Diabetes is one of the fastest growing public health problems in the world, with significant variations in its prevalence and in the major risk factors for type 2 diabetes among ethnic groups.

In this issue of Diabetes, the Perspective by Unnikrishnan et al. (1) focuses on the global prevalence of diabetes, ethnic differences in susceptibility to diabetes, and major determining factors for type 2 diabetes. A major concern today is the increasing number of people with type 2 diabetes in middle-income and low-income countries, such as China and India. Vulnerability to diabetes among immigrants from Korea, the Pacific Islands, South Asia, and the Philippines to the U.S. or Europe compared with the Caucasian population is highlighted. Although obesity and its correlate insulin resistance, as well as genetic factors, have been considered the established determining factors for type 2 diabetes risk, recent evidence shows that early loss of β-cell function plays a much more important role in the pathogenesis of type 2 diabetes, especially in nonobese individuals of southern and eastern Asian origin.

The results from the China National Diabetes Survey have indicated that the prevalence of diabetes in Chinese adults aged ≥20 years increased from 1% in 1980 (2) to 9.7% in 2007–2008 (3) and 11.6% in 2010 (4). One recent pooling of data from 751 studies including 4,372,000 adults from 146 of 200 countries estimated that the number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014, while the global age-standardized diabetes prevalence increased from 4.3% in 1980 to 9.0% in 2014 in men and from 5.0% to 7.9% in women (5). The prevalence and number of adults with diabetes increased at a greater rate in low-income and middle-income countries than in high-income countries. East Asia and South Asia present the largest rises of absolute numbers and had the greatest number of people with diabetes in 2014. However, diabetes prevalence in the pooled data was analyzed based on fasting plasma glucose alone. As such, the authors could have missed some cases of type 2 diabetes. The Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe (DECODE) (6) and Asia (DECODA) (7) studies show that fasting plasma glucose alone only diagnosed ∼68% of new patients with diabetes in Europe and 55% of new patients with diabetes in Asia. In the China National Diabetes Survey, 46.6% of the participants with undiagnosed diabetes had isolated increased 2-h plasma glucose after an oral glucose tolerance test. It seems that 2-h glucose during an oral glucose tolerance test is more sensitive for diagnosing diabetes in Asians when considering postchallenge hyperglycemia as the signature change of β-cell dysfunction in early-phase insulin secretion. Thus, the true estimated prevalence of diabetes in the world should be higher than the data from this pooling analysis.

Although all human ethnic groups are at risk for type 2 diabetes, some ethnic populations, such as Indo-Asians and Native Americans, appear to have a particularly strong genetic predisposition to develop type 2 diabetes (8). An analysis of 7,414 Asian Americans and 140,291 non-Hispanic white adults in the U.S. indicated that Asian Indians, Chinese, and Filipinos were each more likely to develop diabetes than non-Hispanic whites (9). It has been hypothesized that Asians have higher adiposity per unit BMI compared with other racial/ethnic groups, leading to an increased risk of type 2 diabetes at a lower BMI (10,11). A recent study found that β-cell dysfunction had a more pronounced contribution to diabetes among nonobese subjects, whereas insulin resistance contributed more to hyperglycemia among obese subjects (12), which supports the hypothesis by Narayan (13) that Unnikrishnan et al. (1) mentioned in their Perspective. A genetic study sampled from a Chinese national survey also shows that patients with type 2 diabetes with a higher genetic risk score were leaner or had worse β-cell function (14). Thus, Unnikrishnan et al. (1) suggest that further research in type 2 diabetes is needed to reevaluate the treatment algorithm for different phenotypes of obese subjects with more insulin resistance and leaner subjects with more severe β-cell dysfunction.

The prevalence of unhealthy lifestyle factors, such as inactivity and obesity, and their negative health consequences are rapidly increasing in the world. Modification of lifestyle factors is therefore an important strategy for reducing both the incidence of type 2 diabetes and subsequent complications. Several randomized clinical trials such as the Chinese Da Qing IGT and Diabetes Study, the Finnish Diabetes Prevention Study (DPS), and the U.S. Diabetes Prevention Program (DPP) have demonstrated that effective lifestyle intervention strategies (dietary modification and enhanced physical activity) can prevent or delay the progression to type 2 diabetes among high-risk adults with impaired glucose tolerance (15). Studies including the Da Qing IGT and Diabetes Study provided evidence suggesting that for subjects with impaired glucose tolerance, the more insulin resistance there is, the less benefit there is in preventing progression to diabetes with lifestyle change alone despite significant benefits in insulin sensitivity with lifestyle modification (16).

The currently available evidence confirms that obesity, sedentary lifestyle, and unhealthy diet are major contributors to the diabetes epidemic. From the perspective of public health, lifestyle interventions, including increased physical activity and a healthy diet, are effective and safe ways to delay the progression to overt type 2 diabetes in people with impaired glucose tolerance. It would be of great interest to find out whether lifestyle interventions have a similar effect in the general population. NHS England launched a first-in-the-world national primary prevention program in 2016 (17), and the U.S. has made promising progress in determining diabetes trends (18). The next big challenge is to translate evidence into interventional programs at the population level in the most populous developing countries such as China and India (19). The spark of diabetes starts with friction between natural predisposition and nurtured challenges; the lasting rushing winds of insulin resistance fan the flames of the β-cell to burn out. It is fascinating to find the coincidence of geographical overlaps between monsoon regions and areas hit hardest by diabetes in both North America and Asia.

On top of lifestyle modification as the cornerstone of intervention, it is critical, from a professional point of view, to screen and identify high-risk subjects and initiate early intervention to slow or even reverse the progress at the individual level. More detailed and practical cardiometabolic risk stratification tools and more evidence on the most efficient and cost-effective approach to change the natural trajectory of diabetes progression are needed (20). Besides therapeutic lifestyle modification, short-term intensive insulin regimens (21,22), metabolic surgery (23), and oral agents including metformin and thiazolidinediones are all effective in delaying or reversing the progression of prediabetes or newly diagnosed type 2 diabetes. It is critical to understand the mosaic variations in type 2 diabetes and thus develop more specific road maps based on ethnic differences among various populations (Fig. 1). Which subgroups can benefit more from lifestyle modification and/or different agents/procedures? How long can the benefits of β-cell functional improvement and clinical remission of type 2 diabetes be sustained? All these questions are beyond the current more or less “one-size-fits-all” algorithm, and we need the “open sesame” password to unlock the portal to the ultimate tipping point of the diabetes pandemic.

Figure 1

Current understanding of the approaches for prediabetes or newly diagnosed type 2 diabetes (T2DM) in view of variations among ethnicities and individuals. Area 1: potential of adaptation with insulin resistance to environmental perturbation. Area 2: capability of β-cell functional reserve with compensational insulin secretion. Area 3: variation among ethnicities and individuals (insulin secretion and/or insulin sensitivity). Area 4: hyperglycemia. TZD, thiazolidinediones.

Figure 1

Current understanding of the approaches for prediabetes or newly diagnosed type 2 diabetes (T2DM) in view of variations among ethnicities and individuals. Area 1: potential of adaptation with insulin resistance to environmental perturbation. Area 2: capability of β-cell functional reserve with compensational insulin secretion. Area 3: variation among ethnicities and individuals (insulin secretion and/or insulin sensitivity). Area 4: hyperglycemia. TZD, thiazolidinediones.

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Funding. This work was supported by the Chang Jiang Scholars Program and the Program for Changjiang Scholars and Innovative Research Team in University (IRT0947).

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

See accompanying article, p. 1432.

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