Maureen I Harris

Prevalence of Diabetes, Impaired Fasting Glucose, and Impaired Glucose Tolerance in U.S. Adults: The Third National Health and Nutrition Examination Survey, 1988–1994

OBJECTIVE To evaluate the prevalence and time trends for diagnosed and undiagnosed diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults by age, sex, and race or ethnic group, based on data from the Third National Health and Nutrition Examination Survey, 1988–1994 (NHANES 111) and prior Health and Nutrition Examination Surveys (HANESs). RESEARCH DESIGN AND METHODS NHANES III contained a probability sample of 18,825 U.S. adults ≥20 years of age who were interviewed to ascertain a medical history of diagnosed diabetes, a subsample of 6,587 adults for whom fasting plasma glucose values were obtained, and a subsample of 2,844 adults between 40 and 74 years of age who received an oral glucose tolerance test. The Second National Health and Nutrition Examination Survey, 1976–1980, and Hispanic HANES used similar procedures to ascertain diabetes. Prevalence was calculated using the 1997 American Diabetes Association fasting plasma glucose criteria and the 1980–1985 World Health Organization (WHO) oral glucose tolerance test criteria. RESULTS Prevalence of diagnosed diabetes in 1988–1994 was estimated to be 5.1% for U.S. adults ≥20 years of age (10.2 million people when extrapolated to the 1997 U.S. population). Using American Diabetes Association criteria, the prevalence of undiagnosed diabetes (fasting plasma glucose ≥126 mg/dl) was 2.7% (5.4 million), and the prevalence of impaired fasting glucose (110 to <126 mg/dl) was 6.9% (13.4 million). There were similar rates of diabetes for men and women, but the rates for non-Hispanic blacks and Mexican-Americans were 1.6 and 1.9 times the rate for non-Hispanic whites. Based on American Diabetes Association criteria, prevalence of diabetes (diagnosed plus undiagnosed) in the total population of people who were 40–74 years of age increased from 8.9% in the period 1976–1980 to 12.3% by 1988–1994. A similar increase was found when WHO criteria were applied (11.4 and 14.3%). CONCLUSIONS The high rates of abnormal fasting and postchallenge glucose found in NHANES III, together with the increasing frequency of obesity and sedentary lifestyles in the population, make it likely that diabetes will continue to be a major health problem in the U.S

Onset of NIDDM occurs at least 4-7 Yr before clinical diagnosis

Objective To investigate duration of the period between diabetes onset and its clinical diagnosis. Research Design and Methods Two population-based groups of white patients with non-insulin-dependent diabetes (NIDDM) in the United States and Australia were studied. Prevalence of retinopathy and duration of diabetes subsequent to clinical diagnosis were determined for all subjects. Weighted linear regression was used to examine the relationship between diabetes duration and prevalence of retinopathy. Results Prevalence of retinopathy at clinical diagnosis of diabetes was estimated to be 20.8% in the U.S. and 9.9% in Australia and increased linearly with longer duration of diabetes. By extrapolating this linear relationship to the time when retinopathy prevalence was estimated to be zero, onset of detectable retinopathy was calculated to have occurred ∼ 4–7 yr before diagnosis of NIDDM. Because other data indicate that diabetes may be present for 5 yr before retinopathy becomes evident, onset of NIDDM may occur 9–12 yr before its clinical diagnosis. Conclusions These findings suggest that undiagnosed NIDDM is not a benign condition. Clinically significant morbidity is present at diagnosis and for years before diagnosis. During this preclinical period, treatment is not being offered for diabetes or its specific complications, despite the fact that reduction in hyperglycemia, hypertension, and cardiovascular risk factors is believed to benefit patients. Imprecise dating of diabetes onset also obscures investigations of the etiology of NIDDM and studies of the nature and importance of risk factors for diabetes complications.

