Citation Information :
Garg M, Jain A. Association of Cardiometabolic Index and Insulin Resistance with Serum Levels of Peroxisome Proliferator Activated Receptor-γ in Polycystic Ovary Syndrome. Indian J Med Biochem 2020; 24 (2):50-54.
Introduction: Polycystic ovary syndrome or PCOS is also called “Stein-Leventhal Syndrome”. It comprises of many endocrinal disturbances of female reproductive system and manifested variably to be called as a “Syndrome.” Insulin resistance is seen in 30–40% women with PCOS and is accompanied with hyperinsulinemia in about 50–70% of women. Cardiometabolic index (CMI) is a new marker for coronary artery disease and metabolic syndrome. The relationship of CMI and insulin resistance is further explored in the present study using peroxisome proliferator activated receptor-γ (PPAR-γ) serum levels. PPAR-γ or glitazone receptors are involved in improving insulin sensitization, mainly through adipocyte differentiation. Aims and objectives: To study whether there is any association of CMI and insulin resistance with PPAR-γ serum levels. Materials and methods: A hospital-based observational case–control study was conducted in 50 diagnosed cases of PCOS (15–45 years of age) as per revised Rotterdam Criteria along with 50 age-matched apparently healthy women volunteers as controls. Fasting blood samples on D2/D3 were taken to obtain serum for analysis of biochemical and glycemic parameters, including lipid profile and HOMA-IR. PPAR-γ levels were estimated using sandwich enzyme-linked immunosorbent assay. Statistical analysis using SPSS ver. 23 employing independent sample t test for intergroup comparison of means and Pearson\'s correlation coefficient for correlation analysis was done. Results and conclusion: Serum triglyceride levels were found to be significantly higher in cases (121.08 ± 57.6 mg/dL) when compared to controls (97.6 ± 44.2 mg/dL), suggesting that dyslipidemia is associated with PCOS, with hypertriglyceridemia being an important component of it. This study showed significantly lower levels of PPAR-γ in the cases when compared to controls (p value < 0.05). HOMA-IR showed a significant positive correlation with serum TG. CMI also depicted significant and positive correlations with hypertriglyceridemia, HOMA-IR, and PPAR-γ.
Stein IF. Amenorrhoea associated with bilateral polycystic ovaries. Am J Obstet Gynaecol 1935;29(2):181. DOI: 10.1016/S0002-9378(15) 30642-6.
Hayek SE, Bitar L, Hamdar LH, et al. Polycystic ovarian syndrome: an updated overview. Front Physiol 2016;7:1–15. DOI: 10.3389/fphys.2016.00124.
Ramanand SJ, Ghongane BB, Ramanand JB, et al. Clinical characteristics of polycystic ovary syndrome in Indian women. Indian J Endocrinol Metab 2013;17(1):138–145. DOI: 10.4103/2230-8210.107858.
Mohammad MB, Seghinsara AM. Polycystic ovary syndrome (PCOS), diagnostic criteria, and AMH. Asian Pac J Cancer Prev 2017;18(1):17–21.
Shaikh N, Mukherjee A, Shah N, et al. Peroxisome proliferator activated receptor gamma gene variants influence susceptibility and insulin related traits in Indian women with polycystic ovary syndrome. J Assist Reprod Genet 2013;30(7):913–921. DOI: 10.1007/s10815-013-0025-y.
Geller DH, Pacaud D, Gordon CM, et al. State of the art review: Emerging therapies: The use of insulin sensitizers in the treatment of adolescents with PCOS. Int J Pediatr Endocrinol 2011;2011(1):9. DOI: 10.1186/1687-9856-2011-9.
Wehr E, Trummer O, Giuliani A, et al. Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol 2011;164(5):741–749. DOI: 10.1530/EJE-11-0134.
Mukherjee S, Maitra A. Molecular and genetic factors contributing insulin resistance in polycystic ovary syndrome. Indian J Med Res 2010;131:743–776.
Gorniak BG. Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications–a review. Nutr J 2014;13(1):17. DOI: 10.1186/1475-2891-13-17.
Lalloyer F, Staels B. Fibrates, glitazones, and peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol 2010;30(5): 894–899. DOI: 10.1161/ATVBAHA.108.179689.
Xu HE, Lambert MH, Montana VG, et al. Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A 2001;98(24):13919–13924. DOI: 10.1073/pnas.241410198.
Minge CE, Robker RL, Norman RJ. PPAR Gamma: Coordinating metabolic and immune contributions to female fertility. PPAR Res 2008;2008:243791. DOI: 10.1155/2008/243791.
Tenenbaum A, Fisman EZ, Motro M. Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR). Cardiovasc Diabetol 2003;2(1):4. DOI: 10.1186/1475-2840-2-4.
