二甲双胍联合DPP-4抑制剂对2型糖尿病伴慢性牙周炎患者牙槽骨密度的影响

doi:10.19439/j.sjos.2023.04.014

摘要/Abstract

摘要： 目的探讨二甲双胍联合二肽基肽酶4（DPP-4）抑制剂对2型糖尿病伴慢性牙周炎患者牙周组织的影响。方法选择2型糖尿病伴慢性牙周炎患者80例,利用随机数字表法随机分为A组和B组,每组各40例。A组口服二甲双胍同时进行牙周基础治疗;B组在A组的基础上同时口服DPP-4抑制剂。测量2组患者治疗前（T0）及治疗后3个月(T1)、6个月(T2)的牙槽骨密度（BMD）、牙周探诊深度(PD)、临床附着丧失(CAL)、探诊出血(BOP)、糖化血红蛋白(HbA1c)、血磷、血钙、脂联素（ADP）、瘦素（LEP）、白细胞介素6（IL-6）、C反应蛋白（CRP）、肿瘤坏死因子α（TNF-α)等指标。采用SPSS 23.0软件包对数据进行统计学分析。结果 T0时,2组各临床指标均无显著差异;T1、T2时,B组的PD、CAL、BOP、HbAlc显著低于A组(P<0.05）;B组的BMD显著高于A组(P<0.05）;B组的炎症细胞因子水平(IL-6、CRP、TNF-α)、LEP水平显著低于A组,ADP水平显著高于A组(P<0.05）。结论二甲双胍联合DPP-4抑制剂可使2型糖尿病伴慢性牙周炎患者牙槽骨密度增加,并有效改善牙周临床指标和血清生化指标,减轻牙周组织炎症。

关键词: 2型糖尿病, 牙周炎, 二甲双胍, 脂联素, DPP-4抑制剂

Abstract: PURPOSE: To investigate the effect of metformin combined with DPP-4 inhibitor on alveolar bone density in patients with type 2 diabetes mellitus and chronic periodontitis. METHODS: A total of 80 patients with type 2 diabetes mellitus and chronic periodontitis were selected and randomly divided into group A and group B by random number table, with 40 patients in each group. Group A (medication alone group): oral metformin and basic periodontal treatment; Group B (combination group): DPP-4 inhibitor (sitagliptin) was taken orally in addition to group A. Before treatment (T0) and 3 months (T1) and 6 months (T2) after treatment, alveolar bone mineral density (BDM), periodontal probing depth (PD), clinical attachment loss(CAL), probing bleeding (BOP), glycated hemoglobin (HbA1c), serum phosphorus, serum calcium, adiponectin (ADP), leptin (LEP), interleukin-6 (IL-6), C-reactive protein (HS-CRP), tumor necrosis factor (TNF-α) were detected. SPSS 23.0 software package was used for data analysis. RESULTS: Three and 6 months after treatment, PD, CAL, BOP and HbAlc in group B were significantly lower than those in group A(P< 0.05). BDM in group B was significantly higher than that in group A (P< 0.05). Compared with group A, the levels of inflammatory cytokines (IL-6, Hs-CRP, TNF-α) and leptin in group B were significantly decreased, while the level of adiponectin was significantly increased (P< 0.05). CONCLUSIONS: Metformin combined with DPP-4 inhibitor can increase alveolar bone density in patients with type 2 diabetes mellitus and chronic periodontitis, effectively improve periodontal clinical and serum biochemical indicators, and reduce periodontal inflammation.

Key words: Type 2 diabetes mellitus, Periodontitis, Metformin, Adiponectin, DPP-4 inhibitor

中图分类号:

R781.4

刘珂, 艾合买提·艾尼娃, 图尔妮萨古丽·克比尔, 古丽努尔·阿吾提. 二甲双胍联合DPP-4抑制剂对2型糖尿病伴慢性牙周炎患者牙槽骨密度的影响[J]. 上海口腔医学, 2023, 32(4): 410-416.

LIU Ke, AHEMAITI Aniwa, TUERNISAGULI Kebier, GULINUER Awut. Effect of metformin combined with DPP-4 inhibitor on alveolar bone density in patients with type 2 diabetes mellitus and chronic periodontitis[J]. Shanghai Journal of Stomatology, 2023, 32(4): 410-416.

