Dr Ambady Ramachandran MD, Ronald Ching Wan Ma MRCP, Chamukuttan Snehalatha DSc
Prevalence of type 2 diabetes has rapidly increased in native and migrant Asian populations. Diabetes develops at a younger age in Asian populations than in white populations, hence the morbidity and mortality associated with the disease and its complications are also common in young Asian people. The young age of these populations and the high rates of cardiovascular risk factors seen in Asian people substantially increase lifetime risk of cardiovascular disease. Several distinctive features are apparent in pathogenetic factors for diabetes and their thresholds in Asian populations. The economic burden due to diabetes at personal, societal, and national levels is huge. National strategies to raise public awareness about the disease and to improve standard of care and implementation of programmes for primary prevention are urgently needed.
Diabetes and associated complications pose a major health-care burden worldwide and present major challenges to patients, health-care systems, and national economies (panel 1). WHO estimates that between 2000 and 2030, the world population will increase by 37% and the number of people with diabetes will increase by 114%.1 Asia is the major site of a rapidly emerging diabetes epidemic.1, 2 Conservative estimates based on population growth and ageing and rate of urbanisation in Asia show that India and China will remain the two countries with the highest numbers of people with diabetes (79·4 million and 42·3 million, respectively) by 2030.1 Additionally, among the top ten countries, four more are in Asia—Indonesia, Pakistan, Bangladesh, and the Philippines. Prevalences are probably underestimated because changes due to other diabetes-related risk factors have not been considered.
Burden of type 2 diabetes
Prevalence of diabetes is rising worldwide.
The incidence is highest in developing countries, especially in Asia.
Among Asian countries, India and China have the highest numbers of people with diabetes.
The high prevalence and large population size contribute to the huge burden of diabetes on these countries.
The poorest economic strata bear the highest cost burden of diabetes treatment.
The economic cost increases many times with the development of vascular complications.
Developing countries need to increase national capacity for early diagnosis, encourage effective management, and improve primary prevention to combat the rising burden due to this chronic disease.
The world population is expected to reach 7·9 billion by 2025. Six countries account for almost 50% of the population increase every year; among them, three Asian countries, India, China, and Pakistan, contribute 21%, 12%, and 5%, respectively.3 Asian populations are racially heterogeneous and have differing demographic, cultural, and socioeconomic characteristics. Differences in genetic and environmental attributes affecting diabetogenesis could also be heterogeneous. We discuss type 2 diabetes in Asian countries other than Japan.
In 2003, an estimated 194 million adults worldwide had diabetes (5·1%) and 314 million people had impaired glucose tolerance (8·2%).4 These prevalences increased to 6·0% and 7·5% in 2007 and are predicted to increase to 7·3% and 8·0% by 2025.2 380 million people are expected to have diabetes in 2025.2 85—95% of all diabetes cases are of type 2 in developed countries and this percentage is even higher in developing countries.2 Roughly 80% of people with diabetes are in developing countries, of which India and China share the largest contribution. Prevalence estimates (adjusted to world population) of diabetes and impaired glucose tolerance in all Asian countries are high and are expected to increase further during the next two decades.2
The increase is likely to be most substantial in developing countries that are undergoing the most rapid economic growth. The gross domestic product per head in India and China is lower than in some other Asian countries, despite increases of three and five times, respectively, over the past two decades (figure 1). The increases in diabetes prevalence in India and China are especially alarming compared with more developed regions within Asia, showing a mismatch between affluence and diabetes prevalence—an Asian diabetes paradox. Epidemiological data from Asian countries draw attention to the high prevalence of type 2 diabetes in urban and rural populations (table 1).2,5—38 Prevalence of impaired glucose tolerance is high in many Asian countries, suggesting the presence of a large pool of people with potential to develop diabetes.2 In southeast Asia, the estimated prevalence of impaired glucose tolerance was 6·0% in 2007.2 The rapidly increasing rate of diabetes in Asia is associated with a strong gene—environmental interaction, which is propelled by lifestyle changes caused by modernisation. Migrant Asian groups have a higher susceptibility to adverse environmental influences than do co-inhabitants of different races.39
Economic development and prevalence of diabetes in selected Asian countries, 1981—2008
(A) Real gross domestic product per head. Data from the US Department of Agriculture Economic Research Service (http://www.ers.usda.gov/Data/Macroeconomics/Data/HistoricalRealPerCapitaIncomeValues.xls, accessed April 28, 2009). (B) Prevalence of diabetes. Data derived from table 1. GDP=gross domestic product.
Prevalence of diabetes, number of people with diabetes, and percentage of urbanisation in Asian countries
* As projected by WHO.
† Based on fasting plasma glucose.
‡ Estimated prevalence.
§ Crude prevalence.
Asian populations are multiracial and have multifactorial causes of type 2 diabetes. The mechanisms underlying development of the disease are complex and varied, even within these populations. The major aetiological components of type 2 diabetes are impaired insulin secretion and impaired insulin action, which are aggravated by the presence and degree of glucotoxicity. Both components might also be genetically predetermined. Lipotoxicity plays an important part in causing insulin resistance and β-cell damage.40 In the natural history of type 2 diabetes, β-cell function undergoes a series of changes. With the development of obesity and other adverse effects on insulin sensitivity, β cells respond with compensatory hyperinsulinaemia. Such changes are seen even in non-diabetic people with strong familial history of diabetes.41 With increasing duration, β-cell function declines and insulin-to-glucose ratio diminishes, before an ultimate decompensation occurs with expression of clinical diabetes. Asian populations are more insulin resistant than are people of many other races.42—45 Insulin resistance and compensatory hyperinsulinaemia are reported even in children and adolescents of Asian Indian origin.46, 47 These factors probably play a major part in the escalating prevalence of type 2 diabetes in young populations in Asia.
Risk factors for diabetes show substantial racial and geographical variations in expression and intensity. The escalating prevalence of diabetes and cardiovascular diseases in developing countries is mostly related to environmental changes. Asian populations have several important characteristics with respect to biological and environmental risk factors for diabetes (panel 2).
Characteristics of risk factors for type 2 diabetes in Asian countries
Most Asian countries are undergoing a socioeconomic transition.
Increasing levels of modernisation, industrialisation, and economic advancements adversely affect biological and environmental risk factors for diabetes.
Asian populations have low thresholds for conventional risk factors such as age, body-mass index, upper-body adiposity.
Adverse effects on health are manifested on pre-existing genetic predisposition, insulin resistance, and other metabolic features, at a younger age in Asian populations than they are in white populations.
Diabetes develops at least a decade earlier in Asian than in white people. Prevalence of young-onset diabetes is increasing in Asian populations.
Young-onset diabetes and type 2 diabetes in children are common and their rising trend is linked to epigenetic factors, such as maternal imprinting, and to unhealthy lifestyle changes leading to high rates of obesity.
Both the thrifty genotype and thrifty phenotype might be operative in Asian groups.
These characteristics are heterogeneous in Asian populations.
These populations also have high rates of clustering of cardiovascular risk factors—ie, metabolic syndrome even at a young age.
