The Dark Side Of Testosterone Deficiency: Type 2 Diabetes And Insulin Resistance

Main Category: Urology / Nephrology
Also Included In: Diabetes;  Endocrinology
Article Date: 02 Oct 2008 - 1:00 PDT

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UroToday.com - In the online edition of the Journal of Andrology, Dr. Abdulmaged M. Traish and associates reviewed the evidence linking decreased plasma levels of testosterone, type 2 diabetes (T2D), and insulin resistance (IR). They performed a literature search to generate the data in this review, and concluded that androgen deficiency is linked with T2D, IR, metabolic syndrome (MetS), and increased visceral fat deposition, which serves as an endocrine organ, producing inflammatory cytokines that promote endothelial dysfunction and vascular disease. Some of the interesting supporting data are as follow.

The prevalence of T2D has increased in the US and mirrors the increased prevalence in obesity. A systematic review by Ding in 6,426 men suggests that higher testosterone levels are associated with a lower risk of T2D and vice versa. Low sex hormone binding globulin and testosterone predict higher glucose and insulin levels and increased obesity. Another study found that low levels of testosterone and sex hormone binding globulin played a role in the development of IR and T2D. There is also an inverse relationship between total testosterone and IR. Lower total testosterone leads to elevated insulin values, and body fat distribution may influence this relationship, although that is not proven. Thus, testosterone may have a protective function against diabetes in men.

Hypogonadism and T2D are often diagnosed together in the same patient. Above the age of 50, the prevalence of hypogonadism increases with 55% of men between 70 and 79 having hypogonadism compared to 24% in the 50-59 year age group. Individuals with a body mass index of >30 had significantly higher fasting plasma insulin, fasting IR index, C-peptide and lower serum testosterone than men with a BMI <30. One trial found hypogonadism a stronger risk factor for the development of elevated insulin and glucose levels compared to increased weight/obesity.

Androgen deprivation therapy has the same effect as a gradual decline in testicular function. The estimated risk of incident diabetes associated with receiving ADT was 1.36 and these men were more likely to develop diabetes within one year. ADT results in a progressive increase in insulin requirements. Unfavorable metabolic and hormonal profiles are especially strong for long-term ADT therapy. In the short term, Maria A. Yialamas demonstrated that acute ADT for 2 weeks in young healthy men with idiopathic hypogonadotropic hypogonadism reduced insulin sensitivity, suggesting that testosterone modulates insulin sensitivity directly. However, androgen deficiency may also be a consequence of poor metabolic status and thus the relationship may be bidirectional.

After adjusting for age and BMI, patients receiving ADT have significantly higher fasting insulin levels compared to men with CaP not receiving ADT or healthy controls, as reported by Shehzad Basaria. This strengthens the argument for ADT influencing fasting insulin levels more than BMI. On the other hand, testosterone replacement in hypogonadal men reduces fasting insulin and IR. Men with T2D receiving 3 months of testosterone supplementation had decreased fasting glucose, postprandial glucose, mean daily glucose, and HbA1c values, when compared to baseline.

While testosterone biosynthesis is regulated primarily by secretion of LH and the integrity of the hypothalamic pituitary gonadal axis, changes due to insulin/glucose levels in diabetes and how this may alter function remains to be further defined.

Traish AM, Saad F, Guay AT
J Androl. 2008 Sep 4. Epub ahead of print.
doi:10.2164/jandrol.108.005751

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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