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Corresponding author at: Hubert Department of Global Health, Emory University, 1518 Clifton Rd, Atlanta, GA 30322, United States. Tel.: +1 404 712 2763; fax: +1 404 712 2763.
Affiliations
Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, United States
Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, United StatesDepartment of Medicine, School of Medicine, Emory University, Atlanta, GA, United States
Even though the Middle East and North Africa (MENA) region had the highest comparative prevalence of diabetes in 2012, little is known about the nuances of diabetes risk and capacity to address the burdens. To provide a comprehensive overview, we reviewed the literature on diabetes in the MENA region.
Methods
We conducted a systematic search in PubMed between January 1990 and January 2012 for studies on diabetes in the MENA region without language restriction.
Results
There was a paucity of country-specific epidemiology data in the region. Diabetes prevalence varied widely across studies, from 2.5% in 1982 to 31.6% in 2011. Older age and higher body mass index were the most strongly associated risk factors for diabetes. Among people with diabetes, over half did not meet recommended care targets. In addition, macrovascular and microvascular complications were observed in 9–12% and 15–54% of diabetes population, respectively.
Conclusions
This review suggests a need for more representative surveillance data in this noteworthy focal point of the global diabetes epidemic. Such actions will not only help to understand the actual burden of diabetes but also motivate actions on design and implementation of diabetes prevention and control programs.
The Middle East and North Africa (MENA) region has drawn attention in recent years due to their geopolitical significance, and also because of important demographic (e.g., increased life expectancy), lifestyle (e.g., reduced physical activity), and health transitions (e.g., decreased perinatal mortality). The MENA region had the highest comparative prevalence of diabetes in the world in 2012, with four countries in the region among the top ten in terms of prevalence. The International Diabetes Federation (IDF) estimates that 32.8 million adults are affected by diabetes in the MENA region, and by 2030, this number will double to 59.9 million [
Little is, however, known about the nuances of type 2 diabetes risk and the capacity (detection, preventive services, disease management) to address this rapidly emerging chronic condition in MENA. There is heterogeneity across MENA countries in terms of level of development and urbanization, ethnicity, cultural and religious backgrounds, and income distribution within nations. These variations may influence the epidemiology, clinical presentation, quality of care, and health and economic outcomes related to diabetes in the region. Also, while diabetes in Asia and Africa has been well reviewed [
] little is known about these facets of diabetes in MENA. As such, this systematic review is aimed to address the deficits, providing a comprehensive overview of diabetes in the region.
2. Methods
2.1 Search strategy and selection criteria
We searched Pubmed for articles related to diabetes mellitus in the MENA region published from January 1990 to January 2012 without language restriction. We used a combination of search terms (Appendix A) related to diabetes and all MENA countries classified by the World Bank.
Two reviewers independently identified articles and sequentially screened abstracts for inclusion. Disagreements were resolved through discussion with a third author.
The following types of studies were eligible for inclusion: (1) studies reporting diabetes prevalence, incidence, or both; (2) those reporting on risk factors for diabetes (e.g., age, family history, ethnicity, urbanization and migration, adiposity, lifestyle patterns, genetic susceptibility, socioeconomic status (SES), or developmental origins [low birth weight, early life events]); (3) studies investigating pathophysiological mechanisms of diabetes (e.g., insulin resistance, pancreatic beta-cell dysfunction); (4) studies describing diabetes-related microvascular (retinopathy, neuropathy, nephropathy) or macrovascular (cardiovascular and peripheral vascular disease) complications; and (5) studies characterizing quality of diabetes care, patient-reported quality of life, and costs.
Full-texts of eligible articles were retrieved for detailed assessment. Reference lists of selected articles were also manually scanned for additional eligible studies.
Although clinic-based studies have limitations with regard to the representativeness of the sample populations, we included these from studies with multiple clinical settings as the data do offer some meaningful and potentially generalizable insights.
We excluded: studies focused on type 1 diabetes, gestational diabetes, or any uncommon forms of diabetes (e.g., diabetes secondary to chronic pancreatitis); studies with self-reported prevalence data or those that did not define diabetes using standard definitions (World Health Organization or American Diabetes Association); studies based in single clinics/hospitals; studies using non-random sampling; or studies exclusively investigating specific ethnic- or age- groups (e.g., children; elderly).
Two reviewers independently extracted data using standardized data collection spreadsheets and assessed study quality. We also excluded studies that used inappropriate statistical methods and those with response rate <75%.
Given the complexity and the heterogeneity of studies included (spanning clinical, pathophysiology, and public health literatures), we conducted a narrative synthesis of the evidence and findings are presented within each category of interest.
