TABLE 2.

Associations of metabolites with metabolic syndrome

			Original population (n = 594)						Replication population (n = 283)
			Model 1			Model 2			Model 1			Model 2
Pathways		Metabolitesa	% Changeb	95% CI	Pc	% Changed	95% CI	Pc	% Changeb	95% CI	Pe	% Changed	95% CI	Pe
Branched-chain amino acid metabolism	log	Valine	10.3	6.5-14.3	1.1 × 10−6	10.7	6.8-14.8	5.3 × 10−6	12.1	6.6-17.9	1.1 × 10−5	11.8	6.1-17.8	3.6 × 10−5
	log	Isoleucine	10.6	6.5-14.7	1.9 × 10−6	10.9	6.8-15.2	1.2 × 10−5	14.6	8.7-20.8	7.0 × 10−7	14.1	8.1-20.5	3.0 × 10−6
	log	Leucine	10.2	6.6-14.0	3.4 × 10−7	10.8	7.1-14.6	2.1 × 10−6	9.8	4.8-15.1	1.2 × 10−4	10.7	5.4-16.2	6.2 × 10−5
	log	4-Methyl-2-oxopentanoate	7.4	3.2-11.8	0.004	8.0	3.7-12.5	0.009	15.2	8.8-21.9	1.9 × 10−6	15.1	8.5-22.1	4.1 × 10−6
		2-Oxoisopentanoate	8.2	3.6-12.8	0.004	8.0	3.4-12.6	0.02	10.9	4.1-17.7	0.002	11.1	3.2-18.9	0.01
Aromatic amino acid metabolism	log	Phenylalanine	5.0	1.5-8.7	0.02	4.6	1.0-8.3	0.16	5.3	0.7-10.2	0.02	4.3	−0.3 to 9.2	0.07
	log	Tyrosine	5.6	2.2-9.0	0.007	4.3	1.0-7.8	0.15	4.8	−0.1 to 9.8	0.05	3.6	−1.3 to 8.6	0.15
Alanine, aspartate, and glutamate metabolism	log	Alanine	13.3	8.9-17.8	8.5 × 10−8	12.2	7.8-16.8	3.7 × 10−6	19.9	13.5-26.6	3.3 × 10−10	19.4	12.9-26.3	1.7 × 10−9
Alanine-glucose cycle	log	Glutamate	26.2	16.8-36.4	2.6 × 10−7	26.8	17.1-37.3	2.1 × 10−6	28.2	14.4-43.6	2.3 × 10−5	28.0	13.8-44.0	4.7 × 10−5
Glycine, serine, and threonine metabolism	log	Threonine	5.2	1.3-9.2	0.04	5.2	1.2-9.3	0.15	−3.3	−8.5 to 2.1	0.22	−2.7	−7.9 to 2.8	0.33
Lysine metabolism	log	Alpha-aminoadipate	11.9	6.4-17.6	2.0 × 10−4	12.6	7.0-18.5	5.2 × 10−4	16.1	7.2-25.7	2.7 × 10−4	15.8	6.7-25.6	4.7 × 10−4
Cysteine and methionine metabolism	log	Cystine	10.3	6.6-14.2	4.4 × 10−7	9.8	6.1-13.7	1.2 × 10−5	4.4	−1.0 to 10.1	0.11	3.4	−2.0 to 9.2	0.22
Proline and arginine metabolism	log	Proline	12.4	6.3-18.9	4.0 × 10−4	11.8	5.7-18.4	0.006	11.5	3.3-20.4	0.005	12.8	4.5-21.8	0.002
TCA cycle; glycolysis/gluconeogenesis; involved in metabolism of multiple amino acids		Pyruvate	9.9	3.6-16.3	0.01	8.7	2.8-14.7	0.07	20.3	10.0-30.6	1.2 × 10−4	19.0	8.8-29.2	2.9 × 10−4
TCA cycle	log	cis-Aconitate	7.2	1.8-12.8	0.04	5.8	0.5-11.3	0.28	8.8	1.0-17.3	0.03	6.6	−1.3 to 15.0	0.10
Glycolysis/gluconeogenesis, pyruvate metabolism	log	Lactate	10.8	4.6-17.5	0.004	9.4	3.1-16.0	0.06	16.9	7.1-27.6	5.3 × 10−4	14.5	4.7-25.3	0.003
Ketones	log	3-Hydroxybutyrate	−17.9	−28.4 to −5.7	0.02	−19.8	−30.2 to −7.8	0.048	−20.6	−35.4 to −2.3	0.03	−24.8	−39.0 to −7.5	0.007
Glucuronic acid derivatives	log	Mucate	−9.3	−14.4 to −3.8	0.007	−8.9	−14.2 to −3.3	0.05	−14.8	−26.4 to −1.3	0.03	−12.7	−25.1 to 1.7	0.08
Uremic toxins	log	Guanidinosuccinate	−22.6	−34.5 to −8.7	0.01	−20.9	−33.2 to −6.4	0.11	−33.2	−47.3 to −15.3	0.001	−28.2	−43.6 to −8.5	0.008

Model 1: unadjusted. Model 2: adjusted for age, LDL-C levels, current smoker or not, current alcohol drinker or not, physical exercise level (high/low), and calorie intake (high/low).

TCA, tricarboxylic acid.

^aMetabolites labeled “log” were log-transformed.

^bFor log-transformed metabolites, regression coefficients were back-transformed. For normal metabolites, regression coefficients were divided by the means of the non-MetS group.

^cFalse discovery rate P values are shown. P < 0.05 is considered significant.

^dSame as (b) for log-transformed metabolites. For normal metabolites, coefficients were divided by the adjusted means of the non-MetS group.

^eRaw P values are shown. P < 0.05 is considered significant.