Definition and Epidemiology of Type 2 Diabetes Mellitus

Type 2 Diabetes—Definitions and Outcomes

Glucose intolerance ranges from impaired glucose tolerance (IGT) and impaired fasting glucose (together termed prediabetes, a precursor to and risk factor for diabetes) to diabetes. The diagnostic criteria for prediabetes and diabetes are shown in Table 1-1 . Traditionally, diabetes is diagnosed by fasting plasma glucose (FPG) measurements and/or a 2-hour, 75-g oral glucose tolerance test (considered the gold standard for diagnosis of diabetes). In 2009, an international expert committee (including the American Diabetes Association [ADA], the International Diabetes Federation [IDF], and the European Association for the Study of Diabetes) recommended the use of glycosylated hemoglobin A1c (HbA1c) for diabetes diagnosis.

Diabetes can result in severe morbidity and increased mortality as a result of secondary complications, which affect multiple body systems, including the cardiovascular system (cerebrovascular disease and coronary heart disease), renal system (nephropathy), eyes (retinopathy), peripheral nervous system (neuropathy), and limbs (foot ulcers, peripheral vascular disease, amputations). For a more thorough discussion of these diabetes complications, see Chapters 7 , 19 , 23 , 27 , and 28 . Diabetes is also associated with other hitherto underappreciated complications, namely, infections, liver and digestive diseases, falls and mental illness, lung diseases, some cancers, and cognitive decline. Individuals with diabetes also are at an increased risk for other conditions including erectile dysfunction, tuberculosis, sleep apnea, and periodontal disease, ^, and this population reports a lower quality of life than other groups. Furthermore, individuals with diabetes have an increased risk of death from conditions ranging from cardiovascular diseases and kidney failure to infections, mental disorders, and liver disease. Because of the severity of the conditions associated with diabetes, diabetes is associated with an attenuated lifespan.

Diabetes-related complications are not infrequent, and they affect public health systems worldwide ( Fig. 1-1 ). Diabetic retinopathy is the leading cause of blindness in adults in developed countries. ^, An audit of the United Kingdom’s National Health System’s data showed additional risk for complications caused by diabetes: compared with the general population, people with diabetes were 64.9% more likely to be admitted to a hospital with heart failure, 48.0% more likely to have a myocardial infarction (MI), 331% more likely to have an amputation below the ankle, 210% more likely to have an above-ankle amputation, 24.9% more likely to have a stroke, and 139% more likely to require renal replacement therapy. In the United States, diabetes is the leading cause of nontraumatic amputations of the lower limbs, blindness, and kidney failure.

Diabetes is an economically costly disease. Diabetes and its complications lead to increases in work-place absenteeism and loss of productive life-years. ^, In the United States the cost of diabetes was estimated to be $245 billion dollars in 2012. This includes $176 billon dollars in direct medical costs (medications, office visits, hospitalizations, emergency care) and $69 billion in indirect medical costs (unemployment, absenteeism, and reduced productivity resulting from diabetes, and the loss to the workforce because of premature mortality associated with diabetes). The costs to individuals with diabetes is also great; U.S. men and women with diagnosed diabetes have medical expenditures that are 2.3 times higher than they would have if the individual did not have diabetes. In low- and middle-income countries (LMICs), the economic ramifications of diabetes can be even worse than in high-income countries such as the United States. A study conducted in India reported that few patients had health insurance, instead relying on personal savings, loans, mortgages, and property sales to pay for medical bills associated with diabetes care ; in this situation, the high costs of routine diabetes care and treatment of diabetes-related complications are enough to put even comfortable, middle-class Indian families into poverty.

Given the strong evidence that treatment of multiple risk factors simultaneously in patients with diabetes improves outcomes, ^, expert groups recommend that patients with diabetes undergo regular preventative examinations (e.g., foot and eye examinations, measures of urine protein) and manage risk factors associated with diabetes-related complications (e.g., manage blood pressure [BP], plasma lipids, and blood glucose; eliminate tobacco use; undergo treatment of albuminuria with angiotensin-converting enzyme [ACE] inhibitor or angiotensin receptor blocker [ARB] medications; do regular exercise; be referred to a dietician). ^{, ,} Unfortunately, achievement of diabetes care targets is suboptimal. In the United States, even though there have been improvements in process of care and intermediate outcomes, two fifths of patients with diabetes have poor control of low-density lipoprotein (LDL) cholesterol, one fifth have poor glycemic control, and one third have poor BP control. Data collected during a 5-year observational study in Asia, Eastern Europe, Latin America, the Middle East, and Africa show that the situation is worse in LMICs; among 9901 patients with diabetes, 36% had never had an HbA1c measurement, 11% to 36% had not been screened for secondary complications in the previous 2 years, and only 3.6% had achieved optimal LDL, BP, and HbA1c targets.

Global Burden of Diabetes

The burden of noncommunicable diseases (NCDs), such as diabetes, is growing worldwide, and these diseases and conditions already contribute to most mortality and morbidity worldwide. Globally, we are witnessing a major shift from communicable and undernutrition-related diseases to NCDs in adulthood. Disability-adjusted life years (DALYs) from NCDs increased 25% between 1990 and 2010, whereas those resulting from communicable diseases and maternal, neonatal, and nutrition-deficiency disorders decreased by 26.5% in the same time period. A large proportion of the increase in the burdens of NCDs is driven by population growth and ageing, yet almost half of the increase in DALYs from NCDs between 1990 and 2010 resulted from factors other than population growth and ageing.