3. Results
Searches yielded 6765 publications, of which 1205 were selected for full-text review. A total of 101 cross-sectional and 9 cohort publications from all the 22 countries of the MENA region were eligible for inclusion.
There was wide variation in the number of studies conducted in each of the MENA countries. Furthermore, available studies used different research methods and surveyed populations with different age-sex distributions and level of representativeness. As such, caution is advised when trying to compare data across studies.
3.1 Prevalence and incidence
Diabetes prevalence largely differed across the available studies and ranged from 2.5% in Saudi Arabia, 1982 to 31.6% in that country in 2011. High estimates were recorded in studies in recent years – for example, among urban residents of Riyadh, Saudi Arabia (31.6%) [
]. There were very few data regarding rural diabetes prevalence in the region. However in a recent systematic review focused on rural areas of low-middle income countries, the MENA region had the highest pooled prevalence (7.7%; 95% CI: 6.2–9.3), substantially higher than the global average (5.6%; 95% CI: 4.6–6.6) [
Prevalence of diabetes and impaired fasting glucose in the adult population of Iran: National Survey of Risk Factors for Non-Communicable Diseases of Iran.
Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO Consultation. Part 1. Diagnosis and classification of diabetes mellitus.
Very few studies reported the proportion of people with undiagnosed diabetes. The few data that are available show that one-fourth of those with diabetes in Tunisia [
National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants.
]. This systematic analysis of 370 country-years showed an upward trend in diabetes prevalence for most countries in the region, with the highest increase observed in Saudi Arabia (from year 1980 to year 2008: 9.4% to 22% in males; and 8.7% to 21.7% in females) (Fig. 1). There are concerns that diabetes prevalence will continue to increase for two main reasons. First, intermediate hyperglycemia (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) notably affects large proportions of people, with prevalence of IFG reaching 16.8% in Iran [
Prevalence of diabetes and impaired fasting glucose in the adult population of Iran: National Survey of Risk Factors for Non-Communicable Diseases of Iran.
]. Second, data suggest that type 2 diabetes prevalence may be high among children in the MENA region – for example, 30% of Kuwaiti 6- to 18-year-olds were affected by this condition [
Incidence data were very limited. The longitudinal Tehran Lipid and Glucose Study (TLGS) demonstrated a 6.4% cumulative incidence of diabetes among urban Iranian adults over a 6 year follow-up [
Diabetes is a multifactorial condition. Twenty studies investigated risk factors associated with diabetes, of which twelve were cross-sectional, seven were cohort studies, and one was a case control study. Obesity (BMI ≥ 30 kg/m2) was the most commonly reported risk factor with ten studies demonstrating strong associations with diabetes.
Adiposity, in its various forms, appears to be a significant risk factor for type 2 diabetes in MENA region adults [
]. This has been demonstrated in numerous studies across the region (Table 2). As examples, although diabetes risk in Bahrain was higher among older adults (aged 50–79), in females, people with low or no literacy, and those currently married, obesity was still the strongest risk factor for diabetes when adjusted for all factors [
]. Among one million Israeli military enrollees, obesity was associated with elevated diabetes risk (odds ratio [OR] 5.56 for males and 4.42 for females) [
]. Also, in villages in Israel, obesity was associated with higher risk and the disease appeared at earlier age and more commonly among people of Arab origin [
]. Over 3.6 years follow-up of Iranian men and women without diabetes, ORs for diabetes were higher among those with BMI ≥ 30 kg/m2 (OR: 2.4–5.3) and high waist-to-hip ratio (WHR)(OR: 2.6–3.5) [
Trends of diabetes according to body mass index levels in Iran: results of the national surveys of risk factors of non-communicable diseases (1999–2007).
], and Oman (BMI ≥ 30 kg/m2 and WHR ≥ 90th percentile). The BMI threshold where diabetes risk escalates were largely reported from cross-sectional studies and were as low as 21 kg/m2 in one study from Saudi Arabia, 25 kg/m2 in an Iranian study [
Trends of diabetes according to body mass index levels in Iran: results of the national surveys of risk factors of non-communicable diseases (1999–2007).
] and predominantly 30 kg/m2 in most other studies.
