title: Adolescents with clinical type 1 diabetes display reduced red blood cell glucose transporter isoform 1 (GLUT1).
abstract: 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.
authors.affiliation: Department of Pediatrics/Division of Neonatology and Developmental Biology, David Geffen School of Medicine at UCLA & Mattel Children's Hospital UCLA, Los Angeles, CA, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Garg
authors.forename: Manikkavasagar
authors.initials: M
authors.lastname: Thamotharan
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Becker
authors.forename: Sherin U
authors.initials: SU
authors.lastname: Devaskar
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D003072:Cognition Disorders / Q000150:complications; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D015309:Glucose Clamp Technique; D051272:Glucose Transporter Type 1 / Q000097:blood*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D008954:Models, Biological; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C495677:SLC2A1 protein, human; C517652:hemoglobin A1c protein, human
keywords: BBB; RBC glucose transporter 1; T1D; hyperinsulinemic clamp; hypoglycemic clamp