Type 2 diabetes has a strong genetic component and most Asian patients have a first-degree relative with diabetes.48, 49 Much progress has been made in our understanding of the genetics of this disease. Importantly, most of the loci originally associated with diabetes in European populations have been replicated in Asian populations. Whereas monogenic forms of diabetes result from rare genetic mutations with large effects, such as those seen in maturity-onset diabetes of young people,50 most cases of type 2 diabetes are thought to be due to genetic variations that are more common but exert less effect. In early studies, genetic variants in the peroxisome proliferator-activated receptor-γ gene (PPARG)51 and the ATP-sensitive potassium channel Kir6·2 (KCNJ11) were reproducibly associated with type 2 diabetes.52 In Asian populations, the protective effect of the PPARG*A12Ala allele on insulin resistance and risk of type 2 diabetes was not consistently seen.53 Polymorphisms in the gene encoding transcription-factor-7-like protein 2 (TCF7L2) was reported to be associated with type 2 diabetes in 2006.54 With a combined odds ratio of 1·46 for the rs7903146 variant,55 this gene has the strongest effect on type 2 diabetes. However, the at-risk T allele in rs7903146 is rare, and different genetic variations in TCF7L2 are associated with type 2 diabetes in Asian populations.56, 57
Several other genetic variants have been identified through genome-wide association studies, which is a strategy that uses the genotyping of hundreds of thousands of single-nucleotide polymorphisms on a single array. These variants are associated with type 2 diabetes in different Asian groups, including Chinese, Japanese, Korean, and Indian populations (table 2).53—74 A meta-analysis showed that, although risk alleles of the different variants seem to confer similar risk for type 2 diabetes in European and Asian populations, ethnic differences in their frequencies lead to differences in population-attributable risk, showing the need for population-specific studies.65 Two recent Japanese genome-wide association studies replicated several loci previously identified in Europeans, and reported variants in the KCNQ1 gene that are associated with type 2 diabetes in Japanese and other east Asian populations.73, 74
Replicated type 2 diabetes gene nearest to the identified marker
Genetic variants with suggestive association with type 2 diabetes but without genome-wide statistical significance are not included. OR=Odds ratio.
* Approximate effect size for the variant associated with type 2 diabetes.
† No published data.
Most genetic variants associated with type 2 diabetes seem to be related to insulin secretion rather than insulin resistance, and several of the risk alleles are associated with reduced islet-cell function 58, 59, 68, 73, 75, 76 (table 2 and figure 2). One of the variants, FTO, is associated with changes in fat mass and predisposes to diabetes via the effects of obesity; it is the first common variant to be associated with obesity and diabetes in European as well as Asian populations. However, by contrast with European groups, the association in Asian populations is not entirely mediated through body-mass index.77 Mechanisms linking body size with type 2 diabetes seem to vary between Indian and European populations. Several other variants have been linked to obesity, although none has so far been associated with diabetes. The present catalogue of type 2 diabetes risk variants probably accounts for only a small proportion of the genetic basis of type 2 diabetes. Nevertheless, the identification of these variants has provided insights into pathogenesis of type 2 diabetes.
The role of type 2 diabetes genes in insulin secretion
Pancreatic β-cell genes associated with type 2 diabetes are in italics. G6P=glucose-6-phosphate. Adapted from Florez JC. Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: where are the insulin resistance genes? Diabetologia 2008; 51: 1100—10, by kind permission of the author and Springer Science + Business Media.
Urbanisation and migration
Rates of urbanisation are variable, but substantial increases in urbanisation will occur in most Asian countries 5 (table 1). By 2010, the proportion of urbanisation will be more than 50% in Singapore, Korea, Malaysia, the Philippines, and Indonesia, and more than 30% in China, Pakistan, India, and Thailand. The remaining countries (Bangladesh and Sri Lanka) have slow rates of urbanisation. Increasing urbanisation is due to natural population growth and expansion of urban areas. It is also affected by rural to urban migration.78 The expected increase in urban population would be a main determinant, besides ageing, of the rise in the global prevalence of diabetes. Data from Asian countries show the effect of urbanisation on diabetes prevalence.5—38 Physical activity decreases and body-mass index and upper-body adiposity increase substantially with urbanisation.79 Internal rural to urban migration results in similar adverse changes. Most Asian countries, in particular India and China, are experiencing rapid socioeconomic progress and are susceptible to such consequences.
The prevalence of diabetes is increasing in urban and rural populations in both India and China, although prevalence is substantially higher in India than in China (table 1 and figure 1). A nationwide study done in China in 2000 revealed that 7·3% of the population are affected by impaired glucose tolerance, with striking rural—urban differences.14 Importantly, only 30% of the 20 million people estimated to have diabetes on the basis of fasting plasma glucose had previously been diagnosed.14 These findings suggest that China is still in the early stages of an evolving diabetes epidemic. The prevalence will probably rise further as China continues to develop economically and becomes increasingly urban.80 This conclusion is supported by higher prevalence rates in Chinese populations in Hong Kong and Taiwan than in their mainland counterparts.80
Urban lifestyles cause enormous changes in diet, physical activity, and health. Urban populations eat more diverse diets and more macronutrients and animal food than do rural residents, but with higher intake of refined carbohydrates, processed foods, and saturated and total fat and lower intake of fibre. Increasing incomes partly account for these differences, but such changes are evident at any income.81 The effect of nutrition transition is large and most of the emerging epidemic of chronic disorders, such as diabetes, cardiovascular diseases, stroke, and hypertension, are diet related.
Migration to more affluent countries results in high prevalence of diabetes in many populations. This effect is seen, for example, in Asian Indian migrants,39, 42 Chinese groups from mainland China,82 and Japanese migrants 82 to several other countries. The rise in prevalence is a result of environmental and behavioural changes and not due to changed gene frequencies, since the increases have occurred within a few decades.
The results of the Diabetes Epidemiology Collaborative Analysis of Diagnosis Criteria in Asia (DECODA) study have shown several variations in age-specific prevalence within Asian populations.83 In Indian populations, the prevalence of diabetes peaks at 60—69 years of age, whereas in Chinese populations it peaks at age 70—89 years. Indian people have higher age-specific prevalence and higher prevalence of impaired glucose regulation at a younger age than do Chinese people.83 Findings from India,6 Pakistan,25 and Sri Lanka 34 are similar. These differences are probably related to environmental and genetic influences.
