妊娠期糖尿病妇女血浆IL-1Ra水平及其与产后2型糖尿病的相关性研究-现代医学

妊娠期糖尿病妇女血浆IL-1Ra水平及其与产后2型糖尿病的相关性研究

单位：南京医科大学附属南京医院/南京市第一医院妇产科, 江苏南京 210006

分类号：R714.7

出版年·卷·期（页码）：2022·50·第七期（864-870）

摘要：

目的：探究妊娠期糖尿病（gestational diabetes mellitus，GDM）妇女血浆白介素-1受体拮抗剂（IL-1Ra）水平及其与产后2型糖尿病（type 2 diabetes mellitus，T2DM）的相关性。方法：选择2018年6月至2020年12月本院收治的120例GDM患者为研究组，同期选取120例来本院进行体检的妊娠期健康妇女为对照组，探究IL-1Ra在两组血浆中的水平以及其与GDM之间的相关性。对120例GDM患者进行12周的跟踪随访，根据是否发生T2DM再分为A、B两组（A组产后T2DM 52例，B组产后正常68例），通过对比两组患者相关指标，以探究IL-1Ra与产后T2DM发生的相关性。结果：研究组患者C肽、空腹血糖（fasting plasma glucose，FBG）、空腹胰岛素（fasting insulin，FINS）、糖化血红蛋白（glycosylated hemoglobin，HbA1c）水平及胰岛素抵抗指数（insulin resistance index，HOMA-IR）均显著高于对照组，而IL-1Ra水平显著低于对照组，差异均具有统计学意义（P<0.05）。研究组T2DM的发生率在43.33%，A组患者C肽、HbA1c、FBG、FINS水平及HOMA-IR均显著高于B组，而IL-1Ra水平显著低于B组，差异均具有统计学意义（P<0.05）。Spearman相关性分析显示，IL-1Ra水平与产前产后C肽、HbA1c、FBG、FINS水平以及HOMA-IR均呈负相关（均r<0，P<0.05）。Logistic回归分析显示，IL-1Ra、C肽、HbA1c、孕前BMI为GDM产后发生T2DM的影响因素（P<0.05）。ROC曲线分析结果表示，IL-1Ra对GDM的截断点为820 pg·ml^-1，灵敏度为37.92%，特异度为79.53%；IL-1Ra对GDM产后发生T2DM的截断点为889 pg·ml^-1，灵敏度为52.26%，特异度为67.15%。结论：IL-1Ra在GDM患者以及GDM产后T2DM患者血浆中的水平明显降低，IL-1Ra可能参与GDM和GDM产后T2DM的发生和发展。

Objective: To investigate the plasma level of interleukin-1 receptor antagonist(IL-1Ra) in women with gestational diabetes mellitus(GDM) and its correlation with postpartum type 2 diabetes mellitus(T2DM). Methods: From June 2018 to December 2020, we selected 120 cases of patients from our hospital with GDM into study group. And at the same time, we also chose 120 healthy pregnancy women undergoing physical examinations into control group. We had followed up the 120 cases of GDM patients for 12 week and divided them into two groups according to the possible occurrence of T2DM, 52 cases of T2DM in group A and 68 cases without T2DM in group B. By comparing the related indicators of patients in these two groups, the correlation between IL-1Ra and the occurrence of postpartum T2DM was explored. Results: The levels of C-peptide, HbA1c, FBG, FINS, HOMA-IR in the study group were significantly higher than those in the control group, while the levels of IL-1Ra were significantly lower than those in the control group. The data differences were all of statistical significance(P<0.05). The incidence of T2DM in the study group was 43.33%. The levels of C-peptide, HbA1c, FBG, FINS and HOMA-IR in group A were significantly higher than those in group B, while the IL-1Ra was significantly lower than that in group B. The data differences were all statistically significant(P<0.05). Spearman correlation analysis showed that IL-1Ra had a significant negative correlation with C-peptide, HbA1c, FBG, FINS and HOMA-IR before and after delivery(all r<0, P<0.05). Logistic regression analysis showed that IL-1Ra, C-peptide, HbA1c and BMI before pregnancy were the influencing factors of T2DM after GDM(P<0.05). ROC curve analysis showed that the cut-off point of IL-1Ra against GDM was 820 pg·ml^-1, with a sensitivity of 37.92% and a specificity of 79.53%. The cut-off point of IL-1Ra for T2DM in postpartum GDM was 889 pg·ml^-1, with a sensitivity of 52.26% and specificity of 67.15%. Conclusion: IL-1Ra is significantly decreased in plasma of patients with GDM and postpartum T2DM with GDM and possibly involved in the occurrence and development of GDM and postpartum T2DM with GDM.

