Is there any difference in insulin resistance status between cases of benign and malignant ovarian neoplasms? A study on surrogate markers of insulin resistance in Indonesian non‑diabetic women

Winarto,Hariyono; Habiburrahman,Muhammad; Febriana,Irene Shinta; Kusuma,Fitriyadi; Nuryanto,Kartiwa Hadi; Anggraeni,Tricia Dewi; Utami,Tofan Widya; Putra,Andi Darma

doi:10.3892/ol.2022.13609

Is there any difference in insulin resistance status between cases of benign and malignant ovarian neoplasms? A study on surrogate markers of insulin resistance in Indonesian non‑diabetic women

Authors:
- Hariyono Winarto
- Muhammad Habiburrahman
- Irene Shinta Febriana
- Fitriyadi Kusuma
- Kartiwa Hadi Nuryanto
- Tricia Dewi Anggraeni
- Tofan Widya Utami
- Andi Darma Putra
View Affiliations

Affiliations: Division of Gynecologic Oncology, Faculty of Medicine Universitas Indonesia, Dr Cipto Mangunkusumo Hospital, Central Jakarta, DKI Jakarta 10430, Indonesia, Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Indonesia, Dr Cipto Mangunkusumo Hospital, Central Jakarta, DKI Jakarta 10430, Indonesia
Published online on: November 23, 2022 https://doi.org/10.3892/ol.2022.13609
Article Number: 23
Copyright: © Winarto et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The association between insulin resistance (IR) and ovarian neoplasm is little known. The present study attempted to investigate the difference in clinicopathological characteristics, metabolic parameters, and IR prevalence between benign and malignant ovarian neoplasms. The cross‑sectional study involved 52 non‑diabetic women with benign (n=27) and malignant (n=25) diagnoses in a tertiary hospital in Indonesia. Fasting insulin level (FIL), homeostatic model assessment of IR and β‑cell dysfunction (HOMA‑IR and HOMA‑β), fasting IR index (FIRI), and quantitative insulin sensitivity check index (QUICKI) were used as surrogate markers to evaluate IR. Parametric and nonparametric statistical tests were employed to analyze the different parameters between the two groups. Pearson or Spearman's rank test assessed the correlation between markers and clinical variables. Results revealed that patients with benign neoplasms were younger than those with malignant neoplasms (38.63 vs. 47.40 years; P=0.003) and had a higher median body mass index (BMI) than their counterparts (22.98 vs. 18.61 kg/m²; P=0.014). Different characteristics between benign and malignant neoplasm cases were found in menopausal status, ovary side affected, systolic blood pressure, and BMI classes. Endometrial cysts and mucinous carcinoma were the most often diagnosed benign and malignant neoplasms. Malignant neoplasms had a lower median HOMA‑β score than benign neoplasms (49.33 vs. 75.79; P=0.011), indicating more severe β‑cell dysfunction. No significant difference was observed in the prevalence of IR between benign and malignant ovarian neoplasms for the following values of each marker: FIL (25.9% vs. 12.0%), HOMA‑IR (37.0% vs. 28.0%), FIRI (51.9% vs. 48.0%) and QUICKI (81.5% vs. 92.0%). The indicators of FIL, HOMA‑IR, HOMA‑β, FIRI, and QUICKI correlated with each other and confirmed the reliability of these surrogate markers for measuring IR status in ovarian neoplasms. In brief, benign ovarian neoplasms tended to have more IR when compared with malignant ovarian neoplasms. However, this difference was not statistically significant.

