Association Between Serum Vitamin A Levels and Long-term Outcome in Patients with T2DM

Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v7i2.5272

Xuepeng Zhang1, Pingchun Li2, Lina Duo3, Ai Zhong4, Manting Wang5, Yilin Wang5, Wei Xiao6, Xuanyi Zhang7, Yan Deng8

1. Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
2. Department of Critical Care Medicine, West China Hospital/West China School of Nursing, Sichuan University, Chengdu 610041, China
3. Department of Critical Care Medicine, West China Tianfu Hospital, Sichuan University, Chengdu, 610041, China
4. Department of Burn and Plastic Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
5. West China Medical School, Sichuan University, Chengdu 610041, China
6. Xi'an International University, Xi'an 710077, China
7. Shenyang City University, Shenyang 110112, China
8. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China; Laboratory of Mitochondria and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, China

Abstract

Previous studies suggest that vitamin A (VA) may exert potential regulatory effects on insulin sensitivity and glucose metabolism. However, whether serum vitamin A levels influence the long-term prognosis of patients with type 2 diabetes mellitus (T2DM) remains inconclusive. This study enrolled T2DM patients with available serum VA measurements between 1999 and 2018. The all-cause mortality rate serves as the primary outcome metric. When assessing the association between mortality risk and serum vitamin A (VA) levels, the Cox proportional hazards model can be employed. Subgroups are defined according to VA levels using Kaplan-Meier (KM) analysis, followed by estimation of survival outcomes. Restricted cubic spline (RCS) regression was employed to depict the nonlinear associations between serum VA levels and mortality risk. A total, 3,681 T2DM subjects were enrolled in the final analysis, with a mean serum VA concentration of 2.12 ± 0.76 μmol/L. During the follow-up period of patients, the overall all-cause mortality rate hit 36.70%. In unadjusted Cox regression, Elevated serum vitamin A levels were notably linked to an elevated risk of death, with an HR of 1.43 and a 95% CI of 1.33–1.53. After accounting for potential confounding variables, independent association between serum VA and mortality persisted (HR = 1.12, 95% CI: 1.03–1.22). Subjects with serum VA concentrations above 2.09 μmol/L exhibited significantly poorer survival than those below this threshold (P < 0.01). Moreover, RCS modeling revealed a U-shaped pattern linking serum VA levels to mortality risk. Blood vitamin A levels are notably associated with long-term mortality in individuals with type 2 diabetes, and our research findings necessitate further validation in other population groups.

