Evidence for Interindividual Heterogeneity in the Glucose Gradient Across the Human Red Blood Cell Membrane and Its Relationship to Hemoglobin Glycation

• DOI: 10.2337/db07-1820
• Publication Date: 2008-07-01T00:45:07Z
• Authors: Paramjit K. Khera; Clinton H. Joiner; Anthony Carruthers; Christopher J. Li...; Eric P. Smith; Robert S. Franco; Yancey R. Holmes; Robert M. Cohen
• Keywords: Fructosamine

OBJECTIVE—To determine whether interindividual heterogeneity in the erythrocyte (red blood cell [RBC]) transmembrane glucose gradient might explain discordances between A1C and glycemic control based on measured fructosamine. RESEARCH DESIGN AND METHODS—We modeled relationship plasma RBC as concentration distribution (Ci-to-Co ratio) of a nonmetabolizable analog 14C-3-O-methyl (14C-3OMG) inside (Ci) outside (Co) RBCs vitro. We examined that degree glycation hemoglobin comparison with serum proteins (fructosamine), gap. A1C, fructosamine, vitro determination 14C-3OMG glucose-depleted were 26 fasted subjects. RESULTS—The Ci-to-Co ratio 0.89 ± 0.07 for 3-O-methyl-d-glucopyranose (3OMG) ranged widely (0.72–1.04, n = 26). In contrast, urea (1.015 0.022 [range 0.98–1.07], P < 0.0001) did not. Concerning mechanism, representative subset subjects, was retained ghosts, not dependent ATP or external cations, reestablished after reversal gradient. The 3OMG correlated suggesting it independent mean glucose. However, correlate (R2 0.19) gap 0.20), consistent model which differences internal at given contribute to level control. CONCLUSIONS—The data demonstrate gradients across membranes may affect have implications diabetes complications risk assessment.