Review
Diabetes and Anemia: International Diabetes Federation (IDF) – Southeast Asian Region (SEAR) position statement

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Abstract

Anemia is often associated with diabetes mellitus and is known to intensify the risk of developing diabetes-related microvascular and macrovascular complications. There is paucity in understanding of co-existence of these conditions, especially in Southeast Asian countries. Iron and/or erythropoietin deficiencies are the major causes of anemia in diabetes, and diabetic kidney disease plays a key role. Patients with diabetes need to be screened for anemia along with other risk factors and anemia should be corrected appropriately to improve overall clinical outcomes. This position statement aims to provide a comprehensive overview and an algorithm for appropriate management of anemia in patients with diabetes.

Introduction

The co-existence of anemia and diabetes is being increasingly explored as it has a major impact on the overall health status of the patients [1], [2], [3]. The prevalence of concurrent anemia and diabetes mellitus (both type 1 and type 2) ranges from 14% to 45% in different ethnic populations worldwide [4], [5], [6], [7]. Although anemia and diabetes mellitus are increasingly recognized as a major health conditions [8], [9], [10], little is known about the co-existence of these conditions in south-east Asian countries like India, Sri Lanka, Bangladesh, Nepal, Mauritius and Maldives. In India, the prevalence of anemia in patients with diabetes was estimated to be approximately 18% [11], [12].

The risk of anemia in patients with diabetes is estimated to be two- to three-times higher than that of patients without diabetes [5], [13]. Early evidences indicate that the incidence of anemia in patients with diabetes mellitus is typically associated with presence of kidney disease [13], [14]. The risk of developing anemia in patients with diabetes mellitus associated with kidney disease is greater than in those patients having kidney disease of other causes [14]. Nonetheless, the early occurrence of anemia in patients without kidney disease suggests existence of some other causes of anemia in these patients [5]. Patients with poor glycemic control are at a higher risk of developing anemia than patients having good glycemic control; and the risk further increases with onset of kidney disease [15].

Chronic anemia in diabetes mellitus predicts the progression of macrovascular complications such as cardiovascular disease and stroke as well as microvascular complications such as nephropathy and retinopathy [16]. Indeed, the constellation of these modifiable risk factors is often overlooked and if untreated, it is associated with poor outcomes, including impaired quality of life, increased hospitalization and all-cause mortality [3], [17]. Therefore, appropriate screening, prompt detection and correction of anemia are crucial to improve the clinical outcomes in patients with diabetes mellitus. The purpose of this International Diabetes Federation (IDF) – Southeast Asian Region (SEAR) position statement is to provide a comprehensive overview and evidence-based recommendations for the management of anemia in patients with diabetes mellitus.

Section snippets

Pathophysiology of anemia in diabetes: multifactorial mechanism

The etiology and pathophysiology of anemia in both type 1 and type 2 diabetes mellitus is considered to be multifactorial.

Medications

Patients with diabetes mellitus are treated with antihyperglycemic agents (AHAs) along with multiple medications for accompanying comorbid conditions. Metformin, often used as a first line treatment for diabetes mellitus, has been potentially associated with vitamin B12 deficiency due to malabsorption of vitamin B12, contributing to megaloblastic anemia [27]. Reduction in absorption of vitamin B12 may typically begin as early as four months after initiation of the drug; however the clinical

Iron overload and risk of diabetes mellitus

Iron overload status or hemochromatosis can be distinguished as primary or secondary. The primary form of hemochromatosis (also known as hereditary hemochromatosis) is a genetic condition characterized by iron deposition in the parenchymal cells. It usually results from mutations in the genes encoding proteins that are involved in iron homeostasis. Secondary hemochromatosis occurs in conditions where excess iron is secondary to other disease states (e.g. multiple transfusions in β thalassemia

Diabetic kidney disease

Diabetic nephropathy is a common consequence of type 2 diabetes mellitus and it is observed in almost 5% of newly diagnosed diabetes patients [79]. Further, within 10 years of diagnosis, nearly 30–40% of patients may progress to diabetic nephropathy [79]. In these patients, anemia is a common manifestation and can be observed even before any demonstrable changes in renal function [80], [81]. The risk of anemia in patients with diabetes having kidney disease is 2–10-fold greater than in patients

Screening of anemia

According to the World Health Organization (WHO), anemia is defined as level of hemoglobin <13 g/dL in men, <12 g/dL in normal women and <11 g/dL in pregnant women [108]. Evaluation of mean corpuscular hemoglobin (MCH) or mean corpuscular volume (MCV) can distinguish macrocytic anemia (vitamin B12 or folate deficiency) from microcytic or normocytic [109]. Vitamin B12 or folate deficiency can be further confirmed based on the serum levels [110]. Iron status can be clinically assessed by measuring

Management of anemia

A prompt correction of anemia in patients with diabetes (with or without kidney disease) has shown to improve the overall clinical outcome and quality of life and reduce the risk of complications and mortality [114], [115]. The treatment strategy must be made based on the severity of anemia, underlying causes and comorbid conditions. Although the target for maintaining optimal hemoglobin is still undefined, it should be individualized based on the age, clinical status and treatment response. In

Conclusions

In patients with diabetes mellitus (with or without CKD), prompt detection and correction of anemia is important to reduce the risk of adverse outcomes. Treatment with oral or intravenous iron preparations and ESA needs to be individualized based on the patients’ clinical status and comorbid conditions. Overcorrection of anemia with hemoglobin level exceeding 13 g/dL, especially when treating with ESA, can be detrimental. Patients receiving treatment for anemia should be routinely monitored

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