Association Between Leptin and Adiponectin Levels and Sarcopenia in Non-Geriatric Type 2 Diabetes Mellitus Patients

Khoirul Husam; Purwita Wijaya Laksmi; Robert Sinto; Andhika Rachman; Rudy Hidayat; Sukamto Koesnoe; Noto Dwimartutie; Dyah Purnamasari

Authors

Khoirul Husam Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia – Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Purwita Wijaya Laksmi Division of Geriatrics, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia – Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Robert Sinto Division of Infection and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia – Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Andhika Rachman Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia – Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Rudy Hidayat Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia – Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Sukamto Koesnoe Division of Allergy and Immunology, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia – Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Noto Dwimartutie Division of Geriatrics, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia – Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Dyah Purnamasari Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia – Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia

Keywords:

diabetes mellitus, sarcopenia, leptin, adiponectin, non-geriatric

Abstract

Background: Type 2 Diabetes Mellitus (T2DM) in young adults is associated with an increased risk of early sarcopenia due to insulin resistance and inflammation. This insulin resistance and inflammation can be influenced by leptin and adiponectin, which are key adipocytokines produced by adipose cells. However, no studies have examined the relationship between leptin, adiponectin levels, and sarcopenia in T2DM patients under 60 years old. This study aimed to investigate the relationship between leptin, adiponectin levels, and Leptin-to-Adiponectin ratio (LAR) with sarcopenia in non-geriatric T2DM patients. Methods: This cross-sectional study was conducted from January 2021 to April 2022. The subjects consisted of T2DM patients aged 18-59 years at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Baseline data were sourced from a primary study, while stored serum samples were analyzed for leptin and adiponectin using ELISA. Leptin and adiponectin differences were assessed statistically using the Mann-Whitney U test, and the Kruskal-Wallis test was used for additional analysis. Results: Among 97 subjects, 4 (4.1%) had sarcopenia, while 34 out of 93 non-sarcopenic subjects belonged to the possible sarcopenia category. Bivariate analysis results showed significant differences between leptin levels (p=0.005) and the Leptin-to-Adiponectin Ratio (LAR) (p=0.003) with sarcopenia in non-geriatric T2DM patients. Meanwhile, adiponectin levels (p=0.799) did not show statistical differences. Further analysis was conducted among three groups, namely sarcopenia, possible sarcopenia, and non-sarcopenia. The result showed statistically significant differences in leptin and LAR levels between sarcopenia and possible sarcopenia (leptin p=0.004; LAR p=0.007) as well as sarcopenia and non-sarcopenia (leptin p=0.038; LAR p=0.011). Conclusion: Leptin levels and LAR were associated with sarcopenia in a non-geriatric T2DM population.

References

Tarigan TJE, Yunir E, Subekti I, et al. Profile and analysis of chronic diabetes complications in the Outpatient Diabetes Clinic of Cipto Mangunkusumo Hospital, Jakarta. Med J Indones. 2015;24(3):156-162.

Mihardja L, Delima D, Massie RGA, et al. Prevalence of kidney dysfunction in diabetes mellitus and associated risk factors among productive age Indonesians. J Diabetes Metab Disord. 2018;17(1):53-61

Wilmot E, Idris I. Early onset type 2 diabetes: risk factors, clinical impact, and management. Ther Adv Chronic Dis. 2014;5(6):234-244

Shafiee G, Keshtkar A, Soltani A, et al. Prevalence of sarcopenia in the world: a systematic review and meta-analysis of general population studies. J Diabetes Metab Disord. 2017;16:21

Indirayani HW, Widjajanti N, Firdausi H. Hubungan defisiensi kalsidiol serum dan derajat sarkopenia pada komunitas usia lanjut di Surabaya. J Penyakit Dalam Indonesia. 2020;7(1):29-33

Bae EJ, Kim YH. Factors affecting sarcopenia in Korean adults by age groups.

Osong Public Health Res Perspect. 2017;8(3):169-178

Jung HN, Jung CH, Hwang YC. Sarcopenia in youth. Metabolism. 2023;144:155557

Shimabukuro M. Leptin resistance and lipolysis of white adipose tissue: an implication to ectopic fat disposition and its consequences. J Atheroscler Thromb. 2017;24(11):1088-1089.

