The growing pandemic of type 2 diabetes: a crucial need for prevention and improved detection




Paul Z. ZIMMET,AO, MD, PhD, FRACP, FRCP, FTSE
Baker IDI Heart and Diabetes Institute, Caulfield, Melbourne
Victoria, AUSTRALIA

Changes in human behavior and lifestyle associated with globalization have resulted in a dramatic increase in the prevalence and incidence of type 2 diabetes globally. Until recently, there was a strong emphasis on genetic susceptibility, and on environmental and behavioral factors such as a sedentary lifestyle, overly rich nutrition, and obesity (particularly central adiposity). More recently, focus has shifted to the potential contribution of the maternal environment and the impact of in-utero influences, ie, the role of epigenetics. This may be an important factor in the very high prevalences of type 2 diabetes now being seen in nations such as India and China, two countries that numerically bear the main brunt of the epidemic. Type 2 diabetes is appearing increasingly in children and adolescents, and the frequency of diagnosis of pediatric type 2 diabetes is outstripping that of type 1 diabetes in some countries already. The prevention of diabetes and control of its micro- and macrovascular complications will require a major integrated approach directed at societal and individual behavioral change if we are to see significant reduction in the huge premature morbidity and mortality it causes. Diabetes is looming as one of the greatest threats to public health in the 21st century. This is an impelling rationale for strengthening efforts for its prevention and control.

Medicographia. 2011;33:15-21 (see French abstract on page 21)

If anyone had predicted 30 years ago that diabetes mellitus would be one of the biggest public health problems facing the human race in 2010, they would not have been taken seriously. Yet, in 1977, when we published the prevalence of diabetes in the Pacific island nation of Nauru,1 the writing was on the wall. Elsewhere, our studies of the secular rises in type 2 diabetes in the Indian Ocean island nation of Mauritius2,3 were a barometer that provided further predictions of the global epidemic.4

In an earlier review article on the global epidemiology of diabetes published in Medicographia in 1987,5 I pointed out that the mounting problems of chronic noncommunicable disease, and in particular diabetes, raised the important challenge of noncommunicable disease prevention, a 21st-century parallel to the prevention of infectious disease at the turn of the 19th century. Prevention of diabetes is a major challenge that faces nearly every nation and it is now being recognized by the international community. In December 2006, against the background of an escalating diabetes epidemic, the United Nations General Assembly voted unanimously to pass Resolution 61/225 declaring diabetes an international public health issue. For the first time, governments acknowledged that a noninfectious disease could pose as serious a threat to world health as infectious diseases such as HIV/AIDS, tuberculosis, or malaria. This United Nations resolution recognized that tackling diabetes is likely to be one of the most important challenges for the global public health community in the 21st century.

Figure 1
Figure 1. Global projections for the diabetes epidemic: 2010-2030 (millions).

In each box, the top figure represents the number of people with diabetes in that region (millions) in 2010; the middle figure is the projected number of people with diabetes
(millions) in 2030; and the bottom figure is the percentage change from 2010 to 2030.
Modified from reference 6: International Diabetes Federation. IDF Diabetes Atlas. 4th ed. Brussels, Belgium: International Diabetes Federation; 2009:21-27. © 2009, International Diabetes Federation.

Resolution 61/225 declaring diabetes an international public health issue. For the first time, governments acknowledged that a noninfectious disease could pose as serious a threat to world health as infectious diseases such as HIV/AIDS, tuberculosis, or malaria. This United Nations resolution recognized that tackling diabetes is likely to be one of the most important challenges for the global public health community in the 21st century.

The most recent global predictions by the Baker IDI Heart and Diabetes Institute for the International Diabetes Federation (IDF) suggest that currently there are 285 million people with diabetes worldwide.6 This is set to escalate to 438 million by 2030, a 54% increase. Figure 1 shows these data from the 2009 IDF Diabetes Atlas6 with the expected increases in the next 20 years to 2030 by geographic region and the global total. Many of these cases of diabetes will remain undiagnosed, and indeed untreated, particularly in developing nations (Figure 1).