View Figures

View References

1	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI
2	Teng Z, Han R, Huang X, Zhou J, Yang J, Luo P and Wu M: Increase of incidence and mortality of ovarian cancer during 2003–2012 in Jiangsu Province, China. Front Public Health. 4:1462016. View Article : Google Scholar : PubMed/NCBI
3	Winarto H, Welladatika A, Habiburrahman M, Purwoto G, Kusuma F, Utami TW, Putra AD, Anggraeni T and Nuryanto KH: Overall survival and related factors of advanced-stage epithelial ovarian cancer patients underwent debulking surgery in Jakarta, Indonesia: A single-center experience. Open Access Maced J Med Sci. 10:265–280. 2022. View Article : Google Scholar
4	Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, Gaudet MM, Jemal A and Siegel RL: Ovarian cancer statistics, 2018. CA Cancer J Clin. 68:284–296. 2018. View Article : Google Scholar : PubMed/NCBI
5	Aziz MF: Gynecological cancer in Indonesia. J Gynecol Oncol. 20:8–10. 2009. View Article : Google Scholar
6	Devouassoux-Shisheboran M and Genestie C: Pathobiology of ovarian carcinomas. Chin J Cancer. 34:50–55. 2015. View Article : Google Scholar : PubMed/NCBI
7	Beauchamp MC, Yasmeen A, Knafo A and Gotlieb WH: Targeting insulin and insulin-like growth factor pathways in epithelial ovarian cancer. J Oncol. 2010:2570582010. View Article : Google Scholar
8	Kellenberger LD, Bruin JE, Greenaway J, Campbell NE, Moorehead RA, Holloway AC and Petrik J: The role of dysregulated glucose metabolism in epithelial ovarian cancer. J Oncol. 2010:5143102010. View Article : Google Scholar
9	Uzunlulu M, Telci Caklili O and Oguz A: Association between metabolic syndrome and cancer. Ann Nutr Metab. 68:173–179. 2016. View Article : Google Scholar : PubMed/NCBI
10	Tseng YH, Ueki K, Kriauciunas KM and Kahn CR: Differential roles of insulin receptor substrates in the anti-apoptotic function of insulin-like growth factor-1 and insulin. J Biol Chem. 277:31601–31611. 2002. View Article : Google Scholar : PubMed/NCBI
11	Djiogue S, Nwabo Kamdje AH, Vecchio L, Kipanyula MJ, Farahna M, Aldebasi Y and Seke Etet PF: Insulin resistance and cancer: The role of insulin and IGFs. Endocr Relat Cancer. 20:R1–R17. 2013. View Article : Google Scholar : PubMed/NCBI
12	Atsumi T: Diabetes and risk of cancer. Diabetol Int. 6:190–192. 2015. View Article : Google Scholar
13	Joung KH, Jeong JW and Ku BJ: The association between type 2 diabetes mellitus and women cancer: The epidemiological evidences and putative mechanisms. Biomed Res Int. 2015:9206182015. View Article : Google Scholar
14	Igwe EO, Azman A, Nordin A and Mohtarrudin N: Association between HOMA-IR and Cancer in a Medical Centre in Selangor, Malaysia. IJPHCS. 2:21–34. 2015.
15	Ekinci O, Eren T, Kurtoglu Yakici M, Gapbarov A, Aydemir MA, Saglam ZA and Alimoglu O: Relationship Between Metabolic Syndrome and Postmenopausal Breast Cancer. Cir Esp (Engl Ed). 98:540–546. 2020.(In English, Spanish). View Article : Google Scholar : PubMed/NCBI
16	Sun W, Lu J, Wu S, Bi Y, Mu Y, Zhao J, Liu C, Chen L, Shi L, Li Q, et al: Association of insulin resistance with breast, ovarian, endometrial and cervical cancers in non-diabetic women. Am J Cancer Res. 6:2334–2344. 2016.PubMed/NCBI
17	Nam S, Park S, Park HS, Kim S, Kim JY and Kim SI: Association between insulin resistance and luminal B subtype breast cancer in postmenopausal women. Medicine (Baltimore). 95:e28252016. View Article : Google Scholar : PubMed/NCBI
18	Gennari A, Puntoni M, Nanni O, De Censi A, Bruzzi P, Paleari L, Freschi A, Amaducci L, Bologna A, Gianni L and Amadori D: Impact of insulin resistance (IR) on the prognosis of metastatic breast cancer (MBC) patients treated with first-line chemotherapy (CT). J Clin Oncol. 32 (Suppl 15):S5142014. View Article : Google Scholar
19	Doğan İ, Ürün Y and Onur H: Effects of Adjuvant Chemotherapy on Insulin Resistance in Patients with Early Breast Cancer. Cam and Sakura Med J. 2:8–13. 2022. View Article : Google Scholar
20	Alan O, Akin Telli T, Aktas B, Koca S, Ökten IN, Hasanov R, Basoglu T, Arikan R, Demircan NC, Ercelep O, et al: Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment? World J Surg Oncol. 18:2422020. View Article : Google Scholar
21	Martín-Manzo MV, Lara C, Vargas-de-Leon C, Carrero J, Queipo G, Fonseca-Sanchez M, Mejia-Dominguez NR, Kershenobich D, Mummidi S, Zentella-Dehesa A and Hernandez J: Interaction of Breast Cancer and Insulin Resistance on PD1 and TIM3 Expression in Peripheral Blood CD8 T Cells. Pathol Oncol Res. 25:1233–1243. 2019. View Article : Google Scholar
22	Lai Y and Sun C: Association of abnormal glucose metabolism and insulin resistance in patients with atypical and typical endometrial cancer. Oncol Lett. 15:2173–2178. 2018.
