Table 3. Differential urinary metabolites between T2DM with and without nephropathy.
| Class | Name | DN | T2DM | T test. P | VIP | Pathway |
|---|---|---|---|---|---|---|
| Amino acid | L-Valine | 1,4824.5 (9,025.25, 31585.5) | 4,716 (3,303.5, 7020.5) | 9.40E-07 | 2.9 | Propanoate metabolism, transcription/translation, valine, leucine and isoleucine degradation |
| L-Histidine | 10,364 (4,639.75, 18,147.25) | 3,146 (899.25, 4,270.5) | 2.44E-05 | 2.4 | Ammonia recycling, histidine metabolism, transcription/translation | |
| Glycine | 65,575 (39,493.75, 105,077) | 39,768 (20,924, 53,651.75) | 1.03E-04 | 2.2 | Alanine metabolism, ammonia recycling, bile acid biosynthesis, carnitine synthesis, glutathione metabolism, glycine and serine metabolism, methionine metabolism, porphyrin metabolism | |
| Galactonic acid | 54,048 (37,692.25, 93,398.25) | 35,796.5 (19,514.75, 57,736) | 1.00E-03 | 1.6 | Galactose metabolism; metabolic pathways; microbial metabolism in diverse environments | |
| L-Glutamine | 251,416 (123,474, 461,131.5) | 132,467.5 (73,631.75, 241,030.25) | 3.00E-03 | 1.9 | Amino sugar metabolism, ammonia recycling, glutamate metabolism, phenylacetate metabolism, purine metabolism, pyrimidine metabolism, transcription/translation, urea cycle | |
| 4-Hydroxybenzoic acid | 40,798.5 (21,313.75, 115,454.25) | 23,748.5 (14,890.5, 54,047) | 4.00E-03 | 1.7 | Ammonia recycling, aspartate metabolism, transcription/translation | |
| Ketoleucine | 8,137 (4,966, 16,225.25) | 22,470.5 (4,557.75, 49,945.5) | 8.00E-03 | 1.3 | Valine, leucine and isoleucine degradation | |
| L-Serine | 92,666 (71,705.5, 163,200) | 79,442.5 (36,488, 107,665.25) | 1.00E-02 | 1.7 | Ammonia recycling, glycine and serine metabolism, homocysteine degradation, methionine metabolism, sphingolipid metabolism | |
| L-Alanine | 58,922.5 (29,373.75, 95,954.75) | 32,996 (19,712.25, 52,954) | 1.50E-02 | 1.9 | Alanine metabolism, glucose-alanine cycle, glycine and serine metabolism, selenoamino acid metabolism, transcription/translation, urea cycle | |
| L-Threonine | 61,327 (28,033.75, 150,853) | 66,284 (28,502, 105,775) | 1.50E-02 | 1.7 | Glycine and serine metabolism, threonine and 2-oxobutanoate degradation, transcription/translation | |
| L-Glutamic acid | 29,932.5 (18,307, 60,635) | 29,173.5 (15,021.5, 48,765.75) | 3.60E-02 | 1.4 | Alanine metabolism, amino sugar metabolism, ammonia recycling, arginine and proline metabolism, cysteine metabolism, folate metabolism, glucose-alanine cycle, glutamate metabolism, glutathione metabolism, glycine and serine metabolism, histidine metabolism, malate-aspartate shuttle, transcription/translation, urea cycle | |
| Amino acid metabolism | L-Asparagine/L-Aspartic acid | 9.68 (5.958, 20.118) | 4.66 (2.934, 7.522) | 1.71E-04 | 2 | Alanine, aspartate and glutamate metabolism |
| L-Phenylalanine/Phenylpyruvic acid | 30.1 (11.584, 61.208) | 8.09 (4.657, 15.047) | 6.13E-04 | 1.7 | Phenylalanine, tyrosine and tryptophan biosynthesis | |
| Phenylpyruvic acid/L-Phenylalanine | 0.03 (0.016, 0.088) | 0.12 (0.066, 0.215) | 1.20E-02 | 1.6 | Phenylalanine metabolism | |
| Ornithine/L-Arginine | 33.3 (9.814, 65.809) | 23.33 (14.106, 29.792) | 2.20E-02 | 1.5 | Arginine biosynthesis; arginine and proline metabolism | |
| L-Arabinose/L-Arabitol | 3.27 (1.428, 6.406) | 1.17 (0.668, 2.598) | 7.82E-04 | 1.8 | Pentose and glucuronate interconversions | |
| D-Glucose/Trehalose | 4.64 (2.208, 8.466) | 1.5 (0.677, 2.537) | 9.97E-04 | 1.6 | Starch and sucrose metabolism | |
| Fumaric acid/Succinic acid | 1.87 (0.783, 3.783) | 0.58 (0.233, 1.478) | 7.00E-03 | 1.5 | Citrate cycle (TCA cycle) | |
| D-Fructose/Sucrose | 0.11 (0.059, 0.259) | 0.23 (0.071, 0.763) | 1.20E-02 | 1.3 | Starch and sucrose metabolism | |
| Carbohydrates | D-Glucose | 267,788.5 (181,641.25, 363,846.25) | 89,577 (41,878.25, 157,795.5) | 2.12E-10 | 3 | Galactose metabolism, gluconeogenesis, glucose-alanine cycle, glycolysis, lactose degradation, lactose synthesis, transfer of acetyl groups into mitochondria |
| Gluconic acid | 382,496.5 (230,424.25, 531,628.25) | 227,164.5 (124,367.75, 323,271.75) | 3.60E-05 | 2 | Pentose phosphate pathway; metabolic pathways; biosynthesis of secondary metabolites; microbial metabolism in diverse environments; biosynthesis of antibiotics; carbon metabolism | |
