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TABLE 3

Insulin response according to genotype in NGT and IGT subjects (genes with significant effects only)

GeneNGT
IGT
nFirst-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)nFirst-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)
CDC123/ CAMK1D, rs12779790 
    C/C 109 888 (812–971) 257 (239–276) 0.202 (0.182–0.225) 178 (160–199) 103 717 (610–843) 249 (216–286) 0.109 (0.090–0.132) 79 (67–93) 
    C/T 66 792 (714–877) 247 (226–269) 0.202 (0.177–0.230) 162 (146–181) 44 715 (584–875) 208 (174–249) 0.102 (0.081–0.128) 77 (61–97) 
    T/T 720 (540–962) 197 (164–237) 0.221 (0.166–0.295) 154 (122–193) 564 (363–877) 186 (144–239) 0.096 (0.059–0.157) 60 (36–99) 
    P  0.034 0.14 0.89 0.13  0.42 0.0028 0.44 0.37 
THADA, rs7578597 
    C/C 1,109 (1,005–1,224) 388 (355–424) 0.280 (0.247–0.318) 264 (240–290) 920 (359–2,358) 360 (270–478) 0.070 (0.035–0.138) 76 (46–124) 
    C/T 43 843 (728–976) 272 (244–303) 0.249 (0.215–0.288) 192 (164–224) 29 730 (570–936) 257 (209–316) 0.122 (0.092–0.162) 87 (68–112) 
    T/T 136 840 (776–910) 243 (228–259) 0.190 (0.173–0.208) 164 (150–180) 125 710 (606–833) 232 (202–266) 0.104 (0.087–0.125) 76 (64–90) 
    P  0.91* 0.057* 0.0017* 0.073*  0.67* 0.14* 0.32* 0.21* 
ADAMTS9, rs4607103 
    T/T 12 694 (581–830) 207 (171–251) 0.182 (0.122–0.271) 137 (110–170) 487 (340–699) 193 (137–272) 0.093 (0.068–0.127) 52 (37–73) 
    T/C 71 832 (759–912) 245 (224–267) 0.204 (0.180–0.231) 169 (150–191) 54 699 (582–840) 252 (215–296) 0.102 (0.082–0.128) 74 (62–89) 
    C/C 97 867 (788–955) 259 (241–279) 0.204 (0.182–0.228) 176 (160–194) 94 747 (625–892) 227 (196–263) 0.111 (0.092–0.135) 84 (69–102) 
    P  0.11 0.054 0.71 0.12  0.051 0.75 0.22 0.012 
BCL11A, rs10490072 
    C/C 18 976 (828–1,151) 230 (197–269) 0.213 (0.172–0.263) 210 (170–258) 14 740 (553–990) 207 (159–268) 0.127 (0.091–0.177) 84 (60–119) 
    C/T 71 885 (799–979) 261 (241–283) 0.191 (0.168–0.217) 175 (155–197) 55 815 (663–1,000) 231 (196–272) 0.101 (0.082–0.126) 85 (70–104) 
    T/T 91 785 (719–858) 246 (227–267) 0.211 (0.188–0.236) 161 (146–177) 87 670 (570–787) 238 (205–276) 0.108 (0.088–0.132) 74 (62–88) 
    P  0.0066 0.96 0.59 0.019  0.10 0.33 0.73 0.19 
MTNR1B, rs10830963 
    C/C 91 853 (778–936) 243 (226–260) 0.212 (0.189–0.237) 177 (159–196) 96 762 (645–900) 226 (195–263) 0.115 (0.094–0.140) 88 (74–104) 
    C/G 65 882 (802–970) 267 (241–295) 0.188 (0.160–0.221) 172 (154–193) 48 732 (609–879) 260 (218–309) 0.093 (0.075–0.114) 73 (61–87) 
    G/G 21 696 (593–818) 241 (210–276) 0.228 (0.191–0.272) 157 (135–183) 14 509 (410–633) 223 (175–284) 0.096 (0.066–0.141) 53 (40–70) 
    P  0.23 0.49 0.83 0.31  0.0067 0.38 0.078 0.00036 
GeneNGT
IGT
nFirst-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)nFirst-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)