参考文献

[1] Wu CZ, Yuan YH, Liu HH, et al.Epidemiologic relationship between periodontitis and type 2 diabetes mellitus[J]. BMC Oral Health, 2020, 20(1): 204-209.
[2] Baeza M, Morales A, Cisterna C, et al.Effect of periodontal treatment in patients with periodontitis and diabetes: systematic review and meta-analysis[J]. J Appl Oral Sci, 2020, 28: e20190248.
[3] Joshipura KJ, Muñoz-Torres FJ, Dye BA, et al.Longitudinal association between periodontitis and development of diabetes[J]. Diabetes Res Clin Pract,2018, 141: 284-293.
[4] Alvarenga MOP, Miranda GHN, Ferreira RO, et al.Association between diabetic retinopathy and periodontitis-a systematic review[J]. Front Public Health,2021,8: 550614.
[5] Brown RB.Diabetic Complications and phosphate toxicity: a scoping review[J]. Curr Diabetes Rev,2020,16(7): 674-689.
[6] He L.Metformin and systemic metabolism[J]. Trends Pharmacol Sci, 2020, 41(11): 868-881.
[7] 中国老年学会老年医学会老年内分泌代谢专员委员会.老年糖尿病诊疗措施专家共识(2013年版)[J]. 中华内科杂志, 2014, 53(3): 243-251.
[8] DPP-4抑制剂临床应用专家共识[J]. 中华内分泌代谢杂志,2018,34(11): 899-903.
[9] Sun ZG, Li ZN, Zhu HL.The research progress of DPP-4 inhibitors[J]. Mini Rev Med Chem,2020,20(17):1709-1718.
[10] 中华医学会糖尿病学分会.中国2型糖尿病防治指南(2020年版)[J]. 中国糖尿病杂志,2021,13(4): 315-409.
[11] 潘亚萍,刘静波.牙周炎新分类概述[J]. 中国实用口腔科杂志,2021,14(1): 2-4.
[12] 李莉,陈晨,戴洪彬.维吾尔族2型糖尿病性骨质疏松症患者晚期糖基化终产物、受体的表达及其与腰椎骨密度的相关性[J]. 实用预防医学, 2021, 28(7): 846-848.
[13] Ziukaite L, Slot DE, Vand WFA.Prevalence of diabetes mellitus in people clinicall diagnosed with periodontitis: a systematic review and meta-analysis of epidemiologic studies[J]. J Clin Periodontol,2018, 45(6): 650-662.
[14] Losada E, Soldevila B, Ali M, et al.Real-world antidiabetic drug use and fracture risk in 12 277 patients with type 2 diabetes mellitus: a nested case-control study[J]. Osteoporos Int,2018, 29(2): 2079-2086.
[15] Kanazawa I, Tomita T, Miyazaki S, et al.Bazedoxi-fene ameliorates homocysteine-induced apoptosis andaccumulation of advanced glycation end products by reducing oxi datives tress in MC3T3-E1 cells[J]. Calcif Tissue Int, 2017,100(7): 286-297.
[16] Hirshberg B, Parker A, Edelberg H, et al.Safety of saxagliptin: events of special inte rest in 9 156 patients with type 2 diabetes mellitus[J]. Diabetes Metab Res Rev, 2014, 30(7): 556-569.
[17] Choi HJ, Park C, Lee YK, et al.Risk of fractures and diabetesmedications: a nation wide cohort study[J]. Osteoporos Int, 2016, 27(7): 2709-2715.
[18] 杨丕山,王艳,戚向敏,等.糖尿病患者慢性牙周炎治疗后血清肿瘤坏死因子α和糖化血红蛋白的变化[J]. 中华口腔医学杂志,2003,38(5): 364-366.
[19] Simpson TC, Clarkson JE, Worthington HV, et al. Treatment of periodontitis for glycaemic control in people with diabetes mellitus[J]. Cochrane Database Syst Rev, 2022,4(4): CD004714.
[20] Genco RJ, Borgnakke WS.Diabetes as a potential risk for periodontitis: association studies[J]. Periodontol 2000, 2020, 83(1): 40-45.
[21] Lee CY, Kuan YH, Tsai YF, et al.Correlation between diabetes mellitus and periodontitis in Taiwan: a nationwide cohort study[J]. Diabetes Res Clin Pract,2019,150(4): 245-252.
