Abstract
Native Americans are predisposed to insulin resistance and associated cardiovascular risk. Therefore, we studied whether BMI (body mass index) in a population of Cherokee children and adolescents is associated with HDL-C (HDL cholesterol), and the HDL particles Lp (lipoprotein) A-I and LpA-I:A-II. Subjects were grouped by BMI Z score quartiles within three gender-specific age brackets (5–9, 10–14, and 15–19 y) to examine for trends in lipoprotein and HOMA-IR (homeostasis index insulin resistance) values associated with adiposity and age. HDL-C decreased by BMI Z score quartiles in all three age groups for both genders. HDL-C, LpA-I, and LpA-I:A-II decreased with age in boys but not girls. Log HOMA-IR increased by BMI Z score quartiles in all three age groups for both genders. Linear regression modeling showed BMI Z score, triglyceride, and age to be associated with HDL-C, whereas HOMA-IR was associated with LpA-I:A-II but not with HDL-C or LpA-I. When waist circumference was substituted for BMI Z score in the same models, it was associated with HDL-C and both lipoprotein particles. In conclusion, adiposity is more associated with HDL-C lowering than with declines in the lipoprotein particles. HOMA-IR is less associated with HDL-C but may selectively influence LpA-I:A-II. Greater decreases in HDL-C, LpA-I, and LpA-I:A-II with age in boys is attributed to gender-specific hormonal changes. The early onset of HDL lowering in these Native American children and adolescents, particularly boys, warrants intervention strategies to prevent obesity and associated cardiovascular risk.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- BMI:
-
body mass index
- HDL-C:
-
high-density lipoprotein cholesterol
- HOMA-IR:
-
homeostasis index insulin resistance
- Lp:
-
lipoprotein
References
Miller GJ, Miller NE 1975 Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet 1: 16–19
Miller NE, Thelle DS, Forde OH, Mjos OD 1977 The Tromso heart-study. High-density lipoprotein and coronary heart disease: a prospective case-control study. Lancet 1: 965–968
Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR 1977 High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 62: 707–714
Homma S, Ishii T, Malcom GT, Zieske AW, Strong JP, Tsugane S, Hirose N 2001 Histopathological modifications of early atherosclerotic lesions by risk factors—findings in PDAY subjects. Atherosclerosis 156: 389–399
Denke MA, Sempos CT, Grundy SM 1993 Excess body weight. An under-recognized contributor to high blood cholesterol levels in white American men. Arch Intern Med 153: 1093–1103
Denke MA, Sempos CT, Grundy SM 1994 Excess body weight. An under-recognized contributor to dyslipidemia in white American women. Arch Intern Med 154: 401–410
Howard BV, Davis MP, Pettitt DJ, Knowler WC, Bennett PH 1983 Plasma and lipoprotein cholesterol and triglyceride concentrations in the Pima Indians: distributions differing from those of Caucasians. Circulation 68: 714–724
West KM 1974 Diabetes in American Indians and other native populations of the New World. Diabetes 23: 841–855
Weyer C, Bogardus C, Mott DM, Pratley RE 1999 The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 104: 787–794
Parra HJ, Arveiler D, Evans AE, Cambou JP, Amouyel P, Bingham A, McMaster D, Schaffer P, Douste-Blazy P, Luc JL, Richard P, Ducimetiere Fruchart JC, Cambien F 1992 A case-control study of lipoprotein particles in two populations at contrasting risk for coronary heart disease. The ECTIM Study. Arterioscler Thromb 12: 701–707
Genest JJ Jr, Bard JM, Fruchart JC, Ordovas JM, Wilson PF, Schaefer EJ 1991 Plasma apolipoprotein A-I, A-II, B, E and C-III containing particles in men with premature coronary artery disease. Atherosclerosis 90: 149–157
Puchois P, Kandoussi A, Fievet P, Fourrier JL, Bertrand M, Koren E, Fruchart JC 1987 Apolipoprotein A-I containing lipoproteins in coronary artery disease. Atherosclerosis 68: 35–40
Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E 2001 High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet 358: 2026–2033
Freedman DS, Srinivasan SR, Shear CL, Webber LS, Chiang YK, Berenson GS 1987 Correlates of high density lipoprotein cholesterol and apolipoprotein A- I levels in children. The Bogalusa Heart Study. Arteriosclerosis 7: 354–360
Leroux G, Lemieux I, Lamarche B, Cantin B, Dagenais GR, Lupien PJ, Despres JP 2000 Influence of triglyceride concentration on the relationship between lipoprotein cholesterol and apolipoprotein B and A-I levels. Metabolism 49: 53–61
Weyer C, Hanson RL, Tataranni PA, Bogardus C, Pratley RE 2000 A high fasting plasma insulin concentration predicts type 2 diabetes independent of insulin resistance: evidence for a pathogenic role of relative hyperinsulinemia. Diabetes 49: 2094–2101
Srinivasan SR, Myers L, Berenson GS 2002 Predictability of childhood adiposity and insulin for developing insulin resistance syndrome (syndrome X) in young adulthood: the Bogalusa Heart Study. Diabetes 51: 204–209
Reaven P, Nader PR, Berry C, Hoy T 1998 Cardiovascular disease insulin risk in Mexican-American and Anglo-American children and mothers. Pediatrics 101: E12
Woodward GC 1998 The Cherokees. University of Oklahoma Press, Norman, OK
Stoddart ML, Blevins KS, Lee ET, Wang W, Blackett PR 2002 Cherokee Diabetes Study. Association of acanthosis nigricans with hyperinsulinemia compared with other selected risk factors for type 2 diabetes in Cherokee Indians: the Cherokee diabetes study. Diabetes Care 25: 1009–1014
Lee ET, Begum M, Wang W, Blackett PR, Blevins KS, Stoddart M, Tolbert B, Alaupovic P 2004 Type 2 diabetes and impaired fasting glucose in American Indians aged 5-40 years: the Cherokee Diabetes Study. Ann Epidemiol 14: 696–704
Dabelea D, Hanson RL, Bennett PH, Roumain J, Knowler WC, Pettitt DJ 1984 Increasing prevalence of Type II diabetes in American Indian children. Diabetologia 41: 904–910
The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 251: 351–364
Lipid Research Clinics Program 1974 The Manual of Laboratory Operations for Lipid and Lipoprotein Analysis. DHEW Publication No. NIH 75-6288. National Institutes of Health, Bethesda, MD
Alaupovic P, Hodis HN, Knight-Gibson C, Mack WJ, LaBree L, Cashin-Hemphill L, Corder CN, Kramsch DM, Blankenhorn DH 1994 Effects of lovastatin on ApoA- and ApoB-containing lipoproteins. Families in a subpopulation of patients participating in the Monitored Atherosclerosis Regression Study (MARS). Arterioscler Thromb 14: 1906–1913
Sobey WJ, Beer SF, Carrington CA, Clark PM, Frank BH, Gray IP, Luzio SD, Owens DR, Schneider AE, Siddle K, Temple RC, Hales CN 1989 Sensitive and specific two-site immunoradiometric assays for human insulin, proinsulin, 65-66 split and 32-33 split proinsulins. Biochem J 260: 535–541
Gungor N, Saad R, Janosky J, Arslanian S 2004 Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents. J Pediatr 144: 47–55
Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, Wei R, Curtin LR, Roche AF, Johnson CL 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11: 1–190
Marcil M, Bissonnette R, Vincent J, Krimbou L, Genest J 2003 Cellular phospholipid and cholesterol efflux in high-density lipoprotein deficiency. Circulation 107: 1366–1371
Alenezi MY, Marcil M, Blank D, Sherman M, Genest J Jr 2004 Is the decreased high-density lipoprotein cholesterol in the metabolic syndrome due to cellular lipid efflux defect?. J Clin Endocrinol Metab 89: 761–764
Sartipy P, Loskutoff DJ 2003 Expression profiling identifies genes that continue to respond to insulin in adipocytes made insulin-resistant by treatment with tumor necrosis factor-alpha. J Biol Chem 278: 52298–52306
Sadur CN, Eckel RH 1982 Insulin stimulation of adipose tissue lipoprotein lipase. Use of the euglycemic clamp technique. J Clin Invest 69: 1119–1125
