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TABLE 2

Insulin response according to genotype

GenenFirst-phase insulin response (pmol/l)Second-phase insulin response (pmol/l)ISI (μmol · min−1 · kg−1 · pmol−1 · l−1)DI (μmol · min−1 · kg−1)n (GLP-1, Arg)GLP-1–stimulated insulin release (pmol/l)*Arginine-stimulated insulin release (pmol/l)*
JAZF1, rs864745 
    C/C 73 727 (652–812) 262 (236–292) 0.141 (0.122–0.162) 107 (95–121) 26 1,034 (799–1,337) 1,728 (1,495–1,998) 
    C/T 161 723 (672–778) 239 (223–255) 0.155 (0.142–0.170) 111 (103–120) 48 1,374 (1,122–1,683) 1,992 (1,727–2,297) 
    T/T 100 759 (686–841) 263 (243–286) 0.160 (0.145–0.177) 124 (111–139) 49 1,200 (951–1,514) 2,233 (1,969–2,532) 
    P  0.54 0.80 0.15 0.07  0.63 0.018 
CDC123/ CAMK1D, rs12779790 
    A/A 212 755 (704–810) 260 (245–275) 0.155 (0.143–0.168) 117 (109–127) 74 1,318 (1,094–1,588) 2,181 (1,979–2,403) 
    A/G 110 713 (656–774) 238 (220–258) 0.153 (0.138–0.169) 112 (101–123) 48 1,106 (881–1,389) 1,817 (1,588–2,078) 
    G/G 12 617 (478–797) 200 (176–228) 0.146 (0.108–0.198) 94 (71–125) 1,142 (913–1,428) 1,486 (1,322–1,671) 
    P  0.10 0.0049 0.68 0.16  0.24 0.015 
TSPAN8/LGR5, rs7961581 
    T/T 159 738 (687–793) 253 (237–270) 0.149 (0.135–0.164) 113 (103–123) 47 1,253 (1,028–1,529) 2,094 (1,860–2,357) 
    T/C 141 724 (668–784) 247 (229–265) 0.158 (0.142–0.175) 113 (105–123) 65 1,222 (994–1,503) 2,024 (1,797–2,280) 
    C/C 34 738 (613–889) 254 (219–295) 0.160 (0.135–0.190) 118 (97–142) 11 1,148 (796–1,657) 1,710 (1,362–2,146) 
    P  0.88 0.84 0.34 0.72  0.73 0.24 
THADA, rs7578597 
    C/C 905 (484–1694) 365 (317–421) 0.125 (0.067–0.230) 121 (80–182) NA NA 
    C/T 72 739 (662–825) 271 (247–296) 0.180 (0.160–0.204) 127 (113–142) 25 1,783 (1,352–2,352) 2,605 (2,236–3,035) 
    T/T 261 732 (689–778) 244 (232–257) 0.147 (0.137–0.158) 110 (103–118) 98 1,120 (970–1,292) 1,897 (1,744–2,064) 
    P  0.77 0.019 0.0069 0.039  0.0016 0.00023 
ADAMTS9, rs4607103 
    T/T 20 549 (467–646) 206 (172–246) 0.136 (0.106–0.175) 83 (69–99) 777 (597–1,011) 1,632 (1,335–1,994) 
    T/C 119 725 (668–787) 256 (238–274) 0.152 (0.137–0.169) 111 (101–123) 47 1,291 (1,028–1,621) 1,990 (1,753–2,260) 
    C/C 187 767 (714–824) 252 (237–268) 0.157 (0.145–0.171) 121 (112–130) 69 1,244 (1,032–1,498) 2,094 (1,866–2,350) 
    P  0.0059 0.26 0.32 0.0026  0.38 0.18 
NOTCH2/ADAM30, rs2641348 
    A/A 253 736 (692–782) 248 (234–262) 0.152 (0.141–0.163) 114 (107–121) 94 1,226 (1,045–1,438) 2,035 (1,858–2,228) 
    A/G 73 746 (661–841) 256 (230–285) 0.154 (0.133–0.179) 113 (97–131) 27 1,228 (896–1,683) 2,036 (1,671–2,482) 
    G/G 10 654 (502–852) 278 (242–319) 0.189 (0.156–0.229) 121 (96–152) 1,323 (1,100–1,593) 1,398 (1,251–1,563) 
    P  0.76 0.33 0.37 0.89  0.93 0.59 
DCD, rs1153188 
