Anemia in Patients with Diabetes Mellitus: Prevalence and Progression

Aim: Anemia is found to contribute to the development and progression of micro and macro-vascular complications of diabetes. This study aimed to determine the prevalence of anemia in patients with diabetes and the occurrence of micro and macro vascular complications in them. Method: This was a retrospective study of 227 Saudi patients with diabetes regularly followed up as outpatients for one year. Patient's demographic profile, history of stroke, ischemic heart disease (IHD), and concomitant hypertension (HT) along with the most recent values of complete blood picture and renal function tests were collected from the database of the health center. Results: The prevalence of anemia in our study population is 55.5%, which is two to three times more common as compared to the result from previous studies. Anemia was six times more common (53.9%) compared to the previous study for the same GFR value (GFR > 60 mL/min/1.73 m2) and half of them in stage one kidney disease. Conclusion: Anemia is a common accompaniment with diabetes and it is seen early even in the absence of renal impairment which necessitate early screening of anemia and further studies to know the possible etiology.


Introduction
Diabetes is a major public health problem worldwide. Globally it is estimated that 382 million people suffer from diabetes with a prevalence of 8.3%. Saudi Arabia with a prevalence of (23.9%), is one of the top 10 countries with higher prevalence of diabetes [1].
Several studies suggest that anemia is twice as common in diabetics compared with non-diabetics [2]. Despite these facts, anemia is unrecognized in 25% of the diabetic patients [3]. Anemia also develops earlier and is more severe in patients with diabetes than in patients with renal impairment from other causes [4]. Additionally, the risk of anemia is higher in people with diabetic nephropathy compared with people with nephropathy from other causes and is associated with a more rapid decline in the GFR [5,6]. However, it develops whilst serum creatinine is within the normal range in 5% of the cases [5]. Recent studies have linked anemia with relatively low serum erythropoietin in persons with either type 1 or type 2 diabetes, even without advanced kidney disease or overt uremia [7]. The etiology of anemia in diabetes is multifactorial and includes inflammation, nutritional deficiencies, concomitant autoimmune diseases, drugs, and hormonal changes in addition to kidney disease [3]. Anemia is found to contribute to the development and progression of micro-and macro-vascular complications of diabetes, which has a negative impact on the quality of life and an additional burden on the health of the patients [4,8]. It is therefore important to diagnose and correct anemia among diabetic patients early.6 This study aimed to determine the prevalence of anemia in diabetics and the occurrence of micro and macro vascular complications in them.

Material and Methods
This was a retrospective study of Saudi diabetic patients regularly followed up as outpatients at the primary health center attached to King Faisal University, Al Ahsa. Data was collected with the approval of Health center's ethics committee.

Subjects
All diabetic patients attending the Out Patient Department between 1st January 2010 and 31st December 2011, were included in the study evaluation.

Determination of variables
Patient's demographic profile, history of stroke, ischemic heart disease (IHD), and concomitant hypertension (HT) along with complete blood picture and renal function tests were collected from the database of the health center. The most recent values were used for the analysis. Estimated glomerular filtration rate (GFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation formula was used to define renal failure.

Definition of Diabetes
Diabetes was diagnosed, when the fasting glucose value was >125 mg/dL, or random blood glucose >200 mg/dL or patients on treatment for diabetes. The diagnosis of diabetes was based on the "Definition and description of diabetes mellitus" from American Diabetes Association 2010 [9]. General Medicine: Open Access

Statistical analysis
Descriptive analysis were used to characterize the study sample by demographics, including sex, age, prevalence of hypertension, stroke, heart disease in relation to anemia and kidney function. The result was presented in the form of tables, using frequencies percentage, mean and standard deviation to describe the study sample in relation to relevant variables. P-value less than 0.05 was taken as statistical significant. Chi-square statistics was used for testing the association between the categorical variables. All the data were manually checked for its clarity and completeness, then coded, entered and transported to IBM SPSS version 22.0 software package for analysis.

Study groups
Two hundred and twenty seven diabetic patients were evaluated, 112 (49.3%) were men and 115 (50.7%) were women. Mean age of the patients was 57.8 ± 17.1. Clinical characteristics of the patients were shown in Table 1.

Discussion
Anemia is common in diabetes, potentially contributing to the pathogenesis of diabetes complications [15]. The prevalence of anemia in our study population is 55.5%, which is two to three times more common as compared to the result from previous studies (19-25%) [5,16]. Approximately one in two patients (126/227) had anemia as defined by gender-specific WHO guidelines.
Prevalence of anemia in patients with diabetes correlated with renal impairment. The percentage of anemic patient with GFR<60mL/min/ 1.73 m 2 (46%) which is comparable to the result from other study (36%) [5]. However, it is about two time more when compared to nonanemic patient in the same stages (17.8%) and this is may be explained that anemia increase the progression of renal impairment as compared to those without anemia who are allocated in the early stages of kidney disease (Figure 3). Although anemia in diabetic patient correlated with degree of renal impairment, in our study anemia was six times more common (53.9%), compared to the previous study (9%) for the same GFR value (GFR>60 mL/min/1.73 m 2 ) and half of them in stage one kidney disease unlike in previous study [5,16,17]. Despite the predominance of patients with anemia in the early stages of chronic kidney disease, their numbers are progressively decreasing with progression of kidney disease and this may be explained by increased morbidity and mortality as anemia closely associated with vascular complications. Though the current recommendations for screening for anemia in the UK, target patients with stage 3 CKD (eGFR<60 ml ⁄ min per 1.73 m 2 ), In our study it would fail to detect 53.9% of patients with diabetes and anemia with who have an EGFR>60 ml⁄min per 1.73 m 2 [5]. So, ideally our patients with diabetes should be screened for anemia from the onset of diabetes.
Our study has several limitations. First, although the prevalence of anemia is high as compared to the previous studies, the main etiology for anemia was not investigated which is very crucial, as hemoglobinopathies are quite common in Saudi Arabia and the variation of measured prevalence depends on the population studied and definition used [18]. Secondly, the interval between the diagnosis of diabetes and the onset of anemia was not known in this retrospective study. Therefore, the ideal timing for anemia screening remains unclear or vague.

Conclusion
Anemia is a common accompaniment with diabetes and it is seen early even in the absence of renal impairment. So, it may have further role in the development and progression of both micro and macrovascular complications.