Sex Hormone Binding Globulin Reflects Chronic Insulin Exposure in Children and Young Adults with and without Diabetes.

Danielson, Kirstie K.; Drum, Melinda L.; Hampton, Latrisha; Lipton, Rebecca B.

Sex hormone binding globulin (SHBG) is down-regulated by insulin, and is an important determinant of sex hormone bioavailability. The effects of diabetes and of insulin resistance in nondiabetics on SHBG, particularly in children and young adults, are poorly understood. These questions were addressed using data on individuals with diabetes diagnosed <18 years of age (n=38) and nondiabetic siblings (n=37) from the Chicago Childhood Diabetes Registry Family Study. Fasting blood was collected to measure SHBG (≥ 10 years of age), glucose, insulin, and C-peptide. Percent body fat, BMI, and demographic and diabetes characteristics were also obtained. Insulin resistance was determined by calculating HOMA2-IR for the nondiabetic siblings. The sample included Non-Hispanic white (37%) and black (40%), Hispanic (10%), and other (13%) race/ethnicities, and mean age was 16 years (10-32 years). The diabetes sample included type 1 (71%), type 2 (9%), and mixed (20%) diabetes, and all were treated with insulin, with 64, 33, and 29%, respectively, using intensive insulin therapy (≥3 injections/day or pump). Mean onset age was 9 years (0-14 years) and mean HbA1c was 8% (4-13%). No nondiabetic sibling had an HbA1c >6% or met criteria for insulin resistance. SHBG levels did not vary by diabetes type and types were therefore combined. In regression analysis, accounting for family clustering and adjusting for age, gender, percent body fat, and BMI z-score, SHBG was higher in individuals with diabetes than in nondiabetic siblings (p<0.001). SHBG did not differ by race/ethnicity. In similar analyses stratified by diabetes status, the presence of C-peptide in those with diabetes for ≥2 years was associated with lower SHBG (ng/dL) than no detectable C-peptide (β=-10.7, p<0.01, r²=0.82). This association did not differ by diabetes type. Fasting insulin, intensity of insulin treatment, HbA1c, and duration were not associated with SHBG. In the nondiabetic siblings, HOMA2-IR was negatively associated with SHBG (β=-9.3, p<0.05, r²=0.41). Fasting insulin and C-peptide were not associated with SHBG. SHBG therefore appears to reflect chronic insulin exposure: endogenous insulin production with diabetes, and insulin resistance with normal beta-cell function. The effects of altered insulin levels inherent to diabetes and insulin resistance on the bioavailability of sex hormones and sex hormone-dependent processes in children and young adults now need to be determined.

GLOBULINS; SEX hormones; INSULIN resistance; DIABETES in children; DIABETES in adolescence; DIABETES complications

Diabetes, 2007, Vol 56, pA265

0012-1797

Academic Journal