Associations of C-peptide with cardiometabolic parameters in women aged 25–44 years with different metabolic phenotypes

The development of atherosclerotic diseases is pathogenetically associated with an increase in insulin resistance, an indirect marker of which is the C-peptide. In addition, literature data indicate the intrinsic proatherogenic effects of C-peptide. In recent years, the concept of separating metabolically healthy (MHP) and unhealthy phenotype (MUHP) at different body weights has become increasingly widespread. It believed that the key difference between MHP and MUHP is the more pronounced insulin resistance in the latter, but there are no clear data on the association of C-peptide with MHP or MUHP. Aim of the study was to investigate the association of C-peptide level with different metabolic phenotypes in women aged 25–44 years. Material and methods. The study was conducted on the basis of a representative sample of women aged 25–44 years (n = 1513, of which 840 women). The analysis included indicators of 655 women. The definition of MHP and MUHP carried out using the IDF criteria, 2005 for the diagnosis of metabolic syndrome. Anthropometric measurements, biochemical and hormonal blood tests have been carried out in groups divided by the body mass index (BMI). The level of C-peptide was determined by the method of multiplex analysis. Results. C-peptide content in the examined sample was 0.9 [0.5; 1.3] ng/ml (Me [Q1; Q3]), with MHP – 0.8 [0.5; 1.1] ng/ml, with MUHP – 1.3 [0.7; 1.8] ng/ml, p < 0.0001. With an increase in BMI, the median of C-peptide increased both in MHP (from 0.8 [0.4; 1.1] to 1.2 [0.8; 1.7] ng/mL, p_trend < 0.0001) and with MUHP (from 0.8 [0.2; 1.2] to 1.5 [0.9; 2.1] ng/mL, p_trend = 0.006). The frequency of MUHP in the 4th quartile of the C-peptide is 2.7 times higher than in the 1st quartile (p < 0.0001), and the frequency of MHP – 1.6 times lower (p = 0.001). C-peptide content correlated with anthropometric parameters, glucose, lipid concentration, transaminase activity, kidney filtration capacity. A C-peptide level of more than 1.33 in young women indicates a high probability of having MUHP with maximum sensitivity and specificity (Se = 49.3 %, Sp = 85.9 %). Conclusions. In women with MUHP, C-peptide content is 38.5 % higher than in women with MHP. The frequency of MUHP in the 4th quartile of the C-peptide is 3.2 times higher than in the 1st quartile. The level of C-peptide above 1.33 ng/ml is associated with the presence of MUHP.

1. Lee S.H., Park S.Y., Choi C.S. Insulin Resistance: From Mechanisms to Therapeutic Strategies. Diabetes Metab. J., 2022; 46 (1): 15–37. doi: 10.4093/dmj.2021.0280

2. Vejrazkova D., Vankova M., Lukasova P., Vcelak J., Bendlova B. Insights into the physiology of C-peptide. Physiol. Res., 2020; 69 (2): 237–243. doi: 10.33549/physiolres.934519

3. Wahren J. C-peptide and the pathophysiology of microvascular complications of diabetes. J. Intern. Med., 2017; 281 (1): 3–6. doi: 10.1111/joim.12541

4. Hills C.E., Brunskill N.J. Intracellular signalling by C-peptide. Exp. Diabetes Res., 2008; 2008: 635158. doi: 10.1155/2008/635158

5. Harnishsingh B., Rama B. Is C-peptide a predictor of severity of coronary artery disease in metabolic syndrome? An observational study. Indian Heart J., 2018; 70 (3): 105–109. doi: 10.1016/j.ihj.2018.07.005

6. Alves M.T., Ortiz M.M.O., Dos Reis G.V.O.P., Dusse L.M.S., Carvalho M.D.G., Fernandes A.P., Gomes K.B. The dual effect of C-peptide on cellular activation and atherosclerosis: Protective or not? Diabetes Metab. Res. Rev., 2019; 35 (1): e3071. doi: 10.1002/dmrr.3071

7. Mustafina S.V., Vinter D.A., Rymar O.D., Scherbakova L.V., Gafarov V.V., Panov D.O., Gromova E.A., Gafarova A.V., Verevkin E.G., Nikitenko T.I., Bobak M., Malyutina S.K. Obesity phenotypes and the risk of myocardial infarction: a prospective cohort study. Rus. J. Cardiol., 2019; (6): 109–114. (In Russ.) https://doi.org/10.15829/1560-4071-2019-6-109-114]

8. Kozupeeva D.A., Mustafina S.V. Metabolically healthy obesity and atherosclerosis related diseases (scientific review). Ateroscleroz, 2016; 12 (2): 42–47. (In Russ.).