23	Momenimovahed Z, Tiznobaik A, Taheri S and Salehiniya H: Ovarian cancer in the world: Epidemiology and risk factors. Int J Womens Health. 11:287–299. 2019. View Article : Google Scholar : PubMed/NCBI
24	Serin IS, Tanriverdi F, Yilmaz MO, Ozcelik B and Unluhizarci K: Serum insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, leptin concentrations and insulin resistance in benign and malignant epithelial ovarian tumors in postmenopausal women. Gynecol Endocrinol. 24:117–121. 2008. View Article : Google Scholar
25	Otokozawa S, Tanaka R, Akasaka H, Ito E, Asakura S, Ohnishi H, Saito S, Miura T, Saito T and Mori M: Associations of serum isoflavone, adiponectin and insulin levels with risk for epithelial ovarian cancer: Results of a case-control study. Asian Pac J Cancer Prev. 16:4987–4991. 2015. View Article : Google Scholar : PubMed/NCBI
26	Lukanova A, Lundin E, Toniolo P, Micheli A, Akhmedkhanov A, Rinaldi S, Muti P, Lenner P, Biessy C, Krogh V, et al: Circulating levels of insulin-like growth factor-I and risk of ovarian cancer. Int J Cancer. 101:549–554. 2002. View Article : Google Scholar : PubMed/NCBI
27	Dahlan MS: Sample Size in Medical and Health Research. 5th edition. Epidemiologi Indonesia; Jakarta: 2019, (In Indonesian).
28	Sharma SK, Mudgal SK, Thakur K and Gaur R: How to calculate sample size for observational and experiential nursing research studies? Natl J Physiol Pharm Pharmacol. 10:1–8. 2020. View Article : Google Scholar
29	Timmerman D, Ameye L, Fischerova D, Epstein E, Melis GB, Guerriero S, Van Holsbeke C, Savelli L, Fruscio R, Lissoni AA, et al: Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: Prospective validation by IOTA group. BMJ. 341:c68392010. View Article : Google Scholar : PubMed/NCBI
30	Abramowicz JS and Timmerman D: Ovarian mass-differentiating benign from malignant: The value of the International Ovarian Tumor Analysis ultrasound rules. Am J Obstet Gynecol. 217:652–660. 2017. View Article : Google Scholar
31	Badan Pusat Statistik/BPS-Statistics Indonesia, . Concept of Population, Age, Marital Status, Children Ever Born, Children Still Alive, and Place of Birth in Indonesia. Concept. 2021.https://www.bps.go.id/subject/12/kependudukan.htmlDecember 10–2021
32	Mulyana W: Rural-urban linkages: Indonesia case study. Working Group: Development with Territorial Cohesion. Territorial Cohesion for Development Program Rimisp. 1–36. 2014.
33	Badan Pusat Statistik/BPS-Statistics Indonesia, . Regulation of the Head of the Central Statistics Agency Number 120 of 2020: Classification of Urban and Rural Areas in Java, Indonesia [In Indonesian]. Book Chapter Java. 2nd ed. BPS; Jakarta: pp. 1–692. 2010
34	Badan Pusat Statistik/BPS-Statistics Indonesia, . Regulation of the Head of the Central Statistics Agency Number 120 of 2020: Classification of Urban and Rural Areas in Sumatra, Indonesia [In Indonesian]. Book Chapter Sumatera. 2nd ed. BPS; Jakarta: pp. 1–681. 2010
35	Klar M, Hasenburg A, Hasanov M, Hilpert F, Meier W, Pfisterer J, Pujade-Lauraine E, Herrstedt J, Reuss A and du Bois A: Prognostic factors in young ovarian cancer patients: An analysis of four prospective phase III intergroup trials of the AGO Study Group, GINECO and NSGO. Eur J Cancer. 66:114–124. 2016. View Article : Google Scholar : PubMed/NCBI
36	Lalrinpuii E, Bhageerathy PS, Sebastian A, Jeyaseelan L, Vinotha Thomas, Thomas A, Chandy R and Peedicayil A: Ovarian Cancer in Young Women. Indian J Surg Oncol. 8:540–547. 2017. View Article : Google Scholar
37	Encinas G, Maistro S, Pasini FS, Katayama ML, Brentani MM, Bock GH and Folgueira MA: Somatic mutations in breast and serous ovarian cancer young patients: A systematic review and meta-analysis. Rev Assoc Med Bras (1992). 61:474–483. 2015. View Article : Google Scholar : PubMed/NCBI
