Figure 1 A B

Figure 2

Figure 3 AB P = Insulin secretion Years from screening CC CT/TT

Figure 4 A C B D

Figure 5 A B CD P=

Calcineurin Mitochondrion ATP-sensitive K + channel Insulin receptor GLP-1 Α2-adrenergic receptor Insulin- containing granules Insulin granule exocytosis Glucokinase Voltage-gated Ca 2+ channel Intracellular Ca+ stores Glucose transporter (GLUT2) Glucose Glucose 6-phosphate Glycolysis  cAMP MTNR1B  Ca 2+ Endoplasmic reticulum ß-cell proliferation KCNQ1 IRS1 SLC30A8 WFS1 GCK KCNJ11 ADRA2A TCF7L2 WFS1 THADA KCNQ1 Figure 6 CDKN2A/B,JAZF1,NOTCH,TCF1, THADA, HHEX, TCF7L2, WFS1, CDKAL1 TCF7L2 Nucleus