Advances in obesity and type 2 diabetes mellitus research

doi:10.3877/cma.j.issn.2095-9605.2025.01.009

Abstract

Abstract:

The increasing prevalence of obesity and type 2 diabetes mellitus （T2DM） in modern society is strongly associated.As a major risk factor for T2DM，obesity contributes to disease progression through multiple mechanisms，including adipose tissue fibrosis，activation of adipose tissue macrophage（ATM），secretion of inflammatory cytokines，dysregulation of protein kinase C ε （PKC-ε） signaling，disruptions in amino acid metabolism，and both genetic and environmental influences.Effective weight management strategies，such as lifestyle modifications，pharmacotherapy，and bariatric surgery，play a crucial role in controlling obesity and T2DM.This review summarizes recent advances in elucidating the intricate relationship between obesity and T2DM.

Key words: Obesity, Type 2 diabetes mellitus (T2DM), Insulin resistance, Adipose tissue, Fibrosis, Inflammatory cytokines, Protein kinase C ε (PKC-ε), Amino acid metabolism

Hang Men, Zhou Li, Shuai Han. Advances in obesity and type 2 diabetes mellitus research[J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(01): 62-69.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhfpydxbdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-9605.2025.01.009

https://zhfpydxbdzzz.cma-cmc.com.cn/EN/Y2025/V11/I01/62

Figures/Tables 4

References 61

［1］	Bluher M.Obesity：global epidemiology and pathogenesis ［J］.Nat Rev Endocrinol，2019，15（5）：288-298.
［2］	Phelps NH，Singleton RK，Zhou B，et al.Worldwide trends in underweight and obesity from 1990 to 2022：a pooled analysis of 3663 population-representative studies with 222 million children，adolescents，and adults ［J］.The Lancet，2024，403（10431）：1027-1050.
［3］	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 ［J］.Lancet，2023，402（10397）：203-234.
［4］	Abel ED，Gloyn AL，Evans-Molina C，et al.Diabetes mellitus—Progress and opportunities in the evolving epidemic ［J］.Cell，2024，187（15）：3789-3820.
［5］	Wang T，Lu J，Shi L，et al.Association of insulin resistance and betacell dysfunction with incident diabetes among adults in China：a nationwide，population-based，prospective cohort study ［J］.Lancet Diabetes Endocrinol，2020，8（2）：115-124.
［6］	Gudipaty L，Rosenfeld NK，Fuller CS，et al.Different β-cell secretory phenotype in non-obese compared to obese early type 2 diabetes ［J］.Diabetes Metab Res Rev，2020，36（5）：e3295.
［7］	Pan XF，Wang L，Pan A.Epidemiology and determinants of obesity in China ［J］.Lancet Diabetes Endocrinol，2021，9（6）：373-392.
［8］	Chen K，Shen Z，Gu W，et al.Prevalence of obesity and associated complications in China：A cross-sectional，real-world study in 15.8 million adults ［J］.Diabetes Obes Metab，2023，25（11）：3390-3399.
［9］	陈颖，夏明锋，李小英.体脂分布与糖尿病风险［J］.中华糖尿病杂志，2017（04）：218-220.
［10］	Chai Y，Liu Y，Yang R，et al.Association of body mass index with risk of prediabetes in Chinese adults：A population-based cohort study ［J］.J Diabetes Investig，2022，13（7）：1235-1244.
［11］	Ahmad E，Lim S，Lamptey R，et al.Type 2 diabetes［J］.The Lancet，2022，400（10365）：1803-1820.
［12］	Loos RJF，Yeo GSH.The genetics of obesity：from discovery to biology ［J］.Nature Reviews Genetics，2022，23（2）：120-133.
［13］	Luo M，Yu C，Del PCB，et al.Accelerometer-measured intensityspecific physical activity，genetic risk and incident type 2 diabetes：a prospective cohort study ［J］.Br J Sports Med，2023，57（19）：1257-1264.
［14］	苏青，臧丽.胰岛素抵抗的历史、机制和管理［J］.中华糖尿病杂志，2023（01）：6-13.
［15］	Ruze R，Liu T，Zou X，et al.Obesity and type 2 diabetes mellitus：connections in epidemiology，pathogenesis，and treatments ［J］.Front Endocrinol （Lausanne），2023，14：1161521.