Chen L, Chen R, Wang H, et al. Mechanisms linking inflammation to insulin resistance. Int J Endocrinol. 2015;2015:508409

Zhu J, Guo B, Gan X, et al. Association of circulating leptin and adiponectin with periodontitis: a systematic review and meta-analysis. BMC Oral Health. 2017;17(1):104.

Chen LK, Woo J, Assantachai P, et al. Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment. J Am Med Dir Assoc. 2020;21(3):300-307.e2

Kim TN, Park MS, Yang SJ, et al. Prevalence and determinant factors of sarcopenia in patients with type 2 diabetes: the Korean Sarcopenic Obesity Study (KSOS) [published correction appears in Diabetes Care. 2010;33(10):2294]. Diabetes Care. 2010;33(7):1497-1499. doi:10.2337/dc09-2310

Lin YL, Wang CH, Lai YH, et al. Negative correlation between leptin serum levels and sarcopenia in hemodialysis patients. Int J Clin Exp Pathol. 2018;11(3):1715- 23.

Hsu YT, Lin JY, Lin CJ, et al. Association of possible sarcopenia or sarcopenia with body composition, nutritional intakes, serum vitamin D levels, and physical activity among patients with type 2 diabetes mellitus in Taiwan. Nutrients. 2023;15(18):3892.

Kao TW, Peng TC, Chen WL, et al. Higher serum leptin levels are associated with a reduced risk of sarcopenia but a higher risk of dynapenia among older adults. J Inflamm Res. 2021;14:5817-25.

Yang ZY, Chen WL. Examining the association between serum leptin and sarcopenic obesity. J Inflamm Res. 2021;14:3481-7. doi:10.2147/JIR.S322420

Shimokata H, Ando F, Otsuka R. Longitudinal association between serum adiponectin and sarcopenia in a community-living population. Innov Aging. 2017;1(Suppl 1):1125. doi:10.1093/geroni/igx004.4114

Komici K, Dello Iacono A, De Luca A, et al. Adiponectin and sarcopenia: a systematic review with meta-analysis. Front Endocrinol (Lausanne). 2021;12:633117.

Li CW, Yu K, Shyh-Chang N, et al. Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention. J Cachexia Sarcopenia Muscle. 2019;10(3):586-600.

Can B, Kara O, Kizilarslanoglu MC, et al. Serum markers of inflammation and oxidative stress in sarcopenia. Aging Clin Exp Res. 2017;29:745-52.

Hamrick MW, Herberg S, Arounleut P, et al. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice. Biochem Biophys Res Commun. 2010;400(3):379-83.

Minniti G, Pescinini-Salzedas LM, Minniti GAdS, et al. Organokines, sarcopenia, and metabolic repercussions: the vicious cycle and the interplay with exercise. Int J Mol Sci. 2022;23(21):13452.

Park SW, Goodpaster BH, Strotmeyer ES, et al. Accelerated loss of skeletal muscle strength in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes Care. 2007;30(6):1507-12.

Morigny P, Houssier M, Mouisel E, et al. Adipocyte lipolysis and insulin resistance. Biochimie. 2016;125:259-66.

Kohara K, Ochi M, Tabara Y, et al. Leptin in sarcopenic visceral obesity: possible link between adipocytes and myocytes. PLoS One. 2011;6(9):e24633.

Bungau S, Behl T, Tit DM, et al. Interactions between leptin and insulin resistance in patients with prediabetes, with and without NAFLD. Exp Ther Med. 2020;20(6):197.

Liu C, Feng X, Li Q, et al. Adiponectin, TNF-α, and inflammatory cytokines and risk of type 2 diabetes: a systematic review and meta-analysis. Cytokine. 2016;86:100-9.

Liao PJ, Ting MK, Wu IW, et al. Higher leptin-to-adiponectin ratio strengthens the association between body measurements and the occurrence of type 2 diabetes mellitus. Front Public Health. 2021;9:678-81.

Al-Hamodi Z, Al-Habori M, Al-Meeri A, Saif-Ali R. Association of adipokines, leptin/adiponectin ratio and C-reactive protein with obesity and type 2 diabetes mellitus. Diabetol Metab Syndr. 2014;6(1):99.