Lipid Accumulation Product (LAP) and Visceral Adiposity Index (VAI) as Markers of Insulin Resistance and Metabolic Associated Disturbances in Young Argentine Women with Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS) is an endocrine disorder. PCOS women are at high risk of developing insulin resistance (IR) and cardiovascular disorders since young age. We aimed to study the reliability of lipid accumulation product (LAP) and visceral adiposity index (VAI) as markers of metabolic disturbances (MD) associated with IR in young reproductive aged PCOS patients. We also evaluated the association between LAP and VAI and the presence of hyperandrogenism. In a cross-sectional study, 110 PCOS patients and 88 control women (18–35 years old) were recruited. PCOS patients were divided into 2 groups, as hyperandrogenic and non-hyperandrogenic considering the signs of hyperandrogenism (clinical or biochemical). Anthropometric measurements were taken and blood samples collected. Metabolic and anthropometric characteristics and their association with IR and associated MD were evaluated and LAP and VAI were calculated. LAP and VAI were compared with TC/HDL-c and TG/HDL-c to define the best markers of MD in this population. Independently of the phenotype, young PCOS patients showed high IR and dyslipidemia. Both LAP and VAI showed to be more effective markers to assess MD and IR in these young women than TG/HDL-c or TC/HDL-c [cut-off values: LAP: 18.24 (sensitivity: 81.43% specificity: 73.49%), positive predictive value (PPV): 75.0%, negative predictive value (NPV): 77.27%, VAI: 2.19 (sensitivity: 81.16% specificity: 72.15% PPV: 74.65% NPV: 72.22%)]. LAP and VAI are representative markers to assess MD associated with IR in young PCOS patients. All PCOS patients, independently of their androgenic condition, showed high metabolic risk.

Key words

hyperandrogenism - polycystic ovary syndrome - insulin resistance - cardiovascular risk - metabolic syndrome

