Table 2. Differential serum metabolites betweenT2DM with and without nephropathy.
| Class | Name | DN | T2DM | T test. P | VIP | Pathway |
|---|---|---|---|---|---|---|
| Alcohols | Glycerol | 598,034.5 (388,745.25, 1,166,327) | 387,146 (312,706.75, 526,477) | 8.09E-04 | 1.4 | Galactose metabolism, glycerolipid metabolism |
| Myoinositol | 438,968.5 (215,182.25, 1,198,811.75) | 170,756.5 (114,897.5, 289,559.5) | 6.18E-05 | 1.4 | Galactose metabolism, inositol metabolism, inositol phosphate metabolism, phosphatidylinositol phosphate metabolism | |
| Amino Acid | 1-Methylhistidine | 15,612 (7,125.5, 39,741) | 8,910.5 (6,143, 12,853.75) | 1.21E-04 | 1.3 | Histidine metabolism |
| 5-Hydroxylysine | 2,092.5 (1,624.5, 4,172.25) | 1,141.5 (727, 1,643.75) | 3.11E-04 | 1.6 | Lysine degradation; metabolic pathways | |
| Alpha-ketoisovaleric acid | 3,640 (1,992.5, 6,487) | 2,190.5 (1,425.25, 3,217.5) | 1.00E-03 | 1.4 | Valine, leucine and isoleucine degradation | |
| Beta-Alanine | 10,038 (8,363.25, 15,552.5) | 7,151.5 (6,114, 8,661) | 1.50E-04 | 1.4 | Aspartate metabolism, beta-alanine metabolism, propanoate metabolism, pyrimidine metabolism | |
| Creatinine | 338,468 (224,928.75, 1,273,947.25) | 254,810.5 (179,753.5, 344,497.5) | 6.36E-04 | 1.2 | Arginine and proline metabolism; metabolic pathways | |
| L-Cysteine | 60,307.5 (43,832, 82,471.5) | 44,044 (34,087.25, 56,694.75) | 5.15E-04 | 1.4 | Cysteine metabolism, glutathione metabolism, glycine and serine metabolism, methionine metabolism, pantothenate and CoA biosynthesis, taurine and hypotaurine metabolism, transcription/translation | |
| L-Cystine | 175,895 (120,707.75, 238,916) | 117,730.5 (87,831.5, 169,729.25) | 2.00E-03 | 1.3 | Cysteine and methionine metabolism; metabolic pathways; ABC transporters; ferroptosis; protein digestion and absorption | |
| L-Glutamic acid | 279,299.5 (167,237.25, 397,382) | 426,439.5 (312,734.5, 578,261) | 2.28E-06 | 1.5 | 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 | |
| L-Glutamine | 2,323,035 (1,899,199, 2,747,632.5) | 2,845,450 (2,567,941.25, 3,055,334.25) | 2.28E-06 | 1.8 | Amino sugar metabolism, ammonia recycling, glutamate metabolism, phenylacetate metabolism, purine metabolism, pyrimidine metabolism, transcription/translation, urea cycle | |
| L-Isoleucine | 321,465 (283,167.75, 441,564.5) | 271,347.5 (220,161.75, 359,676) | 4.00E-03 | 1.2 | Transcription/Translation, Valine, Leucine and Isoleucine Degradation | |
| L-Lysine | 640,215 (549,289.25, 689,639.5) | 515,362.5 (424,460.5, 599,079.5) | 7.57E-04 | 1.5 | Biotin metabolism, carnitine synthesis, lysine degradation, transcription/translation | |
| L-Phenylalanine | 433,113 (323,081.25, 575,814) | 620,982.5 (530,573.75, 707,172.25) | 3.02E-06 | 1.6 | Phenylalanine and tyrosine metabolism, transcription/translation | |
| L-Proline | 961,090.5 (58,2251.5, 1,158,145) | 516,571 (459,014.75, 757,644.75) | 8.32E-04 | 1.2 | Arginine and proline metabolism, transcription/translation | |
| L-Threonine | 280,966 (212,282.5, 433,769.75) | 248,005.5 (192,284.5, 298,326) | 5.00E-03 | 1.2 | Glycine and serine metabolism, threonine and 2-oxobutanoate degradation, transcription/translation | |
