【作者】 王爽；

【导师】 李玲；

【作者基本信息】 中国医科大学 ， 内分泌（专业学位）， 2022， 硕士

【摘要】 目的:葡萄糖目标范围内时间(time in range,TIR)是指葡萄糖在目标范围内的时间或百分比,已有国际指南将TIR确定为1型糖尿病(type 1 diabetes mellitus,T1DM)合并妊娠患者血糖评估的重要方法且发现TIR与其产科结局相关,对于2型糖尿病(type 2 diabetes mellitus,T2DM)合并妊娠、妊娠期显性糖尿病(overt diabetes mellitus,ODM)及妊娠期糖尿病(gestational diabetes mellitus,GDM)患者的TIR目标值因缺乏数据暂未作出推荐。本文将探究伴有高危因素的T2DM合并妊娠、ODM及GDM患者TIR与产科结局、血糖控制指标及临床治疗手段的相关性。方法:本研究为一项前瞻性观察性研究,选取2019.11.1-2022.1.1期间于中国医科大学附属盛京医院内分泌门诊就诊、伴有高危妊娠因素的T2DM合并妊娠、GDM及ODM患者61名,于孕28-32周、孕35-37周分别来院佩戴6天回顾性CGM设备获取TIR,本研究TIR是指葡萄糖在3.5～7.8mmol/L内的时间或百分比,患者于孕28-32周佩戴6天动态血糖监测获得的数据定义为TIR1,于孕35-37周获得的数据定义为TIR2,通过不同分组,探究TIR与产科结局之间的相关关系。(1)根据TIR1是否大于90%分为TIR1-H组(TIR≥90%)和TIR1-L组(TIR<90%),同理,将TIR2分为TIR2-H组和TIR2-L组。应用描述性分析方法描述受试者一般临床特征,应用独立样本t检验、卡方检验比较两组血糖控制指标及产科结局差异。(2)根据两次TIR1、TIR2反应的血糖波动情况分为三组:(1)两次TIR均大于等于90%定义为TIR1-H+TIR2-H组,n=19(2)只有一次TIR大于等于90%定义为TIR1-H or TIR2-H组,n=7(3)两次TIR均小于90%定义于TIR1-L+TIR2-L组,n=7。应用ANOVA方差分析、卡方检验比较三组之间产科结局差异;(3)根据妊娠结局分为有不良妊娠结局组和无不良妊娠结局组,比较两组TIR有无差异。结果:(1)TIR与血糖控制指标的关系:血糖控制较差的TIR1-L组的FPG、2h-PG、GA和Hb A1c均有升高倾向(P>0.05);TIR1水平与同期的FPG1呈显著负相关(r=-0.28,P=0.03),TIR1水平与同期的Hb A1C1呈显著负相关(r=-0.35,P=0.006)。(2)TIR对高血糖、低血糖的反应程度:65.6%的患者可以于孕28-32周达到90%的葡萄糖在理想范围的的TIR,72.7%的患者可以于孕35-37周达到90%的葡萄糖在理想范围的TIR,且第一次CGM时血糖较差的TIR1-L组在进行第二次CGM时出现血糖改善的比率更高(P=0.009);血糖控制较差的TIR1-L组的葡萄糖高于目标范围时间(time above range,TAR)显著高于TIR1-H组(P<0.0001);TIR1-L+TIR2-L组的TAR最高(P<0.0001),TIR1-H or TIR2-H组的葡萄糖低于目标范围时间(time below range,TBR)最高(P=0.048);TIR1水平与同期的TAR1呈显著负相关(r=-0.95,P<0.0001),TIR2水平与同期的TAR2呈显著负相关(r=-0.82,P<0.0001)。(3)TIR与治疗手段的相关性:血糖控制较差的TIR1-L组的胰岛素使用率明显高于TIR2-H组(85.7%vs.52.5%,P=0.01),这种情况在TIR2组也有相似表现(100%vs.41.7%,P=0.003),且TIR2-L组的ODM和PGDM患者比例显著高于TIR2-H组(P=0.04)。(4)TIR与产科结局的相关性:TIR 2水平与新生儿出生体重呈现明显负相关(r=-0.36,P=0.04),与1分钟Apgar评分呈现明显负相关(r=0.46,P=0.007);TIR1与LGA相关,风险比具有统计学意义(OR=0.94,P=0.04),TIR2与LGA也存在同样相关关系(OR=0.90,P=0.04);对于其他新生儿及母亲结局暂未发现随着TIR水平的降低出现不良结局风险的变化趋势。结论:孕28-32周和孕35-37周由动态血糖监测获得的TIR(葡萄糖在3.5～7.8mmol/L内的时间或百分比)低于90%都会增加大于胎龄儿的风险。更多还原