［16］	Speijer D.Oxygen radicals shaping evolution：why fatty acid catabolism leads to peroxisomes while neurons do without it：FADH（2）/NADH flux ratios determining mitochondrial radical formation were crucial for the eukaryotic invention of peroxisomes and catabolic tissue differentiation ［J］.Bioessays，2011，33（2）：88-94.
［17］	Bean C，Audano M，Varanita T，et al.The mitochondrial protein Opa1 promotes adipocyte browning that is dependent on urea cycle metabolites ［J］.Nat Metab，2021，3（12）：1633-1647.
［18］	Bean C，Audano M，Varanita T，et al.Author Correction：The mitochondrial protein Opa1 promotes adipocyte browning that is dependent on urea cycle metabolites ［J］.Nat Metab，2022，4（2）：300.
［19］	Franco LP，Morais CC，Cominetti C.Normal-weight obesity syndrome：diagnosis，prevalence，and clinical implications ［J］.Nutr Rev，2016，74（9）：558-570.
［20］	Jayedi A，Soltani S，Motlagh SZ，et al.Anthropometric and adiposity indicators and risk of type 2 diabetes：systematic review and doseresponse meta-analysis of cohort studies ［J］.BMJ，2022，376：e067516.
［21］	Cao E，Watt MJ，Nowell CJ，et al.Mesenteric lymphatic dysfunction promotes insulin resistance and represents a potential treatment target in obesity ［J］.Nat Metab，2021，3（9）：1175-1188.
［22］	Marcelin G，Gautier EL，Clement K.Adipose Tissue Fibrosis in Obesity：Etiology and Challenges ［J］.Annu Rev Physiol，2022，84：135-155.
［23］	Shen H，Huang X，Zhao Y，et al.The Hippo pathway links adipocyte plasticity to adipose tissue fibrosis ［J］.Nat Commun，2022，13（1）：6030.
［24］	Shoelson SE，Lee J，Goldfine AB.Inflammation and insulin resistance［J］.J Clin Invest，2006，116（7）：1793-1801.
［25］	Lu X，Kong X，Wu H，et al.UBE2M-mediated neddylation of TRIM21 regulates obesity-induced inflammation and metabolic disorders ［J］.Cell Metab，2023，35（8）：1390-1405.
［26］	Lei L M，Lin X，Xu F，et al.Exosomes and Obesity-Related Insulin Resistance ［J］.Front Cell Dev Biol，2021，9：651996.
［27］	周芸，张惠莉.NLRP3炎症小体与胰岛素抵抗的研究进展［J］.临床医学进展，2023，13（6）：9223-9229.
［28］	Qin Q，Shou J，Li M，et al.Stk24 protects against obesity-associated metabolic disorders by disrupting the NLRP3 inflammasome ［J］.Cell Rep，2021，35（8）：109161.
［29］	Pan Y，Hui X，Hoo R，et al.Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation ［J］.J Clin Invest，2019，129（2）：834-849.
［30］	Petersen MC，Madiraju AK，Gassaway BM，et al.Insulin receptor Thr1160 phosphorylation mediates lipid-induced hepatic insulin resistance ［J］.J Clin Invest，2016，126（11）：4361-4371.
［31］	Brandon AE，Liao BM，Diakanastasis B，et al.Protein Kinase C Epsilon Deletion in Adipose Tissue，but Not in Liver，Improves Glucose Tolerance ［J］.Cell Metab，2019，29（1）：183-191.
［32］	Schmitz-Peiffer C.Deconstructing the Role of PKC Epsilon in Glucose Homeostasis［J］.Trends Endocrinol Metab，2020，31（5）：344-356.
［33］	Zheng ZG，Xu YY，Liu WP，et al.Discovery of a potent allosteric activator of DGKQ that ameliorates obesity-induced insulin resistance via the sn-1，2-DAG-PKCε signaling axis ［J］.Cell Metab，2023，35（1）：101-117.
［34］	陆心月，郑旭，王志钢，等.哺乳动物细胞氨基酸转运体及胞内感受机制研究进展［J］.生命科学，2022，34（09）：1155-1167.
［35］	王敏，欧杨，袁祥莲，等.肥胖程度和类型与2型糖尿病患者血清氨基酸关系的差异［J］.中华糖尿病杂志，2024，16（1）：69-76.
［36］	Zhao H，Zhang F，Sun D，et al.Branched-Chain Amino Acids Exacerbate Obesity-Related Hepatic Glucose and Lipid Metabolic Disorders via Attenuating Akt2 Signaling［J］.Diabetes，2020，69（6）：1164-1177.
［37］	Ma QX，Zhu WY，Lu XC，et al.BCAA-BCKA axis regulates WAT browning through acetylation of PRDM16 ［J］.Nat Metab，2022，4（1）：106-122.
［38］	Zhou Q，Sun WW，Chen JC，et al.Phenylalanine impairs insulin signaling and inhibits glucose uptake through modification of IRβ ［J］.Nat Commun，2022，13（1）：4291.
［39］	Aminian A，Kashyap SR，Wolski KE，et al.Patient-reported outcomes after metabolic surgery versus medical therapy for diabetes：Insights from the STAMPEDE randomized trial ［J］.Ann Surg，2021，274（3）：524-532.