We found a single cohort from Israel examining the impact of adolescent BMI on diabetes incidence which noted a 9.8% increased risk for each unit increase in BMI over 17.4 years of follow-up [
]. The high prevalence of obesity in the MENA region might be related to high frequency of physical inactivity, as suggested by a large 2004 Behavioral Risk Factor Survey of 3334 Jordanian adults where 50% of participants reported no physical activity at all [
Older age was associated with increased prevalence of diabetes among Palestinian refugees attending primary clinics across Jordan, Gaza Strip, Lebanon, and Syria [
Family history of diabetes increased the risk of incident diabetes by 1.6, 1.8, and 2.4 times in studies among Palestinians, Iranians, and Kuwaitis, respectively [
]. In a case-control study investigating genetic factors, the K121Q polymorphism of the ENPP1 (involved in insulin down-regulation) was associated with type 2 diabetes in the presence of obesity among Moroccan adults aged ≥40 years [
]. Single nucleotide polymorphisms (SNPs) such as carriers of homozygous TCF7L2 genotype, had 56% higher risks of diabetes than CC genotype carriers in Tunisia [
]. A smaller study of 48 patients in Gaza also reported that the presence of allele 2 (calpain-10-allele) in SNP-44 elevated the risk of type 2 diabetes by 2.7-fold [
]. A recent study in Bahrain showed that the homozygous genotype where angiotensin-converting enzyme gene is deleted was more frequent among people with diabetes than in healthy adults [
]. Hypertension and dyslipidemia were common among people with diabetes in the MENA region with 25–53% and 35–60% having these co-existing risk factors, respectively [
In Yemen, amongst people with diabetes with a median duration of 6.3 years, 25.4% had previous or current coronary heart disease (CHD), stroke, or peripheral vascular disease (PVD) [
] were 10.5%, 17.8%, and 28%, respectively. Further, diabetes increased the risks of myocardial infarction (MI) three-fold in an Israeli nationwide survey in 2003 [
]. In Iranian people with diabetes, the hazard ratio of incident cardiovascular events was 2.9 (95% CI: 2.2–3.8) compared with those without diabetes [
Data regarding renal complications of diabetes in the region are available from Iran, Jordan, UAE, Syria, and Egypt. The differences in measurement methods, terminology, and definitions across studies made it difficult to compare results. We grouped studies regarding microalbuminuria (MA) [an early indicator of diabetic nephropathy], diabetic nephropathy (more advanced chronic kidney disease (CKD)), and end-stage renal disease requiring dialysis or kidney transplantation.
The prevalence of MA ranged from 21 to 61% among people with diabetes from Iran, UAE, and Egypt [
Diabetic nephropathy (defined as an estimated Glomerular filtration rate (GFR) <60 ml/min and/or a urine albumin-to-creatinine ratio (ACR) ≥2.5 mg/mmol in males or ≥3.5 in females) was highly prevalent in people with diabetes for 3 years in the UAE (40.8%) [
Data regarding visual complications of diabetes in the MENA region were available from nine countries (Table 3). There was heterogeneity across study populations in terms of duration of disease, risk factor control, and methods of outcome assessment.
Table 3Complications of diabetes in the Middle East and North Africa region.
Diabetic neuropathy, foot ulceration, peripheral vascular disease and potential risk factors among patients with diabetes in Bahrain: a nationwide primary care diabetes clinic-based study.
Diabetic neuropathy, foot ulceration, peripheral vascular disease and potential risk factors among patients with diabetes in Bahrain: a nationwide primary care diabetes clinic-based study.
Diabetic retinopathy (DR) was assessed using retinal photography or fundoscopy (Table 3). Across nine MENA countries, retinopathy affected 17–54% of people with diabetes aged 49–60 years [
Knowledge, attitude and practice of ministry of health primary health care physicians in the management of type 2 diabetes mellitus: a cross-sectional study in the Al Hasa District of Saudi Arabia, 2010.
Prevalence and determinants of diabetic retinopathy in Al hasa region of saudi arabia: primary health care centre based cross-sectional survey, 2007–2009.
In terms of different stages of DR progression, mild non-proliferative diabetic retinopathy (NPDR) was the most prevalent stage of DR observed among 9–65% of people with diabetes in Iran, Qatar, and Saudi Arabia [
Prevalence and determinants of diabetic retinopathy in Al hasa region of saudi arabia: primary health care centre based cross-sectional survey, 2007–2009.
Prevalence and determinants of diabetic retinopathy in Al hasa region of saudi arabia: primary health care centre based cross-sectional survey, 2007–2009.
Prevalence and determinants of diabetic retinopathy in Al hasa region of saudi arabia: primary health care centre based cross-sectional survey, 2007–2009.
