The Effect of Testosterone Supplement on Insulin Sensitivity, Glucose Effectiveness, and Acute Insulin Response After Glucose Load in Male Type 2 Diabetics

Abstract

Our understanding of the effect of androgens on insulin action and glucose metabolism is incomplete. Several different models and methods have been used to study androgen effects, with some studies indicating that higher testosterone levels are associated with increased insulin resistance. In polycystic ovary syndrome, where high testosterone levels are frequently found, affected patients have a higher risk of diabetes. In contrast, increased insulin resistance was found in both hypergonadotropic and hypogonadotropic men with hypoandrogenism, patients with Klinefelter's syndrome and men with idiopathic gonadotropin deficiency. Insulin resistance is considered to be one of the cornerstones in the state that ultimately leads to clinically established type 2 diabetes mellitus. In addition, men with type 2 diabetes have relative hypogonadism. Therefore, supplementation with testosterone might play a role in improving both insulin resistance and hypogonadism. The study population consisted of 11 male patients with type 2 diabetes. Their mean age was 57.7 +/- 3.41 years, the body mass index (BMI) was 24.4 +/- 1.02 kg/m2, and the waist-to-hip ratio (W/H) was 0.91 +/- 0.05. The patients were all treated with oral hypoglycemic agents. The men received androgen injections every 3 weeks intramuscularly for 12 weeks. The injections were testosterone depot 100 mg/3 weeks. Insulin sensitivity, glucose effectiveness and area under acute insulin response were calculated from "minimal model" algorithms. There were no significant differences in the value of BMI, W/H ratios, plasma lipid concentrations, testosterone, homeostasis model assessment (HOMA) of insulin sensitivity, and beta-cell function, before and after supplementation of testosterone. Furthermore, the insulin sensitivity (SI) (1.04 +/- 0.25, 1.11 +/- 0.36 x 10(-5) min(-1/)pM; p = 0.43), glucose effectiveness (EG) (0.018 +/- 0.003, 0.017 +/- 0.002 min(-1); p = 0.29), and acute insulin response (AIR) after a glucose load (45.7 +/- 24.3, 50.1 +/- 32.5 pM; p = 0.45) did not change significantly after supplmentation with testosterone. In our study, there was no improvement of SI, EG, and AIR after 3 months of Testosterone Depot treatment in type 2 diabetes, but we believe that duration and dosage of the androgen therapy might play an important role in improving insulin sensitivity. The mechanisms by which testosterone causes insulin resistance is unknown, and larger studies on androgen treatment in type 2 diabetic patients are necessary.

Testosterone deficiency impairs glucose oxidation through defective insulin and its receptor gene expression in target tissues of adult male rats

“…Testosterone, an anabolic steroid, plays an important role in this direction (Lemoine et al, 2002;Livingstone and Collison, 2002;Boyanov et al, 2003;Tsai et al, 2004;Mayes and Watson, 2004;Inaba et al, 2005;Lee et al, 2005). Therefore, metabolic activities of tissues are likely to change with experimental or pathological manipulation of hormones (Mainwaring and Mangan, 1973).…”

The role of testosterone in type 2 diabetes and metabolic syndrome in men

“…A study in hypogonadal men with type 2 diabetes has shown that testosterone replacement also improves glycemic control, although this study was non-blinded (14). By contrast, two studies replacing testosterone in men with type 2 diabetes and hypogonadism found little or no effect on glycemic control (15,16), but a more recent study analyzing the effects of testosterone administration to 24 hypogonadal men (10 treated with insulin) older than 30 years old with type 2 diabetes found that testosterone replacement therapy reduced insulin resistance (as measured by homeostatic model index) and improved glycemic control in hypogonadal men with type 2 diabetes (17). A recent study in newly diagnosed men showed convincingly that addition of testosterone to a regimen of diet and exercise produced significantly better results than diet and exercise on glycemic control and reversal of the metabolic syndrome (13).…”

Testosterone for the aging male; current evidence and recommended practice

“…In contrast, an uncontrolled study of 150 mg intramuscular testosterone given to 10 patients, average age 64 years, with diabetes and hypogonadism found no signifi cant change in diabetes control, fasting glucose or insulin levels (Corrales et al 2004). Another uncontrolled study showed no benefi cial effect of testosterone treatment on insulin resistance, measured by HOMA and 'minimal model' of area under acute insulin response curves, in 11 patients with type 2 diabetes aged between 33 and 73 years (Lee et al 2005). Body mass index was within the normal range in this population and there was no change in waist-hip ratio or weight during testosterone treatment.…”