Supplementary Data

SUPPLEMENTARY DATA

SUPPLEMENTARY DATA: Exercise response variation in PCr recovery rate and insulin

sensitivity relates to muscle epigenomic profiles in individuals with type 2 diabetes

Natalie A. Stephens, PhD 1, *, Bram Brouwers, PhD 1, *, Alexey M. Eroshkin, PhD 3, Fanchao Yi, MSc

1, Heather H. Cornnell, PhD 1, Christian Meyer, MD 1, Bret H. Goodpaster, PhD 1, 2, Richard E. Pratley,

MD 1, 2, Steven R. Smith, MD 1, 2, Lauren M. Sparks, PhD 1, 2

1 Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL, USA

2 Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA

3 Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA

* These authors contributed equally to this work.

Running title: Exercise response variation in type 2 diabetes

Registered with ClinicalTrials.gov: NCT01911104

Corresponding author:

Lauren M. Sparks, PhD

Translational Research Institute for Metabolism and Diabetes

301 E. Princeton Street

Orlando, FL 32804

Tel: 407-303-7114

Fax: 407-303-7199

E-mail: [email protected]

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA Supplementary Figure S1. (A) Plasma glucose levels during the last 20 minutes of the steady state during the hyperinsulinemic-euglycemic clamp (glucose was measured every 5 minutes) pre- and post- training in Non-Responders and Responders. (B) Average plasma insulin levels during the steady state of the hyperinsulinemic-euglycemic clamp pre- and post-training in Non-Responders and Responders.

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA Supplementary Figure S2. Correlation analysis between pre-training DNA methylation levels in muscle tissue based on the CpG content and neighborhood content and the functional genome distribution and pre-training values for PCr recovery rate (k) and insulin sensitivity (M-value).

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA Supplementary Figure S3. Correlation analysis between pre-training DNA methylation levels in muscle tissue based on the CpG content and neighborhood content and the functional genome distribution and training-induced changes (Δ) for PCr recovery rate (k) and HbA1c.

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA Supplementary Figure S4. Correlation analysis between pre-training DNA methylation levels in myogenic progenitor cells (HSkMCs) based on the CpG content and neighborhood content and the functional genome distribution and pre-training values for PCr recovery rate (k) and HbA1c.

Supplementary Figure S5. Correlation analysis between pre-training DNA methylation levels in myogenic progenitor cells (HSkMCs) based on the CpG content and neighborhood content and the functional genome distribution and training-induced changes (Δ) for PCr recovery rate (k) and HbA1c.

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA Supplementary Table 1. CpG methylation sites that showed significantly different methylation between Non-Responders (NR) and Responders (R) in muscle tissue.

