老年2型糖尿病患者骨代谢异常的影响因素.pdf

临床研究老年 2 型糖尿病患者骨代谢异常的影响因素王明春1,郭锐2(湖北文理学院附属医院襄阳市中心医院:1内分泌科,2公共卫生处,湖北 襄阳 441021)【摘 要】目的 调查襄阳市老年 2 型糖尿病(T2DM)患者骨代谢异常现状,并分析其影响因素。方法 选择 2020 年 1 月至2022 年 1 月襄阳市中心医院就诊的 1236 例老年 T2DM 患者为研究对象,发放调查问卷,统计骨质疏松(OP)发生率。根据患者骨密度检测结果,将确诊为 OP 的患者分为 OP 组(n=374),未确诊 OP 但骨密度下降者分为骨密度下降组(n=266),骨密度正常者分为对照组(n=596)。采用 SPSS 20.0 统计软件进行数据分析。根据数据类型,分别采用 t 检验或2检验进行组间比较。采用有序多分类 logistic 回归分析老年 T2DM 患者发生骨代谢异常的影响因素。结果 1236 例老年 T2DM 患者中,374 例确诊为OP(30.26%)。有序多分类 logistic 回归分析结果显示,年龄80 岁(OR=3.710,95%CI 1.5888.668)、女性(OR=3.586,95%CI 1.8317.024)、T2DM 病程13 年(OR=2.563,95%CI 1.9943.293)、糖化血红蛋白9.0%(OR=2.197,95%CI 1.1374.244)及低密度脂蛋白胆固醇4.1mol/L(OR=3.401,95%CI 1.3628.494)是影响老年 T2DM 患者骨代谢状态的危险因素;体质量指数24.0kg/m2(OR=0.493,95%CI 0.3180.765)及 25-羟基-维生素 D330g/L(OR=0.381,95%CI 0.2350.617)是其保护因素。结论 襄阳市老年 T2DM 患者 OP 及骨密度下降检出率与全国平均水平相当,注重老年 T2DM 患者骨密度检查,同时积极控制血糖、参加体育锻炼、加强维生素 D 摄入,在改善老年 T2DM 患者骨代谢异常中具有一定意义。【关键词】老年人;骨质疏松症;糖尿病,2 型【中图分类号】R587.2 【文献标志码】A 【DOI】10.11915/j.issn.1671-5403.2024.02.018收稿日期:2023-04-19;接受日期:2023-05-24基金项目:湖北省自然科学基金重点项目(2022CFA020)通信作者:郭锐,E-mail:Influencing factors of abnormal bone metabolism in elderly patients with type 2 diabetes mellitusWang Mingchun1,Guo Rui2(1Department of Endocrinology,2Public Health Department,Affiliated Hospital of Hubei University of Arts and Science,Xiangyang Central Hospital,Xiangyang 441021,Hubei Province,China)【Abstract】Objective To investigate the status quo of abnormal bone metabolism in elderly patients with type 2 diabetes mellitus(T2DM)in Xiangyang City,and to analyze its influencing factors.MethodsTotally1 236 elderly patients with T2DM admitted to Xiangyang Central Hospital from January 2020 to January 2022 were selected as the study subjects.Questionnaires were distributed to calculate the incidence rate of osteoporosis(OP)and understand the status quo of osteoporosis in elderly T2DM population in Xiangyang City.The patients with OP were assigned as OP group(n=374),the patients with decreased bone mineral density were classified as the decreased bone mineral density group(n=266),and the patients with normal bone mineral density were set as control group(n=596).The influencing factors of OP in elderly T2DM population in Xiangyang City were explored.SPSS statistics 20.0 was