Abbott BD, Wood CR, Watkins AM, et al. Peroxisome proliferator-activated receptors alpha, beta, and gamma mRNA and protein expression in human fetal tissues. PPAR Res 2010. 2010. DOI: 10.1155/2010/690907.
Molavi B, Rassouli N, Bagwe S, et al. A review of thiazolidinediones and metformin in the treatment of type 2 diabetes with focus on cardiovascular complications. Vasc Health Risk Manag 2007;3(6): 967–973.
Kintscher U, Law RE. PPARγ-mediated insulin sensitization: the importance of fat versus muscle. Am J Physiol Endocrinol Metab 2005;288(2):E287–E291. DOI: 10.1152/ajpendo.00440.2004.
Shi WR, Wang HY, Chen S, et al. Estimate of prevalent diabetes from cardiometabolic index in general Chinese population: a community-based study. Lipids Health Dis 2018;17(236):1–9. DOI: 10.1186/s12944-018-0886-2.
Day C. Thiazolidinediones: a new class of antidiabetic drugs. Diabet Med 1999;16(3):179–192. DOI: 10.1046/j.1464-5491.1999.00023.x.
Ravikumar B, Gerrard J, Dalla Man C, et al. Pioglitazone decreases fasting and postprandial endogenous glucose production in proportion to decrease in hepatic triglyceride content. Diabetes 2008;57(9):2288–2295. DOI: 10.2337/db07-1828.
Staels B, Dallongeville J, Auwerx J, et al. Mechanism of action of fibrates on lipid & lipoprotein metabolism. Circulation 1998;98(19):2088–2093. DOI: 10.1161/01.CIR.98.19.2088.
Quinn CE, Hamilton PK, Lockhart CJ, et al. Thiazolidinediones: Effects on insulin resistance and the cardiovascular system. Br J Pharmacol 2008;153(4):636–645. DOI: 10.1038/sj.bjp.0707452.
Papalou O, Livadas S, Karachalios A, et al. White blood cells levels and PCOS: direct and indirect relationship with obesity and insulin resistance, but not with hyperandogenemia. Hormones 2015;14(1): 91–100.
Bahcecı M, Aydemır M, Tuzcu A. Effects of oral fat and glucose tolerance test on serum lipid profile, apolipoprotein, and CRP concentration, and insulin resistance in patients with polycystic ovary syndrome. Fertil Steril 2007;87(6):1363–1368. DOI: 10.1016/j.fertnstert.2006.11.031.
Legro RS, Finegood D, Dunaif A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998;83(8):2694–2698. DOI: 10.1210/jc.83.8.2694.
Park SY, Cho YJ, Lee SR, et al. Triglyceride is a useful surrogate marker for insulin resistance in korean women with polycystic ovary syndrome. Yonsei Med J 2015;56(3):785–792. DOI: 10.3349/ymj.2015.56.3.785.
Tai ES, Corella D, Deurenberg-Yap M, et al. Differential effects of the C1431T and Pro12Ala PPARgamma gene variants on plasma lipids and diabetes risk in an asian population. J Lipid Res 2004;45(4):674–685. DOI: 10.1194/jlr.M300363-JLR200.
Jiang X, Ye X, Guo W, et al. Inhibition of HDAC3 promotes ligandindependent PPARγ activation by protein acetylation. J Mol Endocrinol 2014;53(2):191–200. DOI: 10.1530/JME-14-0066.
Semple RK, Chatterjee VK, O’Rahilly S. PPAR gamma and human metabolic disease. J Clin Invest 2006;116(3):581–589. DOI: 10.1172/JCI28003.
Wakabayashi I. A U-shaped relationship between alcohol consumption and cardiometabolic index in middle-aged men. Lipids Health Dis 2016;15(1):50. DOI: 10.1186/s12944-016-0217-4.
Studen KB, Pfeifer M. Cardiometabolic risk in polycystic ovary syndrome. Endocr Connect 2018;7(7):R238–R251. DOI: 10.1530/EC-18-0129.
Barber TM, Vojtechova P, Franks S. The impact of hyperandrogenism in female obesity and cardiometabolic diseases associated with polycystic ovary syndrome. Horm Mol Biol Clin Investig 2013;15(3): 91–103. DOI: 10.1515/hmbci-2013-0014.
Ehrmann DA, Liljenquist DR, Kasza K, et al. PCOS/troglitazone study group. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metabol 2006;91(1):48–53. DOI: 10.1210/jc.2005-1329.
Abbott DH, Dumesic DA, Franks S. Developmental origin of polycystic ovary syndrome – a hypothesis. J Endocrinol 2002;174(1):1–5. DOI: 10.1677/joe.0.1740001.
Elbers JMH, Asscheman H, Seidell JC, et al. Long-term testosterone administration increases visceral fat in female to male transsexuals. J Clin Endocrinol Metabol 1997;82(7):2044–2047. DOI: 10.1210/jc.82.7.2044.