Adiposity Indexes as Phenotype-Specific Markers of Preclinical Metabolic Alterations and Cardiovascular Risk in Polycystic Ovary Syndrome: A Cross-Sectional Study
Fernanda Missio Mario
1
Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, 90035-003
2
Federal Institute of Education, Science and Technology of Rio Grande do Sul, Porto Alegre, Brazil 90030-041
,
Scheila Karen Graff
1
Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, 90035-003
,
Poli Mara Spritzer
1
Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, 90035-003
3
Laboratory of Molecular Endocrinology, Department of Physiology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil, 90035-003
Polycystic ovary syndrome (PCOS) is a common condition in women of reproductive age. 2 PCOS phenotypes (classic and ovulatory) are currently recognized as the most prevalent, with important differences in terms of cardiometabolic features. We studied the performance of different adiposity indexes to predict preclinical metabolic alterations and cardiovascular risk in 234 women with PCOS (173 with classic and 61 with ovulatory PCOS) and 129 controls. Performance of waist circumference, waist-to-height ratio, conicity index, lipid accumulation product, and visceral adiposity index was assessed based on HOMA-IR ≥ 3.8 as reference standard for screening preclinical metabolic alterations and cardiovascular risk factors in each group. Lipid accumulation product had the best accuracy for classic PCOS, and visceral adiposity index had the best accuracy for ovulatory PCOS. By applying the cutoff point of lipid accumulation product<34, we identified a subgroup of patients without cardiometabolic alterations (P<0.05) in the group with classic PCOS, a population at higher risk for hypertension, dyslipidemia, and impaired glucose tolerance. In ovulatory PCOS, visceral adiposity index ≥ 1.32 was capable of detecting women with significantly higher blood pressure and less favorable glycemic and lipid variables as compared to ovulatory PCOS with lower visceral adiposity index (P<0.05). These results suggest LAP ≥ 34 as the best marker for classic PCOS, and VAI ≥ 1.32 for ovulatory PCOS women. Both indexes can be easily calculated with measures obtained in routine clinical practice and may be useful to detect cardiometabolic risk and secure early interventions.
References
1 Yildiz BO, Bozdag G, Yapici Z et al. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod 2012; 27: 3067-3073
2 March WA, Moore VM, Willson KJ et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 2010; 25: 544-551
4 Lim SS, Davies MJ, Norman RJ et al. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2012; 18: 618-637
5 Carmina E, Bucchieri S, Esposito A et al. Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab 2007; 92: 2500-2505
6 Toscani M, Migliavacca R, Sisson de Castro JA et al Estimation of truncal adiposity using waist circumference or the sum of trunk skinfolds: a pilot study for insulin resistance screening in hirsute patients with or without polycystic ovary syndrome. Metabolism 2007; 56: 992-997
7 Wiltgen D, Spritzer PM. Variation in metabolic and cardiovascular risk in women with different polycystic ovary syndrome phenotypes. Fertil Steril 2010; 94: 2493-2496
8 Wild RA, Rizzo M, Clifton S et al. Lipid levels in polycystic ovary syndrome: systematic review and meta-analysis. Fertil Steril 2011; 95: 1073-1079.e1071-1011
9 Moran LJ, Misso ML, Wild RA et al. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2010; 16: 347-363
11 Ehrmann DA, Liljenquist DR, Kasza K et al. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91: 48-53
12 Legro RS, Kunselman AR, Dodson WC et al. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999; 84: 165-169
13 Hudecova M, Holte J, Olovsson M et al. Diabetes and impaired glucose tolerance in patients with polycystic ovary syndrome--a long term follow-up. Hum Reprod 2011; 26: 1462-1468
14 Dunaif A, Segal KR, Futterweit W et al. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989; 38: 1165-1174
16 Diamanti-Kandarakis E, Dunaif A.. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 2012; 33: 981-1030
17 Diamanti-Kandarakis E. Spritzer PM. Sir-Petermann T et al. Insulin resistance and polycystic ovary syndrome through life. Curr Pharm Des 2012; 18: 5569-5576
18
Group REA-SPCW
. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19-25
19 Azziz R, Carmina E, Dewailly D et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009; 91: 456-488
20 Panidis D, Tziomalos K, Misichronis G et al. Insulin resistance and endocrine characteristics of the different phenotypes of polycystic ovary syndrome: a prospective study. Hum Reprod 2012; 27: 541-549
21 Daan NM, Louwers YV, Koster MP et al. Cardiovascular and metabolic profiles amongst different polycystic ovary syndrome phenotypes: who is really at risk?. Fertil Steril 2014; 102: 1444-1451.e1443
22 Legro RS, Arslanian SA, Ehrmann DA et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2013; 98: 4565-4592