used for data analysis.t test or Chi-square test was performed for comparison between groups according to the data types.Ordinal multivariate logistic regression analysis was used to analyze the related factors affecting the occurrence of abnormal bone metabolism in elderly patients with T2DM.Results Among 1 236 elderly patients with T2DM,374 cases(30.26%)were diagnosed with OP.Ordinal multivariate logistic regression analysis showed that age80 years(OR=3.710,95%CI 1.588-8.668),female(OR=3.586,95%CI 1.831-7.024),T2DM course13 years(OR=2.563,95%CI 1.994-3.293),glycosylated hemoglobin A1c9.0%(OR=2.197,95%CI 1.137-4.244),and low-density lipoprotein cholesterol4.1 mol/L(OR=3.401,95%CI 1.362-8.494)were risk factors affecting bone metabolism status in elderly patients with T2DM,and body mass index24.0 kg/m2(OR=0.493,95%CI 0.318-0.765)and 25-hydroxy vitamin D330 g/L(OR=0.381,95%CI 0.235-0.617)were protective factors.Conclusion The detection rates of OP and bone mass loss in elderly patients with T2DM in Xiangyang City are similar to the national average level.Paying attention to bone mineral density examination in elderly patients with T2DM,actively controlling blood glucose,participating in physical exercise and strengthening vitamin D intake are of certain signifi-cance in improving abnormal bone metabolism in elderly patients with T2DM.【Key words】aged;osteoporosis;diabetes mellitus,type 2This work was supported by the Key Project of Natural Science Foundation of Hubei Province(2022CFA020).Corresponding author:Guo Rui,E-mail:13807272600 39中华老年多器官疾病杂志 2024年2月28日 第23卷 第2期 Chin J Mult Organ Dis Elderly,Vol.23,No.2,Feb 28,2024 2 型糖尿病(type 2 diabetes mellitus,T2DM)是全身性代谢异常疾病,其可同时发生骨密度下降,甚至全身性骨质疏松(osteoporosis,OP),增加老年人跌倒后骨折风险1,2。探讨 T2DM 患者骨代谢现状及其相关因素,有效防控骨密度下降与 OP 发生,在提高患者预后中具有重要意义。人群的骨代谢状况存在地域性差异3,襄阳市位于湖北省西北部,兼备南北气候特点,但尚无研究对该地区的老年T2DM 患者骨代谢异常状况及相关因素进行调查,基于以上背景进行本研究。1 对象与方法1.1 研究对象 选择 2020 年 1 月至 2022 年 1 月于襄阳市中心医院就诊的 1 236 例老年 T2DM 患者为研究对象。纳入标准:(1)年龄60 岁;(2)均符合 T2DM 相关诊断标准;(3)均为襄阳市常住人口。排除标准:(1)合并自身免疫性疾病;(2)合并恶性肿瘤;(3)合并肝肾功能障碍;(4)参与研究前 6 个月内服用糖皮质激素或钙剂。根据患者骨密度检测结果,将发生 OP 者分为 OP 组(n=374);未发生 OP 但骨密度下降者分为骨密度下降组(n=266),骨密度正常者分为对照组(n=596)。本研究经襄阳市中心医院伦理委员会批准(伦理批号:2019078),参与者均知情且同意。