Testosterone concentration and insulin sensitivity in young men with type 1 and type 2 diabetes

Abstract

Objective Reduced testosterone, a recognized comorbidity of reduced insulin sensitivity (IS) and type 2 diabetes (T2D), has also been reported in adult males with type 1 diabetes (T1D). However, there are limited data on how early reduced testosterone occurs, and whether it is related to the reduced IS in T1D. Leptin, a modulator of the HPG-axis, may also influence testosterone in T1D. We hypothesized that IS and leptin would be associated with total testosterone (TT), and free androgen index (FAI) in adolescent males with T1D. Methods T1D (n=35), T2D (n=13), lean (n=13) and obese (n=9) adolescent males had IS measured by hyperinsulinemic-euglycemic clamps (glucose infusion rate [GIR]), in addition to leptin, SHBG, TT, and FAI. The cohort was stratified into those with T1D (n=35) and those without (n=35). Results TT and SHBG were lower in T2D boys vs. lean controls, and GIR and leptin correlated with FAI and TT in non-T1D participants. However, despite being insulin resistant, adolescent males with T1D had normal TT and FAI, unrelated to GIR. In T1D, leptin was inversely associated with TT (p=0.005) and FAI (p=0.01), independent of puberty, HbA1c, diabetes duration, BMI z-score and GIR. Conclusion Leptin accounted for a significant proportion of the variability of testosterone in T1D. However, despite reduced IS, there was no association between IS and testosterone in T1D adolescents. These observations suggest that the mechanisms affecting testosterone may differ between adolescent males with and without T1D.

Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet

“…Previous evidence demonstrated that low serum T concentrations and poor semen quality were associated with visceral obesity [7,16], IR, and type 2 diabetes [17,18]. Additionally, obesity can cause and aggravate IR.…”

Insulin Pump Therapy – Influence on Body Fat Redistribution, Skeletal Muscle Mass and Ghrelin, Leptin Changes in T1D Patients

“…It has been reported that testosterone induces meal free fatty acid (FFA) uptake preferentially into abdominal subcutaneous adipose tissue (SAT) resulting in a decreased uptake in visceral adipose tissue (VAT) [24]. The biological effect of testosterone is most likely enhanced by decreasing leptin levels, and an inverse correlation between leptin levels and testosterone was reported by Kelsey et al [25]. Even though we did not measure testosterone levels, we assume that decreasing leptin levels contributed to a decrease of visceral fat and an increase of subcutaneous skinfold thickness in the trunk area induced by testosterone.…”

RAS and sex differences in diabetic nephropathy

“…In some studies, men with T1DM do not appear to have a high prevalence of androgen deficiency (45,52). However, Maric et al demonstrated that diabetes without renal disease was associated with decreased testosterone and estrogen levels compared with healthy nondiabetic adult men.…”

“…Poor glycemic control in Korean men with T2DM resulted in increased levels of fasting plasma glucose and HbA 1c values, the major markers of diabetes, which appeared to be associated with testosterone deficiency (53). In addition, diabetic men had also lower levels of sex hormonebinding globulin (SHBG) compared with nondiabetic men (10,52). In fact, several prospective studies have shown that diabetes and metabolic syndrome are more strongly predicted by low SHBG than by low testosterone (41,55,128).…”