Diabetes mellitus (DM) is one of the most common endocrine disorders known and was first recognized as a disease entity by ancient Indian and Egyptian physicians more than 3000 years ago. The term ‘diabetes’ was derived from the Greek word diabinein, basically meaning ‘to pass through’, as it was believed that the polyuria associated with diabetes was nothing more than a free flow of water from the mouth to the urinary system. The word ‘mellitus’, a Latin word meaning ‘honey-sweet’, was added in 1675 by Thomas Willis, a British physician and neuroanatomist, to distinguish the sweet urine of DM patients from that of patients suffering from diabetes insipidus.1 Diabetes mellitus, therefore, is a marriage between Greek and Latin words. A century after Willis, Matthew Dobson showed that the sweet taste of urine from diabetic patients was in fact due to excess glucose.1
What effect does diabetes mellitus have on the body?
Diabetes mellitus is a chronic disease that affects the anabolism and catabolism of several key nutrients including carbohydrates, proteins, lipids and body electrolytes. The abnormal metabolism of these building blocks of the body leads to biochemical as well as morphological alterations in cells, tissues and organs.2 As lipid metabolism is altered, the accumulation of lipid products in the walls of blood vessels is enhanced in patients suffering from DM.3 Symptoms associated with DM include weight loss, polydipsia, polyuria and sweet-smelling urine.2
Classification of diabetes mellitus
Increased knowledge about the pathophysiology of DM has played a significant role in the way its classification has evolved in the past 20 years. The classification of DM has moved from one based on insulin need to one based on the pathophysiology of the disease. In 2010, the American Diabetes Association introduced a revised classification, taking into account physiological as well as morphological changes. The following categories of DM have been described:
Type 1 DM (T1DM). This is associated with pancreatic beta-cell lesion that leads to a significantly low insulin level. The lesion may be caused by antibodies directed against proteins in the plasma membrane of pancreatic beta-cells. These antibodies may also include those acting against islet cells, insulin and glutamic acid decarboxylase. Idiopathic pancreatic beta-cell destruction has also been described.4
Type 2 DM (T2DM). This is indicated when the secretory capacity of pancreatic beta-cells is impaired, with a notable presence of insulin resistance. This is the most common type of diabetes, accounting for more than 90% of all cases of DM. It is strongly associated with obesity and other components of the metabolic syndrome, including hyperlipidaemia.
Type 3 DM (T3DM). Alzheimer's disease is considered by some investigators as T3DM5 because of impaired glucose uptake in the central nervous system.
Gestational DM. This is usually diagnosed during the course of pregnancy.6 Most patients who have gestational DM continue to carry the disease after pregnancy.
Diabetes mellitus of other causes. This may include DM caused by genetic impairment of pancreatic beta-cells or abnormal coding of insulin release and action, drug- and toxin-induced DM, and other types that may not fit into the previous four categories. It has been shown that patients with mutations in insulin receptors may also develop a variety of other conditions including polycystic ovarian disease and acanthosis nigricans.7
Type 2 DM accounts for more than 90% of all cases of DM and will therefore be the focus of this review.
Risk factors for the development of type 2 diabetes mellitus
In addition to physical inactivity discussed below, several other factors have been implicated in the pathogenesis of diabetes:
Nutrition. The quantity and composition of the food we eat does have an impact on whether or not we develop T2DM. Obesity is strongly associated with T2DM. Intake of calorie-rich food and saturated fat may play a role in the development of obesity and T2DM.10
Ethnicity. The prevalence of T2DM has been shown to be higher in some ethnic groups. Studies have indicated that the prevalence of T2DM is higher among South African Indians than among their South African11,12 counterparts of a different ethnic origin. Moreover, the Pima Indians are more prone to developing T2DM than any other ethnic group living in the same environment.13
Urban location. It appears logical that people living in rural areas will likely be engaged in more physical activity than urban dwellers. In fact, recent studies have shown that urban dwellers are more likely than people living in rural areas to have metabolic syndrome.14