• References

• 1 Guastella E, Longo RA, Carmina E. Clinical and endocrine characteristics of the main polycystic ovary syndrome phenotypes. Fertil Steril 2010; 94: 2197-2201
• 2 Rotterdam EA-SPcwg. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19: 41-47
• 3 Apridonidze T, Essah PA, Iuorno MJ, Nestler JE. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90: 1929-1935
• 4 Cussons AJ, Watts GF, Burke V, Shaw JE, Zimmet PZ, Stuckey BG. Cardiometabolic risk in polycystic ovary syndrome: a comparison of different approaches to defining the metabolic syndrome. Hum Reprod 2008; 23: 2352-2358
• 5 Amsterdam EA-SrPCWG. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS). Hum Reprod 2012; 27: 14-24
• 6 Du T, Yuan G, Zhang M, Zhou X, Sun X, Yu X. Clinical usefulness of lipid ratios, visceral adiposity indicators, and the triglycerides and glucose index as risk markers of insulin resistance. Cardiovasc Diabetol 2014; 13: 146
• 7 Wiltgen D, Benedetto IG, Mastella LS, Spritzer PM. Lipid accumulation product index: a reliable marker of cardiovascular risk in polycystic ovary syndrome. Hum Reprod 2009; 24: 1726-1731
• 8 Panidis D, Tziomalos K, Misichronis G, Papadakis E, Betsas G, Katsikis I, Macut D. Insulin resistance and endocrine characteristics of the different phenotypes of polycystic ovary syndrome: a prospective study. Hum Reprod 2012; 27: 541-549
• 9 Rubinstein AL, Irazola VE, Calandrelli M, Elorriaga N, Gutierrez L, Lanas F, Manfredi JA, Mores N, Olivera H, Poggio R, Ponzo J, Seron P, Chen CS, Bazzano LA, He J. Multiple cardiometabolic risk factors in the Southern Cone of Latin America: a population-based study in Argentina, Chile, and Uruguay. Int J Cardiol 2015; 183: 82-88
• 10 Albayrak S, Ozhan H, Aslantas Y, Ekinozu I, Tibilli H, Kayapinar O, Melen Study I. Predictors of major adverse cardiovascular events; results of population based MELEN study with prospective follow-up. Eur Rev Med Pharmacol Sci 2015; 19: 1446-1451
• 11 DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214-E223
• 12 Kahn HS. The “lipid accumulation product” performs better than the body mass index for recognizing cardiovascular risk: a population-based comparison. BMC Cardiovasc Disord 2005; 5: 26
• 13 Amato MC, Giordano C, Pitrone M, Galluzzo A. Cut-off points of the visceral adiposity index (VAI) identifying a visceral adipose dysfunction associated with cardiometabolic risk in a Caucasian Sicilian population. Lipids Health Dis 2011; 10: 183
• 14 Amato MC, Giordano C, Galia M, Criscimanna A, Vitabile S, Midiri M, Galluzzo A, AlkaMeSy Study G. Visceral Adiposity Index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care 2010; 33: 920-922
• 15 Hosseinpanah F, Barzin M, Erfani H, Serahati S, Ramezani Tehrani F, Azizi F. Lipid accumulation product and insulin resistance in Iranian PCOS prevalence study. Clin Endocrinol (Oxf) 2014; 81: 52-57
• 16 Oh JY, Sung YA, Lee HJ. The visceral adiposity index as a predictor of insulin resistance in young women with polycystic ovary syndrome. Obesity 2013; 21: 1690-1694
• 17 Nascimento JX, Chein MB, de Sousa RM, Ferreira Ados S, Navarro PA, Brito LM. Importance of lipid accumulation product index as a marker of CVD risk in PCOS women. Lipids Health Dis 2015; 14: 62
• 18 Neeland IJ, Turer AT, Ayers CR, Powell-Wiley TM, Vega GL, Farzaneh-Far R, Grundy SM, Khera A, McGuire DK, de Lemos JA. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA 2012; 308: 1150-1159
• 19 Hajer GR, van Haeften TW, Visseren FL. Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 2008; 29: 2959-2971
• 20 Millan J, Pinto X, Munoz A, Zuniga M, Rubies-Prat J, Pallardo LF, Masana L, Mangas A, Hernandez-Mijares A, Gonzalez-Santos P, Ascaso JF, Pedro-Botet J. Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention. Vascular health and risk management 2009; 5: 757-765
• 21 McLaughlin T, Reaven G, Abbasi F, Lamendola C, Saad M, Waters D, Simon J, Krauss RM. Is there a simple way to identify insulin-resistant individuals at increased risk of cardiovascular disease?. Am J Cardiol 2005; 96: 399-404
• 22 Escobar-Morreale HF, Carmina E, Dewailly D, Gambineri A, Kelestimur F, Moghetti P, Pugeat M, Qiao J, Wijeyaratne CN, Witchel SF, Norman RJ. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update 2012; 18: 146-170
• 23 Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, Monauni T, Muggeo M. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 2000; 23: 57-63
• 24 Lepor NE, Vogel RE. National Cholesterol Education Program Adult Treatment P, III. Summary of the third report of the National Cholesterol Education Program Adult Treatment Panel III. Rev Cardiovasc Med 2001; 2: 160-165
• 25 Graffigna MN, Litwak L, Abdala MM, Akel Aranda C, Gutt S, Ledesma L, Levalle O, Toro JM, Migliano M, MPdl Puente, Pombo F, Rodriguez M, Scatlier H, Tarruella M, Yuma M, Cavallero E. Homa index in healthy subjects. Determinación del índice homa en sujetos presuntamente sanos. Estudio epidemiológico multicéntrico (resultados preliminares). Rev Argent Endocrinol Metab 2005; 42: 12-19
• 26 Di Rienzo JA, Casanoves F, Balzarini MG, Gonzalez L, Tablada M, Robledo CW. InfoStat Version. 2011
• 27 Siniawski D, Massonm W, Sorroche P, Casañas L, Krauss J, Cagide A. Correlation between Apolipoprotein B-to-Apolipoprotein A1 Ratio and Total-to-HDL-Cholesterol Ratio in a Healthy Population: Should Castelli Index be Updated?. Rev Argent Cardiol 2011; 79: 33-38
• 28 Salazar MR, Carbajal HA, Espeche WG, Leiva Sisnieguez CE, Balbin E, Dulbecco CA, Aizpurua M, Marillet AG, Reaven GM. Relation among the plasma triglyceride/high-density lipoprotein cholesterol concentration ratio, insulin resistance, and associated cardio-metabolic risk factors in men and women. Am J Cardiol 2012; 109: 1749-1753
• 29 Jousilahti P, Vartiainen E, Tuomilehto J, Puska P. Sex age, cardiovascular risk factors, and coronary heart disease: a prospective follow-up study of 14 786 middle-aged men and women in Finland. Circulation 1999; 99: 1165-1172
• 30 Echiburu B, Crisosto N, Maliqueo M, Perez-Bravo F, de Guevara AL, Hernandez P, Cavada G, Rivas C, Clavel A, Sir-Petermann T. Metabolic profile in women with polycystic ovary syndrome across adult life. Metabolism 2016; 65: 776-782
• 31 Ladron de Guevara A, Fux-Otta C, Crisosto N, Szafryk de Mereshian P, Echiburu B, Iraci G, Perez-Bravo F, Sir-Petermann T. Metabolic profile of the different phenotypes of polycystic ovary syndrome in two Latin American populations. Fertil Steril 2014; 101: 1732-1739 and 1731–1732
• 32 Wild RA, Carmina E, Diamanti-Kandarakis E, Dokras A, Escobar-Morreale HF, Futterweit W, Lobo R, Norman RJ, Talbott E, Dumesic DA. Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab 2010; 95: 2038-2049
• 33 Motta AB. The role of obesity in the development of polycystic ovary syndrome. Curr Pharm Des 2012; 18: 2482-2491
• 34 Zhao Y, Qiao J. Ethnic differences in the phenotypic expression of polycystic ovary syndrome. Steroids 2013; 78: 755-760
• 35 Catelli ML, Alvarez-Iglesias V, Gomez-Carballa A, Mosquera-Miguel A, Romanini C, Borosky A, Amigo J, Carracedo A, Vullo C, Salas A. The impact of modern migrations on present-day multi-ethnic Argentina as recorded on the mitochondrial DNA genome. BMC Genet 2011; 12: 77
• 36 Avena S, Via M, Ziv E, Perez-Stable EJ, Gignoux CR, Dejean C, Huntsman S, Torres-Mejia G, Dutil J, Matta JL, Beckman K, Burchard EG, Parolin ML, Goicoechea A, Acreche N, Boquet M, Rios Part Mdel C, Fernandez V, Rey J, Stern MC, Carnese RF, Fejerman L. Heterogeneity in genetic admixture across different regions of Argentina. PLoS One 2012; 7: e34695
• 37 Amato MC, Verghi M, Galluzzo A, Giordano C. The oligomenorrhoic phenotypes of polycystic ovary syndrome are characterized by a high visceral adiposity index: a likely condition of cardiometabolic risk. Hum Reprod 2011; 26: 1486-1494