Metabolite Profile of Treatment-Naive Metabolic Syndrome Subjects in Relation to Cardiovascular Disease Risk
Abstract
:1. Introduction
2. Results
2.1. Baseline Characteristics
2.2. Metabolites in Relation to Peripheral Insulin Resistance
2.3. Metabolites in Relation to Cardiovascular Disease Risk
2.4. Metabolites in Relation to Lipolysis
3. Discussion
4. Materials and Methods
4.1. Study Design and Population
4.2. Clinical Parameters and Framingham Score
4.3. Metabolite Analysis
4.4. Two-Step Hyperinsulinemic Euglycemic Clamp and Lipolysis
4.5. Statistical Analysis and Machine Learning Models
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Overall | IR (Rd < 37.3) | N-IR (Rd ≥ 37.3) | p-Value | |
---|---|---|---|---|
n | 132 | 92 | 40 | |
Age (years) | 53.83 (9.38) | 53.61 (10.31) | 54.35 (6.89) | 0.678 |
BMI (kg/m2) | 33.91 [31.45, 37.05] | 34.50 [31.58, 38.69] | 33.40 [30.82, 35.00] | 0.024 |
Weight (kg) | 115.40 [102.10, 124.62] | 117.70 [105.45, 130.32] | 108.45 [99.95, 118.17] | 0.003 |
Syst (mmHg) | 143.61 (18.20) | 144.59 (18.63) | 140.72 (16.85) | 0.326 |
Diast (mmHg) | 89.45 (11.11) | 90.58 (10.93) | 86.14 (11.15) | 0.063 |
Gluc (mmol/L) | 5.72 (0.66) | 5.74 (0.70) | 5.68 (0.55) | 0.599 |
Insulin (pmol/L) | 109.00 [70.75, 141.75] | 123.00 [93.00, 158.50] | 69.00 [54.75, 87.00] | <0.001 |
Rd (μmol kg−1 min−1) | 31.37 [22.65, 40.02] | 27.00 [19.86, 33.01] | 48.10 [41.08, 55.45] | <0.001 |
HbA1c (mmol/mol) | 39.00 [36.00, 41.00] | 39.00 [36.00, 42.00] | 38.50 [37.00, 40.75] | 0.58 |
HOMA-IR | 3.70 [2.50, 5.16] | 4.29 [3.19, 5.46] | 2.55 [1.90, 3.05] | <0.001 |
Total chol (mmol/L) | 5.00 [4.59, 5.89] | 5.09 [4.56, 5.85] | 4.90 [4.63, 6.02] | 0.831 |
LDL (mmol/L) | 3.30 [2.70, 4.10] | 3.26 [2.70, 4.00] | 3.38 [2.66, 4.15] | 0.974 |
HDL (mmol/L) | 1.08 [0.93, 1.23] | 1.04 [0.93, 1.21] | 1.10 [0.96, 1.33] | 0.268 |
Trig (mmol/L) | 1.40 [1.12, 1.79] | 1.42 [1.16, 1.80] | 1.23 [1.10, 1.66] | 0.097 |
ALAT (U/L) | 33.00 [26.00, 41.00] | 34.00 [27.00, 43.00] | 31.00 [22.50, 36.25] | 0.022 |
CRP (mg/L) | 2.00 [1.30, 4.35] | 2.20 [1.37, 4.70] | 2.00 [1.05, 3.80] | 0.544 |
Leuko (10E9/L) | 6.01 (1.41) | 6.02 (1.37) | 5.95 (1.57) | 0.845 |
REE (kcal/day) | 1939.00 [1804.00, 2190.50] | 1952.00 [1806.00, 2246.70] | 1924.00 [1760.00, 2083.25] | 0.172 |
Biochemical Annotation | Subpathway Annotation | Super-Pathway Annotation | Low Framingham (n = 42, Median [IQR])) | High Framingham (n = 69, median [IQR]) |
---|---|---|---|---|
Eicosapentaenoate (EPA) | Long-Chain Polyunsaturated Fatty Acid (n3 and n6) | Lipid | 0.85 [0.69, 1.20] | 1.19 [0.91, 1.65] |