| N-Acetyl-L-aspartic acid | 27,759 (10,844, 179,723.5) | 29,926.5 (15,873.25, 46,000.5) | 3.00E-03 | 1.1 | Aspartate metabolism | |
| Pyroglutamic acid | 1,992,442.5 (1415175, 2640418.75) | 1,439,163 (1,185,021.5, 1,782,831.75) | 3.00E-03 | 1.1 | Glutathione metabolism | |
| Alpha-ketoisovaleric acid/L-Valine | 0.01 (0.003, 0.01) | 0 (0.002, 0.005) | 4.08E-04 | 1.3 | Valine, leucine and isoleucine degradation; pantothenate and CoA biosynthesis | |
| Beta-Alanine/L-Aspartic acid | 0.09 (0.061, 0.144) | 0.05 (0.037, 0.076) | 4.86E-05 | 1.5 | Pantothenate and CoA biosynthesis; beta-Alanine metabolism | |
| L-Glutamic acid/Oxoglutaric acid | 25.75 (20.325, 42.947) | 69.01 (40.097, 153.817) | 4.25E-04 | 1.4 | Arginine biosynthesis | |
| L-Glutamic acid/Pyroglutamic acid | 0.14 (0.092, 0.174) | 0.3 (0.222, 0.384) | 3.38E-12 | 2.1 | Glutathione metabolism | |
| L-Tyrosine/L-Phenylalanine | 1.87 (1.318, 2.323) | 1.21 (0.861, 1.49) | 1.00E-03 | 1.5 | Phenylalanine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis | |
| Sarcosine/Dimethylglycine | 0.03 (0.018, 0.036) | 0.02 (0.017, 0.026) | 9.00E-03 | 1.4 | Glycine, serine and threonine metabolism | |
| Sarcosine | 9,147 (8,219.75, 10,872.75) | 8,519.5 (7,869.5, 8,961.25) | 2.30E-02 | 1.3 | Glycine and serine metabolism | |
| Carbohydrates | D-Glucuronic acid | 90,337.5 (16,006.25, 165,173.25) | 23,810.5 (12,463, 53,869.25) | 7.63E-04 | 1.1 | Inositol metabolism, starch and sucrose metabolism |
| D-Maltose | 29,752 (11,850.25, 74833) | 16,010.5 (10,526.75, 24,970.5) | 4.20E-04 | 1.1 | Starch and sucrose metabolism | |
| D-Mannose | 1,056,861 (494,489.5, 1326627.5) | 1,442,658.5 (905,777.75, 2,018,569.5) | 3.36E-04 | 1.3 | Fructose and mannose degradation, galactose metabolism | |
| D-Threitol | 13,649.5 (8,991, 51,131.5) | 5,438.5 (3,241.5, 7,278.5) | 3.04E-05 | 1.5 | NA | |
| Erythritol | 66,013 (49,723, 173,745.75) | 32,681 (25,459.25, 42,582.5) | 3.46E-05 | 1.4 | NA | |
| Erythrose | 535,478.5 (354,430.5, 92,3590) | 249,182.5 (52,987, 324,922.75) | 9.57E-09 | 1.8 | NA | |
| Fructose 6-phosphate | 516,665.5 (371,837.5, 627,208) | 934,897 (717,232, 1,136,517.25) | 2.50E-10 | 2 | Amino sugar metabolism, fructose and mannose degradation, gluconeogenesis, glycolysis, pentose phosphate pathway | |
| Galactonic acid | 44,632 (17,963, 138,125.5) | 15,075 (11,043, 31,052) | 2.29E-05 | 1.4 | Galactose metabolism; metabolic pathways; microbial metabolism in diverse environments | |
| Isomaltose | 8,272.5 (2,733.75, 19,707.75) | 4,314 (2,844, 6,996.25) | 5.60E-04 | 1.1 | NA | |
| L-Arabitol | 110,028 (65,100.75, 240,871) | 55,786 (43,840.25, 67,209) | 3.28E-07 | 1.7 | Pentose and glucuronate interconversions; metabolic pathways | |
| L-Sorbose | 214,365.5 (172,933, 306,600.5) | 370,879 (293,727, 451,143.5) | 6.97E-06 | 1.7 | NA | |
| Mannitol | 429,528.5 (98,217.25, 1,399,185.25) | 116,745 (50,414.5, 306,783.75) | 1.54E-04 | 1.3 | Fructose and mannose metabolism; ABC transporters; phosphotransferase system (PTS) | |
| L-Arabinose/L-Arabitol | 0.22 (0.143, 0.436) | 0.46 (0.393, 0.6) | 1.56E-05 | 1.5 | Pentose and glucuronate interconversions | |
