Effects of intraperitoneal insulin versus subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus

Aims: Elevated sex hormone-binding globulin (SHBG) concentrations have been described in patients with type 1 diabetes mellitus (T1DM), probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII), or subcutaneous (SC), influences SHBG concentrations among T1DM patients. Methods: Post hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (+/- 13) years, diabetes duration 23 (+/- 11) years, and hemoglobin A1c (HbA1c) 8.7 (+/- 1.1) (72 (+/- 12) mmol/mol). As secondary outcomes, testosterone, 17-beta-estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were analyzed. Results: Estimated mean change in SHBG was -10.3 nmol/L (95% CI: -17.4, -3.2) during CIPII and 3.7 nmol/L (95% CI: -12.0, 4.6) during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was -6.6 nmol/L (95% CI: -17.5, 4.3); -12.7 nmol/L (95% CI: -25.1, -0.4) for males and -1.7 nmol/L (95% CI: -24.6, 21.1) for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; -15.8 nmol/L (95% CI: -24.2, -7.5) and -8.3 nmol/L (95% CI: -14.4, -2.2), respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2 U/L (95% CI: 0.1, 2.2) among males. Conclusions: SHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids.