|Year : 2019 | Volume
| Issue : 2 | Page : 55-63
Prevalence and correlates of anemia in type 2 diabetes mellitus: A study of a Nigerian outpatient diabetic population
Oyindamola Ibukun Awofisoye1, Jokotade Oluremilekun Adeleye2, John Ayodele Olaniyi3, Arinola Esan4
1 Department of Internal Medicine, Limi Cardiocare Hospital, Abuja, Nigeria
2 Department of Internal Medicine, Endocrinology Division, University of Ibadan, Ibadan, Nigeria
3 Department of Hematology, University of Ibadan, Ibadan, Nigeria
4 Department of Internal Medicine, Endocrinology Division, University College Hospital, Ibadan, Nigeria
|Date of Submission||06-Dec-2018|
|Date of Acceptance||10-Mar-2019|
|Date of Web Publication||20-Jun-2019|
Dr. Oyindamola Ibukun Awofisoye
Department of Internal Medicine, Limi Cardiocare Hospital, Abuja
Background: Anemia is reportedly common in type 2 diabetes mellitus (T2DM), and it is often unrecognized or overlooked, despite its contribution to the morbidity and mortality. With the growing burden of diabetes in sub-Saharan Africa, the occurrence of anemia among T2DM patients needs to be adequately characterized. Objective: We aimed to determine the prevalence and correlates of anemia among Nigerian patients with T2DM attending a tertiary outpatient clinic. Materials and Methods: It was a cross-sectional study involving 155 patients with T2DM and 78 controls without diabetes. Full blood count, serum creatinine, fasting plasma glucose, glycosylated hemoglobin (HbA1c), and spot urinary albumin–creatinine ratio were determined in the patients. The frequency and determinants of anemia among the participants were determined. Results: Anemia was found in 45.2% of the T2DM patients, compared to 28.2% of the controls (P = 0.012). The T2DM patients were twice as likely to have anemia as the controls. Among the T2DM patients with anemia, majority (68.6%) had a normocytic anemia, while 25.7% and 5.7% had microcytic and macrocytic anemia, respectively. The independent predictors of anemia were longer duration of diabetes and lower estimated glomerular filtration rate (eGFR) with odds ratio of 2.1 and 4.7, respectively. Conclusion: Anemia is common in T2DM patients including those with normal eGFR. Longer duration of diabetes and declining eGFR were the major factors associated with anemia. Screening for anemia is recommended for patients with T2DM as part of their routine annual evaluation, especially in those with longer disease duration and eGFR <60 ml/min.
Keywords: Anemia, diabetes mellitus, Nigeria, renal
|How to cite this article:|
Awofisoye OI, Adeleye JO, Olaniyi JA, Esan A. Prevalence and correlates of anemia in type 2 diabetes mellitus: A study of a Nigerian outpatient diabetic population. Sahel Med J 2019;22:55-63
|How to cite this URL:|
Awofisoye OI, Adeleye JO, Olaniyi JA, Esan A. Prevalence and correlates of anemia in type 2 diabetes mellitus: A study of a Nigerian outpatient diabetic population. Sahel Med J [serial online] 2019 [cited 2020 Jan 20];22:55-63. Available from: http://www.smjonline.org/text.asp?2019/22/2/55/260841
| Introduction|| |
As the burden of diabetes escalates, it is projected that developing countries will suffer the largest increment in the prevalence of diabetes. Attendant to this increase in prevalence will be increase in the associated diabetes-related morbidity and mortality. Anemia, which has been reported to be common in type 2 diabetes mellitus (T2DM), is often unrecognized or ignored. Anemia has been reported to contribute significantly to the morbidity and mortality associated with diabetes.
The reported prevalence of anemia among T2DM patients ranges from 11% to 55%,,, partly reflecting the level of socioeconomic development of the study regions. Although renal impairment is a major determinant of anemia among DM patients, several other factors have been thought to be contributory. These factors include anemia of chronic disease, erythropoietin resistance, nutritional deficiencies, and low testosterone.,,, Inappropriate dietary restrictions and medications such as metformin and renin–angiotensin–aldosterone system blockers may also be contributory.,
The presence of anemia may be particularly dangerous to the health of people with diabetes, with worsening of cardiovascular risk and hypoxia-induced end-organ damage., Thus, diabetes retinopathy, nephropathy, and healing of foot ulcers may be worsened by the presence of anemia.,, Furthermore, anemia is associated with reduced exercise tolerance and may also impact on the accuracy of glycosylated hemoglobin (HbA1c).
Anemia among patients with T2DM has not been adequately characterized in sub-Saharan Africa. This cross-sectional study aimed to determine the prevalence of anemia and the factors associated with its presence among patients with diabetes attending an outpatient clinic.
| Materials and Methods|| |
Setting and population
This study was a cross-sectional study involving patients who were receiving care for T2DM at the diabetes clinic of a tertiary hospital in Southwestern Nigeria. The study was carried over a 6-month period.
Design and sampling
Consenting patients, aged 30 years and above, already diagnosed with T2DM, and who were being managed at the diabetes clinic were recruited into the study. Patients with an existing diagnosis of heart failure, chronic renal failure, malignancy, acute illnesses, or hematological disorders such as sickle cell disease and thalassemia were excluded from the study. In addition, patients who are pregnant, those with recent hemorrhage or those involved in blood donation, patients with hormone replacement, and those under androgen or erythropoietin therapy were also excluded from the study.
Every third patient attending the clinic on clinic days was selected. If patient is not eligible or declines to participate, the next patient was selected. This was done until the sample size was reached.
Controls without diabetes were recruited from people presenting for medical checkup at the wellness center of the same hospital. This is a center at the general outpatient clinic of the same hospital where apparently healthy people present for routine tests and health education. It was a convenience sampling with consecutive selection of people who were in the study age group (age >30 years), satisfied the inclusion criteria, and gave consent.
Ethical clearance was obtained from the Joint Institution Review Committee of the Hospital (Registration number UI/EC/19/0390) on 15th May 2014. Informed consent was obtained from participants. All procedures aligned with 2013 Helsinki declaration.
Data were collected on sociodemographic variables and medical history (duration of diabetes, coexisting hypertension, medications, and alcohol and cigarette consumption). The blood pressure, weight, height, and waist and hip circumference were also measured.
The hemoglobin concentration and erythrocyte parameters were analyzed with an automated flow cytometer (Mindray BC-3000Plus - Mindray Medical International Limited, Mindray Building, High-tech Industrial Park, Nanshan, Shenzhen, China). Fasting plasma glucose was analyzed using the hexokinase method. The hexokinase method was used as it is less subject to interference from medications and possible elevated serum creatinine. The glycated hemoglobin was analyzed using a Clover A1c analyzer (Infopia Co., Ltd. 891 Hogye-Dong Dongan-gu, Anyang Gyeonggi-do, South Korea). Urinary albumin (immunoturbidimetric assay) and urine creatinine (enzymatic method) were used to calculate the albumin–creatinine ratio (ACR). Serum creatinine was measured by the enzymatic method and the estimated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease Study formula.
Anemia was defined according to the WHO criteria (hemoglobin concentration of <13 mg/dl in males and <12 mg/dl in nonpregnant females).
ACR values between 30 and 299 mg/g (3.0–29.9 mg/mmol) were classified as microalbuminuria, whereas values below and above this were classified as normoalbuminuria and macroalbuminuria, respectively.
Erythrocyte mean corpuscular volume (MCV) of 80–95 fl was classified as normal, whereas values less than and greater than this were classified as microcytosis and macrocytosis, respectively.
Type 2 diabetics in this study refer to patients who were already diagnosed with T2DM – based on laboratory criteria and supporting clinical features.
The data were analyzed using SPSS version 21 (IBM SPSS Statistics, Version 21 (IBM Corp, Armonk, New York, USA)). The prevalence of anemia among the patients was determined, and characteristics of the patients with anemia were compared to those without anemia.
Results were presented as frequency (percentages), mean and standard deviation (SD), or median and range as appropriate.
The differences in the clinical and laboratory parameters of T2DM patients with and without anemia were compared using t-test, Mann–Whitney U-test, Chi-square test, and Fishers' exact test. The strength of association between hemoglobin level and different continuous variables was determined using correlation analysis. The independent variables associated with anemia were determined using logistic regression analysis. Calculated P < 0.05 was considered statistically significant.
| Results|| |
A total of 150 patients with T2DM and 78 controls without diabetes were recruited for the study. The mean age of the patients with diabetes was 60.3 ± 10.2 years and 71% were females; this was comparable to the controls (57.7 ± 10.9 years, 78.2% of females). The duration of diagnosis of diabetes mellitus ranged from 1 to 36 years, with a median of 7 years, and 80.6% had co-existing hypertension. The mean body mass index (BMI) among the patients with diabetes was 27.1 ± 4.96 kg/m2, with majority (64.5%) being overweight or obese. The other details of the sociodemographic and clinical characteristics are shown in [Table 1] and [Table 2].
|Table 1: Sociodemographic characteristics of the study participants with and without diabetes|
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|Table 2: Clinical and laboratory characteristics of the study participants with and without diabetes|
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Among the patients with diabetes, the mean (SD) hemoglobin concentration was 12.2 (±1.53) g/dl compared to 13.0 (±1.38) g/dl among the controls (P < 0.001). Anemia was present in 70 (45.2%) patients with diabetes compared to 22 (28.2%) controls (P = 0.012). Among the patients with diabetes, those with anemia did not significantly differ from those without anemia in terms of age, gender, and level of education (P > 0.05). However, patients with anemia had a longer median duration of diabetes diagnosis compared to those without anemia (10 years vs. 6 years; P = 0.020). Among the patients with anemia, 55.2% has had diabetes diagnosis for 10 years or more compared to 44.8% among those without anemia (P = 0.028) [Table 3]. Anemia occurred to a similar extent among those who had hypertension and those who did not (44.0% vs. 50.0%; P > 0.05). Anemia was most common among the overweight patients (56.5%) and least common among the obese patients (31.6%); however, there was no significant association between anemia and either of waist circumference or waist–hip ratio [Table 4].
|Table 3: Sociodemographic characteristics of participants with diabetes with and without anemia|
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|Table 4: Clinical and laboratory characteristics of participants with diabetes with and without anemia|
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On correlational analysis, hemoglobin concentration had a significant negative relationship with the duration of diabetes diagnosis (r = −0.22, P = 0.005), but not with age, duration of hypertension diagnosis, waist circumference, or BMI [Table 5].
|Table 5: Correlation between hemoglobin concentration and selected variables|
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The median eGFR was 69.6 (17.0–303.8) ml/min among patients with anemia, which was significantly lower than 102.3 (38.1–280.3) ml/min among patients without anemia (P = 0.010). A larger proportion of the patients with anemia had overt nephropathy (eGFR <60 ml/min) compared to patients without anemia (66.7% vs. 33.3%; P = 0.004). On further analysis, hemoglobin concentration had a positive correlation with eGFR (rho = +0.339, P < 0.001), whereas there was no significant correlation among the controls (rho = −0.05, P = 0.648).
Overall, 32.9% of the patients with diabetes had increased ACR. There was no association between urinary ACR and the presence of anemia. The median ACR among the patients with and without anemia were similar (14.6 vs. 15.2 mg/g; P = 0.637) [Table 2]. Furthermore, there was no significant linear correlation between hemoglobin concentration and log10 ACR (Pearson's r = −0.086, P = 0.287).
There was no significant difference in the mean fasting plasma glucose (FPG) between patients with and without anemia. The mean glycated hemoglobin was lower among patients with anemia (7.0 ± 1.23% vs. 7.5% ±1.63%); however, this did not attain statistical significance (P = 0.053) [Table 4].
Furthermore, there was no significant difference between T2DM patients with anemia and those without anemia regarding the use of medications (metformin, sulfonylureas, insulin, thiazolidinediones, aspirin, statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and vitamins) (P > 0.05).
On logistic regression analysis, only eGFR (odds ratio 4.7 [1.96–11.37]) and duration of diagnosis of diabetes mellitus (odds ratio [1.04–4.25]) remained independent predictors of anemia. Patients who had been diagnosed with diabetes for 10 years or more were more likely to have anemia compared to those who have had it for less than 10 years. Patients with eGFR of <60/min were five times more likely to have anemia compared to those who had eGFR of >90 ml/min [Table 6].
|Table 6: Independent risk factors associated with anemia in patients with type 2 diabetes mellitus|
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| Discussion|| |
This study was carried out to determine the frequency of anemia among patients with T2DM and the factors associated with anemia. Anemia was common among patients with T2DM with a frequency of 45.2%. This was significantly higher than that in the age- and gender-comparable controls. Patients with T2DM were twice as likely as controls to have anemia in this study.
Various studies conducted among patients with T2DM also found anemia to be common, with frequencies ranging from 11% to 55%,,,, with the highest reported prevalence from Saudi Arabia. The frequency of anemia in this study is similar to what was recently reported in neighboring Cameroon where a prevalence of 41.4% was reported among T2DM patients in a specialist outpatient setting. A similar prevalence (46.4%) was also reported among T2DM patients in Trinidad and Tobago. A much lower prevalence of 19% was found among Ethiopians with T2DM. The high altitude of the study location in Ethiopia compared to our study location (1712 m vs. 250 m) may be contributory to the lower prevalence as anemia is generally less common in regions of high altitude due to the altitudinal hypoxia that stimulates erythropoiesis. A lower prevalence of 15.3% was reported among Nigerian T2DM patients in Benin, southern part of Nigeria. Including only patients with “normal” serum creatinine (<133 μmol/L) may have accounted for the lower prevalence of anemia in that study, as renal disease is a major risk factor for anemia. A lower mean packed cell volume among T2DM patients compared to controls was also found in another study in southern part of Nigeria, but the prevalence of anemia was not reported.
Majority of the T2DM patients with anemia had a normocytic anemia, which is consistent with anemia of chronic disease, similar to other reports., The distribution of MCV among the anemic T2DM patients was not remarkably different from those without anemia or the controls. Thus, macrocytosis and microcytosis commonly associated with Vitamin B12 and iron-deficiency anemia, respectively, occurred to a similar extent in the T2DM patients with and without anemia.
As expected, hemoglobin concentration was higher among male T2DM patients compared to females. However, this physiologically higher Hb concentration in males has been incorporated into the gender-based WHO definition of anemia. In this study, there was no gender predisposition to anemia among the T2DM patients. Although the association of anemia with male gender has been reported among Chinese T2DM patients, majority of other studies did not find any gender association.,, This suggests that any surveillance or intervention considered for anemia among T2DM patients should include males and females alike, unlike for anemia among the reproductive age group in which emphasis is placed on females.
Patients who had DM for more than 10 years were twice as likely to have anemia compared to those who had DM for 10 years or less, independent of renal function and other factors. This is not surprising as longer exposure to hyperglycemia and target organ damage likely puts patients at higher risk of complications including anemia. This finding is useful in the early identification of patients who are at higher risk of anemia. If screening for anemia among T2DM patients is considered, duration of diabetes diagnosis longer than 10 years may be a criterion for selecting the high-risk patients to be screened. Another study from sub-Saharan Africa also found a strong association between the duration of diabetes diagnosis and the presence of anemia. Apart from renal disease, erythrocyte abnormalities, bone marrow erythropoietin resistance, and low testosterone are mechanisms by which chronic hyperglycemia is thought to contribute to anemia.
Hypertension, which frequently accompanies T2DM, was not associated with the presence of anemia in this study. Other studies similarly did not find any independent association between hypertension and the presence of anemia among T2DM patients. Chen et al. and Bonakdaran et al. reported an association which was lost after correcting for eGFR., Goldhaber et al. also reported no significant association. The lack of association between hypertension and anemia among T2DM patients suggests that the presence of hypertension is not a useful feature in identifying T2DM patients at higher risk of anemia.
Obesity has been associated with the release of cytokines and hepcidin, which may impair iron utilization, increasing the risk of anemia. An obesity paradox has been reported among the general population in Chinese and Columbian women, where anemia was found to be less common among overweight/obese people., The study in Cameroon similarly found a positive correlation between waist circumference and hemoglobin concentration, suggesting that obese individuals were less likely to be anemic. However, in this study, although anemia appeared less common among obese compared to normal/overweight T2DM patients, this was not statistically significant after adjusting for confounders. Additionally, there was no association with anemia, when BMI was analyzed as a continuous variable. Furthermore, other studies did not find any independent association between BMI and anemia among T2DM patients.,,. The association between BMI and anemia was simmilarly lacking in studies among the general population in East Nigeria and North America., The Obesity paradox for anemia in some populations is unclear; however, overnutrition in those areas may be associated with increased consumption of iron, protein, and other micronutrients which may be protective against iron-deficiency anemia.
