Testosterone deficiency in men – a BMI-independent risk factor for the incidence of type 2 diabetes mellitus?
Testosterone (T) deficiency in men is associated with type 2 diabetes mellitus (T2DM). BMI, higher in T2DM patients, associated with lower T levels, may be a major confounder.
METHODS:
We followed 991 male USAF veterans with 6 medical examinations completed over 20 years within the Ranch Hand Study (Agent Orange exposure). Strong motivation not to drop out makes outcome related loss-to-follow-up bias small, if any.
RESULTS:
Comparing mean testosterone levels across cycles (1 - 6), men without T2DM had consistently higher T than T2DM men with mean difference 100 ng/dl, with no differences in T trends for early- and late-diagnosed diabetics. Among men combining high T and low BMI, only 8% are diabetic, whereas among men combining low T and high BMI, 42% are diabetic.
Decreasing T and increasing BMI are both independently associated with higher fasting glucose. Men combining high T and low BMI had mean fasting glucose of 100 mg/dl, while those combining low T and high BMI 114 mg/dl. Difference is small, pattern is consistent across cycles (p< .0001). No BMI-by-T interaction effect on fasting glucose was observed.
Declining T was risk factor for high fasting glucose. Comparing 20-year profiles, men without T2DM had lower BMI and higher T from the outset than T2DM men.
T was inversely related to fasting glucose, independently of BMI and age. The effect is small. Among men of similar BMI, those in upper third of T had mean fasting glucose about ten mg/dl below men in lower third of T, a greater difference than between upper and lower thirds of BMI.
No differences between Ranch Hand subjects and controls were observed.
CONCLUSIONS:
Low testosterone was an independent risk factor for high fasting glucose comparable to aging and obesity, but a weak predictor with unclear causality of T2DM.