Online ISSN: 2149-3189
2015
Monthly
Nicaea Medical Publishing
Türkiye

Atherogenic Burden and Insulin Resistance in Non-Obese Women with Polycystic Ovary Syndrome: A Comparative Study with Healthy Controls

Burak Andaç, Mehtap Navdar Başaran, Gözde Nur Eren
DOI
https://doi.org/10.18621/eurj.1815977
Abstract
Objectives: Polycystic ovary syndrome (PCOS) is associated with elevated cardiovascular disease (CVD) risk due to metabolic derangements. Although obesity contributes to CVD, the independent contribution of PCOS remains controversial. This study aimed to compare insulin resistance (IR) and atherogenic lipid indices across body mass index (BMI) categories within PCOS, to evaluate the diagnostic performance of atherogenic indices between non-obese PCOS and healthy controls, and to derive exploratory, data-driven thresholds that may inform cardiovascular risk assessment in non-obese PCOS.
Methods: This single-center case-control study enrolled 65 treatment-naïve women newly diagnosed with PCOS (Rotterdam criteria 2003) and 100 age-matched healthy controls. A panel of IR and composite atherogenic lipid indices (e.g., Lipid Accumulation Product [LAP], Visceral Adiposity Index [VAI], Triglyceride-Glucose [TyG] Index) was compared between groups.
Results: Within PCOS, atherogenic lipid indices were similar in obese versus non-obese subgroups. Non-obese PCOS demonstrated significantly higher atherogenic lipid and IR indices compared to controls (all P<0.05). Receiver operating characteristic (ROC) curve analysis identified LAP (Area under the curve [AUC] =0.747, 95% confidence intervals [CI]: 0.647-0.844, threshold=18.05), VAI (AUC=0.707, 95% CI: 0.605-0.811, threshold=1.15), and TyG (AUC=0.701, 95% CI: 0.583-0.814, threshold=8.29) as the three best indices distinguishing non-obese PCOS from healthy controls.
Conclusions: Elevated atherogenic lipid and IR indices in non-obese PCOS compared to non-obese controls, alongside similar atherogenic markers between obese and non-obese PCOS groups are consistent with the notion that PCOS may independently contribute to atherogenesis beyond obesity-related mechanisms. In this exploratory analysis, data-driven thresholds for LAP, VAI and TyG were identified in non-obese PCOS. These values require external validation in larger, multi-center cohorts before they can be considered for routine CVD risk screening or monitoring.
Keywords
Polycystic Ovary Syndrome, Lipid Accumulation Product, Triglyceride-Glucose Index, Visceral Adiposity Index
References

1. Helvaci N, Yildiz BO. Polycystic ovary syndrome as a metabolic disease. Nat Rev Endocrinol. 2025;21(4):230-244. doi: 10.1038/s41574-024-01057-w.

2. Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod. 2016;31(12):2841-2855. doi: 10.1093/humrep/dew218.

3. Barbieri RL, Ehrmann DA. Clinical manifestations of polycystic ovary syndrome in adults. In: Harris MB, editor. UpToDate. Waltham, MA: UpToDate; Updated Aug 27, 2025. Accessed Oct 25, 2025. Available from: https://www.uptodate.com/contents/clinical-manifestations-of-polycystic-ovary-syndrome-in-adults

4. de Groot PC, Dekkers OM, Romijn JA, Dieben SW, Helmerhorst FM. PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis. Hum Reprod Update. 2011;17(4):495-500. doi: 10.1093/humupd/dmr001.

5. Wild RA. Polycystic ovary syndrome: a risk for coronary artery disease? Am J Obstet Gynecol. 2002;186(1):35-43. doi: 10.1067/mob.2002.119180.

6. Elci E, Kaya C, Cim N, Yildizhan R, Elci GG. Evaluation of cardiac risk marker levels in obese and non-obese patients with polycystic ovaries. Gynecol Endocrinol. 2017;33(1):43-47. doi: 10.1080/09513590.2016.1203893.

