1 Arquivos Brasileiros de Endocrinologia & Metabologia 2002 Vol: 46(3):. DOI: 10.1590/S0004-27302002000300008

Relação da homocisteinemia com a sensibilidade à insulina e com fatores de risco cardiovascular em um grupo indígena brasileiro

Relationship of Homocysteine, Insulin Sensitivity and Cardiovascular Risk Factors among the Brazilian Parkatêjê Indians. Hyperhomocysteinemia is an independent cardiovascular risk factor. There are controversies about a possible relation between homocysteine and insulin resistance/sensitivity. To test the relation between homocysteinemia and insulin sensitivity, serum total homocysteine concentrations (HPLC) were measured in samples from ninety Parkatêjê Indians (90% of the adult population, without admixture). Insulin sensitivity (%S) was estimated by HOMA. A diabetic woman was excluded from the analysis involving glycaemia, insulin, proinsulin, HbA1c and %S. Hyperhomocysteinemia and fasting hyperinsulinemia were found in 26.7% and 25.8% of Indians, respectively. Log-transformed (ln) homocysteine was positively correlated with systolic (r= 0.22) and diastolic (r= 0.21) blood pressure, triglycerides (r= 0.39) and uric acid (r= 0.40), after adjustment for age and sex, but not with insulin, proinsulin and ln %S. Ln homocysteine was similar among the quartiles of %S and between the subjects with and without fasting hyperinsulinemia. Insulin, proinsulin and ln %S were similar between the subjects with and without hyperhomocisteinemia. Correlations between variables related to cardiovascular risk were observed, but not between these variables and insulin or ln %S. Perhaps this finding could be a peculiar characteristic of this group. In conclusion, the variations in serum homocysteine levels were not related to insulin, proinsulin and %S among the Parkatêjê. (Arq Bras Endocrinol Metab 2002;46/3:260-268)

  1. Boushey CJ, Beresford SAA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA274 , 1049-57 (1995) .
  2. Eikelboom JW, Lonn E, Genest Jr J, Hankey G, Yusuf S. Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med131 , 363-75 (1999) .
  3. Graham IM, Daly LE, Refsum HM, Robinson K, Brattström LE, Ueland PM, et al. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA277 , 1775-81 (1997) .
  4. Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJC, Jakobs C, Bouter LM, et al. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus. A population-based study. Arterioscler Thromb Vasc Biol18 , 133-8 (1998) .
  5. Reaven GM. Role of insulin resistance in human disease (Syndrome X): an expanded definition. Annu Rev Med44 , 121-31 (1993) .
  6. Gray RS, Fabsitz RR, Cowan LD, Lee ET, Howard BV, Savage PJ. Risk factor clustering in the insulin resistance syndrome. The Strong Heart Study. Am J Epidemiol148 , 869-78 (1998) .
  7. Jacobs RL, House JD, Brosnan ME, Brosnan JT. Effects of streptozocin-induced diabetes and of insulin treatment on homocysteine metabolism in the rat. Diabetes47 , 1967-70 (1998) .
  8. Fonseca V, Dicker-Brown A, Ranganathan S, Song W, Barnard RJ, Fink L, et al. Effects of a high fat-sucrose diet on enzymes in homocysteine metabolism in the rat. Metabolism49 , 736-41 (2000) .
  9. Fonseca VA, Mundaliar S, Schmidt B, Fink LM, Kern PA, Henry RR. Plasma homocysteine concentrations are regulated by acute hyperinsulinemia in nondiabetic but not type 2 diabetic subjects. Metabolism 47 , 686-9 (1998) .
  10. Nagai Y, Takamura T, Nohara E, Yamashita H, Kobayashi K. Acute hyperinsulinemia reduces plasma concentrations of homocysteine in healthy men. [letter; comment]. Diabetes Care22:1004 , (1999) .
  11. Pavía C, Ferrer I, Valls C, Artuch R, Colomé R, Vilaseca MA. Total homocysteine in patients with type 1 diabetes. Diabetes Care23 , 84-7 (2000) .
  12. Cotellessa M, Minniti G, Cerone R, Prigione F, Calevo MG, Lorini R. Low plasma homocysteine concentrations in patients with type 1 diabetes. [letter; comment]. Diabetes Care24 , 969-71 (2001) .
  13. Araki A, Sako Y, Ito H. Plasma homocysteine concentrations in Japanese patients with non-insulin-dependent diabetes mellitus: effect of parenteral methylcobalamin treatment. Atherosclerosis103 , 149-57 (1993) .
  14. Munshi MN, Stone A, Fink L, Fonseca V. Hyperhomocysteinemia following a methionine load in patients with non-insulin-dependent diabetes mellitus and macrovascular disease. Metabolism45 , 133-5 (1996) .
  15. Buysschaert M, Dramais A, Wallemacq PE, Hermans MP. Hyperhomocysteinemia in type 2 diabetes. Diabetes Care23 , 1816-22 (2000) .
  16. Bostom AG, Lathrop L. Hyperhomocysteinemia in end-stage renal disease: prevalence, etiology, and potential relationship to arteriosclerotic outcomes. Kidney Int52 , 10-20 (1997) .
  17. Gallistl S, Sudi K, Mangge H, Erwa W, Borkenstein M. Insulin is an independent correlate of plasma homocysteine levels in obese children and adolescents. Diabetes Care23 , 1348-52 (2000) .
  18. Giltay EJ, Hoogeveen EK, Elbers JMH, Gooren LJG, Asscheman H, Stehouwer CDA. Insulin resistance is associated with elevated plasma total homocysteine levels in healthy, non-obese subjects. [letter; comment]. Atherosclerosis139 , 197-8 (1998) .
  19. Abbasi F, Facchini F, Humphreys MH, Reaven GM. Plasma homocysteine concentrations in healthy volunteers are not related to differences in insulin-mediated glucose disposal. Atherosclerosis146 , 175-8 (1999) .
  20. Godsland IF, Rosankiewicz JR, Proudler AJ, Johnston DG. Plasma total homocysteine concentrations are unrelated to insulin sensitivity and components of the Metabolic Syndrome in healthy men. J Clin Endocrinol Metab86 , 719-23 (2001) .
  21. Ricardo CA. Gavião. In: Ricardo CA, editor. Povos Indígenas no Brasil. Vol. 8: Sudeste do Pará (Tocantins). São Paulo:CEDI 1985, 53-99 .
  22. Vieira-Filho JPB, Russo EMK, Juliano Y. As proteínas glicosiladas dos índios Paracategê. Arq Bras Endocrinol Metabol31 , 33-4 (1987) .
  23. Ubbink JB, Vermaak WJH, Bissbort S. Rapid high-performance liquid chromatographic assay for total homocysteine levels in human serum. J Chromatogr565 , 441-6 (1991) .
  24. Bartels H, Böhmer M, Heierli C. Serum Kreatininbestimmung ohne enteiweissen. Clin Chim Acta 37 , 193-7 (1972) .
  25. Siedel J, Hägele EO, Ziegenhorn J, Wahlefeld AW. Reagent for the enzymatic determination of serum cholesterol with improved lipolytic efficiency. Clin Chem29 , 1075-80 (1983) .
  26. Siedel J, Schmuck R, Staepels J, Town MH. Long term stable liquid ready-to-use monoreagent for the enzymatic assay of serum or plasma triglycerides (GPO-PAP method). AACC Meeting. Abstract 34. Clin Chem39:1127 , (1993) .
  27. Sugiuchi H, Uji Y, Okabe H, Irie T, Uekama K, Kayahara N, et al. Direct measurement of High Density Lipoprotein Cholesterol in serum with polyethylene glycol-modified enzymes and sulfated a-cyclodextrin. Clin Chem41 , 717-23 (1995) .
  28. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem18 , 499-502 (1972) .
  29. Kageyama N. A direct colorimetric determination of uric acid in serum and urine with uricase-catalase system. Clin Chim Acta31 , 421-6 (1971) .
  30. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia28 , 412-9 (1985) .
  31. Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program [letter; comment]. Diabetes Care21 , 2191-2 (1998) .
  32. World Health Organization (WHO). Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO Consultation. Part 1: Diagnosis and classification of diabetes mellitus. Geneva:World Health Organization , (1999) .
  33. Robinson K, Mayer EL, Miller DP, Green R, van Lente F, Gupta A, et al. Hyperhomocysteinemia and low pyridoxal phosphate. Common and independent reversible risk factors for coronary artery disease. Circulation92 , 2825-30 (1995) .
  34. Sociedade Brasileira de Cardiologia. Consenso Brasileiro sobre Dislipidemias - detecção-avaliação-tratamento. Arq Bras Cardiol67 , 110-28 (1996) .
  35. World Health Organization (WHO) Expert Committee. Hypertension control. Technical Report Series n. 862. Geneva:World Health Organization , (1996) .
  36. Berquó E, Gotlieb SLD, Souza JMP. Bioestatística. São Paulo:EPU , (1986) .
  37. Haffner SM, Miettinen H, Stern MP. The homeostasis model in the San Antonio Heart Study. Diabetes Care20(7) , 1087-92 (1997) .
  38. Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity. Diabetes Care 23 , 57-63 (2000) .
  39. Shaw JTE, McWhinney B, Tate JR, Kesting JB, Marczak M, Purdie D, et al. Plasma homocysteine levels in indigenous Australians. Med J Aust170 , 19-22 (1999) .
  40. Dudman NPB, Guo XG, Crooks R, Xie L, Silberberg JS. Assay of plasma homocysteine: light sensitivity of the fluorescent 7-benzo-2-oxa-1,3-diazole-4-sulfonic acid derivative, and use of appropriate standards. Clin Chem42:2028 , (1996) .
  41. Nygard O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE, et al. Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA274(19) , 1526-33 (1995) .
  42. Jacques PF, Rosenberg IH, Rogers G, Selhub J, Bowman BA, Gunter EW, et al. Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr69 , 482-9 (1999) .
  43. Arnesen E, Refsum H, Bonaa KH, Ueland PM, Forde OH, Nordrehaug JE. Serum total homocysteine and coronary heart disease. Int J Epidemiol24(4) , 704-9 (1995) .
  44. Olszewski AJ, Szostak WB, Bialkowska M, Rudnicki S, McCully KS. Reduction of plasma lipid and homocysteine levels by pyridoxine, folate, cobalamin, choline, riboflavin, and troxerutin in atherosclerosis. Atherosclerosis75 , 1-6 (1989) .
  45. Malinow MR, Levenson J, Giral P, Nieto FJ, Razavian M, Segond P, et al. Role of blood pressure, uric acid, and hemorheological parameters on plasma homocyst(e)ine concentration. Atherosclerosis114 , 175-83 (1995) .
  46. Coitinho DC, Leão MM, Recine E, Sichieri R. Ministério da Saúde. Instituto Nacional de Alimentação e Nutrição-INAN. Condições nutricionais da população brasileira: adultos e idosos. Brasília:INAN , (1991) .
  47. Mancilha-Carvalho JJ, Baruzzi RG, Howard PF, Poulter N, Alpers MP, Franco LJ, et al. Blood pressure in four remote populations in the INTERSALT study. Hypertension14 , 238-46 (1989) .
  48. Fleming-Moran M, Santos RV, Coimbra Jr CEA. Blood pressure levels of the Suruí and Zoró Indians of the Brazilian Amazon: group- and sex-specific effects resulting from body composition, health status, and age. Hum Biol63 , 835-61 (1991) .
  49. Pavan L, Casiglia E, Braga LMC, Winnicki M, Puato M, Pauletto P, et al. Effects of a traditional lifestyle on the cardiovascular risk profile: the Amondava population of the Brazilian Amazon. Comparison with matched African, Italian and Polish populations. J Hypertens17 , 749-56 (1999) .
  50. Welty TK, Lee ET, Yeh J, Cowan LD, Go O, Fabsitz RR, et al. Cardiovascular disease risk factors among American Indians. The Strong Heart Study. Am J Epidemiol142 , 269-87 (1995) .
  51. Baruzzi R, Franco L. Ameridians of Brazil. In: Trowell HC, Burkitt DP, editors. Western diseases: their emergence and prevention. London:Edward Arnold 1981, 138-53 .
  52. Mancilha-Carvalho JJ, Crews DE. Lipid profiles of Yanomamo Indians of Brazil. Prev Med19 , 66-75 (1990) .
  53. Zimmet P. The pathogenesis and prevention of diabetes in adults: genes, autoimmunity and demography. Diabetes Care18 , 1050-64 (1995) .
  54. Jaross W. Genetic background of the Metabolic Syndrome. In: Hanefeld M, Leonhardt W, eds. The Metabolic Syndrome. Jena:Gustav Fischer Verlag 1997, 112-9 .
  55. Chiu KC, Cohan P, Lee NP, Chuang L. Insulin sensitivity differs among ethnic groups with a compensatory response in b-cell function. Diabetes Care23 , 1353-8 (2000) .