12
Diabetes Mellitus in Native Americans: The Problem and Its Implications

K.M. Venkat Narayan

Introduction

Diabetes mellitus is a group of metabolic disorders characterized by abnormally high levels of blood glucose secondary to inefficient insulin action and/or secretion. The disease often leads to significant disability, including renal failure, blindness, and limb amputation, and to premature death.

Diabetes was apparently rare among Native Americans until the middle part of the twentieth century (Joslin, 1940; West, 1974; Sievers and Fisher, 1985). However, since World War II, it has become one of the most common serious diseases among many Native American tribes (Sievers and Fisher, 1985); in 1987, there were at least 72,000 Native Americans in the United States with diagnosed diabetes (Newman et al., 1990). Diabetes occurring in Native Americans is almost exclusively the type referred to as NIDDM or non-insulin-dependent diabetes mellitus (Sievers and Fisher, 1985). The Pima Indians have the highest recorded prevalence and incidence of NIDDM in the world (Knowler et al., 1978; King and Rewers, 1991). High rates have also been observed among other Native American tribes (Sievers and Fisher, 1985; Gohdes, 1986; Young and Shah,

I wish to thank my colleagues, Drs. Maximilian de Courten, Richard Fernandes, Robert Hanson, Bill Knowler, Robert Nelson, and David Pettitt, for their help and advice. I am also grateful to the members of the Gila River Indian Community for their enormous contribution to the understanding of diabetes.



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--> 12 Diabetes Mellitus in Native Americans: The Problem and Its Implications K.M. Venkat Narayan Introduction Diabetes mellitus is a group of metabolic disorders characterized by abnormally high levels of blood glucose secondary to inefficient insulin action and/or secretion. The disease often leads to significant disability, including renal failure, blindness, and limb amputation, and to premature death. Diabetes was apparently rare among Native Americans until the middle part of the twentieth century (Joslin, 1940; West, 1974; Sievers and Fisher, 1985). However, since World War II, it has become one of the most common serious diseases among many Native American tribes (Sievers and Fisher, 1985); in 1987, there were at least 72,000 Native Americans in the United States with diagnosed diabetes (Newman et al., 1990). Diabetes occurring in Native Americans is almost exclusively the type referred to as NIDDM or non-insulin-dependent diabetes mellitus (Sievers and Fisher, 1985). The Pima Indians have the highest recorded prevalence and incidence of NIDDM in the world (Knowler et al., 1978; King and Rewers, 1991). High rates have also been observed among other Native American tribes (Sievers and Fisher, 1985; Gohdes, 1986; Young and Shah, I wish to thank my colleagues, Drs. Maximilian de Courten, Richard Fernandes, Robert Hanson, Bill Knowler, Robert Nelson, and David Pettitt, for their help and advice. I am also grateful to the members of the Gila River Indian Community for their enormous contribution to the understanding of diabetes.

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--> 1987), as well as in many diverse societies worldwide that have recently adapted to western culture (Prior and Tasman-Jones, 1981; Cameron et al., 1986; Zimmet et al., 1990). It is not entirely clear why the frequency has increased among Native Americans during this century, and the question is the subject of considerable research attention. While it is reasonable to conjecture a genetic predisposition to NIDDM, the role of environmental factors is of undoubted importance in explaining the dramatic increase in rates of NIDDM among many populations. Many of the known environmental determinants are potentially modifiable and offer immediate prospects for preventing or postponing NIDDM (Knowler and Narayan, 1994; Knowler et al., 1995). The complications of diabetes, which account for the increased mortality and morbidity among diabetic subjects, may also be prevented or delayed by systematic application of current knowledge (The DCCT Research Group, 1993; Weir et al., 1994). With a view to informing and influencing health policy, this paper: reviews the magnitude of the problem of NIDDM among Native American populations; summarizes current knowledge about the determinants of NIDDM; describes the major complications of NIDDM; assesses the potential for preventing or delaying NIDDM and its main complications; and suggests research directions that can facilitate the prevention of NIDDM and its complications in Native Americans.   Pima Indian Study Pima Indians, living in a geographically defined part of the Gila River Indian Community of Arizona, have participated in a longitudinal study of diabetes and its complications since 1965 (Bennett et al., 1971), from which much of our current understanding of diabetes among Native Americans has been obtained. As this paper repeatedly refers to data from the Pimas, a brief description of this study and of the Pimas is presented. Approximately every 2 years, each resident of the study area who is at least 5 years old is invited for an examination that includes a medical history; a physical examination; an oral glucose tolerance test; and measurements of height and weight, serum lipids, serum insulin, and urinary proteins. The same standardized methods are used for subjects of all ages, and DNA samples are also collected for genetic studies (Knowler et al., 1990). The Pimas originated from a much larger group of Native Americans

