The Dual Role of Adiponectin and Leptin in Type 2 Diabetes

Main Article Content

Muna Sadeq Hameed
Manal F. AL-Khakani

Keywords

Insulin Resistance, Adiponectin, Leptin, Type 2 diabetes mellitus, Biomarkers

Abstract

Type 2 diabetes mellitus (T2DM), a prevalent metabolic condition, is characterised by insulin resistance and inadequate insulin secretion, which leads to elevated blood sugar levels. Adipose tissue secretes two hormones called adiponectin and leptin., play significant roles in metabolic regulation. In this work, the role of leptin and adiponectin in the pathogenesis of type 2 diabetes is examined. The study included 90 participants, comprising of 30 healthy individuals and 60 patients with T2DM, were selected. Clinical and demographic data were collected, and Various parameters were assessed through the analysis of blood samples.. T2DM patients exhibited lower adiponectin levels and higher leptin levels compared to healthy controls. Additionally, they demonstrated higher levels of parameters measured in blood samples, including fasting blood glucose (FBG), insulin levels, HOMA-IR (Homeostatic Model Assessment of Insulin Resistance), total cholesterol (TC), triglycerides (TG), LDL cholesterol (LDL-C), and lower levels of HDL cholesterol (HDL-C). Age, body mass index (BMI), leptin, FBG, HOMA-IR, total cholesterol, triglycerides, and LDL-c all had favourable relationships with adiponectin. Conversely, it exhibited a negative correlation with high-density lipoprotein levels. Leptin correlated positively with age, BMI, adiponectin, insulin, and HOMA-IR. Adiponectin and leptin hold potential as diagnostic markers for T2DM. Understanding their interactions is crucial for developing targeted therapies and effective type 2 diabetes mellitus management.