N-acetyltyrosine | Tyrosine Metabolism | Amino Acid | 0.93 [0.82, 1.17] | 1.22 [0.88, 1.57] |
1-stearoyl-2-docosahexaenoyl-GPE (18:0/22:6) * | Phosphatidylethanolamine (PE) | Lipid | 0.79 [0.60, 1.05] | 1.21 [0.77, 1.50] |
Docosahexaenoylcholine | Fatty Acid Metabolism (Acyl Choline) | Lipid | 0.81 [0.62, 1.28] | 1.14 [0.89, 1.58] |
Heneicosapentaenoate (21:5n3) | Long-Chain Polyunsaturated Fatty Acid (n3 and n6) | Lipid | 0.26 [0.26, 0.60] | 0.71 [0.26, 1.70] |
Androstenediol (3alpha, 17alpha) monosulfate (2) | Androgenic Steroids | Lipid | 1.16 [0.91, 1.69] | 0.81 [0.65, 1.02] |
3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) | Fatty Acid, Dicarboxylate | Lipid | 0.68 [0.26, 1.63] | 1.61 [0.62, 2.62] |
1-palmitoyl-2-docosahexaenoyl-GPE (16:0/22:6) * | Phosphatidylethanolamine (PE) | Lipid | 0.74 [0.58, 1.19] | 1.23 [0.78, 1.45] |
1-palmitoyl-2-stearoyl-GPC (16:0/18:0) | Phosphatidylcholine (PC) | Lipid | 0.96 [0.84, 1.02] | 1.04 [0.93, 1.12] |
lanthionine | Methionine, Cysteine, SAM, and Taurine Metabolism | Amino Acid | 0.23 [0.23, 0.38] | 0.69 [0.23, 1.22] |
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Warmbrunn, M.V.; Koopen, A.M.; de Clercq, N.C.; de Groot, P.F.; Kootte, R.S.; Bouter, K.E.C.; ter Horst, K.W.; Hartstra, A.V.; Serlie, M.J.; Ackermans, M.T.; et al. Metabolite Profile of Treatment-Naive Metabolic Syndrome Subjects in Relation to Cardiovascular Disease Risk. Metabolites 2021, 11, 236. https://doi.org/10.3390/metabo11040236
Warmbrunn MV, Koopen AM, de Clercq NC, de Groot PF, Kootte RS, Bouter KEC, ter Horst KW, Hartstra AV, Serlie MJ, Ackermans MT, et al. Metabolite Profile of Treatment-Naive Metabolic Syndrome Subjects in Relation to Cardiovascular Disease Risk. Metabolites. 2021; 11(4):236. https://doi.org/10.3390/metabo11040236
Chicago/Turabian StyleWarmbrunn, Moritz V., Annefleur M. Koopen, Nicolien C. de Clercq, Pieter F. de Groot, Ruud S. Kootte, Kristien E. C. Bouter, Kasper W. ter Horst, Annick V. Hartstra, Mireille J. Serlie, Mariette T. Ackermans, and et al. 2021. "Metabolite Profile of Treatment-Naive Metabolic Syndrome Subjects in Relation to Cardiovascular Disease Risk" Metabolites 11, no. 4: 236. https://doi.org/10.3390/metabo11040236
APA StyleWarmbrunn, M. V., Koopen, A. M., de Clercq, N. C., de Groot, P. F., Kootte, R. S., Bouter, K. E. C., ter Horst, K. W., Hartstra, A. V., Serlie, M. J., Ackermans, M. T., Soeters, M. R., van Raalte, D. H., Davids, M., Nieuwdorp, M., & Groen, A. K. (2021). Metabolite Profile of Treatment-Naive Metabolic Syndrome Subjects in Relation to Cardiovascular Disease Risk. Metabolites, 11(4), 236. https://doi.org/10.3390/metabo11040236