Prevalence of Diabetes and Impaired Glucose Tolerance and Plasma Glucose Levels in U.S. Population Aged 20–74 Yr

The prevalence of physician-diagnosed diabetes and of undiagnosed diabetes and impaired glucose tolerance (IGT) that meet National Diabetes Data Group (NDDG) and World Health Organization (WHO) criteria have been estimated for the U.S. population aged 20–74 yr from the 1976–1980 National Health and Nutrition Examination Survey. This survey included a demographic/medical history questionnaire administered in the participants home and a detailed examination composed of a physicians exam, special clinical procedures, other tests, and collection of blood and urine specimens. Survey participants were selected from 1970 census data through a stratified multistage probability sampling scheme. Of 17,390 eligible residents aged 20–74 yr, 15,357 (88.3%) participated in the interview and are the basis for estimates of diagnosed diabetes; 11,858 (68%) participated in the exam. A half sample of 5901 examinees was selected to receive a 75-g oral glucose tolerance test (OGTT) performed in the morning after an overnight 10- to 16-h fast. Of these examinees, valid OGTT data were obtained for 3772 people without a medical history of diabetes, and these are the basis for estimates of undiagnosed diabetes and IGT. The major reasons for incomplete OGTT data were inability of participants to attend the examination center in the morning and lack of adherence to the fasting instructions. Despite the relatively low response rates, evidence is presented that data on both the interviewed sample and those receiving the OGTT, when adjusted for the 1970–1980 census characteristics by age, race, sex, income, and geographic location, are representative of the U.S. population. Extrapolation of these data to the U.S. population aged 20–74 yr indicates a total diabetes prevalence of 6.6% by NDDG criteria, or more than 8 million people with diabetes. The prevalence of undiagnosed diabetes (3.2%) was almost equal to that of previously diagnosed diabetes (3.4%). Total rates of diabetes increased with age, from 2.0% at age 20–44 yr to 17.7% at age 65–74 yr. Rates were approximately equal by sex but were greater in Blacks than in Whites. The prevalence of undiagnosed diabetes by WHO criteria (3.4%) was similar to that by NDDG criteria, but the rate of impaired glucose tolerance (11.2%) was more than twice the NDDG estimate (4.6%). Both obesity and parental history of diabetes were associated with significantly higher rates of diabetes and IGT. Fasting plasma glucose was relatively insensitive to age, but 1-h and 2-h post-75-g glucose values increased significantly with age.

Undiagnosed NIDDM: Clinical and Public Health Issues

U ndiagnosed NIDDM is highly prevalent in the U.S. population, reaching 10-20% in people >50 yr of age, with even higher rates in blacks and Mexican Americans. Recent data show that retinopathy begins developing at least 7 yr before clinical diagnosis of NIDDM, and that onset of NIDDM probably occurs at least 12 yr before its clinical diagnosis. Significant complications are present in patients at diagnosis; for example, 21% of newly diagnosed patients have retinopathy. Thus, during the time that diabetes remains undiagnosed and, consequently, while it remains untreated, retinopathy and other complications of diabetes are developing. Other data confirm that undiagnosed NIDDM is not a benign condition. The prevalence of macrovascular disease in undiagnosed NIDDM is about equal to that found in diagnosed diabetes, and rates of CHD in both diagnosed and undiagnosed diabetes are about twice that for nondiabetic individuals. Mortality in undiagnosed diabetes is also equal to that of diagnosed diabetes, and both are significantly higher than in nondiabetic individuals. Risk factors for microand macrovascular complications in undiagnosed NIDDM are very common and are as frequent as in diagnosed NIDDM. Prevalence of hypertension is 61%, hypercholesterolemia is 49%, LDL cholesterol >130 mg/dl is 62% (>95% of whom have CHD or >2 risk factors for heart disease), hypertriglyceridemia is 28%, obesity is 50% for men and 82% for women, and cigarette smoking is 32%. Effective treatment for hyperglycemia and other risk factors for diabetic complications is available, including dietary and pharmacological therapy and lifestyle and behavioral changes. However, such treatment is either not being offered, in the case of hyperglycemia, or would likely be offered with greater intensity if the clinician were aware that the patient had diabetes. No national programs are currently available to address the issue of undiagnosed diabetes, including screening programs to detect the 6.3 million cases in the U.S. In contrast, major national efforts have been launched by the American Heart Association to fight hypertension and hyper-

