2型糖尿病胰岛β细胞功能衰竭与心功能不全的临床研究

Study of pancreatic β-cell dysfunction and heart failure in type 2 diabetes mellitus

目的探讨2型糖尿病（T2DM）患者胰岛β细胞功能衰竭与心功能不全的临床表现特点及相关激素的改变，寻找针对糖尿病心功能不全的干预靶点。方法选取2008年1月至4月四川省人民医院门诊及住院部收治的T2DM患者96例（A组）、健康体检者35名（B组，健康对照）。将A组按病程和心力衰竭症状分为：新诊断及病程〈2年T2DM患者33例（A1组）、病程〉2年未出现临床显性心力衰竭症状和体征的T2DM患者32例（A2组）、病程〉2年且已出现临床显性心力衰竭症状和体征的T2DM患者31例（A3组）。入选者均测空腹血糖（FPG）、胰岛素（FINS）、真胰岛素（TI）、胰岛素原（PI）1次，注射胰岛素治疗A组患者测空腹C肽1次，以胰岛素分泌指数（Homa—Is）判定胰岛B细胞分泌功能；所有入选者均测定脑钠素（BNP）并采用心脏彩色多普勒测定左室射血分数（LVEF）、二尖瓣口舒张早期流速峰值E峰／舒张晚期流速峰值A峰（E／A）、舒张早期波e峰／舒张晚期波a峰（e／a）、峰值肺静脉血流收缩期S波／峰值肺静脉舒张早中期D波（S／D）以判定心脏功能。应用方差分析进行各组数据分析比较。结果随着T2DM病程的进展，Homa—Is进行性下降（B组为110．0±76．3、A1组为45．0±22．7、A2组为15．0±14．0、A3组为5．8±2．4，F=6．34，P〈0．05），A3组TI及PI与其余各组比较有明显的降低。BNP随胰岛B细胞分泌功能的降低出现了显著增高[B组为（75±19）ng／L、A1组为（810±185）ng／L、A2组为（1060±264）ng／L、A3组为（2071±785）ng／L，F=8．89，P〈0．05]；心脏彩超T2DM组较健康对照组E／A、e／a、S／D、LVEF均有明显下降，随着胰岛β细胞分泌功能下降差异愈明显。结论随着T2DM病程延长及胰岛β细胞功能逐渐衰竭，真胰岛素、胰岛素原分泌水平减少及心肌舒张顺应性减低和收缩力下降，使得心脏泵功能发生与供能相关的代谢障碍，从而影响和加重心力衰竭。

Objective To investigate the clinical features and related hormone changes of diabetic cardiac insufficiency and pancreatic β-cell dysfunction in type 2 diabetes mellitus （ T2DM ） . Methods From January to April 2008,96 patients with T2DM （ group A ） and 35 healthy volunteers with a normal glucose tolerance （NGT） （group B） were enrolled in this study. According to the course of T2DM and symptom of heart failure, the patients in group A were divided into three groups ： group A1 ： newly-diagnosed T2DM or course of T2DM 〈 2 years, n = 33 ; group A2 ： course of T2DM 〉 2 years without obvious signs and symptoms of heart failure, n = 32 ; group A3 ： course of T2DM 〉 2 years with obvious clinical signs and symptoms of heart failure, n = 31. The serum fasting plasma glucose （FPG）, fasting insulin（ FINS）, true insulin（ TI）, proinsulin（PI） and brain natriuretic peptide（BNP） were detected in all the subjects. The ratio between early diastolic peak flow velocity and atrium peak flow velocity （ E/A ） , the lateral wall of mitral annular movement（e/a）, pulmonary venous peak systolic velocities and diastolic velocities （S/D） and left ventricular ejection fraction （LVEF） stage in all subjects were examined by echocardiogram. Variance analysis was used for data analysis among the 4 groups. Results The Homa-Is decreased with the progression of T2DM （ group B ： 110.0 ±76. 3, group A1：45.0 ±22.7, group A2 ： 15. 0 ±14. 0, group A3 ： 5.8 ±2. 4 ; F = 6. 34, P 〈 0. 05 ） ; it indicated that the secretary function of 13-cell declined significantly with the progress of T2DM. The serum level of BNP was significantly increased accompanied the function declines of pancreatic 13-cell （ group B ： （75 ±19 ） ng/L, group A1 ： （ 810 ±185 ） ng/L, group A2 ： （ 1060 ±264 ） ng/L, group A3：（2071 ±785） ng/L; F=8. 89,P 〈0. 05）. The serum level of TI and PI in group A3 were all significantly lower than those in group B, A1 and A2 （ all P 〈 0. 05）. The values of E/A, e/a, S/D and LVEF in group A were all significantly lower than those in group B （ all P 〈 0. 05 ）. Conclusion With the functional declines of pancreatic 13-cell in T2DM, the myocardial contractility and diastolic function declines, meanwhile the TI and PI secretion reduces, and these changes finally induce metabolic disorders which can aggravate heart failure.