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Peripheral insulin-like factor 3 concentrations are reduced in men with type 2 diabetes mellitus: effect of glycemic control and visceral adiposity on Leydig cell function

¹ Endocrinology and Diabetology Unit, Department of Medical-Surgical Sciences, Università degli Studi di Milano, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milano, Italy² Endocrine Unit, Department of Medical Sciences, IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, 20122 Milan, Italy³ Endocrinology Unit, Department of Medical Sciences, S. Giuseppe Hospital of Milan, Università degli Studi di Milano, 20123 Milan, Italy

(Correspondence should be addressed to S Corbetta; Email: sabrina.corbetta{at}unimi.it)

Background and aim: Hypogonadism frequently occurs in men with type 2 diabetes mellitus (T2DM), while the role of glycemic control and visceral obesity is still unclear. This study aimed to assess the Leydig cell function, including the new sensitive marker insulin-like factor 3 (INSL3), in T2DM patients without overt hypogonadism and the influence of either glycemic control or visceral adiposity.

Subjects and methods: Thirty T2DM patients (age 57.1±6.2 years, body mass index (BMI) 28.0±4.3) without overt hypogonadism and 30 age- and BMI-matched controls were studied. Anthropometric, glycometabolic parameters and testosterone, SHBG, LH, INSL3 levels, bioavailable and free testosterone (BT and cFT) were evaluated. The human chorionic gonadotrophin (hCG) test was also performed.

Results: Patients had lower total testosterone (452.6±130.0 vs 512.6±117.3 ng/dl, P=0.06), BT (189.7±36.4 vs 237.1±94.1 ng/dl, P=0.002), cFT (8.1±1.6 vs 10.1±4.0 ng/dl, P=0.002), and higher LH levels (3.5±1.6 vs 2.6±1.2 mU/ml, P=0.01) versus controls. Serum INSL3 concentrations were also lower in patients (1.1±0.3 vs 1.5±0.7 ng/ml, P=0.01). These hormonal parameters, including INSL3, did not differ between T2DM patients with poor or good glycemic control (HbA1c>9 or <7% respectively). In patients, waist circumferences (97.9±12.4 cm) negatively correlated with INSL3 (P=0.03) and basal, as well as hCG-stimulated testosterone levels (P=0.04 and 0.004 respectively). Basal or stimulated hormonal levels and INSL3 concentrations were not different between patients with (40%) or without erectile dysfunction.

Conclusions: An early impairment of the overall Leydig cell function is present in men with T2DM, mainly related to visceral adiposity rather than to glycemic control.