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Adolescents with clinical type 1 diabetes display reduced red blood cell glucose transporter isoform 1 ( GLUT1 )
Author(s) -
Garg Meena,
Thamotharan Manikkavasagar,
Becker Dorothy J,
Devaskar Sherin U
Publication year - 2014
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/pedi.12127
Subject(s) - glut1 , glucose transporter , medicine , glucose transporter type 1 , hypoglycemia , endocrinology , hemoglobin , type 1 diabetes , red blood cell , glucose clamp technique , glucose uptake , diabetes mellitus , insulin , insulin resistance , pancreatic hormone
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 90 min (clamp I) or ˜3 mmol/L for 45 min (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 (90 min) or 3 mmol/L (45 min) 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.