James P. Boyle

The Evolving Diabetes Burden in the United States

Diabetes was first described in ancient times with the cardinal symptoms of polyuria, polydipsia, and polyphagia (1). The use of uniform diagnostic criteria provided a means to reliably track the disease and unveiled a worldwide epidemic that emerged during the second half of the 20th century and is now extending into the 21st century (2-4). This report examines the evolution of the diabetes epidemic in the United States and the burden imposed by its complications. Classification of Diabetes Mellitus There are 3 major types of diabetes (5). Type 1 diabetes usually involves children and was previously called insulin-dependent diabetes mellitus or juvenile-onset diabetes. It develops when the bodys immune system destroys pancreatic cells, which make insulin. Type 1 diabetes accounts for 5% to 10% of all diagnosed cases of diabetes in the United States. Type 2 diabetes, previously called noninsulin-dependent diabetes mellitus or adult-onset diabetes, usually begins as insulin resistance, in which target tissues do not use insulin properly. It accounts for approximately 90% to 95% of all diagnosed cases of diabetes. Gestational diabetes is glucose intolerance diagnosed during pregnancy with return to a normal metabolic state after delivery. Other, lesser types of diabetes result from specific genetic conditions (such as maturity-onset diabetes of youth), surgery, drugs, malnutrition, infections, and other illnesses; these account for 1% to 5% of all diagnosed cases of diabetes (5). Diagnosis of Diabetes Uniform diagnostic criteria for diabetes were first recommended by the American Diabetes Association and the World Health Organization in 1979 and 1980 and were updated in the late 1990s (5, 6). Currently, when typical symptoms of diabetes are present (for example, polyuria, polydipsia, or unexplained weight loss), a casual (that is, at any time without regard to the last meal) plasma glucose level of 11.1 mmol/L (200 mg/dL) or greater confirms the diagnosis. In addition, the diagnosis can be made with a fasting plasma glucose level of 7.0 mmol/L (126 mg/dL) or greater or an oral glucose tolerance test with a 2-hour value of 11.0 mmol/L (200 mg/dL) or greater. A positive diagnostic test result should be followed by a repeated test on a different day to confirm the clinical diagnosis. In contrast, for epidemiologic studies, a single fasting plasma glucose or 2-hour oral glucose tolerance test measurement is used to estimate the prevalence of diabetes in a population. Tracking the Diabetes Epidemic Currently, 3 periodic national surveys track diabetes prevalence in the United States. The National Health Interview Survey and National Health and Nutrition Examination Survey (NHANES) use national population-based samples and query persons in face-to-face interviews about whether they have been told by their health care provider that they have diabetes. A third survey, the Behavioral Risk Factors Surveillance System, asks a similar question of state-based population samples during telephone interviews of residents. Unlike the other 2 surveys, NHANES includes a laboratory-based examination that measures glucose levels and identifies persons with undiagnosed diabetes. All 3 surveys provide national estimates of the prevalence of diagnosed diabetes. Only the Behavioral Risk Factors Surveillance System provides state-based estimates, and only NHANES provides estimates of undiagnosed diabetes. Prevalence In 2002, an estimated 6.3% of the U.S. population (about 18.2 million persons) had diabetes (7). Diabetes affects various sociodemographic groups unequally. According to data from the National Health Interview Survey, persons 65 years of age or older make up almost 40% of all persons with diagnosed diabetes, and the prevalence in this age group is more than 10 times that in persons younger than 45 years of age (8). Minority race and ethnic groups, including black persons, Hispanic persons, and Native Americans, are disproportionately affected; the prevalence of diagnosed diabetes is generally 2 to 4 times higher in these groups than in the majority population (Figure 1) (7, 8). Figure 1. Prevalence of diagnosed diabetes in people 20 years of age and older by age and race or ethnicity, United States, 2002. The longest running of the surveys, the National Health Interview Survey, found a 4- to 8-fold increase over the last half-century in the number of persons who received a diagnosis of diabetes (1.6 million in 1958 and 12.1 million in 2000) and the prevalence of diagnosed diabetes in the United States (0.9% in 1958 and 4.4% in 2000) (Figure 2) (8, 9). Increases occurred across all demographic categories, including sex, race or ethnicity, and age (8). Between 1990 and 2001, data from the Behavioral Risk Factors Surveillance System indicate that the largest relative increases in diagnosed diabetes occurred in persons 30 to 39 and 40 to 49 years of age (95% and 83%, respectively); increases in