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

Abstract

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have markedly elevated plasma C-reactive protein (CRP) concentrations (V.B., R.T., S.D., A. Chandel, A.C., H.G., P.D., unpublished observ a t i o n s ) , a n i n d e x o f s y s t e m i c inflammation, we have now studied whether patients with hypogonadotrophic hypogonadism have lower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...

Prevalence of subnormal testosterone concentrations in men with type 2 diabetes and chronic kidney disease

“…This is consistent with the known erythropoietic effect of testosterone. We have previously shown that hemoglobin concentrations are lower in hypogonadal type 2 diabetic men without CKD (30). Our current data indicate that this is true in type 2 diabetic men with CKD as well.…”

Hematological changes during androgen deprivation therapy

“…Testosterone levels remained associated with anemia independent of confounders such as age, renal function, systemic inflammation and iron stores, and determined a remarkable 6%-8% of the total variability in hemoglobin levels. 15 These findings that testosterone deficiency may contribute to an increased frequency of anemia in men with diabetes, confirmed elsewhere, 16 are important not only because of the high prevalence of low testosterone levels in men with diabetes, 17 but also because of the overlapping symptomatology of hypogonadism with anemia. 18 Whether diabetic men presenting with anemia should be screened for testosterone deficiency and vice versa deserves further study.…”

“…While earlier animal and human studies have shown that androgens increase the synthesis and secretion of erythropoietin, 10 a more recent prospective study showed that while testosterone dose-dependently increased hemoglobin and hematocrit levels in chemically castrated men, there was no associated increase in erythropoietin. 23 In addition, in population-based studies of men with 15,16 and without diabetes, 21 low testosterone remained a risk factor for anemia independent of erythropoietin levels. Consistent with the notion that hemopoietic actions of androgens are erythropoietin-independent are findings from studies in men undergoing hemodialysis, which found that concurrent androgen therapy not only augmented the anti-anemic effects of erythropoietin, but also reduced the erythropoietin dose necessary to maintain the target hemoglobin level.…”

Study to evaluate serum free testosterone and hsCRP concentration to predict low hematocrit in type 2 diabetes mellitus

“…Thus, LH and FSH concentrations in the normal reference range would be considered to be "low" when associated with low serum free testosterone concentrations. 2 While C-reactive protein levels was measured by using a high sensitivity enzyme linked immunosorbant Assay kit. hsCRP levels >3 mg/l were termed "high" because those concentrations are known to be associated with increased cardiovascular events.…”

“…Low serum testosterone level is also associated with high c-reactive protein levels which is a marker of ongoing systemic inflammation. 2 The male diabetic patients who have low free serum Testosterone level and high c-reactive protein levels have an association with low hematocrit and a frequent occurrence of mild normochromic normocytic anemia. Testosterone is known to stimulate the proliferation of erythroid progenitors, largely by erythropoietinindependent mechanisms.…”