DIABETES/METABOLISM RESEARCH AND REVIEWS RESEARCH Diabetes Metab Res Rev 2014; 30: 291–296. Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/dmrr.2491
ARTICLE
Diabetes mellitus with normal renal function is associated with anaemia Chagai Grossman1,5*† Zamir Dovrish2† Nira Koren-Morag3,5 Gil Bornstein4,5 Avshalom Leibowitz4,5 1
Rheumatology Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel
2
Internal Medicine D, Meir Hospital, Kfar Saba, Israel
3
Department of Epidemiology and Preventive Medicine, Tel Aviv University, Tel Aviv, Israel
4
Department of Internal Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, Israel
5
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel *Correspondence to: Chagai Grossman, Rheumatology Unit, The Chaim Sheba Medical Center, Tel Hashomer, 52621, Israel. E-mail: [email protected]
†
Chagai Grossman and Zamir Dovrish equally contributed to this work and are co-first authors of this manuscript.
Abstract Background Anaemia is a common complication of diabetes mellitus (DM), usually related to renal failure. There is scarce information as to the levels of haemoglobin (Hb) and the rate of anaemia in diabetic patients with normal renal function. We, therefore, evaluated haemoglobin levels and the rate of anaemia in diabetic subjects with normal renal functions [estimated glomerular filtration rate (eGFR) > 60 mL/min]. Methods The charts of 9250 subjects who attended the Institute of Periodic Medical Examinations at the Chaim Sheba Medical Center for a routine yearly check-up were reviewed. Four hundred and forty-five subjects with type 2 DM and normal renal function were indentified and compared with those without DM who were routinely examined at the same time. Subjects’ electronic records were used to build a biochemical and clinical database. Results Mean haemoglobin levels were lower in subjects with DM than in those without (14.2 vs. 14.7 g/dL, respectively; p < 0.001). Anaemia was observed in 48 (10.8%) subjects in the diabetic group and in only 12 (2.7%) in the nondiabetic group (p < 0.001). Multivariate analysis revealed that age, gender, history of gastrointestinal disease, use of beta blockers, renal function and DM were independent determinants of haemoglobin levels. After adjustment for age, gender, history of gastrointestinal tract diseases and renal function, DM remained a significant determinant of anaemia with an odds ratio of 2.15 (confidence interval: 1.07–4.31). Conclusions Anaemia is more common in diabetic patients even when eGFR > 60 mL/min. Copyright © 2013 John Wiley & Sons, Ltd. Keywords
diabetes mellitus; renal functions; haemoglobin; anaemia
Introduction
Received: 9 June 2013 Revised: 22 September 2013 Accepted: 21 October 2013
Copyright © 2013 John Wiley & Sons, Ltd.
Anaemia is a common complication of diabetes mellitus (DM) and is usually related to renal failure [1,2]. The rate of anaemia is higher in patients with diabetic nephropathy than in patients with nondiabetic renal disease with similar levels of renal function [3–7]. Anaemia is an independent risk factor for the development and progression of cardiovascular disease and chronic renal disease and may also contribute to the development and progression of diabetic retinopathy and other diabetic complications [8–10]. Several mechanisms
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have been suggested explaining anaemia associated with DM, the most important being erythropoietin deficiency due to tubulointerstitial renal changes [11]. Several antidiabetic agents such as thiazolidinediones and biguanides may contribute to the development of anaemia [12–14]. Moreover, drugs widely used in diabetic patients that block the renin angiotensin system, such as angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), may also contribute to the development of anaemia [15–17]. Most studies assessing the prevalence of anaemia in diabetic patients included patients with different levels of renal impairment [3,4,18]. The aim of this study was to assess the haemoglobin (Hb) levels and rate of anaemia in diabetic patients with normal renal function. For this purpose, we compared Hb levels and the rate of anaemia in a group of diabetic patients with normal renal function with those in a group of nondiabetic patients. We also studied the effect of antidiabetic and antihypertensive drugs on Hb levels in diabetic patients.
Patients and methods Subjects During 2010, the charts of 9250 subjects who attended the Institute of Periodic Medical Examinations at the Chaim Sheba Medical Center for a routine yearly check-up were reviewed. Four hundred and forty-five patients were diagnosed with type 2 DM and normal renal function [estimated glomerular filtration rate (eGFR) > 60 mL/min]. Type 2 DM was diagnosed when fasting plasma glucose was >126 mg/dL (7.0 mmol/L) on two separate readings, a history of DM was reported, or when the subject used insulin or oral hypoglycaemic medications. For each diabetic subject, a nondiabetic subject with normal renal function was examined on the same day and at the same time. These subjects served as controls. Included in the study were patients with normal renal function [serum creatinine levels were 60 mL/min]. Patients were excluded if they had a known iron deficiency or vitamin B12 deficiency anaemia.
Data collection Data were collected using electronic records. The following variables were recorded: age, sex, height and weight, blood pressure levels, fasting glucose levels, HbA1c, serum urea and creatinine levels, Hb and mean corpuscular volume, list of medications, data on duration and severity of type 2 DM and comorbidities. We specifically considered the Copyright © 2013 John Wiley & Sons, Ltd.
history of gastrointestinal tract disease because these diseases could be a source of chronic blood loss. A positive history of gastrointestinal tract disease was defined when a subject had a history of oesophageal reflux, peptic disease, diverticulosis or haemorrhoids. eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation [19]. Hypercholesterolemia was defined when the measured fasting total cholesterol was >200 mg/dL (5.3 mmol/L) or the patient reported using cholesterol lowering medications. Anaemia was defined when Hb was
ARTICLE
Diabetes mellitus with normal renal function is associated with anaemia Chagai Grossman1,5*† Zamir Dovrish2† Nira Koren-Morag3,5 Gil Bornstein4,5 Avshalom Leibowitz4,5 1
Rheumatology Unit, The Chaim Sheba Medical Center, Tel-Hashomer, Israel
2
Internal Medicine D, Meir Hospital, Kfar Saba, Israel
3
Department of Epidemiology and Preventive Medicine, Tel Aviv University, Tel Aviv, Israel
4
Department of Internal Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, Israel
5
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel *Correspondence to: Chagai Grossman, Rheumatology Unit, The Chaim Sheba Medical Center, Tel Hashomer, 52621, Israel. E-mail: [email protected]
†
Chagai Grossman and Zamir Dovrish equally contributed to this work and are co-first authors of this manuscript.
Abstract Background Anaemia is a common complication of diabetes mellitus (DM), usually related to renal failure. There is scarce information as to the levels of haemoglobin (Hb) and the rate of anaemia in diabetic patients with normal renal function. We, therefore, evaluated haemoglobin levels and the rate of anaemia in diabetic subjects with normal renal functions [estimated glomerular filtration rate (eGFR) > 60 mL/min]. Methods The charts of 9250 subjects who attended the Institute of Periodic Medical Examinations at the Chaim Sheba Medical Center for a routine yearly check-up were reviewed. Four hundred and forty-five subjects with type 2 DM and normal renal function were indentified and compared with those without DM who were routinely examined at the same time. Subjects’ electronic records were used to build a biochemical and clinical database. Results Mean haemoglobin levels were lower in subjects with DM than in those without (14.2 vs. 14.7 g/dL, respectively; p < 0.001). Anaemia was observed in 48 (10.8%) subjects in the diabetic group and in only 12 (2.7%) in the nondiabetic group (p < 0.001). Multivariate analysis revealed that age, gender, history of gastrointestinal disease, use of beta blockers, renal function and DM were independent determinants of haemoglobin levels. After adjustment for age, gender, history of gastrointestinal tract diseases and renal function, DM remained a significant determinant of anaemia with an odds ratio of 2.15 (confidence interval: 1.07–4.31). Conclusions Anaemia is more common in diabetic patients even when eGFR > 60 mL/min. Copyright © 2013 John Wiley & Sons, Ltd. Keywords
diabetes mellitus; renal functions; haemoglobin; anaemia
Introduction
Received: 9 June 2013 Revised: 22 September 2013 Accepted: 21 October 2013
Copyright © 2013 John Wiley & Sons, Ltd.
Anaemia is a common complication of diabetes mellitus (DM) and is usually related to renal failure [1,2]. The rate of anaemia is higher in patients with diabetic nephropathy than in patients with nondiabetic renal disease with similar levels of renal function [3–7]. Anaemia is an independent risk factor for the development and progression of cardiovascular disease and chronic renal disease and may also contribute to the development and progression of diabetic retinopathy and other diabetic complications [8–10]. Several mechanisms
C. Grossman et al.
292
have been suggested explaining anaemia associated with DM, the most important being erythropoietin deficiency due to tubulointerstitial renal changes [11]. Several antidiabetic agents such as thiazolidinediones and biguanides may contribute to the development of anaemia [12–14]. Moreover, drugs widely used in diabetic patients that block the renin angiotensin system, such as angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), may also contribute to the development of anaemia [15–17]. Most studies assessing the prevalence of anaemia in diabetic patients included patients with different levels of renal impairment [3,4,18]. The aim of this study was to assess the haemoglobin (Hb) levels and rate of anaemia in diabetic patients with normal renal function. For this purpose, we compared Hb levels and the rate of anaemia in a group of diabetic patients with normal renal function with those in a group of nondiabetic patients. We also studied the effect of antidiabetic and antihypertensive drugs on Hb levels in diabetic patients.
Patients and methods Subjects During 2010, the charts of 9250 subjects who attended the Institute of Periodic Medical Examinations at the Chaim Sheba Medical Center for a routine yearly check-up were reviewed. Four hundred and forty-five patients were diagnosed with type 2 DM and normal renal function [estimated glomerular filtration rate (eGFR) > 60 mL/min]. Type 2 DM was diagnosed when fasting plasma glucose was >126 mg/dL (7.0 mmol/L) on two separate readings, a history of DM was reported, or when the subject used insulin or oral hypoglycaemic medications. For each diabetic subject, a nondiabetic subject with normal renal function was examined on the same day and at the same time. These subjects served as controls. Included in the study were patients with normal renal function [serum creatinine levels were 60 mL/min]. Patients were excluded if they had a known iron deficiency or vitamin B12 deficiency anaemia.
Data collection Data were collected using electronic records. The following variables were recorded: age, sex, height and weight, blood pressure levels, fasting glucose levels, HbA1c, serum urea and creatinine levels, Hb and mean corpuscular volume, list of medications, data on duration and severity of type 2 DM and comorbidities. We specifically considered the Copyright © 2013 John Wiley & Sons, Ltd.
history of gastrointestinal tract disease because these diseases could be a source of chronic blood loss. A positive history of gastrointestinal tract disease was defined when a subject had a history of oesophageal reflux, peptic disease, diverticulosis or haemorrhoids. eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation [19]. Hypercholesterolemia was defined when the measured fasting total cholesterol was >200 mg/dL (5.3 mmol/L) or the patient reported using cholesterol lowering medications. Anaemia was defined when Hb was