Abstract 322 | pdf Downloads 207

References

1. Acar, E. M., Ilter, N., & Elbeg, S. (2019). Association of Leptin, Resistin, and High-Molecular-Weight Adiponectin Levels with Psoriasis Area and Severity Index Scores, Obesity, and Insulin Resistance in Psoriasis Patients. Dermatologica Sinica, 37(1), 33. https://doi.org/10.4103/DS.DS_9_18
2. Ahmad, H., Ahmed, Z., Kashif, S., Liaqat, S., & Afreen, A. (2022). Study of metabolic syndrome indicators in newly diagnosed diabetes mellitus type 2 patients in Pakistani population. Nutrition and Health. https://doi.org/10.1177/02601060221144140/SUPPL_FILE/SJ-DOCX-1-NAH-10.1177_02601060221144140.DOCX
3. An, J., Nichols, G. A., Qian, L., Munis, M. A., Harrison, T. N., Li, Z., Wei, R., Weiss, T., Rajpathak, S., & Reynolds, K. (2021). Prevalence and incidence of microvascular and macrovascular complications over 15 years among patients with incident type 2 diabetes. BMJ Open Diabetes Research and Care, 9(1), e001847. https://doi.org/10.1136/BMJDRC-2020-001847
4. Bae, J. C., Cho, N. H., Kim, J. H., Hur, K. Y., Jin, S. M., & Lee, M. K. (2020). Association of Body Mass Index with the Risk of Incident Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality: A Community-Based Prospective Study. Endocrinology and Metabolism, 35(2), 416. https://doi.org/10.3803/ENM.2020.35.2.416
5. Bidulescu, A., Dinh, P. C., Sarwary, S., Forsyth, E., Luetke, M. C., King, D. B., Liu, J., Davis, S. K., & Correa, A. (2020). Associations of leptin and adiponectin with incident type 2 diabetes and interactions among African Americans: The Jackson heart study. BMC Endocrine Disorders, 20(1), 1–11. https://doi.org/10.1186/S12902-020-0511-Z/TABLES/4
6. Bilovol, O. M., Knyazkova, I. I., Al-Travneh, O. V., Bogun, M. V., & Berezin, A. E. (2020). Altered adipocytokine profile predicts early stage of left ventricular remodeling in hypertensive patients with type 2 diabetes mellitus. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14(2), 109–116. https://doi.org/10.1016/J.DSX.2020.01.011
7. Blüher, M., & Mantzoros, C. S. (2015). From leptin to other adipokines in health and disease: Facts and expectations at the beginning of the 21st century. Metabolism, 64(1), 131–145. https://doi.org/10.1016/J.METABOL.2014.10.016
8. Faber, C. L., Deem, J. D., Phan, B. A., Doan, T. P., Ogimoto, K., Mirzadeh, Z., Schwartz, M. W., & Morton, G. J. (2021). Leptin receptor neurons in the dorsomedial hypothalamus regulate diurnal patterns of feeding, locomotion, and metabolism. ELife, 10, 1–14. https://doi.org/10.7554/ELIFE.63671
9. Festa, A., D’Agostino, R., Howard, G., Mykkänen, L., Tracy, R. P., & Haffner, S. M. (2000). Chronic subclinical inflammation as part of the insulin resistance syndrome: The insulin resistance atherosclerosis study (IRAS). Circulation, 102(1), 42–47. https://doi.org/10.1161/01.CIR.102.1.42
10. Gdsteinol, N., Haim, Y., Mattar, P., Hadadi-Bechor, S., Maixner, N., Kovacs, P., Blüher, M., & Rudich, A. (2019). Leptin stimulates autophagy/lysosome-related degradation of long-lived proteins in adipocytes. Adipocyte, 8(1), 51–60. https://doi.org/10.1080/21623945.2019.1569447
11. González-González, J. G., Violante-Cumpa, J. R., Zambrano-Lucio, M., Burciaga-Jimenez, E., Castillo-Morales, P. L., Garcia-Campa, M., Solis, R. C., González-Colmenero, A. D., & Rodríguez-Gutiérrez, R. (2022). HOMA-IR as a predictor of Health Outcomes in Patients with Metabolic Risk Factors: A Systematic Review and Meta-analysis. High Blood Pressure and Cardiovascular Prevention, 29(6), 547–564. https://doi.org/10.1007/S40292-022-00542-5/METRICS
12. Jiménez-Cortegana, C., Hontecillas-Prieto, L., García-Domínguez, D. J., Zapata, F., Palazón-Carrión, N., Sánchez-León, M. L., Tami, M., Pérez-Pérez, A., Sánchez-Jiménez, F., Vilariño-García, T., de la Cruz-Merino, L., & Sánchez-Margalet, V. (2022). Obesity and Risk for Lymphoma: Possible Role of Leptin. International Journal of Molecular Sciences 2022, Vol. 23, Page 15530, 23(24), 15530. https://doi.org/10.3390/IJMS232415530
13. Kaur, J. (2014). A comprehensive review on metabolic syndrome. Cardiology Research and Practice, 2014. https://doi.org/10.1155/2014/943162
