What is diabetes? How many American Indians and Alaska Natives have diabetes? What risk factors increase the chance that American Indians and Alaska Natives will develop type 2 diabetes? How does diabetes affect American Indian and Alaska Native women during pregnancy? How does diabetes affect cardiovascular Health in American Indians and Alaska Natives? How do diabetes complications affect American Indians and Alaska Natives? Does diabetes cause an inordinate number of deaths in American Indians and Alaska Natives? How Is NIDDK addressing the problem of diabetes in American Indians? Points to remember References

Diabetes mellitus is one of the most serious health challenges facing American Indians and Alaska Natives in the United States today. The disease is very common in many tribes, and morbidity and mortality from diabetes can be severe.

This population includes all people who derive their origins from any of the original peoples of North America and who continue to maintain cultural identification through tribal affiliations or community recognition. Great diversity in culture, language, location, lifestyles, and genetic heritage exists among American Indians and Alaska Natives. More than 500 Native American tribal organizations, with many differences in language and culture, exist in the United States.

In 1990, the U.S. Bureau of the Census used self-identification to classify people as part of this group. The American Indian and Alaska Native population was estimated at about 2 million.1 Between the 1980 and the 1990 census, a 38 percent increase occurred in the number of people who identified themselves as American Indians or Alaska Natives. This increase reflects an actual rise in the number of people who identify themselves as part of this group, as well as improvements in counting methodology. In 1990, more than half of the American Indian and Alaska Native population lived in the following seven states: Alaska, Arizona, California, New Mexico, North Carolina, Oklahoma, and Washington.

The 1990 census in Alaska showed a total of 85,698 self-identified Alaska Natives. Alaska Natives include three main population groups: Eskimo, Indian, and Aleut.² Within these three groups are further divisions based on geographic location and linguistic and cultural differences.

Within the estimated 2 million self-identified American Indians, about 1.2 million live on 33 reservations served by the Indian Health Service (IHS).¹ Increasingly, tribal organizations are contracting directly with the Federal Government to operate health care facilities on reservations. The following data on American Indians are drawn primarily from information about American Indians living on reservations, not from American Indians living outside the reservations.

Most American Indians and Alaska Natives with diabetes have type 2 diabetes, which usually develops in adults but can develop in children or adolescents. Type 2 diabetes is caused by the body’s resistance to the action of insulin and by impaired insulin secretion. It can be managed with healthy eating, physical activity, oral diabetes medications, and/or injected insulin. Until recently, type 2 diabetes was rarely diagnosed in children and adolescents. However, type 2 diabetes is now common in American Indian children age 10 and older.3 A small number of American Indians (about 2 to 4 percent) have type 1 diabetes, which usually develops before age 20 and is managed with insulin, healthy eating, and physical activity.

About 15 percent of American Indians and Alaska Natives who receive care from the Indian Health Service have been diagnosed with diabetes, a total of 105,000 people. On average, American Indians and Alaska Natives are 2.6 times as likely to have diagnosed diabetes as non-Hispanic whites of a similar age.5 The available data probably under-estimate the true prevalence of diabetes in this population. For example, 40 to 70 percent of American Indian adults age 45 to 74 were found to have diabetes in a recent screening study in three geographic areas.6 Data from the Navajo Health and Nutrition Survey, published in 1997, showed that 22.9 percent of Navajo adults age 20 and older had diabetes. Fourteen percent had a history of diabetes, but another 7 percent were found to have undiagnosed diabetes during the survey.⁷

Type 2 diabetes is becoming increasingly common in youth. Researchers studying 5,274 Pima Indian children from 1967 to 1996 found that the prevalence of type 2 diabetes in girls ages 10 to 14 increased from 0.72 percent in the period 1967 to 1976 to 2.88 percent in the period 1987 to 1996.3 Reports include an increasing incidence in First Nation populations in Canada.⁸

In 1998, about 70,000 of the 2.3 million self-identified American Indians/Alaska Natives who receive care from the IHS had diabetes.⁹ Diabetes rates for American Indians vary by tribal group, as shown in Table 1.

Diabetes is particularly common among middle-age and older American Indians and Alaska Natives. Its prevalence in American Indians and Alaska Natives, compared with that of non-Hispanic whites by age group and sex, is shown in Table 2.

