Subcutaneous injection of hydrogen gas is a novel effective treatment for type 2 diabetes

Abstract Aims/Introduction In previous studies, hydrogen gas (H 2) administration has clearly shown effectiveness in inhibiting diabetes. Here, we evaluated whether subcutaneous injection of H 2 shows enhanced efficacy against type 2 diabetes mellitus induced in mice by a high‐fat diet and low‐dose streptozotocin treatment. Material and Methods H 2 was injected subcutaneously at a dose of 1 mL /mouse/week for 4 weeks. Type 2 diabetes mellitus‐associated parameters were then evaluated to determine the effectiveness of subcutaneous H 2 administration. Results The bodyweight of H 2 ‐treated mice did not change over the course of the experiment. Compared with the untreated control animals, glucose, insulin, low‐density lipoprotein and triglyceride levels in the serum were significantly lower in treated mice, whereas high‐density lipoprotein cholesterol in the serum was significantly higher. Glucose tolerance and insulin sensitivity were both improved in H 2 ‐treated mice. Diabetic nephropathy analysis showed significant reductions in urine volume, urinary total protein and β2‐microglobulin, kidney/bodyweight ratio, and kidney fibrosis associated with subcutaneous injection of H 2 . Conclusions Subcutaneous injection of H 2 significantly improves type 2 diabetes mellitus and diabetic nephropathy‐related outcomes in a mouse model, supporting further consideration of subcutaneous injection as a novel and effective route of clinical H 2 administration.