Islet RNA-seq analysis combined with GLIS3 ChIP-seq analysis revealed apparent direct regulation of a variety of diabetes related genes, including Slc2a2 and Mafa.
A significantly increased HbA1c was found among patients with type 2 diabetes and with GADA-positive diabetes carrying rare GLIS3 variants compared to non-carriers of rare GLIS3 variants with diabetes (p = 0.02 and p = 0.004, respectively).
Significant factors for diabetes progression included age at screening, Ab number, HLA genotypes, rs6476839 [GLIS family zinc finger 3 (GLIS3)], and rs3184504 [SH2B adaptor protein 3 (SH2B3)].
The increasing understanding of the mechanisms of GLIS3 in β cell development, survival and function maintenance will provide new insights into disease pathogenesis and potential therapeutic target identification to combat diabetes.
Those with an elevated fasting plasma glucose [impaired fasting glucose or IFG] with or without an elevated HbA1c [non -diabetic hyperglycaemia; NDH] are randomised into three treatment arms: a control arm receiving no trial intervention, an arm receiving an intensive bespoke group-based diet and physical activity intervention, and an arm receiving the same intervention with enhanced support from people with T2DM trained as diabetes prevention mentors [DPM].
The present data suggest that altered expression of the candidate gene GLIS3 may contribute to both type 1 and 2 type diabetes by favouring beta cell apoptosis.