In Pima Indians, the most widely studied American Indian group, the prevalence of type 2 diabetes was approximately 50 percent in individuals ages 30 to 64.¹

During the period from 1986 to 1993, the prevalence of diabetes in Alaska Natives for all ages (adjusted to the 1980 U.S. population) increased by 29 percent, from 15.2 to 19.6 cases per 1,000 people.10 Of these, most had type 2 diabetes.

The prevalence of type 2 diabetes in Alaska Natives varies by subgroup:

Type 1 Diabetes

Type 1 diabetes is relatively rare in American Indians and Alaska Natives. Most cases of type 1 diabetes are seen in people who have both American Indian and Caucasian heritage.¹

That American Indians and Alaska Natives Will Develop Type 2 Diabetes? Two categories of risk factors increase the chance of type 2 diabetes. The first is genetics. The second is medical and lifestyle risk factors, including obesity, diet, and physical inactivity. Individuals with impaired glucose tolerance, impaired fasting glucose, or insulin resistance are at higher risk of progressing to diabetes.

Genetic background is a determining factor in the prevalence of type 2 diabetes. In both the Choctaw Indians and the Pima Indians, the more full-blooded individuals were found to have the highest prevalence of type 2 diabetes, as compared with those of more mixed heritage.¹ In Pima Indians, diabetes rates were found to be highest in children whose parents developed diabetes at an early age.¹

Although the specific genes responsible for the inheritance of type 2 diabetes have not been located, NIDDK scientists studying the Pima Indians have identified a gene called FABP2 that may play a role in insulin resistance.¹¹ More recent studies have shown that a variant in the PPPIR³ gene that is more common in Pimas than Caucasians is associated with type 2 diabetes and insulin resistance.¹²

Medical and Lifestyle Risk Factor

Obesity

Obesity is a major risk factor for type 2 diabetes among all races and ethnic groups. Increasing rates of obesity have been measured in many American Indian and Alaska Native communities. In Pima Indians, 95 percent of those with diabetes are overweight.¹³

The study of obesity and energy metabolism in Pima Indians has not identified exact causes but has revealed that Pima Indian families share the trait of low metabolic rate. This trait is considered predictive of weight gain and development of type 2 diabetes. A "thrifty gene" is also thought to cause a genetic predisposition to obesity, although this gene has not been identified. The thrifty gene theory, first proposed in 1962, suggests that populations of indigenous people who experienced alternating periods of feast and famine gradually adapted by developing a way to store fat more efficiently during periods of plenty to better survive famines.¹⁴

The degree to which obesity is a risk factor for diabetes depends greatly on the location of the excess weight. Central or upper-body obesity is a stronger risk factor for type 2 diabetes than excess weight carried below the waist. In young Pima Indians, waist-to-hip ratio, a measure of central obesity, was more strongly associated with diabetes than body mass index, a measure of overall obesity.¹

Both diet and physical activity have changed for many members of American Indian and Alaska Native groups over the past several decades. Diets are higher in fat and calories than traditional diets; physical activity has decreased.1 Changes in diet and physical activity are associated with the increased prevalence of type 2 diabetes. For example, Pima Indians living in Mexico who consumed a more traditional diet (less animal fat and more complex carbohydrates) had a lower prevalence of type 2 diabetes than Pima Indians living in Arizona. Pima Indians in Mexico also expended more calories through activity.¹⁴

Prediabetes (Impaired Glucose Tolerance and Impaired Fasting Glucose)

Recent recommendations describe two categories of the physiological state between normal blood glucose and the diabetic range of blood glucose. Individuals are described as having impaired glucose tolerance (a 2-hour glucose value of between 140 and 199 mg/dL during the oral glucose tolerance test) or impaired fasting glucose (a fasting plasma glucose value between 110 and 125 mg/dL).⁴

American Indians with impaired glucose tolerance have a higher incidence of diabetes than those whose glucose tolerance test results are in the normal range.¹⁵

Hyperinsulinemia (higher than normal levels of fasting insulin) and insulin resistance (the inability of the body to use its own insulin to properly control blood glucose) are both associated with an increased risk of developing type 2 diabetes. Hyperinsulinemia often predates diabetes by several years. Studies of Pima Indians have shown that both increased insulin secretion and insulin resistance occur in conjunction with impaired glucose tolerance.¹