Toxic chemicals. Chemicals in the form of drugs or environmental contaminants may destroy pancreatic beta-cells and cause diabetes. The use of steroids, diuretics and β-adrenoreceptor agonists has been linked to impaired fasting glucose and T2DM in susceptible individuals.15
Complications of diabetes mellitus
The course of T2DM is chronic, costly and sometimes frustrating. It is also marred by mild to severe acute as well as long-term complications, which target the vascular system in particular. Diabetes-induced vascular impairment eventually leads to micro- as well as macrovascular complications.16 As an intact blood circulation is needed for optimal tissue perfusion, impaired blood flow will eventually lead to other, well-known, long-term complications of DM including nephropathy and neuropathy. The cumulative effect of these complications may give rise to cardiovascular diseases, blindness, gastroparesis and many other complications. Increased blood glucose level also adds another compounding factor because of its ability to induce oxidative stress, which is harmful to body tissues16 and will eventually lead to tissue fibrosis and death. The oxidative stress induced by hyperglycaemia reduces the antioxidant protective system (glutathione, dismutase, etc.) of the body.17 Increased blood glucose will also cause glycation of body proteins (advanced glycation products), leading to malfunction of key proteins.18
The global prevalence of DM is currently estimated at about 6% of the world's population. This prevalence is, however, unevenly distributed among different populations. The total number of people suffering from diabetes worldwide was estimated to be about 225 million in 2010. This number has been projected to reach a staggering 350 million in 2030.19
The incidence and prevalence of DM continue to increase because of inappropriate diet and sedentary lifestyles. The changes experienced by a large number of populations may be attributed to the advent of modern civilization. The prevalences of DM and associated risk factors such as obesity have increased markedly, driving the prevalence ranges of T2DM to 0.3–17.9% in Africa, 1.2–14.6% in Asia, 0.7–11.6% in Europe, 4.5–40% in the Middle East and North Africa, 6.69–28.2% in North America, and 2.01–17.4% in South America.2 It is evident, therefore, that there is wide variation in the prevalence of T2DM within a country, between countries on the same continent and between continents. This suggests an important role for environmental and lifestyle factors in the aetiopathogenesis of T2DM. Genetic factors would have to be modified by these environmental factors for T2DM to manifest.
An example of the role of environmental factors in the aetiopathogenesis of T2DM is the contribution of a sedentary lifestyle. Physical activity has been shown to promote insulin sensitivity and, hence, facilitate glucose uptake. This observation is in accordance with the finding that the prevalence of T2DM is significantly lower in rural than in urban areas, most likely because people living in rural areas are more physically active.20
During the last 4–5 decades the countries in the Arabian Gulf, including the United Arab Emirates, Saudi Arabia, Kuwait, Bahrain and Oman, have undergone a rapid socioeconomic and epidemiological transition which has led to a substantial reduction in the prevalence of various communicable diseases, including vaccine-preventable diseases. However, with rapid social and economic growth, lifestyle-related non-communicable diseases have emerged as new health challenges in this region. Diabetes and obesity have increased sharply in recent years and are predicted to increase at an alarming rate in the coming years. The epidemiology of DM in the Arabian Gulf countries is presented in Table 1.
|Country||Prevalence (%)||Sample Size||Reference|
|Saudi Arabia||23.7||16 917||48|
|United Arab Emirates||23.3||817||57|
Bener et al.21 carried out a study between January 2007 and July 2008 among Qatari nationals over 20 years of age. Among a sample of 1117 subjects, the overall prevalence of DM was 16.7% (10.7% previously diagnosed and 5.9% newly diagnosed cases). Impaired glucose tolerance (IGT) was diagnosed in a further 12.5% and impaired fasting glucose (IFG) in 1.3%. Women accounted for a higher proportion of cases of DM (53.2%) than men (46.8%), and incidence peaked in the age group 40–49 years (31.2%).21
Al Mahroos and McKeigue22 carried out a study which included 2128 Bahrainis aged 40–69 years. The age-standardized prevalence of DM was 25% in Jaafari Arabs, 48% in Sunni Arabs and 23% in Iranians.22 More recently, in 2002, a community-based study in 514 adults, aged 30–79 years, reported that the prevalence of DM was 9%.23