There was no association between the use of any of the medications and the presence of anemia. Metformin has been associated with Vitamin B12 deficiency, which in turn can cause megaloblastic anemia. Although metformin therapy has been linked with macrocytic anemia, a recent case–control study did not find any association between metformin use and the presence of anemia or neuropathy, despite lower Vitamin B12 levels. No association was found between the use of renin–angiotensin system (RAS) blockade and the presence of anemia among T2DM patients in this study. This is similar to other reports among T2DM patients., The association between RAS blockade and the presence of anemia has been controversial, but a recent meta-analysis concluded that use of RAS-blocking medications was associated with the presence of anemia. Relatively low doses of RAS-blocking medications were utilized by patients in this study as is common in Nigeria. This may be contributory to the lack of association between RAS blockade and anemia in this study. Larger studies may help further clarify the association between glucose-lowering agents and antihypertensive agents (especially RAS blockers) and the presence of anemia among Nigerian patients with T2DM.
A predominant risk factor associated with the development of anemia among T2DM patients has been the presence of renal disease, manifested as reduced GFR or albuminuria. In this study, both serum creatinine and eGFR correlated significantly with Hb concentration; however, eGFR showed a stronger correlation than serum creatinine. This agrees with the findings from other studies,, and emphasizes the superior value of eGFR over serum creatinine in identifying patients at higher risk of anemia. In contrast, among the controls, there was no significant correlation between Hb concentration and serum creatinine or eGFR. This suggests that, unlike in T2DM patients, renal function was not a significant contributor to anemia observed in the controls in this study.
Anemia was about twice as common among T2DM patients with overt renal impairment (GFR <60 ml/min) compared to those with GFR ≥60 ml/min. Additionally, anemia was five times more common among T2DM patients with overt renal impairment compared with those with GFR ≥90 ml/min. Clearly, declining eGFR should increase the index of suspicion for anemia. However, only 40% of the T2DM patients with anemia had overt renal impairment. This implies that majority (60%) of the anemic T2DM patients had eGFR ≥60 ml/min. which is comparable to 62%–72% reported in other studies.,, This suggests that anemia could be missed in T2DM patients if only those with overt renal impairment are screened.
A high proportion (32.9%) of the T2DM patients had increased urinary ACR, which is comparable to other reports from Nigeria which ranges from 24% to 83%., No association was found between ACR and anemia in this study. While several studies reported a negative correlation between Hb concentration and ACR,,, among patients with T2DM, some studies have reported a lack of significant correlation including a study done in southern part of Nigeria.,, In this study, a negative correlation was found only among the subgroup with macroalbuminuria, which did not attain statistical significance. This suggests that, among Nigerian patients with T2DM, ACR may not be associated with anemia. However, considering the variability in urinary albumin excretion, a single measurement of ACR may not adequately characterize the potential variability of urinary albumin excretion in the patients.
Fifty-four percent of the T2DM patients had good glycemic control (HbA1c <7%). HbA1c tended to be lower in T2DM patients with anemia (despite similar FPG), although it barely missed statistical significance (P = 0.05). Lower HbA1c among T2DM patients with lower hemoglobin concentration has similarly been reported elsewhere., The relationship between HbA1c and anemia depends on the etiology of the anemia. In noniron-deficiency anemia (as in anemia of chronic disease), the reduced hemoglobin concentration and the increased red cell turnover reduce the amount of glycation taking place and thus the HbA1c is “spuriously” lowered. In contrast, glycation of hemoglobin is increased in iron-deficiency anemia, possibly due to increased malondialdehyde which accelerates the rate of glycation. Thus, in the presence of anemia, HbA1c could be misleading. This could cause overtreatment or undertreatment of glycemia, which will unnecessarily increase the risk for hypoglycemia- or hyperglycemia-related complications, respectively.
The potential limitation of the study includes its tertiary hospital-based location, thus the observed prevalence of anemia may not reflect its actual burden among patients with diabetes in the general community at the primary care level. Additionally, the cross-sectional design does not allow for causal inferences to be made. Finally, a single estimation of the urinary albumin excretion may not have adequately characterized albuminuria in the patients due to its potential variability.
| Conclusion|| |
This study highlights that anemia was common among patients with T2DM (45.2%) in our clinical practice. A significantly larger proportion of T2DM patients had anemia compared to the controls. The major variable associated with anemia in this study population was eGFR. Patients with eGFR <60 ml/min/1.732 were five times more likely to have anemia compared to those who had eGFR >90 ml/min/1.732. Duration of diagnosis of diabetes mellitus >10 years also increased the likelihood of anemia. However, none of the other measured variables were associated with the presence of anemia.
The authors appreciate the technical support from the staff of Endocrinology Unit, Haematology Laboratory, Institute of Medical Research and Training in the aspects of patient recruitment and laboratory analysis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]