Progression from Prediabetes to Type 2 Diabetes (T2DM) in 303 Hypogonadal Men With and Without Testosterone Treatment—Eight-Year Real-Life Data from a Registry

Background: Hypogonadism predicts T2DM and is highly prevalent in men with prediabetes.

Methods: Pooled data from 2 ongoing urological registries. 303 men had prediabetes by HbA_1c according to ADA definition. 220 received treatment with 3-monthly injections of testosterone undecanoate (TU; T-group), 83 served as controls (CTRL). Anthropometric and metabolic parameters were measured over 8 years.

Results: Mean follow-up: 6.6 years (T-group), 5.6 years (CTRL). Mean age: 60.6±9.6 years. Under TU, HbA_1c decreased from 5.9±0.2 to 5.5±0.3% at 8 years (p<0.0001). In CTRL, HbA_1c increased from 5.9±0.2 to 6.1±0.6% (p<0.0005). At the last observation, all 220 patients (100%) in the T-group had an HbA_1c <6.5%. In CTRL, 35 men (42.2%) had progressed to T2DM with HbA_1c >6.5% The TyG index, a surrogate parameter for insulin resistance, decreased in the T-group from 9.3±0.4 to 9.0±0.4 at 8 years. In CTRL, the index increased from 8.9±0.6 to 9.3±0.4 at 8 years. At baseline, 158 men (52.1%) were obese, 126 men (41.6%) were overweight and 19 (6.3%) had normal weight. Weight decreased from 96.7±12.3 to 89.0±9.6 kg in the T-group and increased from 92.9±10.4 to 98.2±6.3 kg in CTRL. Waist circumference decreased from 104.2±7.1 to 98.2±6.5 cm in the T-group and increased from 102.5±9.7 to 106±3.2 cm in CTRL. Weight loss was 9.2±8.3% at 8 years in the T-group. In CTRL, weight increased by 9.2±3.9% at 8 years (p<0.0001 for all). Adherence to TU was 100 per cent as all injections were performed and documented in the office.

Conclusion: Testosterone therapy prevented progression from prediabetes to T2DM in hypogonadal men while more than 40% of untreated hypogonadal men developed T2DM. This effect may have been supported by sustained weight loss and been mediated by the invariable increase in lean mass achieved by testosterone.