William H Herman & Liza L Ilag. Encyclopedia of Public Health. Editor: Lester Breslow. Volume 2, Macmillan Reference USA, 2002.
The term “diabetes mellitus” represents a group of conditions characterized by abnormally high blood glucose levels (hyperglycemia). In 1997, nearly 16 million people in the United States had diabetes; approximately 10.3 million were diagnosed with the conditions, while an estimated 5.4 million were undiagnosed. Diabetes may be complicated by uncontrolled hyperglycemia, and treated diabetes may be complicated by abnormally low blood glucose levels (hypoglycemia). Maternal diabetes is associated with an increased incidence of major birth defects. Over time, diabetes may cause complications involving the eyes (retinopathy), kidneys (nephropathy), and nerves (neuropathy). Diabetes is also associated with an increased incidence of cardiovascular disease, including stroke, heart attack, and peripheral vascular disease. In the United States today, diabetes is a leading cause of birth defects, blindness, kidney failure, and nontraumatic leg amputations. It is also a major contributor to cardiovascular disease. Diabetes is the seventh leading cause of death in the United States, and medical care for people with diabetes is estimated to cost over $100 billion per year.
When diabetes is associated with marked hyperglycemia, it produces characteristic symptoms and signs; particularly increased thirst (polydipsia), increased urination (polyuria), and unexplained weight loss. At other times, hyperglycemia sufficient to cause changes in the eyes, kidneys, and nerves, and to increase the risk of cardiovascular disease, may be present without clinical symptoms. During this asymptomatic period, an abnormality in glucose metabolism may be demonstrated by measuring fasting venous glucose or venous glucose after an oral glucose challenge.
Diagnosis
When a patient is symptomatic and the plasma glucose is unequivocally elevated, a diagnosis of diabetes presents no difficulty. When a patient is without clinical symptoms, a diagnosis of diabetes is more difficult. According to a 1997 American Diabetes Association (ADA) report, there are three ways to diagnose diabetes (see Table 1). All require measurement of venous plasma glucose, and each must be confirmed on a subsequent day by any one of the three methods. In general, the oral glucose tolerance test is not recommended for routine clinical use and is performed only in patients with elevated but nondiagnostic fasting plasma-glucose levels with a high index of suspicion for diabetes.
Classification
Once a diagnosis of diabetes mellitus is established, it is necessary to differentiate the various forms of the syndrome. Prior to 1979, diabetes was classified on the basis of age at diagnosis as either juvenile-onset diabetes mellitus (JODM) or adult-onset diabetes mellitus (AODM). In the late 1970s and early 1980s, a new classification system recognized two major forms of diabetes: insulin-dependent diabetes mellitus (IDDM or type I diabetes) and non-insulin-dependent diabetes mellitus (NIDDM or type II diabetes). In 1997, the American Diabetes Association recommended modifications to this classification system that eliminated the terms “insulin-dependent diabetes mellitus” and “non-insulin-dependent diabetes mellitus” and their acronyms. The terms “type 1” and “type 2” were retained, with Arabic numerals replacing the Roman numerals. Other specific types of diabetes were also recognized.
Table 1
| Criteria for the Three Methods Diagnosis of Diabetes Mellitus in Nonpregnant Adults |
| * In the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria should be confirmed by repeat testing on a different day. The third measure (OGTT) is not recommended for routine clinical use. |
| SOURCE: Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (1997). Diabetes Care 20:1183-1197. |
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Type 1 diabetes is caused by pancreatic beta cell (B-cell) destruction. Immune-mediated type 1 diabetes results from cell-mediated autoimmune destruction of the B-cells of the pancreatic islets. This type of diabetes also has strong genetic or human leukocyte antigen (HLA) associations that can be either predisposing or protective. Another form of type 1 diabetes, termed “idiopathic” type 1 diabetes, is strongly inherited but lacks immunologic evidence for B-cell autoimmunity and is not HLA-associated. Most patients with idiopathic type 1 diabetes are of African or Asian descent.
