Efficacy of insulin targeted gene therapy for type 1 diabetes mellitus: A systematic review and meta-analysis of rodent studies

Diabetes mellitus (DM) is a major worldwide public health challenge, for which gene therapy offers a potential therapeutic approach. To date, no systematic review or meta-analysis has been published in this area, so we examined all relevant published studies on rodents to elucidate the overall effects of gene therapy on bodyweight, intraperitoneal glucose tolerance test (IPGTT), fasting blood glucose, and insulin in animals with type 1 DM. The Cochrane Library, PubMed, Embase, ISI Web of Science, SCOPUS, and Google Scholar were systematically searched for potentially relevant studies. Mean±standard deviation (SD) was pooled using a random-effects model. After the primary search, out of 528 studies identified, 16 studies were in concordance with predefined criteria and selected for the final assessment. Of these, 12 studies used viral manipulation, and 4 employed non-viral vectors for gene delivery. The meta-analysis showed gene therapy with a viral vector decreased mean IPGTT (-12.69 mmol/l, P<0.001), fasting blood glucose (-13.51 mmol/l, P<0.001), insulin (398.28 pmol/l, P<0.001), and bodyweight (24.22 g, P<0.001), whereas non-viral vectors reduced fasting glucose (-29.95 mmol/l, P<0.001) and elevated insulin (114.92 pmol/l, P<0.001). Gene therapy has favorable effects on alleviating type 1 DM related factors in diabetic rodents.