[22] Kim J, Kwak HJ, Cha JY, et al.Metformin suppresses lipopolysaccharide(LPS)-induced inflammatory responsein murine macrophages via activating transcription factor-3 (ATF-3) induction[J]. J Biol Chem, 2014, 289(33): 23246-23255.
[23] Vasamsetti SB, Karnewar S, Kanugula AK, et al.Metformin inhibits monocyteto-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis[J]. Diabetes, 2015, 64(5): 2028-2041.
[24] Li R, Wang R, Li H, et al.Short-term and long-term effects of dipeptidyl peptidase-4 inhibitors in type 2 diabetes mellitus patients with renal impairment: a meta-analysis of randomized controlled trials[J]. Diabetes Metab Res Rev,2016,32(6): 460-469.
[25] Sanz M, Ceriello A, Buysschaert M, et al.Scientific evidence on the links between periodontal diseases and diabetes: consensus report and guidelines of the joint workshop periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology[J]. J Clin Periodontol,2018,45(2):138-149.
[26] Malta FS, Garcia RP, Azarias JS, et al.Impact of hyperglycemia and treatment with metformin on ligature-induced bone loss, bone repair and expression of bone metabolism transcription factors[J]. PLoS One,2020,15(8): e0237660.
[27] Tao LY, Lagosz-Cwik KB, Hogervorst JMA, et al.Diabetes medication metformin inhibits osteoclast formation and activity in in vitro models for periodontitis[J]. Front Cell Dev Biol, 2022, 9: 777450.
[28] 张黎,刘育菘,吴芸菲,等.壳寡糖对牙周炎大鼠牙槽骨吸收及Th17/Treg平衡和OPG/RANKL/RANK通路的影响[J].上海口腔医学,2021,30(3): 237-242.
[29] Deschner J, Eick S, Damanaki A, et al.The role of adipokines in periodontal infection and healing[J]. Mol Oral Microbiol,2014,29(6): 258-269.
[30] Pepelassi E, Xynogala I, Perrea D, et al.The effect of experimental periodontitis, experimental diabetes and their combination on the serum levels of adiponectin, leptin, IL-6, IL-18, MCP-1, RANTES and sICAM-1 in rats[J]. J Int Acad Periodontol,2020, 22(1): 1-10.
[31] Zhu J, Guo B, Gan X, et al.Association of circulating leptin and adiponectin with periodontitis: a systematic review and meta-analysis[J]. BMC Oral Health, 2017, 17(1): 104-110.
[32] Su CM, Lee WL, Hsu CJ, et al.Adiponectin induces oncostatin M expression in osteoblasts through the PI3K/Akt signaling pathway[J]. Int J Mol Sci,2015,17(1): 29-34.
[33] 曹思远, 郭阳, 谢晓华, 等. 牙周基础治疗对2型糖尿病患者血清瘦素含量影响研究[J]. 实用口腔医学杂志, 2012, 28(2): 199-203.
[34] Mazor R, Friedmann-Morvinski D, Alsaigh T, et al. Cleavage of the leptin receptor by matrix metalloprotein-ase-2 promotes leptin resistance and obesity in mice[J]. Sci Transl Med, 2018, 10(455): eaah6324.
[35] Smieszek A, Szydlarska J, Mucha A, et al.Enhanced cytocompatibility and osteoinductive properties of sol-gel-derived silica zirconium dioxide coatings by metformin functionalization[J]. J Biomater Appl, 2017, 32(5): 570-586.
[36] Borzouei S, Sheikh V, Ghasemi M, et al.Anti-inflammatory effect of combined sitagliptin and vitamin D3 on cytokines profile in patients with type 2 diabetes mellitus[J]. J Interferon Cytokine Res, 2019, 39(5): 293-301.
[37] 段松海. 牙周基础治疗对2型糖尿病伴慢性牙周炎患者血清生化指标及血糖代谢水平的影响[J]. 牙体牙髓牙周病学杂志, 2018, 28(10): 594-596.