7. Choi YS, Yang HI, Cho S, et al. Serum asymmetric dimethylarginine, apelin, and tumor necrosis factor-α levels in non-obese women with polycystic ovary syndrome. Steroids. 2012;77(13):1352-1358. doi: 10.1016/j.steroids.2012.08.005.

8. Jabbour R, Ott J, Eppel W, Frigo P. Carotid intima-media thickness in polycystic ovary syndrome and its association with hormone and lipid profiles. PLoS One. 2020;15(4):e0232299. doi: 10.1371/journal.pone.0232299.

9. Lopez-Jaramillo P, Gomez-Arbelaez D, Martinez-Bello D, et al. Association of the triglyceride glucose index as a measure of insulin resistance with mortality and cardiovascular disease in populations from five continents (PURE study): a prospective cohort study. Lancet Healthy Longev. 2023;4(1):e23-e33. doi: 10.1016/S2666-7568(22)00247-1.

10. Darroudi S, Soflaee SS, Hosseini ZS, et al. The visceral adiposity index and lipid accumulation product as predictors of cardiovascular events in normal weight subjects. Clin Nutr ESPEN. 2022;52:190-197. doi: 10.1016/j.clnesp.2022.10.015.

11. Duan M, Zhao X, Li S, etbal. Metabolic score for insulin resistance (METS-IR) predicts all-cause and cardiovascular mortality in the general population: evidence from NHANES 2001-2018. Cardiovasc Diabetol. 2024;23(1):243. doi: 10.1186/s12933-024-02334-8.

12. Uysal E, Tammo O, Soylemez E, Incebıyık M, Filiz D, Alci M. Significance of measuring anthropometric and atherogenic indices in patients with polycystic ovary syndrome. BMC Endocr Disord. 2024;24(1):160. doi: 10.1186/s12902-024-01701-6.

13. van der Ham K, Louwers YV, Laven JSE. Cardiometabolic biomarkers in women with polycystic ovary syndrome. Fertil Steril. 2022;117(5):887-896. doi: 10.1016/j.fertnstert.2022.03.008.

14. Brończyk-Puzoń A, Jagielski P, Kulik-Kupka K, Koszowska A, Nowak J, Zubelewicz-Szkodzińska B. Usefulness of a new anthropometric indicator - VAI (Visceral Adiposity Index) in the evaluation of metabolic and hormonal disorders in women with polycystic ovary syndrome. Adv Clin Exp Med. 2017;26(5):825-828. doi: 10.17219/acem/61100.

15. Kałużna M, Czlapka-Matyasik M, Kompf P, et al. Lipid ratios and obesity indices are effective predictors of metabolic syndrome in women with polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2022;13:20420188211066699. doi: 10.1177/20420188211066699.

16. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004.

17. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-419. doi: 10.1007/BF00280883.

18. Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85(7):2402-2410. doi: 10.1210/jcem.85.7.6661.

19. Castelli WP, Abbott RD, McNamara PM. Summary estimates of cholesterol used to predict coronary heart disease. Circulation. 1983;67(4):730-734. doi: 10.1161/01.cir.67.4.730.

20. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. 2012;33(6):981-1030. doi: 10.1210/er.2011-1034.

21. Paradisi G, Steinberg HO, Hempfling A, et al. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation. 2001;103(10):1410-1415. doi: 10.1161/01.cir.103.10.1410.

22. Gomez JMD, VanHise K, Stachenfeld N, Chan JL, Merz NB, Shufelt C. Subclinical cardiovascular disease and polycystic ovary syndrome. Fertil Steril. 2022;117(5):912-923. doi: 10.1016/j.fertnstert.2022.02.028.

23. Usselman CW, Yarovinsky TO, Steele FE, et al. Androgens drive microvascular endothelial dysfunction in women with polycystic ovary syndrome: role of the endothelin B receptor. J Physiol. 2019;597(11):2853-2865. doi: 10.1113/JP277756.

24. Anagnostis P, Paparodis RD, Bosdou JK, et al. Risk of type 2 diabetes mellitus in polycystic ovary syndrome is associated with obesity: a meta-analysis of observational studies. Endocrine. 2021;74(2):245-253. doi: 10.1007/s12020-021-02801-2.

