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Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy
Version of Record online: 30 DEC 2005
Copyright © 2005 American Cancer Society
Volume 106, Issue 3, pages 581–588, 1 February 2006
How to Cite
Basaria, S., Muller, D. C., Carducci, M. A., Egan, J. and Dobs, A. S. (2006), Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy. Cancer, 106: 581–588. doi: 10.1002/cncr.21642
- Issue online: 20 JAN 2006
- Version of Record online: 30 DEC 2005
- Manuscript Revised: 18 AUG 2005
- Manuscript Accepted: 18 AUG 2005
- Manuscript Received: 4 APR 2005
- Johns Hopkins University School of Medicine General Clinical Research Center. Grant Number: M01RR00052
- androgen-deprivation therapy;
- insulin resistance;
- cardiovascular disease
Prostate carcinoma (PCa) is one of the most common malignancies in men. Androgen-deprivation therapy (ADT) is used frequently in the treatment of recurrent and metastatic PCa, rendering these men hypogonadal. Because male hypogonadism is associated with an unfavorable metabolic profile, and men with PCa have high cardiovascular mortality, the authors evaluated the effects of long-term ADT on fasting glucose levels, insulin levels, and insulin resistance.
To evaluate the long-term effects of ADT on fasting glucose and insulin resistance in men with PCa who received ADT and to determine whether these metabolic alterations are a result of hypogonadism, the authors conducted a cross-sectional study at a university-based research institution in the United States. In total, 53 men were evaluated, including 18 men with PCa who received ADT for at least 12 months prior to the onset of the study (the ADT group), 17 age-matched men with nonmetastatic PCa who had undergone prostatectomy and/or received radiotherapy and who were not receiving ADT (the non-ADT group), and 18 age-matched controls (the control group). None of the men had a known history of diabetes mellitus.
The mean age was similar in all 3 groups (P = 0.33). Serum total testosterone levels (P < 0.0001) and free testosterone levels (P < 0.0001) were significantly lower in the ADT group compared with the other groups. Men in the ADT group had a higher BMI compared with the other groups (overall P = 0.005). After adjustment for age and BMI, men in the ADT group had significantly higher fasting levels of the following parameters: 1) Glucose levels were 131.0 ± 7.43 mg/dL in the ADT group compared with 103.0 ± 7.42 mg/dL in the non-ADT group (P = 0.01) and 99.0 ± 7.58 mg/dL in the control group (P < 0.01). 2) Insulin levels were 45.0 ± 7.25 uU/mL in the ADT group compared with 24.0 ± 7.24 uU/mL in the non-ADT group (P = 0.05) and 19.0 ± 7.39 uU/mL in the control group (P = 0.02). 3) Leptin levels were 25.0 ± 2.57 ng/mL in the ADT group compared with 12.0 ± 2.56 ng/mL in the non-ADT group (P < 0.01) and 6.0 ± 2.62 ng/mL in the control group (P < 0.01). 4) The homeostatic model assessment for insulin resistance (HOMAIR) = 17.0 ± 2.78 in the ADT group compared with HOMAIR = 6.0 ± 2.77 in the non-ADT group (P < 0.01) and HOMAIR = 5.0 ± 2.83 in the control group (P = 0.01). There was a significant negative correlation between total and free testosterone levels with fasting glucose, insulin, leptin, and HOMAIR.
The current data suggested 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. This adverse metabolic profile developed independent of age and BMI and appeared to be a direct result of androgen deprivation. Cancer 2006. © 2005 American Cancer Society.