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INTRODUCTION. Anaemia is one of the world’s most common preventable conditions yet it is often overlooked especially in people with diabetes mellitus (DM) It is also considered as a key indicator of chronic kidney disease (CKD) and an important cardiovascular risk factor
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INTRODUCTION • Anaemia is one of the world’s most common preventable conditions yet it is often overlooked especially in people with diabetes mellitus (DM) • It is also considered as a key indicator of chronic kidney disease (CKD) and an important cardiovascular risk factor • The incidence of anaemia in diabetes patients is mostly associated with the presence of renal insufficiency
EPIDEMIOLOGY OF ANAEMIA IN DIABETES MELLITUS • Anaemia is common and more severe in diabetes patients with CKD • It is estimated that one in five patients with DM has anaemia and the severity worsens with advanced stages of CKD • A study conducted by Aditya et al., showed that prevalence of anaemia is more in diabetes patients with CKD (74%), whereas prevalence of anaemia is low in patients with CKD alone (26%) • Thus, it showed a positive link between DM and causation of anaemia in CKD patients
EPIDEMIOLOGY OF ANAEMIA IN DIABETES MELLITUS • A study conducted by Pranay et al., showed that approximately 40% of the diabetic population is anaemic even with normal renal function • Prevalence is higher among male diabetes patients with normocytic and normochromic anaemia
PREVALENCE OF ANAEMIA IN DM • Anaemia is more common and severe in diabetic CKD patients as compared to non-diabetic CKD patients • Diabetic patients with moderate renal impairment had significantly more anaemia than diabetes patients with mild renal failure • Approximately 20% of ambulatory patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) were presented with anaemia • Although anaemia could be indicative of diabetic CKD, lower limit of Hb level within normal range can identify diabetes patients with an increased risk of microvascular complications, morbidity and mortality
PREVALENCE OF ANAEMIA IN DM • In another study, it is documented that one-third of patients with T2DM (28% of males and 33% of females) had anaemia with normochromic normocytic anaemia being the most frequent type • In India, the prevalence of anaemia (Hb <12 g/dL in women and <13 g/dL in men) was 12.3%. Between 40–49 years of age, prevalence of anaemia was higher in women than in men (26.4% in women and 10.3% in men)
EFFECTS OF ANAEMIA ON MAJOR ORGAN SYSTEMS IN DIABETES MELLITUS • Anaemia in diabetes patients might contribute to pathogenesis and progression of cardiovascular disease (CVD), aggravated diabetic nephropathy and retinopathy • However, an emphasis on regular screening for anaemia and for other DM related complications, might help to delay the progression of vascular complications in these patients
EFFECTS OF ANAEMIA ON MAJOR ORGAN SYSTEMS IN DIABETES MELLITUS • Anaemia may be more common in DM and may develop earlier than in patients with renal impairment from other causes • However, patients with DM may be more vulnerable to the effects of anaemia because many have significant CVD and hypoxia–induced organ damage • Anaemia can be considered as a marker of kidney damage in DM and reduced Hb count can show increased risk of microvascular complications, CVD and mortality
RELATIONSHIP BETWEEN ANAEMIA OF CKD WITH DM AND ACE INHIBITORS/ANGIOTENSIN RECEPTOR BLOCKERS • Certain drugs are also implicated as causative factors for development of anaemia in diabetes patients e.g., angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)
CLINICAL FEATURES OF ANAEMIA IN DIABETES MELLITUS • Anaemia in DM can be due to nutritional deficiency of iron containing food or due to deficiency of vitamin B12 or folate • Hence, clinical features may vary according to causative factors • Anaemia has a significant impact on the quality of life of patients with DM due to associated morbidities i.e., multiple hospital admissions, need of blood transfusion frequently, etc
Clinical impact of anaemia in DM • Fatigue, dizziness, palpitation and dyspnoea on minimal exertion • Poor wound healing • Cardiovascular complications such as left ventricular hypertrophy, congestive cardiac failure, ischaemic heart disease and hypertension • Positive co-relation between cardiac dysfunction and increased level of cardiac markers like B-type natriuretic peptide (BNP) and C-reactive protein (CRP)
Clinical impact of anaemia in DM • Decline in kidney function with progressive CKD • Increases risk of retinopathy • Increases incidence of stroke • Hastens the progression of diabetic neuropathy • Reduced cognitive function and mental acuity
Clinical features of anaemia seen due to deficiency of vitamin B12 in DM • Generalised pallor • Glossitis (inflammation of the tongue) • Multiple mouth ulcers • Paraesthesia • Difficulty in walking • Disturbance in vision • Irritability • Mood changes, depression • Depressed cognitive functions
Clinical features of anaemia seen due to folate deficiency in DM All symptoms similar to vitamin B12 deficiency can be seen in anaemia due to folate deficiency. It has certain additional symptoms such as: • Numbness and tingling on the feet and hands • Muscle weakness • Depression
RISK FACTORS FOR DEVELOPMENT OF ANAEMIA IN DIABETES MELLITUS • Advanced age: Risk of anaemia increases with advancing age • Malnutrition: Diet consisting of inadequate nutrition, iron-deficiency, less intake of protein, vitamins and minerals • Poorly controlled diabetes: Inefficient control of DM induces hyperglycaemia causing more oxidative stress and anaemia • Certain drugs: Use of drugs like ACE inhibitors, ARBs, etc., leads to more incidence of anaemia in diabetes patients