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--> who lived in an area that is now in northwestern Mexico and southern Arizona, and have lived for over 2000 years in the valleys of the Gila and Salt rives in what is now Arizona. It is believed that the Pimas derived from the Paleoindians, those Native Americans descended from the first of the three migrations across the Bering Land Bridge from Asia to America (Williams et al., 1985). Originally a desert people who subsisted on riverine agriculture supplemented by hunting and gathering, they expanded their farming system after contact with early European missionaries (Castetter and Bell, 1942). Subsequent development of the region by European settlers resulted in diversion of the Pimas' water supply and curtailment of their farming activities (Lippincott, 1980). Today much of the Pima land is leased to non-Indian farmers, and the Pimas work in sedentary government jobs or as wage laborers on or off the reservation (Pablo, 1983). Magnitude Of The Problem Of Niddm In Native Americans Prevalence Some idea of the prevalence (the proportion of the population that is affected by the disease at a given point in time) of diabetes among Native Americans can be obtained from case registries held at Indian Health Service (IHS) facilities. The prevalence rates of diagnosed diabetes among Native Americans vary across tribes and are generally higher than in the U.S. population as a whole (Carter et al., 1989; Freeman et al., 1989; Acton et al., 1993b; Valway et al., 1993). In one study, the age-adjusted rate of diagnosed diabetes among all IHS patients was 6.9 percent—2.8 times the U.S. all-races rate. Of the 11 IHS areas examined in this study, all except the Alaska Area had a significantly higher prevalence rate of diagnosed diabetes than the U.S. rate (Valway et al., 1993); however, there are indications that the rates of diagnosed diabetes among Alaska Natives may also be increasing (Schraer et al., 1993). Because nearly 50 percent of diabetes may remain undiagnosed (Harris et al., 1987), population-based studies may provide more accurate estimates of true diabetes prevalence. Data on prevalence of NIDDM from population-based studies (Hall et al., 1992; Sugarman et al., 1992; Rith-Najarian et al., 1993; Lee et al., 1995) are available for only a few Native American tribes (see Table 12-1). These data reveal that the prevalence of diabetes among Native Americans is higher for women than for men and that the rates vary among tribes. However, not all these surveys used the World Health Organization (WHO) definition of diabetes (World Health Organization, 1981), and this is likely to have led to an underestimation of

