2型糖尿病患者葡萄糖在目标范围内时间与射血分数保留的心力衰竭的相关性

Association between time in range of glucose and heart failure with preserved ejection fraction in patients with type 2 diabetes

目的 观察2型糖尿病患者射血分数保留的心力衰竭(heart failure with preserved ejection fraction,HFpEF)发生情况,探讨其与葡萄糖在目标范围内时间(time in range,TIR)的相关性。方法 2型糖尿病患者523例,记录年龄、糖尿病病程、体质量指数、吸烟、合并症、药物使用情况、心率、血压、糖化血红蛋白(glycosylated hemoglobin,HbA_(1)c)、N末端脑钠肽前体、估算肾小球滤过率等;应用持续葡萄糖监测系统连续监测14 d,记录变异系数(coefficient of variation,CV)、标准差(standard deviation,SD)、平均血糖波动幅度(mean amplitude of glycemic excursions,MAGE)、TIR。采用HFA-PEFF评分诊断HFpEF(HFA-PEFF评分≥5分),将523例患者分为HFpEF组78例和非HFpEF组445例,比较2组糖尿病病程、HbA_(1)c、TIR等指标。根据TIR四分位数将523例患者分为TIR Q1组(TIR≤64%)136例、TIR Q2组(64%<TIR≤79%)146例、TIR Q3组(79%<TIR≤89%)122例和TIR Q4组(TIR>89%)119例,比较不同TIR组糖尿病病程、HbA_(1)c、HFA-PEFF评分等指标。采用Spearman相关法分析2型糖尿病患者HFA-PEFF评分与年龄、糖尿病病程、HbA_(1)c、TIR、CV、SD、MAGE的相关性;采用多因素logistic回归分析2型糖尿病患者发生HFpEF的影响因素。结果 TIR Q1组年龄大于TIR Q4组(P<0.05),糖尿病病程长于TIR Q4组(P<0.05),心率、HbA_(1)c、N末端脑钠肽前体水平、CV、SD、MAGE、HFA-PEFF评分及HFpEF、冠心病、利尿剂使用比率均高于TIR Q4组(P<0.05),体质量指数、估算肾小球滤过率均低于TIR Q4组(P<0.05);TIR Q1组舒张压均低于TIR Q2组、TIR Q3组(P<0.05),与TIR Q4组比较差异无统计学意义(P>0.05)。HFpEF组年龄[63.0(59.0,67.0)岁]大于非HFpEF组[52.0(44.0,59.0)岁](Z=9.836,P<0.001),糖尿病病程[11.0(7.0,15.0)年]长于非HFpEF组[6.0(4.0,10.0)年](Z=6.053,P<0.001),体质量指数[(23.40±3.00)kg/m~2]、TIR[66.0(47.0,80.0)%]均低于非HFpEF组[(25.22±2.86)kg/m~2、79.0(67.0,89.0)%](t=5.151,P<0.001;Z=6.258,P<0.001),HbA_(1)c[9.1(7.4,10.3)%]、N末端脑钠肽前体[2 207.0(1 156.0,3 374.0)ng/L]水平,SD[2.7(2.3,3.3)mmol/L]、MAGE[5.8(5.0,7.2)mmol/L]及冠心病(53.8%)、心房颤动(12.8%)、他汀类药(55.1%)、抗血小板药使用(51.3%)比率均高于非HFpEF组[8.1(6.9,9.7)%、98.0(54.0,264.0)ng/L、2.3(1.8,2.8)mmol/L、5.2(4.1,6.3)mmol/L、17.3%、4.3%、26.1%、18.7%](P<0.05)。2型糖尿病患者HFA-PEFF评分与TIR呈负相关(r=-0.320,P<0.001),与年龄、糖尿病病程、HbA_(1)c、CV、SD、MAGE均呈正相关(r=0.270,P<0.001;r=0.120,P=0.006;r=0.210,P<0.001;r=0.150,P=0.001;r=0.696,P<0.001;r=0.480,P<0.001)。年龄(OR=1.123,95%CI:1.017~1.240,P=0.021)、糖尿病病程(OR=1.105,95%CI:1.012~1.224,P=0.033)、冠心病(OR=4.866,95%CI:2.862~8.274,P<0.001)、心房颤动(OR=2.792,95%CI:1.796~6.148,P=0.002)、HbA_(1)c(OR=1.084,95%CI:1.007~1.135,P=0.041)、N-末端脑钠肽前体(OR=1.004,95%CI:1.003~1.005,P<0.001)、TIR(OR=2.339,95%CI:1.433~5.877,P=0.004)是2型糖尿病患者发生HFpEF的影响因素。结论 高龄、糖尿病病程长、有冠心病和心房颤动、高水平HbA_(1)c和N-末端脑钠肽前体、低TIR的2型糖尿病患者发生HFpEF的风险增大,TIR越低越易发生HFpEF。

