Electronic Supplementary Material 1: Significance values for baseline metabolites associated with baseline clinical measures by univariate analysis. Gray-shaded cells indicate correlations with p>0.05. Purple-shaded cells indicate correlations with p<0.05 but q>0.2. Corr = direction of correlation between metabolite and clinical measure.

Glucose / Insulin / HOMA-IR / C-peptide
Metabolite / p<
0.05 / Corr / p-value / q-value / Corr / p-value / q-value / Corr / p-value / q-value / Corr / p-value / q-value
Glucose / 4 / Pos. / 0.00003 / 0.0058 / Pos. / 0.014 / 0.23 / Pos. / 0.0044 / 0.12 / Pos. / 0.0015 / 0.29
Lactic acid / 4 / Pos. / 0.031 / 0.63 / Pos. / 0.0086 / 0.2 / Pos. / 0.0077 / 0.12 / Pos. / 0.023 / 0.7
Glutamic acid / 4 / Pos. / 0.00098 / 0.13 / Pos. / 0.00014 / 0.021 / Pos. / 0.00004 / 0.0055 / Pos. / 0.043 / 0.74
Glycine / 3 / Neg. / 0.055 / 0.79 / Neg. / 0.00004 / 0.015 / Neg. / 0.000015 / 0.0048 / Neg. / 0.0025 / 0.29
Asparagine / 3 / Neg. / 0.15 / 0.85 / Neg. / 0.012 / 0.23 / Neg. / 0.014 / 0.18 / Neg. / 0.018 / 0.64
Aminomalonate / 3 / Neg. / 0.30 / 0.92 / Neg. / 0.0034 / 0.15 / Neg. / 0.0014 / 0.054 / Neg. / 0.019 / 0.64
Alanine / 3 / Pos. / 0.012 / 0.43 / Pos. / 0.0047 / 0.16 / Pos. / 0.00099 / 0.044 / Pos. / 0.099 / 0.77
3-hydroxybutanoic acid / 3 / Neg. / 0.0041 / 0.31 / Neg. / 0.00052 / 0.033 / Neg. / 0.00085 / 0.044 / Neg. / 0.24 / 0.89
Glycerol / 3 / Neg. / 0.02 / 0.51 / Neg. / 0.015 / 0.23 / Neg. / 0.017 / 0.19 / Pos. / 0.44 / 0.94
Linoleic acid / 3 / Neg. / 0.035 / 0.67 / Neg. / 0.0004 / 0.03 / Neg. / 0.00074 / 0.044 / Neg. / 0.47 / 0.94
Azelaic acid / 3 / Neg. / 0.031 / 0.63 / Neg. / 0.0078 / 0.2 / Neg. / 0.0057 / 0.12 / Neg. / 0.47 / 0.94
2-aminoadipic acid / 2 / Pos. / 0.13 / 0.85 / Pos. / 0.069 / 0.53 / Pos. / 0.039 / 0.28 / Pos. / 0.012 / 0.55
Nicotinic acid / 2 / Neg. / 0.036 / 0.67 / Neg. / 0.13 / 0.59 / Neg. / 0.048 / 0.32 / Neg. / 0.055 / 0.74
Valine / 2 / Pos. / 0.12 / 0.85 / Pos. / 0.0089 / 0.2 / Pos. / 0.0023 / 0.072 / Pos. / 0.11 / 0.77
Leucine / 2 / Pos. / 0.04 / 0.7 / Pos. / 0.066 / 0.53 / Pos. / 0.015 / 0.19 / Pos. / 0.11 / 0.77
Aspartic acid / 2 / Pos. / 0.16 / 0.85 / Pos. / 0.044 / 0.46 / Pos. / 0.021 / 0.21 / Pos. / 0.14 / 0.81
Hydroxylamine / 2 / Neg. / 0.28 / 0.92 / Neg. / 0.0084 / 0.2 / Neg. / 0.0075 / 0.12 / Neg. / 0.25 / 0.89
5-Oxoproline / 2 / Neg. / 0.65 / 0.92 / Neg. / 0.02 / 0.27 / Neg. / 0.041 / 0.29 / Neg. / 0.51 / 0.94
Palmitoleic acid / 2 / Neg. / 0.077 / 0.79 / Neg. / 0.0038 / 0.15 / Neg. / 0.0056 / 0.12 / Pos. / 0.53 / 0.94
Tyrosine / 2 / Pos. / 0.30 / 0.92 / Pos. / 0.027 / 0.34 / Pos. / 0.018 / 0.2 / Pos. / 0.72 / 0.99
Oleic acid / 2 / Neg. / 0.19 / 0.85 / Neg. / 0.0038 / 0.15 / Neg. / 0.0067 / 0.12 / Neg. / 0.94 / 0.99
Fructose / 1 / Pos. / 0.82 / 0.92 / Pos. / 0.29 / 0.7 / Pos. / 0.61 / 0.68 / Pos. / 0.01 / 0.55
Malate / 1 / Neg. / 0.97 / 0.94 / Neg. / 0.74 / 0.88 / Neg. / 0.85 / 0.73 / Pos. / 0.038 / 0.74
Proline / 1 / Pos. / 0.086 / 0.79 / Pos. / 0.11 / 0.56 / Pos. / 0.028 / 0.26 / Pos. / 0.052 / 0.74
Uric acid / 1 / Pos. / 0.016 / 0.48 / Pos. / 0.3 / 0.71 / Pos. / 0.16 / 0.49 / Pos. / 0.48 / 0.94
Sucrose / 1 / Neg. / 0.019 / 0.51 / Neg. / 0.71 / 0.88 / Neg. / 0.36 / 0.6 / Neg. / 0.77 / 0.99