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--> TABLE 12-1 Age-Adjusted Prevalence of Diabetes Among Native Americans from Population-based Studies     Prevalencea (%)     Author Study Population Male Female Total Lee et al. (1995) Men and women aged 45-74:         Pima/Maricopa/Papago, Arizona 65 72 70   Apache, Caddo, Comanche, Delaware, Fort Sill Apache, Kiowa, Wichita, Oklahoma 38 42 40   Oglala, Sioux, Cheyenne River Sioux, Devils Lake Sioux, Dakota 33 46 40 Rith-Najarian et al. (1993)b Men and women of all ages, Red Lake Chippewa Indians 13 16 15 Sugarman et al. (1992)b Men and women aged 20-74, Navajo Indians, Shiprock 14 18 17 Hall et al. (1992)b Men and women aged >20 years, Navajo Indians, Many Farms-Rough Rock 11 14 12 a Prevalence rates are standardized to the U.S. general population for the relevant ages. b These studies did not use the WHO criteria for NIDDM (World Health Organization, 1985), and therefore the prevalence rates are likely to be underestimates. prevalence in some studies (Hall et al., 1992; Sugarman et al., 1992; Rith-Najarian et al., 1993). Overall, the prevalence of diabetes among Native Americans is higher than the rate of 6.6 percent for the U.S. population at large (Harris et al., 1987). Evidence for a higher prevalence of diabetes among Native Americans is also available from an epidemiological study that compared the Pima Indians with a predominantly white population of Rochester, Minnesota (Knowler et al., 1978). This study found that the Pimas had an age-sex standardized diabetes prevalence rate 12.7 times that of Caucasians and that, in contrast to the picture among the Pimas, diabetes prevalence in Rochester was higher for men than for women. Diabetes among the Pimas is remarkably frequent at younger ages, and it is especially striking that about 50 percent of Pima adults over 35 years of age have NIDDM (Knowler et al., 1981). The prevalence of diabetes among the Pimas, defined by the oral glucose tolerance test (World Health Organization, 1985), has increased over three successive decades (Figure 12-1). Overall, the prevalence increased by 29 percent in men during 1965-1974 (17.62 percent) and 1985-1994 (22.69 percent) and by 35 percent in women during the same period (1965-1974:23.10 percent, 1985-1994:31.24 percent). Why is the prevalence of diabetes increasing among Native Americans?

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--> FIGURE 12-1 Age-sex specific prevalence of diabetes in Pima Indians in three time periods. Prevalence rates were estimated from data for all subjects examined in each of the 10-year periods 1965-1974, 1975-1984, and 1985-1994. SOURCE: Updated from Knowler et al. (1990). Prevalence can increase for two reasons: improvement in survival and/or increase in the rate of development of new cases. The length of survival following the onset of diabetes may have increased over a period of time, probably as a result of better treatment or a change in the natural history of the disease. However, diabetes contributes little to mortality rates among people under the age of 55 (Pettitt et al., 1982), and an improvement in survival is thus an unlikely explanation for the increase in prevalence among younger Native Americans. This suggests that at least part of the increase in prevalence among Native Americans may be due to an increase in the incidence (the rate at which new cases develop) of the disease. Incidence The Pimas have the highest reported incidence of diabetes in the world—19 times the rate of diagnosed diabetes among the predominantly white population of Rochester, Minnesota (Knowler et al., 1978), and a high incidence of the disease has also been reported among other Native American tribes (Rith-Najarian et al., 1993). Figure 12-2 shows the age-sex specific incidence of diabetes among Pima Indians during three successive decades. As reported earlier (Knowler et al., 1990), the incidence rates vary by age, peaking between 35 and 44 years in men in 1965-1974 and between 45 and 54 years in men in more recent years. In women, the incidence rates peak between 45 and 54 years in 1965-1974 and 1985-1994 and between 55 and 64 years in 1975-1984. The incidence of diabetes has also increased over three successive decades at most ages and in both men

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--> FIGURE 12-2 Age-sex specific incidence rates of diabetes among Pima Indians during three decades. Incidence rates are expressed as new cases of diabetes per 1000 person-years (PYR) of observation of nondiabetic subjects. Cases and PYRs are divided into three time periods: 1965-1974, 1975-1984, and 1985-1994. SOURCE: Updated from Knowler et al. (1990). and women. Overall, in men, controlled for age, the incidence increased by 102 percent, from 11.79/1000 person-years (PYR) in 1965-1974 to 23.82/1000 PYR in 1985-1994. During this period, the incidence in women, controlled for age, increased by 87 percent, from 15.19/1000 PYR in 1965-1974 to 28.41/1000 PYR in 1985-1994. Why is the incidence of diabetes increasing among Native Americans? While it is likely that there is an underlying genetic susceptibility to diabetes, the dramatic increase in incidence over a relatively short period of time emphasizes the overriding importance of environmental determinants. The discussion now turns to the determinants of diabetes, both genetic and environmental. Determinants Of Niddm Genetic Factors The risk of diabetes is associated with the degree of Indian heritage (Drevets, 1965; Brousseau et al., 1979; Knowler et al., 1986). Diabetes aggregates in Native American families (Lee et al., 1985; Knowler et al., 1990), and the risk of diabetes occurring at an early age is strongly transmitted from parent to offspring, but diabetes occurring at an older age in parents has less effect on the risk of diabetes in offspring (Knowler et al., 1990). Diabetes among Pima Indians is associated with the HLA-A2 phenotype

