1型糖尿病患者胰岛移植后血糖水平调节

Authors

Michael R. Rickels MD, MS

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.

编辑： 霄雁    来源：丁香园