Table 2
| Incidence of Diagnosed Diabetes per 1,000 Population by Age, United States, 1994. | |||
| Age Group | |||
| 0-4 | 45-64 | 65+ | Total |
| SOURCE: Centers for Disease Control and Prevention (1997). Diabetes Surveillance, 1997. Atlanta, GA: CDC. | |||
| 1.59 | 7.20 | 8.84 | 3.61 |
Type 1 diabetes accounts for approximately 5 percent of diagnosed diabetes in the United States—approximately 500,000 Americans have type 1 diabetes. Type 1 diabetes commonly occurs in childhood and adolescence, but it can occur at any age. Patients with type 1 diabetes are prone to ketoacidosis (decompensated diabetes with hyperglycemia and presence of abnormal acids [ketones] in the blood). Many affected patients have no family history of diabetes. Although most patients with type 1 diabetes are lean when they are diagnosed, the presence of obesity is not incompatible with the diagnosis.
Type 2 diabetes is characterized by both impairment of insulin secretion and defects in insulin action. It is often unclear which abnormality is the primary cause of hyperglycemia. Although patients with this type of diabetes may have insulin levels that appear normal or elevated, insulin levels are always low relative to the elevated plasma glucose levels. Thus, insulin secretion is defective in these patients and insufficient to compensate for the degree of insulin resistance. Although the specific origin of type 2 diabetes is not known, autoimmune destruction of B-cells does not occur. Although type 2 diabetes is associated with a strong genetic predisposition, the genetics of this form of diabetes are complex and not clearly defined.
Type 2 diabetes accounts for approximately 95 percent of diagnosed diabetes in the United States (9.8 million cases), and for the vast majority of the cases of undiagnosed diabetes. The risk of type 2 diabetes increases with age, obesity, and physical inactivity. As such, it is often regarded as a disease associated with a modern Western lifestyle. Type 2 diabetes occurs more frequently in women with prior gestational diabetes and in individuals with hypertension and dyslipidemia. Affected patients often have a family history of diabetes. Type 2 diabetes is more common in African Americans, Hispanic Americans, and Native Americans than in non-Hispanic white Americans. Ketoacidosis seldom occurs spontaneously in type 2 diabetes, but it may arise in association with the stress of another illness. Approximately 70 percent of patients with type 2 diabetes are obese.
Treatment
Large, prospective, randomized, controlled clinical trials in both type 1 and type 2 diabetes have demonstrated that normal or near-normal blood glucose control can delay or prevent the development of major birth defects and the development and progression of complications affecting the eyes, kidneys, and nerves. Accordingly, the goals for management for both type 1 and type 2 diabetes are to achieve glucose levels as close to the nondiabetic range as possible while minimizing the side-effects of treatment (hypoglycemia and weight gain).
In nondiabetic subjects, blood glucose levels are between 70 and 90 mg/dl (milligrams per deciliter) in the fasting state and rise to 120 to 140 mg/dl one to two hours after meals. These values reflect normal glucose tolerance. Average glucose levels may be assessed by measurement of glycosylated hemoglobin (hemoglobin A1c), is a measure of the average blood glucose level over the previous two to four months. In nondiabetic subjects, hemoglobin A1c is generally less than 6.1 percent, and in poorly controlled diabetic subjects, it may rise to 12 percent or higher.
In general, the goals of treatment are to achieve blood glucose and hemoglobin A1c levels as close to the nondiabetic range as possible with diet, physical activity, and medications.
Diet. In type 1 diabetes, diet is designed to provide adequate nutrients for growth and development and for the maintenance of ideal body weight. The recommended diet includes approximately 20 percent of daily calories from protein, 30 percent from fat, and 50 percent from complex carbohydrates. Simple sugars are limited to prevent excessive glucose excursions, and carbohydrate content is distributed into regular meals and snacks so that a similar quantity of carbohydrate is consumed at approximately the same time each day.
Table 3
| Prevalence of diagnosed diabetes per 1,000 population by age, sex, and race, United States, 1994 | |||||
| Age Group | |||||
| Population | 0-44 | 45-64 | 65-74 | 75+ | Total |
| From Centers for Disease Control and Prevention. Diabetes Surveillance, 1997. Atlanta, GA. U.S. Department of Health and Human Services, 1997. | |||||
| white males | 7.8 | 57.7 | 96.0 | 106.8 | 28.4 |
| black males | 10.6 | 120.8 | 171.8 | 120.6 | 35.9 |
| white females | 7.9 | 51.9 | 97.2 | 89.2 | 30.5 |
| black females | 12.1 | 134.5 | 171.8 | 173.5 | 47.9 |
| Total | 8.3 | 62.2 | 101.5 | 103.3 | 30.8 |
In type 2 diabetes, caloric content is adjusted to achieve and maintain an ideal body weight or, in those who are obese, to produce gradual weight loss or at least weight maintenance. Dietary composition may also be adjusted in light of intercurrent conditions. For example, sodium may be restricted for patients with hypertension, and both total fat and saturated fat may be restricted for those with high cholesterol.