Both long- and short-term consequences of diabetes during pregnancy are evident in American Indians and Alaska Natives. Congenital abnormalities in infants born to women with type 2 diabetes are as common as those observed in women with type 1 diabetes. Other complications seen in pregnancies in women with type 2 diabetes included increased rates of toxemia and perinatal mortality.¹

Gestational diabetes, in which blood-glucose levels are elevated above normal during pregnancy, occurs in about 2 to 5 percent of all American pregnant women. Perinatal problems such as macrosomia (large body size) and neonatal hypoglycemia (low blood sugar) are higher in babies born to women with gestational diabetes. Although blood-glucose levels generally return to normal after childbirth, an increased risk of developing gestational diabetes in future pregnancies remains. In addition, studies show that many women with gestational diabetes will develop type 2 diabetes later in life.

The prevalence of gestational diabetes in certain groups of American Indians and Alaska Natives is as follows:

Followup studies of American Indian women with gestational diabetes found a high risk of developing subsequent diabetes: 27.5 percent of Pima Indian women developed diabetes within 4 to 8 years, and 30 percent of Zuni Indian women developed diabetes within 6 months to 9 years after pregnancy.¹

Longitudinal studies of diabetes in Pima Indians have shown that adult offspring of women with diabetes during pregnancy have significantly higher rates of diabetes than adult offspring of women without diabetes, showing the possible effect of the diabetic intrauterine environment. In fact, 45 percent of adult offspring of Pima Indian women who were diagnosed with type 2 diabetes predating pregnancy developed diabetes by age 20 to 24. In comparison, only 1.4 percent of adult offspring of women without diabetes during pregnancy went on to develop diabetes by age 24.16 The strongest single risk factor for diabetes in Pima children was exposure to diabetes in utero.³

Diabetes is a major risk factor for cardiovascular disease in all American Indian populations, and cardiovascular disease is the leading cause of death.¹⁷ All heart-related deaths from 1975 to 1984 in Pima Indians occurred in those with diabetes.¹ Recent studies of cardiovascular mortality in Arizona, Oklahoma, North Dakota, and South Dakota revealed that cardiovascular mortality was higher in American Indians compared with that of non-Hispanic whites in the United States.¹⁸

Little information is available on stroke rates in American Indians. The incidence of stroke in Alaska Natives was greatest among Eskimos, followed by Aleuts and Indians. The overall incidence of stroke in Eskimo women was higher than in any other group studied.²

Hypertension (high blood pressure) in American Indians in the United States appears to be less prevalent than in the general population.1 However, recent studies of American Indians in Arizona and Oklahoma showed that the prevalence of hypertension was higher than that of non-Hispanic whites in a national survey.¹⁷

Diabetic Retinopathy

Diabetic retinopathy is a deterioration of the blood vessels in the eye caused by high blood-glucose levels. It can lead to impaired vision and, ultimately, to blindness. One study showed a 49 percent prevalence of diabetic retinopathy in Oklahoma Indians.¹ Pima Indians also have excessive rates of diabetic retinopathy.¹⁴

The incidence of cataract extraction among Pima Indians with diabetes was more than twice the rate of people without diabetes.¹

From 1987 to 1990, American Indians with diabetes experienced end-stage renal disease (the final stage of kidney disease associated with kidney failure and dialysis) six times more frequently than did non-Hispanic whites.1 Especially high rates of diabetic nephropathy (kidney disease) were seen in Alaska Native, Cherokee, Chippewa, Navajo, Oklahoma, Pima, Sioux, and Zuni tribes.¹ In 1989, end-stage renal disease was a leading cause of death among Pima Indians with diabetes.¹⁴

Among Alaska Natives, women were more likely to develop end-stage renal disease and more likely to die of renal failure than men. The overall incidence of dialysis caused by diabetic renal disease from 1986 until 1993 in Alaska Natives was two per 1,000 person-years of diabetes.²

Rates of lower extremity amputation are high in some American Indians but vary by tribe. Several studies indicate a higher amputation rate among men than among women. Loss of protective sensation as detected by a screening monofilament test identified diabetic individuals at high risk for amputation and foot ulceration.¹⁹

Among Pima Indians, the periodontal disease rate was 2.6 times higher in people with diabetes than in those without it. Poor glycemic control among American Indians has been associated with an increased risk of periodontal disease.¹