Among NCDs, the growth of diabetes appears to be especially dramatic and worrisome. As a cause of death, diabetes has advanced in ranking from 15 in 1990 to 9 in 2010. High blood glucose and associated cardiometabolic risk factors (e.g., physical inactivity, overweight and obesity, low fruit and vegetable intake) are now consistently among the top 10 risk factors for mortality globally, and across high-, middle-, and low-income countries alike. ^, Furthermore, high blood glucose, high body mass index (BMI), diets low in fruits and vegetables, diets low in whole grains, and physical inactivity and low physical activity were among the leading risk factors for DALYs globally in 2010, and they ranked high as risk factors for DALYs in all regions of the world. Overall, over the past two decades, there has been a steady and disturbing increase in mean BMI and mean FPG globally, and this trend is affecting almost all countries of the world, barring a few exceptions, with the rate of increase most acute among developing countries undergoing industrial transformation in their economies. ^, In contrast, mean BP and mean total cholesterol levels have decreased globally, largely driven by decreases in high-income countries, although their levels have increased in many developing countries. ^,

These changes in BMI and glucose levels have translated into increases in prevalence of diabetes worldwide. The number of people with diabetes is increasing in every country of the world ( Table 1-2 ), although prevalence estimates are conservative given that in 50% to 80% of those with the disease it remains undetected. According to the latest IDF Diabetes Atlas, at least 382 million people worldwide had diabetes in 2013, 80% of whom lived in LMICs. By 2035 the number of people with diabetes will rise to 592 million, although the growth may be greater given the overall population trends of increasing weight, aging, and urbanization.

Although there are differences in diabetes risk by ethnicity (e.g., Native Americans, Hispanics, Blacks, and Asians in the United States have higher risks than non-Hispanic whites; Indians in the United Kingdom have higher risks than their Caucasian counterparts; Indians have higher risks than Chinese and Malays in Singapore), it is generally true that the rise in diabetes prevalence is affecting all ethnic groups. Similarly, both genders are affected by the increasing prevalence of diabetes. As a consequence, on a global level the number of people with diabetes is projected to increase between 2013 and 2035 in every continent (+109% increase in Africa; +96% in the Middle East and North Africa; +71% in South-East Asia; +60% in South and Central America; +46% in the Western Pacific; +37% in North America and the Caribbean; and +22% in Europe; see Table 1-2 ).

The steepest growth in the number of people with diabetes is occurring in LMICs. In fact, 7 of the top 10 countries worldwide in terms of number of people with diabetes are already LMICs, and by 2030 only 1 of the top 10 countries will be other than an LMIC ( Table 1-3 ). The number of adults with diabetes in LMICs is expected to increase at a pace that far exceeds that of developing countries (69% increase in developing countries compared with a 20% increase in developed countries by 2030). In terms of diabetes prevalence, the top 10 countries or territories of the world are the Tokelau (37.5%), Federated States of Micronesia (35%), Marshall Islands (34.9%), Kiribati (28.8%), Cook Island (25.7%), Vanuatu (24%), Saudi Arabia (24%), Nauru (23.3%), Kuwait (23.1%), and Qatar (22.9%).

Although the burden of diabetes is already staggering, two additional patterns are a cause for further concern. First, the number of young people with diabetes is high and increasing. The highest numbers of people with diabetes worldwide are in the economically productive age group of 40 to 59 years, and half the people who die from diabetes are under the age of 60 years—a pattern of major concern to global economic productivity and development, the health and economic costs of the disease itself notwithstanding. ^, In 2011 there were an estimated 490,100 children aged 0 to 14 years with T1DM worldwide, and an estimated 778,000 new cases of T1DM were being diagnosed each year, representing a 3.0% increase in annual incidence. Furthermore, there has been an increase in occurrence of T2DM, traditionally believed to be a disease of adults, at younger ages. There is uncertainty about the actual prevalence and incidence of youth-onset diabetes, because data are limited; however, reports suggest that T2DM may account for 10% to 30% of all youth-onset diabetes patients and that certain ethnic groups (e.g., Native Americans, Asian Indians) may be at especially high risk. The best-characterized data available are from the SEARCH for Diabetes in Youth study, a multicenter investigation in the United States. The SEARCH study has reported a physician-diagnosed T2DM prevalence of 0.01/1000 among 0 to 9 year olds, and among 10 to 19 year olds the prevalence ranged from 1.74/1000 in American Indians to 0.19/1000 in non-Hispanic whites.

Second, whereas the growth of diabetes was largely believed to have been an urban phenomenon, a recent systematic review of diabetes in rural parts of LMICs indicates that the diabetes epidemic is rapidly spreading through rural areas across the world. The pooled prevalence of rural diabetes among LMICs was estimated to be 5.6%, and moreover, it had quintupled in a 25-year time period. Although the IDF projects a 47% rise in the number of people with diabetes globally by 2030, these rural data suggest that the rise may be even higher because an estimated 55% of LMIC populations worldwide live in rural areas.