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--> (Williams et al., 1981), and genetic markers on chromosome 4q and 7q have been linked to insulin resistance (the underlying abnormality in NIDDM) among this population (Prochazka et al., 1993, 1995). However, knowledge concerning the genetics of NIDDM is still rudimentary, and it may be hoped that research will lead to a better understanding of the pathogenesis of the disease. Environmental Factors A number of potentially modifiable factors, including obesity, dietary composition, and physical inactivity, are thought to contribute to the progression from genetic susceptibility to NIDDM (Saad et al., 1988; Tuomilehto et al., 1992; Knowler et al., 1995). Obesity Obesity is a powerful and well-established risk factor for the development of NIDDM (Knowler et al., 1981). As shown in Figure 12-3, the age-sex adjusted incidence of diabetes among Pima Indians increases with body mass index (BMI), a measure of obesity. Compared with those with a BMI <20 kg/m2, Pima Indians with a BMI of 20-25 have a 13.6-fold higher incidence of NIDDM, and those with a BMI of 25-30 have a 21.6-fold higher incidence (Knowler et al., 1981). Furthermore, the incidence of diabetes increases with the duration of obesity (BMI (>30 kg/m2); compared with Pima Indians with less than 5 years of obesity, those with 5-10 years of obesity have 1.4 times the incidence of NIDDM, while those with at least 10 years of obesity have 2.4 times the incidence (Everhart et al., 1992). The distribution of body fat may also be important, with central obesity having been found to be related to the risk of the disease (Knowler et al., 1991; Hall et al., 1991; Warne et al., 1995). The prevalence of obesity among Native Americans is higher than among the U.S. general population in both males and females and at all ages (Broussard et al., 1991). The reasons for higher obesity among Native Americans are not entirely clear. Broussard et al. (1991) estimated that the overall prevalence of obesity1 among Native Americans was 13.7 percent for men and 16.5 percent for women, higher than the U.S. rates of 9.1 percent and 8.2 percent, respectively. Data from the Pimas are consistent with this finding. Furthermore, the mean BMI among Pima adults has increased over time (Figure 12-4), and a secular increase in the prevalence 1   BMI >95th percentile of the National Health and Nutrition Examination Survey (NHANES) II reference: BMI(kg/m2 >31.1 for men, >32.3 for women).

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--> FIGURE 12-3 Age-sex adjusted incidence of diabetes by body mass index (BMI), with 95 percent confidence intervals. SOURCE: Knowler et al. (1990). of overweight has been reported among the Navajo Indians (Hall et al., 1992). Pima children have also, on average, become heavier during this century and continue to do so (Knowler et al., 1991). Diet Diet has been linked with the development of diabetes for over 2,500 years (Gulabkunverba, 1949). The precise role of dietary factors, which has been reviewed elsewhere (Knowler et al., 1993), remains ambiguous. However, evidence suggests that a high-fat diet may be related to the development of the disease (Eriksson and Lingärde, 1991; Marshall et al., 1994). Few data are available for Native Americans linking dietary factors with the development of NIDDM, except for one study of the Pima Indians that found a possible association with a high-calorie diet (Bennett et al., 1984). The traditional Pima diet, derived from local agricultural produce, is believed to have been high in fiber and low in fat (Knowler et al., 1990), but this diet appears to have changed during this century and is now more or less similar to the diet in the rest of the United States (Smith et al., 1996). Similar secular changes in the diet of other Native American

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--> FIGURE 12-4 Mean body mass index (BMI) among Pimas for two periods and among the U.S. white population. The Pima data from each period were used for all subjects examined in each of the 8-year periods 1965-1972 and 1981-1988. The U.S. data are from the National Health and Nutrition Examination Survey (NHANES) II. SOURCE: Modified from Knowler et al. (1991). populations are believed to have occurred; in particular, the fat content of Indian diets has increased dramatically—from 17 percent of total calories in the pre-European contact diet, to 28 percent in the reservation diet, to 38 percent in the current diet (Jackson, 1994). Physical Activity There is evidence that increased physical activity may have a protective effect on the development of NIDDM (Frisch et al., 1986; Schranz et al., 1991; Manson et al., 1991, 1992; Helmrich et al., 1991). As shown in Figure 12-5, the age-adjusted prevalence of NIDDM among Pima Indians aged 15-36 was lower with higher amounts of leisure physical activity in the preceding year. Among those aged 37-57, those with the lowest levels of physical activity had the highest prevalence of the disease (Kriska et al., 1993). When the exercise habits of 49 Zuni Indians of New Mexico presenting with NIDDM were compared with those of 99 nondiabetic controls (Benjamin et al., 1993), subjects with diabetes were found to be less likely to exercise frequently than those without. The hypothesis that high

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--> FIGURE 12-5 Age-adjusted prevalence and 95 percent confidence interval of NIDDM by tertile groups of past-year leisure physical activity among subjects aged 15-36 (upper panel) and 37-59 (lower panel). SOURCE: Modified from Kriska et al. (1993). levels of physical activity may be protective against NIDDM is consistent with the observation that diabetes was apparently rare among Native Americans in the past, when they were a physically active agricultural and hunter-gatherer society.

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--> Complications Of Niddm NIDDM is associated with premature mortality and significant morbidity, including renal failure, limb amputation, blindness, ischemic heart disease, adverse outcomes of pregnancy, gum disease, neuropathy, acute glycemic complications, lipid abnormalities, and psychosocial problems. The discussion here is limited to mortality, end-stage renal disease (ESRD), and lower-extremity amputation (LEA). Mortality Overall, Native Americans have higher death rates than the U.S. general population (Program Statistics Branch, 1986; U.S. Department of Health and Human Services, 1985), a fact confirmed by detailed investigations in Canada (Mao et al., 1986) and among specific U.S. Native American populations (Mahoney et al., 1989; Sievers et al., 1990). The patterns of death among members of the Seneca Nation of Indians in New York State between 1955 and 1984 were compared with those of the general New York State population (Mahoney et al., 1989). As seen in Figure 12-6, compared with the New York State population, a greater-than-expected number of both male and female members of the Seneca Nation died from all causes, from infectious diseases, from diabetes, from liver cirrhosis, from accidents and injuries, and from suicides, while a lower-than-expected number died from cancers and cardiovascular diseases. A similar pattern of deaths was found among the Pima Indians (Sievers et al., 1990), and the age- and sex-adjusted average annual death rate in the Gila River Indian Community (1639/100,000) was 1.9 times the 1980 rate for the United States, all races (878/100,000). Death rates were higher among Pima men than women, and Pima men had an age-adjusted death rate 2.3 times that of U.S. men, all races. Furthermore, young Pima men aged 25-34 had 6.6 times the mortality rate of men of the same age in the U.S. general population. The age-sex adjusted death rate among the Pimas was 11.9 times the rate of the United States, all races, for diabetes, 5.9 times the rate for accidents, 6.5 times the rate for cirrhosis, and 4.3 times the rate for suicide. Pima Indian men and women with diabetes have higher death rates than those without, and the age-sex adjusted death rate among diabetic subjects was found to be 1.7 times that among nondiabetic subjects (Sievers et al., 1992). The major cause of this higher risk of death among diabetic subjects is increased deaths from kidney disease, ischemic heart disease, and infections. A study among Oklahoma Indians (Lee et al., 1993a) also confirmed higher death rates among diabetic than nondiabetic subjects and demonstrated that on average, Oklahoma Indians developing