One of the hallmarks of diabetes in Asian countries is the rapidly increasing prevalence of young-onset diabetes. A high prevalence of maturity-onset diabetes in the young has been reported in India.84 In China, from 1994 to 2000, there was an 88% increase in prevalence in the 35—44 years age group.14 Data from southern India show that the prevalence of diabetes in people younger than 44 years has increased from 25·0% of the total prevalence in 2000 to 35·7% in 2006.6, 8 Factors that have contributed to the epidemic of obesity and young-onset diabetes are the rapid transition in dietary habits, reduced physical activity, changing pattern in leisure activities, longer working hours, and decreasing sleep hours.80, 85, 86 Asian people with young-onset diabetes have substantial phenotypic heterogeneity, many with positive family history, impaired β-cell function, no islet autoantibodies, and coexistence of cardiometabolic risk factors.49, 87 This tendency to impaired β-cell secretory function might be due to genetic factors, although visceral adiposity and lipotoxicity, low birthweight and maternal imprinting,88 β-cell loss and amyloid deposits might also have contributory roles.80, 89
Type 2 diabetes in children is increasing at an alarming rate, especially in Asian children in both native lands and in migrant populations.90 Its prevalence in the UK is 14 times higher in Asian children than in white European children.91 Population-based and community-based studies of type 2 diabetes in children are few,92 but several clinic-based studies have been done.87, 90 The epidemic of type 2 diabetes in children is expected to become worse with the increasing rate of obesity in children in developing countries.90 The 2002 National Nutrition and Health Survey in China showed that 4·1% of children aged 7—12 years and 5·6% of children aged 12—18 years were overweight, and the respective obesity prevalences were 2·5% and 1·6%.93 In Hong Kong, the results of a community-based study showed that 8—10% of children aged 12—13 years were obese.94
Adipose tissue and insulin resistance
The prevalence of insulin resistance and metabolic syndrome is high in Asian people.95 Features of insulin resistance are manifested in children and adolescents of south Asian origin even in the absence of obesity.46, 47 Obesity is a major determinant of type 2 diabetes, and is associated with many metabolic aberrations that impair insulin sensitivity.96, 97 These abnormalities include excess lipolysis causing increased concentrations of non-esterified fatty acids and triglycerides in blood and skeletal muscle. Glucose uptake by muscle is suppressed. Obesity also impairs insulin action by changing secretion of cytokines, specifically of leptin and adiponectin,98 and leads to proinflammatory conditions.99 Features of insulin resistance, including hypertriglyceridaemia 100, 101 and increased abdominal or visceral fat,43—45 are seen even in non-obese Asian populations. Insulin resistance has been studied extensively in Asian Indian groups. Hyperinsulinaemia, a characteristic of insulin resistance, is common in Asian people, especially in southeast Asian populations.43—45
Unusually, Asian Indian groups have high concentrations of non-esterified fatty acids in plasma during fasting despite relative hyperinsulinaemia, and this concentration is not suppressed by oral glucose administration.43 They also concomitantly have high plasma leptin and low plasma adiponectin concentrations. These changes are independent of obesity or intra-abdominal fat distribution. With development of obesity, these abnormalities will be aggravated.42, 43
Asian people generally have a lower body-mass index than do people of many other races, but the association between body-mass index and glucose intolerance is as strong as in any other population. Asian populations seem to differ from European populations in associations between body-mass index and percentage of body fat and health risks. On the basis of the evidence, a WHO expert consultation concluded that a substantially increased risk of type 2 diabetes and cardiovascular diseases occurs at body-mass index lower than 25 kg/m2. However, for Asian populations there is no uniform threshold for body-mass index to identify people who are overweight and obese. Although the WHO body-mass index figure should be retained as an international classification, individual countries could make decisions about the definition of increased risk for their populations.102 WHO recommends that a body-mass index of 18·5—22·0 kg/m2 is healthy for Asian people.102 The International Diabetes Federation criteria for healthy waist circumference for Asian people is less than 90 cm for men and less than 80 cm for women.103 Revised guidelines for diagnosis of obesity, abdominal obesity, and metabolic syndrome in Asian Indian populations were put forward by a consensus group in India.104 According to these guidelines, the criteria are a healthy body-mass index of 18·0—22·9 kg/m2, an overweight body-mass index of 23·0—24·9 kg/m2, and obesity greater than or equal to 25 kg/m2. The healthy waist circumference limits are 90 cm for men and 80 cm for women.
Abdominal obesity is a characteristic feature in many Asian populations, especially in southeast Asia. Insulin resistance is associated with visceral and subcutaneous fat content.105 Young south Asian men in the USA had insulin resistance even without increased intraperitoneal fat mass, unlike the white population studied.42 The ethnic difference in Asian Indian people could be mostly related to the higher amount of truncal fat and to the large dysfunctional subcutaneous fat cells,106 rather than to presence of excess visceral fat. Glucose disposal rate and plasma adiponectin concentration are inversely related to fat-cell size. South Asian groups generally have a low rate of glucose disposal and low adiponectin concentrations, but high leptin concentrations.42 A high proportion of body fat is seen even in newborn babies. A large, prospective study in India has shown that Indian newborn babies are thinner, shorter, and lighter than UK babies, but are relatively fat because of paucity of non-fat tissues.88
Fatty acid influx to the liver is an important pathogenetic factor for fatty liver and is also a determinant of excess triglyceride-rich lipoproteins. Dyslipidaemia in type 2 diabetes is more severe in the presence of fatty liver. Ectopic fat accumulation in the liver and skeletal muscle are important determinants of insulin resistance and can also predispose to development of type 2 diabetes.107 The twin cycle hypothesis put forth in a review by Taylor 108 explains the cycle of reactions linking muscle insulin resistance, ectopic fat deposition in the liver and islets, hepatic insulin resistance, and β-cell dysfunction eventually resulting in onset of type 2 diabetes (figure 3). Such pathogenetic mechanisms are likely to be operating in Asian people who have features of insulin resistance and have been adversely affected by maladaptation to modernisation and affluence.
The twin vicious cycles in pathogenesis of type 2 diabetes108
Cycle A: Development of fatty liver, which leads to increases in basal plasma glucose and basal insulin secretion leading to hepatic insulin resistance. Cycle B: Sequence of changes in tissues when exposed to higher concentrations of triacylglycerols that leads to decreased insulin response to ingested glucose. Postprandial response to glucose becomes blunted. These vicious cycles have inhibitory effects on islet-cell functions leading to a sudden onset of clinical diabetes.
Low adiponectin concentrations in plasma in Asian people have been linked to low insulin sensitivity and high prevalence of diabetes and cardiovascular diseases.109 In Asian populations, low adiponectin concentrations are predictive of type 2 diabetes.110 However, the investigators did not find a direct association between adiponectin and insulin resistance or other cardiometabolic risk variables.111 A study in migrant south Asian women in the USA 112 had similar findings. The mechanism by which adiponectin is linked with diabetes might also differ in south Asian populations. More detailed studies are needed to explain the mechanisms underlying insulin resistance in these populations.
Asian Indian people produce higher amounts of adenosine triphosphate despite being more insulin resistant, and have higher intramuscular triglyceride concentrations than do white people in the USA.113 Concentrations of intramuscular triglycerides are similarly high in Asian Indian people with and without diabetes, suggesting a possible difference in the association of insulin resistance and diabetes in this population.113 Moreover, in Asian Indian populations, plasma triglycerides and non-muscle triglycerides are strongly associated with insulin sensitivity.114
A pathophysiological link has been shown between obstructive sleep apnoea and excess visceral fat, independent of overall body fat.115 Obstructive sleep apnoea might be directly related to insulin resistance in both obese and non-obese people.116 Physical inactivity and sleep deprivation might also be contributing factors for many of the inflammatory, oxidative, endothelial, and coagulation abnormalities that are associated with obstructive sleep apnoea.115
Intrauterine environment and imprinting
Intrauterine and postnatal environment can affect future risk of diabetes and cardiovascular disease via fetal programming.117 The thrifty genotype and thrifty phenotype hypotheses seem to apply to Asian populations. Maternal undernutrition, infant’s low birthweight, and rapid postnatal child growth are all associated with increased risk of diabetes in offspring, and these factors might be especially relevant to developing countries such as India 88 and China.118 Additionally, offspring of women who are obese or have diabetes are at increased risk of diabetes and other cardiometabolic complications.117—119 In view of the increase in childhood obesity and increasing number of women with young-onset diabetes in Asia, this link will further exacerbate the situation by creating a vicious cycle of diabetes begetting diabetes.