Relation to CpG content Functional genome p-value Fold Change Fold Change (Description) # CpG site Gene Name and neighborhood content distribution (R vs. NR) (R vs. NR) (R vs. NR) 1 cg24652288 C11orf52 N_Shore Body 0.001 -1.254 Down 2 cg07918723 PIEZO2 Open_Sea Body 0.016 -1.520 Down 3 cg27260867 LINC01044 N_Shore Body 0.034 1.362 Up 4 cg00426486 S_Shelf Intergenic 0.007 1.312 Up 5 cg05411132 XRCC6P5 S_Shore TSS1500 0.018 1.185 Up 6 cg03813151 ZC3H12D Island Body 0.023 1.156 Up 7 cg16288318 LINC01044 S_Shore TSS1500 0.029 1.195 Up 8 cg02840179 DLGAP2-AS1 Open_Sea Body 0.030 1.265 Up 9 cg11502198 ABT1 Island 1stExon 0.000 3.996 Up 10 cg10387963 ADAM3A Island Body 0.048 1.660 Up 11 cg06978117 C11orf53 Open_Sea Body 0.002 1.214 Up 12 cg12163508 HSD17B7P2 Island TSS200 0.021 1.996 Up 13 cg22452837 Open_Sea Intergenic 0.043 2.296 Up 14 cg25138752 N_Shelf Intergenic 0.027 -1.808 Down 15 cg04850659 ESPNP N_Shelf Body 0.023 1.419 Up 16 cg07011961 PRDM9 Open_Sea TSS200 0.021 1.234 Up 17 cg03554573 C11orf53 Open_Sea Body 0.001 1.362 Up 18 cg09166973 PRDM9 Open_Sea TSS200 0.046 1.192 Up 19 cg04459447 N_Shelf Intergenic 0.039 1.470 Up 20 cg20100745 NDRG1 N_Shore 5URT 0.008 -1.289 Down 21 cg00859129 GPSM2 S_Shelf 5URT 0.029 -1.161 Down 22 cg11849573 Open_Sea Intergenic 0.003 1.302 Up 23 cg13926174 Open_Sea Intergenic 0.031 1.467 Up 24 cg20771240 LOC100128239 N_Shore Body 0.001 1.288 Up 25 cg14081974 TOLLIP Island Body 0.009 4.060 Up 26 cg21634283 N_Shore Intergenic 0.011 1.728 Up 27 cg17655970 LINC01044 Island Body 0.004 1.920 Up 28 cg05845592 SULT1A1 Island 1stExon 0.015 6.405 Up 29 cg11515089 Open_Sea Intergenic 0.032 1.184 Up 30 cg22653957 ALPPL2 Island Body 0.024 1.399 Up 31 cg25210835 GSTM5 Open_Sea TSS200 0.033 1.700 Up 32 cg21569714 SAP30L-AS1 Open_Sea Body 0.011 -1.170 Down 33 cg04772025 Open_Sea Intergenic 0.015 1.411 Up 34 cg03716984 Open_Sea Intergenic 0.010 1.302 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 35 cg16609260 N_Shore Intergenic 0.035 1.503 Up 36 cg24820672 LINC01044 N_Shore Body 0.008 1.473 Up 37 cg10989862 LOC100287834 N_Shore TSS200 0.039 -1.405 Down 38 cg14075454 HLA-DRB1 S_Shore Body 0.023 1.428 Up 39 cg25774148 AGRN Island Body 0.002 1.154 Up 40 cg21232488 TRIM31 Open_Sea Body 0.036 1.410 Up 41 cg25844605 LINC00654 Open_Sea TSS1500 0.018 1.434 Up 42 cg07939587 Island Intergenic 0.049 1.281 Up 43 cg05473536 SSTR5 S_Shore 1stExon 0.011 1.563 Up 44 cg07189673 Open_Sea Intergenic 0.033 1.134 Up 45 cg00186815 ERICH1-AS1 N_Shelf Body 0.026 1.208 Up 46 cg19169023 TYRO3 S_Shore Body 0.000 1.243 Up 47 cg20285974 Open_Sea Intergenic 0.018 -1.285 Down 48 cg25390787 CRISP2 Open_Sea 5URT 0.012 1.762 Up 49 cg16988262 S_Shore Intergenic 0.004 -1.252 Down 50 cg19961153 ALPPL2 N_Shore TSS1500 0.028 1.985 Up 51 cg26990102 EN1 Island TSS1500 0.039 -1.387 Down 52 cg18339359 SLC25A37 Open_Sea Body 0.021 2.469 Up 53 cg17204288 GAGE2A S_Shore 5URT 0.048 1.350 Up 54 cg18173235 N_Shelf Intergenic 0.028 -1.482 Down 55 cg16796151 PTPRN2 N_Shore Body 0.035 -1.304 Down 56 cg05485137 MKX S_Shore TSS1500 0.036 1.356 Up 57 cg17739038 HIC1 Island TSS1500 0.045 1.225 Up 58 cg24047440 SMIM19 Island TSS1500 0.038 1.650 Up 59 cg09584492 ARHGAP33 N_Shore TSS1500 0.026 2.122 Up 60 cg26757221 Open_Sea Intergenic 0.018 1.392 Up 61 cg24467349 GSTM5 Open_Sea TSS200 0.021 1.770 Up 62 cg16788050 Island Intergenic 0.017 1.756 Up 63 cg12109260 N_Shelf Intergenic 0.012 1.144 Up 64 cg07304536 Open_Sea Intergenic 0.001 1.360 Up 65 cg14316660 S_Shore Intergenic 0.017 -1.550 Down 66 cg14629771 LOC100128239 Island Body 0.015 1.464 Up 67 cg16705086 INSL3 N_Shore Body 0.026 1.162 Up 68 cg27596297 Open_Sea Intergenic 0.041 1.312 Up 69 cg02444433 PRDM9 Open_Sea TSS1500 0.040 1.248 Up 70 cg04392266 Island Intergenic 0.023 1.305 Up 71 cg13832669 N_Shore Intergenic 0.017 -1.524 Down 72 cg11912754 Island Intergenic 0.020 1.202 Up 73 cg27256468 PKP1 Island 5URT 0.002 2.536 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 74 cg04058281 Open_Sea Intergenic 0.003 1.232 Up 75 cg27244972 YBEY N_Shore Body 0.038 -1.537 Down 76 cg11320369 BCOR N_Shelf 5URT 0.027 2.579 Up 77 cg09506081 DPP6 N_Shore 3UTR 0.045 1.261 Up 78 cg12440062 CRISP2 Open_Sea TSS200 0.012 1.736 Up 79 cg06946452 EN1 Island TSS1500 0.024 -1.330 Down 80 cg14646974 HSD17B7P2 Island Body 0.006 2.454 Up 81 cg03486986 LINC01044 S_Shore TSS1500 0.034 1.894 Up 82 cg16320888 Open_Sea Intergenic 0.042 -1.523 Down 83 cg21687740 Island Intergenic 0.050 1.531 Up 84 cg14659346 ALPP Island Body 0.033 2.105 Up 85 cg20803293 GSTM5 Open_Sea TSS200 0.012 1.480 Up 86 cg10950028 GSTM1 S_Shore Body 0.015 1.336 Up 87 cg11424828 MYOM2 Island Body 0.047 1.269 Up 88 cg08900396 RPH3AL N_Shelf Body 0.027 2.358 Up 89 cg11680055 GSTM1 Island TSS200 0.001 2.114 Up 90 cg26425256 Island Intergenic 0.028 -1.537 Down 91 cg22337407 Open_Sea Intergenic 0.019 1.840 Up 92 cg07508773 WDSUB1 Island 5URT 0.013 74.868 Up 93 cg13446859 TRIM31 Open_Sea Body 0.016 1.201 Up 94 cg25472530 PRDM9 Open_Sea TSS200 0.032 1.327 Up 95 cg15812020 TPTE2P1 Island Body 0.005 1.437 Up 96 cg08720028 Open_Sea Intergenic 0.019 -2.233 Down 97 cg11168104 LOC101929034 Island TSS1500 0.024 1.206 Up 98 cg08587775 Island Intergenic 0.043 2.824 Up 99 cg09858108 Island Intergenic 0.048 1.435 Up 100 cg14274989 EN1 Island TSS1500 0.002 -1.774 Down 101 cg18298927 Island Intergenic 0.001 1.317 Up 102 cg09744766 LOC102723373 Island Body 0.027 1.821 Up 103 cg16115627 DPP6 Island 3UTR 0.032 1.373 Up 104 cg24278027 LOC102723373 Island TSS200 0.014 2.575 Up 105 cg16113156 Island Intergenic 0.019 1.247 Up 106 cg16180556 GSTM1 Island TSS200 0.015 2.407 Up 107 cg24506221 GSTM1 Island TSS200 0.018 9.630 Up 108 cg15146462 Island Intergenic 0.012 1.276 Up 109 cg00059374 Open_Sea Intergenic 0.023 1.272 Up 110 cg23771956 Island Intergenic 0.024 1.177 Up 111 cg13391079 Island Intergenic 0.045 1.219 Up 112 cg17529386 Island Intergenic 0.033 1.138 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 113 cg06470855 Island Intergenic 0.007 1.172 Up 114 cg07472199 ZNF843 Island 5URT 0.002 1.155 Up 115 cg10522818 OTOP1 Island 1stExon 0.007 1.302 Up 116 cg11969330 CYP4V2 Open_Sea Body 0.040 -1.450 Down 117 cg06559318 HLA-DRB6 Open_Sea Body 0.026 -3.218 Down 118 cg20869257 PKP1 Island 1stExon 0.014 1.419 Up 119 cg25645064 Open_Sea Intergenic 0.027 1.444 Up 120 cg12858902 GSTM5 Open_Sea TSS200 0.010 2.059 Up 121 cg07964753 Open_Sea Intergenic 0.038 -1.200 Down 122 cg05338009 ZNF331 Island TSS1500 0.022 1.323 Up 123 cg00802903 S_Shelf Intergenic 0.023 1.294 Up 124 cg07662121 MPV17L Island 1stExon 0.023 6.404 Up 125 cg03665457 HSD17B7P2 Island Body 0.004 2.443 Up 126 cg08901307 Open_Sea Intergenic 0.001 -1.176 Down 127 cg20182709 NSUN6 Open_Sea Body 0.031 -1.363 Down 128 cg11340603 SYT1 Open_Sea Body 0.029 1.279 Up 129 cg04160515 LINC01107 Open_Sea Body 0.021 1.295 Up 130 cg13799572 KIRREL3 Open_Sea Body 0.020 1.504 Up 131 cg10148932 N_Shelf Intergenic 0.025 -1.242 Down 132 cg01148975 KSR1 Open_Sea 5URT 0.021 1.171 Up 133 cg07416792 ADGRA3 Open_Sea Body 0.007 1.477 Up 134 cg26232565 Open_Sea Intergenic 0.014 -1.438 Down 135 cg26590106 HLA-DRB1 N_Shelf Body 0.029 -3.005 Down 136 cg19075727 HLA-DPB2 Open_Sea TSS1500 0.046 -1.154 Down 137 cg12818023 LOC101927415 S_Shore TSS1500 0.026 -1.245 Down 138 cg03358370 PAQR5 Open_Sea 5URT 0.046 -1.269 Down 139 cg19389973 AOAH Open_Sea Body 0.022 -1.823 Down 140 cg03192273 Open_Sea Intergenic 0.047 5.865 Up 141 cg14629612 HLCS Open_Sea Body 0.010 -2.701 Down 142 cg13914841 S_Shelf Intergenic 0.024 -1.265 Down 143 cg08425455 TMCO3 S_Shore Body 0.043 -1.467 Down 144 cg01509409 ATF6 Open_Sea Body 0.042 1.763 Up 145 cg06139856 PCNX Open_Sea Body 0.039 -2.579 Down 146 cg21844184 Open_Sea Intergenic 0.002 1.314 Up 147 cg11628320 IFNAR2 Open_Sea Body 0.012 -3.524 Down 148 cg18591413 GYS2 Open_Sea Body 0.046 -1.226 Down 149 cg09009380 PKP1 Island 1stExon 0.005 1.444 Up 150 cg10369879 Open_Sea Intergenic 0.048 -1.596 Down 151 cg19249420 FOXL1 S_Shore TSS200 0.030 1.322 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 152 cg27009374 S_Shore Intergenic 0.044 -1.239 Down 153 cg04922606 FAM120B Island Body 0.033 -5.405 Down 154 cg12397118 ANKRD10 Open_Sea Body 0.027 1.861 Up 155 cg21052905 Open_Sea Intergenic 0.028 -1.348 Down 156 cg18558257 Open_Sea Intergenic 0.015 1.232 Up 157 cg23119178 EGLN3 Open_Sea Body 0.009 -1.188 Down 158 cg04344225 LINC00709 Open_Sea Body 0.026 1.614 Up 159 cg23893060 Open_Sea Intergenic 0.014 -1.393 Down 160 cg00247094 TBC1D16 N_Shore Body 0.049 1.289 Up 161 cg04637592 Open_Sea Intergenic 0.038 -2.471 Down 162 cg00959922 FOXL1 S_Shore TSS1500 0.011 1.185 Up 163 cg10553121 WWOX Open_Sea Body 0.001 -1.283 Down 164 cg03020379 PTGER1 S_Shore TSS1500 0.036 -1.525 Down 165 cg03482074 Island Intergenic 0.020 1.315 Up 166 cg08884363 STAC2 N_Shelf Body 0.012 -1.409 Down 167 cg00634258 TNFRSF9 N_Shelf Body 0.026 1.136 Up 168 cg21235746 LINC00654 Open_Sea Body 0.046 1.407 Up 169 cg17342925 S_Shelf Intergenic 0.023 -1.519 Down 170 cg17220237 NPSR1 Open_Sea Body 0.014 -1.302 Down 171 cg23972165 Open_Sea Intergenic 0.017 -1.386 Down 172 cg16339761 Open_Sea Intergenic 0.008 1.437 Up 173 cg11236727 N_Shore Intergenic 0.014 -1.434 Down 174 cg15696309 Open_Sea Intergenic 0.013 1.229 Up 175 cg02926217 RUVBL1 Open_Sea Body 0.024 -1.208 Down 176 cg09641432 NFATC1 S_Shore Body 0.038 -1.271 Down 177 cg00541777 COLEC11 Open_Sea TSS1500 0.032 1.191 Up 178 cg07460842 Island Intergenic 0.005 1.764 Up 179 cg16971657 PAK2 Open_Sea 5URT 0.041 -1.620 Down 180 cg04051447 Open_Sea Intergenic 0.032 -1.414 Down 181 cg13528314 CD38 Open_Sea Body 0.013 -1.187 Down 182 cg26429017 C2orf82 Open_Sea TSS200 0.033 -1.289 Down 183 cg16664858 LRRC15 Open_Sea 5URT 0.028 1.180 Up 184 cg14575169 ITGB2-AS1 Open_Sea TSS1500 0.015 -1.175 Down 185 cg06675602 FAM118B S_Shelf 5URT 0.021 -1.207 Down 186 cg07303167 RIBC1 Open_Sea Body 0.044 1.364 Up 187 cg07555084 Open_Sea Intergenic 0.043 1.198 Up 188 cg14068309 EIF2B1 Open_Sea 3UTR 0.006 1.354 Up 189 cg05670149 Open_Sea Intergenic 0.042 -1.228 Down 190 cg12471283 Open_Sea Intergenic 0.001 -1.455 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 191 cg04850148 CCL4L1 Open_Sea Body 0.049 1.303 Up 192 cg00440797 HLA-DRB5 S_Shelf Body 0.037 -1.735 Down 193 cg11468315 Island Intergenic 0.030 -2.938 Down 194 cg05149320 CD244 Open_Sea TSS1500 0.007 -1.217 Down 195 cg11800135 Open_Sea Intergenic 0.011 1.381 Up 196 cg02320600 SREBF2 Open_Sea Body 0.033 -1.300 Down 197 cg02157463 JPH3 Island Body 0.027 1.932 Up 198 cg00605342 SLC25A37 Open_Sea Body 0.024 -1.201 Down 199 cg07413957 CYB5B Open_Sea Body 0.014 -1.432 Down 200 cg03534180 LOC100507065 Open_Sea Body 0.030 -1.183 Down 201 cg21954381 Open_Sea Intergenic 0.012 -1.212 Down 202 cg13947301 ITPR1 Open_Sea Body 0.042 -1.450 Down 203 cg24925741 N_Shore Intergenic 0.030 3.220 Up 204 cg13211008 ESYT2 Open_Sea Body 0.016 4.190 Up 205 cg18670846 Open_Sea Intergenic 0.019 -1.184 Down 206 cg19182918 KRT40 Open_Sea 5URT 0.022 -1.236 Down 207 cg15845365 MYO10 Open_Sea Body 0.023 -2.399 Down 208 cg12179578 SLC4A8 Open_Sea 3UTR 0.004 2.920 Up 209 cg00759426 MPZL3 Open_Sea Body 0.033 -1.518 Down 210 cg26279587 Open_Sea Intergenic 0.025 -1.329 Down 211 cg07482223 SFTA2 Open_Sea 3UTR 0.001 1.452 Up 212 cg02265440 Open_Sea Intergenic 0.006 -1.444 Down 213 cg25259265 ADPRHL1 Open_Sea 5URT 0.001 -1.525 Down 214 cg23009831 Open_Sea Intergenic 0.001 -2.760 Down 215 cg03440127 Open_Sea Intergenic 0.005 -1.311 Down 216 cg12206353 ARHGEF28 Open_Sea Body 0.039 -1.272 Down 217 cg24415895 LOC105376360 Island Body 0.026 1.283 Up 218 cg05710090 Open_Sea Intergenic 0.002 1.146 Up 219 cg06075393 RASSF2 Open_Sea 5URT 0.045 1.603 Up 220 cg15785681 N_Shelf Intergenic 0.001 -1.485 Down 221 cg02269385 Open_Sea Intergenic 0.021 -1.192 Down 222 cg16167088 XRCC6P5 S_Shore TSS200 0.011 1.199 Up 223 cg15930598 Open_Sea Intergenic 0.008 1.426 Up 224 cg14362791 Open_Sea Intergenic 0.007 -1.190 Down 225 cg11198398 Open_Sea Intergenic 0.006 -1.448 Down 226 cg07964848 MKX S_Shore TSS1500 0.035 1.375 Up 227 cg25958766 LINC00654 Open_Sea TSS200 0.029 1.319 Up 228 cg01277952 Open_Sea Intergenic 0.004 -1.171 Down 229 cg27483217 N_Shore Intergenic 0.011 -2.598 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 230 cg02947374 N_Shore Intergenic 0.027 -1.164 Down 231 cg19783563 LINC01044 Island TSS200 0.012 1.334 Up 232 cg03981535 RNPEP N_Shore TSS1500 0.021 1.495 Up 233 cg25172968 C17orf74 Open_Sea 1stExon 0.032 -1.232 Down 234 cg21967713 DIP2C Open_Sea Body 0.021 -1.257 Down 235 cg19546583 Island Intergenic 0.037 1.697 Up 236 cg17889618 NTPCR N_Shore TSS1500 0.016 -1.291 Down 237 cg11012487 SREBF2 Open_Sea Body 0.000 -1.412 Down 238 cg03229588 Open_Sea Intergenic 0.045 1.193 Up 239 cg04900489 Open_Sea Intergenic 0.048 2.082 Up 240 cg19013242 Open_Sea Intergenic 0.022 -1.469 Down MEF2BNB- 241 cg02784731 MEF2B Open_Sea Body 0.034 1.228 Up 242 cg10109763 NRG1 N_Shore TSS1500 0.043 2.475 Up 243 cg03266453 EN1 Island TSS1500 0.007 -1.707 Down 244 cg21044329 TMEM132E Open_Sea Body 0.012 -1.274 Down 245 cg00103771 HLA-DRB6 Open_Sea Body 0.048 -2.156 Down 246 cg05108024 SULT2B1 Open_Sea Body 0.028 -1.784 Down 247 cg12393104 RTN4R S_Shelf Body 0.019 1.180 Up 248 cg25520068 GSTM5 Open_Sea TSS200 0.007 2.484 Up 249 cg09619282 PLCL2 S_Shelf Body 0.010 -1.225 Down 250 cg13452812 Open_Sea Intergenic 0.044 1.569 Up 251 cg05036212 N_Shore Intergenic 0.023 -1.429 Down 252 cg07493237 IL26 Open_Sea TSS1500 0.039 1.218 Up 253 cg08942800 CRISP2 Open_Sea TSS200 0.024 1.353 Up 254 cg08757828 Open_Sea Intergenic 0.024 1.308 Up 255 cg23694597 Open_Sea Intergenic 0.035 -1.291 Down 256 cg02154276 GARNL3 Open_Sea Body 0.043 -1.762 Down 257 cg13026556 TMEM170A N_Shelf Body 0.029 1.178 Up 258 cg10169393 Open_Sea Intergenic 0.001 1.195 Up 259 cg04819618 Open_Sea Intergenic 0.002 1.369 Up 260 cg16514085 HLA-DRB1 Island Body 0.034 2.140 Up 261 cg25174111 MUS81 S_Shelf Body 0.008 1.992 Up 262 cg19791271 TBC1D16 S_Shelf 3UTR 0.026 1.748 Up 263 cg05731870 N_Shore Intergenic 0.047 -1.503 Down 264 cg16037139 Open_Sea Intergenic 0.008 2.333 Up 265 cg16050480 POPDC3 S_Shore TSS1500 0.048 -1.163 Down 266 cg19261904 Open_Sea Intergenic 0.035 -1.198 Down 267 cg05624812 SYCP2L Open_Sea Body 0.028 -1.444 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 268 cg27467876 SLC39A14 Open_Sea Body 0.001 -3.696 Down 269 cg23403192 