1.2 方法1.2.1 骨密度检测及 OP 诊断采用 Discovery-Hologic 双能 X 线吸收骨密度检查仪测定股骨颈、髋部及腰椎部的骨密度(bone mineral density,BMD)值。T2DM 合并 OP 诊断参照 2017 年中国原发性骨质疏松症诊疗指南4中相关标准。1.2.2实验室检查指标采用日立 7180 全自动生化分析仪检测患者实验室指标,包括空腹血糖(fasting blood glucose,FBG)、餐后2h 血糖(2 h blood glucose,2hPG)、空腹胰岛素(fasting insulin,FINS)、糖 化 血 红 蛋 白(glycosylated hemoglobin A1c,HbA1c)、空腹 C 肽(fasting C-peptide,F-CP)、胰岛素样生长因子(insulin-like growth factor,IGF-1)、雌二醇(estradiol,E2)、孕酮(progesterone,P)、睾酮(testosterone,T)、促卵泡激素(follicle stimulating hormone,FSH)、促黄体生成素(luteinizing hormone,LH)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、总 胆 固 醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、甲状旁腺素(parathyroid hormone,PTH)、三碘甲腺原氨酸(triiodothyronine,T3)、促甲状腺激素(thyroid stimu-lating hormone,TSH)、游离甲状腺素(free thyroxine,FT4)、甲状腺素(thyroxine,T4)、维生素 D3(vitamin D3,VD3)、血钙(Ca)、血磷(P)、碱性磷酸酶(alka-line phosphatase,ALP)。其中 VD3 水平采用 25-羟基维生素 D325-(OH)-D3水平表示,化学发光微粒子免疫法检测;PTH 采用化学发光法检测。1.2.3 问卷调查 自行设计调查问卷,调查患者性别、年龄、体质量指数(body mass index,BMI)、T2DM病程、吸烟史、饮酒史、居住地、体育锻炼、钙剂补充、骨折史、日照时间等资料。(1)吸烟定义:每天至少一支香烟,持续 1 年以上。(2)饮酒史定义:平均每日纯酒精摄入量,男性25 g,女性15 g。(3)体育锻炼按照中国高血压防治指南分为3 次/周与3 次/周。(4)25-(OH)-D330g/L 为维生素 D 充足,30g/L 为维生素 D 缺乏。(5)BMI18.5 kg/m2为偏瘦,18.524.0kg/m2为正常,24.0kg/m2为超重。(6)TC6.2 mml/L 和(或)TG2.3 mmol/L 和(或)LDL-C4.1 mmol/L 和(或)HDL-C9.0%为血糖控制不佳。1.3 统计学处理 采用 SPSS 20.0 统计软件进行数据分析。计量资料以均数标准差(xs)表示,多组间比较采用单因素方差分析,组内两两比较采用 LSD-t 检验;两组间比较采用独立样本 t 检验。计数资料以例数(百分率)表示,组间比较采用2检验。采用有序多分类logistic 回归分析老年 T2DM 患者骨代谢异常的影响因素。P0.05 为差异有统计学意义。2 结 果2.1 3 组患者一般人口学、生活习惯及实验室资料比较 1236 例老年 T2DM 患者中,374 例患者确诊为OP(30.26%),266 例骨密度下降(21.52%),596 例骨密度正常(48.22%)。其中 669 例女性中有 249 例发生 OP(37.22%),567 例男性中有 125 例发生 OP(22.05%),女性 OP 发生率高于男性,差异有统计学意义(2=33.484,P0.001)。单因素分析提示,年龄、性别、T2DM 病程、BMI、HbA1c、LDL-C、25-(OH)-D3 水平均是影响老年T2DM 患者 OP 发生的相关因素。此外,年龄、性别、体育锻炼、每日接受日照时间、T2DM 病程、BMI、HbA1c、LDL-C、25-(OH)-D3 水平均是影响老年T2DM 患者骨密度下降的相关因素(表 1)。49中华老年多器官疾病杂志 2024年2月28日 第23卷 第2期 Chin J Mult Organ Dis Elderly,Vol.23,No.2,Feb 28,2024表 1 3 组患者一般人口学、生活习惯及实验室资料比较Table 1 Comparison of general demographics,living habits and laboratory data among three groupsItemControl group(n=596)Decreased bone mineral density group(n=266)OP group(n=374)F/2P valueAgen(%)24.4750.001 60-80 years361(60.57)140(52.63)166(44.39)#80 years 235(39.43)126(47.37)208(55.61)#Gendern(%)52.4050.001 