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/C73727 (652–812)262 (236–292)0.141 (0.122–0.162)107 (95–121)261,034 (799–1,337)1,728 (1,495–1,998)
    C/T161723 (672–778)239 (223–255)0.155 (0.142–0.170)111 (103–120)481,374 (1,122–1,683)1,992 (1,727–2,297)
    T/T100759 (686–841)263 (243–286)0.160 (0.145–0.177)124 (111–139)491,200 (951–1,514)2,233 (1,969–2,532)
    P0.540.800.150.070.630.018
CDC123/ CAMK1D, rs12779790
    A/A212755 (704–810)260 (245–275)0.155 (0.143–0.168)117 (109–127)741,318 (1,094–1,588)2,181 (1,979–2,403)
    A/G110713 (656–774)238 (220–258)0.153 (0.138–0.169)112 (101–123)481,106 (881–1,389)1,817 (1,588–2,078)
    G/G12617 (478–797)200 (176–228)0.146 (0.108–0.198)94 (71–125)11,142 (913–1,428)1,486 (1,322–1,671)
    P0.100.00490.680.160.240.015
TSPAN8/LGR5, rs7961581
    T/T159738 (687–793)253 (237–270)0.149 (0.135–0.164)113 (103–123)471,253 (1,028–1,529)2,094 (1,860–2,357)
    T/C141724 (668–784)247 (229–265)0.158 (0.142–0.175)113 (105–123)651,222 (994–1,503)2,024 (1,797–2,280)
    C/C34738 (613–889)254 (219–295)0.160 (0.135–0.190)118 (97–142)111,148 (796–1,657)1,710 (1,362–2,146)
    P0.880.840.340.720.730.24
THADA, rs7578597
    C/C3905 (484–1694)365 (317–421)0.125 (0.067–0.230)121 (80–182)0NANA
    C/T72739 (662–825)271 (247–296)0.180 (0.160–0.204)127 (113–142)251,783 (1,352–2,352)2,605 (2,236–3,035)
    T/T261732 (689–778)244 (232–257)0.147 (0.137–0.158)110 (103–118)981,120 (970–1,292)1,897 (1,744–2,064)
    P0.77†0.019†0.0069†0.039†0.0016†0.00023†
ADAMTS9, rs4607103
    T/T20549 (467–646)206 (172–246)0.136 (0.106–0.175)83 (69–99)7777 (597–1,011)1,632 (1,335–1,994)
    T/C119725 (668–787)256 (238–274)0.152 (0.137–0.169)111 (101–123)471,291 (1,028–1,621)1,990 (1,753–2,260)
    C/C187767 (714–824)252 (237–268)0.157 (0.145–0.171)121 (112–130)691,244 (1,032–1,498)2,094 (1,866–2,350)
    P0.00590.260.320.00260.380.18
NOTCH2/ADAM30, rs2641348
    A/A253736 (692–782)248 (234–262)0.152 (0.141–0.163)114 (107–121)941,226 (1,045–1,438)2,035 (1,858–2,228)
    A/G73746 (661–841)256 (230–285)0.154 (0.133–0.179)113 (97–131)271,228 (896–1,683)2,036 (1,671–2,482)
    G/G10654 (502–852)278 (242–319)0.189 (0.156–0.229)121 (96–152)21,323 (1,100–1,593)1,398 (1,251–1,563)
    P0.760.330.370.890.930.59
DCD, rs1153188
    T/T24811 (670–982)279 (243–321)0.169 (0.136–0.210)128 (103–160)51,448 (1,143–1,834)2,068 (1,467–2,915)
    T/A120726 (675–781)248 (231–267)0.154 (0.138–0.171)113 (103–124)401,018 (757–1,368)1,976 (1,723–2,268)
    A/A192732 (678–790)247 (232–263)0.152 (0.140–0.165)113 (104–123)781,336 (1,151–1,551)2,043 (1,845–2,262)
    P0.550.290.490.480.270.83
VEGFA, rs9472138
    C/C176722 (674–774)245 (231–260)0.156 (0.145–0.169)114 (106–123)681,207 (1,014–1,436)1,908 (1,715–2,121)
    C/T131765 (704–832)263 (243–284)0.153 (0.136–0.172)117 (106–130)481,278 (989–1,652)2,203 (1,942–2,498)
    T/T28695 (578–835)229 (197–268)0.141 (0.115–0.174)101 (83–123)71,096 (556–2,161)1,922 (1,267–2,917)
    P0.770.800.440.550.970.35
BCL11A, rs10490072
    C/C32810 (703–934)226 (199–256)0.169 (0.141–0.201)132 (111–158)13812 (595–1,108)1,774 (1,553–2,028)
    C/T126799 (738–866)255 (237–274)0.145 (0.131–0.161)120 (110–132)491,266 (978–1,639)2,073 (1,814–2,369)
    T/T178685 (637–737)251 (236–268)0.157 (0.144–0.171)107 (99–116)611,311 (1,139–1,508)2,040 (1,810–2,300)
    P0.00310.390.920.0100.0600.41
HNF1B, rs757210
    C/C118746 (696–799)255 (237–274)0.149 (0.134–0.166)112 (103–122)511,218 (966–1,535)2,049 (1,792–2,342)
    C/T145737 (672–809)251 (233–270)0.154 (0.139–0.170)116 (105–128)491,265 (1,034–1,546)2,034 (1,828–2,263)
    T/T71704 (634–782)240 (218–263)0.161 (0.144–0.179)111 (99–125)231,174 (874–1,577)1,946 (1,586–2,387)
    P0.380.330.350.990.930.70
WFS1, rs10010131
    A/A39623 (527–737)258 (217–306)0.160 (0.128–0.200)99 (84–117)111,564 (1,155–2,120)2,311 (1,773–3,011)
    A/G176751 (701–804)257 (243–272)0.149 (0.138–0.162)114 (106–123)661,298 (1,086–1,551)2,066 (1,854–2,303)
    G/G119749 (686–818)238 (221–257)0.158 (0.143–0.175)119 (108–131)461,072 (848–1,356)1,900 (1,663–2,171)
    P0.140.210.810.090.0580.18
MTNR1B, rs10830963
    C/C187757 (706–813)239 (226–253)0.163 (0.150–0.177)122 (112–131)571,044 (865–1,259)1,869 (1,675–2,085)
    C/G113758 (700–821)270 (248–294)0.139 (0.123–0.157)110 (101–120)491,440 (1,142–1,814)2,157 (1,868–2,490)
    G/G35561 (487–647)239 (207–276)0.158 (0.132–0.190)90 (77–106)171,360 (1,084–1,705)2,231 (1,973–2,523)
    P0.0100.270.220.00150.0260.037
  • 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.