【Abstract】 Objective: Time in range(TIR)is the time or percentage of glucose within the target range.International guidelines have identified TIR as an important method for blood glucose assessment in patients with T1 DM complicated by pregnancy and found that TIR is associated with obstetric outcomes.TIR is expected to become an important indicator for glycemic control and management in patients with hyperglycemia during pregnancy.This study investigated the relationship between TIR and obstetric outcomes in T2 DM patients combined with pregnancy,GDM or ODM with high-risk factors.Methods: This study is a prospective observational study.A total of 61 patients with T2 DM complicated with pregnancy,GDM and ODM with high-risk pregnancy factors who visited the Endocrinology Clinic of Shengjing Hospital Affiliated to China Medical University from 2019.11.1 to 2022.1.1 were selected.28-32 weeks of gestation and 35-37 weeks of gestation respectively came to the hospital to wear retrospective CGM equipment for 6 days to obtain TIR.In this study,TIR refers to the time or percentage of glucose within 3.5-7.8 mmol/L.The data obtained from 28-32 weeks of 6-day continuous blood glucose monitoring was defined as TIR1,and the data obtained at 35-37 weeks of gestation was defined as TIR2.Through different groups,the correlation between TIR and obstetric outcomes was explored.(1)According to whether TIR1 is greater than 90%,it is divided into TIR1-H group(TIR≥90%)and TIR1-L group(TIR<90%).Similarly,TIR2 is divided into TIR2-H group and TIR2-L group.Descriptive analysis was used to describe the general clinical characteristics of the subjects,and independent samples t test and chi-square test were used to compare the differences in blood glucose control indicators and obstetric outcomes between the two groups.(2)According to the two TIR1 and TIR2 blood glucose fluctuations,they were divided into three groups:(1)TIR1-H+TIR2-H group with both TIR≥90%,n=19(2)Only one of the two TIR data is greater than or equal to 90% defined as TIR1-H or TIR2-H group,n=7(3)Both TIR1<90% and TIR2<90% were defined in TIR1-L+TIR2-L group,n=7.ANOVA analysis of variance and chi-square test were used to compare the differences in obstetric outcomes among the three groups;(3)According to pregnancy outcomes,they were divided into groups with adverse pregnancy outcomes and groups without adverse pregnancy outcomes,and compared whether there was any difference in TIR between the two groups.Results:(1)The relationship between TIR and blood sugar control indicators: FPG,2h-PG,GA and Hb A1 c in the TIR1-L group with poor blood sugar control all tended to increase(P>0.05);the level of TIR1 was significantly higher than that of FPG1 in the same period.Negative correlation(r=-0.28,P=0.03),TIR 1 level was significantly negatively correlated with Hb A1C1 in the same period(r=-0.35,P=0.006).(2)The degree of TIR response to hyperglycemia and hypoglycemia: 65.6% of patients can reach 90% TIR at 28-32 w of pregnancy,72.7% of patients can reach 90% of TIR at35-37 w of pregnancy,and the first time The TIR1-L group with poor glycemic control at CGM had a higher rate of glycemic improvement at the second CGM(P=0.009);the TIR1-L group with poor glycemic control had a time above range glucose(TAR)were significantly higher than those in the TIR1-H group(P<0.0001);the TAR in the TIR1-L+TIR2-L group was the highest(P<0.0001),and the time below range(TBR)in the TIR1-H or TIR2-H group was the highest(P=0.048);the level of TIR 1 was significantly negatively correlated with TAR1 in the same period(r=-0.95,P<0.0001),and the level of TIR 2 was significantly negatively correlated with TAR2 in the same period(r=-0.82,P<0.0001).(3)Correlation between TIR and treatment methods: the insulin use rate in the TIR1-L group with poor blood sugar control was significantly higher than that in the TIR2-H group(85.7%vs.52.5%,P=0.01).Similar performance was also observed(100%vs.41.7%,P=0.003),and the proportion of ODM and PGDM patients in the TIR2-L group was significantly higher than that in the TIR2-H group(P=0.04).(4)Correlation between TIR and obstetric outcomes: TIR 2 level was significantly negatively correlated with neonatal birth weight(r=-0.36,P=0.04),and significantly negatively correlated with 1-minute Apgar score(r=0.46,P=0.007);TIR1 was associated with LGA,and the hazard ratio was statistically significant(OR=0.94,P=0.04),and TIR2 was also associated with LGA(OR=0.90,P=0.04);for other neonatal and maternal outcomes,temporary No trend in the risk of adverse outcomes was found with decreasing TIR levels.Conclusion: TIR(time or percentage of glucose within3.5～7.8mmol/L)of less than90% obtained by continuous glucose monitoring at 28-32 week and 35-37 week of gestation increases the risk of large-for-gestational-age infants.更多还原