Exercise. Exercise lowers blood glucose and improves glucose tolerance in diabetics. Other benefits of exercise are reductions in LDL cholesterol and triglycerides levels, and improvements in HDL cholesterol, improvements in blood pressure, improved cardiovascular fitness, and an increased sense of well-being and quality of life. Because exercise may potentiate the hypoglycemic effect of injected insulin and may, paradoxically, result in elevated blood glucose levels and the rapid development of ketosis in type 1 diabetic patients in poor metabolic control, the goal of management in type 1 diabetes is to permit people to enjoy and participate safely in physical and sport activities. In type 2 diabetes, exercise is frequently prescribed as an adjunct to reduced-calorie diets for weight reduction and to improve insulin resistance.
Medications. Because patients with type 1 diabetes are absolutely insulin deficient, treatment requires insulin injections. Although one or two injections per day are often adequate to prevent symptoms of hyperglycemia, intensive therapy employing three or four insulin injections per day, or continuous subcutaneous insulin infusion, may be necessary to achieve near-normal glucose control.
Both oral medications and injected insulin are used for the treatment of type 2 diabetes. Four groups of oral agents are currently available: insulin secretagogues, which enhance nutrient-stimulated insulin secretion; the biguanides, which suppress abnormal glucose production by the liver; the thiazolidinediones, which reduce insulin resistance at the level of muscle and fat; and the alpha-glucosidase inhibitors, which slow the breakdown and absorption of carbohydrates and reduce postprandial glucose excursions. To the extent that these four groups of oral medications have different mechanisms of action, they can be used clinically in combination. When oral agents are ineffective in controlling hyperglycemia or achieving glycemic goals, insulin is added or substituted.
Monitoring
Self-monitoring of blood glucose is integral to modern diabetes therapy. A lancet is used to obtain a small drop of blood, which is placed on a reagent strip and inserted in a small battery-powered meter. The meter reports the blood glucose level in less than a minute. Results of self-monitoring of blood glucose are used to guide adjustments in diet, exercise, and medications, for the monitoring and treatment of hypoglycemia, and in the home management of intercurrent illness.
Incidence and Prevalence
The number of people developing diabetes and the number of people with diabetes are increasing worldwide. In 2000, it was estimated that 154 million persons, or 4.2 percent of the world’s population, twenty years of age and older had diabetes. By the year 2025, it is estimated that nearly 300 million persons, or 5.4 percent of the world’s population, twenty years of age and older will have diabetes. The major part of this increase will occur in developing countries due to the aging of the population and increasing urbanization (associated with increased body weight and decreased physical activity).
In 1994, there were 939,000 Americans newly diagnosed with diabetes, with a disproportionate number among the elderly and minority populations. The incidence of diagnosed diabetes was3.61 cases per 1,000 persons per year in 1994 (see Table 2).
In 1994, about 8 million persons in the United States (3.1 percent of the population) reported that they had diabetes. The prevalence of diagnosed diabetes increases with age (see Table 3).
Mortality
Diabetes is the seventh leading cause of deaths in the United States. The highest death rates due to diabetes are observed in older Americans and in minority populations. Death certificates underestimate diabetes mortality because of underreporting of diabetes. Only about 10 percent of people with diabetes who die have diabetes listed as the underlying cause of death on their death certificates, and only about 40 percent have it listed anywhere on their death certificates. Diabetes was the underlying cause of death for approximately 57,000 Americans in 1994, and diabetes was recorded on the death certificate of approximately 182,000 Americans. In 1994, black women had the highest death rates due to diabetes, followed by white women and men. That same year, 44 percent of all diabetes-related deaths (80,000 deaths) had cardiovascular disease listed as the underlying cause. Of these deaths, approximately 60 percent were caused by ischemic heart disease and 15 percent by stroke.