［40］	Vahtera V，Pajarinen J，Kivimäki M，et al.Cohort study on incidence of new-onset type 2 diabetes in patients after bariatric surgery and matched controls ［J］.Br J Surg，2024，111（4）：znae105.
［41］	Elmaleh-Sachs A，Schwartz JL，Bramante CT，et al.Obesity management in adults：A review ［J］.JAMA，2023，330（20）：2000-2015.
［42］	Lingvay I，Sumithran P，Cohen RV，et al.Obesity management as a primary treatment goal for type 2 diabetes：time to reframe the conversation ［J］.Lancet，2022，399（10322）：394-405.
［43］	Perdomo CM，Cohen RV，Sumithran P，et al.Contemporary medical，device，and surgical therapies for obesity in adults ［J］.Lancet，2023，401（10382）：1116-1130.
［44］	Jiang C，Cifu AS，Sam S.Obesity and weight management for prevention and treatment of type 2 diabetes ［J］.JAMA，2022，328（4）：389-390.
［45］	Qian J，Xiao Q，Walkup MP，et al.Association of timing of moderateto-vigorous physical activity with changes in glycemic control over 4 years in adults with type 2 diabetes from the look AHEAD trial ［J］.Diabetes Care，2023，46（7）：1417-1424.
［46］	Lean M，Leslie WS，Barnes AC，et al.Durability of a primary careled weight-management intervention for remission of type 2 diabetes：2-year results of the DiRECT open-label，cluster-randomised trial ［J］.Lancet Diabetes Endocrinol，2019，7（5）：344-355.
［47］	Boutari C，Demarsilis A，Mantzoros CS.Obesity and diabetes ［J］.Diabetes Research and Clinical Practice，2023，202：110773.
［48］	Garvey WT，Batterham RL，Bhatta M，et al.Two-year effects of semaglutide in adults with overweight or obesity：the STEP 5 trial ［J］.Nature Medicine，2022，28（10）：2083-2091.
［49］	Pratley RE，Aroda VR，Lingvay I，et al.Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes （SUSTAIN 7）：a randomised，open-label，phase 3b trial［J］.Lancet Diabetes Endocrinol，2018，6（4）：275-286.
［50］	Jastreboff AM，Aronne LJ，Ahmad NN，et al.Tirzepatide once weekly for the treatment of obesity ［J］.N Engl J Med，2022，387（3）：205-216.
［51］	Gao L，Lee BW，Chawla M，et al.Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region：the SURPASS-AP-Combo trial ［J］.Nat Med，2023，29（6）：1500-1510.
［52］	Jensen SBK，Blond MB，Sandsdal RM，et al.Healthy weight loss maintenance with exercise，GLP-1 receptor agonist，or both combined followed by one year without treatment：a post-treatment analysis of a randomised placebo-controlled trial ［J］.eClinicalMedicine，2024：102475.
［53］	Tsagkaraki E，Nicoloro SM，Desouza T，et al.CRISPR-enhanced human adipocyte browning as cell therapy for metabolic disease ［J］.Nat Commun，2021，12（1）：6931.
［54］	Horn DB，Almandoz JP，LookM.What is clinically relevant weight loss for your patients and how can it be achieved？ A narrative review［J］.Postgrad Med，2022，134（4）：359-375.
［55］	Courcoulas A P，Patti M E，Hu B，et al.Long-term outcomes of medical management vs bariatric surgery in type 2 diabetes ［J］.JAMA，2024，331（8）：654-664.
［56］	Mingrone G，Panunzi S，De Gaetano A，et al.Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes：10-year follow-up of an open-label，single-centre，randomised controlled trial ［J］.Lancet，2021，397（10271）：293-304.
［57］	中国医师协会外科医师分会肥胖和糖尿病外科医师委员会，中国肥胖代谢外科研究协作组.中国肥胖代谢外科数据库：2022年度报告［J/CD］.中华肥胖与代谢病电子杂志，2023，9（2）：83-91.
［58］	Eisenberg D，Shikora SA，Aarts E，et al.2022 American Society of Metabolic and Bariatric Surgery （ASMBS） and International Federation for the Surgery of Obesity and Metabolic Disorders （IFSO）Indications for Metabolic and Bariatric Surgery ［J］.Obes Surg，2023，33（1）：3-14.
［59］	李威杰，秦晓光，毛忠琦，等.单吻合口胃旁路术的研究进展［J］.中华消化外科杂志，2022（11）：1403-1408.
［60］	Ruban A，Miras AD，Glaysher MA，et al.Duodenal-jejunal bypass liner for the management of type 2 diabetes mellitus and obesity：a multicenter randomized controlled trial ［J］.Ann Surg，2022，275（3）：440-447.
［61］	刘毓，杨豪俊，汤黎明，等.内镜下减重手术的研究进展［J］.实用临床医药杂志，2022，26（22）：139-143.

