Hormonal-metabolic trajectory of menopausal transition in a normoglycemic cohort of women with different blood pressure levels

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L.A. Ruyatkina D.S. Ruyatkin L.V. Shcherbakova


Introduction. The gradual clustering of cardio-metabolic factors in women depending on age and decline of ovarian function justifies attention to the phenotype of the formation of the metabolic syndrome during the menopausal transition depending on the presence of hypertension without dysglycemia.

Aim. To evaluate the association of indicators of the functional state of the pituitary-ovarian axis with markers of metabolic syndrome (MetS) and parameters of insulin resistance (IR) in a cohort of normoglycemic women aged 35-59 years with different levels of blood pressure.

Patients and methods. In a cohort of women 35–59 years old without dysglycemia (n = 88), 58 women had hypertension, 30 were normotensive. It was determined: body mass index (BMI), waist circumference (WC), levels of blood pressure, triglycerides (TG), HDL-C, insulin, follicle-stimulating hormone (FSH) and estradiol, fasting glucose (FG); TyG and HOMA2-IR indices. Using SPSS (version 17) assessed the median (25; 75%); intergroup differences using the Mann-Whitney test; correlation analyzes: Spearman (R) and partial correlation (Rрс) to level out the influence of age.

Results. In the general cohort of women, the influence of postmenopausal duration, FSH and estradiol levels on MetS and TyG parameters depended on age, except for the correlation of postmenopausal duration with FG (Rpc = 0.313; p = 0.004). The range of associations of MetS markers with each other and TyG in the group of patients with hypertension is similar to those in the general cohort of women. In both cohorts, the interrelations between FG, WC, insulin and TyG remained relevant with partial correlation. The Index TyG, associated with HOMA2-IR (R=0.600; p<0.001; Rpc=0.426; p<0.001), had a greater range of connections with MetS components, as well as with FSH (R=0.312; p=0.017; Rpc =0.286; p=0.030) and estradiol (R= -0.393; p=0.002; Rpc = -0.376; p=0.004) in the presence of hypertension.

Conclusion. The influence of indicators of the functional state of the pituitary-ovarian axis on MetS and TyG markers was revealed, along with a spectrum of associations of parameters and factors in the formation of menopausal MetS with IR indices, especially TyG. Correlation relations between FG with postmenopausal duration and MetS components, as well as estradiol in case of hypertension, reflect a high risk of progression to dysglycemia.

Keywords: metabolic syndrome, menopausal transition, hypertension, insulin resistance, TyG index, HOMA2 family indices, fasting glycemia, follicle-stimulating hormone, estradiol

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RUYATKINA, L.A.; RUYATKIN, D.S.; SHCHERBAKOVA, L.V.. Hormonal-metabolic trajectory of menopausal transition in a normoglycemic cohort of women with different blood pressure levels. Medical Research Archives, [S.l.], v. 12, n. 1, jan. 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4972>. Date accessed: 03 mar. 2024. doi: https://doi.org/10.18103/mra.v12i1.4972.
Review Articles


1. Ou YJ, Lee JI, Huang SP, Chen SC, Geng JH, Su CH. Association between Menopause, Postmenopausal Hormone Therapy and Metabolic Syndrome. J Clin Med. 2023; 12(13):4435. doi: 10.3390/jcm12134435.

2. Jeong HG, Park H. Metabolic Disorders in Menopause. Metabolites. 2022;12(10):954. doi: 10.3390/metabo12100954.

3. Jouyandeh Z, Nayebzadeh F, Qorbani M, Asadi M. Metabolic syndrome and menopause. J Diabetes Metab Disord. 2013;12(1):1. doi: 10.1186/2251-6581-12-1

4. Janssen I, Powell LH, Crawford S, Lasley B, Sutton-Tyrrell K. Menopause and the metabolic syndrome: the Study of Women's Health Across the Nation. Arch Intern Med. 2008;168(14):1568-75. doi: 10.1001/archinte.168.14.1568

5. Meloni A, Cadeddu C, Cugusi L, et al. Gender Differences and Cardiometabolic Risk: The Importance of the Risk Factors. International Journal of Molecular Sciences. 2023;24(2):1588. doi:10.3390/ijms24021588