The mechanism underlying such transgenerational inheritance of disease risk is under intense investigation; it is thought to involve epigenetic silencing of target genes via methylation or histone modification during development, resulting in a mismatch between the metabolic phenotype that was programmed during development and the nutritionally rich adult environment.117 Again, this mismatch might be most pronounced in countries that are undergoing the most rapid economic development. Improved understanding of the effect of maternal imprinting is needed to help to address the epidemic of diabetes in Asia.
Diagnosis and complications
The latest WHO report on the definition and diagnosis of diabetes recommended that the oral glucose tolerance test be retained as a diagnostic test.120 The need to identify postprandial hyperglycaemia seems especially relevant in Asian populations. In the DECODA study,83 more than half the patients with diabetes had isolated postprandial hyperglycaemia, which is also a powerful predictor of cardiovascular disease and premature death.121 In Asian populations, fasting plasma glucose 83, 122 and glycosylated haemoglobin (HbA1c) concentrations 123 have much lower sensitivity than does 2 h postglucose concentration for detection of diabetes.
Owing to the early onset of disease, Asian patients with diabetes are at high risk of developing long-term diabetic complications. In urban areas, prevalence of diabetes is lower in poor socioeconomic strata than in high-income groups, but glycaemic control is poor, so the occurrence of vascular complications is higher.101, 124 Few population-based data are available for vascular complications of diabetes from developing countries. In Asian countries, an estimated 30% of people with type 2 diabetes have retinopathy. In North America, the prevalence of diabetic end-stage renal disease is nearly 80% higher in Asian than in white patients with diabetes; however, rates of below-the-knee amputations are 60—69% lower and the incidence of cardiovascular disease is 24—33% lower.125 Although the prevalence of peripheral vascular complications is low in Asian Indian people, because of the large population the number with foot complications is high. Prevalence of neuropathy is high and it is a risk factor for foot infections.126
High rates of cardiovascular complications have been reported in native and migrant south Asian populations.127 Heterogeneity in the occurrence of cardiovascular risk variables is manifested in migrant south Asian groups, based on their socioeconomic strata.127 Possible discrepancies in adjustment for comorbidities might explain the conflicting findings. Within Asia, susceptibility to vascular complications varies. In the WHO Multinational Study of Vascular Disease in Diabetes, Chinese patients with diabetes had much lower rates of coronary artery disease than did patients in other centres, but they had substantially higher rates of retinopathy and nephropathy.128 A high prevalence of nephropathy was also shown in the results of the Microalbuminuria Prevalence (MAP) study, which noted a prevalence of 40% for microalbuminuria and 20% for macroalbuminuria in hypertensive patients with type 2 diabetes in Asia.129 In addition to genetic factors, the tendency towards visceral adiposity is also likely to contribute to development of cardiovascular and renal complications.130
The diabetes health-care situation is similar across most developing countries. Economic disparities, scarcity of adequate health-care facilities, and low educational status prevalent in these countries pose major hurdles for achievement of optimum glycaemic control. The cost of diabetes care is high and is increasing worldwide. The economic burden is very high, especially in developing countries, and more so in the lower economic groups, who spend 25—34% of their income on diabetes care.131, 132 The cost of care increases substantially when complications occur or when admission to hospital, surgery, or insulin treatment is needed. The results of a few studies suggest that treatment of patients with diabetes in developing countries is far from optimum.133, 134
In the International Diabetes Management Practice Study, investigators analysed diabetes care outcome in urban areas in 18 countries, including eight countries from Asia, and showed that about a third of patients who were treated by diabetologists or endocrinologists had reached the goal of HbA1c concentrations of less than 7%.134 However, the proportion was similar in other developing regions, namely eastern Europe, Latin America, and Africa. Up to 40% of patients were not screened for risk factors or complications. In developing countries, factors pertinent to patients, doctors, and health-care systems all affect glycaemic control.134
Prevention and future action
Prevention of obesity and diabetes is more cost effective than is the treatment of complications resulting from diabetes. A 2—3% reduction in energy intake or an extra 10—15 min of walking each day could offset weight gain in roughly 90% of the population in China.85 Lifestyle intervention can have a sustained benefit, with a 43% reduction in incidence of diabetes over a 20-year period.135 The results of a primary prevention study in India have also shown that lifestyle modification is effective with an approximate reduction of 30% in comparison with the control group.136 Lifestyle modification was the most cost-effective intervention for prevention of diabetes in high-risk groups.137
The challenges for diabetes care in India, China, and other Asian countries will include improved education to alert the population to risk factors for diabetes, training of patients to manage their disease more effectively, and development of more structured care delivery and management of cardiometabolic risk factors.138, 139 A mismatch of national health-care budget and health-care burden, especially due to the epidemic of non-communicable diseases, poses a huge challenge in most countries. More data are needed for the economics of diabetes and the quality of life and cost-effectiveness of various interventions. Well targeted basic research is needed to provide insight into feasible strategies for prevention of diabetes and its complications.
A UN resolution has recognised type 2 diabetes as a serious epidemic for which urgent steps to improve management and prevent disease development are needed. It urges member states to develop national policies towards these goals.140 In many Asian countries (eg, India, China, Pakistan, Bangladesh, Malaysia, Vietnam, and Singapore), governments have initiated national programmes for prevention and control of non-communicable diseases. Programmes targeting greater public awareness of these diseases and strategies to build national capacity by training medical and paramedical personnel to manage the disorders are expected to curb the epidemic.
Search strategy and selection criteria
We searched PubMed using the keywords “diabetes in developing countries”, “diabetes in Asia”, “type 2 diabetes in Asia”, “risk of diabetes in Asian populations”, “obesity and diabetes in Asians”, “genetics of type 2 diabetes in Asian populations”, “Chinese”, “polymorphisms”, and “adipokines and diabetes in Asian populations”. Peer-reviewed reports published between 1980, and 2009, in English and Chinese were included. Several International Diabetes Federation and WHO publications were used, in addition to reviews and book chapters. We also searched the reference lists of reports identified by the search strategy and selected those judged relevant.
All authors have seen and approved the revised version of the Seminar. AR had final responsibility for the decision to submit for publication.
Conflicts of interest
We declare that we have no conflicts of interest.
We thank S Selvam and C J Thirupurasundari for help with compiling the references, L Vijaya and A Bobby for secretarial assistance, J Chan for her helpful comments, and J C Florez for permission to reproduce figure 2. RM acknowledges research funding support from the research fund of the Department of Medicine and Therapeutics, Chinese University of Hong Kong, the Research Grants Council of Hong Kong (CUHK4724/07M), and the Innovation and Technology Fund of the Government of the Hong Kong Special Administrative Region (ITS/088/08).
1 Wild S, Roglic G, Green A, Sicree R, King G. Global prevalence of diabetes. Estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27: 1047-1052. CrossRef | PubMed
2 Sicree R, Shaw J, Zimmet P. Prevalence and projections. In: Gan D, ed. Diabetes atlas. Brussels: International Diabetes Federation, 2006: 16-104.