25. Phelan N, O'Connor A, Kyaw-Tun T, et al. Lipoprotein subclass patterns in women with polycystic ovary syndrome (PCOS) compared with equally insulin-resistant women without PCOS. J Clin Endocrinol Metab. 2010;95(8):3933-3939. doi: 10.1210/jc.2009-2444.

26. Rudnicka E, Suchta K, Grymowicz M, et al. Chronic Low Grade Inflammation in Pathogenesis of PCOS. Int J Mol Sci. 2021;22(7):3789. doi: 10.3390/ijms22073789.

27. Kyrou I, Panagiotakos DB, Kouli GM, et al. Lipid accumulation product in relation to 10-year cardiovascular disease incidence in Caucasian adults: The ATTICA study. Atherosclerosis. 2018;279:10-16. doi: 10.1016/j.atherosclerosis.2018.10.015.

28. Hosseinpanah F, Barzin M, Mirbolouk M, Abtahi H, Cheraghi L, Azizi F. Lipid accumulation product and incident cardiovascular events in a normal weight population: Tehran Lipid and Glucose Study. Eur J Prev Cardiol. 2016;23(2):187-193. doi: 10.1177/2047487314558771.

29. Ioachimescu AG, Brennan DM, Hoar BM, Hoogwerf BJ. The lipid accumulation product and all-cause mortality in patients at high cardiovascular risk: a PreCIS database study. Obesity (Silver Spring). 2010;18(9):1836-1844. doi: 10.1038/oby.2009.453.

30. Wehr E, Gruber HJ, Giuliani A, Möller R, Pieber TR, Obermayer-Pietsch B. The lipid accumulation product is associated with impaired glucose tolerance in PCOS women. J Clin Endocrinol Metab. 2011;96(6):E986-990. doi: 10.1210/jc.2011-0031.

31. Wiltgen D, Spritzer PM. Variation in metabolic and cardiovascular risk in women with different polycystic ovary syndrome phenotypes. Fertil Steril. 2010;94(6):2493-2496. doi: 10.1016/j.fertnstert.2010.02.015.

32. Macut D, Tziomalos K, Božić-Antić I, et al. Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome. Hum Reprod. 2016;31(6):1347-1353. doi: 10.1093/humrep/dew076.

33. Yuan Y, Hu X, Jin J, et al. Transition of visceral adiposity index and risk of cardiovascular disease in middle-aged and older Chinese adults. Arch Gerontol Geriatr. 2024;121:105356. doi: 10.1016/j.archger.2024.105356.

34. Lazzer S, D'Alleva M, Isola M, et al. Cardiometabolic Index (CMI) and Visceral Adiposity Index (VAI) Highlight a Higher Risk of Metabolic Syndrome in Women with Severe Obesity. J Clin Med. 2023;12(9):3055. doi: 10.3390/jcm12093055.

35. Xu C, Guo Y, Zhang S, et al. Visceral adiposity index and the risk of heart failure, late-life cardiac structure, and function in ARIC study. Eur J Prev Cardiol. 2023;30(12):1182-1192. doi: 10.1093/eurjpc/zwad099.

36. 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(6):1486-1494. doi: 10.1093/humrep/der088.

37. Liu X, Tan Z, Huang Y, et al. Relationship between the triglyceride-glucose index and risk of cardiovascular diseases and mortality in the general population: a systematic review and meta-analysis. Cardiovasc Diabetol. 2022;21(1):124. doi: 10.1186/s12933-022-01546-0.

There are 37 references in total.
How to Cite
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Andaç B, Navdar Başaran M, Eren GN. Atherogenic Burden and Insulin Resistance in Non-Obese Women with Polycystic Ovary Syndrome: A Comparative Study with Healthy Controls. Eur Res J. Published online March 14, 2026:1-13. doi:10.18621/eurj.1815977
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  • Article Type Research Article
  • Submitted February 21, 2026
  • Published March 14, 2026
  • Issue 2026: Online First
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