6. Sherling DH, Perumareddi P, Hennekens CH. Metabolic Syndrome: Clinical and Policy Implications of the New Silent Killer. Journal of Cardiovascular Pharmacology and Therapeutics. 2017;22(4):365-367. doi:10.1177/1074248416686187

7. Roa-Díaz ZM, Raguindin PF, Bano A, et al. Menopause and cardiometabolic diseases: What we (don't) know and why it matters. Maturitas. 2021, 152:48-56. doi: 10.1016/j.maturitas.2021.06.01

8. Stefanska A, Cembrowska P, Kubacka J, Kuligowska-Prusinska M, Sypniewska G. Gonadotropins and Their Association with the Risk of Prediabetes and Type 2 Diabetes in Middle-Aged Postmenopausal Women. Dis Markers. 2019;2384069. doi: 10.1155/2019/2384069.

9. De Paoli M, Zakharia A, Werstuck GH. The Role of Estrogen in Insulin Resistance: A Review of Clinical and Preclinical Data. Am J Pathol.2021;191(9):1490-1498. doi: 10.1016/j.ajpath.2021.05.011

10. Moccia P, Belda-Montesinos R, Monllor-Tormos A, Chedraui P, Cano A. Body weight and fat mass across the menopausal transition: hormonal modulators. Gynecol Endocrinol. 2022;38(2):99-104. doi: 10.1080/09513590.2021.2004395.

11. Chen Y, Wang C, Sun B, et al. Associations of follicle-stimulating hormone and luteinizing hormone with metabolic syndrome during the menopausal transition from the National Health and Nutrition Examination Survey. Front Endocrinol (Lausanne). 2023; 14:1034934. doi: 10.3389/fendo.2023.1034934;

12. Lakhno I, Korovai S, Struk T, Pak S. The pathogenic pathways of cardiovascular disease in perimenopausal women. Prz Menopauzalny. 2023;59-63. doi: 10.5114/pm.2023.127902

13. Nappi RE, Simoncini T. Menopause transition: a golden age to prevent cardiovascular disease. Lancet Diabetes Endocrinol. 2021;9(3):135-137. doi: 10.1016/S2213-8587(21)00018-8

14. Maas AHEM, Rosano G, Cifkova R, et al. Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists. Eur Heart J. 2021; 42(10):967-984. doi: 10.1093/eurheartj/ehaa1044. Erratum in: Eur Heart J. 2022;43(25):2372

15. de Cuevillas B, Alvarez-Alvarez I, Riezu-Boj JI, et al. The hypertriglyceridemic-waist phenotype as a valuable and integrative mirror of metabolic syndrome traits. Sci. Rep. 2021; 11(1):21859. doi: 10.1038/ s41598-021-01343-x.

16. Alberti KGMM, Zimmet P, Shaw J. Metabolic syndrome – a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet. Med. 2006;23(5):469-80. doi: 10.1111/j.14645491.2006.01858. x.

17. Stanciu S, Rusu E, Miricescu D, et al. Links between metabolic syndrome and hypertension: the relationship with the current antidiabetic drugs. Metabolites. 2023; 13(1):87. doi: 10.3390/metabo13010087.

18. da Silva AA, do Carmo JM, Li X, Wang Z, Mouton AJ, Hall JE. Role of Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic Syndrome Revisited. Can J Cardiol. 2020;36(5):671-682. doi: 10.1016/j.cjca.2020.02.066

19. Wenger NK, Arnold A, Bairey Merz CN, et al. Hypertension Across a Woman's Life Cycle. J Am Coll Cardiol. 2018;71(16):1797-1813. doi: 10.1016/j.jacc.2018.02.033.

20. Ji H, Kim A, Ebinger JE, et al. Sex Differences in Blood Pressure Trajectories Over the Life Course. JAMA Cardiol. 2020;5(3):19-26. doi: 10.1001/jamacardio.2019.5306. Erratum in: JAMA Cardiol. 2020;5(3):364.

21. Li Q, Wang X, Ni Y, et al. Epidemiological characteristics and risk factors of T2DM in Chinese premenopausal and postmenopausal women. Lipids Health Dis. 2019;18(1):155. doi: 10.1186/s12944-019-1091-7.

