短期胰岛素强化治疗对初诊2型糖尿病患者下丘脑-垂体-肾上腺轴功能的影响

Effects of Short-term Intensive Insulin Therapy on Hypothalamic-pituitary-adrenal Axis Function in Newly-diagnosed Type 2 Diabetic Patients

目的观察短期胰岛素强化治疗对初诊2型糖尿病(T2DM)患者下丘脑-垂体-肾上腺(HPA)轴功能及相关代谢指标的影响。方法对29例初诊T2DM患者进行为期约2周〔平均(12.7±2.7)d〕的胰岛素强化治疗(持续皮下胰岛素输注或多次皮下胰岛素注射)。比较治疗前后8:00、16:00、24:00患者的血浆皮质醇、促肾上腺皮质激素(ACTH)水平及24h尿总皮质醇(UTC)水平,血糖〔空腹血糖(FPG)、糖负荷后2h血糖(2hPG)〕、血脂〔总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)〕及超敏C-反应蛋白(hs-CRP)水平,计算胰岛素分泌指数(HOMA-β)、胰岛素抵抗指数(HOMA-IR)和糖负荷后早相胰岛β细胞分泌指数(△I30′/△G30′)。结果经短期胰岛素强化治疗后,患者8:00、16:00、24:00血浆皮质醇水平〔分别为(508±188)nmol/L、(170±96)nmol/L、(40±29)nmol/L〕及24hUTC〔(956±410)nmol/24h〕与治疗前〔分别为(609±260)nmol/L、(291±167)nmol/L、(94±98)nmol/L和(1488±727)nmol/24h〕比较,差异均有统计学意义(P<0.05);但各时点血浆ACTH水平与治疗前比较,差异无统计学意义(P>0.05)。治疗后患者FPG、2hPG、TC、TG、LDL-C、hs-CRP水平及HOMA-IR〔分别为(7.1±1.2)mmol/L、(18.9±2.9)mmol/L、(3.9±0.9)mmol/L、(1.3±0.6)mmol/L、(2.2±0.7)mmol/L、(1.0±1.1)mg/L、(1.8±1.3)〕较治疗前〔分别为(12.9±3.0)mmol/L、(27.0±5.2)mmol/L、(4.9±1.3)mmol/L、(3.2±3.7)mmol/L、(2.9±1.0)mmol/L、(2.6±2.8)mg/L和(3.7±3.5)〕降低,而HDL-C水平及HOMA-β、△I30′/△G30′〔分别为(1.16±0.30)mmol/L、(38±27)和(2.3±2.4)〕较治疗前〔分别为(1.04±0.29)mmol/L、(17±16)和(1.0±1.1)〕增加,差异均有统计学意义(P<0.01)。结论短期胰岛素强化治疗能明显改善初诊T2DM患者的糖脂代谢和胰岛分泌功能,缓解胰岛素抵抗,有效降低血、尿皮质醇水平,促进HPA轴功能恢复。

Objective To observe the effects of short-term intensive insulin therapy on hypothalamic-pituitary-adrenal axis（HPAA） function and related metabolic parameters in newly diagnosed patients with type 2 diabetes mellitus（T2DM）.Methods Twenty-nine newly-diagnosed T2DM patients were treated with continuous subcutaneous insulin infusion or multiple injections for about 2 weeks,averaging 12.66 ± 2.70 d.Levels of plasma cortisol and adrenocorticotropic hormone（ACTH）at hours 8,16,24,and 24h urinary total cortisol（UTC）,fasting plasma glucose（FPG）,2 h postprandial glucose（2 hPG）,serum lipids,insulin secretion index（HOMA-β）,insulin resistance index（HOMA-IR）,△I30/△G30,hs-CRP were determined before and after therapy.Results After short-term intensive insulin therapy,levels of plasma cortisol at hours 8,16,24（508±188 nmol/L,170±96 nmol/L,40±29 nmol/L,respectively） and 24 h UTC（956±410 nmol/24 h）decreased（P〈0.05）;FPG,2 hPG,TC,TG,LDL-C,hs-CRP and HOMA-IR were decreased significantly after treatment（7.1±1.2 mmol/L,18.9±2.9 mmol/L,3.9±0.9 mmol/L,1.3±0.6 mmol/L,2.2±0.7 mmol/L,1.0±1.1 mg/L,1.8±1.3,respectively）as compared with the basal levels before therapy（12.9±3.0 mmol/L,27.0±5.2 mmol/L,4.9±1.3 mmol/L,3.2±3.7 mmol/L,2.89±0.95 mmol/L,2.6±2.8 mg/L,3.7±3.5,respectively）（P〈0.01）,while the levels of HDL-C,HOMA-β,△I30 /△G30 were increased significantly（1.16±0.30 mmol/L,38±27,2.32±2.41） as compared with the basal levels before therapy（1.04±0.29 mmol/L,17±16 and 0.95±1.08,respectively）（P〈0.01）,but no difference was noted in plasma ACTH at hours 8,16,24（P〉0.05）.Conclusion Short-term intensive insulin therapy can improve remarkably the functions of glucose and lipid metabolism,and insulin secretion,alleviate insulin resistance,lower effectively the level of hematuria cortisol,and promote the recovery of HPAA function.