CDC123/ CAMK1D, rs12779790 
    C/C 109 888 (812–971) 257 (239–276) 0.202 (0.182–0.225) 178 (160–199) 103 717 (610–843) 249 (216–286) 0.109 (0.090–0.132) 79 (67–93) 
    C/T 66 792 (714–877) 247 (226–269) 0.202 (0.177–0.230) 162 (146–181) 44 715 (584–875) 208 (174–249) 0.102 (0.081–0.128) 77 (61–97) 
    T/T 720 (540–962) 197 (164–237) 0.221 (0.166–0.295) 154 (122–193) 564 (363–877) 186 (144–239) 0.096 (0.059–0.157) 60 (36–99) 
    P  0.034 0.14 0.89 0.13  0.42 0.0028 0.44 0.37 
THADA, rs7578597 
    C/C 1,109 (1,005–1,224) 388 (355–424) 0.280 (0.247–0.318) 264 (240–290) 920 (359–2,358) 360 (270–478) 0.070 (0.035–0.138) 76 (46–124) 
    C/T 43 843 (728–976) 272 (244–303) 0.249 (0.215–0.288) 192 (164–224) 29 730 (570–936) 257 (209–316) 0.122 (0.092–0.162) 87 (68–112) 
    T/T 136 840 (776–910) 243 (228–259) 0.190 (0.173–0.208) 164 (150–180) 125 710 (606–833) 232 (202–266) 0.104 (0.087–0.125) 76 (64–90) 
    P  0.91* 0.057* 0.0017* 0.073*  0.67* 0.14* 0.32* 0.21* 
ADAMTS9, rs4607103 
    T/T 12 694 (581–830) 207 (171–251) 0.182 (0.122–0.271) 137 (110–170) 487 (340–699) 193 (137–272) 0.093 (0.068–0.127) 52 (37–73) 
    T/C 71 832 (759–912) 245 (224–267) 0.204 (0.180–0.231) 169 (150–191) 54 699 (582–840) 252 (215–296) 0.102 (0.082–0.128) 74 (62–89) 
    C/C 97 867 (788–955) 259 (241–279) 0.204 (0.182–0.228) 176 (160–194) 94 747 (625–892) 227 (196–263) 0.111 (0.092–0.135) 84 (69–102) 
    P  0.11 0.054 0.71 0.12  0.051 0.75 0.22 0.012 
BCL11A, rs10490072 
    C/C 18 976 (828–1,151) 230 (197–269) 0.213 (0.172–0.263) 210 (170–258) 14 740 (553–990) 207 (159–268) 0.127 (0.091–0.177) 84 (60–119) 
    C/T 71 885 (799–979) 261 (241–283) 0.191 (0.168–0.217) 175 (155–197) 55 815 (663–1,000) 231 (196–272) 0.101 (0.082–0.126) 85 (70–104) 
    T/T 91 785 (719–858) 246 (227–267) 0.211 (0.188–0.236) 161 (146–177) 87 670 (570–787) 238 (205–276) 0.108 (0.088–0.132) 74 (62–88) 
    P  0.0066 0.96 0.59 0.019  0.10 0.33 0.73 0.19 
MTNR1B, rs10830963 
    C/C 91 853 (778–936) 243 (226–260) 0.212 (0.189–0.237) 177 (159–196) 96 762 (645–900) 226 (195–263) 0.115 (0.094–0.140) 88 (74–104) 
    C/G 65 882 (802–970) 267 (241–295) 0.188 (0.160–0.221) 172 (154–193) 48 732 (609–879) 260 (218–309) 0.093 (0.075–0.114) 73 (61–87) 
    G/G 21 696 (593–818) 241 (210–276) 0.228 (0.191–0.272) 157 (135–183) 14 509 (410–633) 223 (175–284) 0.096 (0.066–0.141) 53 (40–70) 
    P  0.23 0.49 0.83 0.31  0.0067 0.38 0.078 0.00036 

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 take into account the family relatedness when computing the standard errors. First- and second-phase GSIS were adjusted for study center, family relatedness, age, sex, BMI, and ISI. ISI and DI were adjusted for study center, family relatedness, glucose tolerance status, age, sex, and BMI.

*P values are for the recessive model.

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