Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Basaria
Shehzad
S
Department of Medicine, Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, and National Institut on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. sbasari1@jhmi.edu
Muller
Denis C
DC
Carducci
Michael A
MA
Egan
Josephine
J
Dobs
Adrian S
AS
D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects*; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D002318:Cardiovascular Diseases / Q000209:etiology; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D003430:Cross-Sectional Studies; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D012307:Risk Factors
D000726:Androgen Antagonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin