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Colegio de Medicina Interna de México.

2014, Number 4

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Med Int Mex 2014; 30 (4)

Diminished Sensitivity to Insulin in a Group of Non-Diabetic Non-Obese Patients with Hypertriglyceridemia

Castro-Sansores CJ, Hernández-Escalante V, Arjona-Villicaña R, Cabrera AZ, Vivas-Rosel ML

Language: Spanish
References: 46
Page: 381-392
PDF size: 522.62 Kb.


ABSTRACT

Background: Diabetes mellitus and dyslipidemias are ones of the most frequent diseases in Mexico. Although resistance to insulin and type 2 diabetes mellitus are multifactorial, high levels of triglycerides have a lypotoxic effect over peripheral tissues that can significantly reduce sensitivity to insulin.
Objective: To determine sensitivity to insulin in a group of non-diabetic non-obese patients with hypertriglyceridemia, and to compare them with a group of healthy subjects without hypertriglyceridemia.
Material and method: A case-control and analytical study was performed with patients from the Internal Medicine Clinic al Hospital Regional Mérida, ISSSTE, who met inclusion criteria. We determined glucose, total cholesterol, HDL-C and triglycerides, LDL-C was calculated using the Friedewald formula –whenever triglycerides levels were >350mg/ dL, LDL cholesterol was measured directly–, insulin was measured by radioimmunoassay. Determinations of the homeostasis model to measure sensitivity to insulin (HOMA-S) and insulin-secreting capacity (HOMA-B) were done using the HOMA calculator software, version 2.2, of the Diabetes trials unit, University of Oxford, UK.
Results: We included 202 subjects, 80 (40%) male; the average age was of 48 years (limits: 20-65). According to inclusion criteria, 102 (50.5%) met criteria for hypertriglyceridemia, and 100 (49.5%) were deemed normolypemic. Sensitivity to insulin (HOMA-S) was significantly diminished (79.8% vs 110.6%, p‹0.0001) and insulin resistance (HOMA-IR) was significantly increased (1.7% vs 1.1%, p‹0.0001) in hypertriglyceridemic patients as compared to normolypemic subjects.
Conclusions: Sensitivity to insulin is significantly reduced in patients with hypertriglyceridemia as compared to normolypemic subjects. Lipid alterations, particularly hypertriglyceridemia, reduce sensitivity to insulin, and could participate, among other factors, in type 2 diabetes mellitus physiopathology.


REFERENCES

  1. Velázquez-Monroy O, Rosas Peralta M, Lara Esqueda A, Pastelin Hernández G y col. Prevalencia e interrelación de enfermedades crónicas no transmisibles y factores de riesgo cardiovascular en México: Resultados finales de la 391 Castro-Sansores CJ y col. Sensibilidad a la insulina e hipertrigliceridemia Encuesta Nacional de Salud (ENSA) 2000. Arch Cardiol Mex 2003;73:62-77.

  2. Secretaría de Salud. http://sinais.salud.gob.mx/

  3. World Health Organization. Diabetes Programme. http:// www.who.int/diabetes/en/

  4. Lara A, Rosas M, Pastelón G, Aguilar C y col. Hipercolesterolemia e hipertensión arterial en México. Consolidación urbana actual con obesidad, diabetes y tabaquismo. Arch Cardiol Mex 2004;74:231-245.

  5. Munguía-Miranda C, Sánchez-Barrera RG, Hernández- Saavedra D, Cruz-López M. Dyslipidemia prevalence and its relationship with insulin resistance on a population of apparently healthy subjects. Salud Pública Méx 2008;50:375-382.

  6. Meaney E, Lara-Esqueda A, Ceballos-Reyes GM, Asbun J, et al. Cardiovascular risk factors in the urban Mexican population: the FRIMEX study. Public Health 2007;121:378-384.

  7. Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. J Clin Invest 1995;95:158-166.

  8. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-1053.

  9. Laakso M, Lehto S. Epidemiology of risk factors for cardiovascular disease in diabetes and impaired glucose tolerance. Atherosclerosis 1998;137:S65-S73.

  10. Boden G. Effects of free fatty acids (FFA) on glucose metabolism: significance for insulin resistance and type 2 diabetes. Exp Clin Endocrinol Diabetes 2003;111:121-124.

  11. Boden G, Laakso M. Lipids and glucose in type 2 diabetes: what is the cause and effect? Diabetes Care 2004;27:2253- 2259.

  12. 12.- Wilding JPH. The importance of free acids in the development of type 2 diabetes. Diabet Med 2007;24:934-945.

  13. Paolisso G, Tataranni PA, Foley JE, Bogardus C, et al. A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia 1995;38:1213-1217.

  14. Pankow JS, Duncan BB, Schmidt MI, Ballantyne CM, et al. Fasting plasma free fatty acids and risk of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes Care 2004;27:77-82.

  15. Sako Y, Grill VE. A 48-hour lipid infusion in the rat timedependently inhibits glucose-induced insulin secretion and B cell oxidation through a process likely coupled to fatty acid oxidation. Endocrinology 1990;127:1580-1589.

  16. Elks ML. Chronic perifusion of rat islets with palmitate suppresses glucose-stimulated insulin release. Endocrinology 1993;133:208-214.

  17. Zhou YP, Grill VE. Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle. J Clin Invest 1994;93:870-876.

  18. Gremlich S, Bonny C, Waeber G, Thorens B. Fatty acids decrease IDX-1 expression in rat pancreatic islets and reduce GLUT2, glucokinase, insulin, and somatostatin levels. J Biol Chem 1997;272:30261-30269.

  19. Ritz-Laser B, Meda P, Constant I, Klages N, et al. Glucoseinduced preproinsulin gene expression is inhibited by the free fatty acid palmitate. Endocrinology 1999;140:4005- 4014.

  20. Shimabukuro M, Zhou YT, Levi M, Unger RH. Fatty acidinduced- cell apoptosis: a link between obesity and diabetes. Proc Natl Acad Sci USA 1998;95:2498-2502.

  21. Lupi R, Dotta F, Marselli L, Del Guerra S, et al. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes 2002;51:1437-1442.

  22. Boden G, Chen X, Iqbal N. Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetic and nondiabetic subjects. Diabetes 1998;47:1609-1612.

  23. Dobbins RL, Chester MW, Daniels MB, McGarry JD, Stein DT. Circulating fatty acids are essential for efficient glucosestimulated insulin secretion after prolonged fasting in humans. Diabetes 1998;47:1613-1618.

  24. Kashyap S, Belfort R, Gastaldelli A, Pratipanawatr T, et al. A sustained increase in plasma free fatty acids impairs insulin secretion in non-diabetic subjects genetically predisposed to develop type 2 diabetes. Diabetes 2003;52:2461-2474.

  25. Al-Mahmood K, Ismail AA, Rashid FA, Wan Mohamed WB. Isolated hypertriglyceridemia: an insulin-resistant state with or without low HDL cholesterol. J Atheroscler Thromb 2006;13:143-148.

  26. Summer AE, Finley KB, Genovese DJ, Criqui MH, Boston RC. Fasting triglyceride and the triglyceride-HDL ratio are not markers of insulin resistance in African Americans. Arch Intern Med 2005;165:1395-1400.

  27. Aguilar-Salinas CA, Rojas R, Gómez-Pérez FJ, Valles V y col. Características de los casos con dislipidemias mixtas en un estudio de población: resultados de la Encuesta Nacional de Enfermedades Crónicas. Salud Pública Méx 2002;44:546-553.

  28. Aguilar-Salinas CA, Olaiz G, Valles V, Ríos Torres JM, et al. High prevalence of low HDL cholesterol concentrations and mixed hyperlipidemia in a Mexican nationwide survey. J Lipid Res 2001;42:1298-1307.

  29. Bloomgarden ZT. Measures of insulin sensitivity. Clin Lab Med 2006;26:611-633.

  30. HOMA Calculator. The Oxford Centre for Diabetes, Endocrinology and Metabolism. http://www.dtu.ox.ac.uk/index. php?maindoc=/homa/

  31. Aguilar-Salinas C, Gómez-Pérez FJ, Rull J, Villalpando S, et al. Prevalence of dyslipidemias in the Mexican National Health and Nutrition Survey 2006. Salud Pública Méx 2010;52:S44-S53. 392 Medicina Interna de México Volumen 30, Núm. 4, julio-agosto, 2014

  32. Karhapää P, Malkki M, Laasko M. Isolated low HDL cholesterol: An insulin-resistant state. Diabetes 1994;43:411-417.

  33. Bonora E, Kieschl S, Willeit J, Oberhollenzer F, et al. Prevalence of insulin resistance in metabolic disorders: The Bruneck study. Diabetes 1998;47:1643-1649.

  34. Tai ES, Emmanuel SC, Chew SK, Tan BY, Tan CE. Isolated low HDL cholesterol: an insulin-resistant state only in the presence of fasting hypertrigliceridemia. Diabetes 1999;48:1088-1092.

  35. González-Chávez A, Simental-Mendía LE, Elizondo-Argueta S. Elevated triglycerides/HDL-cholesterol ratio associated with insulin resistance. Cir Cir 2011;79:126-131.

  36. Sum CF, Wang KW, Tan CE, Fok KC, et al. Hyperinsulinemia in non-obese subjects with hypertriglyceridemia: a preliminary report. Ann Acad Med Singapore 1992;21:10-13.

  37. Moro E, Gallina P, Pais M, Cazzolato G, et al. Hypertriglyceridemia is associated with increased insulin resistance in subjects with normal glucose tolerance: evaluation in a large cohort of subjects assessed with the 1999 World Health Organization criteria for the classification of diabetes. Metabolism 2003;52:616-619.

  38. Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G. Interaction between free fatty acids and insulin in the acute control of very low-density lipoprotein production in humans. J Clin Invest 1995;95:158-166.

  39. Olofsson SO, Andersson L, Haversen L, Olsson C, et al. The formation of lipid droplets: possible role in the development of insulin resistance/type 2 diabetes. Prostaglandins Leukot Essent Fatty Acids 2011;85:215-218.

  40. Pan DA, Lillioja S, Kriketos AD, et al. Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 1997;46:983-988.

  41. Weisberg SP, McCann D, Desai M, Rosenbaum M, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796-1808.

  42. Nguyen MT, Favelyukis S, Nguyen AK, Reichart D, et al. A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Tolllike receptors 2 and 4 and JNK-dependent pathways. J Biol Chem 2007;282:35279-35292.

  43. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 2010;72:219-246.

  44. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 1995;95:2409-2415.

  45. Hotamisligil GS, Spiegelman BM. Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes 1994;43:1271-1278.

  46. Córdova-Villalobos JA, Barriguete-Meléndez JA, Lara- Esqueda A, Barquera S, et al. Chronic noncommunicable diseases in Mexico: epidemiologic synopsis and integral prevention. Salud Pública Méx 2008;50:419-427.




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