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Department of Medicine, Children’s Hospital, Boston, MA 02115
2To whom correspondence should be addressed. E-mail: david.ludwig{at}tch.harvard.edu.
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INTRODUCTION |
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 TOP INTRODUCTION LITERATURE CITED |
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,2
). Significant differences in socioeconomic status and conventional heart disease risk factors exist among racial/ethnic groups in the United States, Canada and the UK (3
–6
). However, these differences do not fully account for the observed disparities in disease prevalence (3
–6
), suggesting the presence of other biological factors.
In recent years, attention has been focused on the importance of the insulin resistance syndrome (IRS, also called Syndrome X) as an underlying cause of both diabetes and heart disease (7
,8
). In this syndrome, insulin resistance and compensatory hyperinsulinemia place the pancreatic B-cell under chronic stress, and give rise to a variety of well known and novel heart disease risk factors, including glucose intolerance, hypertension, dyslipidemia, endothelial dysfunction, hypercoagulability and chronic inflammation. In the United States, the prevalence of IRS differs among racial/ethnic groups and increases with age, exceeding 40% in older adults (9
,10
). IRS has been noted in African-American children as young as 5 y of age (11
).
Obesity is a major cause of insulin resistance and, as a consequence, of IRS, although many genetic and lifestyle factors also affect insulin resistance (10
,12
–15
). Thus, a fundamental issue in understanding disparities in diabetes and heart disease risk is how the natural history of IRS might differ among racial/ethnic groups. Data from the laboratories of Silva Arslanian (16
) and Michael Goran (17
) address this point. First- and second-phase insulin responses were higher in African-American than in Caucasian children after adjusting for body mass index (BMI). Moreover, differences in insulin sensitivity and secretion between African-American and Caucasian children remained, after taking body composition, fat distribution, dietary patterns and physical activity level into account (17
,18
).
In this context, the study by Dickinson et al. (19
) in this issue of The Journal of Nutrition is of particular interest. The investigators fed 60 lean, healthy young adults from five racial/ethnic groups white bread providing 75 g available carbohydrate, and measured changes in plasma glucose and insulin concentrations for a 2-h period. Mean fasting glucose concentrations were very similar among the groups. However, Southeast Asian and Chinese subjects showed markedly higher postprandial glycemia than European Caucasians, with 1.5- to 2.0-fold higher mean incremental areas under the glucose curve. In fact, several Southeast Asian subjects had postprandial responses that would have met criteria for the diagnosis of impaired glucose tolerance. Mean incremental area under the insulin curve was 1.9- to 2.7-fold higher among Southeast Asians, Chinese and Asian Indians compared with European Caucasians. The groups also differed significantly in insulin sensitivity, as assessed by homeostasis model assessment or the hyperinsulinemic euglycemic clamp technique; European Caucasians were most sensitive, whereas Southeast Asians were most resistant. The results do not appear to be attributable to the effects of sex, age, BMI or birth weight because these potentially confounding variables were either controlled for or matched among groups.
These findings have three major implications. Abnormalities in glucose homeostasis are prevalent among individuals of certain racial/ethnic groups in the absence of obesity and advanced age, demonstrating an apparent predisposition to development of IRS. Pathophysiological abnormalities related to diabetes and heart disease risk may occur in apparently healthy individuals earlier than previously recognized. Also, measurements taken in fasting subjects may not reveal important abnormalities in glucose homeostasis, consistent with findings from a recent study of obese children (20
).
It is tempting to ascribe these racial/ethnic differences to genetic influences (21
). Indeed, several genes or genetic loci have been identified that appear to increase risk for IRS in certain populations (22
). However, other factors may also explain, at least in part, the present observations. Under- or overnutrition at critical stages of fetal development appears to induce permanent changes in metabolism, neuroendocrine function or body composition that result in insulin resistance and B-cell dysfunction (23
–25
). It is especially noteworthy that intrauterine influences may be racial/ethnic group specific, in that low birth weight appears to increase risk for IRS in African Americans to a greater extent than in Caucasians (26
). Duration of breast-feeding during infancy has been related to body composition later in life (27
). A number of lifestyle factors may also affect risk for insulin resistance, independent of BMI, including diet (e.g., macronutrient composition, fiber, glycemic index, fatty acid profile and dairy consumption) (10
,14
,15
,28
–30
), physical activity level and fitness (12
) and perhaps psychosocial stress. As recognized by the authors, the present study cannot adequately assess how these factors may have contributed to their findings. A review of studies comparing racial/ethnic differences in glucose tolerance over time emphasizes the difficulty in distinguishing between genetic and acquired influences. For example, African Americans in one urban center in the United States during the 1960s had lower 1-h blood glucose concentration and less glycosuria after consumption of oral glucose compared with Caucasians, even after taking into account measures of adiposity (31
). By contrast, disorders in glucose homeostasis appear to be more common in African Americans than in Caucasians today (10
).
How might the findings from this and related studies be used to decrease disparities in diabetes and heart disease between racial/ethnic groups? Clearly more research into the biological origins of IRS among different populations and with larger subject number is required. Nevertheless, two points pertaining to screening and prevention in high risk racial/ethnic groups warrant careful consideration at this time. First, oral glucose tolerance testing, rather than measurement of fasting glucose concentration, may be necessary to identify individuals at highest risk of diabetes and heart disease in a timely fashion. Second, diets that minimize postprandial glycemia, i.e., reduced carbohydrate (14
,15
), low glycemic index (29
) or both (32
), may have particular benefit for certain populations.
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FOOTNOTES |
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3 See related article: J Nutr. 132: 2574-2579, 2002
Manuscript received 7 June 2002. Revision accepted 18 June 2002.
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LITERATURE CITED |
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TOPINTRODUCTIONLITERATURE CITED |
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1. Anonymous () Race Initiative Summary Report on Cardiovascular Disease. U.S. Department of Health & Human Services Available at: www.raceandhealth.hhs.gov/3rdpgblue/cardio/cvdrep122.pdf. (accessed July 16, 2002).
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11. Young-Hyman, D., Schlundt, D. G., Herman, L., De Luca, F. & Counts, D. (2001) Evaluation of the insulin resistance syndrome in 5- to 10-year-old overweight/obese African-American children. Diabetes Care 24:1359-1364.
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13. Facchini, F. S., Hollenbeck, C. B., Jeppesen, J., Chen, Y. D. & Reaven, G. M. (1992) Insulin resistance and cigarette smoking. Lancet 339:1128-1130.[Medline]
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17. Ku, C. Y., Gower, B. A., Hunter, G. R. & Goran, M. I. (2000) Racial differences in insulin secretion and sensitivity in prepubertal children: role of physical fitness and physical activity. Obes. Res. 8:506-515.[Medline]
18. Lindquist, C. H., Gower, B. A. & Goran, M. I. (2000) Role of dietary factors in ethnic differences in early risk of cardiovascular disease and type 2 diabetes. Am. J. Clin. Nutr. 71:725-732.
19. Dickinson, S., Colagiuri, S., Faramus, E., Petocz, P. & Brand-Miller, J. C. (2002) Postprandial hyperglycemia and reduced insulin sensitivity differ among lean young adults of different ethnicities. J. Nutr. 132:2578-2583.
20. Sinha, R., Fisch, G., Teague, B., Tamborlane, W. V., Banyas, B., Allen, K., Savoye, M., Rieger, V., Taksali, S., Barbetta, G., Sherwin, R. S. & Caprio, S. (2002) Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N. Engl. J. Med. 346:802-810.
21. Pedersen, O. (1999) Genetics of insulin resistance. Exp. Clin. Endocrinol. Diabetes 107:113-118.[Medline]
22. Duggirala, R., Blangero, J., Almasy, L., Arya, R., Dyer, T. D., Williams, K. L., Leach, R. J., O’Connell, P. & Stern, M. P. (2001) A major locus for fasting insulin concentrations and insulin resistance on chromosome 6q with strong pleiotropic effects on obesity-related phenotypes in nondiabetic Mexican Americans. Am. J. Hum. Genet. 68:1149-1164.[Medline]
23. Dabelea, D., Pettitt, D. J., Hanson, R. L., Imperatore, G., Bennett, P. H. & Knowler, W. C. (1999) Birth weight, type 2 diabetes, and insulin resistance in Pima Indian children and young adults. Diabetes Care 22:944-950.[Abstract]
24. Phillips, D. I. (1998) Birth weight and the future development of diabetes. A review of the evidence. Diabetes Care 21(Suppl.):B150-B155.
25. Whitaker, R. C. & Dietz, W. H. (1998) Role of the prenatal environment in the development of obesity. J. Pediatr. 132:768-776.[Medline]
26. Li, C., Johnson, M. S. & Goran, M. I. (2001) Effects of low birth weight on insulin resistance syndrome in Caucasian and African-American children. Diabetes Care 24:2035-2042.
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28. Ludwig, D. S., Pereira, M. A., Kroenke, C. H., Hilner, J. E., Van Horn, L., Slattery, M. L. & Jacobs, D. R., Jr. (1999) Dietary fiber, weight gain, and cardiovascular disease risk factors in young adults. J. Am. Med. Assoc. 282:1539-1546.
29. Ludwig, D. S. (2002) The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. J. Am. Med. Assoc. 287:2414-2423.
30. Lovejoy, J. C. (1999) Dietary fatty acids and insulin resistance. Curr. Atheroscler. Rep. 1:215-220.[Medline]
31. Dales, L. G., Siegilaub, A. B., Feldman, R., Friedman, G. D., Seltzer, C. C. & Collen, M. F. (1974) Racial differences in serum and urine glucose after glucose challenge. Diabetes 23:327-332.[Medline]
32. Ebbeling, C. B. & Ludwig, D. S. (2001) Treating obesity in youth: should dietary glycemic load be a consideration?. Adv. Pediatr. 48:179-212.[Medline]
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