USP16 N_Shore TSS1500 0.046 1.260 Up 270 cg04773134 CTU2 N_Shelf Body 0.043 1.633 Up 271 cg24373584 Open_Sea Intergenic 0.046 -1.623 Down 272 cg00836161 N_Shelf Intergenic 0.033 2.146 Up 273 cg00896220 CCL4L1 Open_Sea TSS1500 0.003 -1.157 Down 274 cg12313868 Open_Sea Intergenic 0.032 1.290 Up 275 cg23947654 TANC1 Open_Sea Body 0.035 -2.044 Down 276 cg22419711 Open_Sea Intergenic 0.015 -1.209 Down 277 cg17348244 DNAAF5 Open_Sea Body 0.009 -4.887 Down 278 cg19045700 Open_Sea Intergenic 0.002 -1.304 Down 279 cg02479473 Open_Sea Intergenic 0.009 -1.171 Down 280 cg10973622 IMMT S_Shore TSS1500 0.042 1.413 Up 281 cg15309905 CPEB2-AS1 Open_Sea Body 0.026 -1.285 Down 282 cg08296461 MVB12B Open_Sea Body 0.012 -1.383 Down 283 cg14198221 TMEM229B S_Shore TSS1500 0.048 -1.576 Down 284 cg12886054 CD244 Open_Sea TSS1500 0.008 -1.207 Down 285 cg03104113 Open_Sea Intergenic 0.034 1.279 Up 286 cg20409752 CAMTA1 Island Body 0.036 -1.312 Down 287 cg07876831 TMCO3 N_Shelf Body 0.029 -1.602 Down 288 cg10041443 IST1 Open_Sea Body 0.009 1.161 Up 289 cg05376982 GSTM5 Open_Sea TSS200 0.005 1.355 Up 290 cg27088421 PPP3CC Open_Sea 3UTR 0.012 -1.741 Down 291 cg04515987 Open_Sea Intergenic 0.014 1.630 Up 292 cg25704368 TTTY20 N_Shore TSS1500 0.050 1.415 Up 293 cg12381317 PFKM S_Shore 5URT 0.001 -1.301 Down 294 cg27245312 Open_Sea Intergenic 0.044 1.144 Up 295 cg10662395 HCN2 S_Shore Body 0.011 -1.724 Down 296 cg06779232 PTPRN2 S_Shore Body 0.049 1.469 Up 297 cg24765360 N_Shore Intergenic 0.041 -1.492 Down 298 cg25593510 GSTM5 Open_Sea TSS1500 0.010 1.530 Up 299 cg26976060 S_Shelf Intergenic 0.040 1.546 Up 300 cg24432632 Open_Sea Intergenic 0.030 -1.326 Down 301 cg12418535 EN1 S_Shore TSS1500 0.044 -1.425 Down 302 cg03369169 FAM107B Open_Sea Body 0.000 -1.383 Down 303 cg24175014 Open_Sea Intergenic 0.007 1.428 Up 304 cg22206167 Open_Sea Intergenic 0.041 -1.302 Down 305 cg10786572 S_Shore Intergenic 0.038 -1.326 Down 306 cg06054159 MYOM2 N_Shelf Body 0.047 1.539 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 307 cg16268937 Open_Sea Intergenic 0.048 -1.698 Down 308 cg10005146 SSH2 Open_Sea Body 0.007 1.812 Up 309 cg22365757 LCE1D Open_Sea TSS1500 0.048 -1.710 Down 310 cg27158636 LOC102723373 Island Body 0.013 1.547 Up 311 cg24403268 ANKRD20A5P Island TSS200 0.012 1.740 Up 312 cg13462173 N_Shore Intergenic 0.016 1.431 Up 313 cg10122899 P2RX7 Open_Sea Body 0.001 -1.482 Down 314 cg17095797 FOXL1 S_Shore TSS200 0.020 1.284 Up 315 cg20086657 Island Intergenic 0.003 -1.544 Down 316 cg04861073 S_Shore Intergenic 0.020 -3.736 Down 317 cg11169363 Open_Sea Intergenic 0.041 1.154 Up 318 cg16490805 S_Shelf Intergenic 0.017 -1.391 Down 319 cg06212876 LINC00161 Open_Sea Body 0.048 1.256 Up 320 cg05407200 S_Shelf Intergenic 0.036 -1.634 Down 321 cg12500040 Open_Sea Intergenic 0.002 -6.894 Down 322 cg14811585 NCOA7 Open_Sea Body 0.030 3.171 Up 323 cg08283200 SOX5 Open_Sea Body 0.045 1.662 Up 324 cg10618621 SLC15A5 Open_Sea Body 0.049 -1.390 Down 325 cg15230952 N_Shelf Intergenic 0.039 -1.287 Down 326 cg02047954 RABGAP1L Open_Sea TSS1500 0.001 -2.514 Down 327 cg00860182 MFAP3L Open_Sea 5URT 0.029 1.247 Up 328 cg17219203 HSD17B7P2 Island TSS200 0.006 1.705 Up 329 cg04265523 Open_Sea Intergenic 0.002 -1.208 Down 330 cg08973053 Open_Sea Intergenic 0.017 -1.241 Down 331 cg14170447 AIM1 Open_Sea Body 0.031 1.311 Up 332 cg12921769 Open_Sea Intergenic 0.037 1.233 Up 333 cg03690824 TENM2 Island Body 0.027 1.711 Up 334 cg08356333 Open_Sea Intergenic 0.005 -1.254 Down 335 cg27526649 N_Shore Intergenic 0.003 -1.281 Down 336 cg03332173 Open_Sea Intergenic 0.016 -1.293 Down 337 cg05996077 Open_Sea Intergenic 0.008 -1.176 Down 338 cg20295248 LINC00654 Open_Sea TSS200 0.013 1.626 Up 339 cg06961873 TMEM57 Open_Sea 3UTR 0.013 -1.746 Down 340 cg10811640 Open_Sea Intergenic 0.002 -3.790 Down 341 cg07456472 F11 Open_Sea Body 0.043 1.795 Up 342 cg19080354 ATHL1 N_Shore TSS1500 0.044 3.808 Up 343 cg20790798 LOC101929034 Island TSS1500 0.033 1.207 Up 344 cg15556277 PLIN Open_Sea Body 0.024 -1.230 Down 345 cg10960055 Open_Sea Intergenic 0.019 2.034 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 346 cg02761835 Open_Sea Intergenic 0.019 -1.488 Down 347 cg21970086 PRUNE2 Open_Sea Body 0.049 1.759 Up 348 cg26108171 Open_Sea Intergenic 0.011 1.313 Up 349 cg14673729 N_Shelf Intergenic 0.001 -1.201 Down 350 cg17509180 MIR99AHG Open_Sea Body 0.006 1.403 Up 351 cg06615479 GLP2R Open_Sea TSS200 0.030 1.258 Up 352 cg25116412 TTC25 Open_Sea Body 0.035 -1.298 Down 353 cg15837943 ITM2C S_Shelf 5URT 0.038 1.405 Up 354 cg08410850 POLH S_Shelf 5URT 0.009 -1.186 Down 355 cg03291732 FAM168A Open_Sea 5URT 0.047 -1.271 Down 356 cg08600378 URAD Open_Sea TSS200 0.009 2.578 Up 357 cg14421879 APOL6 Open_Sea TSS1500 0.001 1.568 Up 358 cg12788672 GSTCD S_Shore 5URT 0.010 1.263 Up 359 cg06836435 Open_Sea Intergenic 0.019 1.419 Up 360 cg08083088 SLC37A4 N_Shore 5URT 0.031 -1.192 Down 361 cg07909498 Open_Sea Intergenic 0.004 2.894 Up 362 cg06508490 CAT Open_Sea Body 0.025 1.351 Up 363 cg04021548 NLGN4Y N_Shore TSS1500 0.047 1.350 Up 364 cg06815373 PTPRN2 S_Shore Body 0.049 -1.267 Down 365 cg05068341 S_Shelf Intergenic 0.022 -1.603 Down 366 cg13081109 Open_Sea Intergenic 0.006 1.134 Up 367 cg06352538 TESPA1 Open_Sea TSS1500 0.050 1.310 Up 368 cg06012992 Island Intergenic 0.038 -1.199 Down 369 cg11102724 Open_Sea Intergenic 0.042 5.562 Up 370 cg14554813 PGM5P2 Open_Sea Body 0.032 1.180 Up 371 cg23237314 HCG4B Island Body 0.038 1.735 Up 372 cg13249244 N_Shore Intergenic 0.003 1.516 Up 373 cg21028981 Open_Sea Intergenic 0.010 -1.197 Down 374 cg04683479 Open_Sea Intergenic 0.028 -1.289 Down 375 cg16769623 N_Shelf Intergenic 0.007 -1.536 Down 376 cg12507795 Island Intergenic 0.029 -1.319 Down 377 cg22168386 TNFRSF19 Open_Sea Body 0.048 -1.218 Down 378 cg07581633 Open_Sea Intergenic 0.024 -1.145 Down 379 cg19126050 EML1 Open_Sea Body 0.017 1.232 Up 380 cg09851284 Open_Sea Intergenic 0.044 -1.168 Down 381 cg10053235 RAD51B Open_Sea Body 0.031 -1.241 Down 382 cg18235790 Open_Sea Intergenic 0.007 -1.166 Down 383 cg27055313 Island Intergenic 0.019 1.932 Up 384 cg02290163 Open_Sea Intergenic 0.040 -1.239 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 385 cg25037777 Open_Sea Intergenic 0.045 -1.288 Down 386 cg00893657 GAREM Open_Sea Body 0.014 -1.210 Down 387 cg22926869 HHLA2 Open_Sea TSS200 0.007 -1.371 Down 388 cg05732866 Open_Sea Intergenic 0.019 1.389 Up 389 cg24298759 Open_Sea Intergenic 0.018 1.417 Up 390 cg21663357 PDE7B Open_Sea Body 0.043 -1.295 Down 391 cg16500150 Open_Sea Intergenic 0.004 1.288 Up 392 cg13883027 Open_Sea Intergenic 0.014 2.079 Up 393 cg05276469 Island Intergenic 0.039 3.049 Up 394 cg20161548 LUZP1 Open_Sea 5URT 0.048 -1.436 Down 395 cg22836207 Open_Sea Intergenic 0.001 -2.387 Down 396 cg06487085 S_Shelf Intergenic 0.032 1.960 Up 397 cg22026089 PDZRN4 Open_Sea TSS1500 0.034 -2.118 Down 398 cg18665594 Open_Sea Intergenic 0.011 1.325 Up 399 cg25109618 PTPRN2 Island Body 0.019 -1.604 Down 400 cg26690407 S_Shore Intergenic 0.006 2.058 Up 401 cg11393028 POU5F1B Open_Sea TSS1500 0.037 2.194 Up 402 cg18586262 N_Shore Intergenic 0.049 -1.290 Down 403 cg20083297 HLA-DRB6 Open_Sea TSS1500 0.035 -1.613 Down 404 cg01549082 Open_Sea Intergenic 0.032 -1.271 Down 405 cg09091619 Open_Sea Intergenic 0.013 -1.154 Down 406 cg16300918 Open_Sea Intergenic 0.000 1.538 Up 407 cg15189793 HAND2-AS1 N_Shelf Body 0.017 1.165 Up 408 cg13102742 Open_Sea Intergenic 0.007 -2.046 Down 409 cg00095677 ATP2A3 Open_Sea Body 0.035 1.310 Up 410 cg10309005 CYP4V2 Open_Sea Body 0.025 -1.190 Down 411 cg22280068 NLRP6 N_Shelf Body 0.048 1.306 Up 412 cg16868350 Open_Sea Intergenic 0.001 1.123 Up 413 cg14437002 Island Intergenic 0.003 -1.270 Down 414 cg03193182 LOC101927769 Open_Sea TSS1500 0.012 1.281 Up 415 cg08138685 S_Shelf Intergenic 0.028 -2.131 Down 416 cg13367169 N_Shore Intergenic 0.028 -1.497 Down 417 cg10774352 Open_Sea Intergenic 0.004 -1.245 Down 418 cg11288419 SLC18A1 Open_Sea Body 0.030 1.182 Up 419 cg06107030 Open_Sea Intergenic 0.004 -1.438 Down 420 cg18286930 Open_Sea Intergenic 0.048 -1.195 Down 421 cg08570243 LINC00116 Island Body 0.015 1.847 Up 422 cg17499156 Open_Sea Intergenic 0.013 -1.353 Down 423 cg07674804 Open_Sea Intergenic 0.036 -1.435 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 424 cg22774704 FGF12 Open_Sea Body 0.025 2.536 Up 425 cg07652488 S_Shelf Intergenic 0.046 -1.216 Down 426 cg05355592 PTPRG Open_Sea Body 0.048 -1.271 Down 427 cg26389052 PDXK S_Shore Body 0.034 2.115 Up 428 cg18644089 Open_Sea Intergenic 0.031 -1.214 Down 429 cg15828613 S_Shelf Intergenic 0.016 1.387 Up 430 cg15611600 GPALPP1 Island TSS1500 0.002 2.279 Up 431 cg23112360 PLEKHM2 Open_Sea Body 0.007 -1.258 Down 432 cg09768983 Open_Sea Intergenic 0.004 1.297 Up 433 cg22509179 RUNX3 Island Body 0.050 1.161 Up 434 cg26585981 OR4S1 Open_Sea TSS1500 0.004 -1.168 Down 435 cg13670411 RAC1 Open_Sea Body 0.024 -1.289 Down 436 cg19424094 LRRC8B Open_Sea 5URT 0.005 -1.122 Down 437 cg23468456 S_Shore Intergenic 0.009 -1.499 Down 438 cg13639211 Open_Sea Intergenic 0.043 -1.745 Down 439 cg02602925 N_Shelf Intergenic 0.042 -1.331 Down 440 cg26680678 PBX1 Open_Sea Body 0.024 -1.218 Down 441 cg26450240 Open_Sea Intergenic 0.002 2.163 Up 442 cg27170757 RIBC1 Open_Sea Body 0.015 1.186 Up 443 cg11528086 COL13A1 Open_Sea Body 0.045 -1.296 Down 444 cg22668013 HYAL4 Open_Sea 5URT 0.037 -1.316 Down 445 cg06769296 LOC100128239 Island Body 0.000 1.536 Up 446 cg15199699 LINC01389 Open_Sea Body 0.006 1.404 Up 447 cg02675432 PSMD14 Open_Sea Body 0.047 -1.553 Down 448 cg26132114 Island Intergenic 0.008 1.236 Up 449 cg09495738 Island Intergenic 0.015 -3.083 Down 450 cg21744189 Open_Sea Intergenic 0.038 1.331 Up 451 cg01967537 Open_Sea Intergenic 0.003 1.155 Up 452 cg25063469 Open_Sea Intergenic 0.042 -1.227 Down 453 cg00932835 COLEC12 Open_Sea Body 0.014 1.431 Up 454 cg20814213 PRR25 S_Shore Body 0.003 -1.186 Down 455 cg06114987 FOXL1 S_Shore TSS1500 0.020 1.154 Up 456 cg12361223 Open_Sea Intergenic 0.028 1.370 Up 457 cg07649585 TICAM1 S_Shore TSS1500 0.040 -1.226 Down 458 cg19052410 PWRN1 Open_Sea Body 0.008 1.231 Up 459 cg23449993 PIK3R3 Open_Sea Body 0.040 -1.130 Down 460 cg00180644 Open_Sea Intergenic 0.038 -2.020 Down 461 cg23719124 GSTM5 Open_Sea 5URT 0.003 1.271 Up 462 cg06335123 CDC123 Open_Sea Body 0.002 -1.520 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 463 cg26135622 JUP N_Shore 5URT 0.047 -1.263 Down 464 cg25030143 Open_Sea Intergenic 0.011 1.425 Up 465 cg13562929 SFMBT2 Open_Sea Body 0.011 1.174 Up 466 cg10764750 Open_Sea Intergenic 0.000 -1.270 Down 467 cg05364766 LOC349160 Open_Sea Body 0.029 -1.522 Down 468 cg03796003 KCTD5 Island Body 0.023 1.836 Up 469 cg09158015 N_Shore Intergenic 0.001 -2.278 Down 470 cg15892341 PLA1A Open_Sea Body 0.018 -1.309 Down 471 cg27005118 COX10 N_Shore TSS1500 0.007 1.662 Up 472 cg15834632 RCC2 S_Shore Body 0.017 -1.191 Down 473 cg20800221 OAS2 Open_Sea Body 0.002 -1.238 Down 474 cg02648613 Open_Sea Intergenic 0.013 -1.320 Down 475 cg00898157 S_Shore Intergenic 0.017 -1.410 Down 476 cg06889975 N_Shelf Intergenic 0.009 1.179 Up 477 cg07678469 Open_Sea Intergenic 0.027 1.457 Up 478 cg02456976 Open_Sea Intergenic 0.041 1.403 Up 479 cg12614980 Open_Sea Intergenic 0.046 -1.210 Down 480 cg06738063 MLLT4 Open_Sea 3UTR 0.022 -1.784 Down 481 cg04156365 WDR72 Open_Sea Body 0.045 -2.081 Down 482 cg23029597 RSRC2 N_Shore Body 0.036 -1.195 Down 483 cg02040546 LRRC74A Open_Sea Body 0.000 1.452 Up 484 cg00435273 C2orf76 Open_Sea 5URT 0.024 -1.413 Down 485 cg16763089 LINC00654 Open_Sea TSS200 0.020 1.637 Up 486 cg19930004 Island Intergenic 0.018 -1.633 Down 487 cg26810966 LOC728989 Open_Sea TSS1500 0.022 -1.328 Down 488 cg16048421 ANKRD30BP3 Open_Sea Body 0.047 -1.233 Down 489 cg21152981 TMCO3 S_Shelf 5URT 0.032 -1.184 Down 490 cg01678900 Open_Sea Intergenic 0.016 -1.490 Down 491 cg23012654 Open_Sea Intergenic 0.044 -1.439 Down 492 cg09941601 N_Shelf Intergenic 0.021 1.332 Up 493 cg06748804 Open_Sea Intergenic 0.023 -1.282 Down 494 cg06028808 Open_Sea Intergenic 0.011 1.382 Up 495 cg19997606 CGNL1 Open_Sea 3UTR 0.029 -1.302 Down 496 cg04520693 S_Shelf Intergenic 0.047 -1.838 Down 497 cg03154433 TFAP2A N_Shore Body 0.015 1.304 Up 498 cg17413172 Open_Sea Intergenic 0.030 -1.173 Down 499 cg18433519 KIAA0319 Island TSS200 0.042 2.146 Up 500 cg15145341 TPTE2P1 Island Body 0.000 1.429 Up 501 cg07530027 PTPRE Open_Sea 5URT 0.037 1.549 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 502 cg08199273 GLRX3 Island TSS200 0.030 1.453 Up 503 cg21294301 Open_Sea Intergenic 0.008 1.610 Up 504 cg26724949 N_Shore Intergenic 0.048 1.522 Up 505 cg01218414 CCZ1 N_Shore TSS1500 0.007 1.160 Up 506 cg17577442 LOC101929034 N_Shore TSS200 0.027 1.158 Up 507 cg05991929 Open_Sea Intergenic 0.040 -1.338 Down 508 cg03224005 Open_Sea Intergenic 0.049 -1.353 Down 509 cg16175700 KIAA1456 Open_Sea 5URT 0.040 1.630 Up 510 cg16292782 KIF1B N_Shelf Body 0.008 -1.273 Down 511 cg04312578 Open_Sea Intergenic 0.022 -1.373 Down 512 cg12534577 LINC01122 Open_Sea Body 0.049 1.542 Up 513 cg22210905 Open_Sea Intergenic 0.010 1.495 Up 514 cg20968048 Open_Sea Intergenic 0.016 -1.449 Down 515 cg09209679 FAM19A5 Open_Sea Body 0.041 -2.886 Down 516 cg26021304 ZFP57 Open_Sea TSS200 0.042 -1.388 Down 517 cg14752068 N_Shelf Intergenic 0.018 -1.635 Down 518 cg22681945 Open_Sea Intergenic 0.001 -1.877 Down 519 cg21710255 CRISP2 Open_Sea TSS1500 0.024 1.278 Up 520 cg21141470 Open_Sea Intergenic 0.018 -1.304 Down 521 cg01649497 LOC101927815 Open_Sea Body 0.025 1.543 Up 522 cg21993023 CRADD Open_Sea Body 0.015 -1.351 Down 523 cg19508985 Open_Sea Intergenic 0.006 1.245 Up 524 cg01667892 PRDM9 Open_Sea TSS200 0.029 1.224 Up 525 cg20370184 SLC44A4 Open_Sea Body 0.024 -6.184 Down 526 cg23576855 AHRR S_Shelf Body 0.028 1.225 Up 527 cg12759288 KRT40 Open_Sea 5URT 0.012 -1.177 Down 528 cg00123214 RWDD3 S_Shelf 5URT 0.020 -1.715 Down 529 cg12718582 S_Shore Intergenic 0.012 -1.163 Down 530 cg13468767 N_Shelf Intergenic 0.026 -1.453 Down 531 cg11519740 Open_Sea Intergenic 0.010 -2.336 Down 532 cg05848650 MB21D2 Open_Sea Body 0.011 -1.224 Down 533 cg14912375 LINC01237 S_Shore Body 0.015 -1.318 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA Supplementary Table 2. CpG methylation sites that showed significantly different methylation between Non-Responders (NR) and Responders (R) in myogenic progenitor cells (HSkMCs).