Electronic Supplementary Material 2: Significance values for baseline metabolites associated with baseline clinical measures by multivariate analysis.

Glucose / Insulin / HOMA / C-peptide
Est. of Eff. / Corr / p-value / Est. of Eff. / Corr / p-value / Est. of Eff. / Corr / p-value / Est. of Eff. / Corr / p-value
Glutamic acid / 1.1 / Pos. / 4.2
e-04 / NS / NS / NS / 1.2 / Pos. / 2.3
e-05 / NS / NS / NS
Glucose / 5.5 / Pos. / 1.7
e-05 / NS / NS / NS / 3.5 / Pos. / 1.5
e-03 / 4.9 / Pos. / 5.2
e-04
3-Hydroxybutanoic acid / -0.88 / Neg. / 6.1
e-04 / -0.85 / Neg. / 2.4
e-04 / -0.91 / Neg. / 7.0
e-05 / NS / NS / NS
Glycine / NS / NS / NS / -1.9 / Neg. / 3.4
e-05 / -2.2 / Neg. / 2.6
e-06 / NS / NS / NS
Asparagine / NS / NS / NS / NS / NS / NS / NS / NS / NS / -1.3 / Neg. / 1.5
e-04
2-Aminoadipic acid / NS / NS / NS / NS / NS / NS / NS / NS / NS / 1.7 / Pos. / 2.9
e-03

Electronic Supplementary Material 3:Significance values for change in metabolite levels associated with change in clinical measure levels by univariate analysis. Gray-shaded cells indicate correlations with p>0.05. Purple-shaded cells indicate correlations with p<0.05 but q>0.2. Corr = direction of correlation between metabolite and clinical measure.

Glucose / Insulin / HOMA-IR / C-peptide
Metabolite / Sig. / Corr. / p-value / q-value / Corr. / p-value / q-value / Corr / p-value / q-value / Corr. / p-value / q-value
Glucose / 3 / Pos. / 0.019 / 0.9 / Pos. / 0.016 / 0.89 / Pos. / 0.0087 / 0.88 / Pos. / 0.05 / 0.78
Galactosyl-glycerate / 1 / Neg. / 0.038 / 0.91 / Pos. / 0.17 / 0.89 / Pos. / 0.45 / 0.88 / Pos. / 0.088 / 0.78
Isoleucine / 2 / Neg. / 0.044 / 0.91 / Pos. / 0.091 / 0.89 / Pos. / 0.26 / 0.88 / Pos. / 0.038 / 0.78
Glucuronic Acid / 2 / Neg. / 0.91 / 0.92 / Pos. / 0.013 / 0.89 / Pos. / 0.12 / 0.88 / Pos. / 0.044 / 0.78
Ketoleucine / 1 / Neg. / 0.82 / 0.91 / Pos. / 0.024 / 0.89 / Pos. / 0.072 / 0.88 / Pos. / 0.063 / 0.78
Alanine / 2 / Pos. / 0.54 / 0.91 / Pos. / 0.087 / 0.89 / Pos. / 0.041 / 0.88 / Pos. / 0.013 / 0.76
Fructose / 1 / Neg. / 0.89 / 0.92 / Pos. / 0.11 / 0.89 / Pos. / 0.29 / 0.88 / Pos. / 0.0044 / 0.76
Arabitol / 1 / Neg. / 0.21 / 0.91 / Pos. / 0.45 / 0.89 / Neg. / 0.89 / 0.94 / Pos. / 0.044 / 0.78

Electronic Supplementary Material 4: Significance values for post-treatment metabolites associated with post-treatment clinical measures by univariate analysis. Gray-shaded cells indicate correlations with p>0.05. Purple-shaded cells indicate correlations with p<0.05 but q>0.2. Corr = direction of correlation between metabolite and clinical measure.