22. Majnarić LT, Martinović I, Šabanović Š, et al. The eff ct of hypertension duration and the age of onset on CV risk factors expression in perimenopausal women. Int. J. Hypertens. 2019; 2019:9848125. doi: 10.1155/2019/9848125.

23. Jung ES, Choi EK, Park BH, Chae SW. Serum Follicle-Stimulating Hormone Levels Are Associated with Cardiometabolic Risk Factors in Post-Menopausal Korean Women. J Clin Med. 2020;9(4):1161. doi: 10.3390/jcm9041161

24. Af Geijerstam , Engvall J., Östgren CJ, et al. Home blood pressure compared with offi ce blood pressure in relation to dysglycemia. Am. J. Hypertens. 2022;35(9):810-819. doi: 10.1093/ajh/hpac082

25. Mumusoglu S, Yildiz BO. Metabolic Syndrome During Menopause. Curr Vasc Pharmacol. 2019;17(6):595-603. doi: 10.2174/1570161116666180904094149

26. Paschou SA, Papanas N. Type 2 Diabetes Mellitus and Menopausal Hormone Therapy: An Update. Diabetes Ther. 2019;10(6):2313-2320. doi: 10.1007/s13300-019-00695-y.

27. Stevenson JC, Tsiligiannis S, Panay N. Cardiovascular Risk in Perimenopausal Women. Curr Vasc Pharmacol. 2019;17(6):591-594. doi: 10.2174/1570161116666181002145340.

28. Zhu D, Chung HF, Dobson AJ, et al. Type of menopause, age of menopause and variations in the risk of incident cardiovascular disease: pooled analysis of individual data from 10 international studies. Hum Reprod. 2020;35(8):1933-1943. doi: 10.1093/humrep/deaa124.

29. El Khoudary SR, Santoro N, Chen HY, et al. Trajectories of estradiol and follicle-stimulating hormone over the menopause transition and early markers of atherosclerosis after menopause. Eur J Prev Cardiol. 2016;23(7):694-703. doi:10.1177/2047487315607044;

30. Bertone-Johnson ER, Virtanen JK, Nurmi T, et al. Follicle-Stimulating Hormone Levels and Subclinical Atherosclerosis in Older Postmenopausal Women. Am J Epidemiol. 2018;187(1):16-26. doi: 10.1093/aje/kwx174

31. Ottarsdottir K, Tivesten Å, Li Y, et al. Cardiometabolic Risk Factors and Endogenous Sex Hormones in Postmenopausal Women: A Cross-Sectional Study. J Endocr Soc. 2022; 6(6): bvac050. doi: 10.1210/jendso/bvac050. Erratum in: J Endocr Soc. 2022;7(1): bvac177.

32. Armeni E, Kopanos S, Verykouki E, et al. The severity of menopausal symptoms is associated with diabetes, and cardiometabolic risk factors in middle-aged women. Minerva Endocrinol (Torino). 2023. doi: 10.23736/S2724-6507.23.03905-2. Epub ahead of print. PMID: 37671810.

33. Ramezankhani A, Azizi F, Hadaegh F. Gender differences in changes in metabolic syndrome status and its components and risk of cardiovascular disease: a longitudinal cohort study. Cardiovasc Diabetol. 2022; 21(1):227. doi: 10.1186/s12933-022-01665-8.

34. Khan SH, Sobia F, Niazi NK, et al. Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance. Diabetol. Metab. Syndr. 2018;10: 74. doi: 10.1186/s13098-018-0376-8.

35. Tao LC, Xu JN, Wang TT, et al. Triglyceride-glucose index as a marker in cardiovascular diseases: landscape and limitations. Cardiovasc Diabetol. 2022; 21(1):68. doi: 10.1186/s12933-022-01511-x.

36. Lee JH, Heo SJ, Kwon YJ. Sex-Specific Comparison Between Triglyceride Glucose Index and Modified Triglyceride Glucose Indices to Predict New-Onset Hypertension in Middle-Aged and Older Adults. J Am Heart Assoc. 2023;12(18): e030022. doi: 10.1161/JAHA.123.030022.