Diabetes in America: Epidemiology and Scope of the Problem

Epidemiological studies performed over the past 40 years have shown that the prevalence of diagnosed diabetes has increased dramatically in the U.S. and that a substantial proportion of the population has undiagnosed diabetes, impaired fasting glucose, and impaired glucose tolerance. Diabetes is most prevalent in minority populations, such as African-Americans, Native Americans, and Mexican Americans. Increasing prevalence of diabetes has led to increases in microvascular complications such as blindness, end-stage renal disease, and lower limb amputations. Poor glycemic control contributes to the high incidence of these complications, yet community-based studies of diabetic patients show their mean fasting plasma glucose concentration is generally >180 mg/dl compared with 100 mg/dl for nondiabetic individuals. In people with diabetes, risk factors for cardiovascular disease including elevated fasting plasma glucose, blood pressure, total cholesterol, triglycerides, and obesity partly explain the high proportion of deaths (60–70%) caused by cardiovascular disease in people with diabetes. More intensive diabetes management and improved glycemic control could minimize long-term complications of the disease and would be expected to reduce the morbidity, mortality, and costs associated with diabetes.

Comparison of Diabetes Diagnostic Categories in the U.S. Population According to 1997 American Diabetes Association and 1980–1985 World Health Organization Diagnostic Criteria

OBJECTIVE To compare the 1997 American Diabetes Association (ADA) and the 1980–1985 World Health Organization (WHO) diagnostic criteria in categorization of the diabetes diagnostic status of adults in the U.S. RESEARCH DESIGN AND METHODS Analyses are based on a probability sample of the U.S. population age 40–74 years in the 1988–1994 Third National Health and Nutrition Examination Survey (NHANES III). People with diabetes diagnosed before the survey were identified by questionnaire. For 2,844 people without diagnosed diabetes, fasting plasma glucose was obtained after an overnight 9 to < 24-h fast, HbA1c was measured, and a 2-h oral glucose tolerance test was administered. RESULTS Prevalence of diagnosed diabetes in this age-group is 7.9%. Prevalence of undiagnosed diabetes is 4.4% by ADA criteria and 6.4% by WHO criteria. The net change of −2.0% occurs because 1.0% are classified as having undiagnosed diabetes by ADA criteria but have impaired or normal glucose tolerance by WHO criteria, and 3.0% are classified as having impaired fasting glucose or normal fasting glucose by ADA criteria but have undiagnosed diabetes by WHO criteria. Prevalence of impaired fasting glucose is 10.1% (ADA), compared with 15.6% for impaired glucose tolerance (WHO). For those with undiagnosed diabetes by ADA criteria, 62.1% are above the normal range for HbA1c compared with 47.1% by WHO criteria. Mean HbA1c is 7.07% for undiagnosed diabetes by ADA criteria and 6.58% by WHO criteria. CONCLUSIONS The number of people with undiagnosed diabetes by ADA criteria is lower than that by WHO criteria. However, those individuals classified by ADA criteria are more hyperglycemic, with higher HbA1c values and a greater proportion of values above the normal range. This fact, together with the simplicity of obtaining a fasting plasma glucose value, may result in the detection of a greater proportion of people with undiagnosed diabetes in clinical practice using the new ADA diagnostic criteria.

Geographic differences in the risk of insulin-dependent diabetes mellitus: the importance of registries.

There are marked geographic differences in the incidence of insulin-dependent diabetes mellitus (IDDM); for example, children in countries such as Finland are over 35 times more likely to develop IDDM than children in Japan. An understanding of the reasons for the geographic differences is likely to be important for understanding and, hopefully, preventing IDDM. There are problems, however, because of the lack of registries with adequate standardization. The major needs for the future studies include (1) to clarify the definition of IDDM for epidemiologic study, (2) to establish a standardized approach for IDDM registries, (3) to use registries to evaluate viral, immunologic, and genetic differences in order to explain differential risks across populations, and (4) to encourage the development of new population-based registries worldwide.