Glucose / Insulin / HOMA-IR / C-peptide
Metabolite / p
<0.05 / Corr. / p-value / q-value / Corr. / p-value / q-value / Corr / p-value / q-value / Corr. / p-value / q-value
Glucose / 3 / Pos. / 7.2 e-07 / 0.0001 / Pos. / 0.034 / 0.72 / Pos. / 0.0063 / 0.55 / Pos. / 0.78 / 0.83
Glutamic Acid / 3 / Pos. / 0.024 / 0.61 / Pos. / 0.029 / 0.72 / Pos. / 0.015 / 0.55 / Pos. / 0.1 / 0.8
Maltose / 1 / Pos. / 0.033 / 0.61 / Pos. / 0.14 / 0.95 / Pos. / 0.059 / 0.93 / Pos. / 0.079 / 0.8
Lauric acid / 4 / Neg. / 0.04 / 0.61 / Neg. / 0.034 / 0.72 / Neg. / 0.027 / 0.67 / Neg. / 0.017 / 0.8
Myristic acid / 2 / Neg. / 0.04 / 0.61 / Neg. / 0.12 / 0.95 / Neg. / 0.085 / 0.97 / Neg. / 0.5 / 0.83
Linoleic acid / 2 / Neg. / 0.067 / 0.67 / Neg. / 0.025 / 0.72 / Neg. / 0.01 / 0.55 / -1.1 / 0.29 / 0.83
Alanine / 3 / Pos. / 0.088 / 0.67 / Pos. / 0.01 / 0.69 / Pos. / 0.013 / 0.55 / Pos. / 0.01 / 0.8
Glycine / 3 / Neg. / 0.092 / 0.67 / Neg. / 0.0002 / 0.07 / Neg. / 0.0006 / 0.16 / Neg. / 0.024 / 0.8
Palmitoleic acid / 2 / Neg. / 0.095 / 0.67 / Neg. / 0.023 / 0.72 / Neg. / 0.015 / 0.55 / Neg. / 0.55 / 0.83
Isocitric Acid / 2 / Pos. / 0.11 / 0.67 / Pos. / 0.058 / 0.86 / Pos. / 0.041 / 0.82 / Pos. / 0.05 / 0.8
3-Hydroxybutanoic Acid / 2 / Neg. / 0.15 / 0.69 / Neg. / 0.01 / 0.69 / Neg. / 0.0034 / 0.45 / Neg. / 0.16 / 0.83
Aminomalonate / 3 / Neg. / 0.2 / 0.74 / Neg. / 0.014 / 0.69 / Neg. / 0.043 / 0.82 / Neg. / 0.041 / 0.8
Oleic Acid / 2 / Neg. / 0.27 / 0.76 / Neg. / 0.043 / 0.79 / Neg. / 0.03 / 0.67 / Neg. / 0.54 / 0.83
Azelaic Acid / 1 / Neg. / 0.41 / 0.76 / Neg. / 0.0064 / 0.69 / Neg. / 0.013 / 0.55 / Neg. / 0.082 / 0.8
N-Methylalanine / 1 / Neg. / 0.85 / 0.85 / Neg. / 0.046 / 0.8 / Neg. / 0.07 / 0.93 / Neg. / 0.15 / 0.83
Proline / 1 / Pos. / 0.37 / 0.76 / Pos. / 0.07 / 0.92 / Pos. / 0.1 / 0.97 / Pos. / 0.036 / 0.8
Succinic Acid / 1 / Neg. / 0.66 / 0.8 / Neg. / 0.22 / 0.95 / Neg. / 0.31 / 0.97 / Neg. / 0.035 / 0.8
Lactic Acid / 1 / Pos. / 0.92 / 0.85 / Pos. / 0.067 / 0.91 / Pos. / 0.15 / 0.97 / Pos. / 0.012 / 0.8

Electronic Supplementary Material 5: Significance values for post-treatment metabolites associated with post-treatment clinical measures by multivariate analysis.

