新诊2型糖尿病患者的胰岛素抵抗与胰岛功能改变及肾血管内皮功能障碍

Endothelial dysfunction of renal blood vessels,change of islet function and insulin resistance in newly diagnosed type 2 diabetes mellitus patients

目的:探讨糖尿病高血糖状态对胰岛功能、肾脏血管内皮毒性作用与胰岛素抵抗(IR)的临床意义.方法:选择符合1999年WHO糖尿病诊断标准且伴微量白蛋白尿(MU,即尿白蛋白排泄率(UAER)≥20μg/min,<200μg/min)、除外其他MU原因、空腹血糖(FBS)>10 mmol/L、餐后2 h血糖(2hBS)>15 mmol/L的新诊2型糖尿病患者32例,观察体质量指数(BMI)、腰臀比(WHR)、FBS、空腹胰岛素(FINS)、空腹C肽(FCP)、果糖胺(FA)、UAER、尿内皮素(UET-1)、血内皮素(SET-1),计算稳态模型β细胞功能指数(HOMA-Is)与IR指数(HOMA-IR),应用胰岛素强化治疗,血糖下降(避免低血糖反应且FBS<7 mmol/L与2hBS<9 mmol/L)平稳2 wk后复查上述指标进行对比.结果:治疗前后FBS[(15.0±3.2)mmol/Lvs(6.8±0.9)mmol/L],FA[(3.90±0.38)mmol/Lvs(2.41±0.29)mmol/L],HOMA-Is[(2.8±0.9)vs(4.3±0.6)],HOMA-IR[(1.8±0.9)vs(1.3±0.4)],UAER[(53±20)μg/minvs(22±8)μg/min],UET-1[(244±19)pg/minvs(142±28)pg/min],SET-1[(153±32)pg/mLvs(104±21)pg/mL]对比差别有统计学意义(P<0.01),FBS,HOMA-Is,HOMA-IR分别与UAER,UET-1,SET-1有相关关系(P<0.01或P<0.05).结论:糖尿病肾病的发生发展与IR以及胰岛功能减退导致继发持续性高血糖毒性损害及失去正常效应胰岛素水平对肾脏血管内皮的保护作用有关;IR、胰岛功能减退、高血糖与内皮功能障碍的相互作用可能是关键环节.

AIM： To study the clinical significance of insulin resistance, endothelial cytotoxicity of renal blood vessels and islet function in hyperglycemia of diabetes. METHODS： Based on 1999 WHO diagnosis criteria for diabetic mellitus, microalbuminuria（ MU ,20μg/min≤UAER 〈200 μg/min）, fasting blood sugar（FBS） 〉 10 mmol/L,2 hBS 〉 15 mmol/L, and excluding other causes of MU,32 newly diagnosed type 2 diabetic patients were investigated for body mass index （BMI）, waist-to-hip ratio （WHR）, FBS, fasting serum insulin （ FINS）, fasting C peptide （ FCP ）, fructosamine （ FA ）, urine albumin excretion ratio （UAER） , urine endothelin-1 （ UET-1 ） , serum endothelin-1 （ SET- 1 ） , HOMA insulin secretion index （HOMA-Is） and HOMA insulin resistance index（ HOMAIR）. These indices before insulin intensive treatment were compared with those of post-inslin intensive treatment after blood sugar declined （ without hypoglycemia reaction, FBS〈7 mmol/L, and 2 hBS 〈9 mmol/L）steadily for 2 weeks. RESULTS ： FBS [ （ 15.0 ± 3.2 ） mmoL/L vs （ 6.8 ± 0. 9 ） mmoL/L],FA[（3.90±0.38） vs（2.41±0.29） mmol/L],HO- MA-Is[（2.8±0.9） vs（4.3±0.6）], HOMA-IR[（1.8±0.9） vs（1.3±0.4）],UAER[（53±20） vs（22±8） μg/min],UET-1 [（244±19） vs（142 ±28） pg/min],and SET-1[（153 ±32） vs （ 104 ± 21 ） pg/mL] were significantly different（ P 〈 0.01 ） between pie-treatment and post-treatment; and FBS, HOMA-Is and HOMA-IR were respectively significantly correlated wih UAER, UET-1, SET-1 （ P 〈 0.05 ）. CONCLUSION ： The occurrence and development of diabetic nephropathy is correlated with insulin resistance, sustaining hyperglycemia cytotoxicity and losting safeguard with endothelin of kidney in normal insulin level after islet β-cell function decline. The interaction among insulin resistance, islet β-cell function decline, hyperglycemia and endothelial dysfunction probably is pivotal element for the pathogenesis of diabetic nephropathy.