TABLE 2

Quantitative metabolic traits in the population-based Inter99 cohort including 5,970 middle-aged subjects with normal glucose tolerance (n = 4,522), impaired fasting glycemia (n = 503), impaired glucose tolerance (n = 693), or screen-detected and treatment-naïve type 2 diabetes (n = 252) stratified according to genotype

rs1111875 (HHEX/KIF11/IDE)
rs4402960 (IGF2BP2)
rs10811661 (CDKN2A/B)
rs9300039
TTTCCCPaddPdomPrecGGGTTTPaddPdomPrecCCCTTTPaddPdomPrecAAACCCPaddPdomPrec
n1,0282,6752,0172,7732,4325411541,6084,036489394,742
Men/women (n)519/5091,318/1,3571,001/1,0161,368/1,4051,230/1,202261/28078/76813/7951,992/2,04425/23456/4832,358/2,384
Age (years)46.2 ± 7.746.2 ± 7.946 ± 8.046.1 ± 7.946.1 ± 8.046.4 ± 7.746.4 ± 8.146.3 ± 7.946.1 ± 7.847.4 ± 7.145.9 ± 8.046.1 ± 7.9
BMI (kg/m2)26.2 ± 4.526.3 ± 4.626.1 ± 4.50.50.70.226.1 ± 4.626.2 ± 4.526.3 ± 4.60.40.40.526.2 ± 4.126.2 ± 4.626.2 ± 4.50.80.90.826 ± 4.526.1 ± 4.526.2 ± 4.60.40.70.4
Fasting serum insulin (pmol/l)34 (24–51)35 (24–52)34 (24–50)0.70.60.934 (23–50)35 (24–52)35 (24–52)0.40.60.335 (25–47)35 (24–53)34 (24–51)0.710.730 (23–47)35 (24–52)34 (24–51)0.40.60.3
Serum insulin at 30 min (pmol/l)260 (190–380)251 (178–363)233 (167–331)3 × 10−11*1 × 10−6*2 × 10−9*248 (176–358)243 (178–348)242 (176–358)0.10.080.7244 (175–352)254 (177–365)242 (174–348)0.0050.30.004*258 (174–378)247 (178–354)244 (175–353)0.60.70.6
Serum insulin at 120 min (pmol/l)156 (97–268)159 (98–259)154 (93–247)0.20.40.2154 (96–252)159 (97–257)160 (94–265)0.30.30.4171 (103–248)161 (101–258)155 (93–254)0.060.80.04151 (96–251)155 (93–261)157 (97–254)0.90.80.9
Fasting plasma glucose (mmol/l)5.5 ± 0.75.6 ± 0.95.5 ± 0.70.30.10.85.5 ± 0.75.6 ± 0.95.5 ± 0.70.70.70.15.5 ± 0.65.5 ± 0.95.5 ± 0.80.030.40.035.6 ± 1.35.5 ± 0.75.5 ± 0.80.80.80.8
Plasma glucose at 30 min (mmol/l)8.6 ± 1.98.7 ± 1.98.7 ± 1.90.020.020.18.7 ± 1.88.7 ± 28.7 ± 1.80.50.50.88.8 ± 1.88.7 ± 1.98.7 ± 1.90.30.30.29.1 ± 2.78.7 ± 28.7 ± 1.910.50.9
Plasma glucose at 120 min (mmol/l)6.1 ± 2.06.2 ± 2.16.2 ± 2.20.30.40.36.1 ± 2.16.3 ± 2.26.3 ± 20.040.020.66.0 ± 1.46.2 ± 2.26.2 ± 2.10.40.40.56.2 ± 2.76.2 ± 2.16.2 ± 2.10.40.60.4
HOMA-IR (mmol/l × pmol/l)8.2 (5.6–12.4)8.5 (5.7–13.1)8.2 (5.7–12.9)0.60.40.98.2 (5.5–12.7)8.4 (5.7–13.1)8.7 (5.7–13.1)0.50.60.58.4 (5.8–11.8)8.3 (5.6–13.2)8.3 (5.7–12.9)10.817.2 (5.0–13.2)8.6 (5.5–13.2)8.3 (5.7–12.7)0.40.70.3
BIGTT-Si9.1 (6.4–12.3)9.0 (6.2–11.9)9.4 (6.4–12.1)0.10.80.059.2 (6.5–12.2)9.1 (6.3–11.4)9.3 (5.8–12.2)0.30.20.89.7 (6.7–12.0)9.3 (6.4–12.1)9.1 (6.3–12.1)0.80.40.99.0 (6.7–13.4)9.2 (6.4–11.9)9.2 (6.4–12.1)0.80.50.9
Insulinogenic indexinsulin26.9 (18.3–40.5)24.9 (16.9–36.5)22.5 (15.5–34.1)1 × 10−13*2 × 10−8*1 × 10−10*24.8 (16.9–36.4)24.1 (16.4–36.3)24.0 (17.2–37.1)0.10.060.724.9 (17.3–37.5)25.1 (17.2–37.7)24.0 (16.5–35.7)0.003*0.40.002*25.1 (17.8–38.8)25.1 (17.5–36.3)24.4 (16.7–36.4)0.50.60.6
BIGTT-AIR1,680 (1,330–2,140)1,650 (1,300–2,080)1,580 (1,250–2,040)6 × 10−7*1 × 10−4*2 × 10−5*1,620 (1,280–2,070)1,630 (1,290–2,090)1,630 (1,280–2,130)0.80.80.71,620 (1,320–1,970)1,660 (1,310–2,150)1,610 (1,270–2,060)0.0070.80.001*1,610 (1,300–2,080)1,650 (1,290–2,070)1,620 (1,280–2,080)0.610.6
  • Data are median (interquantile range) or means ± SD (age, BMI, and values of plasma glucose). Values of plasma glucose, serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), insulinogenic indexinsulin, and BIGTT-AIR were logarithmically transformed before statistical analysis. Calculated P values were adjusted for age, sex, and BMI, where appropriate, assuming an additive (Padd), dominant (Pdom), or recessive (Prec) model. Homeostasis model assessment of insulin resistance was calculated as fasting plasma glucose (mmol/l) multiplied by fasting serum insulin (pmol/l) and divided by 22.5. Insulinogenic indexinsulin was calculated as (serum insulin at 30 min [pmol/l] − fasting serum insulin [pmol/l])/plasma glucose at 30 min (mmol/l). BIGTT-Si and BIGTT-AIR uses information on sex and BMI combined with analysis of plasma glucose and serum insulin levels at the time points 0, 30, and 120 min to provide indexes for Si and AIR that highly correlate with indexes obtained during an IVGTT and were calculated as described elsewhere (13).

  • *

    * Statistically significant at the 5% level after correcting of multiple testing of traits and models within this cohort and variant using a permutation procedure.