参考文献：

[1] CHIEFARI E, ARCIDIACONO B, FOTI D, et al. Gestational diabetes mellitus:an updated overview[J].J Endocrinol Invest, 2017, 40(9):899-909.
[2] PLOWS J F, STANLEY J L, BAKER P N, et al. The pathophysiology of gestational diabetes mellitus[J].Int J Mol Sci, 2018, 19(11):3342.
[3] SZMUILOWICZ E D, JOSEFSON J L, METZGER B E. Gestational diabetes mellitus[J].Endocrinol Metab Clin North Am, 2019, 48(3):479-493.
[4] JAWAD F, EJAZ K. Gestational diabetes mellitus in South Asia:epidemiology[J].J Pak Med Assoc, 2016, 66(9 Suppl 1):S5-7.
[5] MOON J H, KWAK S H, JANG H C. Prevention of type 2 diabetes mellitus in women with previous gestational diabetes mellitus[J].Korean J Intern Med, 2017, 32(1):26-41.
[6] WEI Q, CHEN X, CHEN H. Association of single nucleotide polymorphisms of the IL-6, IL-10, and TNF-α genes with susceptibility to gestational diabetes mellitus[J].Genet Test Mol Biomarkers, 2020, 24(7):390-398.
[7] NURSAL A F, INANIR A, RUSTEMOGLU A, et al. IL-1β and IL-1Ra variant profiles in Turkish patients with diabetic peripheral neuropathy[J].Endocr Metab Immune Disord Drug Targets, 2019, 19(2):150-158.
[8] 李珍, 江强, 区岛良, 等.应用IL-2Ra对肝移植术后糖代谢异常患者预后的影响[J].肝脏, 2019, 24(7):780-782.
[9] SIRIMARCO M P, GUERRA H M, LISBOA E G, et al. Diagnostic protocol for gestational diabetes mellitus(GDM)(IADPSG/ADA, 2011):influence on the occurrence of GDM and mild gestational hyperglycemia(MGH) and on the perinatal outcomes[J].Diabetol Metab Syndr, 2017, 9:2.
[10] DAVIES M J, D'ALESSIO D A, FRADKIN J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association(ADA) and the European Association for the Study of Diabetes(EASD)[J].Diabetes Care, 2018, 41(12):2669-2701.
[11] DENNEY J M, QUINN K H. Gestational diabetes:underpinning principles, surveillance, and management[J].Obstet Gynecol Clin North Am, 2018, 45(2):299-314.
[12] MOON J H, KWAK S H, JANG H C. Prevention of type 2 diabetes mellitus in women with previous gestational diabetes mellitus[J].Korean J Intern Med, 2017, 32(1):26-41.
[13] SALOMON C, SCHOLZ-ROMERO K, SARKER S, et al. Gestational diabetes mellitus is associated with changes in the concentration and bioactivity of placenta-derived exosomes in maternal circulation across gestation[J].Diabetes, 2016, 65(3):598-609.
[14] MUSTAD V A, HUYNH D T T, LóPEZ-PEDROSA J M, et al. The role of dietary carbohydrates in gestational diabetes[J].Nutrients, 2020, 12(2):385.
[15] YUEN L, WONG V W, SIMMONS D. Ethnic disparities in gestational diabetes[J].Curr Diab Rep, 2018, 18(9):68.
[16] DE GENNARO G, PALLA G, BATTINI L, et al. The role of adipokines in the pathogenesis of gestational diabetes mellitus[J].Gynecol Endocrinol, 2019, 35(9):737-751.
