TY - JOUR
T1 - Circulating metabolic biomarkers of renal function in diabetic and non-diabetic populations
AU - Barrios, Clara
AU - Zierer, Jonas
AU - Würtz, Peter
AU - Haller, Toomas
AU - Metspalu, Andres
AU - Gieger, Christian
AU - Thorand, Barbara
AU - Meisinger, Christa
AU - Waldenberger, Melanie
AU - Raitakari, Olli
AU - Lehtimäki, Terho
AU - Otero, Sol
AU - Rodríguez, Eva
AU - Pedro-Botet, Juan
AU - Kähönen, Mika
AU - Ala-Korpela, Mika
AU - Kastenmüller, Gabi
AU - Spector, Tim D
AU - Pascual, Julio
AU - Menni, Cristina
PY - 2018/10/15
Y1 - 2018/10/15
N2 - Using targeted NMR spectroscopy of 227 fasting serum metabolic traits, we searched for novel metabolic signatures of renal function in 926 type 2 diabetics (T2D) and 4838 non-diabetic individuals from four independent cohorts. We furthermore investigated longitudinal changes of metabolic measures and renal function and associations with other T2D microvascular complications. 142 traits correlated with glomerular filtration rate (eGFR) after adjusting for confounders and multiple testing: 59 in diabetics, 109 in non-diabetics with 26 overlapping. The amino acids glycine and phenylalanine and the energy metabolites citrate and glycerol were negatively associated with eGFR in all the cohorts, while alanine, valine and pyruvate depicted opposite association in diabetics (positive) and non-diabetics (negative). Moreover, in all cohorts, the triglyceride content of different lipoprotein subclasses showed a negative association with eGFR, while cholesterol, cholesterol esters (CE), and phospholipids in HDL were associated with better renal function. In contrast, phospholipids and CEs in LDL showed positive associations with eGFR only in T2D, while phospholipid content in HDL was positively associated with eGFR both cross-sectionally and longitudinally only in non-diabetics. In conclusion, we provide a wide list of kidney function-associated metabolic traits and identified novel metabolic differences between diabetic and non-diabetic kidney disease.
AB - Using targeted NMR spectroscopy of 227 fasting serum metabolic traits, we searched for novel metabolic signatures of renal function in 926 type 2 diabetics (T2D) and 4838 non-diabetic individuals from four independent cohorts. We furthermore investigated longitudinal changes of metabolic measures and renal function and associations with other T2D microvascular complications. 142 traits correlated with glomerular filtration rate (eGFR) after adjusting for confounders and multiple testing: 59 in diabetics, 109 in non-diabetics with 26 overlapping. The amino acids glycine and phenylalanine and the energy metabolites citrate and glycerol were negatively associated with eGFR in all the cohorts, while alanine, valine and pyruvate depicted opposite association in diabetics (positive) and non-diabetics (negative). Moreover, in all cohorts, the triglyceride content of different lipoprotein subclasses showed a negative association with eGFR, while cholesterol, cholesterol esters (CE), and phospholipids in HDL were associated with better renal function. In contrast, phospholipids and CEs in LDL showed positive associations with eGFR only in T2D, while phospholipid content in HDL was positively associated with eGFR both cross-sectionally and longitudinally only in non-diabetics. In conclusion, we provide a wide list of kidney function-associated metabolic traits and identified novel metabolic differences between diabetic and non-diabetic kidney disease.
U2 - 10.1038/s41598-018-33507-7
DO - 10.1038/s41598-018-33507-7
M3 - Article (Academic Journal)
C2 - 30323304
SN - 2045-2322
VL - 8
SP - 15249
JO - Scientific Reports
JF - Scientific Reports
IS - 1
ER -