    T/T 24 811 (670–982) 279 (243–321) 0.169 (0.136–0.210) 128 (103–160) 1,448 (1,143–1,834) 2,068 (1,467–2,915) 
    T/A 120 726 (675–781) 248 (231–267) 0.154 (0.138–0.171) 113 (103–124) 40 1,018 (757–1,368) 1,976 (1,723–2,268) 
    A/A 192 732 (678–790) 247 (232–263) 0.152 (0.140–0.165) 113 (104–123) 78 1,336 (1,151–1,551) 2,043 (1,845–2,262) 
    P  0.55 0.29 0.49 0.48  0.27 0.83 
VEGFA, rs9472138 
    C/C 176 722 (674–774) 245 (231–260) 0.156 (0.145–0.169) 114 (106–123) 68 1,207 (1,014–1,436) 1,908 (1,715–2,121) 
    C/T 131 765 (704–832) 263 (243–284) 0.153 (0.136–0.172) 117 (106–130) 48 1,278 (989–1,652) 2,203 (1,942–2,498) 
    T/T 28 695 (578–835) 229 (197–268) 0.141 (0.115–0.174) 101 (83–123) 1,096 (556–2,161) 1,922 (1,267–2,917) 
    P  0.77 0.80 0.44 0.55  0.97 0.35 
BCL11A, rs10490072 
    C/C 32 810 (703–934) 226 (199–256) 0.169 (0.141–0.201) 132 (111–158) 13 812 (595–1,108) 1,774 (1,553–2,028) 
    C/T 126 799 (738–866) 255 (237–274) 0.145 (0.131–0.161) 120 (110–132) 49 1,266 (978–1,639) 2,073 (1,814–2,369) 
    T/T 178 685 (637–737) 251 (236–268) 0.157 (0.144–0.171) 107 (99–116) 61 1,311 (1,139–1,508) 2,040 (1,810–2,300) 
    P  0.0031 0.39 0.92 0.010  0.060 0.41 
HNF1B, rs757210 
    C/C 118 746 (696–799) 255 (237–274) 0.149 (0.134–0.166) 112 (103–122) 51 1,218 (966–1,535) 2,049 (1,792–2,342) 
    C/T 145 737 (672–809) 251 (233–270) 0.154 (0.139–0.170) 116 (105–128) 49 1,265 (1,034–1,546) 2,034 (1,828–2,263) 
    T/T 71 704 (634–782) 240 (218–263) 0.161 (0.144–0.179) 111 (99–125) 23 1,174 (874–1,577) 1,946 (1,586–2,387) 
    P  0.38 0.33 0.35 0.99  0.93 0.70 
WFS1, rs10010131 
    A/A 39 623 (527–737) 258 (217–306) 0.160 (0.128–0.200) 99 (84–117) 11 1,564 (1,155–2,120) 2,311 (1,773–3,011) 
    A/G 176 751 (701–804) 257 (243–272) 0.149 (0.138–0.162) 114 (106–123) 66 1,298 (1,086–1,551) 2,066 (1,854–2,303) 
    G/G 119 749 (686–818) 238 (221–257) 0.158 (0.143–0.175) 119 (108–131) 46 1,072 (848–1,356) 1,900 (1,663–2,171) 
    P  0.14 0.21 0.81 0.09  0.058 0.18 
MTNR1B, rs10830963 
    C/C 187 757 (706–813) 239 (226–253) 0.163 (0.150–0.177) 122 (112–131) 57 1,044 (865–1,259) 1,869 (1,675–2,085) 
    C/G 113 758 (700–821) 270 (248–294) 0.139 (0.123–0.157) 110 (101–120) 49 1,440 (1,142–1,814) 2,157 (1,868–2,490) 
    G/G 35 561 (487–647) 239 (207–276) 0.158 (0.132–0.190) 90 (77–106) 17 1,360 (1,084–1,705) 2,231 (1,973–2,523) 
    P  0.010 0.27 0.22 0.0015  0.026 0.037 
GenenFirst-phase insulin response (pmol/l)Second-phase insulin response (pmol/l)ISI (μmol · min−1 · kg−1 · pmol−1 · l−1)DI (μmol · min−1 · kg−1)n (GLP-1, Arg)GLP-1–stimulated insulin release (pmol/l)*Arginine-stimulated insulin release (pmol/l)*
JAZF1, rs864745 
    C/C 73 727 (652–812) 262 (236–292) 0.141 (0.122–0.162) 107 (95–121) 26 1,034 (799–1,337) 1,728 (1,495–1,998) 