Infections related to diabetes in American Indians are of particular concern. A study in Sioux Indians showed that those with diabetes were 4.4 times more likely to develop tuberculosis than were Sioux Indians without diabetes. Mortality in Pima Indians with infectious diseases is significant, according to a study that found that five out of six people who died from a serious infection (coccidioidomycosis) had diabetes. In 1987, tuberculosis mortality among American Indians was 5.8 times higher than the rate among all races in the United States.¹

From 1984 to 1986, diabetes was the sixth leading cause of death among American Indians and Alaska Natives in the United States.²⁰

Because mortality rates are based on the underlying cause of death on death certificates, the impact of diabetes on mortality among American Indians and Alaska Natives has been underestimated. Diabetes contributes to several of the leading causes of death in American Indians: heart disease, cerebrovascular disease, pneumonia, and influenza. In addition, one study found that American Indian heritage was underreported on death certificates by 65 percent. Between 1986 and 1988, the adjusted mortality rate for diabetes in American Indians was 4.3 times the rate in non-Hispanic whites.1 Age- and sex-adjusted death rate studies of Pima Indians from 1975 to 1984 found that the mortality rate for diabetes was nearly 12 times greater than the 1980 mortality rate for all races in the United States.¹ Both the duration of the disease and the presence of proteinuria (indicating kidney disease) were factors associated with increased mortality.

According to the Alaska Area Native Health Service, the mortality rate for diabetes in Alaska Natives from 1986 to 1993 was 43.2 per 1,000 person-years of diabetes. Average age at death was 70.3 years. Mortality rates were similar for Aleuts, Eskimos, and Indians.²

Diabetes Prevention Program

In 1996, NIDDK launched its Diabetes Prevention Program (DPP). The goal of this research effort was to learn how to prevent or delay type 2 diabetes in people with impaired glucose tolerance (IGT), a strong risk factor for type 2 diabetes.

The findings of the DPP, which were released in August 2001, showed that people at high risk for type 2 diabetes could sharply lower their chances of developing the disease through diet and exercise. In addition, treatment with the oral diabetes drug metformin also reduced diabetes risk, though less dramatically. These results were so striking that the DPP’s external data monitoring board advised ending the trial early.²¹

Participants randomly assigned to intensive lifestyle intervention reduced their risk of getting type 2 diabetes by 58 percent. On average, this group maintained their physical activity at 30 minutes per day, usually with walking or other moderate intensity exercise, and lost 5 to 7 percent of their body weight. Participants randomized to treatment with metformin reduced their risk of getting type 2 diabetes by 31 percent.

Of the 3,234 participants enrolled in the DPP, 45 percent were from minority groups that suffer disproportionately from type 2 diabetes: African Americans, Hispanic Americans, Asian Americans and Pacific Islanders, and American Indians. The trial also recruited other groups known to be at higher risk for type 2 diabetes, including individuals age 60 and older, women with a history of gestational diabetes, and people with a first-degree relative with type 2 diabetes. Participants ranged from age 25 to 85, with an average age of 51.

Lifestyle intervention successfully reduced the risk of getting type 2 diabetes for both men and women, and across all the ethnic groups. It reduced the development of diabetes in people age 60 and older by 71 percent. Metformin was also effective in men and women and in all the ethnic groups, but was relatively ineffective in the older volunteers and in those who were less overweight.

Researchers will continue to analyze the data to determine whether the interventions reduced cardiovascular disease and atherosclerosis, major causes of death in people with type 2 diabetes. The DPP is the first major trial to show that diet and exercise can effectively delay diabetes in a diverse American population of overweight people with IGT.

1. Gohdes, D. (1995). Diabetes in North American Indians and Alaska Natives. In National Diabetes Data Group, Diabetes in America (NIH Publication No. 95-1468, 2nd ed., pp. 683-701). Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.

2. Schraer, C. D., Adler, A. I., Mayer, A. M., Halderson, K. R., & Trimble, B. A. (1997). Diabetes complications and mortality among Alaska Natives: 8 years of observation. Diabetes Care, 20(3), 314-316.

3. Dabelea, D., Hanson, R. L., Bennett, P. H., Roumain, J., Knowler, W. C., & Pettitt, D. J. (1998). Increasing prevalence of type II diabetes in American Indian children. Diabetologia, 41(8), 904-910.

4. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. (1997). Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 20(7), 1183-1197.