3 WHO. The world health report 2004: changing history. Geneva: World Health Organization, 2004.
4 Sicree R, Shaw J, Zimmet P. Executive Summary. In: Gan D, ed. Diabetes atlas. Brussels: International Diabetes Federation and World Diabetes Foundation, 2003.
5 UN. World population prospects: the 2007 revision population database. http://esa.un.org/unup. (accessed April 10, 2009).
6 Ramachandran A, Mary S, Yamuna A, Murugesan N, Snehalatha C. High prevalence of diabetes and cardiovascular risk factors associated with urbanization in India. Diabetes Care 2008; 31: 893-898. CrossRef | PubMed
7 Mohan V, Deepa M, Deepa R, et al. Secular trends in the prevalence of diabetes and impaired glucose tolerance in urban South India—the Chennai urban rural epidemiology study (CURES-17). Diabetologia 2006; 49: 1175-1178. CrossRef | PubMed
8 Ramachandran A, Snehalatha C, Kapur A, et alDiabetes Epidemiology Study Group in India (DESI). High prevalence of diabetes and impaired glucose tolerance in India: national urban diabetes survey. Diabetologia 2001; 44: 1094-1101. CrossRef | PubMed
9 Ramachandran A, Snehalatha C, Latha E, Vijay V, Viswanathan M. Rising prevalence of NIDDM in an urban population in India. Diabetologia 1997; 40: 232-237. CrossRef | PubMed
10 Ramachandran A, Snehalatha C, Dharmaraj D, Viswanathan M. Prevalence of glucose intolerance in Asian Indians. Urban-rural difference and significance of upper body adiposity. Diabetes Care 1992; 15: 1348-1355. PubMed
11 Ramachandran A, Jali MV, Mohan V, Snehalatha C, Viswanathan M. High prevalence of diabetes in an urban population in south India. BMJ 1988; 297: 587-590. PubMed
12 Tian H, Song G, Xie H, Zhang H, Tuomilehto J, Hu G. Prevalence of diabetes and impaired fasting glucose among 769 792 rural Chinese adults. Diabetes Res Clin Pract 2009; 84: 273-278. CrossRef | PubMed
13 Dong Y, Gao W, Nan H, et al. Prevalence of type 2 diabetes in urban and rural Chinese populations in Qingdao, China. Diabet Med 2005; 22: 1427-1433. CrossRef | PubMed
14 Gu D, Reynolds K, Duan X, et al. Prevalence of diabetes and impaired glucose tolerance in the Chinese adult population: international collaborative study of cardiovascular disease in Asia (InterASIA). Diabetologia 2003; 46: 1190-1198. CrossRef | PubMed
15 Wang K, Li T, Xiang H, et al. Study on the epidemiological characteristics of diabetes mellitus and IGT in China. Zhonghua Liu Xing Bing Xue Za Zhi 1998; 19: 282-285. (in Chinese). PubMed
16 Pan XR, Yang WY, Li GW, Liu J. Prevalence of diabetes and its risk factors in China, 1994. National Diabetes Prevention and Control Cooperative Group. Diabetes Care 1997; 11: 1664-1669. PubMed
17 Li G, Hu Y, Pan X. Prevalence and incidence of NIDDM in Daqing city. Chin Med J (Engl) 1996; 109: 599-602. PubMed
18 A mass survey of diabetes mellitus in a population of 300,000 in 14 provinces and municipalities in China. Zhonghua Nei Ke Za Zhi 1981; 20: 678-683. (in Chinese). PubMed
19 Janus ED, Watt NM, Lam KS, et al. The prevalence of diabetes, association with cardiovascular risk factors and implications of diagnostic criteria (ADA 1997 and WHO 1998) in a 1996 community-based population study in Hong Kong Chinese. Hong Kong Cardiovascular Risk Factor Steering Committee. Diabet Med 2000; 17: 741-745. CrossRef | PubMed
20 Cockram CS, Woo J, Lau E, et al. The prevalence of diabetes and impaired glucose tolerance among Hong Kong Chinese adults of working age. Diabetes Res Clin Pract 1993; 21: 67-73. CrossRef | PubMed
21 Wu DM, Pai L, Chu NF, et al. Prevalence and clustering of risk factors among healthy adults in a Chinese population: the MJ Health Screening Center Study in Taiwan. Int J Obes 2001; 25: 1189-1195. CrossRef | PubMed
22 Kim SM, Lee JS, Lee J, et al. Prevalence of diabetes and impaired fasting glucose in Korea: Korean national health and nutrition survey 2001. Diabetes Care 2006; 29: 226-231. PubMed
23 Aekplakorn W, Abbott-Klafter J, Premgamone A, et al. Prevalence and management of diabetes and associated risk factors by regions of Thailand: third national health examination survey 2004. Diabetes Care 2007; 30: 2007-2012. CrossRef | PubMed
24 Aekplakorn W, Stolk RP, Neal B, et alfor the InterASIA collaborative group. The prevalence and management of diabetes in Thai adults: the international collaborative study of cardiovascular disease in Asia. Diabetes Care 2003; 26: 2758-2763. CrossRef | PubMed
25 Shera AS, Jawad F, Maqsood A. Prevalence of diabetes in Pakistan. Diabetes Res Clin Pract 2007; 76: 219-222. CrossRef | PubMed
26 Shera AS, Rafique G, Khawaja IA, Baqai S, King H. Pakistan national diabetes survey: prevalence of glucose intolerance and associated factors in Baluchistan province. Diabetes Res Clin Pract 1999; 44: 49-58. CrossRef | PubMed
27 Hussain A, Rahim MA, Khan AK Azad, Ali SMK, Vaaler S. Type 2 diabetes in rural and urban population: diverse prevalence and associated risk factors in Bangladesh. Diabet Med 2005; 22: 931-936. CrossRef | PubMed
28 Sayeed MA, Mahtab H, Khanam P Akter, et al. Diabetes and impaired fasting glycemia in a rural population of Bangladesh. Diabetes Care 2003; 26: 1034-1039. CrossRef | PubMed
29 Sayeed MA, Hussain MZ, Banu A, Rumi MA, Khan AK Azad. Prevalence of diabetes in a suburban population of Bangladesh. Diabetes Res Clin Pract 1997; 34: 149-155. CrossRef | PubMed
30 Lee WR. The changing demography of diabetes mellitus in Singapore. Diabetes Res Clin Pract 2000; 50: S35-S39. CrossRef | PubMed
31 Mafauzy M, Mokhtar N, Mohamad WB, Musalmah M. Diabetes mellitus and associated cardiovascular risk factors in north-east Malaysia. Asia Pac J Public Health 1999; 11: 16-19. PubMed
32 National health and morbidity surveys 1 & 2. Kuala Lumpur: Institute of Public Health, Ministry of Health Malaysia, 1985 & 1996.