Just to give a perspective, type 2 diabetes has reached epidemic proportions inmany developing nations and someMiddle- Eastern nations, as well as in disadvantaged minorities in developed countries, eg, Australian Aboriginals and Torres Strait Islanders;7 Native-, African-, and Mexican-Americans in the USA;8-10 and also in Asian Indians and Chinese.9,10

Table I illustrates the dramatic rises in diabetes prevalence in several Asian nations compared to the prevalence in the USA. The increases in Asia are much greater. Compared with a 1.5-fold increase in the USA from 1978-2000, South Korea experienced a dramatic 5.1-fold increase between 1971 and 2001.11

We, and others, have reviewed the epidemiology of type 2 diabetes in great detail elsewhere.9,10 Rather than provide a repeat of these earlier papers, this review focuses on more recent studies which underline the dramatic escalation in the number of cases of diabetes in both developed and developing nations.

Table I
Table I. The multiplicative increase in diabetes prevalence in selected
Asian nations compared with the United States of America.

Modified from reference 11: Yoon et al. Lancet. 2006;368:1681-1688. © 2006, Elsevier Ltd.

One of the most recent and largest studies of diabetes in a white population is the AUStralian DIABetes and obesity study (AUSDIAB).12 In 2000, AUSDIAB studied 11 247 adults and provided the first national Australian data on the prevalence and incidence of diabetes.12,13 In comparisons of AUSDIAB with the only previous Australian population–based study to include an oral glucose tolerance test (OGTT) (in Busselton, Western Australia), we were able to show that there was a rapidly rising prevalence of diabetes in Australia, with a more than doubling of the age-specific prevalence of diabetes from 1981 to 2000 (Figure 2). In 2005, there was a follow-up study that found that the age-standardized annual incidence of diabetes for men and women was 0.8% (95% CI, 0.6 to 0.9) and 0.7%(95%CI, 0.5 to 0.8), respectively.13 The annual incidence was 0.2% (95% CI, 0.2 to 0.3), 2.6% (95% CI, 1.8 to 3.4), and 3.5% (95% CI, 2.9 to 4.2) in those with normoglycemia, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG), respectively, at baseline. In those with IFG, the incidence was significantly higher in women (4.0% vs 2.0%), while in those with IGT, it was significantly higher in men (4.4% vs 2.9%). In age- and sex-adjusted models, glycated hemoglobin (HbA1c) was a predictor of diabetes in the whole population, in those with normoglycemia and in those with IGT or IFG at baseline. The incidence of diabetes was 10-20 times greater in those with IGT or IFG than in those with normoglycemia at baseline. The AUSDIAB data reflect, in general, the status of diabetes in developed nations with a predominantly white population. What is also noteworthy is the more pronounced earlier age of onset of type 2 diabetes in the AUSDIAB cohort.

Much more dramatic and reflective of the rise and rise of diabetes are the data emerging from Asian nations as they experience the influence of modernization and industrialization, and their economies begin to blossom.6,10,14 The “epicenter” for the diabetes epidemic is in Asia, with India and China having the highest number of cases of type 2 diabetes.6 As was mentioned earlier, if our 1975 study in the Pacific island of Nauru1 was one of the first warnings of the potential global epidemic, our subsequent studies in the Indian Ocean nation of Mauritius, another barometer of the potential escalation, have provided further data. Its multiethnic population of some 1.3 million inhabitants predominantly comprises Asian Indians, Creoles (mainly African), and Chinese. This distribution of ethnic groups in Mauritius reflects approximately two-thirds of the world population,4 providing a microcosm of the global picture.

Our serial studies in Mauritius apart from demonstrating a high prevalence and incidence of diabetes have demonstrated a notable secular prevalence increase from 12.8% in 1987, to 15.2%in 1992, and 17.9% in 1998.15 Our latest study, in 2006, shows a further increase in prevalence to 23.4% (unpublished data). Consequently, the results from this small island population have suggested that modernization could have a very serious impact on diabetes rates in both India and China, in terms of the impact on both health as well as on the national economy.8 Indeed, this has turned out to be the case. This, evidence that the prevalence of type 2 diabetes doubled in Singaporean Chinese between 1984 and 1992,16 and the high prevalence of diabetes in Taiwan17 have provided alarming indicators of the size of a potential future epidemic in the People’s Republic of China.

Figure 2
Figure 2. Trends in diabetes prevalence (%) in Australia 1981-2000.

Abbreviation: AUSDIAB, AUStralian DIABetes and obesity study.