37. Son DH, Lee HS, Lee YJ, Lee JH, Han JH. Comparison of triglyceride-glucose index and HOMA-IR for predicting prevalence and incidence of metabolic syndrome. Nutr Metab Cardiovasc Dis. 2022;32(3):596-604. doi: 10.1016/j.numecd.2021.11.017.

38. Khan SH, Sobia F, Niazi NK, et al. Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance. Diabetol. Metab. Syndr. 2018;10: 74. doi: 10.1186/s13098-018-0376-8.].

39. Park HM, Lee HS, Lee YJ, Lee JH. The triglyceride-glucose index is a more powerful surrogate marker for predicting the prevalence and incidence of type 2 diabetes mellitus than the homeostatic model assessment of insulin resistance. Diabetes Res Clin Pract. 2021; 180:109042. doi: 10.1016/j.diabres.2021.109042.

40. Er LK, Wu S, Chou HH, et al. Triglyceride Glucose-Body Mass Index Is a Simple and Clinically Useful Surrogate Marker for Insulin Resistance in Nondiabetic Individuals. PLoS One. 2016;11(3): e0149731. doi: 10.1371/journal.pone.0149731.

41. Alberti KGMM, Eckel RH, Grundy SM, et al. Harmonizing the Metabolic Syndrome. Circulation. 2009;120(16):1640-1645. doi:10.1161/CIRCULATIONAHA.109.192644

42. Kytikova OY, Antonyuk MV, Kantur TA, Novgorodtseva TP, Denisenko YK. Prevalence and biomarkers in metabolic syndrome. Obesity and metabolism. 2021;18(3):302-312. (In Russ.) doi:10.14341/omet12704.

43. Stevenson JC, Tsiligiannis S, Panay N. Cardiovascular Risk in Perimenopausal Women. Curr Vasc Pharmacol. 2019; 17(6):591-594. doi: 10.2174/1570161116666181002145340.

44. Lau ES, Michos ED. Blood Pressure Trajectories Through the Menopause Transition: Different Paths, Same Journey. Circulation Research. 2022;130(3):323-325. doi:10.1161/CIRCRESAHA.122.320664.

45. Karvonen-Gutierrez C, Kim C. Association of Mid-Life Changes in Body Size, Body Composition and Obesity Status with the Menopausal Transition. Healthcare (Basel). 2016;4(3):42. doi: 10.3390/healthcare4030042.

46. Nappi RE, Chedraui P, Lambrinoudaki I, Simoncini T. Menopause: a cardiometabolic transition. Lancet Diabetes Endocrinol. 2022; 10(6):442-456. doi: 10.1016/S2213-8587(22)00076-6.

47. Ryczkowska K, Adach W, Janikowski K, Banach M, Bielecka-Dabrowa A. Menopause and women's cardiovascular health: is it really an obvious relationship? Arch Med Sci. 2022; 19(2):458-466. doi: 10.5114/aoms/157308.

48. Zhang C, Zhao M, Li Z, Song Y. Follicle-Stimulating Hormone Positively Associates with Metabolic Factors in Perimenopausal Women. Int J Endocrinol. 2020:7024321. doi: 10.1155/2020/7024321

49. Veldhuis-Vlug AG, Woods GN, Sigurdsson S, et al. Serum FSH Is Associated With BMD, Bone Marrow Adiposity, and Body Composition in the AGES-Reykjavik Study of Older Adults. J Clin Endocrinol Metab. 2021; 106(3): e1156-e1169. doi: 10.1210/clinem/dgaa922.

50. Tepper PG, Randolph JF Jr, McConnell DS, et al. Trajectory clustering of estradiol and follicle-stimulating hormone during the menopausal transition among women in the Study of Women's Health across the Nation (SWAN). J Clin Endocrinol Metab. 2012; 97(8):2872-80. doi: 10.1210/jc.2012-1422.

51. Costa R, Tuomainen TP, Virtanen J, Niskanen L, Bertone-Johnson E. Associations of reproductive factors with postmenopausal follicle stimulating hormone. Womens Midlife Health. 2022;8(1):8. doi: 10.1186/s40695-022-00079-6.