Male335(56.21)107(40.23)125(33.42)Female261(43.79)159(59.77)249(66.58)Place of residencen(%)3.1340.209 Urban 246(41.28)103(38.72)170(45.45)Rural350(58.72)163(61.28)204(54.55)Alcohol drinkingn(%)153(25.67)55(20.68)90(24.06)2.5080.285Smokingn(%)171(28.69)75(28.20)114(30.48)0.4990.779Exercise frequency of sports instituten(%)15.5620.001 3 times/week395(66.28)190(71.43)292(78.07)3 times/week201(33.72)76(28.57)82(21.93)Sunlight exposuren(%)12.5720.002 30 min/d393(65.94)206(77.44)270(72.19)30 min/d203(34.06)60(22.56)104(27.81)Regular calcium supplementationn(%)260(43.62)130(48.87)180(48.13)2.9120.233T2DM course(years,xs)12.231.7113.111.7615.151.63#319.6300.001BMI(kg/m2,xs)24.743.3223.023.3522.163.16#66.1960.001FBG(mmol/L,xs)8.961.548.841.689.021.611.3340.2642hPG(mmol/L,xs)1.660.271.670.311.630.252.3140.099FINS(U/ml,xs)1.420.341.430.331.390.211.9950.137HbA1c(%,xs)6.351.757.881.8410.232.15#426.5560.001IGF-1(ng/ml,xs)91.4410.3789.9411.3590.4811.171.9760.139E2(pmol/L,xs)21.262.0320.962.1521.152.12 2.1510.117Progesterone(ng/L,xs)0.230.070.220.080.230.072.5440.079T(ng/L,xs)35.065.1635.255.6334.894.79 0.4930.611FSH(U/L,xs)40.275.1540.025.1840.155.12 0.2430.784LH(mIU/ml,xs)22.792.6322.773.1123.112.45 1.9920.137HDL-C(mmol/L,xs)1.160.261.170.271.150.240.6240.536LDL-C(mmol/L,xs)2.810.713.020.753.440.63#86.9260.001TC(mmol/L,xs)5.411.215.461.195.361.150.7350.480TG(mmol/L,xs)1.810.281.840.251.830.261.3840.251PTH(pg/ml,xs)21.753.2621.513.4122.043.31 2.6220.073T3(nmol/L,xs)1.490.311.500.351.520.270.9900.372T4(nmol/L,xs)93.7912.2593.8913.1194.5411.370.4540.635TSH(mIU/L,xs)1.730.321.740.331.720.260.4430.642FT4(pmol/L,xs17.262.7417.112.8417.152.38 0.3510.70425-(OH)-D3(g/L,xs)36.034.4327.484.0524.153.47#965.8880.001Ca2+(mmol/L,xs)2.130.322.090.352.160.364.3010.014P(mmol/L,xs)1.140.241.160.261.120.252.6350.072ALP(U/L,xs)19.893.4919.963.5220.153.31 0.6300.533T2DM:type 2 diabetes mellitus;BMI:body mass index;FBG:fasting blood glucose;2hPG:2 h blood glucose;FINS:fasting insulin;HbA1c:glycosy-lated hemoglobin A1c;IGF-1:insulin-like growth factor;E2:estradiol;T:testosterone;FSH:follicle stimulating hormone;LH:luteinizing hormone;HDL-C:high-density lipoprotein cholesterol;LDL-C:low-density lipoprotein cholesterol;TC:total cholesterol;TG:triglyceride;PTH:parathyroid hormone;T3:triiodothyronine;T4:thyroxine;TSH:thyroid stimulating hormone;FT4:free thyroxine;ALP:alkaline phosphatase;OP:osteoporosis.Compared with control group,P0.05;compared with decreased bone mineral density group,#P 9.0%及 LDL-C 4.1mmol/L 均是影响老年 T2DM 患者骨代谢状态的危险因素;BMI24.0 kg/m2及 25-(OH)-D330g/L 是其保护因素(表 2)。