5. National Diabetes Information Clearinghouse. (2002). National diabetes statistics. (NIH publication 02-3892. Fact sheet). Available at: www.niddk.nih.gov/health/diabetes/pubs/dmstats/dmstats.htm. Accessed April 4, 2002.

6. Lee, E. T., Howard, B. V., Savage, P. J., Cowan, L. D., Fabsitz, R. R., Oopik, A. J., Yeh, J., Go, O., Robbins, D. C., & Welty, T. K. (1995). Diabetes and impaired glucose tolerance in three American Indian populations aged 45-74 years. Diabetes Care, 18(5), 599-610.

7. Will, J. C., Strauss, K. F., Mendlein, J. M., Ballew, C., White, L., & Peter, D. G. (1997). Diabetes mellitus among Navajo Indians: Findings from the Navajo Health and Nutrition Survey. Journal of Nutrition, 127(Suppl. 10), 2106S-2113S.

8. Rosenbloom, A. L., Joe, J. R., Young, R. S., & Winter, W. E. (1999). Emerging epidemic of type 2 diabetes in youth. Diabetes Care, 22(2), 345-354.

9. Ríos Burrows, N. (1999, July 23). Data based on personal communication. Indian Health Service, Headquarters Diabetes Program, and Centers for Disease Control and Prevention, Division of Diabetes Translation.

10. Ríos Burrows, N. (1999, July 26). Data based on personal communication. Indian Health Service, Headquarters Diabetes Program, and Centers for Disease Control and Prevention, Division of Diabetes Translation.

11. Baier, L. J., Sacchettini, J. C., Knowler, W. C., Eads, J., Paolisso, G., Tataranni, P. A., Mochizuki, H., Bennett, P. H., Bogardus, C., & Prochazka, M. (1995). An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance. Journal of Clinical Investigation, 95(3), 1281-1287.

12. Xia, J., Scherer, S. W., Cohen, P. T. W., Majer, M., Xi, T., Norman, R. A., Knowler, W. C., Bogardus, C., & Prochazka, M. (1998). A common variant in PPP1R3 associated with insulin resistance and type 2 diabetes. Diabetes, 47(9), 1519-1524.

13. National Institute of Diabetes and Digestive and Kidney Diseases. (1995). The Pima Indians: Pathfinders for health (NIH Publication No. 95-3821. Booklet). Washington, DC: U.S. Government Printing Office.

14. Carter, J. S., Pugh, J. A., & Monterrosa, A. (1996). Non-insulin-dependent diabetes mellitus in minorities in the United States. Annals of Internal Medicine, 125(3), 221-232.

15. Knowler, W. C., Saad, M. F., Pettitt, D. J., Nelson, R. G., & Bennett, P. H. (1993). Determinants of diabetes mellitus in the Pima Indians. Diabetes Care, 16(Suppl. 1), 216-227.

16. Pettitt, D. J., Aleck, K. A., Baird, R. H., Carraher, M. J., Bennett, P. H., & Knowler, W. C. (1988). Congenital susceptibility to NIDDM: Role of intrauterine environment. Diabetes, 37(5), 622-628.

17. Welty, T. K., Lee, E. T., Yeh, J., Cowan, L. D., Go, O., Fabsitz, R. R., Le, N., Oopik, A. J., Robbins, D. C., & Howard, B. V. (1995). Cardiovascular disease risk factors among American Indians: The Strong Heart Study. American Journal of Epidemiology, 142(3), 269-287.

18. Lee, E. T., Cowan, L. D., Welty, T. K., Sievers, M., Howard, W. J., Oopik, A., Wang, W., Yeh, J., Devereux, R. B., Thoades, E. R., Fabsitz, R. R., Go, O., & Howard, B. V. (1998). All-cause mortality and cardiovascular disease mortality in three American Indian populations, aged 45-74, 1984-1988. American Journal of Epidemiology, 147(11), 995-1008.

19. Rith-Najarian, S. J., Stolusky, T., & Gohdes, D. M. (1992). Identifying diabetic patients at high risk for lower-extremity amputation in a primary health care setting: A prospective evaluation of simple screening criteria. Diabetes Care, 15(10), 1386-1389.

20. Gohdes, D., Kaufman, S., & Valway, S. (1993). Diabetes in American Indians. Diabetes Care, 16(Suppl. 1), 239-243.

21. Diabetes Prevention Program Research Group. (2002). Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New England Journal of Medicine, 346, 393-403.