14. Lee, C. H., Lui, D. T. W., Cheung, C. Y. Y., Fong, C. H. Y., Yuen, M. M. A., Chow, W. S., Woo, Y. C., Xu, A., & Lam, K. S. L. (2020). Higher Circulating Adiponectin Concentrations Predict Incident Cancer in Type 2 Diabetes – The Adiponectin Paradox. The Journal of Clinical Endocrinology & Metabolism, 105(4), e1387–e1396. https://doi.org/10.1210/CLINEM/DGAA075
15. Li, X., Liao, M., Shen, R., Zhang, L., Hu, H., Wu, J., Wang, X., Qu, H., Guo, S., Long, M., & Zheng, H. (2018). Plasma Asprosin Levels Are Associated with Glucose Metabolism, Lipid, and Sex Hormone Profiles in Females with
Metabolic-Related Diseases. Mediators of Inflammation, 2018. https://doi.org/10.1155/2018/7375294
16. Li, Y., Feng, D., Esangbedo, I. C., Zhao, Y., Han, L., Zhu, Y., Fu, J., Li, G., Wang, D., Wang, Y., Li, M., Gao, S., & Willi, S. M. (2020). Insulin resistance, beta-cell function, adipokine profiles and cardiometabolic risk factors among Chinese youth with isolated impaired fasting glucose versus impaired glucose tolerance: the BCAMS study. BMJ Open Diabetes Research and Care, 8(1), e000724. https://doi.org/10.1136/BMJDRC-2019-000724
17. Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Ranganathan, S., Kern, P. A., & Friedman, J. M. (1995). Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Medicine 1995 1:11, 1(11), 1155–1161. https://doi.org/10.1038/nm1195-1155
18. Magliano, D. J., Sacre, J. W., Harding, J. L., Gregg, E. W., Zimmet, P. Z., & Shaw, J. E. (2020). Young-onset type 2 diabetes mellitus - implications for morbidity and mortality. Nature Reviews. Endocrinology, 16(6), 321–331. https://doi.org/10.1038/S41574-020-0334-Z
19. Meier-Kriesche, H. U., Arndorfer, J. A., & Kaplan, B. (2002). The impact of body mass index on renal transplant outcomes: a significant independent risk factor for graft failure and patient death. Transplantation, 73(1), 70–74. https://doi.org/10.1097/00007890-200201150-00013
20. Osei, K., Gaillard, T., & Schuster, D. (2005). Plasma Adiponectin Levels in High Risk African-Americans with Normal Glucose Tolerance, Impaired Glucose Tolerance, and Type 2 Diabetes**. Obesity Research, 13(1), 179–185. https://doi.org/10.1038/OBY.2005.23
21. Owecki, M., Miczke, A., Nikisch, E., Pupek-Musialik, D., & Sowiski, J. (2011). Serum resistin concentrations are higher in human obesity but independent from insulin resistance. Experimental and Clinical Endocrinology and Diabetes, 119(2), 117–121. https://doi.org/10.1055/S-0030-1263111/ID/42
22. Özkan, E. A., Sadigov, A., & Öztürk, O. (2022). Evaluation of Serum Omentin-1, Vaspin, Leptin, Adiponectin Levels in Obese/Overweight Children and Their Relationship With Non-Alcoholic Fatty Liver Disease. Clinical Nutrition Research, 11(3), 194. https://doi.org/10.7762/CNR.2022.11.3.194
23. Pannacciulli, N., Vettor, R., Milan, G., Granzotto, M., Catucci, A., Federspil, G., De Giacomo, P., Giorgino, R., & De Pergola, G. (2003). Anorexia Nervosa Is Characterized by Increased Adiponectin Plasma Levels and Reduced Nonoxidative Glucose Metabolism. The Journalof Clinical Endocrinology & Metabolism, 88(4), 1748–1752. https://doi.org/10.1210/JC.2002-021215
24. Papargyri, P., Zapanti, E., Salakos, N., Papargyris, L., Bargiota, A., & Mastorakos, G. (2018). Links between HPA axis and adipokines: clinical implications in paradigms of stress-related disorders. Https://Doi.Org/10.1080/17446651.2018.1543585, 13(6), 317–332. https://doi.org/10.1080/17446651.2018.1543585
25. Patti, M. E., & Kahn, B. B. (2004). Nutrient sensor links obesity with diabetes risk. Nature Medicine 2004 10:10, 10(10), 1049–1050. https://doi.org/10.1038/nm1004-1049
26. Reinehr, T., Roth, C., Menke, T., & Andler, W. (2004). Adiponectin before and after Weight Loss in Obese Children. The Journal of Clinical Endocrinology & Metabolism, 89(8), 3790–3794. https://doi.org/10.1210/JC.2003-031925
27. Samuel, V. T., Petersen, M. C., Gassaway, B. M., Vatner, D. F., Rinehart, J., & Shulman, G. I. (2019). Considering the Links Between Nonalcoholic Fatty Liver Disease and Insulin Resistance: Revisiting the Role of Protein Kinase C ε. Hepatology, 70(6), 2217–2220. https://doi.org/10.1002/HEP.30829
28. Sarwar, N., Aspelund, T., Eiriksdottir, G., Gobin, R., Seshasai, S. R. K., Forouhi, N. G., Sigurdsson, G., Danesh, J., & Gudnason, V. (2010). Markers of Dysglycaemia and Risk of Coronary Heart Disease in People without Diabetes: Reykjavik Prospective Study and Systematic Review. PLOS Medicine, 7(5), e1000278. https://doi.org/10.1371/JOURNAL.PMED.1000278
