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).
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.
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.
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)].
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.