3 讨 论 有研究数据表示,大约 1/3 的 T2DM 患者合并OP5-7,T2DM 患者骨密度高于非糖尿病患者的情况下,也存在骨折风险8。中华医学会骨质疏松和骨矿盐疾病分会开展的中国骨质疏松症流行病学调查结果显示,中国 65 岁及以上人群 OP 患病率为 32.00%9。本研究结果显示,襄阳市老年T2DM 患者 OP 检出率为 30.26%,与全国平均水平相当。T2DM 合并骨代谢异常的危险因素众多,由于各地区饮食与自然环境的差异,不同地域的骨代谢异常高危因素之间也存在不同。本研究结果显示,年龄80 岁、女性、T2DM 病程13 年、HbA1c 9.0%及 LDL-C4.1 mmol/L 均是影响老年 T2DM患者骨代谢状态的危险因素;BMI24.0 kg/m2及25-(OH)-D330g/L 是其保护因素。年龄、性别及 T2DM 病程是造成骨代谢异常的常见因素。其中年龄与 BMD 之间呈正相关,随着年龄的增长,骨代谢异常风险呈上升趋势10,11。本研究中,女性T2DM 患 者 OP 发 生 率 高 于 男 性(37.22%和22.05%),女性绝经后,雌激素及其受体水平明显下降,缺乏雌激素保护后,女性骨量会明显下降,OP发生风险也更高12。Kwon 等13研究显示,T2DM病程每增加 15 年,患者骨密度将减少 10%。因此,建议做好年长老人、女性以及 T2DM 病程长者的骨密度检测及OP 筛查。BMI24.0kg/m2被很多研究证实为OP 的保护因素14,而本研究证实 BMI24.0 kg/m2是骨代谢异常的保护因素。尽管高 BMI 对骨骼健康有益,但高 BMI 也易引起心血管疾病、脂质代谢紊乱等问题,故明确 BMI 分界点,有助于患者权衡体质量控制水平。此外,本研究还发现部分血生化指标与老年T2DM 患者骨代谢状态有关。HbA1c 水平升高提示患者血糖控制不佳,而高血糖会增加机体渗透性利表 2 襄阳市老年 T2DM 患者骨代谢状态的有序多分类 logistic 回归分析Table 2 Ordinal multivariate logistic regression analysis of bone metabolism status in elderly patients with T2DM in Xiangyang CityFactorSEWald2OR95%CIP valueAge(control:60-80 years)80 years1.3110.4339.1673.7101.588-8.6680.003Gender(control:male)Female1.2770.34313.8613.5861.831-7.0240.001T2DM course(control:13 years)13 years0.9410.12854.0452.5631.994-3.2930.001BMI(control:18.5-24.0 kg/m2)9.0%0.7870.3365.4862.1971.137-4.2440.020LDL-C(control:4.1 mmol/L)4.1 mmol/L1.2240.4676.8703.4011.362-8.4940.00925-(OH)-D3(control:30 g/L)30 g/L-0.9650.24615.3880.3810.235-0.6170.001T2DM:type 2 diabetes mellitus;BMI:body mass index;HbA1c:glycosylated hemoglobin A1c;LDL-C:low-density lipoprotein cholesterol.69中华老年多器官疾病杂志 2024年2月28日 第23卷 第2期 Chin J Mult Organ Dis Elderly,Vol.23,No.2,Feb 28,2024尿,排出大量钙磷,减少骨量,促进 OP 及骨密度下降发生15。血脂代谢紊乱可通过抑制骨髓间充质干细胞成骨分化,破坏骨细胞,参与骨代谢。本研究中 LDL-C 水平升高将增加骨代谢异常风险16。25-(OH)-D3 水平与糖代谢及骨代谢之间关系密切,25-(OH)-D3 水平不足将影响骨转换,增加骨密度下降及 OP 发生风险。综上所述,注重年长及女性 T2DM 老年患者骨密度检查,同时积极控制血糖、参加体育锻炼、加强VD 摄入,在改善襄阳市老年 T2DM 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