Objective To observe the occurrance of heart failure with preserved ejection fraction(HFpEF) in patients with type 2 diabetes and to investigate its correlation with the time in range(TIR) of glucose.Methods Totally 523 patients with type 2 diabetes were included.The age,duration of diabetes,body mass index,smoking,comorbidities,medication use,heart rate,blood pressure,glycosylated hemoglobin(HbA_1c),N-terminal pro-brain natriuretic peptide(NT-proBNP),and estimated glomerular filtration rate(eGFR) were recorded.Continuous glucose monitoring system was used to moniter the coefficient of variation(CV),standard deviation(SD),mean amplitude of glycemic excursions(MAGE) and TIR for 14 days.HFpEF was confirmed when the HFA-PEFF score was ≥5,and 523 patients were divided into HFpEF group(n=78) and non-HFpEF group(n=445).The duration of diabetes,HbA_1c,TIR and other indicators were compared between two groups.According to the quartiles of TIR,523 patients were divided into 136 patients with TIR of ≤64%(TIR Q1 group),146 patients with TIR of 64% to ≤79%(TIR Q2 group),122 patients with TIR of 79% to ≤89%(TIR Q3 group) and 119 patients with TIR of 89%(TIR Q4 group).The duration of diabetes,HbA_1c,HFA-PEFF score and other indicators were compared among different TIR groups.Spearman correlation method was used to analyze the correlations of HFA-PEFF score with the age,duration of diabetes,HbA_1c,TIR,CV,SD and MAGE in patients with type 2 diabetes.Multivariate logistic regression analysis was used to analyze the influencing factors of HFpEF in patients with type 2 diabetes.Results Compared with TIR Q4 group,TIR Q1 group had older patients(P<0.05),longer duration of diabetes(P<0.05),and lower heart rate,HbA_(1c) level,NT-probNP level,SD,CV,MAGE,HFA-PEFF score,incidences of HFpEF and coronary heart disease,diuretic application,body mass index and eGFR(P<0.05).The diastolic blood pressure was lower in TIR Q1 group than that in TIR Q2 and TIR Q3 groups(P<0.05),and showed no significant difference compared with TIR Q4 group(P<0.05).The patients were older in HFpEF group [63.0(59.0,67.0) years] than those in non-HFpEF group [52.0(44.0,59.0) years](Z=9.836,P<0.001).The duration of diabetes was longer,and the body mass index and TIR were lower in HFpEF group [11.0(7.0,15.0) years,(23.40±3.00) kg/m~2,66.0(47.0,80.0)%] than those in non-HFpEF group [6.0(4.0,10.0) years,(25.22±2.86) kg/m~2,79.0(67.0,89.0)%](Z=6.053,P<0.001;t=5.151,P<0.001;Z=6.258,P<0.001).HbA_1c,NT-proBNP,SD,MAGE,incidences of coronary heart disease and atrial fibrillation,and rates of statins and antiplatelet agents application were higher in HFpEF group [9.1(7.4,10.3)%,2 207.0(1 156.0,3 374.0) ng/L,2.7(2.3,3.3) mmol/L,5.8(5.0,7.2) mmol/L,53.8%,12.8%,55.1%,51.3%] than those in non-HFpEF group [8.1(6.9,9.7)%,98.0(54.0,264.0) ng/L,2.3(1.8,2.8) mmol/L,5.2(4.1,6.3) mmol/L,17.3%,4.3%,26.1%,18.7%](P<0.05).The HFA-PEFF score was negatively correlated with TIR(r=-0.320,P<0.001),and positively correlated with the age,duration of diabetes,HbA_1c,CV,SD and MAGE(r=0.270,P<0.001;r=0.120,P=0.006;r=0.210,P<0.001;r=0.150,P=0.001;r=0.696,P<0.001;r=0.480,P<0.001).The age(OR=1.123,95%CI:1.017-1.240,P=0.021),duration of diabetes(OR=1.105,95%CI:1.012-1.224,P=0.033),coronary heart disease(OR=4.866,95%CI:2.862-8.274,P<0.001),atrial fibrillation(OR=2.792,95%CI:1.796-6.148,P=0.002),HbA_1c(OR=1.084,95%CI:1.007-1.135,P=0.041),NT-proBNP(OR=1.004,95%CI:1.003-1.005,P<0.001) and TIR(OR=2.339,95%CI:1.433-5.877,P=0.004) were the influencing factors of HFpEF in patients with type 2 diabetes.Conclusion The type 2 diabetes patients with old age,long duration of diabetes,complications of coronary heart disease and atrial fibrillation,high levels of HbA_(1c) and NT-proBNP and low TIR are at a high risk of HFpEF,and the lower the TIR,the higher the incidence of HFpEF.