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--> the lines of some of the successful coronary heart disease prevention studies (World Health Organization, 1981; Farquhar et al., 1983; Farquhar, 1984; Lefebrve et al., 1987). Such action would be a further step forward from some preliminary efforts already evident in a few communities (Leonard et al., 1986; Heath et al., 1987; Heath et al., 1991). Potential Benefit from Prevention The impact of NIDDM on various adverse outcomes can be quantified by calculation of attributable risk fraction (AF) and population attributable risk fraction (PARF) (Miettinen, 1974). Suitable data for the Pima Indians were used to assess the potential impact of diabetes prevention on mortality, ESRD, and LEA, with the results shown in Table 12-2. AF and PARF were estimated as suggested by Levin (1953); the details of the computation are shown in the footnotes to Table 12-2. Among the Pimas, diabetes is associated with an excess incidence of 14.3 percent of all deaths, 92.1 percent of ischemic heart disease deaths, 94.4 percent of ESRD, and 96.6 percent of LEA. The potential for decreasing the incidence of mortality, ESRD, and LEA by reducing the current prevalence of diabetes (27.6 percent) among TABLE 12-2 Potential for Reduction of NIDDM Complications by Preventing Diabetes in Pima Indians Complication RRa AFb(%) PARFc(%) Mortality (Sievers et al., 1992) All causes 1.6 37.5 14.3 All natural causes 1.7 41.2 16.2 Ischemic heart disease 43.4 97.7 92.1 Stroke 1.3 23.1 7.7 Infectious diseases 1.3 23.1 7.7 End-stage renal disease (Nelson et al., 1988a) 62.0 98.4 94.4 Lower-extremity amputation (Nelson et al., 1988b) 104.0 99.0 96.6 a RR = Risk ratio (ratio of incidence of complication in diabetic subjects relative to nondiabetic subjects). b AF = Attributable or etiologic fraction (the proportion of the complication that can be attributable to diabetes): RR-1/RR. c PARF = Population attributable risk fraction or prevented fraction (the proportion of incidence of the complication in the population associated with diabetes): P(RR - 1)/1 + P(RR - 1), where P is the prevalence of diabetes, which was 27.6 percent during 1984-1994.

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--> TABLE 12-3 Estimated Percentage Reductions in the Incidence of Various Diabetes Complications If Current Prevalence of Diabetes Were Reduced to Five New Target Levels.   Expected % reduction in incidenceb if diabetes prevalence were reduced to: Complication PARF1a(%) 25% 20% 15% 10% 5% All-causes mortality 14.3 1.5 4.0 6.5 9.1 11.7 Natural-causes mortality 16.2 1.5 4.5 7.4 10.4 13.3 IHD mortality 92.1 8.1 24.8 41.9 58.6 75.4 Stroke mortality 7.7 0.8 2.1 3.6 4.9 6.3 Infectious disease mortality 7.7 0.8 2.1 3.6 4.9 6.3 End-stage renal disease 94.4 9.7 26.3 43.4 60.3 77.3 Lower-extremity amputation 96.6 8.1 27.7 44.3 61.4 79.1 a PARF1 = Population attributable risk fraction under the current diabetes prevalence of 27.6 percent. b Expected (%) reduction in incidence = {1 - (PARF1/1 - PARF2)}*100, where PARF2 is PARF at reduced prevalence of diabetes. the Pimas to five target levels of 25, 20, 15, 10, and 5 percent was estimated as shown in the footnotes for Table 12-3 (Ruta et al., 1993). These estimates assume that diabetes and other potential risk factors bear a constant relationship with mortality, ESRD, and LEA at all levels of diabetes prevalence. As shown in Table 12-3, even small decreases in the prevalence of diabetes can result in considerable reduction in diabetes complications, particularly ESRD and LEA. Furthermore, if the prevalence of diabetes among the Pimas could be reduced to 6.6 percent, the rate among the U.S. general population, the following reduction in the incidence of diabetes complications could result: 10.9 percent of deaths from all causes, 74.7 percent of deaths from ischemic heart disease, 71.9 percent of ESRD, and 73.9 percent of LEA. Prevention of diabetes is therefore worth considering. However, as in most real-life healthcare situations, the question may not be simply whether diabetes is worth preventing, but rather how much diabetes is worth preventing, given resource constraints? The kind of information presented in Table 12-3 allows the estimation of marginal benefits (for example, the extra benefit from reduction in the incidence of complications if the prevalence of diabetes were reduced by an extra 5 percent). Such estimation can support policy decisions, especially if it can be combined with data on estimated costs of achieving a given reduction in the prevalence of diabetes.