Relation to CpG content and Functional genome p-value Fold Change Fold Change (Description) # CpG site Gene Name neighborhood content distribution (R vs. NR) (R vs. NR) (R vs. NR) 1 cg07918723 Open_Sea Body 0.045 -1.577 Down 2 cg00426486 S_Shelf Intergenic 0.016 1.643 Up 3 cg16288318 RP11-315H15.1 S_Shore TSS1500 0.032 1.503 Up 4 cg10387963 ADAM3A Island Body 0.026 1.872 Up 5 cg01128482 HOXD3 S_Shore TSS200 0.011 2.007 Up 6 cg15760709 Open_Sea Body 0.008 1.426 Up 7 cg16468843 ATP2B2 Island TSS1500 0.008 1.631 Up 8 cg04459447 N_Shelf Intergenic 0.031 1.539 Up 9 cg07916022 LYPD1 Island 3UTR 0.013 1.306 Up 10 cg08522426 RP11-649A16.1 N_Shelf Intergenic 0.000 2.565 Up 11 cg22702707 CA5B Island TSS1500 0.028 2.983 Up 12 cg20771240 RP11-713P17.3 N_Shore Body 0.000 2.684 Up 13 cg21634283 N_Shore Intergenic 0.039 1.541 Up 14 cg17655970 RP11-315H15.1 Island Body 0.001 5.373 Up 15 cg26899005 HCFC1 Open_Sea 3UTR 0.025 1.342 Up 16 cg05824174 Open_Sea Body 0.022 -2.487 Down 17 cg25687358 DUOXA1 S_Shore Body 0.037 1.634 Up 18 cg24904436 ARHGAP39 S_Shore Body 0.040 -1.558 Down 19 cg24820672 RP11-315H15.1 N_Shore Body 0.012 1.914 Up 20 cg25618439 S_Shore Intergenic 0.031 1.648 Up 21 cg10627377 TKTL2 Island TSS200 0.029 1.350 Up 22 cg07705650 Open_Sea Intergenic 0.025 1.750 Up 23 cg20447730 Island Intergenic 0.021 1.388 Up 24 cg06684201 N_Shore Body 0.010 -1.401 Down 25 cg03278514 Open_Sea Intergenic 0.047 -3.483 Down 26 cg18051461 HIC1 Island TSS1500 0.009 1.754 Up 27 cg19961153 ALPPL2 N_Shore TSS1500 0.006 2.832 Up 28 cg18021902 WRAP73 Island TSS1500 0.020 1.429 Up 29 cg18339359 SLC25A37 Open_Sea Body 0.032 2.222 Up 30 cg22607164 Open_Sea Intergenic 0.004 1.317 Up 31 cg07192718 TMEM61 N_Shore TSS1500 0.009 1.406 Up 32 cg16091952 ZNF354C S_Shore 5URT 0.012 1.432 Up 33 cg09584492 ARHGAP33 N_Shore TSS1500 0.017 2.120 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 34 cg05649108 Island Body 0.033 6.367 Up 35 cg24467349 GSTM5 Open_Sea TSS200 0.041 2.648 Up 36 cg16788050 Island Intergenic 0.014 1.857 Up 37 cg14316660 S_Shore Intergenic 0.040 -1.676 Down 38 cg04392266 Island Intergenic 0.002 1.513 Up 39 cg17628491 RPTOR N_Shelf Body 0.047 -1.529 Down 40 cg03486986 RP11-315H15.1 S_Shore TSS1500 0.005 3.579 Up 41 cg24541426 HOXD3 S_Shore 5URT 0.026 1.762 Up 42 cg20803293 GSTM5 Open_Sea TSS200 0.049 2.071 Up 43 cg21778348 HOXA-AS3 Island Body 0.036 1.445 Up 44 cg08816590 PDE1B Open_Sea TSS1500 0.024 -2.060 Down 45 cg11680055 GSTM1 Island TSS200 0.011 2.927 Up 46 cg07752120 Open_Sea Intergenic 0.018 1.588 Up 47 cg22337407 Open_Sea Intergenic 0.035 1.870 Up 48 cg19787013 RECQL4 S_Shelf Body 0.021 -2.381 Down 49 cg13711424 S_Shore Body 0.009 1.649 Up 50 cg12311815 LYPD1 Island 3UTR 0.014 1.364 Up 51 cg22151941 HIC1 Island TSS1500 0.006 2.682 Up 52 cg16115627 DPP6 Island 3UTR 0.021 1.770 Up 53 cg18862481 TRH Island 1stExon 0.000 2.132 Up 54 cg16180556 GSTM1 Island TSS200 0.033 4.149 Up 55 cg15292765 Open_Sea Body 0.008 1.804 Up 56 cg24506221 GSTM1 Island TSS200 0.026 11.807 Up 57 cg02344911 HOXC8 Island 1stExon 0.000 -2.398 Down 58 cg15146462 RP11-317J19.1 Island Intergenic 0.006 1.667 Up 59 cg10471832 RBM44 Island 1stExon 0.001 1.352 Up 60 cg06065141 HIC1 Island TSS1500 0.033 1.846 Up 61 cg27502298 Open_Sea Intergenic 0.029 -1.328 Down 62 cg01376826 N_Shore Body 0.010 -6.065 Down 63 cg13830619 Open_Sea Intergenic 0.029 -1.444 Down 64 cg11969330 CYP4V2 Open_Sea Body 0.036 -1.672 Down 65 cg06559318 HLA-DRB6 Open_Sea Body 0.011 -3.316 Down 66 cg08415785 NR0B1 S_Shore TSS1500 0.034 1.778 Up 67 cg01067139 Island Intergenic 0.002 1.779 Up 68 cg26130488 TBX4 Island Intergenic 0.007 1.600 Up 69 cg08515884 RP11-24J23.2 Open_Sea Body 0.024 1.717 Up 70 cg06376196 Open_Sea Body 0.013 -1.926 Down 71 cg16109381 CHRM5 Open_Sea 5URT 0.028 -2.073 Down 72 cg18112748 RPS6KC1 Open_Sea 5URT 0.043 1.407 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 73 cg00524136 RP11-47I22.3 Open_Sea TSS200 0.045 -2.206 Down 74 cg06553867 Open_Sea Intergenic 0.042 -1.412 Down 75 cg13799572 Open_Sea Body 0.037 1.452 Up 76 cg08138245 N_Shelf Intergenic 0.028 1.943 Up 77 cg18313151 CLUL1 Open_Sea 5URT 0.009 1.409 Up 78 cg16661099 Open_Sea Intergenic 0.022 -1.540 Down 79 cg26590106 N_Shelf Body 0.042 -2.520 Down 80 cg11437253 RP11-649A16.1 Island Intergenic 0.003 1.477 Up 81 cg14629612 Open_Sea Body 0.049 -2.250 Down 82 cg15858978 Open_Sea Intergenic 0.002 -1.721 Down 83 cg13117487 Open_Sea Intergenic 0.028 1.359 Up 84 cg00975375 Island Intergenic 0.001 1.460 Up 85 cg06139856 Open_Sea Body 0.013 -2.931 Down 86 cg11628320 Open_Sea Body 0.001 -4.327 Down 87 cg22599996 EGR2 Open_Sea Intergenic 0.023 1.374 Up 88 cg10875004 WDFY3 Open_Sea 5URT 0.034 1.601 Up 89 cg27009374 RP11-292F22.7 S_Shore Intergenic 0.019 -1.470 Down 90 cg12397118 ANKRD10 Open_Sea Body 0.042 1.604 Up 91 cg07575056 MAPKAP1 Open_Sea Body 0.001 1.676 Up 92 cg16065899 ALX4 S_Shore TSS1500 0.025 1.627 Up 93 cg22750984 PPCDC Open_Sea Intergenic 0.031 -1.598 Down 94 cg04344225 RP4-660B20.1 Open_Sea Body 0.014 1.747 Up 95 cg00715139 Open_Sea Body 0.035 -2.274 Down 96 cg17813879 SH2D4A Open_Sea 3UTR 0.036 1.356 Up 97 cg26906343 Open_Sea Body 0.002 1.401 Up 98 cg04063547 RHCE Open_Sea TSS1500 0.049 1.526 Up 99 cg27365701 DUSP6 N_Shore Body 0.037 1.903 Up 100 cg08884363 N_Shelf Body 0.028 -1.379 Down 101 cg10456132 RP11-171A24.2 Open_Sea TSS1500 0.002 -1.420 Down 102 cg17220237 Open_Sea Body 0.019 -1.378 Down 103 cg20476019 Open_Sea Body 0.025 -1.750 Down 104 cg20512044 Open_Sea Body 0.048 -1.538 Down 105 cg05526364 Open_Sea Body 0.006 -2.419 Down 106 cg01469168 LIMA1 Open_Sea Body 0.041 1.313 Up 107 cg00161838 ANKRD10 Open_Sea Body 0.022 1.652 Up 108 cg16702469 CCDC141 Open_Sea Body 0.008 1.403 Up 109 cg21810086 IL7R Open_Sea TSS1500 0.025 -2.086 Down 110 cg04484376 ARSE Open_Sea 1stExon 0.019 1.673 Up 111 cg16664858 LRRC15 Open_Sea 5URT 0.006 1.458 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 112 cg04506342 BAZ2B Open_Sea 5URT 0.043 -1.806 Down 113 cg17025037 Open_Sea Body 0.031 1.772 Up 114 cg16020483 CASZ1 S_Shelf 5URT 0.045 -2.835 Down 115 cg07303167 RIBC1 Open_Sea Body 0.045 1.657 Up 116 cg02799905 Open_Sea Body 0.005 -2.277 Down 117 cg11910375 HOXA-AS3 S_Shore Body 0.045 1.528 Up 118 cg12471283 Open_Sea Intergenic 0.002 -1.470 Down 119 cg01234121 RP11-335O13.8 Open_Sea Body 0.007 -7.084 Down 120 cg17462814 CCNL1 Open_Sea Body 0.008 -1.908 Down 121 cg15686265 Open_Sea Intergenic 0.044 -2.150 Down 122 cg14496239 HEATR2 Island Body 0.033 -1.758 Down 123 cg15620499 LY6G6E S_Shelf Body 0.002 1.416 Up 124 cg27286626 Open_Sea Intergenic 0.008 -1.381 Down 125 cg15850874 Open_Sea Body 0.019 2.201 Up 126 cg05752891 MAP3K13 N_Shore TSS1500 0.017 1.427 Up 127 cg23728836 U1 Open_Sea Intergenic 0.046 -4.130 Down 128 cg06283052 Open_Sea Intergenic 0.009 -2.164 Down 129 cg07413957 CYB5B Open_Sea Body 0.004 -1.785 Down 130 cg07895205 BCAR3 Open_Sea 5URT 0.032 1.433 Up 131 cg24925741 N_Shore Intergenic 0.018 4.763 Up 132 cg13211008 Open_Sea Body 0.026 3.824 Up 133 cg09798253 ATP13A4-AS1 Open_Sea Body 0.008 -1.452 Down 134 cg04750595 Open_Sea Intergenic 0.021 1.452 Up 135 cg02966448 CPEB4 S_Shelf TSS1500 0.045 -1.336 Down 136 cg15845365 Open_Sea Body 0.003 -4.472 Down 137 cg12179578 Open_Sea 3UTR 0.001 4.949 Up 138 cg22454297 LRMP Open_Sea 5URT 0.030 1.281 Up 139 cg07482223 SFTA2 Open_Sea 3UTR 0.015 1.460 Up 140 cg02518609 EPC1 Open_Sea Body 0.005 -1.511 Down 141 cg02265440 RP11-486O13.2 Open_Sea Intergenic 0.006 -1.719 Down 142 cg25259265 ADPRHL1 Open_Sea 5URT 0.004 -1.492 Down 143 cg13689756 NSMAF Open_Sea Body 0.024 -1.415 Down 144 cg23009831 Open_Sea Intergenic 0.007 -2.316 Down 145 cg00448770 Open_Sea Body 0.018 1.370 Up 146 cg12095712 RP11-411K7.1 Open_Sea Body 0.043 -2.828 Down 147 cg27472701 MET Open_Sea 5URT 0.007 1.321 Up 148 cg02675264 N_Shore Intergenic 0.015 1.626 Up 149 cg18140087 Open_Sea Body 0.010 -1.707 Down 150 cg23345300 HOXD-AS2 N_Shelf Body 0.015 -1.372 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 151 cg02079756 CTB-7E3.1 Open_Sea Body 0.017 2.066 Up 152 cg13910785 N_Shelf Body 0.029 -4.438 Down 153 cg06075393 RASSF2 Open_Sea 5URT 0.044 1.532 Up 154 cg00167628 Open_Sea Body 0.014 2.158 Up 155 cg00794198 MUM1L1 Open_Sea 5URT 0.015 1.644 Up 156 cg18256118 Open_Sea Intergenic 0.026 -1.957 Down 157 cg15785681 N_Shelf Intergenic 0.005 -1.426 Down 158 cg23646059 CTC-441N14.2 Open_Sea 5URT 0.047 -1.532 Down 159 cg15930598 Open_Sea Intergenic 0.001 1.516 Up 160 cg10590338 Open_Sea Intergenic 0.011 -4.039 Down 161 cg07065257 Open_Sea Body 0.012 -1.816 Down 162 cg27483217 N_Shore Intergenic 0.043 -2.341 Down 163 cg01511234 RP11-24B21.1 Open_Sea Body 0.037 -1.751 Down 164 cg22173191 C12orf75 Open_Sea Intergenic 0.035 1.573 Up 165 cg05567468 MET Open_Sea 5URT 0.019 -1.447 Down 166 cg19546583 Island Intergenic 0.006 1.983 Up 167 cg19243717 Open_Sea Intergenic 0.001 2.255 Up 168 cg03316062 Open_Sea Intergenic 0.012 -1.401 Down 169 cg23135533 TRDN Open_Sea TSS1500 0.008 -1.637 Down 170 cg13920856 TANC1 Open_Sea 5URT 0.032 -1.582 Down 171 cg00847221 Open_Sea Intergenic 0.024 2.104 Up 172 cg01819555 Open_Sea Intergenic 0.004 -1.664 Down 173 cg21408813 S_Shelf Intergenic 0.006 -2.564 Down 174 cg27066203 Open_Sea Body 0.047 -1.816 Down 175 cg14593372 Open_Sea Intergenic 0.021 -1.610 Down 176 cg14228103 PTN Open_Sea 5URT 0.032 2.412 Up 177 cg05108024 Open_Sea Body 0.018 -1.846 Down 178 cg27288153 Open_Sea Body 0.027 1.429 Up 179 cg13053653 HOXD3 N_Shore 3UTR 0.036 1.477 Up 180 cg27625131 N_Shore Intergenic 0.035 -1.799 Down 181 cg12453623 Open_Sea Intergenic 0.045 -1.534 Down 182 cg09804328 RP11-320M16.2 Open_Sea 5URT 0.038 -1.558 Down 183 cg04956949 WBSCR22 S_Shore Body 0.050 1.758 Up 184 cg25520068 GSTM5 Open_Sea TSS200 0.023 3.077 Up 185 cg09619282 PLCL2 S_Shelf Body 0.002 -1.369 Down 186 cg02283106 CA5B Island TSS1500 0.027 1.969 Up 187 cg01441501 Open_Sea Intergenic 0.036 1.610 Up 188 cg27610545 TRHDE Open_Sea Body 0.002 -1.499 Down 189 cg04819618 Open_Sea Intergenic 0.014 1.871 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 190 cg16345566 S_Shore Body 0.017 1.955 Up 191 cg26575584 RP11-486O13.2 Open_Sea Intergenic 0.007 -2.075 Down 192 cg25174111 MUS81 S_Shelf Body 0.048 1.769 Up 193 cg24384830 RP11-277P12.7 Open_Sea 5URT 0.007 1.405 Up 194 cg18223474 RP11-960L18.1 Open_Sea Intergenic 0.005 1.659 Up 195 cg02923394 Open_Sea Intergenic 0.003 1.709 Up 196 cg13681850 Open_Sea Intergenic 0.024 1.592 Up 197 cg04582254 N_Shore Body 0.039 -1.793 Down 198 cg18385852 ACTN1 Open_Sea Body 0.048 -1.495 Down 199 cg04366032 HEPH Open_Sea 5URT 0.048 -1.547 Down 200 cg18750960 HOXD3 Island 1stExon 0.016 1.645 Up 201 cg12969193 HOXD9 S_Shore Body 0.013 1.662 Up 202 cg16956496 Open_Sea Body 0.041 1.528 Up 203 cg06599983 MPZ Open_Sea Body 0.002 -2.199 Down 204 cg14685356 SYNE1 Open_Sea Body 0.011 1.756 Up 205 cg27467876 Open_Sea Body 0.003 -3.712 Down 206 cg02662417 ARID1B Open_Sea Body 0.010 -1.542 Down 207 cg24933714 IGF1R N_Shore Body 0.048 -1.485 Down 208 cg20601028 Open_Sea Intergenic 0.019 -1.800 Down 209 cg19257111 PTPLAD1 Open_Sea Body 0.020 -1.937 Down 210 cg05404009 Open_Sea Body 0.050 1.434 Up 211 cg21375506 Open_Sea Body 0.007 1.445 Up 212 cg07175786 RP11-202G18.1 Open_Sea Intergenic 0.025 -1.702 Down 213 cg02362518 S_Shore TSS1500 0.041 1.582 Up 214 cg01206193 Open_Sea Intergenic 0.006 1.510 Up 215 cg27531206 Open_Sea Body 0.049 -1.471 Down 216 cg23947654 Open_Sea Body 0.045 -2.173 Down 217 cg17348244 HEATR2 Open_Sea Body 0.002 -6.733 Down 218 cg04795640 ADORA2A Open_Sea 5URT 0.012 -1.542 Down 219 cg00093099 S_Shore Body 0.016 1.405 Up 220 cg20177995 MAP2 Open_Sea 5URT 0.030 -1.348 Down 221 cg03956212 ANKRD44-IT1 Open_Sea Body 0.026 -2.091 Down 222 cg04328575 Open_Sea Body 0.040 -1.770 Down 223 cg27185978 Open_Sea Body 0.000 -1.351 Down 224 cg03654147 RP5-865N13.2 Open_Sea Intergenic 0.018 1.370 Up 225 cg09048205 RP11-43F13.1 Open_Sea Body 0.012 -1.468 Down 226 cg07876831 TMCO3 N_Shelf Body 0.041 -1.702 Down 227 cg21406720 N_Shore Intergenic 0.031 -1.647 Down 228 cg01473155 N_Shelf Intergenic 0.004 1.619 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 229 cg08447175 Open_Sea Intergenic 0.011 1.665 Up 230 cg04808223 Open_Sea Body 0.012 1.405 Up 231 cg11598658 NAV3 Open_Sea Body 0.045 -1.782 Down 232 cg19085846 Open_Sea Body 0.037 1.744 Up 233 cg13175739 STYK1 Open_Sea 5URT 0.010 1.544 Up 234 cg21958069 MIR196A1 N_Shelf TSS200 0.010 1.432 Up 235 cg01666088 SLA Open_Sea Body 0.045 -1.510 Down 236 cg26279336 HOXB-AS3 S_Shore Body 0.002 1.797 Up 237 cg27461730 Open_Sea Intergenic 0.003 -2.245 Down 238 cg18144710 Open_Sea Body 0.011 -1.904 Down 239 cg25837045 Open_Sea Intergenic 0.007 1.536 Up 240 cg07337200 S_Shelf Body 0.005 1.655 Up 241 cg10408165 Open_Sea Intergenic 0.018 2.059 Up 242 cg26487259 PEAK1 N_Shore 5URT 0.007 1.626 Up 243 cg14601662 Open_Sea Intergenic 0.029 -3.295 Down 244 cg07149083 RP11-420N3.2 Open_Sea Intergenic 0.020 2.343 Up 245 cg01828169 Open_Sea Intergenic 0.003 -1.672 Down 246 cg07167122 Open_Sea Intergenic 0.019 -1.766 Down 247 cg19574388 RP11-448G15.3 Open_Sea