From a very low prevalence of diabetes in 1980 in Shanghai where the prevalence of type 2 diabetes was less than 1%, the prevalence has risen markedly to 6.9%.18 In addition, a report from Qingdao showed a dramatic secular increase in prevalence, eg, between 2001/2002 and 2006, the urban prevalence in men aged 35 to 75 years increased from 11.3% to 19.2%.19 At the time, it was suggested that China had the second highest number of people with diabetes in the world after India.6

However, a more recent report with results from a 2007/2008 national study among Chinese adults has put China well in front.20 A nationally representative sample of 46 239 adults, 20 years of age and over, was selected from 14 provinces and municipalities. Previously diagnosed diabetes was determined on the basis of self-report. The rest of the participants underwent an OGTT. The age-standardized prevalence of all diabetes was 9.7% (men, 10.6%; women, 8.8%) and for prediabetes it was 15.5% (men, 16.1%; women, 14.9%). Extrapolated nationally, the authors point out that this reflects 92.4 million adults with diabetes and 148.2 million adults with prediabetes. The prevalence of diabetes was higher among urban residents than among rural residents (11.4% vs 8.2%). The results indicate that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed. This is likely to be a significant understatement of the profound impact this will have on their health system, especially as modernization and industrialization gather pace.

A similar large secular increase in diabetes has occurred in India and, indeed, other Asian nations.6,11,14 India once led the world with the largest number of diabetic subjects. It had earned the dubious distinction of being the world “capital” for diabetes, a title that now more appropriately belongs to China! In an urban national study reported in 2001, the age standardized prevalence of type 2 diabetes was 12.1%. The highest rates were seen in the southern part of India with 13.5% in Chennai and 16.6% in Hyderabad.21 A more recent study showed a dramatic secular increase in diabetes from 13.9% in 2000 to 18.6% in 2006,22 a rise of 34% in a relatively short period.

Other “hot spots” for diabetes include the Gulf region in the Middle East, another area where the epidemic is taking hold.10 A survey conducted in Qatar among Qatari nationals above 20 years of age showed that the prevalence of diabetes was high at 16.7%.23 Diagnosed diabetes constituted 10.7%, while newly diagnosed cases accounted for 5.9%. IGT was diagnosed in 12.5%and IFG occurred in 1.3%. Interestingly, prevalence can vary depending on population within a country. A 1999/2000 study in the United Arab Emirates covered both the local community and expatriate workers.24 The crude prevalence of diabetes was 20%. It was higher, at 25%, in citizens from the United Arab Emirates than in expatriates (with a prevalence of 13%-19%, depending on their original country of origin). The authors stated that prompt action would be needed in order to avert a major public health crisis. In Oman, another Gulf nation, the prevalence of diabetes by fasting plasma glucose ≥7 mmol/L in the capital, Muscat, was 17.7% compared to 10.5% in rural areas.25 The prevalence of selfreported diabetes was 4.3%. Similarly, a high prevalence of diabetes has been noted in other countries in that region, including Saudi Arabia and Kuwait.10

Type 2 diabetes in children–the emerging threat

There is now a major emerging global phenomenon that reveals a new perspective of the global diabetes epidemic. This is the younger age of onset being seen in type 2 diabetes, which was formerly considered a disease of adults.4 However, in recent years, type 2 diabetes is appearing at a younger age, not only in the young adult population, but also in adolescents and, occasionally, in children.4,26 As might be expected, the majority of the cases are being seen in ethnic groups already shown to be at high risk of type 2 diabetes such as the Pima Indians.27 Until now, type 1 diabetes has been the major form seen in children, but it seems likely that type 2 diabetes is set to become the predominant form within the next 10 years in many ethnic groups and potentially also in white children. Type 2 diabetes has already been reported in children from Japan and other Asian nations, the USA, the Pacific Islands, Hong Kong, Australia, and the United Kingdom.4 In Japan, type 2 diabetes is already more common in children than type 1 diabetes. Type 2 diabetes accounts for 80 percent of cases of diabetes in childhood in that country.28 This is certainly an emerging public health problem of significant proportions as the fall in the age of onset of type 2 diabetes is an important factor influencing the future burden of the disease. Onset in childhood heralds many years of disease and an accumulation of the full range of both micro- and macrovascular complications, particularly as compliance to hypoglycemic medications is often an issue.27

The risk determinants for type 2 diabetes in children and adolescents are similar to those seen in adults, with obesity almost always being present.29 In-utero exposure to hyperglycemia now appears to be an additional risk factor to having a family history of diabetes,30 and suggests that better management of diabetes in pregnancy and prevention of gestational diabetes may reduce the risk of diabetes developing in the offspring.