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--> Prevention of Complications In addition to the potential reduction in complications that could result from preventing NIDDM, a number of other measures could prevent or delay the onset of complications in subjects with diabetes. Early Detection of NIDDM A large proportion of subjects with NIDDM remain undiagnosed (Harris et al., 1987) and might benefit from early detection and treatment. However, there are a number of questions concerning which people would benefit from such early-detection activities. As noted earlier, being a Native American is a major risk factor for developing NIDDM. According to the American Diabetes Association (1989), all individuals with at least one risk factor for NIDDM should be identified through community screening programs (defined as screening not performed under the direct and close supervision of a physician), and individuals indicating symptoms should be referred for medical evaluation. Blood Glucose Control Complications of NIDDM in Native Americans are related to the concentration of blood glucose (Dorf et al., 1976; Pettitt et al., 1980; Nelson et al., 1989; Lee et al., 1992). It has been shown that tight control of blood glucose can prevent or delay the onset of complications, but this evidence is based on subjects with insulin-dependent diabetes mellitus (IDDM) (The Diabetes Control and Complications Trial Research Group, 1993). However, it is believed that the beneficial effect of glucose control in forestalling complications of IDDM may also apply to NIDDM (Weir et al., 1994). What is not clear is the means of achieving blood glucose control and their relative benefits and risks. Early Detection and Management of Complications Structured approaches aimed at early detection and management of hypertension, dyslipidemia, retinopathy, lower extremity problems, and nephropathy are also known to be of benefit in limiting the complications of diabetes (Weir et al., 1994). Essential features of many of these activities are good coordination, active patient involvement, a multidisciplinary team approach, acceptance of standards of care, and regular evaluation. A number of such programs have been implemented successfully within IHS facilities (Acton et al., 1993a; Newman et al., 1993b).

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--> Research To Facilitate Prevention Of Niddm And Its Complications Understanding of the genetics of NIDDM among Native Americans is important and may lead to better identification of high-risk subjects and possibly to the development of newer treatments. Similarly, a well-designed clinical trial evaluating the efficacy and effectiveness of interventions aimed at preventing or delaying the progression from impaired glucose tolerance to NIDDM in Native Americans is also a priority. In addition to these topics, which are already receiving substantial attention, three key research areas can be emphasized. Population-based Primary Prevention Given the high prevalence of diabetes in Native American communities and the nature of the risk factors involved, much can be gained from implementing and evaluating a well-designed population-based life-style intervention study in selected communities. Such approaches are likely to complement clinical trials among high-risk individuals. Blood Glucose Control Multicenter studies in Native American communities aimed at understanding optimal ways of achieving blood glucose control in NIDDM subjects would facilitate the prevention of diabetic complications. Economic Appraisal Economic appraisal can assist in the optimal allocation of resources aimed at improving health. The total economic and social costs of diabetes and its complications among Native Americans should be estimated, and detailed assessments of the marginal costs and marginal benefits of various interventions should be undertaken. References Acton, K., S. Valway, S. Helgerson, J.D. Huy, K. Smith. V. Chapman, and D. Gohdes 1993a Improved diabetes care for American Indians. Diabetes Care 16 (suppl. 1):372-375. Acton, K., B. Rogers, G. Campbell, C. Johnson, and D. Gohdes 1993b Prevalence of diagnosed diabetes and selected related conditions six reservations in Montana and Wyoming. Diabetes Care 16 (suppl. 1):263-266. American Diabetes Association 1989 Screening for diabetes: Position statement. Diabetes Care 12(8):588-590.

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