Diabetes is a chronic disease of impaired glucose metabolism resulting from a deficiency in the action of the hormone insulin. There may be a quantitative deficiency of insulin, production of an abnormal insulin, peripheral resistance to its action or a combination of deficits. The elucidation of insulin's role in the pathogenesis of diabetes and the eventual use of purified, and now biologically synthesized, insulin in the treatment of diabetes is a major accomplishment of modern medicine. Prior to the introduction of insulin in the 1920s, most patients with insulin-dependent diabetes died within two years of onset.
There are two major forms of diabetes. Insulin-dependent diabetes mellitus (IDDM) occurs in those 10% of diabetics who depend on insulin for prevention of ketoacidosis. IDDM most often develops in persons under 20 years of age and is also called juvenile onset, type I, and ketosis or acidosis-prone diabetes. Noninsulin-dependent diabetes mellitus (NIDDM) usually has its onset in adulthood and constitutes 90-95% of all cases. Although some persons with NIDDM may take insulin, most do not require insulin to prevent ketoacidosis. Other names for NIDDM are maturity onset type II, and ketosis- or acidosis-resistant diabetes.
Although there is some overlap in the use of insulin among those with insulin-dependent and noninsulin-dependent diabetes, the disease processes are pathological and genetically distinct. IDDM probably results from the destruction of the insulin-producing beta cells of the pancreas by an auto-immune process that may be precipitated by a viral infection. NIDDM, which in over 75% of cases occurs to overweight persons, is characterized by a gradual decline in beta cell function and varying degrees of peripheral resistance to insulin.
Gestational diabetes is a normally transient condition of impaired glucose metabolism occurring in 2%-5% of pregnancies. After delivery, 98% of gestational diabetes cases resolve; however, about 25% of women with gestational diabetes go on to develop NIDDM later in life. Diabetes is rarely caused by other disease processes that affect the pancreas.
Incidence and Prevalence
The 1982, National Health Interview Survey (NHIS) found that about 2.54% of the American population, or about 5.77 million Americans, had been diagnosed as having diabetes.
The 1976-80 National Health and Nutrition Examination Survey (NHANES II) revealed that 3.2% of the adult (20-74 years) U.S. population without a history of diabetes had glucose tolerance tests suggestive of diabetes, including 3.6% of females, 2.8% of males, 3.0% of whites and 4.4% of Blacks.
Each year over 500,000 persons are newly diagnosed as diabetic in the United States.
Insulin Dependent Diabetes Mellitus (IDDM). The incidence of IDDM in the white population under 20 years of age is approximately 15 per 100,000 per year; among other races the incidence is 11 per 100,000 per year.
From 1965-1980, incidence rates for IDDM remained relatively unchanged at 12-14 per 100,000 children aged 20 years and under.
After age 20, the incidence of IDDM remains stable at 5 per 100,000 per year.
Noninsulin-Dependent Diabetes Mellitus (NIDDM). The increases in incidence of diabetes in the 1960s noted above resulted in part from increased screening efforts and from availability of blood glucose measurement technology.
According to 1979-81 data, the incidence of diabetes in the U.S. among males was 21.9 per 10,000 and among females 23.4 per 10,000 for all ages combined.
Gestational Diabetes. Gestational diabetes occurs in about 2.4% of all pregnancies in the US., or approximately 86,000 pregnancies per year.
A 1980 National Natality and Fetal Mortality Survey showed that the relative risk of perinatal mortality to infants of mothers with gestational diabetes was 2.2 times that of infants of nondiabetic mothers.
Congenital malformations occur in 7.93% of births to mothers without diabetes, compared to 12.19% of births to mothers with IDDM and NIDDM, and to 6.41% of mothers with gestational diabetes.
Infants born to mothers with established diabetes (IDDM or NIDDM) are at increased risk of macrosomia (55%), hypoglycemia (40%), respiratory distress syndrome (25%) and congenital malformations (40%) as well as cardiomegaly, hyperbilirubinemia, hypocalcemia, hypomagnesemia, thrombosis and abnormal clotting.
Patients who develop gestational diabetes (GDM) appear to have a 16 times higher risk of developing NIDDM than those without GDM. In one study, 24.7% of patients with GDM followed 22-28 years postpartum, eventually developed NIDDM.
Insulin-Dependent Diabetes Mellitus (IDDM). The prevalence of IDDM among school-age children in the U.S. is approximately 160-180 per 100,000, or about 1 child in 600. An estimated 120,000 children have IDDM in the United States.
The 1976 National Health Interview Survey (NHIS) reported the following prevalence rates (per 100,000 population) for IDDM among persons 16 years of age or under: white males 200 (per 100,000), white females 140, nonwhite males 150, nonwhite females 110.