| Sucrose | 1,200,070 (410,986.25, 1,750,933.5) | 267,627.5 (108,851.5, 665,185.75) | 6.89E-05 | 2.3 | Galactose metabolism, starch and sucrose metabolism | |
| L-Cystine | 133,144.5 (72,901, 283,660.5) | 44,629 (16,423, 104,929.5) | 1.00E-03 | 2 | Cysteine and methionine metabolism; metabolic pathways; ABC transporters; ferroptosis; protein digestion and absorption | |
| D-Galactose | 247,989.5 (167,010.5, 353,676.75) | 151,497 (88,382, 237,218.75) | 2.00E-03 | 1.6 | Galactose Metabolism, Lactose Degradation, Nucleotide Sugars Metabolism | |
| Mannitol | 257,485.5 (177,979, 411,349.25) | 399,367 (266,932.25, 641,879.75) | 3.00E-03 | 1.4 | Fructose and mannose metabolism; ABC transporters; phosphotransferase system (PTS) | |
| D-Ribose | 304,110.5 (148,998.75, 452,514.75) | 199,112 (160,690.25, 289,500.5) | 5.00E-03 | 1.4 | Pentose phosphate pathway | |
| D-Threitol | 45,409.5 (31,440, 66,992.5) | 34,121 (19,136, 47,399.5) | 8.00E-03 | 1.3 | NA | |
| D-Fructose | 104,449.5 (49,230.25, 185,290) | 64,712.5 (30,731.75, 106,221) | 1.70E-02 | 1.2 | Amino sugar metabolism, fructose and mannose degradation, galactose metabolism, starch and sucrose metabolism | |
| L-Arabinose | 442,924 (337,962, 666,296.25) | 350,838.5 (184,538.25, 468,567.25) | 2.90E-02 | 1.2 | Pentose and glucuronate interconversions; ascorbate and aldarate metabolism; amino sugar and nucleotide sugar metabolism; metabolic pathways; ABC transporters | |
| Hormone | Normetanephrine | 5,526 (2,798.5, 10,694.25) | 8,911.5 (3,673.25, 19,318.5) | 1.50E-02 | 1.4 | Tyrosine metabolism |
| Nucleotide | Xanthine | 8,609.5 (5,751.25, 12,169.5) | 15,018 (7,303.5, 26,031.75) | 7.00E-03 | 1.6 | Purine metabolism |
| Uridine | 3,777 (2,104.75, 6,605.5) | 2,230.5 (1,601.25, 4,315.25) | 1.50E-02 | 1.4 | Pyrimidine metabolism | |
| Cytidine | 434.5 (148.5, 720) | 174.5 (84.75, 439.25) | 2.00E-02 | 1.4 | Pyrimidine metabolism | |
| Inosine | 2,835.5 (1,850, 5,864.75) | 4,552.5 (2,281, 14,824.75) | 2.50E-02 | 1.1 | Purine metabolism | |
| Nucleotide metabolism | Inosine/Adenosine | 0.35 (0.19, 0.599) | 0.51 (0.301, 1.445) | 1.30E-02 | 1.1 | Purine metabolism |
| Uracil/Uridine | 2.01 (0.726, 3.555) | 4.38 (1.92, 9.464) | 1.70E-02 | 1.2 | Pyrimidine metabolism | |
| Organic acids | Oxalic acid | 15,214.5 (7,031.5, 29,221.25) | 6,881.5 (4,141.25, 9,998) | 4.63E-04 | 1.4 | Purine metabolism; chloroalkane and chloroalkene degradation; glyoxylate and dicarboxylate metabolism; metabolic pathways; microbial metabolism in diverse environments |
| p-Hydroxyphenylacetic acid | 194,089.5 (116,303, 313,946.25) | 261,616.5 (167,321.75, 786,099.25) | 8.24E-04 | 1.7 | Tyrosine metabolism | |
| L-Asparagine | 148,956 (71,175.5, 246,210.25) | 67,998 (39,736.5, 132,908.75) | 4.00E-03 | 1.9 | Ubiquinone biosynthesis | |
| Phenylpyruvic acid | 6,991 (3,393.5, 19,416.25) | 21,715 (12,861, 39,259.75) | 8.00E-03 | 1.5 | Phenylalanine and tyrosine metabolism | |
| Hydroxyphenyllactic acid | 83,610 (39,609.25, 132,933.5) | 178,418.5 (75,759, 275,474.25) | 2.40E-02 | 1.2 | NA | |
| Hippuric acid | 1331,521 (545,393.5, 2,606,043) | 928,768 (330,140.25, 1,618,823.25) | 2.50E-02 | 1.4 | Phenylalanine metabolism | |
| L-Xylonate | 319,783.5 (226,142.25, 471,741.5) | 192,075.5 (124,227.5, 342,688) | 2.50E-02 | 1.4 | Pentose and glucuronate interconversions; ascorbate and aldarate metabolism | |
| Citramalic acid | 20,538.5 (9,175.25, 43,236.75) | 11,130.5 (6,810.25, 25,437.25) | 3.00E-02 | 1.2 | NA | |
| L-Lactic acid | 430,096.5 (201,968.75, 737,092.5) | 200,346.5 (91,188.75, 407,080) | 4.50E-02 | 1.5 | Gluconeogenesis, pyruvate metabolism | |
| Phenols | 1,2,3-Trihydroxybenzene | 23,996 (6,720, 48,837) | 33,284.5 (8,821.25, 85,409.75) | 3.50E-02 | 1.3 | Aminobenzoate degradation; microbial metabolism in diverse environments; catecholamine transferase inhibitors |
Differential metabolites were selected according to VIP ≥1.5 and P<0.05. Values are expressed as medians (IQRs). P values were calculated from t test for continuous variables and adjusted by FDR method; VIP, variable influence on projection.