Carbohydrate Intolerance in Gonadal Dysgenesis: Evidence for Insulin Resistance and Hyperglucagonemia

Abstract

To determine the pathogenesis of carbohydrate intolerance associated with gonadal dysgenesis, plasma glucose, insulin, glucagon, and growth hormone responses to oral glucose and intravenous tolbutamide, arginine and insulin were evaluated in 21 nonobese patients, 7–19 years old. Glucose intolerance was present in 9 of 21 nonobese patients (42.8%). Insulin levels, the area under the insulin curve after oral glucose and intravenous tolbutamide and the insulin to glucose ratio were significantly greater in patients than in controls (p < 0.005). The decrease in plasma glucose following intravenous tolbutamide was significantly less in patients than in controls (p < 0.05) despite insulin levels which were greater than in controls (p < 0.05). After intravenous insulin, plasma glucose fell significantly less in patients than in controls (p < 0.01). Plasma glucagon levels and the area under the glucagon curve after oral glucose and arginine infusion were significantly greater in patients than in controls (p < 0.005 and p < 0.01, respectively). The increase in glucagon after insulin-induced hypoglycemia was significantly less in patients than in controls (p < 0.025). Fasting and stimulated growth hormone levels and the mean 24-hour growth hormone concentration were similar in patients and controls. These results indicate that glucose intolerance occurs frequently in gonadal dysgenesis and is associated with normal or increased insulin secretory responses. These abnormalities are probably due to insulin resistance and hyperglucagonemia. The decrease in insulin action does not appear to result from excessive growth hormone secretion or treatment with anabolic steroids or estrogen-progesterone medications.

Recombinant Human Growth Hormone and Oxandrolone in Treatment of Short Stature in Girls with Turner Syndrome

“…impaired carbohydrate tolerance is frequently observed, the incidence has previously been reported as 26-43% [29][30][31]. This is due to a combination of inadequate insulin release and resistance to insulin at least in part due to disturbed intestinal glucoregulation [30][31][32][33].…”

“…Initially, hyperinsulinism is present followed by a decrease in (Tcell reserve, and. finally, beyond the third decade of life, overt diabetes mellitus occurs in 15% of women with TS [31,32,34], Both GH and anabolic steroids affect carbohydrate metabolism. GH has been shown to antagonize insulin actions and in normal people may lead to increased blood glucose and insulin levels associated with impaired glu cose utilization [35][36][37].…”

Medical Problems of Adult Turner’s Syndrome

“…This suggests defective suppression of the Randle cycle, perhaps mediated in part by the inappropriately low level of insulin [20]. Several studies have found a positive family history of type 2 diabetes, with an unusually high frequency, but this does not seem to explain the observed glucose intolerance, since Turner’s patients with a negative family history also exhibit these characteristics [19, 21, 22, 23]. Intervention studies in postmenopausal women have shown that transdermal 17β-oestradiol exerts either moderately positive effects on glucose metabolism [24]or no effect at all [25].…”

Effect of Growth Hormone and Oxandrolone Treatment on Glucose Metabolism in Turner Syndrome

“…Girls with TS have an even higher incidence of impaired glucose tolerance [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12]and, therefore, an increased risk of developing diabetes mellitus in adulthood [2, 3, 5, 6, 13]. Stoppoloni et al [14]showed an increase in insulin resistance in 4 patients with TS (age 13–21 years) using an euglycaemic hyperinsulinaemic glucose clamp technique.…”