    C/T 161 723 (672–778) 239 (223–255) 0.155 (0.142–0.170) 111 (103–120) 48 1,374 (1,122–1,683) 1,992 (1,727–2,297) 
    T/T 100 759 (686–841) 263 (243–286) 0.160 (0.145–0.177) 124 (111–139) 49 1,200 (951–1,514) 2,233 (1,969–2,532) 
    P  0.54 0.80 0.15 0.07  0.63 0.018 
CDC123/ CAMK1D, rs12779790 
    A/A 212 755 (704–810) 260 (245–275) 0.155 (0.143–0.168) 117 (109–127) 74 1,318 (1,094–1,588) 2,181 (1,979–2,403) 
    A/G 110 713 (656–774) 238 (220–258) 0.153 (0.138–0.169) 112 (101–123) 48 1,106 (881–1,389) 1,817 (1,588–2,078) 
    G/G 12 617 (478–797) 200 (176–228) 0.146 (0.108–0.198) 94 (71–125) 1,142 (913–1,428) 1,486 (1,322–1,671) 
    P  0.10 0.0049 0.68 0.16  0.24 0.015 
TSPAN8/LGR5, rs7961581 
    T/T 159 738 (687–793) 253 (237–270) 0.149 (0.135–0.164) 113 (103–123) 47 1,253 (1,028–1,529) 2,094 (1,860–2,357) 
    T/C 141 724 (668–784) 247 (229–265) 0.158 (0.142–0.175) 113 (105–123) 65 1,222 (994–1,503) 2,024 (1,797–2,280) 
    C/C 34 738 (613–889) 254 (219–295) 0.160 (0.135–0.190) 118 (97–142) 11 1,148 (796–1,657) 1,710 (1,362–2,146) 
    P  0.88 0.84 0.34 0.72  0.73 0.24 
THADA, rs7578597 
    C/C 905 (484–1694) 365 (317–421) 0.125 (0.067–0.230) 121 (80–182) NA NA 
    C/T 72 739 (662–825) 271 (247–296) 0.180 (0.160–0.204) 127 (113–142) 25 1,783 (1,352–2,352) 2,605 (2,236–3,035) 
    T/T 261 732 (689–778) 244 (232–257) 0.147 (0.137–0.158) 110 (103–118) 98 1,120 (970–1,292) 1,897 (1,744–2,064) 
    P  0.77 0.019 0.0069 0.039  0.0016 0.00023 
ADAMTS9, rs4607103 
    T/T 20 549 (467–646) 206 (172–246) 0.136 (0.106–0.175) 83 (69–99) 777 (597–1,011) 1,632 (1,335–1,994) 
    T/C 119 725 (668–787) 256 (238–274) 0.152 (0.137–0.169) 111 (101–123) 47 1,291 (1,028–1,621) 1,990 (1,753–2,260) 
    C/C 187 767 (714–824) 252 (237–268) 0.157 (0.145–0.171) 121 (112–130) 69 1,244 (1,032–1,498) 2,094 (1,866–2,350) 
    P  0.0059 0.26 0.32 0.0026  0.38 0.18 
NOTCH2/ADAM30, rs2641348 
    A/A 253 736 (692–782) 248 (234–262) 0.152 (0.141–0.163) 114 (107–121) 94 1,226 (1,045–1,438) 2,035 (1,858–2,228) 
    A/G 73 746 (661–841) 256 (230–285) 0.154 (0.133–0.179) 113 (97–131) 27 1,228 (896–1,683) 2,036 (1,671–2,482) 
    G/G 10 654 (502–852) 278 (242–319) 0.189 (0.156–0.229) 121 (96–152) 1,323 (1,100–1,593) 1,398 (1,251–1,563) 
    P  0.76 0.33 0.37 0.89  0.93 0.59 
DCD, rs1153188 
    T/T 24 811 (670–982) 279 (243–321) 0.169 (0.136–0.210) 128 (103–160) 1,448 (1,143–1,834) 2,068 (1,467–2,915) 
    T/A 120 726 (675–781) 248 (231–267) 0.154 (0.138–0.171) 113 (103–124) 40 1,018 (757–1,368) 1,976 (1,723–2,268) 
    A/A 192 732 (678–790) 247 (232–263) 0.152 (0.140–0.165) 113 (104–123) 78 1,336 (1,151–1,551) 2,043 (1,845–2,262) 
    P  0.55 0.29 0.49 0.48  0.27 0.83 
VEGFA, rs9472138 