other age groups were 40% in persons 18 to 29 years of age, 49% in persons 50 to 59 years of age, 42% in persons 60 to 69 years of age, and 33% in persons 70 years of age or older (10, 11). Although the magnitude of the increase varied, the prevalence of diagnosed diabetes among adults increased in every state in the United States (Figure 3). Trends are also disturbing in children and adolescents, in whom type 2 diabetes is increasingly being recognized, but as yet less commonly than type 1 diabetes (12). Studies of estimates of the incidence of type 1 diabetes in the United States, which are limited by sparse data, do not find a consistent patternsome show an increase, some show a decrease, and some remain unchanged (13). Figure 2. Prevalence of diagnosed diabetes and the number of people with diagnosed diabetes in the United States, 1958 to 2000. Figure 3. Prevalence of diagnosed diabetes (including gestational diabetes) by state in the United States, 1990 to 2001. The NHANES found that diabetes is undiagnosed in approximately one third of all persons with diabetes and that this fraction has changed little over time (14). Many factors may have affected these uptrends in the prevalence of diabetes, including changes in diagnostic criteria, improved or enhanced detection, decreasing mortality, changes in demographic characteristics of the population (for example, aging), and growth in minority populations in whom the prevalence and incidence of diabetes are increasing. Diabetes Complications Morbidity Cardiovascular Disease Data on cardiovascular disease among the diabetic population are scant. However, in 2000, 37.2% of diabetic persons age 35 years and older reported receiving a diagnosis of a cardiovascular disease (8). Prevalence of ischemic heart disease among persons with diabetes was about 14 times the rate among those without diabetes in persons 18 to 44 years of age (2.7% vs. 0.2 %), 3 times as high in persons 45 to 64 years of age (14.3% vs. 4.7%), and almost twice as high in those 65 years of age or older (20% vs. 12%) (15). Other studies have shown that the absolute rates of cardiovascular disease in persons with diabetes are higher in men than in women (as in the general population), but the relative risk (comparing those with and without diabetes) is higher in women than in men (relative risk, 2 to 4 for women and 1.5 to 2.5 for men) (16, 17). Eye, Kidney, and Lower-Extremity Disease Visual impairment and blindness are major disabling complications of diabetes. Diabetic retinopathy, the leading cause of blindness (visual acuity 20/200) in persons age 20 to 64 years, accounts for 12% of all new cases of blindness and leads to 12 000 to 24 000 new cases each year in the United States (18). Considerable visual impairment (best corrected [for example, with glasses] visual acuity in either eye < 20/40) among persons with diabetes is much more common than blindness and is associated with reduced functional status. A national population-based survey based on self-reports found that 25% of all persons with diabetes had considerable visual impairment, approximately double the proportion among persons without diabetes (19). Impairment among persons with diabetes can have several causes. Some are specific to diabetes, such as macular edema and diabetic retinopathy, and others are not specific to diabetes but occur more commonly in diabetic than in nondiabetic persons. Examples of conditions not specific to diabetes are cataracts (32% vs. 20% in persons 65 to 74 years of age) and glaucoma (6.0% vs. 2.3% in persons 65 to 74 years of age) (20-23). In the United States in 2000, diabetic nephropathy accounted for more than 40% of new cases of end-stage renal disease (that is, kidney failure that requires dialysis or transplantation) (8). Persons with diabetes are the fastest-growing group of recipients of dialysis and transplantation (8). Several factors may account for the increase in incidence, including greater recognition of the etiologic role of diabetes, more use of treatments for end-stage renal disease, a true increase in the incidence of diabetes-related end-stage renal disease, or a combination of these factors. Lower-extremity disease, which includes peripheral neuropathy and peripheral arterial disease or both, results in elevated rates of lower-extremity amputations among persons with diabetes. An estimated 15% of persons with diabetes will have a diabetic foot ulcer during their lifetime (24); of these, 6% to 43% will ultimately undergo a lower-extremity amputation (25). Among persons with diabetes who have had an amputation, as many as 85% may have had a preceding foot ulcer (25). Currently, more than half of all nontraumatic lower-extremity amputations in the United States occur among people with diagnosed diabetes (8). An analysis of the 1999 to 2000 NHANES found that an estimated 8.1% of the diabetic population age 40 years or older have peripheral arterial disease (defined as an ankle to brachial artery blood pressure ra