[1]	Society for Integrated Health of Metabolic and Bariatric Surgery Chinese, Society for Metabolic and Bariatric Surgery Chinese, Obesity and Metabolic Surgery Collaborative Chinese. Chinese expert consensus on medical knowledge dissemination in metabolic and bariatric surgery（2024 edition） [J]. Chinese Archives of General Surgery(Electronic Edition), 2025, 19(01): 1-8.
[2]	Jiajie Lu, Shuai Yan, Weihua Cai, Jinzhu Wu. Analysis of the related factors of weight rebound after sleeve gastrectomy in patients with obesity [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2025, 19(03): 349-352.
[3]	Lixia Zhao, Chunxia Wang, Yifeng Chen, Dongping Hu, Weisheng Zhang, Tao Wang, Honglai Zhang. Effects of visceral obesity on early complications after laparoscopic radical resection for rectal cancer [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2025, 19(01): 35-39.
[4]	Lingkai Meng, Dayong Li, Ning Wang, Guiming Wang, Bingnan Zhang, Ruotong Li, Lifeng Pan. Effect and mechanism of sleeve gastrectomy on obese rats with type 2 diabetes mellitus [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(06): 638-642.
[5]	Peiyu Gu, Lei Cao, Chengying Liu, Liqiang Cao, Jie Li, Xiaowen Wang. Mechanism analysis of IR-780 inhibits idiopathic pulmonary fibrosis by regulating glycolytic process [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2025, 18(01): 8-14.
[6]	Bokai Cheng, Guang Yang. Progress of research on application of hyperinsulinemic-euglycemic clamp technique for assessing insulin resistance in patients with chronic kidney disease [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(06): 334-339.
[7]	Jiana Shi, Linyan Qian, Kaiyue Ji, Jinwen Qi, Qing Hu, Jiabin Sun. Discussion of application of traditional Chinese medicine in atherosclerosis from the perspective of browning of white adipose tissue [J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(09): 853-858.
[8]	Hao Li, Qishuai Chen, Fazhu Fei, Ningwei Zhang, Yuandong Li, Shuochen Wang, Bin Ren. Progress in noninvasive diagnosis of liver fibrosis in chronic liver disease [J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(09): 863-867.
[9]	Ruimin Zhang, Hongmei Zhu, Yanjun Liu. Current status and prospects of clinical research on metabolic and bariatric surgery in China [J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(01): 1-10.
[10]	Yuan Zhang, Zhongyang Zhang, Jiebin Xie, Dianyuan Liang, Zhenghang Yu, Yixing Ren. The mechanism of action and research progress of novel anti-obesity medications [J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(01): 11-18.
[11]	Wenbo Wang, Yaoquan Cao, Liyong Zhu. Recent developments in novel anti-obesity medications [J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(01): 19-25.
[12]	Mengdie Li, Yong Wang. Prospects of Tirzepatide in optimizing metabolic and bariatric surgery [J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(01): 26-32.
[13]	Yujia Song, Hua Meng. Clinical research status and progress of novel anti-obesity medications targeting nutrient-stimulatory hormone receptors [J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(01): 33-39.
[14]	He Wang, Mengjie Hu, Tianai Wang, Zixuan Mei, Cheng Gong, Dingyu Pan, Zhen Li. Progress in the application of novel anti-obesity medications in the treatment of obesity [J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(01): 40-45.
[15]	Chang Zhang, Kunming Zhou, Zhenya Huang, Hongru Sun, Hongwei Lin. Utilization of a transumbilical horizontal incision according to umbilical anatomy in single-incision laparoscopic bariatric surgery [J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(01): 46-52.

Please choose a citation manager

Content to export