The prevalence of IDDM for all age groups in the U.S. is estimated to be 160 per 100,000.
Noninsulin-Dependent Diabetes Mellitus (NIDDM). According to the 1982 NHIS data, 2.54% of the U.S. population or 5.77 million persons reported having diabetes. A 1976-80 NHANES screening survey revealed that an additional 3.2% of those aged 20-74 had undiagnosed type II diabetes.
There has been a 10-fold increase in the total number of diagnosed cases (prevalence) of diabetes, from 0.5 million diabetics in 1936 to 5.4 million in 1979-81.
Since 1973, the incidence of diabetes has declined from 2.97 per 1,000 to 2.27 in 1979-81; however, the prevalence increased during that period from 20.4 per 1,000 to 24.7 per 1,000 as a result of a 19% decline in diabetes mortality from 1970-1984.
[Mortality rates are determined by the National Center for Health Statistics (NCHS) on the basis of the listed cause of death on death certificates. These data tend to underestimate diabetes mortality due to underreporting of diabetes on death certificates, especially among older people with multiple chronic conditions. NCHS data, as well as other estimates making allowances for underreporting, are presented for comparison purposes.]
Provisional figures from the National Center for Health Statistics for 1984 list diabetes mellitus as the seventh leading cause of death in the U.S., with 36,830 deaths in 1984, for a mortality rate of 15.6 deaths per 100,000 population.
In addition to being the cause of 34,583 deaths in 1982, diabetes was listed as a contributing cause of death in an additional 95,000 deaths.
An estimated 349,000 diabetics died from all causes in 1980, for a diabetic mortality rate of 154 per 100,000 general population.
A study of insurance applicants revealed an 11-fold excess mortality for those who develop diabetes before age 15 and a 23-fold excess mortality for those who develop diabetes after age 40.
Age-adjusted diabetes mortality rates for nonwhite races are approximately 1.5 times those for whites.
Ischemic heart diseases are involved in about 60% of diabetes deaths, and cerebrovascular disease in about 25% of diabetes deaths.
Insulin-Dependent Diabetes Mellitus Mortality. The mortality rate for IDDM diabetics with onset before 17 years is about 3 per 1,000 diabetics per year below 25 years and about 20 per 1,000 per year at 25 years and above.
White males and white females with IDDM have similar mortality rates that are 5 and 11 times greater than for nondiabetics of the same age.
Blacks with IDDM have mortality rates (12.3 per 1,000 diabetics) that are twice the mortality rates of whites with IDDM (6.1 per 1,000).
About 12% of persons with IDDM die within 20 years of onset.
Over 50% of deaths to IDDM diabetics under 20 years of age are a result of acute complications of diabetes. Over the age of 30, 47% of deaths to IDDM diabetes are a result of renal disease and 24% a result of heart disease.
Noninsulin-Dependent Diabetes Mellitus Mortality. Survival for 25 years after the diagnosis of noninsulin dependent diabetes mellitus is about 70%-80% of expected survival in the general adult population.
The increased diabetes mortality rates among Blacks probably reflects diabetes prevalence rates for Blacks, which are more than double the rates among whites in those 45 years of age and over. The diabetes case fatality rate measures the number of deaths involving diabetes per 1,000 diabetics (as opposed to the 100,000 general population used as the denominator in death rates). The case fatality rates for diabetes in 1978 for all ages were as follows: white males, 25.4; white females, 25.3; Black males, 19.7; and Black females, 18.6.
Complications of Diabetes
Ketoacidosis. The annual incidence of diabetic ketoacidosis (DKA) ranges from 3-8 episodes per 1,000 diabetics. DKA episodes occur at the onset of diabetes for 20%-30% of newly diagnosed diabetics. Infection and noncompliance with diet/medication precipitate at least 50% of DKA episodes. The DKA rate in females is about 1.5 times that in males.
DKA is the cause of 9%-10% of deaths due to diabetes. The DKA mortality rate is estimated at 57 deaths per 100,000 diabetics per year.
Retinopathy. Diabetic retinopathy is the leading cause of new cases of blindness in people ages 20-74 years in the U.S., accounting for 12% of new cases. Approximately 8% of those who are legally blind have diabetes as the etiology. 12% of diabetics who have been insulin-dependent for 30 or more years are blind. Blindness due to diabetes is estimated to involve lost income and public welfare expense of $75,000,000 annually.
An estimated 97% of insulin-taking and 80% of noninsulin-taking persons with diabetes for 15 or more years suffer diabetic retinopathy, with 40% of insulin-taking and 5% of noninsulin-taking progressing to the most severe stage, proliferative diabetic retinopathy.
The prevalence of blindness secondary to diabetic retinopathy was twice as common among nonwhites (13.6 per 100,000) as for whites (5.9 per 100,000), according to a 1974 study.