Impact of Recent Increase in Incidence on Future Diabetes Burden: U.S., 2005–2050

In an earlier study, we had forecasted 39 million with diagnosed diabetes in 2050 in the U.S. (1,2). However, since then, national diabetes incidence increased (3) and the relative risk of death among people with diabetes declined (4,5). These changes will impact future forecasts. Incorporating these changes, we now project 48.3 million people with diagnosed diabetes in the U.S. in 2050. We also present age-, sex-, and race/ethnicity-specific forecasts, with Bayesian CIs, of the number of people with diagnosed diabetes through 2050. We used a discrete-time (1-year intervals), incidence-based Markov model with three states (no diagnosed diabetes, diagnosed diabetes, and death) (1). In each cycle of the model, projections are developed for 808 population subgroups defined by age, sex, and race/ethnicity. We estimated the age-, sex-, and race/ethnicity-specific prevalence and incidence of diabetes from the U.S. National Health Interview Survey (6–9) and modeled data for 1984–2004 to improve the precision of 2004 estimates. Models were fit using Bayesian methods with improper flat priors applied to logistic regression. We assessed adequacy of model fit using posterior predictive P values (10). Estimated prevalence of diagnosed diabetes for 2000 and 2004 were 4.35 and 5.37%, respectively, and estimated incidence were 0.42 and 0.53% per year, respectively. The age-, sex-, and race/ethnicity-specific 2004 prevalence estimates were combined with U.S. population data for 2004 (11 …

Comparison of Fasting and 2-Hour Glucose and HbA1c Levels for Diagnosing Diabetes: Diagnostic criteria and performance revisited

OBJECTIVE Nearly two decades ago, the National Diabetes Data Group (NDDG) and the World Health Organization (WHO) Expert Committee on Diabetes Mellitus published diagnostic criteria for diabetes. We undertook this study to compare the performance of three glycemic measures for diagnosing diabetes and to evaluate the performance of the WHO criteria. RESEARCH DESIGN AND METHODS In a cross-sectional population-based sample of 1,018 Egyptians ≥ 20 years of age, fasting and 2-h glucose and HbA1c levels were measured, and diabetic retinopathy was assessed by retinal photograph. Evidence for bimodal distributions was examined for each glycemic measure by fitting models for the mixture of two distributions using maximum likelihood estimates. Sensitivity and specificity for cutpoints of each glycemic measure were calculated by defining the true diabetes state (gold standard) as 1) the upper (diabetic) component of the fitted bimodal distribution for each glycemic measure, and 2) the presence of diabetic retinopathy. Receiver operating characteristic (ROC) curves were constructed to determine the performance of the glycemic measures in detecting diabetes as defined by diabetic retinopathy. RESULTS In the total population, the point of intersection of the lower and upper components that minimized misclassification for the fasting and 2-h glucose and HbA1c were 7.2 mmol/l (129 mg/dl), 11.5 mmol/l (207 mg/dl), and 6.7%, respectively. When diabetic retinopathy was used to define diabetes, ROC curve analyses found that fasting and 2-h glucose values were superior to HbA1c (P < 0.01). The performance of a fasting glucose of 7.8 mmol/l (140 mg/dl) was similar to a 2-h glucose of 12.2–12.8 mmol/l (220–230 mg/dl), and the performance of a 11.1 mmol/l (200 mg/dl) 2-h glucose was similar to a fasting glucose of 6.9–7.2 mmol/l (125–130 mg/dl). CONCLUSIONS Optimal cutpoints for defining diabetes differ according to how diabetes itself is defined. When diabetes is defined as the upper component of the bimodal population distribution, a fasting glucose level somewhat lower than the current WHO cutpoint and a 2-h glucose level somewhat higher than the current WHO cutpoint minimized misclassification. When diabetic retinopathy defines diabetes, we found that the current fasting diagnostic criterion favors specificity and the current 2-h criterion favors sensitivity. These results should prove valuable for defining the optimal tests and cutpoint values for diagnosing diabetes.