33 Baltazar JC, Ancheta CA, Aban IB, Fernando RE, Baquilod MM. Prevalence and correlates of diabetes mellitus and impaired glucose tolerance among adults in Luzon, Philippines. Diabetes Res Clin Pract 2004; 64: 107-115. CrossRef | PubMed
34 Katulanda P, Constantine GR, Mahesh JG, et al. Prevalence and projections of diabetes and pre-diabetes in adults in Sri Lanka—Sri Lanka diabetes cardiovascular study (SLDCS). Diabet Med 2008; 25: 1062-1069. CrossRef | PubMed
35 Samrage SM. Some epidemiological aspects of non insulin dependent diabetes mellitus in a defined populaiton in the Kalutara District of SriLanka. MD thesis, University of Colombo, 1995.
36 Duc Son LN, Kusama K, Hung NT, et al. Prevalence and risk factors for diabetes in Ho Chi Minh City, Vietnam. Diabet Med 2004; 21: 371-376. CrossRef | PubMed
37 Diabetes towards the new millennium. Proceedings of the 3rd International Diabetes Federation Western Pacific Regional Congress, Hong Kong, September, 1996: 91—94.
38 King H, Keuky L, Seng S, Khun T, Toglic G, Pinget M. Diabetes and associated disorders in Cambodia: two epidemiological surveys. Lancet 2005; 366: 1633-1639. Summary | Full Text | PDF(105KB) | CrossRef | PubMed
39 De Courten M, Bennett P, Tuomilehto J, Zimmet P. Epidemiology of NIDDM in non-Europids. In: Alberti KGMM, Zimmet P, DeFronzo RA, eds. International textbook of diabetes mellitus. Chichester: Wiley, 1997: 143-170.
40 Unger RH, Zhou YT. Lipotoxicity of beta-cells in obesity and in other cause of fatty acid spillover. Diabetes 2001; 1: S118-S121. PubMed
41 Snehalatha C, Ramachandran A, Satyavani K, Latha E, Viswanathan V. Study of genetic prediabetic south Indian subjects. Importance of hyperinsulinemia and beta-cell dysfunction. Diabetes Care 1998; 21: 76-79. PubMed
42 Abate N, Chandalia M. Ethnicity, type 2 diabetes & migrant Asian Indians. Indian J Med Res 2007; 125: 251-258. PubMed
43 Abate N, Chandalia M, Snell PG, Grundy SM. Adipose tissue metabolites and insulin resistance in nondiabetic Asian Indian men. J Clin Endocrinol Metab 2004; 89: 2750-2755. CrossRef | PubMed
44 Mckeigue PM, Pierpoing T, Ferrie JE, Marmot MG. Relationship of glucose tolerance and hyperinsulinaemia to body fat pattern in south Asians and Europeans. Diabetologia 1992; 35: 785-791. PubMed
45 Raji A, Seely EW, Arky RA, Simonson DC. Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians. J Clin Endocrinol Metab 2001; 86: 5366-5371. CrossRef | PubMed
46 Ramachandran A, Snehalatha C, Yamuna A, Murugesan N, Narayan KM. Insulin resistance and clustering of cardiometabolic risk factors in urban teenagers in southern India. Diabetes Care 2007; 30: 1828-1833. CrossRef | PubMed
47 Misra A, Vikram NK. High prevalence of obesity and associated risk factors in urban children in India and Pakistan highlights immediate need to initiate primary prevention program for diabetes and coronary heart disease in schools. Diabetes Res Clin Pract 2006; 71: 101-102. CrossRef | PubMed
48 Viswanathan M, McCarthy MI, Snehalatha C, Hitman GA, Ramachandran A. Familial aggregation of type 2 (non-insulin-dependent) diabetes mellitus in south India; absence of excess maternal transmission. Diabetes Med 1996; 13: 232-237. PubMed
49 Ng MC, Lee SC, Ko GTC, et al. Familial early onset type 2 diabetes in Chinese: the more significant roles of obesity and genetics than autoimmunity. Diabetes Care 2001; 24: 667-671. PubMed
50 Fajans SS, Bell GI, Polonsky KS. Molecular mechanisms and clinical pathophysiology of maturity onset diabetes of the young. N Engl J Med 2001; 345: 971-980. CrossRef | PubMed
51 Altshuler D, Hirschhorn JN, Klannemark M, et al. The common PPAR gamma Pro12 Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 2000; 26: 76-80. CrossRef | PubMed
52 Gloyn AL, Weedon MN, Owen KR, et al. Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes 2003; 52: 568-572. CrossRef | PubMed
53 Radha V, Vimaleswaran KS, Babu HN, et al. Role of genetic polymorphism peroxisome proliferators-activated receptor-gamma2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: evidence for heterogeneity. Diabetes Care 2006; 29: 1046-1051. CrossRef | PubMed
54 Grant SF, Thorleifsson G, Reynisdottir I, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 2006; 38: 320-323. CrossRef | PubMed
55 Cauchi S, El Achhab Y, Choquet H, et al. TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis. J Mol Med 2007; 85: 777-782. CrossRef | PubMed
56 Chang YC, Chang TJ, Jiang YD, et al. Association study of the genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene and type 2 diabetes in the Chinese population. Diabetes 2007; 56: 2631-2637. CrossRef | PubMed
57 Ng MC, Park KS, Oh B, et al. Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes 2008; 57: 2226-2233. CrossRef | PubMed
58 Frayling TM. Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genet 2007; 8: 657-662. CrossRef | PubMed
59 Florez JC. Clinical review: the genetics of type 2 diabetes: a realistic appraisal in 2008. J Clin Endocrinol Metab 2008; 93: 4633-4642. CrossRef | PubMed
60 Omori S, Tanaka Y, Takahashi A, et al. Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes 2008; 57: 791-795. CrossRef | PubMed
61 Sakamoto Y, Inoue H, Keshavarz P, et al. SNPs in the KCNJ11-ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population. J Hum Genet 2007; 52: 781-793. CrossRef | PubMed
62 Chandak GR, Janipalli CS, Bhaskar S, et al. Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population. Diabetologia 2007; 50: 63-67. CrossRef | PubMed
63 Bodhini D, Radha V, Dhar M, Narayani N, Mohan V. The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians. Metabolism 2007; 56: 1174-1178. CrossRef | PubMed
64 Sanghera DK, Ortega L, Han S, et al. Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. BMC Med Genet 2008; 9: 59. CrossRef | PubMed
65 Ng MC, Tam CH, Lam VK, So WY, Ma RC, Chan JC. Replication and identification of novel variants at TCF7L2 associated with type 2 diabetes in Hong Kong Chinese. J Clin Endocrinol Metab 2007; 92: 3733-3737. CrossRef | PubMed
66 Hayashi T, Iwamoto Y, Kaku K, Hirose H, Maeda S. Replication study for the association of TCF7L2 with susceptibility to type 2 diabetes in a Japanese population. Diabetologia 2007; 50: 980-984. CrossRef | PubMed
67 Horikoshi M, Hara K, Ito C, Nagai R, Froguel P, Kadowaki T. A genetic variation of the transcription factor 7-like 2 gene is associated with risk of type 2 diabetes in the Japanese population. Diabetologia 2007; 50: 747-751. CrossRef | PubMed
68 Steinthorsdottir V, Thorleifsson G, Reynisdottir I, et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet 2007; 39: 770-775. CrossRef | PubMed
69 Wu Y, Li H, Loos RJ, et al. Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Diabetes 2008; 57: 2834-2842. CrossRef | PubMed
70 Sandhu MS, Weedon MN, Fawcett KA, et al. Common variants in WFS1 confer risk of type 2 diabetes. Nat Genet 2007; 39: 951-953. CrossRef | PubMed
71 Zeggini E, Scott LJ, Saxena R, et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 2008; 40: 638-645. CrossRef | PubMed
72 Gudmundsson J, Sulem P, Steinthorsdottir V, et al. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat Genet 2007; 39: 977-983. CrossRef | PubMed
73 Yasuda K, Miyake K, Horikawa Y, et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet 2008; 40: 1092-1097. CrossRef | PubMed
74 Unoki H, Takahashi A, Kawaguchi T, et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet 2008; 40: 1098-1102. CrossRef | PubMed
75 Lyssenko V, Lupi R, Marchetti P, et al. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest 2007; 117: 2155-2163. CrossRef | PubMed
76 Lyssenko V, Jonsson A, Almgren P, et al. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med 2008; 359: 2220-2232. CrossRef | PubMed
77 Yajnik CS, Janipalli CS, Bhaskar S, et al. FTO gene variants are strongly associated with type 2 diabetes in South Asian Indian. Diabetologia 2009; 52: 247-252. CrossRef | PubMed
78 Leon DA. Cities, urbanization and health. Int J Epidemiol 2008; 37: 4-8. CrossRef | PubMed
79 Ramachandran A, Snehalatha C, Baskar AD, et al. Temporal changes in prevalence of diabetes and impaired glucose tolerance associated with lifestyle transition occurring in the rural population in India. Diabetologia 2004; 47: 860-865. CrossRef | PubMed
80 Chan JC, Cockram CS. Epidemiology of diabetes mellitus in China. In: Ekoe J-M, Rewers M, Williams R, Zimmet P, eds. The epidemiology of diabetes mellitus. Chichester: Wiley, 2008: 179-206.