52. Lou Z, Huang Y, Lan Y, et al. Relationship between years since menopause and lipid variation in postmenopausal women: A cross-sectional study. Medicine (Baltimore). 2023; 102(2): e32684. doi: 10.1097/MD.0000000000032684.

53. Dai Q, Wu S, Cao Z, et al. Trajectories of lipids around the menopause transition in Chinese women: results of the Kailuan cohort study. Fertil Steril. 2023;119(6):1057-1067. doi: 10.1016/j.fertnstert.2023.02.016.

54. Sharma J, McAlister J, Aggarwal NR, et al. Evaluation and management of blood lipids through a woman's life cycle. Am J Prev Cardiol. 2022; 10:100333. doi: 10.1016/j.ajpc.2022.100333.

55. Kautzky-Willer A, Leutner M, Abrahamian H, et al. Geschlechtsspezifische Aspekte bei Prädiabetes und Diabetes mellitus – klinische Empfehlungen (Update 2023) [Sex and gender-specific aspects in prediabetes and diabetes mellitus-clinical recommendations (Update 2023)]. Wien Klin Wochenschr. 2023;135(Suppl 1):275-285. German. doi: 10.1007/s00508-023-02185-5.

56. Xing Z, Kirby R, Alman A. Association of age at menopause with type 2 diabetes mellitus in postmenopausal women in the United States: National Health and Nutrition Examination Survey 2011–2018. Menopause Review/Przegląd Menopauzalny. 2022; 21(4):229-235. doi:10.5114/pm.2022.123514.

57. Seghieri M, Tricò D, Natali A. The impact of triglycerides on glucose tolerance: Lipotoxicity revisited. Diabetes Metab. 2017; 43(4):314-322. doi: 10.1016/j.diabet.2017.04.010.

58. Agarwal T, Lyngdoh T, Dudbridge F, et al. Causal relationships between lipid and glycemic levels in an Indian population: A bidirectional Mendelian randomization approach. PLoS One. 2020;15(1): e0228269. doi: 10.1371/journal.pone.0228269.

59. Yu W, Zhou G, Fan B, et al. Temporal sequence of blood lipids and insulin resistance in perimenopausal women: the study of women's health across the nation. BMJ Open Diabetes Res Care. 2022;10(2): e002653. doi: 10.1136/bmjdrc-2021-002653.

60. Fonseca JNC, Rocha TPO, Nogueira IAL, et al. Metabolic Syndrome and Insulin Resistance by HOMA-IR in Menopause. Int. J. Cardiovasc. Sci. 2018;31(3):201-8. doi:10.5935/2359-4802.20180009.

61. Iozzo P, Beck-Nielsen H, Laakso M, Smith U, Yki-Järvinen H, Ferrannini E. Independent influence of age on basal insulin secretion in nondiabetic humans. European Group for the Study of Insulin Resistance. J Clin Endocrinol Metab. 1999;84(3):863-8. doi: 10.1210/jcem.84.3.5542.

62. Oya J, Nakagami T, Yamamoto Y, et al. Effects of age on insulin resistance and secretion in subjects without diabetes. Intern Med. 2014;53(9):941-7. doi: 10.2169/internalmedicine.53.1580.

63. Kolb H, Kempf K, Martin S. Insulin and aging - a disappointing relationship. Front Endocrinol (Lausanne). 2023; 14:1261298. doi: 10.3389/fendo.2023.1261298.

64. Yang H, Gong R, Liu M, Deng Y, Zheng X, Hu T. HOMA-IR is positively correlated with biological age and advanced aging in the US adult population. Eur J Med Res. 2023; 28(1):470. doi: 10.1186/s40001-023-01448-1.

65. Xu X, Bhagavathula AS, Zhang Y, Ryan PM, Rahmani J, Qi X. Sex Differences in the TyG Index and Cardiovascular Risk Factors in Metabolically Obese Normal Weight Phenotype. Int J Endocrinol. 2022; 2022:1139045. doi: 10.1155/2022/1139045.

66. Simental-Mendía LE, Rodríguez-Morán M, Guerrero-Romero F. The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects. Metab Syndr Relat Disord. 2008;6(4):299-304. doi: 10.1089/met.2008.0034.

