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Low Testosterone and High C-Reactive Protein Concentrations Predict Low Hematocrit in Type 2 Diabetes

From the Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York

Address correspondence and reprint requests to Paresh Dandona, MD, PhD, Diabetes-Endocrinology Center of Western New York, 3 Gates Circle, Buffalo, NY 14209. E-mail: pdandona{at}kaleidahealth.org

OBJECTIVE—After the demonstration that one-third of male patients with type 2 diabetes have hypogonadotrophic hypogonadism, we have shown that patients with hypogonadotrophic hypogonadism also have markedly elevated C-reactive protein (CRP) concentrations. We have now hypothesized that type 2 diabetic subjects with hypogonadotrophic hypogonadism may have a lower hematocrit because testosterone stimulates, whereas chronic inflammation suppresses, erythropoiesis.

RESEARCH DESIGN AND METHODS—Seventy patients with type 2 diabetes at a tertiary referral center were included in this study.

RESULTS—The mean hematocrit in patients with hypogonadotrophic hypogonadism (n = 37), defined as calculated free testosterone (cFT) of <6.5 ng/dl, was 40.6 ± 1.1%, whereas that in eugonadal patients (n = 33) was 43.3 ± 0.7% (P = 0.011). The hematocrit was related to cFT concentration (r = 0.46; P < 0.0001); it was inversely related to plasma CRP concentration (r = 0.41; P < 0.0004). Patients with CRP <3 mg/l had a higher hematocrit (42.7 ± 0.7%) than those with CRP >3 mg/l (39.9 ± 1.1%; P < 0.05). The prevalence of normocytic normochromic anemia (hemoglobin <13 g/dl) was 23% in the entire group, whereas it was 37.8% in the men with hypogonadotrophic hypogonadism and 3% in the eugonadal men (P < 0.01). Erythropoietin concentration was elevated or high normal in all 11 patients with anemia in whom it was tested.

CONCLUSIONS—We conclude that hypogonadotrophic hypogonadism in male type 2 diabetic subjects is associated with a lower hematocrit and a frequent occurrence of mild normocytic normochromic anemia with normal or high erythropoietin concentrations. In these patients, hematocrit is also inversely related to CRP concentration. Thus, low testosterone and chronic inflammatory mechanisms may contribute to mild anemia. Such patients may also have a high risk of atherosclerotic cardiovascular events in view of their markedly elevated CRP concentrations.

Abbreviations: cFT, calculated free testosterone • CRP, C-reactive protein • GFR, glomerular filtration rate • FSH, follicle-stimulating hormone • LH, luteinizing hormone • SHBG, sex hormone–binding globulin

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