Insulin Action in Puberty

TLDR

Patients with insulin‑dependent diabetes mellitus frequently experience poor metabolic control during puberty. The study aimed to determine whether puberty is linked to reduced insulin‑stimulated glucose metabolism by comparing euglycemic clamp results across adults, prepubertal, and pubertal children with and without insulin‑dependent diabetes. The authors performed euglycemic insulin‑clamp studies in adults and prepubertal and pubertal children, measuring insulin‑stimulated glucose metabolism in both diabetic and non‑diabetic groups. Insulin‑stimulated glucose metabolism is markedly lower in pubertal children—both diabetic and non‑diabetic—compared to prepubertal children and adults, with a 33–42 % reduction in diabetic children, an inverse relationship to growth hormone, higher HbA1c in pubertal diabetics, and overall evidence that puberty induces insulin resistance that complicates glycemic control. N Engl J Med 1986; 315:215–9.

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.)