29. Segal, K. R., Landt, M., & Klein, S. (1996). Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes, 45(7), 988–991. https://doi.org/10.2337/DIAB.45.7.988
30. Stasevich, E. M., Zheremyan, E. A., Kuprash, D. V., & Schwartz, A. M. (2023). Interaction Between Adipocytes and B Lymphocytes in Human Metabolic Diseases. Biochemistry (Moscow), 88(2), 280–288. https://doi.org/10.1134/S0006297923020104/METRICS
31. Stefan, N., & Häring, H. U. (2011). The Metabolically Benign and Malignant Fatty Liver. Diabetes, 60(8), 2011–2017. https://doi.org/10.2337/DB11-0231
32. Takeda, Y., Matoba, K., Sekiguchi, K., Nagai, Y., Yokota, T., Utsunomiya, K., & Nishimura, R. (2020). Endothelial Dysfunction in Diabetes. Biomedicines 2020, Vol. 8, Page 182, 8(7), 182. https://doi.org/10.3390/BIOMEDICINES8070182
33. Vivekananda, L., & Faizuddin, M. (2019). Effect of Weight Reduction on the Serum Adiponectin
and Tumor Necrosis Factor-α Levels and the Clinical Parameters of Obese Patients with and without Periodontal Disease. Journal of International Society of Preventive & Community Dentistry, 9(2), 166. https://doi.org/10.4103/JISPCD.JISPCD_447_18
34. Von Frankenberg, A. D., Reis, A. F., & Gerchman, F. (2017). Relationships between adiponectin levels, the metabolic syndrome, and type 2 diabetes: a literature review. Archives of Endocrinology and Metabolism, 61(6), 614–622. https://doi.org/10.1590/2359-3997000000316
35. Waki, H., Yamauchi, T., Kamon, J., Ito, Y., Uchida, S., Kita, S., Hara, K., Hada, Y., Vasseur, F., Froguel, P., Kimura, S., Nagai, R., & Kadowaki, T. (2003). Impaired Multimerization of Human Adiponectin Mutants Associated with Diabetes. Journal of Biological Chemistry, 278(41), 40352–40363. https://doi.org/10.1074/jbc.m300365200
36. Waldman, B., Investigators, on behalf of the F. S., Jenkins, A. J., Investigators, on behalf of the F. S., Davis, T. M. E., Investigators, on behalf of the F. S., Taskinen, M.-R., Investigators, on behalf of the F. S., Scott, R., Investigators, on behalf of the F. S., O’Connell, R. L., Investigators, on behalf of the F. S., Gebski, V. J., Investigators, on behalf of the F. S., Ng, M. K. C., Investigators, on behalf of the F. S., Keech, A. C., & Investigators, on behalf of the F. S. (2014). HDL-C and HDL-C/ApoA-I Predict Long-Term Progression of Glycemia in Established Type 2 Diabetes. Diabetes Care, 37(8), 2351–2358. https://doi.org/10.2337/DC13-2738
37. Wang, X., Bao, W., Liu, J., Ouyang, Y. Y., Wang, D., Rong, S., Xiao, X., Shan, Z. L., Zhang, Y., Yao, P., & Liu, L. G. (2013). Inflammatory Markers and Risk of Type 2 DiabetesA systematic review and meta-analysis. Diabetes Care, 36(1), 166–175. https://doi.org/10.2337/DC12-0702
38. Weyer, C., Funahashi, T., … S. T.-T. J. of, & 2001, undefined. (n.d.). Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. Academic.Oup.Com. Retrieved May 11, 2023, from https://academic.oup.com/jcem/article-abstract/86/5/1930/2848024
39. Weyer, C., Funahashi, T., Tanaka, S., Hotta, K., Matsuzawa, Y., Pratley, R. E., & Tataranni, P. A. (2001). Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. The Journal of Clinical Endocrinology and Metabolism, 86(5), 1930–1935. https://doi.org/10.1210/JCEM.86.5.7463
40. Wu, P., Wen, W., Li, J., Xu, J., Zhao, M., Chen, H., & Sun, J. (2019). Systematic review and meta-analysis of randomized controlled trials on theeffect of SGLT2 Inhibitor on Blood Leptin and Adiponectin Level in Patients with Type 2 Diabetes. Hormone and Metabolic Research, 51(8), 487–494. https://doi.org/10.1055/A-0958-2441/ID/R2018-09-0327-0024
41. Ye, Y., Wu, P., Wang, Y., Yang, X., Ye, Y., Yuan, J., Liu, Y., Song, X., Yan, S., Wen, Y., Qi, X., Yang, C., Liu, G., Lv, C., Pan, X. F., & Pan, A. (2022). Adiponectin, leptin, and leptin/adiponectin ratio with risk of gestational
diabetes mellitus: A prospective nested case-control study among Chinese women. Diabetes Research and Clinical Practice, 191, 110039. https://doi.org/10.1016/J.DIABRES.2022.110039
42. Ylli, D., Sidhu, S., Parikh, T., & Burman, K. D. (2022). Endocrine Changes in Obesity. Perioperative Anesthetic Care of the Obese Patient, 41–49. https://doi.org/10.3109/9781420095319-7