Adolescents with clinical type 1 diabetes display reduced red blood cell glucose transporter isoform 1 (GLUT1)

作者：Garg Meena; Thamotharan Manikkavasagar; Becker Dorothy J; Devaskar Sherin U^*

来源：Pediatric Diabetes, 2014, 15(7): 511-518.

DOI：10.1111/pedi.12127

• BBB
• hyperinsulinemic clamp
• hypoglycemic clamp
• RBC glucose transporter 1
• T1D

Type 1 diabetic (T1D) adolescent children on insulin therapy suffer episodes of both hyper- and hypoglycemic episodes. Glucose transporter isoform GLUT1 expressed in blood-brain barrier (BBB) and red blood cells (RBC) compensates for perturbed circulating glucose toward protecting the supply to brain and RBCs. We hypothesized that RBC-GLUT1 concentration, as a surrogate for BBB-GLUT1, is altered in T1D children. To test this hypothesis, we measured RBC-GLUT1 by enzyme-linked immunosorbent assay (ELISA) in T1D children (n= 72; mean age 15.3 +/- 0.2 yr) and control children (CON; n= 11; mean age 15.6 +/- 0.9 yr) after 12 h of euglycemia and during a hyperinsulinemic-hypoglycemic clamp with a nadir blood glucose of +/- 3.3 mmol/L for 90min (clamp I) or +/- 3 mmol/L for 45min (clamp II). Reduced baseline RBC-GLUT1 was observed in T1D (2.4 +/- 0.17 ng/ng membrane protein); vs. CON (4.2 +/- 0.61 ng/ng protein) (p < 0.0001). Additionally, baseline RBC-GLUT1 in T1D negatively correlated with hemoglobin A1c (HbA1c) (R=-0.23, p< 0.05) but not in CON (R= 0.06, p< 0.9). Acute decline in serum glucose to 3.3 mmol/L (90min) or 3 mmol/L (45min) did not change baseline RBC-GLUT1 in T1D or CON children. We conclude that reduced RBC-GLUT1 encountered in T1D, with no ability to compensate by increasing during acute hypoglycemia over the durations examined, may demonstrate a vulnerability of impaired RBC glucose transport (serving as a surrogate for BBB), especially in those with the worst control. We speculate that this may contribute to the perturbed cognition seen in T1D adolescents.

• 出版日期2014-11