Table 4.

Association [HR (95% CI)] between 1-year changes of lysine, 2-aminoadipic acid and pipecolic acid with type 2 diabetes and cardiovascular disease

	Q1	Q2	Q3	Q4	p linear trend	1 SD increase	1 SD increase (adjusted for 1-year changes in 2-AAA and pipecolic acid)
1-year change lysine
Outcome: T2D
MV adjusted modelb	Ref.	0.72 (0.37–1.40)	0.43 (0.17–1.07)	0.62 (0.29–1.34)	0.215	0.88 (0.65–1.20)	0.80 (0.58–1.10)
Outcome: CVD
MV adjusted modela	Ref.	1.07 (0.63–1.82)	0.93 (0.52–1.66)	0.93 (0.52–1.64)	0.796	0.95 (0.77–1.18)	0.99 (0.80–1.24)

	Q1	Q2	Q3	Q4	p linear trend	1 SD increase	1 SD increase (adjusted for 1-year changes in lysine and pipecolic acid)
1-year change 2-AAA
Outcome: T2D
MV adjusted modelb	Ref.	1.30 (0.63–2.67)	0.95(0.38–2.36)	1.66 (0.82–3.39)	0.214	1.23 (0–96–1.58)	1.29 (0.98–1.70)
Outcome: CVD
MV adjusted modela	Ref.	0.94 (0.52–1.69)	0.97 (0.55–1.72)	0.66 (0.35–1.21)	0.210	0.84 (0.67–1.05)	0.81 (0.63–1.04)

	Q1	Q2	Q3	Q4	p linear trend	1 SD increase	1 SD increase (adjusted for 1-year changes in lysine and 2-AAA)
1-year change pipecolic acid
Outcome: T2D
MV adjusted modelb	Ref.	1.45 (0.54–3.84)	1.22 (0.43–3.46)	1.42 (0.54–3.71)	0.483	1.08 (0.81–1.44)	1.18 (0.88–1.58)
Outcome: CVD
MV adjusted modela	Ref.	0.49 (0.21–1.12)	0.52 (0.24–1.13)	0.93 (0.47–1.84)	0.593	1.03 (0.83–1.28)	1.10 (0.87–1.37)

CVD cardiovascular disease, T2D type 2 diabetes, MV multivariable, 2-AAA 2-aminoadipic acid

^aMultivariable model adjusted for age, sex, intervention, BMI, smoking, dyslipidemia, hypertension, baseline plasma glucose and the respective baseline metabolite

^bMultivariable model adjusted for age, sex, intervention, BMI, smoking, dyslipidemia, hypertension, T2D, family history of CVD and the respective baseline metabolite