The crucial need for screening and prevention

Type 2 diabetes is common and serious, but often asymptomatic in the early stages, which sometimes last up to five years or more. Interventions are available that reduce morbidity and mortality, as well as the risk of developing diabetes,31,32 a compelling argument for screening the population for those at highest risk.

Screening programs should begin with simple tools that are effective in identifying those at highest risk, but which can be used by the general public.33 Those found to be at high risk should undergo further screening and diagnostic blood glucose testing to accurately characterize their glucose tolerance status, and these people should commence a lifestyle intervention program (relevant whether they have diabetes or are at risk of it in the future). Nevertheless, it should be recognized that absolute evidence for the benefit of screening is not yet available.

The cost-effectiveness of screening strategies is the subject of current interest. A very recent study from the USA34 used a mathematical model (the Archimedes model) to estimate the cost-effectiveness of several screening strategies.

Table II
Table II. The AUStralian type 2 Diabetes RISK assessment tool (AUSDRISK).

The authors used person-specific data from a representative sample of the US population to create a simulated population of 325 000 people aged 30 years without diabetes. They found that compared with no screening, all simulated screening strategies reduced the incidence of myocardial infarction (3-9 events prevented per 1000 people screened) and diabetes-related microvascular complications (3-9 events prevented per 1000 people). They concluded that in the USA population, screening for type 2 diabetes is cost effective when started between the ages of 30 years and 45 years, with screening repeated every 3-5 years.

Taking into account the continuing discussions about the effectiveness of screening for undiagnosed type 2 diabetes and identifying those at high risk of developing diabetes in the near future, the following broad approach is recommended:
1. Use of a preliminary screening tool such as FINDRISK (FINnish Diabetes RISK score)35 or AUSDRISK (AUStralian type 2 Diabetes RISK assessment tool)36 (Table II, page 19). These can be done by the general public as well as by health-care professionals.
2. All those identified as being at high risk should enter a lifestyle intervention program and have blood glucose testing.
3. Fasting plasma glucose (FPG) is the initial blood glucose screening test for those at high risk, according to the preliminary screening tool.
4. On the basis of FPG (see below), the following steps should be taken:
_ FPG <5.5 mmol/L – no further blood testing needed _ FPG 5.5-6.9 mmol/L – proceed to OGTT _ FPG ≥7.0 mmol/L – repeat FPG to confirm the clinical diagnosis. The most dramatic increases in type 2 diabetes have occurred in populations where there have been major changes in lifestyle.4,8-10 This entails adverse changes in diet and reductions in physical activity levels, with consequent increases in the prevalence of overweight people and obesity, particularly when excess adiposity is centrally distributed.4

When looking for an opportunity to prevent type 2 diabetes, risk factors should be viewed in terms of being either modifiable, eg, sedentary behavior, or nonmodifiable, eg, genetic, age, or gender (Table III).

Table III
Table III. Modifiable and nonmodifiable risk factors for type 2 diabetes
mellitus.

Abbreviations: IFG, impaired fasting glucose; IGT, impaired glucose tolerance.

An important new area becoming the focus of more attention is the intrauterine environment. The intrauterine environment influences the risk of developing type 2 diabetes.37 Offspring from diabetic pregnancies are often large and heavy at birth, develop obesity in childhood, and are at high risk of developing type 2 diabetes at an early age.30 Quite independently of this, there is increasing interest in the influence of epigenetic scenarios of in-utero exposure to risk factors, eg, poor maternal nutrition, which increases the risk of diabetes, obesity, and cardiovascular disease in adult life.37 This emphasizes the need for a “whole-of-life” approach to the prevention of type 2 diabetes and its complications.

Conclusion

Diabetes is a chronic disease that through its complications can seriously impact the quality of life of individuals and their families through premature illness and death. Because diabetes now affects much of the workforce, it has a major effect on both individual health and national productivity. The socioeconomic consequences of diabetes are likely to significantly impact the economies of many developing nations in addition to their devastating impact on the economies of developed nations, such as the USA, UK, and Australia. With diabetes being one of the greatest threats to public health in the 21st century, the rationale for strengthening efforts to prevent and control this menacing chronic disease is surely impelling.

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Keywords: diabetes mellitus; type 2; epidemic; global; screening; prevention