In February 1990, a World Health Organization (WHO) study was undertaken to assess the impact of DM in Oman.24 The number of new cases of DM treated in hospitals in 1991 was 4.8 per 1000 Omani population, representing almost 6000 diabetic patients.24 In 1989, at the Royal Hospital, Muscat, DM was recorded as the principal diagnosis in 2.6% of all discharges, and in 6% of discharged patients aged 45 years and over.24 Asfour et al.25 carried out a national survey of glucose intolerance and cardiovascular disease risk factors and reported a DM prevalence of 10% and an IGT prevalence of 13% in females and 8% in males. The prevalence of DM rose with age to a maximum of over 30% in both genders, and total glucose intolerance (diabetes and IGT together) exceeded 50% in the seventh (females) and eighth (males) decades of life.25 Al Lawati et al.26 investigated the prevalence of DM and IFG by age, gender and region in 5838 Omani adults aged ≥ 20 years. In 2000, the age-adjusted prevalence of DM among Omanis aged 30–64 years reached 16.1% compared with 12.2% in 1991. IFG was found among 7.1% of males and 5.1% of females. Generally, DM was more common in urban than in rural regions.26 Also in 2000, a cross-sectional survey was carried out in 1968 households with 7011 eligible residents. Among 5788 subjects tested for IFG, the crude prevalence was 17.3% and age-adjusted prevalence was 20.3%.27 In a cross-sectional, community-based study, Al-Shafaee et al.28 reported that 36.1% of Omani adults were prediabetic. The prevalence of metabolic syndrome was found to be 30.8% among men and 58.9% among women, giving an overall prevalence of 45.9%.28 The burden of DM has increased sharply in Oman, rising from 8.3% in 1991 to 11.6% in 2000 among adults aged 20 years and older. The WHO has predicted an increase of 190% in the number of subjects living with DM in Oman over a period of 25 years, rising from 75 000 in 2000 to 217 000 in 2025.29
During the period 1980–1, the annual incidence of DM among Kuwaiti subjects aged 0–29 years was 22.09 per 100 000. There was a very low incidence in the 0–14 and 0–19 year age groups (3.96 per 100 000 and 5.61 per 100 000, respectively), and the total number of female diabetic patients exceeded the number of males by 32%.30 Shaltout et al.31 reported that between January 1992 and December 1993 the prevalence of cases of insulin-dependent DM (IDDM) in children under the age of 15 was 15.4 per 100 000.31 Abdella et al.32 investigated the prevalence of T2DM among the Kuwaiti population in two health areas: Mubarak Health Area (MHA) and Farwania Health Area (FHA). There were 3222 cases in MHA and 5114 in FHA, amounting to a crude prevalence of 7.6% in both areas combined and a prevalence of 5.6% in MHA and 10.0% in FHA. The age-specific prevalence of T2DM in both areas combined rose from 2.64% in the age group 20–39 years to 15.35% and 26.25%, respectively, in the age groups 40–59 years and 60 years and above.32 In 1992, the diabetes registry, a WHO multinational collaborative project, was started in Kuwait. For the years 1992 and 1993, the annual incidence of childhood-onset DM in Kuwait was 15.5 per 100 000.33 Abdella et al.34 carried out a study among the Kuwaiti adult population aged 20 years and older in two out of five governorates during the period September 1995 to June 1996. A total of 3003 subjects (1105 men and 1898 women) took part in the study. The overall prevalence of non-insulin dependent diabetes mellitus (NIDDM) was 14.8% (14.7% in men and 14.8% in women). Prevalence in the age group 20–39 years was 5.7% and in the age group 40–59 years was 18.3%.34
During the period 1995 to 1999 in Kuwait, a total of 129 cases of T1DM were diagnosed in children aged 0–14 years, of whom 68 were Kuwaiti nationals. The incidence was 20.18 per 100 000. Incidence in the age groups 0–4, 5–9 and 10–14 years was 8.12, 21.07 and 34.06 per 100 000, respectively.35 During the period 1992–7, a study in Kuwaiti children aged ≤ 14 years reported a T1DM incidence of 20.1 per 100 000. The incidence among boys was 21.1 per 100 000, slightly higher than the 19.0 per 100 000 seen among girls.36 Another study was carried out during the period October 2000 to September 2002 in Kuwaiti children aged 6–18 years from 182 schools. The prevalence of T1DM was 269.9 per 100 000, with no significant difference in prevalence between male and female students. The prevalence of T1DM was highest in the age group 10–13 years (347.3 per 100 000) and lowest in the age group 6–9 years (182.6 per 100 000).37 The prevalence of T2DM among these children was studied using the 2000–1 educational districts' registers as a sampling frame. T2DM was identified in 45 of the 128 918 children surveyed, giving an overall prevalence of 34.9 per 100 000. The overall age-adjusted prevalence in Kuwaiti children in 2002 was 33.2 per 100 000: 41.6 per 100 000 in boys and 24.6 per 100 000 in girls.38
