FIG. 1.

Evaluation of HOT on accelerated diabetes onset in NOD mice. Prediabetic 10-week-old female NOD mice were given a single intravenous dose of CyP on day 0. A: Control mice (n = 10) received no HOT (median 13.5 days, range 11–36). Therapy consisted of 60-min sessions of HOT-100% at 2.0 ATA starting 1 week before CyP injection. Animals received HOT twice a day (bid) for 1 week (n = 10; median 14 days, range 11–21) or 4 weeks (n = 10; range 11–14 days) or once a day (qd) for 4 weeks (n = 25; range 11–34 days) after CyP administration. Nonfasting glycosuria and glycemia were monitored to determine the time of diabetes onset. Log-rank test, *P < 0.005; **P < 0.5 vs. control. B: Single daily HOT (60-min session, 2.0 ATA) at the indicated oxygen concentrations was started 1 week before CyP injection and continued daily. Time to diabetes onset after CyP injection in untreated controls (n = 34) and animals exposed to HOT-12% (resulting in tissue oxygen levels comparable with ambient air of ∼21% oxygen; n = 8; median 13 days, range 10–14), HOT-21% (ambient air; n = 10; median 11–14 days, range 11–14), and HOT-100% (n = 25). Log-rank test, *P < 0.05 vs. control. C: Insulitis score on pancreatic sections of long-term euglycemic mice or after diabetes onset in control and HOT-100% groups (six sections per mouse, n = 2–3 mice per group). Score 0 = no insulitis, 1 = polar and/or peri-insulitis, 2 = mild insulitis (<50% of the islet area infiltrated), 3 = severe insulitis (≥50% of the islet area infiltrated), and 4 = massive insulitis (≥90% of the islet area infiltrated). The mean insulitis score was 1.48 ± 0.15 in control euglycemic (n = 125 islets), 0.83 ± 0.19 in HOT euglycemic (n = 37 islets; P < 0.05 vs. control diabetic), 2.18 ± 0.17 in control diabetic (n = 76 islets; P < 0.05 vs. control euglycemic), and 1.32 ± 0.16 in HOT diabetic (n = 84 islets; P < 0.05 vs. control diabetic) mice. One-way ANOVA, P < 0.0001.