Keywords

vitamin A, NHANES, diabetes mellitus, mortality

References

[1] HU R. Correlation Study between Serum Vitamin A Level and Carotid Atherosclerosis in Type 2 Diabetes Mellitus[D]. Hebei Medical University, 2023.
[2] REN Y, YANG B W, SUN Y M, et al. Mendelian randomization study on the correlation between micronutrients and type 2 diabetes mellitus and its complications[J]. Chinese Nursing Research, 2025, 17: 2849-2858.
[3] WANG H, SHEN Y, DU Y F, et al. Serum Vitamin Levels and Its Influencing Factors in Patients with Type 2 Diabetes Mellitus[J]. Medical Journal of the Chinese People's Armed Police Forces, 2024, 1: 34-37,43. DOI:10.3969/j.issn.1004-3594.2024.01.008.
[4] ZHAO P T. Dietary Analysis and Nutritional Treatment Effect Study of Gestational Diabetes Mellitus Patients with Pre-pregnancy Overweight and Obesity[D]. Qingdao University, 2021.
[5] SHI Y H, JING Z H, YANG F M. Relationship between changes of serum RBP4, BMP2 levels and osteoporosis in middle-aged and elderly male patients with T2DM[J]. Chinese Journal of Gerontology, 2022, 12: 2890-2892. DOI:10.3969/j.issn.1005-9202.2022.12.011.
[6] KUANG YANPING, WANG LINJING, ZHONG SHUTING, et al. Analysis of Serum Vitamin and Immune Levels in Patients with Type 2 Diabetes Complicated with Infection and Clinical Nursing Research[J]. Journal of Nurses Training, 2012, 27(04):299-301. DOI:10.3969/j.issn.1002-6975.2012.04.004.
[7] HAN LEI, ZHANG PEIHUA, LI HUI, LI YUAN, BI SHULIAN. Detection of Serum Vitamin A Levels in Patients with Type 2 Diabetes Mellitus[J]. Journal of Precision Medicine, 2003(3):287-288.
[8] XU LEI. Supplementing Vitamin A Improves Pancreatic Islet Function[J]. Health and Life, 2017(10):57.
[9] LI TIANSHUANG, WANG MINGTING, GU MAOHONG, et al. Analysis of Nutritional Status, Serum Vitamin A and Retinol Binding Protein 4 Levels in Patients with Gestational Diabetes Mellitus During Pregnancy[J]. Journal of Southeast University (Medical Science Edition), 2020, 39(2):163-168. DOI:CNKI:SUN:NJTD.0.2020-02-006.
[10] LAI XIANGMEI, WANG FEE, ZENG SHENGLAN. Effects of Supplementing Vitamins A, D and E on Blood Glucose and Blood Lipid Related Indicators in Patients with Gestational Diabetes Mellitus[J]. Clinical Medicine, 2020, 40(10):83-86. DOI:10.19528/j.issn.1003-3548.2020.010.034.
[11] ZHANG HUI, CHEN XIAOYAN, HUANG XIAOCHUN, et al. Study on the Relationship Between Vitamin A Deficiency and Chronic Complications of Diabetes Mellitus[J]. New Medicine, 2010(10):668-670. DOI:10.3969/j.issn.0253-9802.2010.10.014.
[12] HE J Q, ZHOU Q, ZENG J, et al. Study on dietary status of patients with type 2 diabetes mellitus and its correlation with blood glucose control[J]. South China Journal of Preventive Medicine, 2017, 43(2): 117-121. DOI:CNKI:SUN:GDWF.0.2017-02-004.
[13] LI P W. Clinical Study on the Correlation Between Serum Retinol-Binding Protein 4 and Diabetic Retinopathy in Type 2 Diabetes Mellitus[D]. Zhengzhou: Zhengzhou University, 2018. DOI: CNKI:CDMD:2.1018.107091.
[14] WANG Q Q, ZHANG A Z. A Comparative Study on Vitamin A and Vitamin E Intake in Self-Designed Diets of Patients with Type 2 Diabetes Mellitus[J]. Zhejiang Medical Journal, 2002, 24(3): 133-134. DOI: 10.3969/j.issn.1006-2785.2002.03.002.
[15] PITTAS A G, DAWSON-HUGHES B, SHEEHAN P, et al. Vitamin D supplementation and prevention of type 2 diabetes[J]. New England journal of medicine, 2019, 381(6): 520-530.
[16] DAS U N. Vitamin C for type 2 diabetes mellitus and hypertension[J]. Archives of medical research, 2019, 50(2): 11-14.
[17] FUENTES-BARRÍA H, AGUILERA-EGUÍA R, FLORES-FERNÁNDEZ C, et al. Vitamin D and type 2 diabetes mellitus: molecular mechanisms and clinical implications—a narrative review[J]. International Journal of Molecular Sciences, 2025, 26(5): 2153.
[18] SU GUANXUN, WANG SHIDONG, LI JIAYUE, et al. Study on Risk Factors of Cardiac Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus[J]. Chongqing Medicine, 2024, 53(3):333-338. DOI:10.3969/j.issn.1671-8348.2024.03.003.
[19] WANG HONGDONG, DU YANHUA, HUANG SHANSHAN, et al. CD9+CD55low Preadipocytes Promote the Occurrence of Type 2 Diabetes Mellitus[J]. Chinese Journal of Endocrinology and Metabolism, 2024, 40(10):830-834. DOI:10.3760/cma.j.cn311282-20240625-00282.
[20] YU DANDAN, ZHOU XUELING, NIU DIEJING, et al. Study on the Correlation Between Plasma Osteopontin Level and Mild Cognitive Impairment in Patients with Type 2 Diabetes Mellitus[J]. National Medical Journal of China, 2024, 104(38):3593-3599. DOI:10.3760/cma.j.cn112137-20240505-01041.
[21] HUANG LI, PAN JIAYUE (Review), YANG YANG (Reviewer). Research Progress on the Mechanism of IGF-1 in Type 2 Diabetes Mellitus and Type 2 Diabetic Nephropathy[J]. Journal of Difficult and Complicated Cases, 2024, 23(2):253-256.
[22] LIU HUAN, HAN PINGPING, SUN LIN, et al. Correlation Between Serum Uric Acid Within Normal Range and Peripheral Neuropathy in Patients with Type 2 Diabetes Mellitus[J]. Journal of Clinical Internal Medicine, 2024, 41(2):121-123.
[23] SAYEDALI E, YALIN A E, YALIN S. Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes[J]. World journal of diabetes, 2023, 14(5): 585.
[24] OU XIAOHONG, AN BO, ZHOU SHUJING, et al. Study on the Correlation Between Serum Uric Acid Level and Morning Peak Blood Pressure in Middle-Aged and Elderly Patients with Type 2 Diabetes Complicated with New-Onset Hypertension[J]. Chinese Journal of General Practitioners, 2026, 25(05):590-594. DOI:10.3760/cma.j.cn114798-20250823-00993.
[25] FARAHMAND M A, DANESHZAD E, FUNG T T et al. What is the impact of vitamin D supplementation on glycemic control in people with type-2 diabetes: a systematic review and meta-analysis of randomized controlled trails[J]. BMC endocrine Disorders, 2023, 23(1): 15.
[26] TOBIAS D K, PRADHAN A D, DURAN E Ket al. Vitamin D supplementation vs. placebo and incident type 2 diabetes in an ancillary study of the randomized Vitamin D and Omega-3 Trial[J]. Nature communications, 2025, 16(1): 3332.
[27] XU YONGQUAN, LIU HAI, DONG Wenli. Effect of Dapagliflozin in the Treatment of Patients with Type 2 Diabetes Complicated with Chronic Heart Failure[J]. Chinese and Foreign Medical Research, 2024, 22(11): 38-42. DOI:10.14033/j.cnki.cfmr.2024.11.010.
[28] JIANG FUSONG, CHENG XINGBO, ZHANG HUI. The Value of Serum Retinol Binding Protein 4 in Type 2 Diabetic Retinopathy[J]. Chinese Journal of Diabetes Mellitus, 2010(5): 5. DOI:10.14033/j.cnki.cfmr.2010.05.005.

Copyright © 2026 Xuepeng Zhang, Pingchun Li, Lina Duo, Ai Zhong, Manting Wang, Yilin Wang, Wei Xiao, Xuanyi Zhang, Yan Deng

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