38	Bozas G, Dimopoulos MA, Kastritis E, Efstathiou E, Koutsoukou V, Rodolakis A, Vlahos G, Voulgaris Z, Papageorgiou T, Gika D, et al: Young age is associated with favorable characteristics but is not an independent prognostic factor in patients with epithelial ovarian cancer: A single institution experience. Oncology. 70:265–272. 2006. View Article : Google Scholar : PubMed/NCBI
39	Winarto H, Habiburrahman M, Dorothea M, Wijaya A, Nuryanto KH, Kusuma F, Utami TW and Anggraeni TD: Knowledge, attitudes, and practices among Indonesian urban communities regarding HPV infection, cervical cancer, and HPV vaccination. PLoS One. 17:e02661392022. View Article : Google Scholar : PubMed/NCBI
40	4Berek JS, Renz M, Kehoe S, Kumar L and Friedlander M: FIGO Cancer Report 2021: Cancer of the ovary, fallopian tube, and peritoneum: 2021 update. Int J Gynaecol Obstet. 155:61–85. 2021. View Article : Google Scholar
41	World Health Organization and International Agency for Research on Cancer, . World Health Organization: WHO Classification of Tumours: Female Genital Tumours. 5th edition. WHO; Geneva, Switzerland: pp. 31–163. 2021
42	Matz M, Coleman MP, Sant M, Chirlaque MD, Visser O, Gore M and Allemani C; & the CONCORD Working Group, : The histology of ovarian cancer: Worldwide distribution and implications for international survival comparisons (CONCORD-2). Gynecol Oncol. 144:405–413. 2017. View Article : Google Scholar
43	Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, Ramirez A, Schlaich M, Stergiou GS, Tomaszewski M, et al: 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension. 75:1334–1357. 2020. View Article : Google Scholar : PubMed/NCBI
44	National Health and Nutrition Examination Survey and Center of Disease Control and Prevention, . Anthropometry Procedures Manual CDC2. 1–65. 2007.
45	Lim JU, Lee JH, Kim JS, Hwang YI, Kim TH, Lim SY, Yoo KH, Jung KS, Kim YK and Rhee CK: Comparison of World Health Organization and Asia-Pacific body mass index classifications in COPD patients. Int J Chron Obstruct Pulmon Dis. 12:2465–2475. 2017. View Article : Google Scholar : PubMed/NCBI
46	Cleveland Clinic, . Fasting Blood Sugar Test. Diagnostics & Testing; 2021, https://my.clevelandclinic.org/health/diagnostics/21952-fasting-blood-sugarDecember 10–2021
47	Gayoso-Diz P, Otero-González A, Rodriguez-Alvarez MX, Gude F, García F, De Francisco A and Quintela AG: Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: Effect of gender and age: EPIRCE cross-sectional study. BMC Endocr Disord. 13:472013. View Article : Google Scholar : PubMed/NCBI
48	Farahani H, Mahmoudi T, Asadi A, Nobakht H, Dabiri R and Hamta A: Insulin Resistance and Colorectal Cancer Risk: The Role of Elevated Plasma Resistin Levels. J Gastrointest Cancer. 51:478–483. 2020. View Article : Google Scholar : PubMed/NCBI
49	Gupta RK, Dholariya SJ, Kaushik S, Gupta SK, Tripathi R and Jain SL: Hyperinsulinemia and Hypoadiponectinemia are Associated with increased risk for occurrence of ovarian cancer in non-diabetic women of North Indian Population. Indian J Clin Biochem. 36:221–227. 2021. View Article : Google Scholar : PubMed/NCBI
50	American Diabetes Association (ADA), . Diagnosis of Diabetes Mellitus. ADA; Arlington, VA: 2022
51	Lunger F, Wildt L and Seeber B: Accurate screening for insulin resistance in PCOS women using fasting insulin concentrations. Gynecol Endocrinol. 29:541–544. 2013. View Article : Google Scholar
52	Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF and Turner RC: Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28:412–419. 1985. View Article : Google Scholar
53	Onishi Y, Hayashi T, Sato KK, Ogihara T, Kuzuya N, Anai M, Tsukuda K, Boyko EJ, Fujimoto WY and Kikuchi M: Fasting tests of insulin secretion and sensitivity predict future prediabetes in Japanese with normal glucose tolerance. J Diabetes Investig. 1:191–195. 2010. View Article : Google Scholar : PubMed/NCBI
