a, PCA plot of RNA sequencing after regressing out batch, sex and age in controls (red dots, n = 7 independent biological samples) and T2D islets (blue squares, n = 8 independent biological samples). Seq., sequencing. b, Heatmap visualization of differentially expressed genes in controls versus T2D islets. c, PCA plot of m6A sequencing after regressing out the batch and sex effects in controls (red dots, n = 7 independent biological samples) and T2D islets (blue squares, n = 8 independent biological samples). d, Heatmap visualization of differentially methylated loci in controls versus T2D islets. e, The gene expression variability of β-cells represented by the coefficient of variation from single-cell RNA sequencing data (GSE81608) in human dispersed islets, comparing controls (n = 12 independent biological samples) and patients with T2D (n = 6 independent biological samples). The stratification of m6A-modified versus non-m6A-modified genes is based on our patient m6A-sequencing data. Box plot shows the median, box edges show first and third quartiles, and whiskers show the minimum and maximum. P values were calculated using the Mann–Whitney–Wilcoxon test. f, Histogram of log-fold change showing the distribution of differential m6A loci fold changes from controls versus T2D. g, GO analyses of differentially m6A-methylated genes in T2D (n = 8 independent biological samples) versus control (n = 7 independent biological samples) islets. P values were calculated according to the hypergeometric test based on the number of physical entities present in both the predefined set and user-specified list of physical entities. h, Representation of insulin/IGF1 pathway and induction of PDX1 expression based on KEGG and Wikipathway annotations depicting several m6A hypomethylated genes (red shade) and unchanged genes (grey shade) in T2D compared to controls (genes filtered for FDR < 0.05). i, Coverage plots of m6A peaks in the IGF1R, TRIB3, PPP3CA, and PDX1 genes comparing T2D (n = 8 independent biological samples) versus controls (n = 7 independent biological samples). Plotted coverages are the medians of the n replicates presented. IP, immunoprecipitation.