I recently had to review a paper on the topic of hypogonadism an diabetes and came across an entire topic that I was not aware of. There has been extensive research done looking at the association between testosterone (free and total), SHBG, and the development of diabetes.
A number of things affect both SHBG as well as testosterone. Age, exercise, obesity just to name a few. However, insulin also affects SHBG levels. Hyperinsulinemia is associated with a reduction in SHBG concentration and SHBG concentration is positively associated with insulin sensitivity. SHBG concentration is also negatively correlated with insulin resistance, insulin levels and glucose concentration. Both insulin and insulin-like growth factor 1 have inhibitory effects on SHBG secretion by Hep G2 cells in vitro. Insulin also suppresses hepatic SHBG synthesis.
Because of this relationship, many papers are studying whether SHBG levels can be predictive of the development of diabetes. Because SHBG binds to its receptor and actually has some actions through g-protein/cAMP pathway, there are studies also looking at whether low levels of SHBG may actually lead to diabetes. If this pans out, perhaps SHBG may be a target in the future for something else we have to raise.
Further Reading:
This article shows that there is a Odds ratio of 1.89 of developing diabetes with a 1SD reduction in SHBG concentration.
From the WFMC...this article shows what little effect treating the elderly with DHEA in women or testosterone in men had on inuslin sensitivity.
A pretty good review article on the topic.
This is very interesting. I think there are better measures and predictors of diabetes, but the relationship with insulin resistance is interesting. I wonder if patients on more insulin would have less SHBG due to more liver suppression from insulin. This could then be a surrogate for later stage diabetes patients. Insulin clamps and IVGTT models are poor in patient with late stages diabetes.
ReplyDeleteWonder if the free testosterone is normal with a low shbg.
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