Symptoms of Sensory Neuropathy in Adults with NIDDM in the U.S. Population

OBJECTIVE To ascertain the prevalence and determinants of sensory neuropathy symptoms through structured interview of a representative sample of people with diabetes in the U.S. population. RESEARCH DESIGN AND METHODS The 1989 National Health Interview Survey consisted of a representative sample of 84,572 persons in the U.S. ≥ 18 yr of age. A household respondent identified all people in the household believed to have diabetes (n = 2829). Subjects who could not be personally interviewed (n = 129) and individuals who stated they did not have diabetes (n = 295) were excluded. A detailed questionnaire was administered to 99.3% of the remaining 2405 subjects. Questions on symptoms of sensory neuropathy included whether during the past 3 mo the subjects had experienced numbness or loss of feeling, pain or tingling, or decreased ability to feel hot or cold. The neuropathy questions were also administered to a representative sample of 20,037 subjects who were not known to have diabetes. RESULTS Prevalence of symptoms of sensory neuropathy was 30.2% among people with IDDM. This prevalence was 36.0% for men with NIDDM and 39.8% for women with NIDDM, compared with 9.8 and 11.8% for nondiabetic men and women, respectively. In logistic regression, factors independently related to symptoms of sensory neuropathy in people with NIDDM included duration of diabetes, hypertension, hyperglycemia, and glycosuria. Long duration of NIDDM (>20 yr) was associated with a twofold increased risk of symptoms of sensory neuropathy compared with those with 0-4 yr of diabetes. Hypertension was associated with a 60% higher likelihood of symptoms. Diabetic individuals whose blood glucose was high all or most of the time or whose urine tests showed glucose all of the time were > 2 times as likely to have symptoms of sensory neuropathy than those who did not report hyperglycemia or glycosuria. Age, sex, ethnicity, cigarette smoking, and height were not determinants of sensory neuropathy. CONCLUSIONS Symptoms of sensory neuropathy affect 30–40% of diabetic patients in the U.S. Men and women are affected equally. Prevalence of these symptoms increases with longer duration of diabetes; hypertension and hyperglycemia predispose to symptoms of sensory neuropathy.

Prevention Conference VI: Diabetes and Cardiovascular Disease Writing Group I: Epidemiology

Individuals with diabetes have increased rates of all forms of cardiovascular (CV) disorders affecting the heart, brain, and peripheral vessels. Epidemiological studies have been powerful tools to study this phenomenon, providing data on prevalence and incidence rates in diverse populations and uncovering risk factors. Studies to date have documented that diabetic CV disease (CVD) is increasing, but there are many unanswered questions concerning the temporal relations between diabetes and CVD, the metabolic and cellular etiologic mechanisms, and the most effective strategies for predicting and reducing CVD risk in patients with diabetes. Epidemiological studies can provide important information concerning all of these issues. This writing group has attempted to describe the scope of the problem based on current data. The group is convinced of the importance of understanding and intervening early in the continuum of events that lead to CVD, starting with the metabolic syndrome as it progresses to impaired fasting glucose (IFG) and ultimately hyperglycemia. The group also addressed the issue of defining CVD risk factors in the patient with diabetes and focused on lifestyle strategies for the prevention and treatment of CVD in individuals with diabetes. This report contains several recommendations for future research, as well as recommendations for American Heart Association (AHA) programs.

Impaired Glucose Tolerance in the U. S. Population

Impaired glucose tolerance (IGT) constitutes two-thirds of all glucose intolerance in the United States and is a major risk factor for diabetes. Despite these findings, the clinical and epidemiological significance of IGT has not been well investigated. The Second National Health and Nutrition Examination Survey, a cross-sectional study in which 75-g 2-h oral glucose tolerance tests (OGTTs) were performed, has provided an opportunity to examine the characteristics of IGT in the U. S. population. Data from the survey have been extrapolated to represent all U. S. residents. The findings indicate that ∼11.2% of Americans aged 20–74 yr have IGT compared to 6.6% with diabetes. Rates of IGT increased with age for White men and women and Black men but declined for Black women >54 yr of age, possibly because greater obesity in Black women precipitated earlier conversion of IGT to diabetes. The distribution of 2-h glucose values showed IGT to be part of a continuum of glucose intolerance extending from normal to diabetes. Individuals with IGT had rates of risk factors for non-insulin-dependent diabetes (age, plasma glucose, past obesity, family history of diabetes, physical inactivity) that were intermediate between those of individuals with normal glucose tolerance and those with diabetes, although current obesity was similar for IGT and diabetes. The proportion of people with medical histories of diabetes-related conditions did not differ between IGT and normal glucose tolerance. However, several cardiovascular findings were more prevalent in individuals with IGT than in those with normal glucose tolerance, including hypertension, serum cholesterol, angina, abnormal heart findings, and medical history of arteriosclerosis and stroke. Both obesity and reported family history of diabetes were associated with higher rates of IGT, with the effect of weight gain on the prevalence of IGT occurring at lower levels than for diabetes.