Effects of inflammation on serum hepcidin and iron metabolism related parameters in patients with type 2 diabetes mellitus: a meta-analysis

doi:10.12307/2026.043

Abstract

Abstract: OBJECTIVE: Disorders in iron metabolism increase the risk of type 2 diabetes mellitus. Hepcidin play an important role in maintaining iron homeostasis in the body, but its level increases with increased inflammation. Changes in hepcidin and iron homeostasis and the extent of their association with inflammation in people with and without type 2 diabetes mellitus are unknown. Meta-analysis was used to evaluate the effect of inflammation on serum hepcidin and iron metabolism related parameters in patients with type 2 diabetes mellitus.
METHODS: CNKI, PubMed, Web of Science and EBSCOhost databases were searched by computer to collect observational studies related to inflammatory index and hepcidin in patients with type 2 diabetes mellitus. The search time was from September 1, 2000 to September 30, 2024. Three researchers independently screened the literature, extracted data and evaluated the quality of the included literature. Meta-analysis was performed by Review Manager 5.3, Stata 17.0 and GraphPad Prism 8.0.2 software.
RESULTS: A total of 15 articles (17 studies) involving 3 159 participants, including 1 357 patients with type 2 diabetes mellitus, were included. Meta-analysis results showed that compared with the control group, patients with type 2 diabetes mellitus had higher levels of serum hepcidin [standardized mean difference (SMD)=0.35, 95% confidence interval (CI) (0.05, 0.65), P < 0.05], serum ferritin (SMD=0.49, 95% CI (0.21, 0.78), P < 0.01) and serum transferrin (SMD=0.19, 95% CI (0.00, 0.37), P < 0.05). Subgroup analysis results indicated that inflammation had a significant effect on serum hepcidin (SMD=0.76, 95% CI (0.17, 1.34), P < 0.05) and serum ferritin (SMD=0.77, 95% CI (0.06, 1.47), P < 0.05) in patients with type 2 diabetes mellitus.
CONCLUSION: Hepcidin concentration is positively correlated with type 2 diabetes mellitus. Inflammation is one of the risk factors of type 2 diabetes mellitus. Early prevention of inflammation has certain significance in preventing iron metabolism disorder in patients with type 2 diabetes mellitus.

Key words: inflammation, hepcidin, type 2 diabetes mellitus, iron metabolism, observational study, meta-analysis, engineered tissue construction

CLC Number:

Wen Xiaolong, Weng Xiquan, Feng Yao, Cao Wenyan, Liu Yuqian, Wang Haitao. Effects of inflammation on serum hepcidin and iron metabolism related parameters in patients with type 2 diabetes mellitus: a meta-analysis[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(5): 1294-1301.

Figures/Tables 8

分析。从整体上看，2型糖尿病患者与对照人群之间的血清抗菌多肽、铁蛋白和转铁蛋白水平有显著差异。 2.3.1 2型糖尿病组与对照组参与者之间的血清抗菌多肽差异共纳入12项病例-对照研究、4项横断面研究、1项非随机对照试验，共涉及3 159名参与者。汇总结果显示，2型糖尿病的影响较大且具有高度异质性(P=0.000，I2=92.2%)，2型糖尿病患者血清抗菌多肽水平高于对照人群[SMD=0.35，95%CI(0.05，0.65)，P=0.023]，合并结果稳健，见图4所示。 2.3.2 炎症水平对不同人群血清抗菌多肽的影响以是否存在炎症反应作为亚组进行分析，结果显示：在参与者均存在炎症反应的情况下，2型糖尿病患者与对照人群之间的血清抗菌多肽水平比较差异有显著性意义，炎症反应会引起2型糖尿病患者血清抗菌多肽水平显著升高[SMD=0.76，95%CI(0.17，1.34)，P=0.01]；在无炎症反应的情况下，2型糖尿病患者与对照组人群之间的血清抗菌多肽水平无显著差异[SMD=0.01，95%CI(-0.32，0.34)，P=0.95]，见图5所示。 2.3.3 次要结局指标次要结局指标包括铁代谢相关参数如血清铁、铁蛋白、转铁蛋白、转铁蛋白受体、转铁蛋白饱和度及总铁结合力。Meta分析汇总表明，大多数铁代谢相关参数在2型糖尿病患者与对照人群中的差异较小(P > 0.05)，仅有血清铁蛋白(共纳入15项研究，共涉及3 019名参与者)和转铁蛋白(共纳入2项研究，共涉及469名参与者)在2型糖尿病组和对照组中有显著差异，2型糖尿病组血清铁蛋白[SMD=0.49，95%CI(0.20，0.78)，P=0.001]和转铁蛋白[SMD=0.19，95%CI(0.00，0.37)，P=0.045]水平显著高于对照组，详见图6，7。亚组分析结果表明，当存在炎症反应的情况下，2型糖尿病患者血清铁蛋白水平显著高于对照人群[SMD=0.77，95%CI(0.06，1.47)，P=0.032]；无论个体是否存在炎症水平，2型糖尿病组与对照组参与者间血清铁、转铁蛋白受体、转铁蛋白饱和度、总铁结合力水平均无显著差异，见表2。 2.4 发表偏倚当纳入的研究数量≥10时采用漏斗图判断发表偏倚，因此，仅对血清抗菌多肽和血清铁蛋白进行分析，漏斗图中均显示主观判断的对称性，见图8。其中两项指标的Egger检验结果显示无显著发表偏倚(P抗菌多肽=0.331，P铁蛋白=0.375)。 2.5 Meta回归分析结果将上述Meta分析中存在的统计学上高度异质性及纳入研究数≥10进行Meta回归，以找到异质性的可能来源，协变量包括样本量、年龄、体质量指数、炎症状态，然而，单变量回归并没有发现任何显著的协变量(P > 0.05)，同时这些协变量的多元回归也无法解释Meta分析的高异质性来源(P > 0.05)，见表3。高异质性的原因可能是由于统计异质性(如不同的研究设计、测量方式等因素)或未被此次研究考虑的协变量之外其他潜在变量所引起。"

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