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Anemia in diabetes: marker or mediator of microvascular disease?

Nature Clinical Practice Nephrology volume 3, pages 20–30 (2007)Cite this article

Abstract

Anemia is a common finding in patients with diabetes due to the high burden of chronic kidney disease in this population. Anemia is more prevalent and is found earlier in patients with diabetes than in those with kidney disease from other causes. The increased risk of anemia in diabetes probably reflects changes in the renal tubulointerstitium associated with diabetic kidney disease, which disrupt the delicate interaction between interstitial fibroblasts, capillaries and tubular cells required for normal hemopoietic function. In particular, the uncoupling of the hemoglobin concentration from renal erythropoietin synthesis seems to be the key factor underlying the development of anemia. Systemic inflammation, functional hematinic deficiencies, erythropoietin resistance and reduced red cell survival also drive anemia in the setting of impaired renal compensation. Although anemia can be considered a marker of kidney damage, reduced hemoglobin levels independently identify diabetic patients with an increased risk of microvascular complications, cardiovascular disease and mortality. Nevertheless, a direct role in the development or progression of diabetic complications remains to be clearly established and the clinical utility of correcting anemia in diabetic patients has yet to be demonstrated in randomized controlled trials. Correction of anemia certainly improves performance and quality of life in diabetic patients. In the absence of additional data, treatment should be considered palliative, and any functional benefits must be matched against costs to the patient and the health system.

Key Points

  • Anemia develops earlier, more frequently, and is more severe, in patients with diabetic (as opposed to nondiabetic) kidney disease

  • Features of the diabetic milieu (systemic inflammation, functional hematinic deficiencies, resistance of bone marrow to erythropoietin, and red cell abnormalities) cause hemoglobin levels to drop

  • Tubular dysfunction results in 'uncoupling' of hemoglobin concentration from renal erythropoietin synthesis, such that erythropoietin production cannot be ramped up when demand increases

  • Reduced hemoglobin level is associated with an increased risk of progression to end-stage renal disease

  • Anemia in diabetes is associated with increased cardiovascular morbidity and mortality, hypertension, retinopathy, neuropathy and foot ulcers

  • The clinical utility of fully correcting anemia in patients with chronic kidney disease has yet to be demonstrated in randomized controlled trials

  • Correcting anemia improves patient performance and quality of life

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Figure 1: Frequency of anemia in patients with type 2 diabetes from Australian general practice (results from the NEFRON study).10
Figure 2: Average change in hemoglobin levels in patients with diabetes but without anemia at baseline.
Figure 3: Anemia and erythropoietin synthesis.
Figure 4: Diabetic patients with anemia require more antihypertensives for the same level of renal function and degree of blood pressure control as individuals without anemia (results from the NEFRON study).10

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  1. Danielle Alberti Memorial Centre for Diabetic Complications, Baker Medical Research Institute, PO Box 6492, Melbourne, Victoria 8008, Australia mthomas@baker.edu.au

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  1. Merlin C Thomas is Head of the Biochemistry of Diabetic Complications laboratory at the Danielle Alberti Memorial Centre for Diabetes Complications, Baker Medical Research Institute, Melbourne, Victoria, Australia.,

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The author declared he has received research grants from Amgen Australia and Janssen-Cilag, both manufacturers of erythropoietin.

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Thomas, M. Anemia in diabetes: marker or mediator of microvascular disease?. Nat Rev Nephrol 3, 20–30 (2007). https://doi.org/10.1038/ncpneph0378

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