9. Phillips C.M. Metabolically healthy obesity across the life course: epidemiology, determinants, and implications. Ann. NY Acad. Sci., 2017; 1391 (1): 85–100. doi: 10.1111/nyas.13230

10. Borodkina D.A., Gruzdeva O.V., Kvitkova L.V., Barbarash O.L. Is visceral obesity the cause of obesity paradox? Problems of Endocrinology. 2016; 62 (6): 33–39. (In Russ.) https://doi.org/10.14341/probl201662633-39

11. Tsygankova O.V., Nikolaev K.Yu., Fedorova E.L., Bondareva Z.G., Ragino Yu.I., Platonov D.Yu., Pustovetova M.G. Risk factors of cardiovascular diseases. look at the woman. Ateroscleroz, 2014; 10 (1): 44–55. (In Russ.).

12. Levin A., Stevens P.E. Summary of KDIGO 2012 CKD Guideline: Behind the scenes, need for guidance and a framework for moving forward. Kidney Int., 2014; 85: 49–61. doi: 10.1038/ki.2013.444

13. Alberti K.G., Zimmet P., Shaw J. Metabolic syndrome – a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med., 2006; 23 (5): 469–480. doi: 10.1111/j.1464-5491.2006.01858.x

14. Hjelmgren O., Gummesson A., Bergström G., Schmidt C. Beta-Cell Function, Self-rated Health, and Lifestyle Habits in 64-Year-Old Swedish Women with Metabolically Healthy Obesity Phenotype. J. Obes Metab. Syndr., 2020; 29 (1): 39–46. doi: 10.7570/jomes19078

15. Litvinova L.S., Vasilenko M.A., Zatolokin P.A., Aksenova N.N., Fattakhov N.S., Vaysbeyn I.Z., Mironyuk N.I., Kirienkova E.V. Adipokines in metabolic processes regulating during obesity treatment. Diabetes mellitus, 2014; 17 (3): 51–59. (In Russ.) https://doi.org/10.14341/DM2014351-59

16. Chen Z., He J., Ma Q., Xiao M. Association Between C-Peptide Level and Subclinical Myocardial Injury.Endocrinol. (Lausanne), 2021; 12: 680501. doi: 10.3389/fendo.2021.680501

17. Kron V., Verner M., Smetana P., Janoutova J., Janout V., Martinik K. Alterations of glycaemia, insulin resistance and body mass index within the C-peptide optimal range in non-diabetic patients. J. Appl. Biomed., 2020; 18 (4): 136–142. doi: 10.32725/jab.2020.018

18. Knyazev Yu.A., Bespalova V.A. International System of Units SI and conversion factors (main laboratory indicators in endocrinology). Problems of Endocrinology, 2000; 46 (3): 45–48. (In Russ.) https://doi.org/10.14341/probl11853

19. Gonzalez-Mejia M.E., Porchia L.M., Torres-Rasgado E., Ruiz-Vivanco G., Pulido-Pérez P., Báez-Duarte B.G., Pérez-Fuentes R. C-Peptide Is a Sensitive Indicator for the Diagnosis of Metabolic Syndrome in Subjects from Central Mexico. Metab. Syndr. Relat. Disord., 2016; 14 (4): 210–216. doi: 10.1089/met.2015.0067

20. Abdullah A., Hasan H., Raigangar V., Bani-Issa W. C-Peptide versus insulin: relationships with risk biomarkers of cardiovascular disease in metabolic syndrome in young arab females. Int. J. Endocrinol., 2012; 2012: 420792. doi: 10.1155/2012/420792

21. Mahmoodi M.R., Najafipour H. Association of C-peptide and lipoprotein(a) as two predictors with cardiometabolic biomarkers in patients with type 2 diabetes in KERCADR population-based study. PLoS One, 2022; 17 (5): e0268927. doi: 10.1371/journal.pone.0268927

22. Patel N., Taveira T.H., Choudhary G., Whitlatch H., Wu W.C. Fasting serum C-peptide levels predict cardiovascular and overall death in nondiabetic adults. J. Am. Heart Assoc., 2012; 1 (6): e003152. doi: 10.1161/JAHA.112.003152

23. Wang T., Li M., Zeng T., Hu R., Xu Y., Xu M., Zhao Z., Chen Y., Wang S., Lin H., Yu X., Chen G., Su Q., Mu Y., Chen L., Tang X., Yan L., Qin G., Wan Q., Gao Z., Wang G., Shen F., Luo Z., Qin Y., Chen L., Huo Y., Li Q., Ye Z., Zhang Y., Liu C., Wang Y., Wu S., Yang T., Deng H., Zhao J., Shi L., Ning G., Bi Y., Wang W., Lu J. Association between insulin resistance and cardiovascular disease risk varies according to glucose tolerance status: a nationwide prospective cohort study. Diabetes Care, 2022; 45 (8): 1863–1872. doi: 10.2337/dc22-0202

24. Qin J., Sun R., Ding D. Effects of serum C-Peptide level on blood lipid and cardiovascular and cerebrovascular injury in patients with type 2 diabetes mellitus: a meta-analysis. Contrast Media Mol. Imaging, 2022; 2022: 6314435. doi: 10.1155/2022/6314435