Global regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023;402(10397):203–34. https://doi.org/10.1016/S0140-6736(23)01301-6. 

International Diabetes Federation. IDF Diabetes Atlas, 10th edn. Brussels, Belgium. 2021. https://www.diabetesatlas.org/

Byndloss M, Devkota S, Duca F, Niess JH, Nieuwdorp M, Orho-Melander M, et al. The gut microbiota and diabetes: research, translation, and clinical applications − 2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum. Diabetologia. 2023;67(9):1760–82. https://doi.org/10.1007/s00125-024-06198-1.

Article  Google Scholar 

Kao K-T, Sabin MA. Type 2 diabetes mellitus in children and adolescents. Aust Fam Physician. 2016;45(6):401–6.

PubMed  Google Scholar 

Song SH, Frier BM. Young adult-onset type 2 diabetes heralds a poor prognosis. Lancet Diabetes Endocrinol. 2024. https://doi.org/10.1016/S2213-8587(24)00282-1.

Article  PubMed  Google Scholar 

Lu X, Xie Q, Pan X, Zhang R, Zhang X, Peng G, et al. Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy. Signal Transduct Target Ther. 2024;9(1):262. https://doi.org/10.1038/s41392-024-01951-9.

Article  PubMed  PubMed Central  Google Scholar 

Yuge H, Okada H, Hamaguchi M, Kurogi K, Murata H, Ito M, et al. Triglycerides/HDL cholesterol ratio and type 2 diabetes incidence: Panasonic Cohort Study 10. Cardiovasc Diabetol. 2023;22(1):308. https://doi.org/10.1186/s12933-023-02046-5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Desoye G, Herrera E. Adipose tissue development and lipid metabolism in the human fetus: the 2020 perspective focusing on maternal diabetes and obesity. Prog Lipid Res. 2020;81:101082. https://doi.org/10.1016/j.plipres.2020.101082.

Article  CAS  PubMed  Google Scholar 

Khan TA, Field D, Chen V, Ahmad S, Mejia SB, Kahleová H, et al. Combination of multiple low-risk lifestyle behaviors and incident type 2 diabetes: a systematic review and dose-response meta-analysis of prospective cohort studies. Diabetes Care. 2023;46(3):643–56. https://doi.org/10.2337/dc22-1024.

Article  PubMed  PubMed Central  Google Scholar 

Arner P, Langin D. Lipolysis in lipid turnover, cancer cachexia, and obesity-induced insulin resistance. Trends Endocrinol Metab. 2014;25(5):255–62. https://doi.org/10.1016/j.tem.2014.03.002.

Article  CAS  PubMed  Google Scholar 

Nikawa J, Tanabe T, Ogiwara H, Shiba T, Numa S. Inhibitory effects of long-chain acyl coenzyme A analogues on rat liver acetyl coenzyme A carboxylase. FEBS Lett. 1979;102(2):223–6.

Article  CAS  PubMed  Google Scholar 

Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797–835. https://doi.org/10.1097/hep.0000000000000323.

Article  PubMed  PubMed Central  Google Scholar 

Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 2020;122(1):4–22. https://doi.org/10.1038/s41416-019-0650-z.

Article  CAS  PubMed  Google Scholar 

Guo J, Chen S, Zhang Y, Liu J, Jiang L, Hu L, et al. Cholesterol metabolism: physiological regulation and diseases. MedComm (NY). 2024;5(2):e476. https://doi.org/10.1002/mco2.476.

Article  CAS  Google Scholar 

Kim H, Kulkarni RN. Insulin/IGF signaling in islet biology and its therapeutic implications. Endocr Rev. 2026. https://doi.org/10.1210/endrev/bnag014.

Article  PubMed  Google Scholar 

Jaldin-Fincati JR, Pavarotti M, Frendo-Cumbo S, Bilan PJ, Klip A. Update on GLUT4 vesicle traffic: a cornerstone of insulin action. Trends Endocrinol Metab. 2017;28(8):597–611. https://doi.org/10.1016/j.tem.2017.05.002.

Article  CAS  PubMed  Google Scholar 

Leto D, Saltiel AR. Regulation of glucose transport by insulin: traffic control of GLUT4. Nat Rev Mol Cell Biol. 2012;13(6):383–96. https://doi.org/10.1038/nrm3351.

