1型糖尿病患者胰岛移植后血糖水平调节

长期患有1型糖尿病(T1D)的患者可能会因缺乏血糖管理和不能识别低血糖症状的加重从而增加严重低血糖的发作风险。我们想搞清楚对长期T1D患者行肝内胰岛移植后对血糖管理和低血糖事件影响。

 

肝内移植患者（n=12）和正常对照组(NL; n=6)术前和术后6个月接受胰高血糖素(1mU/kg/min)降血糖(每小时~80 ~65 ~55和~45 mg/dl)和安装可注射6 6-2H2-glucose (0.05 mg/kg/min)的高血糖(~90 mg/dl)钳，通过同位素稀释法来测量内分泌的胰岛素产量。

 

术前患者有29 ± 4 年的1型糖尿病合并无症状的低血糖(Clarke评分6.3 ± 0.2; HYPO评分2564 ± 715)并通过门静脉注射入9 648 ± 666胰岛当量/kg，结果12患者中有10人不再依赖胰岛素并且HbA1从7.0 ± 0.3降到了5.6 ± 0.1% (P < 0.01)，并且问题性低血糖得到了改善。

 

利用低血糖钳测定，最后一小时的血浆胰高血糖素为移植组术前33 ± 3、 术后60 ± 7和正常对照组81 ± 9 pg/ml (P < 0.001 both vs. PRE)；肾上腺素术前116 ± 18、术后253 ± 22、正常对照组是380 ± 31 pg/ml (P < 0.01 both vs. PRE and NL vs. POST)；非脂肪酸(FFA)术前组50 ± 7、术后组161 ± 37、正常对照组是95 ± 14 μM (P < 0.05 both vs. PRE)；内分泌性的胰岛素产量术前组为0.6 ± 0.10、术后为1.2 ± 0.1、正常对照组是1.4 ± 0.2 mg/kg per min (P < 0.01 both vs. PRE)；自主神经症状为术前2.2 ± 1.0、术后5.3 ± 1.0、正常对照组是5.8 ± 1.8 (P < 0.1 both vs. PRE)。术后的胰高血糖素肾上腺素、FFA EGP、自主神经症状在最后一个小时的检查中显著增加(P < 0.01 for all)。

 

这些结果显示肝内胰岛移植可以增强长期T1D患者的对抗血糖管理和改善其低血糖症状并对那些患有严重无意识的低血糖患者进行支持。

 

Patients with long-standing type 1 diabetes (T1D) may exhibit defective glucose counterregulation and impaired hypoglycemia symptom recognition that substantially increase their risk for experiencing severe hypoglycemia. We sought to determine the effect of intrahepatic islet transplantation on glucose counterregulation and hypoglycemia symptoms in patients with long-standing T1D. Subjects prior to (PRE) and 6 months after (POST) intrahepatic islet transplantation (n=12) and normal controls (NL; n=6) underwent hyperinsulinemic (1 mU/kg/min) hypoglycemic (hourly steps ~80 ~65 ~55 and ~45 mg/dl) and euglycemic (~90 mg/dl) clamps with infusion of 6 6-2H2-glucose (0.05 mg/kg/min) for measurement of endogenous glucose production (EGP) by the isotopic dilution method. Subjects had 29 ± 4 yrs of T1D complicated by hypoglycemia unawareness (Clarke score 6.3 ± 0.2; HYPO score 2564 ± 715) and received 9 648 ± 666 islet equivalents/kg by portal vein infusion resulting in 10/12 insulin-independent with reduction in HbA1c from 7.0 ± 0.3 to 5.6 ± 0.1% (P < 0.01) and amelioration of problematic hypoglycemia. During the final hour of the hypoglycemic clamp plasma glucagon was PRE 33 ± 3 POST 60 ± 7 and NL 81 ± 9 pg/ml (P < 0.001 both vs. PRE) epinephrine was PRE 116 ± 18 POST 253 ± 22 and NL 380 ± 31 pg/ml (P < 0.01 both vs. PRE and NL vs. POST) free fatty acids (FFA) were PRE 50 ± 7 POST 161 ± 37 and NL 95 ± 14 μM (P < 0.05 both vs. PRE) EGP was PRE 0.6 ± 0.10 POST 1.2 ± 0.1 and NL 1.4 ± 0.2 mg/kg per min (P < 0.01 both vs. PRE) and the autonomic symptom response was PRE 2.2 ± 1.0 POST 5.3 ± 1.0 and NL 5.8 ± 1.8 (P < 0.1 both vs. PRE). POST levels of glucagon epinephrine FFA EGP and autonomic symptoms were greater in the final hour under hypo- vs. euglycemic conditions (P < 0.01 for all). These results indicate that intrahepatic islet transplantation can restore glucose counterregulation and improve hypoglycemia symptoms in long-standing T1D and support its consideration in patients with severe hypoglycemia unawareness.