25 Amato MC, Guarnotta V, Forti D et al. Metabolically healthy polycystic ovary syndrome (MH-PCOS) and metabolically unhealthy polycystic ovary syndrome (MU-PCOS): a comparative analysis of four simple methods useful for metabolic assessment. Hum Reprod 2013; 28: 1919-1928
27 Costa EC, Sá JC, Soares EM et al. Anthropometric indices of central obesity how discriminators of metabolic syndrome in Brazilian women with polycystic ovary syndrome. Gynecol Endocrinol 2012; 28: 12-15
28 Saghafi-Asl M, Pirouzpanah S, Ebrahimi-Mameghani M et al. Lipid profile in relation to anthropometric indices and insulin resistance in overweight women with polycystic ovary syndrome. Health Promot Perspect 2013; 3: 206-216
29 Wehr E, Gruber HJ, Giuliani A et al. The lipid accumulation product is associated with impaired glucose tolerance in PCOS women. J Clin Endocrinol Metab 2011; 96: E986-990
30 Nascimento JX, Chein MB. de Sousa RM et al. Importance of lipid accumulation product index as a marker of CVD risk in PCOS women. Lipids Health Dis 2015; 14: 62
31 Oh JY, Sung YA, Lee HJ.. The visceral adiposity index as a predictor of insulin resistance in young women with polycystic ovary syndrome. Obesity (Silver Spring) 2013; 21: 1690-1694
32 Amato MC, Verghi M, Galluzzo A et al. 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
34 Ramezani Tehrani F, Minooee S, Azizi F.. Comparison of various adiposity indexes in women with polycystic ovary syndrome and normo-ovulatory non-hirsute women: a population-based study. Eur J Endocrinol 2014; 171: 199-207
35 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
36 Amato MC, Giordano C, Galia M et al. Visceral Adiposity Index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care 2010; 33: 920-922
39 Jamil AS, Alalaf SK, Al-Tawil NG et al. A case-control observational study of insulin resistance and metabolic syndrome among the four phenotypes of polycystic ovary syndrome based on Rotterdam criteria. Reprod Health 2015; 12: 7
40 Alberti KG, Eckel RH, Grundy SM et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640-1645
41 Friedewald WT, Levy RI, Fredrickson DS.. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
43 Fischer JE, Bachmann LM, Jaeschke R.. A readers' guide to the interpretation of diagnostic test properties: clinical example of sepsis. Intensive Care Med 2003; 29: 1043-1051
46 Jayagopal V, Kilpatrick ES, Jennings PE et al. Biological variation of homeostasis model assessment-derived insulin resistance in type 2 diabetes. Diabetes Care 2002; 25: 2022-2025
47 Xiang S, Hua F, Chen L et al. Lipid accumulation product is related to metabolic syndrome in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 2013; 121: 115-118
48 Macut D, Božić Antić I, Bjekić-Macut J et al. Lipid accumulation product is associated with metabolic syndrome in women with polycystic ovary syndrome. Hormones (Athens) 2016; 15: 35–44
49 Pouliot MC, Després JP, Lemieux S et al. Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women. Am J Cardiol 1994; 73: 460-468
50 Cascella T, Palomba S, De Sio I et al. Visceral fat is associated with cardiovascular risk in women with polycystic ovary syndrome. Hum Reprod 2008; 23: 153-159
51 Gast KB, den Heijer M, Smit JW et al. Individual contributions of visceral fat and total body fat to subclinical atherosclerosis: The NEO study. Atherosclerosis 2015; 241: 547-554
52 Roriz AK, Passos LC, de Oliveira CC et al Evaluation of the accuracy of anthropometric clinical indicators of visceral fat in adults and elderly. PLoS One 2014; 9: e103499
53 Carmina E, Chu MC, Longo RA et al. Phenotypic variation in hyperandrogenic women influences the findings of abnormal metabolic and cardiovascular risk parameters. J Clin Endocrinol Metab 2005; 90: 2545-2549
54 Du T, Yu X, Zhang J et al. Lipid accumulation product and visceral adiposity index are effective markers for identifying the metabolically obese normal-weight phenotype. Acta Diabetol 2015; 52: 855-863
55 Amato MC, Magistro A, Gambino G et al. Visceral adiposity index and DHEAS are useful markers of diabetes risk in women with polycystic ovary syndrome. Eur J Endocrinol 2015; 172: 79-88
56 Carmina E, Bucchieri S, Mansueto P et al. Circulating levels of adipose products and differences in fat distribution in the ovulatory and anovulatory phenotypes of polycystic ovary syndrome. Fertil Steril 2009; 91: 1332-1335
57 DeFronzo RA, Tobin JD, Andres R.. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214-223
58 Bonora E, Targher G, Alberiche M et al. 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
59 Bonora E, Formentini G, Calcaterra F et al. HOMA-estimated insulin resistance is an independent predictor of cardiovascular disease in type 2 diabetic subjects: prospective data from the Verona Diabetes Complications Study. Diabetes Care 2002; 25: 1135-1141
60 Bonora E, Kiechl S, Willeit J et al. Insulin resistance as estimated by homeostasis model assessment predicts incident symptomatic cardiovascular disease in Caucasian subjects from the general population: the Bruneck study. Diabetes Care 2007; 30: 318-324
61 Hanley AJ, Williams K, Stern MP et al. Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study. Diabetes Care 2002; 25: 1177-1184