Projection of Diabetic Retinopathy and Other Major Eye Diseases Among People With Diabetes Mellitus: United States, 2005-2050

OBJECTIVES To estimate the number of people with diabetic retinopathy (DR), vision-threatening DR (VTDR), glaucoma, and cataracts among Americans 40 years or older with diagnosed diabetes mellitus for the years 2005-2050. METHODS Using published prevalence data of DR, VTDR, glaucoma, and cataracts and data from the National Health Interview Survey and the US Census Bureau, we projected the number of Americans with diabetes with these eye conditions. RESULTS The number of Americans 40 years or older with DR and VTDR will triple in 2050, from 5.5 million in 2005 to 16.0 million for DR and from 1.2 million in 2005 to 3.4 million for VTDR. Increases among those 65 years or older will be more pronounced (2.5 million to 9.9 million for DR and 0.5 million to 1.9 million for VTDR). The number of cataract cases among whites and blacks 40 years or older with diabetes will likely increase 235% by 2050, and the number of glaucoma cases among Hispanics with diabetes 65 years or older will increase 12-fold. CONCLUSION Future increases in the number of Americans with diabetes will likely lead to significant increases in the number with DR, glaucoma, and cataracts. Our projections may help policy makers anticipate future demands for health care resources and possibly guide the development of targeted interventions. CLINICAL RELEVANCE Efforts to prevent diabetes and to optimally manage diabetes and its complications are needed.

Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2050: dynamic modeling of incidence, mortality, and population growth.

OBJECTIVE To forecast the number of U.S. individuals aged <20 years with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) through 2050, accounting for changing demography and diabetes incidence. RESEARCH DESIGN AND METHODS We used Markov modeling framework to generate yearly forecasts of the number of individuals in each of three states (diabetes, no diabetes, and death). We used 2001 prevalence and 2002 incidence of T1DM and T2DM from the SEARCH for Diabetes in Youth study and U.S. Census Bureau population demographic projections. Two scenarios were considered for T1DM and T2DM incidence: 1) constant incidence over time; 2) for T1DM yearly percentage increases of 3.5, 2.2, 1.8, and 2.1% by age-groups 0–4 years, 5–9 years, 10–14 years, and 15–19 years, respectively, and for T2DM a yearly 2.3% increase across all ages. RESULTS Under scenario 1, the projected number of youth with T1DM rises from 166,018 to 203,382 and with T2DM from 20,203 to 30,111, respectively, in 2010 and 2050. Under scenario 2, the number of youth with T1DM nearly triples from 179,388 in 2010 to 587,488 in 2050 (prevalence 2.13/1,000 and 5.20/1,000 [+144% increase]), with the greatest increase in youth of minority racial/ethnic groups. The number of youth with T2DM almost quadruples from 22,820 in 2010 to 84,131 in 2050; prevalence increases from 0.27/1,000 to 0.75/1,000 (+178% increase). CONCLUSIONS A linear increase in diabetes incidence could result in a substantial increase in the number of youth with T1DM and T2DM over the next 40 years, especially those of minority race/ethnicity.

A dynamic Markov model for forecasting diabetes prevalence in the United States through 2050

This study develops forecasts of the number of people with diagnosed diabetes and diagnosed diabetes prevalence in the United States through the year 2050. A Markov modeling framework is used to generate forecasts by age, race and ethnicity, and sex. The model forecasts the number of individuals in each of three states (diagnosed with diabetes, not diagnosed with diabetes, and death) in each year using inputs of estimated diagnosed diabetes prevalence and incidence; the relative risk of mortality from diabetes compared with no diabetes; and U.S. Census Bureau estimates of current population, live births, net migration, and the mortality rate of the general population. The projected number of people with diagnosed diabetes rises from 12.0 million in 2000 to 39.0 million in 2050, implying an increase in diagnosed diabetes prevalence from 4.4% in 2000 to 9.7% in 2050.

Investing time in health: do socioeconomically disadvantaged patients spend more or less extra time on diabetes self‐care?

BACKGROUND Research on self-care for chronic disease has not examined time requirements. Translating Research into Action for Diabetes (TRIAD), a multi-site study of managed care patients with diabetes, is among the first to assess self-care time. OBJECTIVE To examine associations between socioeconomic position and extra time patients spend on foot care, shopping/cooking, and exercise due to diabetes. DATA Eleven thousand nine hundred and twenty-seven patient surveys from 2000 to 2001. METHODS Bayesian two-part models were used to estimate associations of self-reported extra time spent on self-care with race/ethnicity, education, and income, controlling for demographic and clinical characteristics. RESULTS Proportions of patients spending no extra time on foot care, shopping/cooking, and exercise were, respectively, 37, 52, and 31%. Extra time spent on foot care and shopping/cooking was greater among racial/ethnic minorities, less-educated and lower-income patients. For example, African-Americans were about 10 percentage points more likely to report spending extra time on foot care than whites and extra time spent was about 3 min more per day. DISCUSSION Extra time spent on self-care was greater for socioeconomically disadvantaged patients than for advantaged patients, perhaps because their perceived opportunity cost of time is lower or they cannot afford substitutes. Our findings suggest that poorly controlled diabetes risk factors among disadvantaged populations may not be attributable to self-care practices.