Intergenic 0.013 -1.338 Down 248 cg09787640 Open_Sea Body 0.035 -2.641 Down 249 cg24175014 Open_Sea Intergenic 0.009 1.779 Up 250 cg04532906 N_Shelf Body 0.035 1.395 Up 251 cg13716778 Open_Sea Intergenic 0.019 -1.415 Down 252 cg17857357 Open_Sea Intergenic 0.040 1.394 Up 253 cg24683680 EVX2 N_Shelf TSS200 0.005 2.389 Up 254 cg01378698 SOCS4 N_Shore 5URT 0.010 -1.585 Down 255 cg07548388 AC133919.6 Open_Sea Body 0.017 1.509 Up 256 cg25487118 SLC25A13 Open_Sea Body 0.039 -1.393 Down 257 cg23473401 Open_Sea Body 0.005 -1.740 Down 258 cg25813100 ZNF385D Open_Sea Intergenic 0.023 1.429 Up 259 cg07197230 CECR2 Open_Sea Body 0.022 -1.488 Down 260 cg22777560 N_Shore Body 0.013 2.398 Up 261 cg01205208 Open_Sea Body 0.000 -1.895 Down 262 cg16246747 ACOXL S_Shore 5URT 0.006 -1.606 Down 263 cg10122899 Open_Sea Body 0.002 -1.595 Down 264 cg17095797 FOXL1 S_Shore TSS200 0.016 2.171 Up 265 cg21771097 U6 Open_Sea 5URT 0.014 -1.450 Down 266 cg08231949 Open_Sea Intergenic 0.048 -1.513 Down 267 cg20086657 Island Intergenic 0.025 -1.570 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 268 cg23564869 Open_Sea Intergenic 0.043 -1.973 Down 269 cg07811864 Open_Sea Intergenic 0.042 2.055 Up 270 cg17371709 NAALADL2 Open_Sea Body 0.023 -1.750 Down 271 cg04861073 S_Shore Intergenic 0.042 -3.488 Down 272 cg16490805 S_Shelf Intergenic 0.025 -1.418 Down 273 cg23584734 RP11-353M9.1 Open_Sea Body 0.007 -1.919 Down 274 cg26336232 Open_Sea Intergenic 0.035 -1.556 Down 275 cg25536014 CTD-2297D10.2 Island Body 0.004 -1.342 Down 276 cg05407200 S_Shelf Intergenic 0.032 -1.708 Down 277 cg18854736 Open_Sea Intergenic 0.029 -1.701 Down 278 cg26388471 Open_Sea Intergenic 0.003 -1.606 Down 279 cg08283200 Open_Sea Body 0.025 1.917 Up 280 cg15050722 SPATS2 Open_Sea Body 0.024 -1.877 Down 281 cg23044178 MICAL2 S_Shelf 5URT 0.045 -1.376 Down 282 cg15230952 DYRK3 N_Shelf Intergenic 0.016 -1.432 Down 283 cg10860832 Open_Sea Intergenic 0.011 -1.895 Down 284 cg07071874 Open_Sea Intergenic 0.040 -2.144 Down 285 cg08356333 Open_Sea Intergenic 0.004 -1.697 Down 286 cg01143579 HIC1 Island TSS1500 0.040 1.555 Up 287 cg23602489 CUX1 Open_Sea Body 0.019 -1.469 Down 288 cg06961873 TMEM57 Open_Sea 3UTR 0.019 -1.707 Down 289 cg06286533 WNK2 Open_Sea Body 0.045 1.500 Up 290 cg10811640 Open_Sea Intergenic 0.008 -3.022 Down 291 cg23169588 TMCO3 N_Shelf Body 0.014 1.377 Up 292 cg08331829 MKKS N_Shore TSS200 0.049 -2.033 Down 293 cg20790798 CTD-2194D22.2 Island TSS1500 0.004 1.344 Up 294 cg08138478 Open_Sea Body 0.006 -1.601 Down 295 cg14157527 S_Shelf Body 0.022 1.470 Up 296 cg26108171 RP11-649A16.1 Open_Sea Intergenic 0.011 1.527 Up 297 cg11277483 C9orf3 N_Shore Body 0.037 1.475 Up 298 cg16507569 N_Shore Body 0.045 1.594 Up 299 cg12377591 CPQ Open_Sea 5URT 0.023 -1.521 Down 300 cg18391610 CA5B Island TSS1500 0.020 2.009 Up 301 cg22997562 Open_Sea Intergenic 0.023 1.782 Up 302 cg11242720 Open_Sea Intergenic 0.041 1.374 Up 303 cg08600378 PRHOXNB Open_Sea TSS200 0.008 2.813 Up 304 cg26993647 CTD-2021J15.2 Open_Sea Intergenic 0.031 -2.080 Down 305 cg14421879 APOL6 Open_Sea TSS1500 0.000 1.729 Up 306 cg12650227 LCE3C Open_Sea TSS1500 0.031 1.684 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 307 cg06508490 Open_Sea Body 0.042 1.399 Up 308 cg11585022 CTC-551A13.2 N_Shore TSS1500 0.030 3.459 Up 309 cg04560372 Open_Sea Intergenic 0.042 2.308 Up 310 cg15725086 RP11-348A11.4 Open_Sea Body 0.014 1.635 Up 311 cg10182293 Open_Sea Body 0.012 -1.868 Down 312 cg13893036 Open_Sea Intergenic 0.004 -1.956 Down 313 cg14429748 ASTN2 Open_Sea Body 0.013 1.683 Up 314 cg25214552 Open_Sea Intergenic 0.023 -1.546 Down 315 cg26796873 TMEM126A S_Shore 5URT 0.020 -1.547 Down 316 cg22134054 Open_Sea Body 0.016 -1.598 Down 317 cg02797907 Open_Sea Intergenic 0.030 -1.498 Down 318 cg06371647 RYR2 Open_Sea Body 0.045 2.632 Up 319 cg10213821 BUD31 N_Shore Body 0.002 -2.235 Down 320 cg06945179 Open_Sea Body 0.015 1.445 Up 321 cg02240494 RP11-616K22.3 S_Shore Body 0.006 -1.292 Down 322 cg25525600 RP11-429B14.1 Open_Sea Intergenic 0.039 -2.053 Down 323 cg21692434 Open_Sea Body 0.003 1.372 Up 324 cg16769623 N_Shelf Intergenic 0.017 -1.701 Down 325 cg25009553 Open_Sea Intergenic 0.037 1.696 Up 326 cg16552533 Open_Sea Intergenic 0.046 -1.340 Down 327 cg20604028 RP11-486M23.2 Open_Sea Intergenic 0.005 -1.442 Down 328 cg24242384 Island Body 0.049 1.869 Up 329 cg27055313 Island Intergenic 0.003 2.664 Up 330 cg26146888 N_Shelf Body 0.022 1.364 Up 331 cg22926869 HHLA2 Open_Sea TSS200 0.003 -1.485 Down 332 cg10531724 ERAP2 Open_Sea Body 0.021 -1.448 Down 333 cg04545078 HECTD2 Open_Sea Body 0.008 -1.429 Down 334 cg01532357 PHF20 Open_Sea Body 0.046 -1.509 Down 335 cg16279695 NDUFA12 Open_Sea Body 0.037 -1.802 Down 336 cg07596617 Open_Sea Intergenic 0.000 1.415 Up 337 cg13883027 Open_Sea Intergenic 0.002 2.712 Up 338 cg22836207 Open_Sea Intergenic 0.003 -2.226 Down 339 cg07851262 Island Body 0.027 1.331 Up 340 cg23618713 RP11-486O13.2 Open_Sea Intergenic 0.049 1.461 Up 341 cg12139369 CDC42EP4 S_Shelf 5URT 0.001 1.869 Up 342 cg10721734 Open_Sea Body 0.020 2.170 Up 343 cg12821056 Open_Sea Intergenic 0.048 1.513 Up 344 cg11878016 SEMA3D S_Shore Intergenic 0.007 1.611 Up 345 cg25109618 Island Body 0.016 -2.048 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 346 cg16198692 CDO1 S_Shore TSS1500 0.049 2.182 Up 347 cg26690407 S_Shore Intergenic 0.024 1.691 Up 348 cg24817351 Open_Sea Body 0.026 -1.577 Down 349 cg10384676 PRLR Open_Sea 5URT 0.017 -1.787 Down 350 cg18575740 RP11-471J12.1 N_Shore Body 0.035 1.604 Up 351 cg18886245 S_Shore Body 0.020 1.681 Up 352 cg13102742 Open_Sea Intergenic 0.033 -1.830 Down 353 cg01242422 N_Shelf 5URT 0.045 -1.626 Down 354 cg23910043 MIR1255B2 Open_Sea TSS1500 0.027 -1.518 Down 355 cg07696877 Open_Sea Intergenic 0.008 -1.468 Down 356 cg08138685 S_Shelf Intergenic 0.016 -2.627 Down 357 cg10774352 Open_Sea Intergenic 0.015 -1.750 Down 358 cg06107030 Open_Sea Intergenic 0.002 -1.950 Down 359 cg19048658 Open_Sea Intergenic 0.019 -2.238 Down 360 cg15103566 AC096559.1 Open_Sea Body 0.018 -1.585 Down 361 cg13401658 Open_Sea Intergenic 0.049 -1.710 Down 362 cg04918548 Open_Sea Intergenic 0.015 1.380 Up 363 cg01188753 ZNFX1-AS1 S_Shore Body 0.032 -1.411 Down 364 cg04132407 Open_Sea Intergenic 0.021 -1.979 Down 365 cg07803859 LCOR N_Shore TSS1500 0.022 1.542 Up 366 cg02432678 EIF2C2 Open_Sea Body 0.030 1.744 Up 367 cg08851607 ASTN1 N_Shelf Body 0.038 1.604 Up 368 cg12670517 GS1-122H1.2 Open_Sea Body 0.012 1.922 Up 369 cg10385522 HLA-DRB1 Open_Sea TSS1500 0.006 -5.287 Down 370 cg07652488 S_Shelf Intergenic 0.012 -1.350 Down 371 cg24744596 Open_Sea Body 0.021 -1.809 Down 372 cg04597221 Open_Sea Body 0.018 2.015 Up 373 cg15828613 RP11-152H18.3 S_Shelf Intergenic 0.015 1.396 Up 374 cg19103950 RP11-325F22.2 Open_Sea Intergenic 0.018 -1.387 Down 375 cg13637193 Open_Sea Body 0.032 -2.559 Down 376 cg03555715 RP11-89M16.1 Open_Sea Body 0.021 -1.512 Down 377 cg15613687 F8 N_Shelf TSS1500 0.019 1.492 Up 378 cg13426510 Open_Sea Body 0.040 -1.635 Down 379 cg07984380 Open_Sea Body 0.024 -4.938 Down 380 cg23468456 RP11-200A1.1 S_Shore Intergenic 0.017 -1.485 Down 381 cg16345059 HHAT Open_Sea Body 0.027 1.770 Up 382 cg21552242 SHOX2 N_Shore 3UTR 0.037 1.642 Up 383 cg27079096 OR52B4 Open_Sea TSS200 0.012 -2.635 Down 384 cg26450240 Open_Sea Intergenic 0.011 2.082 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 385 cg10793307 TUSC1 S_Shore TSS1500 0.041 1.575 Up 386 cg07927909 ADAM3A S_Shore TSS200 0.037 1.707 Up 387 cg06769296 RP11-713P17.3 Island Body 0.001 2.152 Up 388 cg22480773 GLYATL3 Open_Sea TSS1500 0.006 -1.334 Down 389 cg15199699 RP11-511I2.2 Open_Sea Body 0.004 1.490 Up 390 cg12259523 Open_Sea Intergenic 0.039 1.539 Up 391 cg01559641 Open_Sea Intergenic 0.009 -1.797 Down 392 cg09584060 RP11-215N21.1 Open_Sea TSS1500 0.001 1.519 Up 393 cg27064596 Open_Sea Intergenic 0.014 2.593 Up 394 cg12361223 RP11-649A16.1 Open_Sea Intergenic 0.027 1.600 Up 395 cg09746326 DCUN1D2-AS2 Open_Sea Body 0.024 -1.383 Down 396 cg21718113 LCE3C Open_Sea TSS1500 0.014 2.164 Up 397 cg05262382 Island Intergenic 0.028 1.315 Up 398 cg17406597 Open_Sea Intergenic 0.016 -1.500 Down 399 cg02561226 Open_Sea Intergenic 0.044 -1.401 Down 400 cg20516015 Open_Sea Intergenic 0.010 3.218 Up 401 cg05696779 S_Shore 5URT 0.007 3.333 Up 402 cg19689322 KCNQ4 S_Shore Body 0.029 1.393 Up 403 cg25218411 Open_Sea Intergenic 0.039 1.717 Up 404 cg15097422 FBLN2 Open_Sea 5URT 0.034 1.584 Up 405 cg16232867 Open_Sea Intergenic 0.024 2.466 Up 406 cg20726993 RP11-631B21.1 Open_Sea Body 0.003 1.738 Up 407 cg01707943 Open_Sea Intergenic 0.034 -1.502 Down 408 cg03796003 Island Body 0.044 1.777 Up 409 cg03391662 DAAM1 Open_Sea Body 0.017 -1.597 Down 410 cg16989719 N_Shelf Intergenic 0.018 -2.792 Down 411 cg08320351 Open_Sea Body 0.019 -1.521 Down 412 cg27005118 COX10 N_Shore TSS1500 0.002 2.703 Up 413 cg13212048 CCDC57 Open_Sea 5URT 0.022 -1.642 Down 414 cg14401833 Open_Sea Intergenic 0.023 -2.651 Down 415 cg00309970 CHIT1 Open_Sea Intergenic 0.028 1.484 Up 416 cg14766620 AC018816.4 N_Shore Body 0.030 -1.580 Down 417 cg07795618 LIMD1 Open_Sea Body 0.034 1.381 Up 418 cg21296708 PLCB4 Open_Sea 5URT 0.033 1.549 Up 419 cg13226272 Open_Sea Intergenic 0.029 -10.036 Down 420 cg25010415 Open_Sea Body 0.017 2.855 Up 421 cg14742615 S_Shore Intergenic 0.033 1.353 Up 422 cg07388733 Open_Sea Intergenic 0.008 2.351 Up 423 cg22875239 Open_Sea Body 0.029 -1.741 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 424 cg14418968 Open_Sea Body 0.038 -1.695 Down 425 cg02456976 Open_Sea Intergenic 0.011 1.986 Up 426 cg16962612 RP11-543F8.2 Open_Sea Intergenic 0.029 1.529 Up 427 cg06738063 MLLT4 Open_Sea 3UTR 0.015 -1.840 Down 428 cg11486744 Open_Sea Body 0.037 -2.385 Down 429 cg23002857 RP4-724E13.2 Open_Sea Intergenic 0.006 -1.638 Down 430 cg21766474 Open_Sea Body 0.044 -1.605 Down 431 cg15184869 Open_Sea Body 0.044 1.740 Up 432 cg26365743 Open_Sea Body 0.019 -3.125 Down 433 cg22098048 TNNI1 Open_Sea Intergenic 0.037 -1.503 Down 434 cg26576353 N_Shore Intergenic 0.022 -1.449 Down 435 cg16105569 C12orf70 Open_Sea Body 0.018 -1.782 Down 436 cg12212089 Open_Sea Intergenic 0.006 -3.421 Down 437 cg19198148 BCL6 N_Shelf 5URT 0.024 -1.532 Down 438 cg24769381 GAB2 Open_Sea 1stExon 0.042 1.673 Up 439 cg06584796 Open_Sea Body 0.048 -2.150 Down 440 cg20078646 Open_Sea Intergenic 0.041 1.701 Up 441 cg07388969 RP11-346D14.1 Open_Sea Intergenic 0.026 -1.952 Down 442 cg17738613 Open_Sea Body 0.011 2.158 Up 443 cg26679884 N_Shore Body 0.025 -1.996 Down 444 cg19070118 ZNF717 Open_Sea Intergenic 0.022 -2.553 Down 445 cg22769840 Open_Sea Intergenic 0.020 -1.810 Down 446 cg19154950 Open_Sea Intergenic 0.049 -2.461 Down 447 cg22713019 Open_Sea Body 0.027 -1.485 Down 448 cg00854448 N_Shore Body 0.003 1.565 Up 449 cg09838390 RP11-471J12.1 N_Shore Body 0.018 1.464 Up 450 cg11130234 Open_Sea Intergenic 0.044 1.963 Up 451 cg22379359 AF196970.3 S_Shore Intergenic 0.020 -1.353 Down 452 cg07530027 PTPRE Open_Sea 5URT 0.024 1.682 Up 453 cg12576596 Open_Sea Body 0.012 2.746 Up 454 cg17824102 Open_Sea Intergenic 0.038 1.780 Up 455 cg21294301 RP11-431K24.1 Open_Sea Intergenic 0.020 1.575 Up 456 cg21173144 RP11-649A16.1 Open_Sea Intergenic 0.013 1.562 Up 457 cg04442360 SLTM Open_Sea Body 0.012 -1.473 Down 458 cg26724949 N_Shore Intergenic 0.040 3.634 Up 459 cg26501729 Open_Sea Body 0.044 1.463 Up 460 cg25434970 Open_Sea Intergenic 0.022 -1.350 Down 461 cg04713098 RRM1 Open_Sea Body 0.004 1.504 Up 462 cg04312578 Open_Sea Intergenic 0.017 -1.593 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 463 cg12534577 AC007092.1 Open_Sea Body 0.032 1.804 Up 464 cg19665696 ADAP1 Island Body 0.041 2.482 Up 465 cg13483953 Open_Sea Intergenic 0.004 -1.564 Down 466 cg07173352 TAGLN Open_Sea Body 0.021 -2.736 Down 467 cg20968048 Open_Sea Intergenic 0.037 -1.470 Down 468 cg02928365 HLX S_Shelf TSS1500 0.049 1.454 Up 469 cg13323954 Open_Sea Intergenic 0.015 2.966 Up 470 cg09270544 LPP Open_Sea 1stExon 0.035 1.474 Up 471 cg07889413 ZADH2 S_Shore Body 0.048 1.583 Up 472 cg22681945 RP5-1180C18.1 Open_Sea Intergenic 0.007 -1.745 Down 473 cg07748582 AC096559.1 Open_Sea Body 0.012 -2.080 Down 474 cg22021794 N_Shelf Intergenic 0.037 -1.705 Down 475 cg21993023 RP11-887P2.5 Open_Sea Body 0.008 -1.374 Down 476 cg08943895 POLE2 Open_Sea Body 0.048 -1.518 Down 477 cg23836613 Open_Sea Body 0.008 -1.600 Down 478 cg19695597 RP11-47I22.3 Open_Sea TSS1500 0.049 -1.659 Down 479 cg13243685 GLIS3 Open_Sea 5URT 0.047 -1.989 Down 480 cg25134306 UBE2D2 S_Shelf 5URT 0.013 -1.413 Down 481 cg20370184 Open_Sea Body 0.034 -5.405 Down 482 cg13190239 Open_Sea Intergenic 0.036 1.774 Up 483 cg00123214 RWDD3 S_Shelf 5URT 0.036 -1.667 Down 484 cg13980112 FGGY Open_Sea Body 0.024 -2.074 Down 485 cg14144977 PHC2 Open_Sea Body 0.013 -1.424 Down 486 cg04122815 S_Shelf 1stExon 0.010 -1.779 Down 487 cg11519740 Open_Sea Intergenic 0.023 -2.513 Down 488 cg27621997 CCDC86 N_Shore TSS1500 0.036 -2.225 Down 489 cg07252122 KIAA0586 S_Shelf Body 0.037 -1.405 Down 490 cg14912375 S_Shore Body 0.018 -1.539 Down 491 cg04160030 FUCA1 S_Shore TSS1500 0.026 -1.652 Down