RISK FACTORS FOR DEVELOPMENT OF ANAEMIA IN DIABETES MELLITUS • Blood loss: Debridement surgeries, haemoserrous exudates, open and endovascular surgeries, repeated phlebotomies, IV accesses • Systemic inflammation: Repeated infection, antibiotics use, IV line sepsis and diabetic foot • Inhibition of erythropoietin secretion secondary to associated renal disease: Severe sympathetic autonomic neuropathy causes efferent denervation of kidney, causing loss of erythropoietin • Depressed androgen level by DM
EFFECTS OF ANAEMIA ON GLYCOSYLATEDHAEMOGLOBIN (HbA1c) ACCURACY • HbA1c is the most predominant fraction of HbA1 and it is formed by the glycation of terminal valine at the b-chain of Hb • It reflects the patient’s glycaemic status over previous three months • HbA1c is widely used as a screening test for DM and American Diabetes Association (ADA) has recently endorsed HbA1c ≥6.5% as a diagnostic criterion for DM • Iron-deficiency anaemia is commonly found in patients in Indian scenario mostly because of inadequate nutrition
EFFECTS OF ANAEMIA ON GLYCOSYLATEDHAEMOGLOBIN (HbA1c) ACCURACY • Iron-deficiency anaemia elevates HbA1c levels in diabetes patients with controlled plasma glucose levels • Hence, before altering the treatment regimen for diabetes patients, presence of iron-deficiency anaemia should be considered. • Diagnostic mistakes can occur in anaemia with DM. Therefore, in such patients, use of newer modalities for diagnosis such as fructosamine test can be used as it is more accurate for diagnosis • Instead of HbA1c, other blood glucose testing can be performed as part of routine testing and monitoring in diabetes patients
WHEN TO REFER TO A SPECIALIST • In patients with iron-deficiency anaemia showing sub-optimal or no response to oral iron therapy after a 6–8 week trial of iron • If patients are intolerant and have significant side effects then primary investigation for iron-deficiency should be carried out Before switching to parenteral iron therapy in patients who are intolerant to oral iron therapy • Anaemic patients with DM and other co-morbid disease such as CKD, chronic heart disease, peripheral vascular disease (PVD), etc
WHEN TO REFER TO A SPECIALIST • Persistent albuminuria in diabetes patients with anaemia • Persistent unexplained or recurrent anaemia • Rapidly progressive symptomatic anaemia • Anaemic patients with DM showing features such as splenomegaly, lymphadenopathy or cytopenias • Diabetes patients showing leucoerythroblastic anaemia (based on blood film report) or recurrent severe anaemia which is not due to sickle cell disease • Diabetes patients having anaemia due to heavy menstrual bleeding
MANAGEMENT OF ANAEMIA IN DIABETES MELLITUS • The first step in the management of anaemia is evaluating the underlying cause. The treatment of anaemia in DM consists of: • Iron therapy • Erythropoietin stimulating agents (ESA) therapy • Newer drugs
IRON THERAPY Iron supplementation is widely used in anaemia in patients with DM • To treat iron-deficiency • Prevent development of anaemia in ESA treated patients • Raise Hb levels in the presence or absence of ESA treatment • Reduce ESA doses in patients receiving ESA treatment
ESA therapy in anaemic patients with DM • Should be initiated when Hb level is below 9–10 gm/dL • Hb levels should be monitored every week until it reaches a stable level (Hb>11.5 gm/dL) thereafter, monitoring should be done 4 weekly to a 3 monthly • Rate of increase in Hb level should be 1.0–2.0 gm/dL (10–20 g/L) per month • The dose of ESA can be modified depending upon the rise/falls in the Hb level • Patients may develop local pain at the site of injection, flu like symptoms or hypertension during ESA therapy
NEWER DRUGS FOR ANAEMIA IN DM Recently, newer strategies for correcting anaemia have been explored, some of the newely available drugs are • Continuous Erythropoiesis Receptor Activator (CERA) • A pegylated form of recombinant human erythropoietin • CERA has the ability to repeatedly activate the erythropoietin receptor
IMPORTANT RECOMMENDATIONS GIVEN BY KIDNEY DISEASE: IMPROVING GLOBAL OUTCOMES (KDIGO) FOR TREATMENT OF ANAEMIA IN CKD WITH DM • When prescribing iron therapy, balance the potential benefits of avoiding or minimising blood transfusions, ESA therapy and anaemia-related symptoms against the risks of harm in individual patients e.g., anaphylactoid reaction • Route of iron administration should be based on severity of iron-deficiency, availability of venous access, response to prior oral iron therapy, side effects with prior oral or IV iron therapy, patient compliance and cost • Subsequent iron administration should be based on Hb response to current iron therapy, iron status tests, ESA response and clinical features of patients • Iron status test should be evaluated at least every three months for ESA therapy to evaluate iron status
IMPORTANT RECOMMENDATIONS GIVEN BY KIDNEY DISEASE: IMPROVING GLOBAL OUTCOMES (KDIGO) FOR TREATMENT OF ANAEMIA IN CKD WITH DM • The first-dose of IV non-dextran should be given and patient should be monitored for one hour before giving infusion of IV iron dextran • Avoid administering IV iron to patients with active systemic infections • All causes of anaemia should be identified before starting ESA therapy • ESA therapy should not be started if Hb level is more than 10 gm/dL and not be used to maintain Hb concentration if it is above 11.5 gm/dL • Dose initiation and titration should be based on Hb concentration and clinical circumstances of patients and should be given by subcutaneous infusion preferably • Patients should be labeled as hypo-responsive if there is no increase in Hb concentration after one month of ESA therapy
PREVENTION OF ANAEMIA IN DIABETES MELLITUS • The prevention strategies for anaemia in diabetes patients is highly important as the causes of anaemia in DM can be multifactorial. Addressing the root cause on time is required for alleviation of further sequel of anaemic symptoms in diabetes patients
