1. Figure 1 A B

2. Figure 2

3. Figure 3 AB P = 0.003 -.5 0.5 1 Insulin secretion 051015 Years from screening CC CT/TT

4. Figure 4 A C B D

5. Figure 5 A B CD P=

6. 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