81 Popkin BM. Global nutrition dynamics: the world is shifting rapidly towards a diet linked with noncommunicable disease. Am J Clin Nutr 2006; 84: 289-298. PubMed
82 Kawate R, Yamakido M, Nishimoto Y, Bennett PH, Hamman RF, Knowler WC. Diabetes mellitus and its vascular complications in Japanese migrants on the island of Hawaii. Diabetes Care 1979; 2: 161-170. PubMed
83 Qiao Q, Hu G, Tuomilehto J, et alfor the DECODA study group. Age and sex-specific prevalence of diabetes and impaired glucose regulation in 11 Asian cohorts. Diabetes Care 2003; 26: 1770-1780. CrossRef | PubMed
84 Mohan V, Ramachandran A, Snehalatha C, et al. High prevalence of maturity onset diabetes of the young (MODY) among Indians. Diabetes Care 1985; 8: 371-374. PubMed
85 Zhai F, Wang H, Wang Z, Popkin BM, Chen C. Closing the energy gap to prevent weight gain in China. Obes Rev 2008; 1: 107-112. PubMed
86 Yoon KH, Lee JH, Kim JW, et al. Epidemic obesity and type 2 diabetes in Asia. Lancet 2006; 368: 1681-1688. Summary | Full Text | PDF(180KB) | CrossRef | PubMed
87 Ramachandran A, Snehalatha C, Satyavani K, Sivasankari S, Vijay V. Type 2 diabetes in Asian-Indian urban children. Diabetes Care 2003; 26: 1022-1025. CrossRef | PubMed
88 Yajnik CS, Deshmukh US. Maternal nutrition, intrauterine programming and consequential risks in the offspring. Rev Endocr Metab Disord 2008; 9: 203-211. CrossRef | PubMed
89 Zhao HL, Lai FM, Tong PC, et al. Prevalence and clinicopathological characteristics of islet amyloid in Chinese patients with type 2 diabetes. Diabetes 2003; 52: 2759-2766. CrossRef | PubMed
90 Gill T. Young people with diabetes and obesity in Asia: a growing epidemic. Diabetes Voice 2007; 52: 20-22. PubMed
91 Ehtisham S, Barrett TG, Shaw NJ. Type 2 diabetes mellitus in UK children—an emerging problem. Diabet Med 2000; 17: 867-871. CrossRef | PubMed
92 Wei JN, Sung FC, Lin CC, et al. National surveillance for type 2 diabetes mellitus in Taiwanese Children. JAMA 2003; 290: 1345-1350. CrossRef | PubMed
93 Li Y, Yang X, Zhai F, et al. Childhood obesity and its health consequence in China. Obes Rev 2008; 9 (suppl 1): 82-86. CrossRef | PubMed
94 Ko GT, Ozaki R, Wong GW, et al. The problem of obesity among adolescents in Hong Kong: a comparison using various diagnostic criteria. BMC Pediatr 2008; 8: 10. CrossRef | PubMed
95 Joshi SR. Metabolic syndrome—emerging clusters of the Indian phenotype. J Assoc Physicians India 2003; 51: 445-446. PubMed
96 Sinha R, Dufour S, Petersen KF, et al. Assessment of skeletal muscle triglyceride content by 1H nuclear magnetic resonance spectroscopy in lean and obese adolescents: relationships to insulin sensitivity, total body fat, and central adiposity. Diabetes 2002; 51: 1022-1027. CrossRef | PubMed
97 Yu C, Chen Y, Cline GW, et al. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 2002; 277: 50230-50236. CrossRef | PubMed
98 Havel PJ. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr Opin Lipidol 2002; 13: 51-59. CrossRef | PubMed
99 Leinonen E, Hurt-Camejo E, Wiklund O, Hulten LM, Hiukka A, Taskinen MR. Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesion molecules in type 2 diabetes. Atherosclerosis 2003; 166: 387-394. CrossRef | PubMed
100 Snehalatha C, Sivasankari S, Satyavani K, Vijay V, Ramachandran A. Postprandial hypertriglyceridaemia in treated type 2 diabetic subjects—the role of dietary components. Diabetes Res Clin Pract 2000; 48: 57-60. CrossRef | PubMed
101 Misra A, Pandey RM, Ramadevi J, Sharma R, Vikram NK, Khanna N. High prevalence of diabetes, obesity and dyslipidemia in urban slum population in northern India. Int J Obes Relat Metab Disord 2001; 125: 1722-1729. PubMed
102 WHO expert consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004; 363: 157-163. CrossRef | PubMed
103 Alberti KGMM, Zimmet P, Shaw Jfor the IDF Epidemiology Task Force Consensus Group. The metabolic syndrome—a new worldwide definition. Lancet 2005; 366: 1059-1062. Full Text | PDF(64KB) | CrossRef | PubMed
104 Misra A, Chowbey P, Makkar BM, et alfor Consensus Group. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India 2009; 57: 163-170. PubMed
105 Snehalatha C, Ramachandran A, Satyavani K, Vallabi MY, Vijay V. Computed axial tomographic scan measurement of abdominal fat distribution and its correlation to anthropometry and insulin secretion in healthy Asian Indians. Metabolism 1997; 46: 1220-1224. CrossRef | PubMed
106 Chandalia M, Lin P, Seenivasan T, et al. Insulin resistance and body fat distribution in South Asian men compared to Caucasian men. PloS One 2007; 2: 812. PubMed
107 Jarvinen HY. Ectopic fat accumulation: an important cause of insulin resistance in humans. J R Soc Med 2002; 95: 39-45. CrossRef | PubMed
108 Taylor R. Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause. Diabetologia 2008; 51: 1781-1789. CrossRef | PubMed
109 Retnakaran R, Hanley AJG, Zinman B. Does hypoadiponectinmia explain the increased risk of diabetes and cardiovascular disease in south Asians?. Diabetes Care 2006; 29: 1950-1954. CrossRef | PubMed
110 Snehalatha C, Yamuna A, Ramachandran A. Plasma adiponectin does not correlate with insulin resistance and cardiometabolic variables in non-diabetic Asian Indian teenagers. Diabetes Care 2008; 31: 2374-2379. CrossRef | PubMed
111 Snehalatha C, Mukesh B, Simon M, Viswanathan V, Haffner SM, Ramachandran A. Plasma adiponectin is an independent predictor of type 2 diabetes in Asian Indians. Diabetes Care 2003; 26: 3226-3229. CrossRef | PubMed
