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 ϭ 37), defined as calculated free testosterone (cFT) of Ͻ6.5 ng/dl, was 40.6 Ϯ 1.1%, whereas that in eugonadal patients (n ϭ 33) was 43.3 Ϯ 0.7% (P ϭ 0.011). The hematocrit was related to cFT concentration (r ϭ 0.46; P Ͻ 0.0001); it was inversely related to plasma CRP concentration (r ϭ 0.41; P Ͻ 0.0004). Patients with CRP Ͻ3 mg/l had a higher hematocrit (42.7 Ϯ 0.7%) than those with CRP Ͼ3 mg/l (39.9 Ϯ 1.1%; P Ͻ 0.05). The prevalence of normocytic normochromic anemia (hemoglobin Ͻ13 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 Ͻ 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. Diabetes Care 29:2289 -2294, 2006A fter our previous observations that one-third of patients with type 2 diabetes have hypogonadotrophic hypogonadism (1), that type 1 diabetic subjects do not suffer from this condition (2), and that the patients with hypogonadotrophic hypogonadism have markedly elevated plasma C-reactive protein (CRP) concentrations (V.B., R.T., S.D., A. Chandel, A.C., H.G., P.D., unpublished observ a t i o n s ) , a n i n d e x o f s y s t e m i c inflammation, we have now studied whether patients with hypogonadotrophic hypogonadism have lower hemoglobin 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 concentration, an index of systemic inflammation. RESEARCH DESI...

A.C. has received honoraria/consulting fees from Aventis and Eli Lilly. Abbreviations: bioI, bioavailable testosterone; LH, leutinizing hormone; FSH, follicle-stimulating hormone; FT, free testosteron; SHBG, sex hormone-binding globulin; TT, total testosterone. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

We have recently reported (1) that male patients with type 2 diabetes have frequent hypogonadotrophic hypogonadism. We have now asked whether a similar defect may be observed in type 1 diabetic males to determine whether diabetes per se is the cause of hypogonadotrophic hypogonadism. RESEARCH DESIGN ANDMETHODS -Fifty patients with type 1 diabetes (age range 23-58 years) and 50 age-matched patients with type 2 diabetes (age range 28 -51 years) were included in the study. Patients with known history of hypogonadism, panhypopituitarism, or chronic debilitating disease such as renal failure, cirrhosis, or HIV infection were excluded from the study. Fasting blood samples were obtained from the patients, and total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), leutinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured as previously described (1). FT and bioavailable testosterone (bioT) were calculated from SHBG and TT as previously described (1). Hypogonadism was defined as low FT or low calculated FT (2). Mann-Whitney rank-sum test or Student's t test for unpaired data, 2 test, and Spearman's test were used as appropriate (Sigmastat software).RESULTS -The mean TT, FT, calculated FT, and bioT concentrations in type 1 diabetic patients were in the middle of the normal range (Table 1). No patient had subnormal TT concentrations; three patients had supranormal TT, while two patients had subnormal FT and bioT concentrations.The mean TT concentration in patients with type 2 diabetes was significantly lower than that in type 1 diabetic subjects ( Table 1). The prevalence of low TT concentrations was 24 of 50 (48%), while that of low measured and/or calculated FT was 13 of 50 (26%). LH and FSH concentrations in 12 of 13 hypogonadal patients were in the normal range, and were thus inappropriately low. One patient had elevated LH and FSH concentrations and thus had primary hypogonadism. The mean prolactin concentration was lower in type 2 than in type 1 diabetic subjects.The mean SHBG concentration in type 1 diabetic subjects was at the upper end of the reference range. The level of SHBG was higher than normal in 16 patients. The mean SHBG in type 2 diabetic subjects was significantly lower than that in type 1 diabetic subjects (Table 1).In type 1 diabetic subjects, plasma TT concentrations were negatively related to BMI (r ϭ Ϫ0.52, P Ͻ 0.001), as were FT (r ϭ Ϫ0.36, P Ͻ 0.05), calculated FT (r ϭ Ϫ0.36, P Ͻ 0.05), and bioT (r ϭ Ϫ0.36, P Ͻ 0.05). In type 2 diabetic subjects, BMI was also negatively related to FT (r ϭ Ϫ0.55, P Ͻ 0.01), calculated FT (r ϭ Ϫ0.42, P Ͻ 0.05), bioT (r ϭ Ϫ0.45, P ϭ 0.01), and TT (r ϭ Ϫ0.382, P Ͻ 0.01) (Fig. 1). BMI was also inversely related to SHBG (r ϭ Ϫ0.34, P Ͻ 0.05). Plasma FSH concentrations were positively related to age (r ϭ 0.39, P ϭ 0.01) and to LH concentrations (r ϭ 0.38, P ϭ 0.01). In type 2 diabetic subjects, FSH was positively related to age (r ϭ 0.504, P Ͻ 0.01) and LH (r ϭ 0.454, P Ͻ 0.01). The total insulin dose and insulin dose pe...