Complications And Comorbidities Associated With Diabetes
Diabetic Ketoacidosis (DKA). Ketoacidosis is an acute metabolic complication of diabetes associated with hyperglycemia, nausea, vomiting, abdominal pain, dehydration, ketonemia, and acidosis. In 1994, DKA was the primary diagnosis for 89,000 hospital discharges and a listed diagnosis for 113,000 hospital discharges. Clinical trials have demonstrated that improved education in self-management and improved access to care can prevent up to 70 percent of DKA hospitalizations.
Adverse Outcomes of Pregnancy. Each year in the United States, type 1 diabetes complicates approximately 7,000 pregnancies and type 2 diabetes complicates approximately 12,000 pregnancies. Up to 1,700 infants (9%) of mothers with pregnancies complicated by diabetes (in the U.S.) are born with birth defects affecting the brain, spinal cord, heart, kidneys, and skeleton. Clinical trials have demonstrated that with intensive glycemic control before conception and during the first trimester, the incidence of major birth defects may be reduced to 2 percent, the rate that occurs in infants of nondiabetic mothers.
Diabetic Eye Disease. Diabetes is the leading cause of new cases of legal blindness in Americans between twenty and seventy-four years of age. As many as 40,000 Americans become blind each year as a result of diabetes. In type 1 diabetes, most legal blindness is due at least in part to diabetic retinopathy. Timely diagnosis and appropriate laser treatment can prevent up to 90 percent of blindness due to diabetic retinopathy. In type 2 diabetes, cataract, glaucoma, and senile macular degeneration are more frequent causes of blindness.
Diabetic Kidney Disease. Diabetic nephropathy is characterized by hypertension, proteinuria, and progressive renal insufficiency. Diabetes is now the leading cause of end-stage renal disease (kidney failure requiring dialysis or kidney transplant for survival). In 1997, over 33,000 Americans developed end-stage renal disease due to diabetes. Early detection, aggressive blood pressure control, and treatment with angiotensin-converting enzyme inhibitors can reduce the progression of diabetic nephropathy by about 60 percent.
Amputations. Diabetic neuropathy, peripheral vascular disease, and infection predispose people with diabetes to gangrene and amputations. More than half of all nontraumatic lower extremity amputations (LEAs) occur in people with diabetes. In 1994, there were approximately 67,000 diabetes-related hospital discharges with LEA reported as a procedure in the United States. Clinical trials have demonstrated that early detection of insensitive and deformed feet and multidisciplinary foot-care programs can reduce the rate of amputation by more than 50 percent.
Table 4
| Incidence of hospital discharge for cardiovascular disease per 1,000 diabetic population by age and sex, United States, 1994 | |||||
| Age Group | |||||
| Population | 0-44 | 45-64 | 65-74 | 75+ | Total |
| From Centers for Disease Control and Prevention. Diabetes Surveillance, 1997. Atlanta, GA. U.S. Department of Health and Human Services, 1997. | |||||
| males | 34.3 | 110.6 | 228.3 | 264.9 | 146.3 |
| females | 18.3 | 101.8 | 191.3 | 245.8 | 139.6 |
| Total | 26.1 | 105.8 | 207.4 | 253.0 | 142.7 |
Cardiovascular Disease Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in people with diabetes. Stroke, heart attack, and peripheral vascular disease are two to four times more common in people with diabetes than in people without diabetes. In 1994, there were 1,144,000 diabetes-related hospital discharges that had CVD listed as the primary discharge diagnosis (see Table 4). Part of the increased incidence of cardiovascular disease in people with diabetes is due to the greater prevalence of cardiovascular risk factors, including hypertension, dyslipidemia, and cigarette smoking. Clinical trials have demonstrated that pharmacologic treatments for hypertension and dyslipidemia are as effective, if not more effective, in people with diabetes compared to people without diabetes.
Costs of Diabetes
Health care costs incurred by people with diabetes include non-diabetes-related and diabetes-related costs. In the United States, in 1992, the direct cost of non-diabetes-related and diabetes-related medical care incurred by people with diabetes was estimated to be $105.2 billion. The direct cost of medical care attributable to diabetes was estimated to be $45.2 billion and the indirect cost of diabetes was estimated to be $46.6 million (see Table 5).
In 1992, per capita health care expenditures for people with diabetes averaged $9,493, compared to $2,604 for people without diabetes. When adjusted for age, per capita health care expenditures for people with diabetes were approximately $3,800 higher for people with diabetes than for people without diabetes ($6,425 versus $2,604).