p-value Fold-Change Fold-Change (Description) # Gene name (R vs.NR) (R vs. NR) (R vs. NR) 1 ALAS2 0.037 2.536 Up 2 ANKRD9 0.022 -1.618 Down 3 ASB14 0.044 -1.529 Down 4 ASB3 0.012 1.829 Up 5 ATG101 0.006 -1.510 Down 6 ATP5G1 0.018 -1.543 Down 7 ATP5J 0.037 1.693 Up 8 ATP5J2 0.037 1.947 Up 9 C11orf1 0.009 1.675 Up 10 C19orf60 0.023 -1.625 Down 11 C1orf122 0.005 -1.530 Down 12 CCDC101 0.004 -1.522 Down 13 CCDC28B 0.031 -1.724 Down 14 CD52 0.014 2.251 Up 15 CKS2 0.031 1.568 Up 16 COLQ 0.020 -1.549 Down 17 CORO1A 0.011 1.607 Up 18 DBP 0.003 -1.563 Down 19 DDIT3 0.022 -1.561 Down 20 DNLZ 0.001 -1.902 Down 21 DOHH 0.003 -1.563 Down 22 ERAP2 0.049 2.020 Up 23 ERBB3 0.025 1.696 Up 24 ERRFI1 0.021 1.509 Up 25 EVI2B 0.006 1.800 Up 26 FILIP1L 0.012 1.542 Up 27 FYB 0.009 1.537 Up 28 GADD45G 0.023 -2.040 Down 29 GAS5-AS1 0.014 1.518 Up 30 GPR75-ASB3 0.004 -2.016 Down 31 GRIK2 0.001 1.852 Up 32 GSTM1 0.037 -4.532 Down 33 GSTM4 0.006 -1.523 Down 34 GSTO1 0.007 -1.544 Down 35 HCN1 0.047 1.805 Up 36 HEMGN 0.046 1.510 Up 37 HIST1H2BC 0.003 1.593 Up 38 HIST1H4D 0.009 -1.723 Down 39 HIST1H4F 0.011 -1.916 Down 40 HYAL4 0.032 1.988 Up 41 IFRD2 0.025 -1.531 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 42 ITPA 0.011 -1.501 Down 43 KCNJ3 0.044 1.958 Up 44 KCNQ5 0.025 1.613 Up 45 KRBA2 0.018 -1.502 Down 46 KRT10 0.015 1.842 Up 47 LAPTM5 0.037 1.618 Up 48 LINC00116 0.031 -1.538 Down 49 LINC00310 0.033 1.730 Up 50 LOC100289361 0.009 -1.753 Down 51 LOC101926944 0.003 1.559 Up 52 LOC103021295 0.032 7.447 Up 53 LSM3 0.019 1.794 Up 54 LTBP4 0.029 -1.680 Down 55 LYZ 0.044 2.268 Up 56 MASP1 0.039 -1.570 Down 57 MESP1 0.033 -1.686 Down 58 MFAP3L 0.007 -1.931 Down 59 MNDA 0.046 1.683 Up 60 MRPL12 0.021 -1.578 Down 61 MRPS34 0.027 -1.544 Down 62 MYL12A 0.003 1.541 Up 63 MYL3 0.045 -1.832 Down 64 MYOZ2 0.021 1.651 Up 65 NDUFB11 0.024 -1.502 Down 66 NDUFB2 0.016 -1.539 Down 67 NDUFB7 0.018 -1.509 Down 68 NDUFB9 0.032 -1.526 Down 69 NOL3 0.010 -1.591 Down 70 NUDT22 0.023 -1.517 Down 71 NUDT4P1 0.009 4.726 Up 72 NUDT4P2 0.002 -6.761 Down 73 PDK4 0.034 4.072 Up 74 PICALM 0.016 1.503 Up 75 PIM1 0.002 1.533 Up 76 PIM3 0.041 -1.526 Down 77 PIP4K2A 0.006 1.518 Up 78 PLAC9 0.028 -1.609 Down 79 PMVK 0.020 -1.541 Down 80 PPP1R3F 0.045 -1.537 Down 81 PTPRC 0.022 1.698 Up 82 PWWP2B 0.018 -1.652 Down 83 RAC2 0.004 1.598 Up 84 RBM14-RBM4 0.034 -1.580 Down 85 RBP7 0.035 1.570 Up 86 RPL13AP5 0.032 -1.554 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 87 RPL21P28 0.034 -1.715 Down 88 RPL27 0.027 1.677 Up 89 RPLP1 0.036 -1.610 Down 90 RPS11 0.026 1.542 Up 91 RPS27 0.047 1.686 Up 92 RPS27L 0.024 1.609 Up 93 RPS3A 0.012 -1.589 Down 94 RRP7A 0.000 -1.537 Down 95 RSC1A1 0.043 1.654 Up 96 S100A1 0.034 -1.594 Down 97 SCAND1 0.021 -1.520 Down 98 SLC4A1 0.033 1.519 Up 99 SNHG7 0.034 -1.735 Down 100 SNORA22 0.026 5.699 Up 101 SNORA43 0.031 -3.786 Down 102 SNORA49 0.037 -1.802 Down 103 SNORA80A 0.011 4.564 Up 104 SPATA7 0.039 1.551 Up 105 TCAP 0.040 -1.565 Down 106 TCEB2 0.036 -1.772 Down 107 TMED1 0.034 -1.567 Down 108 TMEM126A 0.041 1.794 Up 109 TMEM160 0.034 -1.670 Down 110 TMEM183B 0.001 -2.010 Down 111 TRIM58 0.026 1.633 Up 112 TRIM72 0.021 -1.744 Down 113 UEVLD 0.006 1.521 Up 114 UQCRHL 0.043 -1.521 Down 115 ZNF385A 0.037 1.561 Up 116 ZNF428 0.022 -1.528 Down 117 ZNF496 0.014 -1.547 Down 118 ZNF593 0.032 -1.577 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA Supplementary Table 4. Differentially expressed genes (RNAseq) between Non-Responders (NR) and Responders (R) in myogenic progenitor cells (HSkMCs).