54	Yamauchi K, Sato Y, Nakasone Y and Aizawa T: Comparison of HOMA-IR, HOMA-β% and disposition index between US white men and Japanese men in Japan in the ERA JUMP study: Was the calculation of disposition index legitimate? Diabetologia. 58:1679–1680. 2015. View Article : Google Scholar
55	Imano H, Kitamura A, Yamagishi K, Kiyama M, Ohira T, Cui R, Umesawa M, Okada T and Iso H; CIRCS Investigators, : Abstract P455: Insulin Resistance, Secretion and Risk of Incident Coronary Heart Disease in Non-diabetic Japanese Population: The Circulatory Risk in Communities Study. Circulation. 129:AP4552014. View Article : Google Scholar
56	Singh B and Saxena A: Surrogate markers of insulin resistance: A review. World J Diabetes. 1:36–47. 2010. View Article : Google Scholar : PubMed/NCBI
57	Duncan MH, Singh BM, Wise PH, Carter G and Alaghband-Zadeh J: A simple measure of insulin resistance. Lancet. 346:120–121. 1995. View Article : Google Scholar
58	Tsarouhas K, Tsitsimpikou C, Haliassos A, Georgoulias P, Koutsioras I, Kouretas D, Kogias J, Liosis I, Rentoukas E and Kyriakides Z: Study of insulin resistance, TNF-α, total antioxidant capacity and lipid profile in patients with chronic heart failure under exercise. In Vivo. 25:1031–1037. 2011.PubMed/NCBI
59	Farkas GJ, Gordon PS, Trewick N, Gorgey AS, Dolbow DR, Tiozzo E, Berg AS and Gater DR Jr: Comparison of various indices in identifying insulin resistance and diabetes in chronic spinal cord injury. J Clin Med. 10:55912021. View Article : Google Scholar : PubMed/NCBI
60	Gordon PS, Farkas GJ and Gater DR Jr: Neurogenic Obesity-Induced Insulin Resistance and Type 2 Diabetes Mellitus in Chronic Spinal Cord Injury. Top Spinal Cord Inj Rehabil. 27:36–56. 2021. View Article : Google Scholar
61	Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G and Quon MJ: Quantitative insulin sensitivity check index: A simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 85:2402–2410. 2000. View Article : Google Scholar : PubMed/NCBI
62	Matsuda M and DeFronzo RA: Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp. Diabetes Care. 22:1462–1470. 1999. View Article : Google Scholar : PubMed/NCBI
63	Pratisthita Livy B, Purnamasari D, Rizka A, Soewondo P, Yunir E and Tahapary DL: The Cut-off Values of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) in Indonesian Rural Population. Lancet Preprint. 6:7–20. 2020.
64	Rahman MN, Sukmawati IR, Puspitasari IM and Fattah M: Serum free zinc as a predictor for excessive function of pancreatic beta-cells in central-obese men. Indones Biomed J. 11:262–266. 2019. View Article : Google Scholar
65	AlZadjali MA, Godfrey V, Khan F, Choy A, Doney AS, Wong AK, Petrie JR, Struthers AD and Lang CC: Insulin resistance is highly prevalent and is associated with reduced exercise tolerance in nondiabetic patients with heart failure. J Am Coll Cardiol. 53:747–753. 2009. View Article : Google Scholar
66	Kaur N, Gitanjali, Garg R, Tapasvi C, Chawla S and Kaur N: Correlation of Surrogate Markers of Insulin Resistance with Fasting Insulin in Type 2 Diabetes Mellitus Patients: A Study of Malwa Population in Punjab, India. J Lab Physicians. 13:238–244. 2021. View Article : Google Scholar : PubMed/NCBI
67	Diebetes.co.uk, . Blood Sugar Converter. Calculators and Tools. 2022.https://www.diabetes.co.uk/blood-sugar-converter.htmlApril 12–2022
68	Katalin C: Surrogate Measures of Insulin Resistance in Middle-aged Non-diabetic Subjects. Acta Med Marisiensis. 59:279–284. 2014. View Article : Google Scholar
69	Burzawa JK, Schmeler KM, Soliman PT, Meyer LA, Bevers MW, Pustilnik TL, Anderson ML, Ramondetta LM, Tortolero-Luna G, Urbauer DL, et al: Prospective evaluation of insulin resistance among endometrial cancer patients. Am J Obstet Gynecol. 204:355.e1–7. 2011. View Article : Google Scholar
70	von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC and Vandenbroucke JP: Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ. 335:806 LP–808. 2007. View Article : Google Scholar
