Table 3 Rate Ratio and Rate Difference per 10,000 person-years, for incident type 2 diabetes (95%CI) comparing the 90th to the 10th percentiles of HLS-related metabolites distributions^a

Lipoprotein profile

 VLDL cholesterol

2.12 (1.45–3.08)

< 0.001

2.09 (1.35–3.24)

< 0.001

59.62 (18.18, 101.06)

0.005

60.66 (16.58, 104.74)

0.007

 HDL cholesterol

0.21 (0.07–0.66)

0.008

0.28 (0.10–0.79)

0.02

−52.40 (−88.35, −16.45)

0.004

− 47.56 (− 83.74, − 11.37)

0.01

 IDL cholesterol

1.27 (0.75–2.15)

0.38

1.11 (0.61–2.01)

0.74

9.82 (− 15.46, 35.1)

0.45

6.12 (−24.57, 36.81)

0.70

 VLDL triglycerides

2.07 (1.48–2.91)

< 0.001

2.02 (1.38–2.95)

< 0.001

58.25 (17.54, 98.95)

0.005

56.59 (14.06, 99.12)

0.009

 IDL triglycerides

1.25 (0.69–2.29)

0.46

1.14 (0.60–2.17)

0.69

9.79 (−18.15, 37.73)

0.49

8.52 (−22.84, 39.89)

0.59

 Large VLDL

1.77 (1.36–2.31)

< 0.001

1.67 (1.25–2.24)

< 0.001

48.30 (8.03, 88.58)

0.02

45.59 (4.49, 86.69)

0.03

 Medium VLDL

1.56 (1.20–2.03)

< 0.001

1.48 (1.12–1.95)

< 0.001

43.70 (8.93, 78.48)

0.01

39.86 (3.85, 75.87)

0.03

 Small VLDL

2.34 (1.62–3.37)

< 0.001

2.40 (1.57–3.68)

< 0.001

61.85 (20.86, 102.85)

0.003

62.69 (19.54, 105.84)

0.004

 Small LDL

1.70 (1.20–2.40)

0.003

2.71 (1.52–4.82)

< 0.001

45.69 (6.59, 84.78)

0.02

78.19 (16.82, 139.56)

0.01

 Medium HDL

0.15 (0.05–0.49)

0.002

0.22 (0.07–0.66)

0.007

−54.12 (−84.41, −23.83)

< 0.001

−46.41 (−76.50, −16.31)

0.003

Amino acids

Alanine

0.33 (0.20–0.53)

< 0.001

0.38 (0.24–0.60)

< 0.001

−66.25 (− 106.80, − 25.70)

0.001

−60.72 (− 100.87, − 20.58)

0.003

Creatine phosphate

0.43 (0.22–0.84)

0.01

0.36 (0.18–0.76)

0.007

−36.60 (− 70.68, − 2.52)

0.04

−51.06 (−95.96, − 6.15)

0.03

Creatine

0.34 (0.20–0.59)

< 0.001

0.27 (0.14–0.51)

< 0.001

−49.69 (− 82.80, − 16.57)

0.003

−68.15 (−113.77, − 22.52)

0.003

Cysteine

0.35 (0.20–0.60)

< 0.001

0.29 (0.15–0.55)

< 0.001

−43.89 (− 74.10, − 13.69)

0.004

−57.78 (−97.34, − 18.21)

0.004

Glutamine

0.32 (0.18–0.57)

< 0.001

0.29 (0.15–0.53)

< 0.001

− 51.97 (−88.04, −15.91)

0.005

−62.53 (− 106.14, − 18.91)

0.005

N-acetylglutamine

0.28 (0.18–0.44)

< 0.001

0.27 (0.16–0.44)

< 0.001

− 68.69 (−104.62, − 32.76)

< 0.001

−71.46 (−109.90, − 33.01)

< 0.001

Proline

0.34 (0.19–0.62)

< 0.001

0.33 (0.18–0.61)

< 0.001

− 51.58 (− 88.78, −14.37)

0.007

−58.68 (− 100.91, − 16.44)

0.006

Leucine

0.32 (0.20–0.51)

< 0.001

0.37 (0.23–0.59)

< 0.001

−68.75 (−107.06, − 30.45)

< 0.001

−60.81 (− 97.75, − 23.87)

0.001

Fatty acids

CH2CH2CO-

3.38 (2.07–5.52)

< 0.001

3.03 (1.87–4.91)

< 0.001

64.57 (27.25, 101.89)

< 0.001

60.88 (24.37, 97.39)

0.001

CH2N-

2.79 (1.69–4.60)

< 0.001

2.77 (1.62–4.73)

< 0.001

53.28 (17.86, 88.69)

0.003

59.06 (18.42, 99.70)

0.004

Isobutyrate

0.22 (0.13–0.37)

< 0.001

0.27 (0.16–0.46)

< 0.001

−73.15 (− 109.93, − 36.38)

< 0.001

−65.92 (−101.30, − 30.54)

< 0.001

Fluid balance

Albumin

0.34 (0.20–0.58)

< 0.001

0.26 (0.14–0.50)

< 0.001

−50.89 (− 84.27, −17.52)

0.003

−70.49 (− 116.19, − 24.78)

0.003

Creatinine

0.65 (0.34–1.26)

0.21

0.56 (0.26–1.17)

0.12

− 16.96 (− 46.61, 12.68)

0.26

−22.07 (− 56.62, 12.49)

0.21

Energy metabolism

 Citrate

0.30 (0.16–0.57)

< 0.001

0.27 (0.14–0.55)

< 0.001

−49.90 (− 84.40, − 15.40)

0.005

− 58.56 (−98.87, − 18.26)

0.004

 Pyruvate

0.32 (0.18–0.59)

< 0.001

0.31 (0.16–0.58)

< 0.001

− 49.48 (− 84.04, − 14.92)

0.005

− 56.04 (−94.75, − 17.32)

0.005

 Acetate

0.28 (0.15–0.52)

< 0.001

0.27 (0.15–0.51)

< 0.001

− 62.62 (− 101.68, − 23.55)

0.002

− 68.92 (− 111.80, − 26.04)

0.002

 Acetone

3.19 (1.97–5.15)

< 0.001

2.88 (1.84–4.51)

< 0.001

75.63 (32.20, 119.05)

< 0.001

72.26 (29.49, 115.03)

< 0.001

 3-Hydroxybutyrate

0.36 (0.20–0.64)

< 0.001

0.34 (0.18–0.63)

< 0.001

− 48.61 (− 84.22, − 13.00)

0.007

− 56.27 (− 97.80, − 14.74)

0.008

Products of bacterial co-metabolism

Isopropanol

0.47 (0.23–0.93)

0.03

0.39 (0.18–0.85)

0.02

−31.46 (− 63.24, 0.31)

0.05

−43.23 (− 83.80, − 2.66)

0.04

Trimethylamines

0.29 (0.16–0.53)

< 0.001

0.23 (0.12–0.45)

< 0.001

−52.59 (− 86.57, − 18.61)

0.002

−68.58 (− 112.14, − 25.01)

0.002

Phenylpropionate

0.34 (0.21–0.54)

< 0.001

0.39 (0.26–0.59)

< 0.001

− 70.33 (− 112.40, − 28.25)

0.001

−66.12 (− 108.06, − 24.19)

0.002

Phosphoethanolamines

O-phosphoethanolamine

0.38 (0.20–0.72)

0.003

0.33 (0.17–0.65)

0.002

− 42.53 (− 77.86, −7.19)

0.02

−56.54 (− 101.38, − 11.69)

0.01