Article  CAS  PubMed  Google Scholar 

Peng J, He L. IRS posttranslational modifications in regulating insulin signaling. J Mol Endocrinol. 2018;60(1):R1–r8. https://doi.org/10.1530/jme-17-0151.

Article  PubMed  Google Scholar 

Jeong I, Kim OK. Pathophysiological roles of obesity-induced alterations in extracellular vesicles derived from adipose tissue and adipocytes. Curr Obes Rep. 2026;15(1):7. https://doi.org/10.1007/s13679-026-00685-9.

Article  PubMed  Google Scholar 

Aguirre LE, Colleluori G, Fowler KE, Jan IZ, Villareal K, Qualls C, et al. High aromatase activity in hypogonadal men is associated with higher spine bone mineral density, increased truncal fat and reduced lean mass. Eur J Endocrinol. 2015;173(2):167–74. https://doi.org/10.1530/eje-14-1103.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Haase J, Weyer U, Immig K, Klöting N, Blüher M, Eilers J, et al. Local proliferation of macrophages in adipose tissue during obesity-induced inflammation. Diabetologia. 2014;57(3):562–71. https://doi.org/10.1007/s00125-013-3139-y.

Article  CAS  PubMed  Google Scholar 

Cai W, Ramdas M, Zhu L, Chen X, Striker GE, Vlassara H. Oral advanced glycation endproducts (AGEs) promote insulin resistance and diabetes by depleting the antioxidant defenses AGE receptor-1 and sirtuin 1. Proc Natl Acad Sci U S A. 2012;109(39):15888–93. https://doi.org/10.1073/pnas.1205847109.

Article  PubMed  PubMed Central  Google Scholar 

Ye L, Liang S, Guo C, Yu X, Zhao J, Zhang H, et al. Inhibition of M1 macrophage activation in adipose tissue by berberine improves insulin resistance. Life Sci. 2016;166:82–91. https://doi.org/10.1016/j.lfs.2016.09.025.

Article  CAS  PubMed  Google Scholar 

Arranz A, Doxaki C, Vergadi E, Martinez de la Torre Y, Vaporidi K, Lagoudaki ED, et al. Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization. Proc Natl Acad Sci USA. 2012;109(24):9517–22. https://doi.org/10.1073/pnas.1119038109.

Article  PubMed  PubMed Central  Google Scholar 

Blasetti Fantauzzi C, Iacobini C, Menini S, Vitale M, Sorice GP, Mezza T, et al. Galectin-3 gene deletion results in defective adipose tissue maturation and impaired insulin sensitivity and glucose homeostasis. Sci Rep. 2020;10(1):20070. https://doi.org/10.1038/s41598-020-76952-z.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim SM, Lun M, Wang M, Senyo SE, Guillermier C, Patwari P, et al. Loss of white adipose hyperplastic potential is associated with enhanced susceptibility to insulin resistance. Cell Metabol. 2014;20(6):1049–58. https://doi.org/10.1016/j.cmet.2014.10.010.

Article  CAS  Google Scholar 

Lee MJ, Kim J. The pathophysiology of visceral adipose tissues in cardiometabolic diseases. Biochem Pharmacol. 2024;222:116116. https://doi.org/10.1016/j.bcp.2024.116116.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hammarstedt A, Gogg S, Hedjazifar S, Nerstedt A, Smith U. Impaired adipogenesis and dysfunctional adipose tissue in human hypertrophic obesity. Physiol Rev. 2018;98(4):1911–41. https://doi.org/10.1152/physrev.00034.2017.

Article  CAS  PubMed  Google Scholar 

E A. Lipid Storage, Lipolysis, and Lipotoxicity in Obesity. Adv Exp Med Biol. 2024;1460:97–129. https://doi.org/10.1007/978-3-031-63657-8_4.

Article  PubMed  Google Scholar 

Whytock KL, Goodpaster BH. Unraveling skeletal muscle insulin resistance: molecular mechanisms and the restorative role of exercise. Circ Res. 2025;137(2):184–204.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Copps KD, Hancer NJ, Opare-Ado L, Qiu W, Walsh C, White MF. Irs1 serine 307 promotes insulin sensitivity in mice. Cell Metab. 2010;11(1):84–92.