71	Statistic Tutor: Spearman's correlation, 2021. http://www.statstutor.ac.uk/resources/uploaded/spearmans.pdfDecember 10–2021
72	Beavis AL, Smith AJ and Fader AN: Lifestyle changes and the risk of developing endometrial and ovarian cancers: Opportunities for prevention and management. Int J Womens Health. 8:151–167. 2016.PubMed/NCBI
73	Szpurek D, Moszynski R, Szubert S and Sajdak S: Urban and rural differences in characteristics of ovarian cancer patients. Ann Agric Environ Med. 20:390–394. 2013.PubMed/NCBI
74	Saccò M, Meschi M, Regolisti G, Detrenis S, Bianchi L, Bertorelli M, Pioli S, Magnano A, Spagnoli F, Giuri PG, et al: The relationship between blood pressure and pain. J Clin Hypertens (Greenwich). 15:600–605. 2013. View Article : Google Scholar
75	El-Atat FA, Stas SN, McFarlane SI and Sowers JR: The relationship between hyperinsulinemia, hypertension and progressive renal disease. J Am Soc Nephrol. 15:2816–2827. 2004. View Article : Google Scholar
76	Pérez-Pérez A, Sánchez-Jiménez F, Vilariño-García T and Sánchez-Margalet V: Role of Leptin in Inflammation and Vice Versa. Int J Mol Sci. 21:2020. View Article : Google Scholar
77	Orgel E and Mittelman SD: The links between insulin resistance, diabetes, and cancer. Curr Diab Rep. 13:213–222. 2013. View Article : Google Scholar : PubMed/NCBI
78	Kim SI, Kim HS, Kim TH, Suh DH, Kin K, No JH, Chung HH, Kim YB and Song YS: Impact of underweight after treatment on prognosis of advanced-stage ovarian cancer. J Immunol Res. 2014.1–8. 2014. View Article : Google Scholar
79	Wright JD, Powell MA, Mutch DG, Rader JS, Gibb RK, Gao F and Herzog TJ: Relationship of ovarian neoplasms and body mass index. J Reprod Med. 50:595–602. 2005.PubMed/NCBI
80	Leitzmann MF, Koebnick C, Danforth KN, et al: Body mass index and risk of ovarian cancer. Cancer. 115:812–822. 2009. View Article : Google Scholar : PubMed/NCBI
81	Hernandez AV, Guarnizo M, Miranda Y, Pasupuleti V, Deshpande A, Paico S, Lenti H, Ganoza S, Montalvo L, Thota P and Lazaro H: Association between insulin resistance and breast carcinoma: A systematic review and meta-analysis. PLoS One. 9:e993172014. View Article : Google Scholar : PubMed/NCBI
82	Kundaktepe BP, Durmus S, Cengiz M, Kundaktepe FO, Sozer V, Papila C, Gelisgen R and Uzun H: The significance of insulin resistance in nondiabetic breast cancer patients. J Endocrinol Metab. 11:42–48. 2021. View Article : Google Scholar
83	Gómez JM, Maravall FJ, Gómez N, Navarro MA, Casamitjana R and Soler J: Interactions between serum leptin, the insulin-like growth factor-I system, and sex, age, anthropometric and body composition variables in a healthy population randomly selected. Clin Endocrinol (Oxf). 58:213–219. 2003. View Article : Google Scholar
84	Bjørge T, Lukanova A, Tretli S, Manjer J, Ulmer H, Stocks T, Selmer R, Nagel G, Almquist M, Concin H, et al: Metabolic risk factors and ovarian cancer in the Metabolic Syndrome and Cancer project. Int J Epidemiol. 40:1667–1677. 2011. View Article : Google Scholar
85	Craig ER, Londoño AI, Norian LA and Arend RC: Metabolic risk factors and mechanisms of disease in epithelial ovarian cancer: A review. Gynecol Oncol. 143:674–683. 2016. View Article : Google Scholar
86	Khanlarkhani N, Azizi E, Amidi F, Khodarahmian M, Salehi E, Pazhohan A, Farhood B, Mortezae K, Goradel NH and Nashtaei MS: Metabolic risk factors of ovarian cancer: A review. JBRA Assist Reprod. 26:335–347. 2022.PubMed/NCBI
87	Dixon SC, Nagle CM, Thrift AP, Pharoah PD, Pearce CL, Zheng W, Painter JN; AOCS Group & Australian Cancer Study (Ovarian Cancer), ; Chenevix-Trench G, Fasching PA, et al: Adult body mass index and risk of ovarian cancer by subtype: A Mendelian randomization study. Int J Epidemiol. 45:884–895. 2016. View Article : Google Scholar