The use of population attributable risk to estimate the impact of prevention and early detection of type 2 diabetes on population‐wide mortality risk in US males

The Population Attributable Risk (PAR) represents the proportion of the deaths (in a specified time) in the whole population that may be preventable if a cause of mortality were totally eliminated. This population‐based measure was used to assess the potential impact of three public health interventions for type 2 diabetes (early detection + standard therapy; early detection + intensive therapy; and primary prevention) on the mortality risk from all causes and from cardiovascular (CVD) diseases. Potential reduction in mortality risks for several levels of compliance or implementation (25%, 50%, 75%, 100%) for each intervention were also estimated.Results suggest that among males aged 45–74 years, the interventions may have greater population‐wide impact on total deaths among black males, and greater impact on the CVD deaths among white males. Overall, primary prevention (reduction in all‐cause mortality 6.2–10.0%, and CVD mortality 7.9–9.0%) may offer greater marginal benefit than screening and early treatment (reduction in all‐cause mortality 3.5–8.3%, and CVD mortality 2.8–8.6%). Often the question facing policy makers is not simply whether to but how much of an intervention is worth implementing? Estimated benefits for various intensities of intervention (as provided) may be useful to assess the likely marginal benefits of each intervention, and can be especially useful if combined with estimated marginal costs.

Decreases in Diabetes-Free Life Expectancy in the U.S. and the Role of Obesity

OBJECTIVE With increasing life expectancy in the U.S., it is important to know whether a longer life expectancy means a longer healthy life span or a prolonged period of later-life morbidity. This study examines changes in lifetime without diabetes, a leading cause of morbidity in later life. RESEARCH DESIGN AND METHODS Using demographic methods and nationally representative data, we estimated changes in diabetes-free life expectancy between 1980–1989 and 2000–2004 for adult men and women in the U.S., estimated the contribution of changes in age-specific diabetes rates, and examined the changing effects of weight status on diabetes risks. RESULTS While life expectancy at age 18 for men and women increased between the 1980s and the 2000s, diabetes-free life expectancy at age 18 decreased by 1.7 years for men and 1.5 years for women. The proportion of 18-year-olds who would develop diabetes in their lifetimes increased by almost 50% among women and almost doubled among men. Obese individuals experienced the greatest losses in diabetes-free life expectancy during this period, estimated at 5.6 years for men and 2.5 years for women. CONCLUSIONS Diabetes-free life expectancy decreased for both men and women between 1980–1989 and 2000–2004, and these decreases are almost entirely attributable to large increases in diabetes incidence among obese individuals.

Projections of type 1 and type 2 diabetes burden in the U.S. population aged

OBJECTIVE To forecast the number of U.S. individuals aged <20 years with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) through 2050, accounting for changing demography and diabetes incidence. RESEARCH DESIGN AND METHODS We used Markov modeling framework to generate yearly forecasts of the number of individuals in each of three states (diabetes, no diabetes, and death). We used 2001 prevalence and 2002 incidence of T1DM and T2DM from the SEARCH for Diabetes in Youth study and U.S. Census Bureau population demographic projections. Two scenarios were considered for T1DM and T2DM incidence: 1) constant incidence over time; 2) for T1DM yearly percentage increases of 3.5, 2.2, 1.8, and 2.1% by age-groups 0–4 years, 5–9 years, 10–14 years, and 15–19 years, respectively, and for T2DM a yearly 2.3% increase across all ages. RESULTS Under scenario 1, the projected number of youth with T1DM rises from 166,018 to 203,382 and with T2DM from 20,203 to 30,111, respectively, in 2010 and 2050. Under scenario 2, the number of youth with T1DM nearly triples from 179,388 in 2010 to 587,488 in 2050 (prevalence 2.13/1,000 and 5.20/1,000 [+144% increase]), with the greatest increase in youth of minority racial/ethnic groups. The number of youth with T2DM almost quadruples from 22,820 in 2010 to 84,131 in 2050; prevalence increases from 0.27/1,000 to 0.75/1,000 (+178% increase). CONCLUSIONS A linear increase in diabetes incidence could result in a substantial increase in the number of youth with T1DM and T2DM over the next 40 years, especially those of minority race/ethnicity.