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不同剂量二甲双胍对1型糖尿病患者骨代谢生化指标的影响
马玉萍,吕海宏*,徐霞,刘纯华,谈娇娇,王晨怡,李倩
0
(兰州大学第一医院内分泌科, 兰州 730000
*通信作者)
摘要:
目的 观察使用不同剂量二甲双胍联合胰岛素与单纯使用胰岛素治疗对1型糖尿病患者骨代谢相关生化指标的影响,探讨二甲双胍对骨代谢的作用。方法 本研究为回顾性研究,将128例成年1型糖尿病患者按照治疗方法分为观察组(67例)与对照组(61例),其中观察组使用二甲双胍联合胰岛素控制血糖,对照组单纯使用胰岛素控制血糖。收集两组患者治疗前及连续治疗72周后血糖、糖化血红蛋白、25-羟维生素D[25(OH)D]、骨特异性碱性磷酸酶(BALP)、氨基端中分子片段骨钙蛋白(N-MID OC)、血清钙、血清磷、尿钙/肌酐比值、腰椎骨密度等资料,分析使用二甲双胍联合胰岛素控制血糖对患者骨代谢的影响。将观察组患者依据使用二甲双胍的剂量分为低剂量(0.5 g/d)组(20例)、中剂量(1.0 g/d)组(23例)和高剂量(1.5 g/d)组(24例),分析不同剂量二甲双胍对患者骨代谢指标的影响。结果 治疗前,观察组与对照组血糖、糖化血红蛋白及骨代谢相关指标差异均无统计学意义(P均>0.05)。治疗72周后,两组血糖和糖化血红蛋白均较治疗前下降(P均<0.05),但两组间比较差异无统计学意义(P均>0.05)。观察组患者治疗后BALP、N-MID OC及腰椎骨密度均较治疗前升高且高于对照组治疗后(P均<0.05),25(OH)D、血清钙、血清磷、尿钙/肌酐比值与治疗前及对照组治疗后相比差异无统计学意义(P均>0.05);对照组患者腰椎骨密度及骨代谢相关指标与治疗前比较差异均无统计学意义(P均>0.05)。在观察组患者中,治疗后二甲双胍高剂量组BALP、N-MID OC均高于中剂量组及低剂量组(P均<0.01)。多元线性回归分析显示,二甲双胍剂量与BALP(β=0.266,P=0.035)、N-MID OC(β=0.355,P=0.008)具有正相关关系,与尿钙/肌酐比值(β=-0.296,P=0.026)具有负相关关系。结论 使用二甲双胍联合胰岛素控制血糖对1型糖尿病患者骨组织有一定的保护作用,可能有助于预防糖尿病性骨质疏松症。
关键词:  1型糖尿病  二甲双胍  骨代谢生化标志物  骨密度
DOI:10.16781/j.CN31-2187/R.20200729
投稿时间:2020-05-15修订日期:2021-02-03
基金项目:
Effects of different doses of metformin on biochemical parameters of bone metabolism in patients with type 1 diabetes mellitus
MA Yu-ping,Lü Hai-hong*,XU Xia,LIU Chun-hua,TAN Jiao-jiao,WANG Chen-yi,LI Qian
(Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu, China
*Corresponding author)
Abstract:
Objective To observe the effects of different doses of metformin combined with insulin and insulin alone on bone metabolism-related biochemical parameters in patients with type 1 diabetes mellitus, and to explore the effect of metformin on bone metabolism. Methods In this retrospective study, 128 adult patients with type 1 diabetes mellitus were assigned to observation group or control group according to the treatment methods. Among them, 67 patients in the observation group were treated with metformin combined with insulin to control blood glucose, while 61 patients in the control group were treated with insulin alone. Blood glucose, glycosylated hemoglobin, 25-hydroxyvitamin D (25(OH)D), bone specific alkaline phosphatase (BALP), N-terminal mid-fragment of osteocalcin (N-MID OC), serum calcium, serum phosphorus, urinary calcium to creatinine ratio and lumbar vertebra bone mineral density (BMD) were collected before and after treatment for 72 weeks in the 2 groups to analyze the effect of metformin combined with insulin on bone metabolism. According to the dose of metformin, the patients in the observation group were divided into low-dose (0.5 g/d) group (n=20), medium-dose (1.0 g/d) group (n=23) and high-dose (1.5 g/d) group (n=24). The effects of different doses of metformin on bone metabolism parameters of patients were analyzed. Results Before treatment, there were no significant differences in blood glucose, glycosylated hemoglobin or bone metabolism-related parameters between the observation group and the control group (all P>0.05). After 72 weeks of treatment, blood glucose and glycosylated hemoglobin in the 2 groups were significantly lower than those before treatment (all P<0.05), but there was no significant difference between the 2 groups (both P>0.05). After treatment, BALP, N-MID OC and lumbar vertebra BMD in the observation group were higher than those before treatment and those after treatment in the control group (all P<0.05), while 25(OH)D, serum calcium, serum phosphorus and urinary calcium to creatinine ratio had no significant differences compared with those before treatment or those in the control group (all P>0.05). In the control group, there were no significant differences in lumbar vertebra BMD or bone metabolism-related parameters before and after treatment (all P>0.05). In the observation group, BALP and N-MID OC in the high-dose group were significantly higher than those in the medium-dose group and low-dose group after treatment (all P<0.01). Multiple linear regression analysis showed that metformin dose was positively correlated with BALP (β=0.266, P=0.035) and N-MID OC (β=0.355, P=0.008), and negatively correlated with urinary calcium to creatinine ratio (β=-0.296, P=0.026). Conclusion Metformin used for controling glucose in patients with type 1 diabetes mellitus has a protective effect on bone tissue, and may inhibit the occurrence of osteoporosis.
Key words:  type 1 diabetes mellitus  metformin  biochemical markers of bone metabolism  bone mineral density