Among persons 45-64 in the U.S., the reported prevalence of cataracts and glaucoma was 2.8 and 2.7 times as high, respectively, among diabetics as among all persons.
Renal Disease. Approximately 10% of diabetics have diabetic nephropathy. After 15 years of diabetes, approximately 33% of people with IDDM and 20% of people with NIDDM develop diabetic nephropathy.
Diabetes accounts for about 25% of new cases of end-stage renal disease (ESRD) in the United States. The incidence of diabetic ESRD is 18 per million and the prevalence is 34 per million. End-stage renal disease is 15 times more common among people with IDDM than in people with NIDDM.
The incidence of end-stage renal disease due to diabetic nephropathy in the U.S. in 1980 was nearly 3 times higher among Blacks (40 cases per million population) than among whites (14 per million).
Peripheral Vascular Disease. Peripheral vascular disease occurs in 45% of persons with diabetes of 20 years duration. Approximately 15% of diabetics experience diabetic ulcers on their feet or ankles at some time. Amputations occur in 60 of 10,000 diabetics annually, accounting for 40%-45% of all non-traumatic amputations in the U.S.
Heart Disease. Coronary heart disease is the single most common cause of death in diabetic adults in the U.S. accounting for at least one-third of all deaths in diabetics over age 40.
A 1976 National Health Interview Survey showed that a self-report of a heart attack was 2.5 times more common among diabetic males aged 45-64 years than comparable nondiabetic males, and 4.0 times more common among diabetic females aged 45-64 years than comparable non-diabetic females.
A National Ambulatory Medical Care Survey reported that of all outpatient visits involving diabetes in 1977, 17.5% also involved some form of heart disease.
Hypertension. The 1976-1980 National Health and Nutrition Examination Survey (NHANES-II) reported a history of high blood pressure in 56.2% of adults (20 to 74 years) diagnosed as diabetics and in 50.0% of undiagnosed diabetics versus 21.4% of those with normal glucose tolerance.
In an analysis of death certificates in the U.S. in 1978, diabetes was involved in 10% of deaths due to hypertension, and hypertension was involved in 4.4% of deaths due to diabetes.
Cerebrovascular Disease. The Framingham study indicated that the annual incidence of stroke was about 175 per 10,000 diabetics 65-84 years of age. Numerous studies indicate that the occurrence of stroke in diabetics is 2-6 times greater than in nondiabetics.
Diabetes is implicated in about 7% of deaths due to stroke. Cerebrovascular diseases are present in about 25% of deaths due to diabetes.
Risk Factor Prevalence
Demographic Risk Factors
Age. The peak incidence of IDDM occurs around puberty, ages 10-14 years. The incidence of NIDDM increases with age from about 20 new cases per 10,000 population per year among 25-44 year olds to about 50 new cases per 10,000 per year for those 65 and over.
A national study during 1979-81 revealed that 40% of diabetics are 65 years or older, and 85% are 45 years or older.
Sex. Numerous studies show little evidence for any major difference in the risk of IDDM by sex. The incidence and prevalence of reported NIDDM are 1.8 and 1.4 times greater in women than in men.
Women constitute 52% of the general population and 56.7% of diabetics.
Black women aged 55 years and over have prevalence rates of diabetes that are about 1.5 times that of Black men.
Race. The prevalence of diabetes among Blacks (32.2 cases of diagnosed diabetes per 1,000 population) is 1.4 times higher than the prevalence of diabetes among whites (23.8 per 1,000). However, the prevalence of diabetes among Blacks aged 0-24 years (115 per 1,000) is less than for whites of the same age group (2.0 per 1,000).
In 1979-81, Blacks accounted for 10.3% of the general population, yet constituted 15.4% of diabetics in the U.S.
The relative risk of diabetes among Hispanics is 3.1 times that of whites, and the relative risk for Native Americans is 10.8 times that of whites. The incidence of gestational diabetes, however, is not independently affected by race.
Some American Indian tribes manifest high prevalence rates of diabetes. For adults 35 years or older, 50% of Pimas, 42% of Papagos, 25% of San Carlos Apaches and 13% of Navajos have diabetes. From 1967-1977, the age-adjusted prevalence of diabetes among Pima Indians increased 45%, from 24.0% in 1967 to 34.1% in 1977.
Family History/Genetic Markers
Siblings of children with IDDM have a 7-7.5 times greater risk of developing IDDM than the general population. The risk of NIDDM in siblings of patients with NIDDM is up to 6 times that of age-matched nondiabetic controls. The risk of NIDDM in children of parents with NIDDM is twice that of children of age-matched nondiabetic controls. Women with a family history of overt diabetes are at increased risk of gestational diabetes.