p-value Fold-Change Fold-Change (Description) # Gene name (R vs.NR) (R vs. NR) (R vs. NR) 1 ACKR4 0.004 -2.006 Down 2 ACOT1 0.026 1.657 Up 3 ACSL5 0.042 -1.476 Down 4 ADCY10P1 0.019 1.327 Up 5 AIRE 0.029 -1.855 Down 6 AK5 0.016 1.390 Up 7 ALAD 0.046 -1.341 Down 8 AMOT 0.037 1.357 Up 9 APOL3 0.046 -1.928 Down 10 AQP5 0.037 -1.481 Down 11 AQP7 0.030 -1.378 Down 12 AS3MT 0.020 1.637 Up 13 ATP2A3 0.023 1.385 Up 14 BMPER 0.034 -3.408 Down 15 BPGM 0.012 -1.399 Down 16 BRINP1 0.030 -3.140 Down 17 BST2 0.049 -1.310 Down 18 C10orf32-ASMT 0.026 -1.526 Down 19 C17orf89 0.013 1.303 Up 20 C2orf40 0.009 -1.921 Down 21 C5orf30 0.037 -1.485 Down 22 CACHD1 0.012 -1.423 Down 23 CCL7 0.028 -1.314 Down 24 CD302 0.043 -1.682 Down 25 CDC42EP3 0.009 1.392 Up 26 CDIP1 0.036 1.351 Up 27 CITED4 0.021 -1.508 Down 28 CLEC3B 0.028 -3.079 Down 29 CNPY1 0.024 1.779 Up 30 COL8A1 0.018 -2.612 Down 31 CSF3 0.029 -1.339 Down 32 CTH 0.032 1.358 Up 33 CYP26B1 0.035 -1.397 Down 34 CYP27C1 0.018 -1.320 Down 35 DDX60 0.019 -1.564 Down 36 DIAPH2 0.004 -1.315 Down 37 DMBT1 0.040 2.473 Up 38 DUSP10 0.023 1.534 Up 39 DUSP5 0.022 -1.451 Down 40 EGFL7 0.035 -1.320 Down 41 ELN 0.020 2.434 Up