| L-Glutamine/L-Glutamic acid | 9.28 (6.079, 14.034) | 6.66 (4.532, 8.929) | 1.00E-03 | 1.1 | Glyoxylate and dicarboxylate metabolism; alanine, aspartate and glutamate metabolism | |
| Ribonolactone | 27,147.5 (15,144, 7,7587.5) | 8,821.5 (4,725.5, 14,265.25) | 1.81E-05 | 1.4 | NA | |
| Threonic acid | 51,359.5 (34,386, 201,621.75) | 45,318.5 (30,874.25, 56,184) | 1.00E-03 | 1.2 | NA | |
| Esters | Glycerol 1-octadecanoate | 3,563.5 (26,68.5, 4,804.75) | 10,494.5 (8,536, 12,954) | 2.45E-14 | 2.3 | NA |
| Fatty Acids | Linoleic acid | 162,340.5 (109,351.5, 223,310) | 131,850 (91,854.25, 183,544.5) | 3.60E-02 | 1.2 | Alpha linolenic acid and linoleic acid metabolism |
| Tetracosanoic acid | 6,202.5 (5,134.75, 8,127.75) | 5,272 (4,122, 6,202) | 1.00E-03 | 1.2 | Beta oxidation of very long chain fatty acids | |
| Hormone | Normetanephrine | 3,813.5 (2,690.25, 5,572.75) | 2,953 (2,047.5, 3,518.5) | 5.00E-03 | 1.4 | Tyrosine metabolism |
| Lipids | MG160 | 3,829 (2,292.75, 5,679.5) | 9,908 (7,105.75, 14,048) | 8.20E-06 | 1.3 | NA |
| O-Phosphoethanolamine | 24,043 (19,236, 30,112) | 14,389.5 (10,347.75, 21,184) | 2.29E-05 | 1.5 | Sphingolipid metabolism | |
| Glycerol 3-phosphate/Glycerol | 0.06 (0.019, 0.122) | 0.13 (0.089, 0.153) | 5.41E-04 | 1.2 | Glycerolipid metabolism | |
| Nucleotide | Cytidine | 761.5 (400.75, 2396.25) | 498 (398, 615.5) | 5.05E-04 | 1.2 | Pyrimidine metabolism |
| Hypoxanthine | 44,123.5 (28,191, 77,664.75) | 29,734.5 (22,674.75, 39,268.75) | 3.00E-03 | 1.2 | Purine metabolism | |
| Organic Acids | Benzoic acid | 24,087 (19,048.5, 29,166.5) | 14,903 (13,031.25, 17,855.5) | 3.16E-09 | 2 | NA |
| Fumaric acid | 8,265 (6,316, 10,364.25) | 4,577.5 (3,857.5, 5,716) | 1.05E-06 | 2 | Arginine and proline metabolism, aspartate metabolism, citric acid cycle, mitochondrial electron transport chain, phenylalanine and tyrosine metabolism, tyrosine metabolism, urea cycle | |
| Glyceric acid | 47,358 (37,608.75, 59,286.25) | 35,250 (29,520.75, 44,127.5) | 6.86E-04 | 1.5 | Glycerolipid metabolism, glycine and serine metabolism | |
| L-Lactic acid | 1,806,745 (1,201,846, 2,235,344.25) | 3,155,801 (1,616,732, 4,879,156.25) | 1.15E-04 | 1.3 | Gluconeogenesis, pyruvate metabolism | |
| Maleic acid | 13,293.5 (11,825, 16,123) | 11,344 (10,363.5, 13,526) | 3.00E-03 | 1.4 | NA | |
| Petroselinic acid | 513,132 (322,569.25, 801,835.25) | 416,994 (267,109.5, 580,415.25) | 9.00E-03 | 1.3 | NA | |
| Taurine | 177245.5 (93433.75, 227747.5) | 309,364.5 (206,290.25, 385,725.5) | 2.35E-09 | 1.9 | Bile acid biosynthesis, taurine and hypotaurine metabolism | |
| Uric acid | 292,716.5 (207,345, 341,138.5) | 188,751.5 (146,691.25, 270,719.75) | 4.00E-03 | 1.3 | Purine metabolism | |
| Vanillylmandelic acid | 530 (327.75, 2513.5) | 318 (220.25, 445.75) | 5.37E-04 | 1.2 | Tyrosine metabolism | |
| Phenols | 5-Hydroxydopamine | 6,983.5 (4,712.75, 9,486) | 5,617.5 (3,889, 7,842.5) | 4.20E-02 | 1.1 | NA |
| m-Cresol | 30,252 (8,040.5, 101,712.75) | 13,858 (5,703.75, 26,689.25) | 2.00E-03 | 1.2 | Toluene degradation; microbial metabolism in diverse environments; degradation of aromatic compounds |
Differential metabolites were selected according to VIP >1 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.