Persons with certain genetic markers, or human leukocyte antigens (HLA), have a 2-5 times increased risk for IDDM than persons without those markers. NIDDM is not associated with any genetic markers among whites, but may be associated with some HLA types in Native Americans.
Obesity is not associated with the development of IDDM. However, the prevalence of NIDDM is 3 times as high among obese siblings of diabetic patients as nonobese siblings. Glucose tolerance returns to normal in about 75% of obese hyperglycemic patients who lose weight. Obese women of all ages have a 2-fold increased risk for gestational diabetes compared to non-obese women.
Women who develop gestational diabetes have prepregnancy weights which are, on average, 20 pounds heavier than those who did not develop gestational diabetes.
Children born to mothers over age 35 were nearly twice as likely to develop IDDM as were children born to younger mothers, according to studies in 1982 and 1983.
In the U.S., about 27% of diabetics use insulin, 35% use oral hypoglycemic medications, 14% use diet alone and 24% are not on any of these therapies.
The use of insulin among diabetics increases with the duration of diabetes. Whereas 27% of all diabetics used insulin, 51% of those with diabetes for 15 or more years were using insulin, according to NHANES II.
A 1981-82 study showed that 48% of insulin-dependent diabetics inject insulin more than once a day, compared to 30% of noninsulin-dependent, insulin-using diabetics.
Insulin pumps can deliver a continuous, more physiologic infusion of insulin. As of 1982, about 6,000 insulin pumps had been sold in the U.S.
About 40% of diabetics test their urine for glucose daily. A 1983 survey revealed that 28% of insulin users and 5% of noninsulin-using diabetics test their own blood glucose at home.
The 1980 National Health Interview Survey revealed that diabetes was the primary diagnosis in 16.9 million outpatient contacts with physicians.
A 1981 National Ambulatory Medical Care Survey showed that diabetes was the fourth leading illness-related cause of visits to office-based physicians, following hypertension, acute upper respiratory infections and otitis media.
National Health Interview Surveys reveal that diabetics average about 10 visits to physicians per person per year compared to 3 physician visits per person per year among the general population.
A national survey showed that in 1977, 27.5% of diabetics were hospitalized, compared to 11.3% of nondiabetics that year.
In 1984 in the U.S., 593,000 inpatients were discharged from hospitals with the principal diagnosis of diabetes after an average length of stay of 8.2 days compared to 6.6 days for all conditions.
In 1983, 675,000 hospitalizations occurred with diabetes as the primary diagnosis, and an additional 2,100,000 hospitalizations with diabetes as a secondary diagnosis, for a total of 2,775,000 hospitalizations involving diabetes, or 7.2% of all hospitalizations.
The percentage of total hospitalizations in the U.S. that involve diabetes has increased from 4.6% in 1971 to 7.2% in 1983.
The number of hospital discharges involving diabetes (as primary and other listed diagnosis) has doubled from 1968 when 61.6 discharges per 10,000 U.S. population occurred, to 1983 when 122.5 discharges per 10,000 population occurred.
The 1977 National Nursing Home Survey revealed that 1 in 7 nursing home residents was diabetic, or about 15% of the nursing home population.
The Centers for Disease Control has established diabetes control programs in 20 states. In most states, it was found that while 80% of hospitals offered an inpatient diabetes education service, less than 25% offered these services on an outpatient basis.
The total economic impact of diabetes in the U.S. in 1984 was estimated at $13.8 billion dollars, 54% of which was for direct medical costs, 32% for indirect costs of disability and 14% for indirect costs of mortality.
Of the $387.0 billion, total U.S. health care costs in 1984, 3.6% was attributable to diabetes.
The per capita cost for health care for diabetics in 1980 was $2,078,3 times the cost of health care for nondiabetics, which was $686.
Prospects for Prevention
By preventing obesity, it is possible that the incidence of NIDDM can be reduced by up to 50%, and the incidence of gestational diabetes by 33%.
Improved education and self-management skills can reduce the incidence of diabetic ketoacidosis by up to 70%, and can prevent approximately 50,000 hospitalizations each year.
Prompt diagnosis and appropriate use of laser photocoagulation therapy can reduce the incidence of severe visual loss by approximately 60% in people with proliferative diabetic retinopathy.
Aggressive antihypertensive therapy can reduce by more than 50% the rate at which diabetic nephropathy progresses, and may delay or prevent the development of diabetic end-stage renal disease.
Strict control of blood glucose among women with established diabetes can decrease perinatal mortality from 24% of births to mothers with average blood glucose levels above 150 mg/dl to 15% of births to mothers with blood glucose levels from 100-150 mg/dl and 4% of births to mothers with blood glucose levels below 100 mg/dl.