糖尿病肾脏疾病患者血清β-羟基丁酸浓度与左心室肥厚的关系

Relationship between β-hydroxybutyrate concentration and left ventricular hypertrophy in patients with diabetic kidney disease

目的 探索糖尿病肾脏疾病(diabetic kidney disease, DKD)患者血清β-羟基丁酸(β-hydroxybutyrate, β-OHB)浓度与患者左心室肥厚(left ventricular hypertrophy, LVH)之间的关系,为治疗DKD合并LVH提供新思路。方法 纳入2021年2月至2021年11月在泰州市人民医院就诊的DKD患者99例,采集患者的基线资料、生化指标,于泰州市人民医院检验科利用酶法测定血清β-OHB含量,采用酶联免疫吸附法测定患者血清中NOD样受体蛋白3(NOD-like receptor protein 3,NLRP3)、超敏C反应蛋白(hypersensitive C-reactive protein, hs-CRP)、白细胞介素6(interleukin-6,IL-6)含量,心脏彩色多普勒超声检测患者心脏结构指标,根据LVH诊断标准将患者分为LVH组和非LVH组,用非参数检验分析不同组间患者β-OHB是否具有差异性,Logistic回归分析法分析DKD患者发生LVH的危险因素,Spearman相关性分析β-OHB浓度与心脏结构各个指标及体内炎症因子之间有无相关性。结果 共99例患者被纳入本研究,年龄62(51,74)岁,年龄范围26~89岁,其中男62例,LVH发生率为34.3%,与非LVH组患者相比,收缩压较高[(149.740±4.391) mmHg比(139.620±2.667) mmHg, 1 mmHg=0.133 kPa],男性患者占比(41.2%比73.8%)、血红蛋白[117.5(85.0,131.0) g/L比125.0(107.0,140.0) g/L]、红细胞计数[3.98(2.84,4.27)×10^(12)/L比4.13(3.59,4.73)×10^(12)/L]、红细胞比容[33.15(24.90,37.28)%比36.30(32.15,40.65)%]均较低,差异具有统计学意义(均P<0.05),Spearman相关性分析结果显示NLRP3(r=-0.219,P=0.03)、hs-CRP(r=-0.254,P=0.011)、IL-6(r=-0.218,P=0.03)、左心房内径(r=-0.385,P<0.001)、室间隔厚度(r=-0.228,P=0.023)、左心室质量指数(r=-0.238,P=0.013),多因素Logistic回归法提示收缩压升高是DKD患者发生LVH的独立危险因素,男性、β-OHB浓度≥0.15 mmol/L是DKD患者发生LVH的独立保护因素。结论 β-OHB可能通过抑制体内NLRP3激活炎症因子,从而减轻DKD患者LVH。

Objective To explore the relationship between β-hydroxybutyrate(β-OHB)concentration and left ventricular hypertrophy(LVH)in patients with diabetic kidney disease(DKD)and provide new therapeutic rationales for DKD with LVH.Methods From February 2021 to November 2021,99 DKD patients at Taizhou People’s Hospital were recruited.Baseline profiles and biochemical parameters of patients were collected, NOD-like receptor protein 3(NLRP3),hypersensitive C-reactive protein(hs-CRP)and interleukin-6(IL-6)in serum were measured by enzyme-linked immunosorbent assay.Color Doppler echocardiography was employed for detecting cardiac structural parameters.They were divided into LVH and non-LVH groups according to the diagnostic criteria for LVH.Non-parametric test was utilized for examining whether or not there were differences in β-OHB between the groups.Logistic regression was employed for examining the risk factors of LVH in DKD patients.The correlation between β-OHB concentration and various indicators of cardiac structure and inflammatory factors in body was analyzed by Spearman’s correlation.Results The median age was 62(51,74)(26-89)years.There were 62 males and the incidence of LVH was 34.3%.Compared with non-LVH group, systolic blood pressure was higher[(149.740±4.391) mmHg vs(139.620±2.667) mmHg, 1 mmHg=0.133 kPa],proportion of males(41.2% vs 73.8%),hemoglobin[117.5(85.0,131.0) g/L vs 125.0(107.0,140.0) g/L],RBC count[3.98(2.84,4.27)×10^(12)/L vs 4.13(3.59,4.73)×10^(12)/L]and RBC specific volume[33.15(24.90,37.28)% vs 36.30(32.15,40.65)%]were lower, the differences were statistically significant(all P<0.05).Spearman’s correlation analysis revealed that NLRP3(r=-0.219,P=0.03),hs-CRP(r=-0.254,P=0.011),IL-6(r=-0.218,P=0.03),left atrial diameter(r=-0.385,P=0.001),interventricularseptal thickness(r=-0.228,P=0.023),left ventricular mass index(r=-0.238,P=0.013)and hemoglobin(r=0.241,P=0.016)were correlated with β-OHB.Multivariate Logistic regression revealed that elevated systolic blood pressure was an independent risk factor.Male and β-OHB concentration were independent protective factors for LVH in DKD patients.Conclusion Elevated systolic blood pressure is an independent risk factor for LVH in DKD patients and β-OHB concentration ≥0.15 mmol/L is an independent protective factor for LVH in DKD patients.Compared with non-LVH group, the concentration of β-OHB is lower in DKD group with LVH and β-OHB is negatively correlated with NLRP3.β-OHB may attenuate left ventricular hypertrophy in DKD patients through an inhibition of NLRP3 activating inflammatory factors.