Androgens and insulin resistance in type 1 diabetic men

In healthy men, both high and low serum testosterone concentrations are associated with insulin resistance, whereas low concentration of sex hormone binding globulin (SHBG) is related to reduced insulin sensitivity. The aim of our study was to examine the association of sex hormones, SHBG, dehydroepiandrosterone (DHEAS) and insulin-like growth factor binding protein-1 (IGFBP-1) on insulin sensitivity in type 1 diabetic patients.

We examined 23 male patients with the mean age of 29 +/- 1 years, body mass index 22.9 +/- 0.4 kg/m2, insulin dose 47 +/- 3 units/day, glycosylated haemoglobin (HbA1c) 7.8 +/- 0.3% and duration of diabetes 13 +/- 1 years.

Each patient was studied with a 4-hour euglycaemic (5.5 +/- 0.1 mmol/l), hyperinsulinaemic (612 +/- 26 pmol/l) clamp with indirect calorimetry. Muscle biopsies (quadriceps femoris) for the determination of glycogen synthase were performed in 15 patients before and at the end of the clamp.

Insulin infusion reduced the concentrations of IGFBP-1 by 90% (P < 0.001), DHEAS by 11% (P < 0.001), and SHBG by 4% (P < 0.01), whereas free or bound testosterone levels remained unchanged. The fall in IGFBP-1 level was closely related to the basal concentration (r = 0.99, P < 0.001). Basal SHBG concentration correlated directly with total (r = 0.51, P < 0.05) and non-oxidative glucose disposal (r = 0.41, P < 0.05), and with the decrease in lipid oxidation (r = 0.47, P < 0.05) during insulin infusion. The fall in SHBG was inversely related to the mean (30-240 min) FFA concentration during hyperinsulinaemia (r = -0.64, P < 0.001). The fractional activity of glycogen synthase at the end of insulin infusion correlated directly with fasting SHBG (r = 0.71, P < 0.01) and DHEAS concentrations (r = 0.67, P < 0.01).

In male type 1 diabetic patients: (1) acute hyperinsulinaemia decreases IGFBP-1, DHEAS and SHBG concentrations with the greatest decline in IGFBP-1, (2) SHBG concentration is positively associated with factors indicating good insulin sensitivity, (3) association between fuel homeostasis and SHBG, DHEAS and insulin antagonists suggests a network of these factors in the regulation of insulin action in type 1 diabetic patients.