88	Zeleznik OA, Eliassen AH, Kraft P, Poole EM, Rosner BA, Jeanfavre S, Deik AA, Bullock K, Hitchcock DS, Avila-Pacheco J, et al: A prospective analysis of circulating plasma metabolites Associated with ovarian cancer risk. Cancer Res. 80:1357–1367. 2020. View Article : Google Scholar : PubMed/NCBI
89	Lee S, Choi S, Kim HJ, Chung YS, Lee KW, Lee HC, Huh KB and Kim DJ: Cutoff values of surrogate measures of insulin resistance for metabolic syndrome in Korean non-diabetic adults. J Korean Med Sci. 21:695–700. 2006. View Article : Google Scholar
90	Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, Monauni T and 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. 23:57–63. 2000. View Article : Google Scholar : PubMed/NCBI
91	Robbins DC, Andersen L, Bowsher R, Chance R, Dinesen B, Frank B, Gingerich R, Goldstein D, Widemeyer HM, Haffner S, et al: Report of the American Diabetes Association's Task Force on standardization of the insulin assay. Diabetes. 45:242–256. 1996. View Article : Google Scholar : PubMed/NCBI
92	Mack R, Skurnick B, Sterling-Jean Y, Pedra-Nobre M and Bigg D: Fasting insulin levels as a measure of insulin resistance in American blacks. J Med. 34:31–38. 2003.PubMed/NCBI
93	Yeni-Komshian H, Carantoni M, Abbasi F and Reaven GM: Relationship between several surrogate estimates of insulin resistance and quantification of insulin-mediated glucose disposal in 490 healthy nondiabetic volunteers. Diabetes Care. 23:171–175. 2000. View Article : Google Scholar : PubMed/NCBI
94	Buchanan TA, Watanabe RM and Xiang AH: Limitations in surrogate measures of insulin resistance. J Clin Endocrinol Metab. 95:4874–4876. 2010. View Article : Google Scholar : PubMed/NCBI
95	Haffner SM, Miettinen H and Stern MP: The homeostasis model in the San Antonio Heart Study. Diabetes Care. 20:1087–1092. 1997. View Article : Google Scholar : PubMed/NCBI
96	Legro RS, Finegood D and 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. 83:2694–2698. 1998. View Article : Google Scholar : PubMed/NCBI
97	Jørgensen SW, Hjort L, Gillberg L, Justesen L, Madsbad S, Brøns C and Vaag AA: Impact of prolonged fasting on insulin secretion, insulin action, and hepatic versus whole body insulin secretion disposition indices in healthy young males. Am J Physiol Endocrinol Metab. 320:E281–E290. 2021. View Article : Google Scholar
98	Habib SS, Eshki A, AlTassan B, Fatani D, Helmi H and AlSaif S: Relationship of serum novel adipokine chemerin levels with body composition, insulin resistance, dyslipidemia and diabesity in Saudi women. Eur Rev Med Pharmacol Sci. 21:1296–1302. 2017.
99	Pavelić K, Slijepcević M, Pavelić J, Ivić J, Audy-Jurković S, Pavelić ZP and Boranić M: Growth and treatment of Ehrlich tumor in mice with alloxan-induced diabetes. Cancer Res. 39:1807–1813. 1979.
100	Gates JR, Parpia B, Campbell TC and Chen J: Evaluation of the FIRI (Fasting Insulin Resistance Index) and selected plasma parameters associated with insulin resistance as predictors of cardiovascular mortality in rural Chinese women. Asia Pac J Clin Nutr. 6:200–202. 1997.PubMed/NCBI
101	Mather KJ, Hunt AE, Steinberg HO, Paradisi G, Hook G, Katz A, Quon MJ and Baron AD: Repeatability characteristics of simple indices of insulin resistance: Implications for research applications. J Clin Endocrinol Metab. 86:5457–5464. 2001. View Article : Google Scholar : PubMed/NCBI
102	Chen H, Sullivan G, Yue LQ, Katz A and Quon MJ: QUICKI is a useful index of insulin sensitivity in subjects with hypertension. Am J Physiol Endocrinol Metab. 284:E804–E812. 2003. View Article : Google Scholar : PubMed/NCBI
103	Hettihewa LM, Palangasinghe S, Jayasinghe SS, Gunasekara SW and Weerarathna TP: Comparison of insulin resistance by indirect methods-HOMA, QUICKI and McAuley-With fasting insulin in patients with type 2 diabetes in Galle, Sri Lanka: A pilot study. Online J Health Allied Sci. 5:1–8. 2006.
