Low Testosterone and High C-Reactive Protein Concentrations Predict Low Hematocrit in Type 2 Diabetes VISHAL BHATIA, MBBS, MD AJAY CHAUDHURI, MBBS, MRCP RASHMI TOMAR, MBBS SANDEEP DHINDSA, MBBS HUSAM GHANIM, PHD PARESH DANDONA, MD, PHD 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 sup- presses, 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). Erythropoi- etin 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 nor- mocytic 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. Diabetes Care 29:2289 –2294, 2006 A fter our previous observations that one-third of patients with type 2 di- abetes have hypogonadotrophic hypogonadism (1), that type 1 diabetic subjects do not suffer from this condition (2), and that the patients with hypogona- dotrophic hypogonadism have markedly elevated plasma C-reactive protein (CRP) concentrations (V.B., R.T., S.D., A. Chan- del, A.C., H.G., P.D., unpublished obser- vations), an index of systemic inflammation, we have now studied whether patients with hypogonadotro- phic hypogonadism have lower hemoglo- bin concentrations. Testosterone is known to exert a stimulatory effect on erythropoiesis in the bone marrow (3). Inflammation, on the other hand, is known to suppress erythropoiesis, partly through its direct action on erythropoiesis and partly through its suppression of erythropoietin secretion (4 –7). Thus, we hypothesized that hematocrit in patients with type 2 diabetes is lower in patients with hypogonadotrophic hypogonadism who also have an elevated CRP concentra- tion, an index of systemic inflammation. RESEARCH DESIGN AND METHODS — The study was con- ducted in the Diabetes-Endocrinology Center of Western New York, a tertiary referral center affiliated with the State University of New York and Kaleida Health in Buffalo, New York, and in an endocrinology specialty clinic in Mid- land, Texas. The study was carried out in 70 male patients (50 from Buffalo and 20 from Midland) referred to the centers for management of type 2 diabetes. Patients with a known history of primary or sec- ondary hypogonadism, hypopituitarism, renal failure, cirrhosis, glucocorticoid therapy, or known HIV infection were ex- cluded from the study. Demographic pa- rameters were collected, and height, weight, glucose, and HbA 1c (A1C) were measured. The age of patients (means  SE) was 56.3  1.6 years (range 24 –78), weight was 103.2  2.9 kg (49.5–156), BMI was 32.8  0.9 kg/m 2 (18.4 –54.1), and A1C was 7.74  0.25% (4.7–14). The clinical and biochemical features of the patients are summarized in Table 1. Fasting blood samples were obtained to measure plasma hemoglobin, hematocrit, serum total testosterone, sex hormone– binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hor- mone (FSH), prolactin, glucose, A1C, and plasma CRP. Serum total iron, iron- binding capacity, ferritin, vitamin B 12 , and folate concentrations were measured in all 16 patients who had anemia. Total testosterone was measured by a solid-phase radioimmunoassay (Coat-A- Count; Diagnostic Products, Los Angeles, CA). The lower limit of normal for total testosterone in our clinical laboratory is 10.4 nmol/l (300 ng/dl). SHBG was tested ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● 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@kaleidahealth.org. Received for publication 23 March 2006 and accepted in revised form 22 June 2006. 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. A table elsewhere in this issue shows conventional and Syste `me International (SI) units and conversion factors for many substances. DOI: 10.2337/dc06-0637 © 2006 by the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Pathophysiology/Complications O R I G I N A L A R T I C L E DIABETES CARE, VOLUME 29, NUMBER 10, OCTOBER 2006 2289 Downloaded from http://diabetesjournals.org/care/article-pdf/29/10/2289/591408/zdc01006002289.pdf by guest on 24 June 2022