Glucose / Insulin / HOMA / C-peptide
Est. of Eff. / Corr / p-value / Est. of Eff. / Corr / p-value / Est. of Eff. / Corr / p-value / Est. of Eff. / Corr / p-value
Uridine-like compound / -1.9 / Neg. / 0.007 / NS / NS / NS / NS / NS / NS / NS / NS / NS
Galactosyl-glycerate / -1.3 / Neg. / 0.01 / NS / NS / NS / NS / NS / NS / NS / NS / NS
Glycine / NS / NS / NS / -2.1 / Neg. / 0.000012 / -3.6 / Neg. / 0.000015 / -1.7 / Neg. / 0.0016
Glutamic Acid / NS / NS / NS / 0.92 / Pos. / 0.0064 / NS / NS / NS / NS / NS / NS
3-Hydroxybutanoic Acid / NS / NS / NS / -0.8 / Neg. / 0.00041 / -0.91 / Neg. / 0.000049 / NS / NS / NS
Alanine / NS / NS / NS / NS / NS / NS / NS / NS / NS / 2.7 / Pos. / 0.000036

Electronic Supplementary Material 6: Significance values for baseline metabolites associated with post-treatment clinical measures by univariate analysis. Gray-shaded cells indicate correlations with p>0.05. Purple-shaded cells indicate correlations with p<0.05 but q>0.2. Corr = direction of correlation between metabolite and clinical measure.

Glucose / Insulin / HOMA-IR / C-peptide
Metabolite / p<0.05 / Corr / p-value / q-value / Corr / p-value / q-value / Corr / p-value / q-value / Corr / p-value / q-value
3-Hydroxybutanoic Acid / 3 / Neg. / 0.038 / 0.55 / Neg. / 0.02 / 0.16 / Neg. / 0.0053 / 0.091 / Neg. / 0.57 / 0.98
Alanine / 3 / Pos. / 0.04 / 0.55 / Pos. / 0.0081 / 0.13 / Pos. / 0.009 / 0.091 / Pos. / 0.35 / 0.98
Aminomalonate / 2 / Neg. / 0.34 / 0.68 / Neg. / 0.0018 / 0.052 / Neg. / 0.0053 / 0.091 / Neg. / 0.056 / 0.77
Asparagine / 2 / Neg. / 0.15 / 0.55 / Neg. / 0.014 / 0.13 / Neg. / 0.006 / 0.091 / Neg. / 0.0091 / 0.25
Aspartic Acid / 2 / Pos. / 0.09 / 0.55 / Pos. / 0.013 / 0.13 / Pos. / 0.016 / 0.12 / Pos. / 0.21 / 0.86
Azelaic Acid / 2 / Neg. / 0.058 / 0.55 / Neg. / 0.036 / 0.19 / Neg. / 0.029 / 0.16 / Neg. / 0.22 / 0.86
Ethanolamine / 2 / Neg. / 0.88 / 0.82 / Neg. / 0.045 / 0.2 / Neg. / 0.068 / 0.3 / Neg. / 0.013 / 0.27
Glutamic Acid / 3 / Pos. / 0.0028 / 0.19 / Pos. / 0.025 / 0.16 / Pos. / 0.0086 / 0.091 / Pos. / 0.42 / 0.98
Glycine / 3 / Neg. / 0.16 / 0.57 / Neg. / 0.00002 / 0.0012 / Neg. / 0.000064 / 0.0039 / Neg. / 0.0018 / 0.14
Lactic Acid / 3 / Pos. / 0.14 / 0.55 / Pos. / 0.024 / 0.16 / Pos. / 0.022 / 0.13 / Pos. / 0.0055 / 0.23
Linoleic Acid / 2 / Neg. / 0.057 / 0.55 / Neg. / 0.046 / 0.2 / Neg. / 0.021 / 0.13 / Neg. / 0.75 / 0.98
Threonine / 2 / Pos. / 0.19 / 0.58 / Pos. / 0.033 / 0.19 / Pos. / 0.06 / 0.28 / Pos. / 0.6 / 0.98
Uridine / 1 / Neg. / 0.13 / 0.55 / Neg. / 0.21 / 0.34 / Neg. / 0.21 / 0.39 / Neg. / 0.038 / 0.63
Valine / 1 / Pos. / 0.099 / 0.55 / Pos. / 0.0098 / 0.13 / Pos. / 0.013 / 0.11 / Pos. / 0.57 / 0.98