112 Martin M, Palaniappan LP, Kwan AC, Reaven GM. Ethnic differences in the relationship between adiponectin and insulin sensitivity in south Asian and Caucasian women. Diabetes Care 2008; 31: 798-801. CrossRef | PubMed
113 Nair SK, Bigelow ML, Asmann YW, et al. Asian Indians have enhanced skeletal muscle mitochondrial capacity to produce ATP in association with severe insulin resistance. Diabetes 2008; 57: 1166-1175. CrossRef | PubMed
114 Forouhi NG, Jenkinson G, Thomas EL, et al. Relation of triglyceride stress in skeletal muscle cells to central obesity and sensitivity in European and southern Asian men. Diabetologia 1999; 42: 932-935. CrossRef | PubMed
115 Chin K, Shimizu K, Nakamura T, et al. Changes in intra-abdominal visceral fat and serum leptin levels in patients with obstructive sleep apnea syndrome following nasal continuous positive airway pressure therapy. Circulation 1996; 100: 706-712. PubMed
116 Wolk R, Somers VK. Sleep and the metabolic syndrome. Exp Physiol 2007; 92: 67-78. CrossRef | PubMed
117 Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 2008; 359: 61-73. CrossRef | PubMed
118 Ma RC, Chan JCN. Pregnancy and diabetes scenario around the world: China. Int J Gynaecol Obstet 2009; 1: S42-S45. PubMed
119 Tam WH, Ma RC, Yang XL, et al. Glucose intolerance and cardiometabolic risk in children exposed to maternal gestational diabetes mellitus in utero. Pediatrics 2008; 122: 1229-1234. PubMed
120 WHO/IDF consultation. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. Geneva: World Health Organization, 2006.
121 Nakagami T. Hyperglycaemia and mortality from all causes and from cardiovascular disease in five populations of Asian origin. Diabetologia 2004; 47: 385-394. CrossRef | PubMed
122 Ramachandran A, Snehalatha C, Latha E, Vijay V. Evaluation of the use of fasting plasma glucose as a new diagnostic criterion for diabetes in Asian Indian population. Diabetes Care 1998; 21: 666-667. CrossRef | PubMed
123 Snehalatha C, Ramachandran A, Satyavani K, Vijay V. Limitations of glycosylated haemoglobin as an index of glucose intolerance. Diabetes Res Clin Pract 2000; 47: 129-133. CrossRef | PubMed
124 Ramachandran A, Snehalatha C, Vijay V, Kingh H. Impact of poverty on the prevalence of diabetes and its complications in urban southern India. Diabet Med 2002; 19: 130-135. CrossRef | PubMed
125 Marguerite J, McNeely , Fujimoto WY. Epidemiology of diabetes in Asian North Americans. In: Ekoe JM, Rewers M, Williams R, Zimmet P, eds. The epidemiology of diabetes mellitus. Chichester: Wiley, 2008: 323-337.
126 Ramachandran A, Snehalatha C, Mohan V, Viswanathan M. Vascular complications in Asian Indian non-insulin dependent diabetic patients. J Med Assoc Thai 1987; 2: 180-184. PubMed
127 Bhopal R, Unwin N, White M, et al. Heterogeneity of coronary heart disease risk factors in India, Pakistani, Bangladeshi, and European origin populations: cross sectional study. BMJ 1999; 319: 215-220. PubMed
128 Chi ZS, Lee ET, Lu M, Keen H, Bennett PH. Vascular disease prevalence in diabetic patients in China: standardised comparison with the 14 centres in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia 2001; 44: S82-S86. CrossRef | PubMed
129 Wu AY, Kong NC, de Leon FA, et al. An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients: the MicroAlbuminuria Prevalence (MAP) study. Diabetologia 2005; 48: 17-26. CrossRef | PubMed
130 Luk AO, So WY, Ma RC, et al. Metabolic syndrome predicts new onset of chronic kidney disease in 5,829 patients with type 2 diabetes: a 5-year prospective analysis of the Hong Kong Diabetes Registry. Diabetes Care 2008; 31: 2357-2361. CrossRef | PubMed
131 Ramachandran A, Shobana R, Snehalatha C, et al. Increasing expenditure on health care incurred by diabetic subjects in a developing country: a study from India. Diabetes Care 2007; 30: 252-256. CrossRef | PubMed
132 Yach D, Stuckler D, Brownell KD. Epidemiologic and economic consequences of the global epidemics of obesity and diabetes. Nat Med 2006; 12: 62-66. CrossRef | PubMed
133 Kapur A. Economic analysis of diabetes care. Indian J Med Res 2007; 125: 473-482. PubMed
134 Chan JCN, Gagliardino JJ, Baik SH, et al. Multi-faceted determinants for achieving glycemic control: the International Diabetes Management Practice Study (IDMPS). Diabetes Care 2009; 32: 227-233. CrossRef | PubMed
135 Li G, Zhang P, Wang J, et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet 2008; 371: 1783-1789. Summary | Full Text | PDF(163KB) | CrossRef | PubMed
136 Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay VIndian Diabetes Prevention Programme (IDPP). The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia 2006; 49: 289-297. CrossRef | PubMed
137 Ramachandran A, Snehalatha C, Yamuna A, Mary S, Ping Z. Cost-effectiveness of the interventions in the primary prevention of diabetes among Asian Indians: within-trial results of the Indian Diabetes Prevention Programme (IDPP). Diabetes Care 2007; 30: 2548-2552. CrossRef | PubMed
138 Chan JC, Cockram CS. Diabetes in the Chinese population and its implications for health care. Diabetes Care 1997; 20: 1785-1790. PubMed
139 Murugesan N, Snehalatha C, Shobhana R, Roglic G, Ramachandran A. Awareness about diabetes and its complications in the general and diabetic population in a city in southern India. Diabetes Res Clin Pract 2007; 77: 433-437. CrossRef | PubMed
140 UN. Resolution adopted by the General Assembly. 61/225 World Diabetes Day. Geneva: United Nations, 2007. http://www.un.org/Docs/journal/asp/ws.asp?m=A/RES/61/225. (accessed Feb 20, 2009).