Table 5
| Costs of diabetes mellitus in the United States, 1992 ($ billion) | |||
| Type of Cost | Setting | Attributable to diabetes* | Among People with diabetes** |
| *From Fox-Ray N, Wills S, Thamer M: Direct and Indirect Costs of Diabetes in the United States in 1992. Alexandria, VA: American Diabetes Association, pp. 1-27, 1993. | |||
| **From Rubin RJ, Altman WM, Mendelson DN: Health care expenditures for people with diabetes mellitus, 1992. J Clin Endocrinol Metab 78:809A-809F, 1994. | |||
| Direct | Hospital | 37.2 | 65.2 |
| Nursing home | 1.8 | — | |
| Office | 1.1 | 11.0 | |
| Outpatient | 2.9 | 12.5 | |
| Emergency room | 0.2 | 1.3 | |
| Drugs | 1.7 | 9.9 | |
| Home health | 0.0 | 4.0 | |
| Dental | — | 1.4 | |
| Total | 45.2 | 105.2 | |
| Indirect | Illness | 8.5 | — |
| Disability | 11.2 | — | |
| Death | 27.0 | — | |
| Total | 46.6 | ||
The fact that 62 percent of direct health care costs among people with diabetes and 82 percent of costs directly attributable to diabetes are incurred in the hospital setting suggests that the majority of costs are associated with the treatment of the late, chronic complications of diabetes.
Screening for Type 2 Diabetes
One-third of diabetes in the United States is undiagnosed, and one-third to one-half of all diabetes worldwide is undiagnosed. This finding, combined with the fact that glycemic management can prevent or delay the development of complications, and the fact that diabetic patients may already have complications at clinical diagnosis, have lead some to call for public health screening for type 2 diabetes. In general, screening is appropriate in asymptomatic populations when six specific conditions are met (see Table 6).
Table 6
| Characteristics of Diseases that Warrant Diabetes Screening |
| SOURCE: Engelgau, M. M.; Venkat Narayan, K. M.; and Herman, W. H. (2000). “Screening for Type 2 Diabetes.” Diabetes Care 23:1563-1580. |
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Diabetes imposes substantial morbidity and mortality on the population. The natural history of type 2 diabetes is well understood, and with systematic testing, diabetes can be diagnosed in asymptomatic, preclinical, subjects. Unfortunately, although it is clear that intensified management can improve outcomes, no studies have demonstrated the effectiveness or safety of early treatment. Likewise, there is no consensus as to the optimal approach to screening for type 2 diabetes. Ideally, a screening test should be both sensitive and specific. Generally, however, trade-offs must be made between sensitivity and specificity (increasing sensitivity reduces specificity, and increasing specificity reduces sensitivity). In some health systems, the costs of screening and treatment are reasonable, but in others they are simply unaffordable. Finally, although it is recognized that screening must be an ongoing process, no empirical data exist to indicate the optimal screening frequency.
Questionnaires that use self-reported demographic, behavioral, and past medical history to assign a person to a higher or lower risk group; fasting, random, and postprandial urine glucose tests; fasting, random, and postprandial capillary whole blood and capillary plasma glucose tests; fasting, random, and postprandial venous whole blood and plasma glucose tests; and hemoglobin A1c have all been evaluated as screening tests for diabetes. In general, questionnaires perform rather poorly as screening tests for diabetes. Measurement of glycosuria using a cut-off point greater than or equal to a trace value generally has a low sensitivity and a high specificity. Capillary or venous whole blood or plasma glucose determinations have generally performed better than urine glucose testing. With both urine and blood testing, random, postprandial, and glucose-loaded tests perform better than fasting tests. There is little consensus, however, as to optimal cut-points for defining positive tests. Screening with hemoglobin A1c has suffered from lack of standardization of the assay. Even as this problem has been addressed, the test has generally been found to be specific but less sensitive than glucose measurements.
Accordingly, the American Diabetes Association has recommended that clinicians should be vigilant and recognize clinical histories and signs suggestive of diabetes that warrant testing. Generally, screening of high-risk individuals for type 2 diabetes should be performed only as part of ongoing medical care, understanding that the evidence is incomplete and questions remain as to the benefits and risks of early treatment, the optimal screening methods and cut-points, and screening frequency. Community-based screening for diabetes is generally associated with a low yield and poor follow-up, and it probably does not represent a good use of resources.