[17] CASAGRANDE S S, LINDER B, COWIE C C. Prevalence of gestational diabetes and subsequent type 2 diabetes among U.S. women[J].Diabetes Res Clin Pract, 2018, 141:200-208.
[18] 李庆, 徐金玲, 方红娟, 等.妊娠期糖尿病患者血清IL-17、IL-1β、IL-10水平变化及其与胰岛素抵抗、血脂的关系[J].山东医药, 2019, 59(4):52-54.
[19] 廖洪霞, 魏艳丽, 朱晓燕, 等.siRNA沉默Fox01对STZ诱导的糖尿病大鼠视网膜IL-1β的影响及其作用机制[J].东南大学学报(医学版), 2018, 37(2):183-190.
[20] MARGARYAN S, KRIEGOVA E, FILLEROVA R, et al. Hypomethylation of IL1RN and NFKB1 genes is linked to the dysbalance in IL1β/IL-1Ra axis in female patients with type 2 diabetes mellitus[J].PLoS One, 2020, 15(5):e0233737.
[21] 周洁, 乔国昱, 张蕊.IL-1、hs-CRP和亚临床甲减与妊娠期糖尿病的相关性研究[J].标记免疫分析与临床, 2017, 24(5):510-512, 519.
[22] 杨永红.妊娠糖尿病患者血浆IL-1β水平变化与胰岛素抵抗的关系[J].河北医药, 2015(9):1301-1303.
[23] SCHULZE F, WEHNER J, KRATSCHMAR D V, et al. Inhibition of IL-1beta improves glycaemia in a mouse model for gestational diabetes[J].Sci Rep, 2020, 10(1):3035.
[24] HOWELL K R, POWELL T L. Effects of maternal obesity on placental function and fetal development[J].Reproduction, 2017, 153(3):R97-R108.
[25] GOMEZ-LOPEZ N, MOTOMURA K, MILLER D, et al. Inflammasomes:their role in normal and complicated pregnancies[J].J Immunol, 2019, 203(11):2757-2769.
[26] KATRA P, DEREKE J, NILSSON C, et al. Plasma levels of the interleukin-1-receptor antagonist are lower in women with gestational diabetes mellitus and are particularly associated with postpartum development of type 2 diabetes[J].PLoS One, 2016, 11(5):e0155701.
[27] 胡龙江, 周音频, 曹运兰, 等.NLRP3-ASC-Caspase-1-IL-18/IL-1β-TGF-β信号通路与Ⅱ型糖尿病临床相关性研究[J].西部医学, 2018, 30(3):335-340, 346.
[28] INGOL T T, KUE J, CONREY E J, et al. Perceived barriers to type 2 diabetes prevention for low-income women with a history of gestational diabetes:a qualitative secondary data analysis[J].Diabetes Educ, 2020, 46(3):271-278.
[29] CHAN J Y, LEE K, MAXWELL E L, et al. Macrophage alterations in islets of obese mice linked to beta cell disruption in diabetes[J].Diabetologia, 2019, 62(6):993-999.
[30] FERREIRA N S, BRUDER-NASCIMENTO T, PEREIRA C A, et al. NLRP3 inflammasome and mineralocorticoid receptors are associated with vascular dysfunction in type 2 diabetes mellitus[J].Cells, 2019, 8(12):1595.
[31] SHARMA B R, KIM M S, RHYU D Y. Nelumbo nucifera leaf extract attenuated pancreatic β-cells toxicity induced by interleukin-1β and interferon-γ, and increased insulin secrection of pancreatic β-cells in streptozotocin-induced diabetic rats[J].J Tradit Chin Med, 2016, 36(1):71-77.
[32] 朱艳, 梁子辉, 任韫卓, 等.NLRP3炎症小体介导的炎症反应参与糖尿病导致的肾损伤和脂代谢异常[J].中国病理生理杂志, 2020, 36(1):53-58.

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