PMID- 36205019 OWN - NLM STAT- MEDLINE DCOM- 20230310 LR - 20230402 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 108 IP - 3 DP - 2023 Feb 15 TI - Association of Complement C3 With Incident Type 2 Diabetes and the Mediating Role of BMI: A 10-Year Follow-Up Study. PG - 736-744 LID - 10.1210/clinem/dgac586 [doi] AB - CONTEXT: Impairment of immune and inflammatory homeostasis is reported to be one of the causal factors of diabetes. However, the association of complement C3 levels with incident diabetes in humans remains unclear. OBJECTIVE: This study aimed to examine the association between C3 levels and incident type 2 diabetes mellitus (T2DM), and further explore the potential mediating role of body mass index (BMI) in C3-T2DM associations. METHODS: We determined serum C3 levels of 2662 nondiabetic middle-aged and elderly (64.62 +/- 7.25 years) individuals from the Dongfeng-Tongji cohort at baseline. Cox regression was employed to examine the incidence of T2DM in relationship to C3 levels during 10 years of follow-up. Mediation analysis was further applied to assess potential effect of BMI on the C3-T2DM associations. RESULTS: Overall, 711 (26.7%) participants developed T2DM during 23 067 person-years of follow-up. Higher serum C3 was significantly associated with higher risk of incident T2DM after full adjustment (HR [95% CI] = 1.16 [1.05, 1.27]; per SD higher). Compared with the first quartile of C3 levels, the HR in the fourth quartile was 1.52 (95% CI = [1.14, 2.02]; Ptrend = 0.029). Robust significant linear dose-response relationship was observed between C3 levels and BMI (Poverall < 0.001, Pnonlinear = 0.96). Mediation analyses indicated that BMI might mediate 41.0% of the associations between C3 and T2DM. CONCLUSION: The present prospective study revealed that C3 could be an early biomarker for incident T2DM, and that BMI might play a potential mediating role in the C3-T2DM associations, which provided clues for the pathogenesis of diabetes. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Jiang, Jing AU - Jiang J AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Wang, Hao AU - Wang H AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Liu, Kang AU - Liu K AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. AD - School of Public Health, Guangzhou Medical University, Guangzhou 511436, China. FAU - He, Shiqi AU - He S AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Li, Zhaoyang AU - Li Z AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Yuan, Yu AU - Yuan Y AUID- ORCID: 0000-0001-6932-6920 AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Yu, Kuai AU - Yu K AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Long, Pinpin AU - Long P AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Wang, Jing AU - Wang J AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Diao, Tingyue AU - Diao T AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Zhang, Xiaomin AU - Zhang X AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - He, Meian AU - He M AUID- ORCID: 0000-0002-2096-921X AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Guo, Huan AU - Guo H AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Wu, Tangchun AU - Wu T AUID- ORCID: 0000-0001-9931-5106 AD - Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Complement C3) SB - IM MH - Aged MH - Humans MH - Middle Aged MH - *Body Mass Index MH - *Complement C3/chemistry/metabolism MH - *Diabetes Mellitus, Type 2/diagnosis/metabolism MH - Follow-Up Studies MH - Incidence MH - Prospective Studies MH - Risk Factors OTO - NOTNLM OT - body mass index OT - complement C3 OT - mediation analysis OT - type 2 diabetes EDAT- 2022/10/08 06:00 MHDA- 2023/02/18 06:00 CRDT- 2022/10/07 03:23 PHST- 2022/04/02 00:00 [received] PHST- 2022/10/08 06:00 [pubmed] PHST- 2023/02/18 06:00 [medline] PHST- 2022/10/07 03:23 [entrez] AID - 6751034 [pii] AID - 10.1210/clinem/dgac586 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2023 Feb 15;108(3):736-744. doi: 10.1210/clinem/dgac586.