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 42 EMP1 0.018 -1.520 Down 43 ENPP1 0.011 1.840 Up 44 EPB41L4A 0.016 -1.426 Down 45 FAM107B 0.029 1.424 Up 46 FAM66B 0.001 -1.381 Down 47 FBLN1 0.033 -3.710 Down 48 FBN2 0.024 -2.758 Down 49 FMO3 0.032 -1.760 Down 50 FNDC4 0.028 -1.405 Down 51 FZD4 0.005 -1.545 Down 52 GABRB2 0.039 1.519 Up 53 GALNT16 0.028 -1.542 Down 54 GGT5 0.042 -1.674 Down 55 GNA14 0.005 -2.361 Down 56 GPR137B 0.027 -1.386 Down 57 GSDMB 0.017 -1.307 Down 58 GSTT2B 0.044 1.828 Up 59 HIF1A-AS2 0.005 1.416 Up 60 HIPK2 0.021 -1.327 Down 61 HLA-H 0.035 -2.167 Down 62 HSPA2 0.040 1.532 Up 63 IGSF3 0.016 1.327 Up 64 IL11 0.034 1.490 Up 65 IL13RA2 0.026 -2.129 Down 66 IMMP1L 0.016 1.521 Up 67 INO80B-WBP1 0.040 1.709 Up 68 JCHAIN 0.008 -2.069 Down 69 JUP 0.036 -1.596 Down 70 KANK4 0.026 1.595 Up 71 KCNIP3 0.045 -1.313 Down 72 KIFC3 0.037 1.343 Up 73 KY 0.015 -1.451 Down 74 LAPTM4B 0.036 1.320 Up 75 LBHD1 0.035 -1.315 Down 76 LINC00310 0.030 -1.300 Down 77 LINC00467 0.010 1.317 Up 78 LINC00654 0.020 -1.364 Down 79 LINC00693 0.004 1.553 Up 80 LIPC 0.010 -1.493 Down 81 LOC100133091 0.046 -1.458 Down 82 LOC101926941 0.000 -1.440 Down 83 LOC391322 0.015 -1.497 Down 84 LOC654342 0.032 -1.520 Down 85 LY75 0.007 -1.348 Down 86 MAFB 0.033 -1.519 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 87 MAOA 0.032 -1.500 Down 88 MBP 0.018 -1.945 Down 89 MDGA1 0.048 -1.491 Down 90 MINOS1-NBL1 0.019 1.346 Up 91 MIR320B2 0.042 5.649 Up 92 MYH1 0.000 -1.883 Down 93 NMB 0.014 -1.364 Down 94 NOVA1 0.048 -1.607 Down 95 NR2F1 0.023 -1.774 Down 96 OAS3 0.033 -1.557 Down 97 OTUD1 0.049 1.490 Up 98 PCDHB2 0.042 1.605 Up 99 PCDHGA12 0.030 -1.596 Down 100 PCDHGA7 0.038 -1.456 Down 101 PGD 0.020 1.320 Up 102 PGF 0.025 1.686 Up 103 PHLDA3 0.022 1.354 Up 104 PIK3R3 0.031 1.404 Up 105 PLAC9 0.038 -2.525 Down 106 PLCD4 0.016 -1.470 Down 107 PLCL2 0.048 -1.445 Down 108 PPP1R3G 0.040 1.302 Up 109 PROSER2 0.044 1.358 Up 110 PSG11 0.008 -1.444 Down 111 PSMD5-AS1 0.021 -1.459 Down 112 RARRES3 0.032 -1.894 Down 113 REP15 0.031 -1.324 Down 114 RHOD 0.036 -1.933 Down 115 RNF125 0.001 -1.313 Down 116 RUNX1T1 0.029 -1.357 Down 117 SCARNA18 0.019 -8.728 Down 118 SCN3A 0.008 -1.719 Down 119 SDHAP3 0.021 -1.463 Down 120 SERPINA3 0.030 -1.922 Down 121 SLC25A23 0.045 -1.303 Down 122 SLC47A2 0.033 -1.559 Down 123 SMIM4 0.012 -1.306 Down 124 SNAP91 0.045 -1.637 Down 125 SNORA64 0.018 7.242 Up 126 SPECC1 0.050 1.638 Up 127 SPG20-AS1 0.013 1.387 Up 128 SPRY4-IT1 0.003 -1.547 Down 129 SRPK3 0.043 1.923 Up 130 ST6GAL1 0.048 -1.469 Down 131 STEAP2 0.040 -2.020 Down

©2018 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-0296/-/DC1 SUPPLEMENTARY DATA 132 STEAP4 0.028 -3.231 Down 133 STMN2 0.016 -3.094 Down 134 SYTL3 0.035 1.390 Up 135 TCEA3 0.008 1.683 Up 136 TGFB3 0.018 -1.485 Down 137 TGFBR2 0.016 -1.306 Down 138 THBD 0.045 1.547 Up 139 TLR1 0.034 -1.418 Down 140 TLR3 0.027 -1.461 Down 141 TM4SF20 0.008 -1.467 Down 142 TMEM161B-AS1 0.031 -1.343 Down 143 TMEM233 0.033 1.548 Up 144 TPD52L1 0.002 -1.410 Down 145 UTS2R 0.035 1.699 Up 146 WNT5A 0.015 1.548 Up 147 WWC2-AS1 0.020 -1.617 Down