]. In its advanced stages, DR leads to visual impairment, legal blindness, and/or low vision (defined as best corrected visual acuity less than 20/60, but equal to or better than 20/400 in the better eye). Legal blindness was noted among 5% of those with diabetes and elevated HbA1C levels (∼9%) in Egypt [
Prevalence of neuropathy associated with diabetes was very high in the MENA region. Across available studies, peripheral neuropathy was defined based on composite scores from questionnaires (e.g., Diabetic Neuropathy Symptom score >0; abnormal Neuropathy Disability Score) and/or examinations (e.g., Diabetic Neuropathy Examination score >3) [
Diabetic neuropathy, foot ulceration, peripheral vascular disease and potential risk factors among patients with diabetes in Bahrain: a nationwide primary care diabetes clinic-based study.
]. No studies used monofilament testing. The prevalence of diabetic neuropathy among people in communities with diabetes for ten years was 35% in the UAE and 37% in Bahrain [
Diabetic neuropathy, foot ulceration, peripheral vascular disease and potential risk factors among patients with diabetes in Bahrain: a nationwide primary care diabetes clinic-based study.
]. Diabetic neuropathy was even more common among the clinic-attending population, affecting 54% of outpatients at clinics across Egypt, Lebanon, Jordan, Kuwait, and the UAE [
Diabetic neuropathy, foot ulceration, peripheral vascular disease and potential risk factors among patients with diabetes in Bahrain: a nationwide primary care diabetes clinic-based study.
]. Several factors that are unique to the region increase the risk of neurovascular limb diseases including: harsh weather, habits like walking barefoot, phobia of surgery, and differences in access to the health care [
The relative risk of cancers among people with type 2 diabetes mellitus in Israel over 20 years of follow-up was 1.32 (95% CI 0.96–1.81, P = 0.09) compared with people without diabetes [
Incidence of malignancies in patients with diabetes mellitus and correlation with treatment modalities in a large Israeli health maintenance organization: a historical cohort study.
Incidence of malignancies in patients with diabetes mellitus and correlation with treatment modalities in a large Israeli health maintenance organization: a historical cohort study.
A study from Libya showed that diabetes alone contributes to 5.1% of mortality and contributes significantly to other fatal conditions, particularly coronary artery disease (32.7%) and strokes (20.1%) [
Studies in the MENA region tended to use different clinical care guidelines to define optimal glycemic, blood pressure, and lipid control levels. As a result, we used a set of minimal care guidelines from the IDF as common low thresholds for risk factor control and preventative care goals for people with diabetes [
] were not achieving target control. Even with an HbA1C goal of ≤9% (75 mmol/mol), 49% of primary care clinic patients in Palestine and 22% of patients in Israel were unable to meet care targets [
]. Using fasting blood glucose ≤7.8 mmol/l (140 mg/dl) as a treatment target, data from two randomly-selected health centers in Tunisia showed that 75% of people with diabetes were not achieving control [
For lipid control defined as LDL < 2.6 mmol/l (100 mg/dl), data from primary care clinics in UAE show that 69–79% of people with diabetes were not meeting goals [
] were not meeting targets. Using less stringent targets of <140/90 mmHg, 33% of diabetes patients in Tunisia and Saudi Arabia were still uncontrolled [
Awareness of diabetes status and attitudes regarding diabetes influence patients’ behaviors. In Oman, a study in a semi-urban locality showed that ≥50% of people responded appropriately to questions regarding diabetes complications [
]. However, processes do not always correlate with better outcomes – audits of three diabetes centers in Egypt showed 80% compliance with appointments, but 69.2% of patients with diabetes were still not achieving care targets [
In terms of screening for earlier detection and treatment of complications, the proportion of diabetes patients receiving annual foot examinations varied across countries (32% in Saudi Arabia [
The overall mean score (0–100) of health-related quality of life (by the translated version of the WHO questionnaire) was 63.1 among Emirati population with diabetes and was mostly affected by diabetes duration, presence of its complications, and marital status [
Data regarding costs associated with diabetes are scarce in the region. Studies from four countries reported costs, of which only one study from Iran reported both direct and indirect costs of diabetes [
]. Costs varied considerably across countries, based on income and purchasing power. In Abu Dhabi (UAE) in 2004, average annual direct costs for people with diabetes were US$1,605 which were 9.4 times higher for those with complications [
]. In Iran, annual direct and indirect costs associated with diabetes reported from Tehran in 2004 were $590.7million and $153.5million, respectively, with the largest amounts used for medications, devices, and hospitalizations [
In this comprehensive review of diabetes in the MENA region, we noted a paucity of nationally representative survey data across the region. Most data are derived from small studies that use non-standardized measures and variable diagnostic criteria. Notably, the countries from which data were most commonly cited in this review were Iran, Israel, and Saudi Arabia [
Trends of diabetes according to body mass index levels in Iran: results of the national surveys of risk factors of non-communicable diseases (1999–2007).