104	Scoppola A, Strigari L, Barnabei A, Petasecca P, De Galitiis F, Fulgenzi CAM, Roselli M, De Lorenzo A, Di Renzo L, Marchetti P and Torino F: Insulin resistance as a risk factor for cutaneous melanoma. A case control study and risk-assessment nomograms. Front Endocrinol (Lausanne). 10:7572019. View Article : Google Scholar : PubMed/NCBI
105	Rutter MK, Wilson PWF, Sullivan LM, Fox CS, D'Agostino RB Sr and Meigs JB: Use of alternative thresholds defining insulin resistance to predict incident type 2 diabetes mellitus and cardiovascular disease. Circulation. 117:1003–1009. 2008. View Article : Google Scholar : PubMed/NCBI
106	Conwell LS, Trost SG, Brown WJ and Batch JA: Indexes of insulin resistance and secretion in obese children and adolescents: A validation study. Diabetes Care. 27:314–319. 2004. View Article : Google Scholar : PubMed/NCBI
107	Garg MK, Tandon N, Marwaha RK and Singh Y: Evaluation of surrogate markers for insulin resistance for defining metabolic syndrome in urban Indian adolescents. Indian Pediatr. 51:279–284. 2014. View Article : Google Scholar : PubMed/NCBI
108	Rudvik A and Månsson M: Evaluation of surrogate measures of insulin sensitivity-correlation with gold standard is not enough. BMC Med Res Methodol. 18:642018. View Article : Google Scholar
109	Coppola D, Saunders B, Fu L, Mao W and Nicosia SV: The insulin-like growth factor 1 receptor induces transformation and tumorigenicity of ovarian mesothelial cells and down-regulates their Fas-receptor expression. Cancer Res. 59:3264–3270. 1999.PubMed/NCBI
110	Karasik A, Menczer J, Pariente C and Kanety H: Insulin-like growth factor-I (IGF-I) and IGF-binding protein-2 are increased in cyst fluids of epithelial ovarian cancer. J Clin Endocrinol Metab. 78:271–276. 1994. View Article : Google Scholar : PubMed/NCBI
111	Holly J: Insulin-like growth factor-1 and risk of breast cancer. Lancet. 352:13881998. View Article : Google Scholar
112	D'Esposito V, Passaretti F, Hammarstedt A, Liguoro D, Terracciano D, Molea G, Canta L, Miele C, Smith U, Beguinot F and Formisano P: Adipocyte-released insulin-like growth factor-1 is regulated by glucose and fatty acids and controls breast cancer cell growth in vitro. Diabetologia. 55:2811–2822. 2012. View Article : Google Scholar
113	Sanchez-Garrido MA and Tena-Sempere M: Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies. Mol Metab. 35:2020. View Article : Google Scholar
114	Takemura Y, Ouchi N, Shibata R, Aprahamian T, Kirber MT, Summer RS, Kihara S and Walsh K: Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest. 117:375–386. 2007. View Article : Google Scholar
115	Kalli KR, Falowo OI, Bale LK, Zschunke MA, Roche PC and Conover CA: Functional insulin receptors on human epithelial ovarian carcinoma cells: Implications for IGF-II mitogenic signaling. Endocrinology. 143:3259–3267. 2002. View Article : Google Scholar : PubMed/NCBI
116	Lutz AM, Ray P, Willmann JK, Drescher C and Gambhir SS: 2-Deoxy-2-[F-18]fluoro-D-glucose accumulation in ovarian carcinoma cell lines. Mol Imaging Biol. 9:260–266. 2007. View Article : Google Scholar
117	Shibata K, Kajiyama H, Mizokami Y, Ino K, Nomura S, Mizutani S, Terauchi M and Kikkawa F: Placental leucine aminopeptidase (P-LAP) and glucose transporter 4 (GLUT4) expression in benign, borderline, and malignant ovarian epithelia. Gynecol Oncol. 98:11–18. 2005. View Article : Google Scholar
118	Tsukioka M, Matsumoto Y, Noriyuki M, Yoshida C, Nobeyama H, Yoshida H, Yasui T, Sumi T, Honda K and Ishiko O: Expression of glucose transporters in epithelial ovarian carcinoma: Correlation with clinical characteristics and tumor angiogenesis. Oncol Rep. 18:361–367. 2007.PubMed/NCBI
119	Sheetz MJ and King GL: Molecular understanding of hyperglycemia's adverse effects for diabetic complications. JAMA. 288:2579–2588. 2002. View Article : Google Scholar : PubMed/NCBI
120	Yamagishi S, Nakamura K, Inoue H, Kikuchi S and Takeuchi M: Possible participation of advanced glycation end products in the pathogenesis of colorectal cancer in diabetic patients. Med Hypotheses. 64:1208–1210. 2005. View Article : Google Scholar : PubMed/NCBI
121	Taguchi A, Blood DC, del Toro G, Canet A, Lee DC, Qu W, Tanji N, Lu Y, Lalla E, Fu C, et al: Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature. 405:354–360. 2000. View Article : Google Scholar : PubMed/NCBI
122	Ness RB, Grisso JA, Cottreau C, Klapper J, Vergona R, Wheeler JE, Morgan M and Schlesselman JJ: Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer. Epidemiology. 11:111–117. 2000. View Article : Google Scholar : PubMed/NCBI
123	Benjamin LE: Glucose, VEGF-A, and diabetic complications. Am J Pathol. 158:1181–1184. 2001. View Article : Google Scholar
124	Wang M, Cheng N, Zheng S, Wang D, Hu X, Ren X, Pei H, Ma H, Mu H and Bai Y: Metabolic syndrome and the risk of breast cancer among postmenopausal women in North-West China. Climacteric. 18:852–858. 2015. View Article : Google Scholar
125	DeFronzo RA, Tobin JD and Andres R: Glucose clamp technique: A method for quantifying insulin secretion and resistance. Am J Physiol. 237:E214–E223. 1979.
126	Alberti KG and Zimmet PZ: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 15:539–553. 1998. View Article : Google Scholar : PubMed/NCBI