Abstract / Summary
Abstract Introduction: Trials of Bacillus Calmette-Guérin (BCG) vaccination in long-standing type 1 diabetes mellitus reported HbA1c reductions of more than 10% at 3 years and 18% at 4 years, attributed to increased leukocyte glucose consumption. The glucose disposal this requires has not been quantified. Objective: To test whether leukocyte glucose consumption is quantitatively sufficient to explain these reductions. Methods: We built a Monte Carlo bounding model. HbA1c reductions of 10% and 18% (baseline 7.36%) were converted to mean glucose with the A1C-Derived Average Glucose equation and to required extra glucose disposal, bounding the glucose-dependent disposal share (φ) at 0.3 and 1.0. Immune capacity combined immune mass, resting uptake from 18F-fluorodeoxyglucose positron emission tomography, reprogrammed fraction, and per-cell fold increase from adenosine triphosphate-yield stoichiometry, in three scenarios: T cell/regulatory T cell (Treg) only, trained myeloid lineage, and whole immune system. Results: Required extra disposal was 6.5 to 11.6 mg/min (φ = 0.3) and 21.5 to 38.8 mg/min (φ = 1.0). For an 18% reduction, median capacity-to-demand ratios at φ = 0.3 were 0.006 (T cell/Treg), 0.17 (myeloid), and 0.57 (whole immune system), with sufficiency probabilities of 0%, 5.7%, and 28%; at φ = 1.0, 0.002, 0.05, and 0.17 (0%, 0.2%, 3.2%). Only a 10% reduction at φ = 0.3 with the whole immune system reprogrammed had a median ratio above 1 (1.03; 51%). Conclusion: Leukocyte glucose consumption could explain the reported reductions only under permissive assumptions and widespread immune reprogramming, and is unlikely to do so if reprogramming is limited to T cells or the myeloid lineage.