Chajek T, Eisenberg S 1978 Very low density lipoprotein. Metabolism of phospholipids, cholesterol, and apolipoprotein C in the isolated perfused rat heart. J Clin Invest 61: 1654–1665
Rinninger F, Brundert M, Budzinski RM, Fruchart JC, Greten H, Castro GR 2003 Scavenger receptor BI (SR-BI) mediates a higher selective cholesteryl ester uptake from LpA-I compared with LpA-I:A-II lipoprotein particles. Atherosclerosis 166: 31–40
Pont F, Duvillard L, Florentin E, Gambert P, Verges B 2002 High-density lipoprotein apolipoprotein A-I kinetics in obese insulin resistant patients. An in vivo stable isotope study. Int J Obes Relat Metab Disord 26: 1151–1158
Pietzsch J, Julius U, Nitzsche S, Hanefeld M 1998 In vivo evidence for increased apolipoprotein A-I catabolism in subjects with impaired glucose tolerance. Diabetes 47: 1928–1934
Ikewaki K, Zech LA, Kindt M, Brewer HB Jr, Rader DJ 1995 Apolipoprotein A-II production rate is a major factor regulating the distribution of apolipoprotein A-I among HDL subclasses LpA-I and LpA-I:A-II in normolipidemic humans. Arterioscler Thromb Vasc Biol 15: 306–312
Pietzsch J, Julius U, Nitzsche S, Hanefeld M 1998 In vivo evidence for increased apolipoprotein A-I catabolism in subjects with impaired glucose tolerance. Diabetes 47: 1928–1934
Patsch JR, Prasad S, Gotto AM Jr, Patsch W 1987 High density lipoprotein2. Relationship of the plasma levels of this lipoprotein species to its composition, to the magnitude of postprandial lipemia, and to the activities of lipoprotein lipase and hepatic lipase. J Clin Invest 80: 341–347
Picard F, Boivin A, Lalonde J, Deshaies Y 2002 Resistance of adipose tissue lipoprotein lipase to insulin action in rats fed an obesity-promoting diet. Am J Physiol Endocrinol Metab 282: E412–E418
Eisenberg S, Olivecrona T 1979 Very low density lipoprotein. Fate of phospholipids, cholesterol, and apolipoprotein C during lipolysis in vitro. J Lipid Res 20: 614–623
Tall AR 1993 Plasma cholesteryl ester transfer protein. J Lipid Res 34: 1255–1274
Eisenberg S 1984 High density lipoprotein metabolism. J Lipid Res 25: 1017–1058
Morrison JA, Laskarzewski PM, Rauh JL, Brookman R, Mellies M, Frazer M, Khoury P, deGroot I, Kelly K, Glueck CJ 1979 Lipids, lipoproteins, and sexual maturation during adolescence: the Princeton maturation study. Metabolism 28: 641–649
Beaglehole R, Trost DC, Tamir I, Kwiterovich P, Glueck CJ, Insull W, Christensen B 1980 Plasma high-density lipoprotein cholesterol in children and young adults. The Lipid Research Clinics Program Prevalence Study. Circulation 62: IV83–IV92
Berenson GS, Srinivasan SR, Cresanta JL, Foster TA, Webber LS 1981 Dynamic changes of serum lipoproteins in children during adolescence and sexual maturation. Am J Epidemiol 113: 157–170
Freedman DS, Bowman BA, Srinivasan SR, Berenson GS, Otvos JD 2001 Distribution and correlates of high-density lipoprotein subclasses among children and adolescents. Metabolism 50: 370–376
Patsch JR, Prasad S, Gotto AM Jr, Bengtsson-Olivecrona G 1984 Postprandial lipemia. A key for the conversion of high density lipoprotein2 into high density lipoprotein3 by hepatic lipase. J Clin Invest 74: 2017–2023
Marshall WA 1976 Steroids after birth-puberty. Postgrad Med J 52: 620–624
Faiman C, Winter JS, Reyes FI 1976 Patterns of gonadotrophins and gonadal steroids throughout life. Clin Obstet Gynaecol 3: 467–483
Mowri HO, Patsch W, Smith LC, Gotto AM Jr, Patsch JR 1992 Different reactivities of high density lipoprotein2 subfractions with hepatic lipase. J Lipid Res 33: 1269–1279
Tikkanen MJ, Nikkila EA 1987 Regulation of hepatic lipase and serum lipoproteins by sex steroids. Am Heart J 113: 562–567
Breckenridge WC, Little JA, Alaupovic P, Wang CS, Kuksis A, Kakis G, Lindgren F, Gardiner G 1982 Lipoprotein abnormalities associated with a familial deficiency of hepatic lipase. Atherosclerosis 45: 161–179
Laskarzewski PM, Morrison JA, Gutai J, Khoury PR, Glueck CJ 1983 Longitudinal relationships among endogenous testosterone, estradiol, and Quetelet index with high and low density lipoprotein cholesterols in adolescent boys. Pediatr Res 17: 689–698
Srinivasan SR, Sundaram GS, Williamson GD, Webber LS, Berenson GS 1985 Serum lipoproteins and endogenous sex hormones in early life: observations in children with different lipoprotein profiles. Metabolism 34: 861–867
Srinivasan SR, Elkasabany A, Berenson GS 1998 Distribution and correlates of serum high-density lipoprotein subclasses (LpA-I and LpA-I:A-II) in children from a biracial community. The Bogalusa Heart Study. Metabolism 47: 757–763
Ford ES, Mokdad AH, Giles WH 2003 Trends in waist circumference among U.S. adults. Obes Res 11: 1223–1231
Fernandez JR, Redden DT, Pietrobelli A, Allison DB 2004 Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents. J Pediatr 145: 439–444
Despres JP, Couillard C, Gagnon J, Bergeron J, Leon AS, Rao DC, Skinner JS, Wilmore JH, Bouchard C 2000 Race, visceral adipose tissue, plasma lipids, and lipoprotein lipase activity in men and women: the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) family study. Arterioscler Thromb Vasc Biol 20: 1932–1938
Owens S, Gutin B, Barbeau P, Litaker M, Allison J, Humphries M, Okuyama T, Le NA 2000 Visceral adipose tissue and markers of the insulin resistance syndrome in obese black and white teenagers. Obes Res 8: 287–293
Lemieux S, Despres JP, Moorjani S, Nadeau A, Theriault G, Prud'homme D, Tremblay A, Bouchard C, Lupien PJ 1994 Are gender differences in cardiovascular disease risk factors explained by the level of visceral adipose tissue?. Diabetologia 37: 757–764
Lemieux S, Prud'homme D, Bouchard C, Tremblay A, Despres JP 1993 Sex differences in the relation of visceral adipose tissue accumulation to total body fatness. Am J Clin Nutr 58: 463–467
Goran MI 1999 Visceral fat in prepubertal children: Influence of obesity, anthropometry, ethnicity, gender, diet, and growth. Am J Hum Biol 11: 201–207
Kortelainen ML, Sarkioja T 2001 Visceral fat and coronary pathology in male adolescents. Int J Obes Relat Metab Disord 25: 228–232
Wirth A, Steinmetz B 1998 Gender differences in changes in subcutaneous and intra-abdominal fat during weight reduction: an ultrasound study. Obes Res 6: 393–399
Huang TT, Johnson MS, Figueroa-Colon R, Dwyer JH, Goran MI 2001 Growth of visceral fat, subcutaneous abdominal fat, and total body fat in children. Obes Res 9: 283–289
Gautier JF, Milner MR, Elam E, Chen K, Ravussin E, Pratley RE 1999 Visceral adipose tissue is not increased in Pima Indians compared with equally obese Caucasians and is not related to insulin action or secretion. Diabetologia 42: 28–34
Acknowledgements
The authors thank the Cherokee people and the healthcare and administrative officials of the Cherokee Nation in Tahlequah, OK, for their support and assistance. The authors also thank the administrators and staff of the Cherokee Diabetes Study, Sequoyah High School, and the Cherokee Nation clinics at Stilwell, Salina, Sallisaw, and Jay.
Author information
Authors and Affiliations
Corresponding author
Additional information
The Cherokee Diabetes Study is supported by grant R01 DK47920 from the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the Cherokee Nation.
Rights and permissions
About this article
Cite this article
Blackett, P., Blevins, K., Stoddart, M. et al. Body Mass Index and High-Density Lipoproteins in Cherokee Indian Children and Adolescents. Pediatr Res 58, 472–477 (2005). https://doi.org/10.1203/01.pdr.0000176947.98014.44
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/01.pdr.0000176947.98014.44
This article is cited by
-
An approach to assess and adjust for the influence of multicollinear covariates on metabolomics association patterns—applied to a study of the associations between a comprehensive lipoprotein profile and the homeostatic model assessment of insulin resistance
Metabolomics (2022)
-
Sex differences in HDL ApoC-III in American Indian youth
Biology of Sex Differences (2012)