A cross-sectional household survey of 2487 Kuwaiti nationals aged 50 years and over was performed in 2005–6. the doctor-diagnosed prevalence of hypertension, DM and heart disease in two governorates combined was 53.4%, 50.6% and 17.5%, respectively.39 A survey was carried out in the Kuwaiti adult population in 2007, involving a sample of 562 Kuwaiti public sector employees. The overall prevalence of DM was 21.4%.40
In 1987, a study was performed in 5222 subjects of both genders living in rural areas in the Western Region of Saudi Arabia. The results showed an overall prevalence of 4.3%, rising with age and higher income and also varying with gender: the overall prevalence in women (5.9%) was twice that in men (2.9%).41 In 1992, prevalence of DM was investigated in 12 villages near the city of Abha, the capital of the Southern Region of Saudi Arabia, with a total population of 2150 (290 families). Among the 97% of the target population who agreed to be screened, an overall prevalence of 4.6% was recorded, with prevalence being higher among men (5.5%) than among women (3.6%).42 Another study was conducted in Riyadh to determine the prevalence of DM and IGT. Blood samples (a total 3981) were collected from Saudi adult males and females (2402) and children (1579) during a household screening programme conducted in Riyadh over a period of 2 years from September 1991 to September 1993. The overall prevalence of DM (IDDM and NIDDM) was 4.76% in males and 4.10% in females between 2 and 70 years old. When children aged < 14 years were removed, the prevalence increased to 8.235% and 6.476% in males and females, respectively.43 A household survey was conducted in 34 different areas of Saudi Arabia. Blood samples were collected from 23 493 Saudi male and female subjects. Among the whole group (aged 2–70 years) the prevalence of IDDM, NIDDM and IGT was 0.193%, 5.503% and 0.498%, respectively, in males, and 0.237%, 4.556% and 0.900%, respectively, in females. When grouped on the basis of age there were 8762 children (< 14 years), of whom 15 (0.171%) had IDDM and 13 (0.148%) had maturity-onset diabetes of the young. In the 14–70 year age group, the prevalence of IDDM, NIDDM and IGT was 0.239%, 9.50% and 0.717%, respectively, in males and 0.248%, 6.820% and 1.347%, respectively, in females.44
A household screening study carried out during the period 1992–6 in the adult population (> 14 years) of five different areas of Saudi Arabia demonstrated that overall prevalence of DM was 9.7% in males and 7.0% in females. The prevalence of obesity was 13.05% and 20.26%, respectively, whereas 27.23% of males and 25.20% of females were classed as overweight. Hypertension was recorded in 5.39% of the adult males and 3.65% of adult females.45 The prevalence of glucose intolerance was investigated in 13 177 Saudi subjects in urban and rural communities in different regions of Saudi Arabia. The mean random plasma glucose was higher in urban than in rural areas. The age-adjusted prevalence of DM was higher in urban (males 12.0% and females 14.0%) than in rural populations (males 7.0% and females 7.7%). The lowest prevalence of DM in the urban population was 2%, in subjects aged 15–20 years, and the highest was 49%, in females aged 51–60 years. The lowest prevalence among rural populations was 1%, in subjects aged 15–20 years, and the highest 29%, in females over the age of 60 years.46
In 2000, a study was performed among 3747 patients attending Al-Kharj Armed Forces Hospital. The prevalence of DM in a study sample of 3747 (1683 males and 2064 females) was 2.55% in males and 5.32% in females. Among those aged 35 years and above, the prevalence of DM in males was 8.52% and in females was 19.48%.47 The prevalence of DM among Saudis of both genders between the ages of 30 and 70 years in rural and urban communities was followed over a 5-year period between 1995 and 2000. A total of 16 917 Saudi subjects participated in the study, of whom 4004 were diagnosed with DM. The overall prevalence of DM was 23.7% and the prevalence in males and females was 26.2% and 21.5%, respectively. The prevalence of DM was higher among Saudis living in urban areas (25.5%) than among those in rural areas (19.5%).48
The prevalence of T1DM among 45 682 Saudi children and adolescents (aged 0–19-years) from 11 874 selected households was examined during the period 2001–7. Fifty-two were identified as having T1DM, giving a prevalence of 109.5 per 100 000. The number of males and females was almost equal (26 males and 26 females). The highest prevalence was found in the Central Region (162 per 100 000) and the lowest in the Eastern Region (48 per 100 000). Among children aged 5–6 years, the prevalence was 100 per 100 00, compared with 109 per 100 00 among those aged 7–12 years, 243 per 100 00 in the13–16 years age group and 150 per 100 00 among 17- to 18-year-olds.49
