Serum Prostate-Specific Antigen Levels in Men With Type 2 Diabetes

Serum PSA levels were measured in 1,293 healthy men who underwent general health screening tests and in 224 consecutive Japanese men with type 2 diabetes, aged between 40 and 79 years, recruited from outpatient clinics of Kyoto Prefectural University of Medicine. We excluded the subjects who had evident prostate disease (e.g., prostate cancer, benign prostate hypertrophy, and prostatitis) and subjects whose serum PSA level exceeded 4.0 ng/ml. The number of subjects in the 40–49, 50–59, 60–69, and 70–79 years age-groups were 152, 573, 404, and 164, respectively, among 1,293 healthy men. The number of subjects in the 40–49, 50–59, 60–69, and 70–79 years age-groups were 21, 63, 92, and 48, respectively, among 224 men with type 2 diabetes. We investigated the relationships between serum PSA levels and variables including age, blood pressure, serum lipid concentrations, A1C, BMI, and severity of diabetes complications. Furthermore, we investigated the relationships between serum PSA levels and serum bioavailable testosterone or bioavailable dihydrotestosterone concentrations in a subgroup of 171 randomly selected diabetic patients.

Serum PSA levels (normal range <4.0 ng/ml) were measured by chemiluminescent immunometric assay. Statistical analyses were performed using Stat View software (version 5.0; SAS Institute, Cary, NC). Correlations between serum PSA level and various variables were examined by Pearson's correlation analyses. The following factors were simultaneously considered as independent variables in the multiple regression analysis: age, BMI, A1C, systolic blood pressure, diastolic blood pressure, serum total cholesterol, triglycerides, HDL cholesterol concentration, and presence of diabetes. A P value <0.05 was considered statistically significant. Approval for the study was obtained from the local research ethics committee, and informed consent was obtained from all participants.

Clinical characteristics of subjects enrolled in this study are available in an online appendix (available at http://dx.doi.org/10.2337/dc07-1962). Serum PSA levels in healthy men were 0.81 ± 0.49, 0.96 ± 0.69, 1.17 ± 0.81, and 1.24 ± 0.93 ng/ml in the 40–49, 50–59, 60–69, and 70–79 years age-group, respectively. Serum PSA levels in men with type 2 diabetes were 0.86 ± 0.48, 0.86 ± 0.44, 0.98 ± 0.50, and 1.04 ± 0.56 ng/ml in the 40–49, 50–59, 60–69, and 70–79 years age-group, respectively. Except for age-group 40–49 years, serum PSA levels were lower in diabetic men than in healthy men (Fig. 1).

A positive correlation was found between serum PSA levels and age (r = 0.153, P = 0.0221), and a negative correlation was found between serum PSA levels and serum triglyceride concentration (r = −0.144, P = 0.0308) in men with type 2 diabetes. Multiple regression analysis demonstrated that age (β = 0.185, P < 0.0001), BMI (β = −0.196, P = 0.0360), and presence of diabetes (β = −0.244, P = 0.0120) were independent determinants of serum PSA levels, although A1C, blood pressure, and serum lipid concentrations were not (see online appendix). No correlation was found between serum PSA levels and serum bioavailable testosterone concentrations (r = −0.001, P = 0.9902) and between serum PSA level and serum bioavailable dihydrotestosterone concentrations (r = 0.080, P = 0.2973) in men with type 2 diabetes. Serum PSA levels did not differ between patients treated with and without insulin or based on the severity of diabetic nephropathy or retinopathy (data not shown).

Androgens have been implicated in prostate tumorigenesis. Men with diabetes have significantly lower serum testosterone concentration than nondiabetic men (6), and this may partially explain their lower risk of prostate cancer. Shaneyfelt et al. (7) reported that men whose serum total testosterone concentration was in the highest quartile were 2.34 times more likely to develop prostate cancer in a meta-analysis. However, Monath et al. (8) reported no association between serum PSA levels and serum testosterone concentration, as is the case in this study. Intraprostatic androgen status may be more important than circulating levels in determining risk of prostate cancer. Velicer et al. (9) demonstrated that diabetic men who used insulin or who had microvascular complications had a lower risk of prostate cancer, suggesting that the association between diabetes and a decreased prostate cancer risk may be limited to those with severe diabetes. However, serum PSA levels did not differ between patients treated with and without insulin in this study. Moreover, no association was found between serum PSA levels and the severity of diabetic nephropathy or retinopathy.

Limitations of this study included the fact that we could not measure serum androgen concentrations in healthy subjects; therefore, we could not compare serum androgen concentrations between healthy and diabetic men. Further studies are needed to assess if the results of this study, which refer only to Japanese men between 40 and 79 years of age, are applicable to other populations. In conclusion, serum PSA levels were lower in patients with type 2 diabetes compared with those in healthy men, which is in line with previous reports that patients with type 2 diabetes are at a decreased risk of prostate cancer.