    C/C 176 722 (674–774) 245 (231–260) 0.156 (0.145–0.169) 114 (106–123) 68 1,207 (1,014–1,436) 1,908 (1,715–2,121) 
    C/T 131 765 (704–832) 263 (243–284) 0.153 (0.136–0.172) 117 (106–130) 48 1,278 (989–1,652) 2,203 (1,942–2,498) 
    T/T 28 695 (578–835) 229 (197–268) 0.141 (0.115–0.174) 101 (83–123) 1,096 (556–2,161) 1,922 (1,267–2,917) 
    P  0.77 0.80 0.44 0.55  0.97 0.35 
BCL11A, rs10490072 
    C/C 32 810 (703–934) 226 (199–256) 0.169 (0.141–0.201) 132 (111–158) 13 812 (595–1,108) 1,774 (1,553–2,028) 
    C/T 126 799 (738–866) 255 (237–274) 0.145 (0.131–0.161) 120 (110–132) 49 1,266 (978–1,639) 2,073 (1,814–2,369) 
    T/T 178 685 (637–737) 251 (236–268) 0.157 (0.144–0.171) 107 (99–116) 61 1,311 (1,139–1,508) 2,040 (1,810–2,300) 
    P  0.0031 0.39 0.92 0.010  0.060 0.41 
HNF1B, rs757210 
    C/C 118 746 (696–799) 255 (237–274) 0.149 (0.134–0.166) 112 (103–122) 51 1,218 (966–1,535) 2,049 (1,792–2,342) 
    C/T 145 737 (672–809) 251 (233–270) 0.154 (0.139–0.170) 116 (105–128) 49 1,265 (1,034–1,546) 2,034 (1,828–2,263) 
    T/T 71 704 (634–782) 240 (218–263) 0.161 (0.144–0.179) 111 (99–125) 23 1,174 (874–1,577) 1,946 (1,586–2,387) 
    P  0.38 0.33 0.35 0.99  0.93 0.70 
WFS1, rs10010131 
    A/A 39 623 (527–737) 258 (217–306) 0.160 (0.128–0.200) 99 (84–117) 11 1,564 (1,155–2,120) 2,311 (1,773–3,011) 
    A/G 176 751 (701–804) 257 (243–272) 0.149 (0.138–0.162) 114 (106–123) 66 1,298 (1,086–1,551) 2,066 (1,854–2,303) 
    G/G 119 749 (686–818) 238 (221–257) 0.158 (0.143–0.175) 119 (108–131) 46 1,072 (848–1,356) 1,900 (1,663–2,171) 
    P  0.14 0.21 0.81 0.09  0.058 0.18 
MTNR1B, rs10830963 
    C/C 187 757 (706–813) 239 (226–253) 0.163 (0.150–0.177) 122 (112–131) 57 1,044 (865–1,259) 1,869 (1,675–2,085) 
    C/G 113 758 (700–821) 270 (248–294) 0.139 (0.123–0.157) 110 (101–120) 49 1,440 (1,142–1,814) 2,157 (1,868–2,490) 
    G/G 35 561 (487–647) 239 (207–276) 0.158 (0.132–0.190) 90 (77–106) 17 1,360 (1,084–1,705) 2,231 (1,973–2,523) 
    P  0.010 0.27 0.22 0.0015  0.026 0.037 

Data are estimated means (95% CI) unless otherwise indicated. Alleles identified as risk alleles for type 2 diabetes are indicated in bold. All variables were log transformed before analysis. P values were computed for additive models using linear generalized estimating equations, which takes into account the family relatedness when computing the standard errors. First- and second-phase GSIS and GLP-1– and arginine-stimulated insulin secretion were adjusted for study center, family relatedness, glucose tolerance status, age, sex, BMI, and ISI. ISI and DI were adjusted for study center, family relatedness, glucose tolerance status, age, sex, and BMI.

*Available for 123 subjects from the NTR twin sample.

P values are for the recessive model.

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