During the period 1990–2007, a study was carried out in Saudi patients aged < 15 years who were receiving medical care at the Saudi Aramco Medical Services Organization, Dhahran Health Center, in the Eastern Region. The reported incidence rate of T1DM was 27.52 per 100 000 per year, an increase from 18.05 per 100 000 in the first 9 years of the study period to 36.99 per 100 000 in the last 9 years.50
A 2004 study targeted all Saudi subjects aged 30 years and above residing in the Eastern Province. Among the 197 681 participants with a history of DM, the prevalence of a previously diagnosed DM was found to be 17.2%, whereas the prevalence of newly diagnosed DM was 1.8%.51 A cross-sectional study among patients attending primary care clinics was conducted in June 2009. DM was present in 1792 (30%) of 6024 patients and the prevalence was 34.1% in males and 27.6% in females. The mean age at onset of DM was 57.5 years in males and 53.4 years in females.52 All patients with newly diagnosed T1DM aged 0–12 years living in a north-western city of Saudi Arabia between 2004 and 2009 were identified. In total, 419 patients (249 girls) were diagnosed between 2004 and 2009. The incidence was significantly higher in the 10–12 years age group than in younger children, and higher in girls than in boys (33.0 vs. 22.2 per 100 000).53 In another study, 9149 adult Saudis aged 70–80 years (5357 males and 3792 females), randomly selected from the Riyadh cohort, were recruited to investigate the prevalence of T2DM. The crude prevalence was 23.1%, and the age-adjusted prevalence 31.6%. T2DM prevalence was higher in males (34.7%) than in females (28.6%). The age-adjusted prevalence of obesity was 40.0%, and was higher in females (36.5%) than in males (25.1%). The age-adjusted prevalence of hypertension and coronary artery disease as 32.6% and 6.9%, respectively.54
United Arab Emirates
In 1995, a Bedouin-derived Emirati sample of 322 subjects in the Al Ain region was studied. The overall prevalence of DM was 6% (11% in males and 7% in females aged 30–64 years). Urban residence was associated with higher blood glucose levels and higher body mass index. Twenty-seven per cent of all urban residents were obese. Between 19% and 25% of all subjects (male or female, urban or rural residents) had systolic hypertension (> 140 mmHg), and DM was associated with higher mean systolic and diastolic blood pressure.55 In 2007, the results of a study which looked at the prevalence of DM and its complications in Emirati citizens living in Al Ain were published. The participants comprised 2455 adults living in 452 surveyed households, of whom 10.2% reported having a diagnosis of DM. Among 373 men and non-pregnant women aged 30–64 years, the prevalence of DM (diagnosed and undiagnosed) and prediabetes was 29.0% and 24.2%, respectively. In patients with diagnosed DM, the prevalence of retinopathy, neuropathy, nephropathy, peripheral vascular disease and coronary heart disease was 54.2%, 34.7%, 40.8%, 11.1% and 10.5%, respectively.56 A study in 817 subjects (403 males and 414 females) from Al Ain during the period February 2004 to February 2005 reported a prevalence of 23.3% DM, 20.8% hypertension, 37.3% obesity and 22.7% metabolic syndrome.57 Data collected from 4097 men and women aged ≥ 20 years from the 2000 Emirates National Diabetes study revealed an age-adjusted prevalence of metabolic syndrome of 39.6%.57 A study in primary health-care clinics in Abu Dhabi carried out between May 2009 and October 2010 found that, of 239 patients without a history of T2DM, 14.6% had undiagnosed T2DM and 31% had an increased risk of DM.58
The cost burden of diabetes mellitus and its complications
Al Maskari et al.59 reported on the direct medical costs of DM and its complications in the United Arab Emirates. The total annual direct treatment costs of DM among patients without complications in Al Ain was US$1605, which is 3.2 times higher than the per capita expenditure for health care in the United Arab Emirates during 2004. This cost increased 2.2 times for patients with DM-related microvascular complications, by 6.4 times for patients with macrovascular complications and by 9.4 times for patients with both micro- and macrovascular complications.59
Diabetes mellitus is a common endocrine disorder with a high worldwide prevalence. The prevalence is significantly higher in the Middle East than in other regions of the world, with the exception of some Pacific Islands. The prevalence of DM is particularly high in people aged 50 years and above.