]. There were very few data from North African countries and rural areas. There were also very few cohort studies, with those from Iran and Israel cited multiple times [
Our review highlighted the high region and country-specific prevalence of diabetes. Variation in diabetes prevalence estimates across the region is largely due to dependence on small ad hoc surveys, and use of non-comparable measures and diagnostic criteria. This variation reinforces the need for representative surveillance efforts in order to characterize burdens, and at the same time, to evaluate responsive policies and programs.
Obesity and central obesity were clearly leading risk factors for diabetes in the MENA region. However, the emphasis on obesity has meant that very few studies have investigated the temporal relationships in terms of how behavioral (e.g., nutrition, physical activity) factors and genes interact in influencing the natural history of diabetes. A few studies have shown that physical inactivity and dietary patterns were associated with elevated BMI and waist circumference [
]. Also, the focus on obesity disregards how distribution of adiposity affects risk. Only a few studies localized in Iran and Egypt used measures of central obesity such as WC, WHR, and waist-to-height ratio [
]. Altogether though, our review suggests that lifestyle factors are associated with diabetes risk in MENA countries, implying that culturally-acceptable lifestyle interventions may have sizeable benefits in reducing diabetes incidence.
Diabetes complications were common in the region. Macrovascular complications were found in 9–12% of people with diabetes in the region while microvascular complications were observed in 15–54% of those with diabetes. Neurovascular limb diseases associated with diabetes were notably prevalent across MENA countries and may be related to specific lifestyle and culture norms. Representative data are scarce, however, and the studies available were heterogeneous in terms of designs, methods of assessing and defining presence of complications, and population characteristics.
Control of other risk factors for vascular complications among people with diabetes was generally suboptimal in the region. More than 50% of those with diabetes did not meet glucose, lipid, and/or blood pressure treatment targets. Regular and affordable access to health services and medications may be an important underlying concern as health insurance is relatively uncommon in MENA countries. Stimulating a culture of auditing health services and outcomes will not only help in identifying treatment gaps, but may also stimulate interest in quality ratings, quality improvement strategies, and competition between providers to achieve better health outcomes.
Reviews of this nature are limited by the quantity and quality of the studies available. Studies related to diabetes in the MENA region were not easily comparable due to variation in quality of studies, measures used, and diagnostic criteria chosen. These limitations notwithstanding, our narrative overview contributes to the literature by aggregating all of the relevant data related to diabetes in the region, provides an appraisal of the available epidemiological data, draws attention to important gaps in the literature, and provides insights into issues like quality of care and management that have been long overlooked. We recommend future approaches to measurement, notwithstanding the challenges to fund such efforts. We also recommend representative and regular surveillances as well as more data regarding costs and effectiveness of diabetes prevention and control interventions.
In summary, more representative data and greater use of standardized data collection tools are needed. At the same time, we recommend adaptation of tested lifestyle interventions for diabetes prevention and implementation of effective quality improvement interventions in the region. There are some local models, for example from Kuwait [
], that may be beneficial in terms of contextual relevance. To fulfill all these considerations, other non-health sectors may need to become involved. Coordinated multidisciplinary approaches involving government and non-government actors are required to identify and scale avenues for successful prevention and control of diabetes.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Acknowledgements
We would like to thank Ms. Barbara Abu-Zeid for her assistance with developing and implementing search strategies using Medline. There was no funding source for the current study.
Appendix A. Search term used for systematically reviewing the articles published from 1990 to 2012 on diabetes in the Middle East and North Africa region
Tabled
1
Medline via Pubmed (from January 1990 to January 2011)
#1 “diabetes”
#2 Algeria OR Bahrain OR Djibouti OR Egypt OR Iran OR Iraq OR Jordan OR Kuwait OR Lebanon OR Libya OR Israel OR Morocco OR Oman OR Qatar OR Saudi Arabia OR Sudan OR Syria OR Tunisia OR United Arab Emirates OR Yemen OR (West Bank and Gaza) OR Palestine
National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants.
Prevalence of diabetes and impaired fasting glucose in the adult population of Iran: National Survey of Risk Factors for Non-Communicable Diseases of Iran.
Trends of diabetes according to body mass index levels in Iran: results of the national surveys of risk factors of non-communicable diseases (1999–2007).
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