**7.1 Early metabolic changes**

There is some evidence, that the onset of insulin resistance can be detectable after 3 months of ADT (108, 109). 3-month prospective study using combined androgen blockade with leuprolide and bicalutamide showed a 43% increase in fat mass and a 26% increase in insulin levels from baseline, again indicating development of insulin resistance with increasing adiposity (110). Although there was no significant change in fasting glucose levels, a statistically significant increase in glycosylated hemoglobin was seen (though this increase was within the normal range from 5.46–5.62%). These observations suggest that insulin resistance develops within a few months of initiating ADT; however, this compensatory hyperinsulinemia prevents the development of diabetes.

#### **7.2 Late metabolic changes**

Observational study of a population-based cohort found that men undergoing ADT with GnRH agonists had a higher risk of incident diabetes (11%), coronary artery disease (25%), myocardial infarction, and sudden death (111). Interestingly, orchiectomy was associated only with a higher risk of diabetes. In some men, this risk was evident within 4 months of starting ADT. These findings suggest that although both medical and surgical modalities of ADT result in increased metabolic burden, GnRH analogs are also associated with cardiovascular events.

After 12 months of ADT, serum fasting glucose increased significantly (112), suggesting that men with PCa who are receiving long-term ADT are at risk for developing insulin resistance and hyperglycemia, thus leading to their increased risk of cardiovascular disease (113).

A retrospective study which enrolled 396 patients with a median follow-up of 60.1 months, 36 (11.3%) patients developed new- onset diabetes mellitus (NODM). In 77 patients with pre-existing diabetes, there was an increase of >/=10% in serum HbA1c or fasting glucose levels in 15 (19.5%) and 22 (28.6%), respectively. On multivariate analysis, a BMI of >/=30 kg/m(2) was associated with an increased risk of developing NODM (odds ratio 4.65, P = 0.031) (114).

In conclusion, patients receiving ADT for PCa with or with no history of diabetes should have routine surveillance of glycaemic control, with appropriate preventive and treatment measures.