67. 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.

68. Moccia P, Belda-Montesinos R, Monllor-Tormos A, Chedraui P, Cano A. Body weight and fat mass across the menopausal transition: hormonal modulators. Gynecol Endocrinol. 2022;38(2):99-104. doi: 10.1080/09513590.2021.2004395.

69. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care, 2004,27(6):1487-95. doi:10.2337/diacare.27.6.1487.

70. Kvandova M, Puzserova A, Balis P. Sexual Dimorphism in Cardiometabolic Diseases: The Role of AMPK. Int J Mol Sci. 2023; 24(15):11986. doi: 10.3390/ijms241511986.

71. Alemany M. Estrogens and the regulation of glucose metabolism. World J Diabetes. 2021;12(10):1622-1654. doi: 10.4239/wjd.v12.i10.1622.

72. Coyoy A, Guerra-Araiza C, Camacho-Arroyo I. Metabolism Regulation by Estrogens and Their Receptors in the Central Nervous System Before and After Menopause. Horm Metab Res. 2016;48(8):489-96. doi: 10.1055/s-0042-110320.

73. Muniyappa R, Chen H, Montagnani M, Sherman A, Quon MJ. Endothelial dysfunction due to selective insulin resistance in vascular endothelium: insights from mechanistic modeling. Am J Physiol Endocrinol Metab. 2020;319(3):E629-E646. doi: 10.1152/ajpendo.00247.2020.

74. Lee DH, Park JE, Kim SY, Jeon HJ, Park JH. Association between the triglyceride-glucose (TyG) index and increased blood pressure in normotensive subjects: a population-based study. Diabetol Metab Syndr. 2022; 14(1):161. doi: 10.1186/s13098-022-00927-5.

75. Lin CH, Wei JN, Fan KC, et al. Different cutoffs of hypertension, risk of incident diabetes and progression of insulin resistance: A prospective cohort study. J Formos Med Assoc. 2022 Jan;121(1 Pt 1):193-201. doi: 10.1016/j.jfma.2021.02.022.

76. Li M, Zhang J, Yang G, et al. Effects of Anterior Pituitary Adenomas' Hormones on Glucose Metabolism and Its Clinical Implications. Diabetes Metab Syndr Obes. 2023; 16:409-424. doi: 10.2147/DMSO.S397445.

77. Park SK, Harlow SD, Zheng H, et al. Association between changes in oestradiol and follicle-stimulating hormone levels during the menopausal transition and risk of diabetes. Diabet Med. 2017;34(4):531-538. doi: 10.1111/dme.13301.

78. El Khoudary SR. Gaps, limitations and new insights on endogenous estrogen and follicle stimulating hormone as related to risk of cardiovascular disease in women traversing the menopause: A narrative review. Maturitas. 2017; 104:44-53. doi: 10.1016/j.maturitas.2017.08.003.

79. He L, Fan B, Li C, Qu Y, Liu Y, Zhang T. Association between Body Mass Index and Diabetes Mellitus Are Mediated through Endogenous Serum Sex Hormones among Menopause Transition Women: A Longitudinal Cohort Study. Int J Environ Res Public Health. 2023;20(3):1831. doi: 10.3390/ijerph20031831.

80. Golubeva JA, Sheptulina AF, Elkina AY, Liusina EO, Kiselev AR, Drapkina OM. Which Comes First, Nonalcoholic Fatty Liver Disease or Arterial Hypertension? Biomedicines. 2023; 11(9):2465. doi: 10.3390/biomedicines11092465.

81. Muniyappa R, Chen H, Montagnani M, Sherman A, Quon MJ. Endothelial dysfunction due to selective insulin resistance in vascular endothelium: insights from mechanistic modeling. Am J Physiol Endocrinol Metab. 2020;319(3):E629-E646. doi: 10.1152/ajpendo.00247.2020.

82. Artunc F, Schleicher E, Weigert C, Fritsche A, Stefan N, Häring HU. The impact of insulin resistance on the kidney and vasculature. Nat Rev Nephrol. 2016; 12(12):721-737. doi: 10.1038/nrneph.2016.145.