TY - JOUR
T1 - Metabolic diversity of progressive kidney disease in 325 patients with type 1 diabetes (the FinnDiane Study)
AU - Mäkinen, Ville Petteri
AU - Tynkkynen, Tuulia
AU - Soininen, Pasi
AU - Peltola, Tomi
AU - Kangas, Antti J.
AU - Forsblom, Carol
AU - Thorn, Lena M.
AU - Kaski, Kimmo
AU - Laatikainen, Reino
AU - Ala-Korpela, Mika
AU - Groop, Per Henrik
PY - 2012/3/2
Y1 - 2012/3/2
N2 - Type 1 diabetic patients with varying severity of kidney disease were investigated to create multimetabolite models of the disease process. Urinary albumin excretion rate was measured for 3358 patients with type 1 diabetes. Prospective records were available for 1051 patients, of whom 163 showed progression of albuminuria (8.3-year follow-up), and 162 were selected as stable controls. At baseline, serum lipids, lipoprotein subclasses, and low-molecular weight metabolites were quantified by NMR spectroscopy (325 samples). The data were analyzed by the self-organizing map. In cross-sectional analyses, patients with no complications had low serum lipids, less inflammation, and better glycemic control, whereas patients with advanced kidney disease had high serum cystatin-C and sphingomyelin. These phenotype extremes shared low unsaturated fatty acids (UFAs) and phospholipids. Prospectively, progressive albuminuria was associated with high UFAs, phospholipids, and IDL and LDL lipids. Progression at longer duration was associated with high HDL lipids, whereas earlier progression was associated with poor glycemic control, increased saturated fatty acids (SFAs), and inflammation. Diabetic kidney disease consists of diverse metabolic phenotypes: UFAs, phospholipids, IDL, and LDL may be important in the subclinical phase, high SFAs and low HDL suggest accelerated progression, and the sphingolipid pathway in advanced kidney injury deserves further research.
AB - Type 1 diabetic patients with varying severity of kidney disease were investigated to create multimetabolite models of the disease process. Urinary albumin excretion rate was measured for 3358 patients with type 1 diabetes. Prospective records were available for 1051 patients, of whom 163 showed progression of albuminuria (8.3-year follow-up), and 162 were selected as stable controls. At baseline, serum lipids, lipoprotein subclasses, and low-molecular weight metabolites were quantified by NMR spectroscopy (325 samples). The data were analyzed by the self-organizing map. In cross-sectional analyses, patients with no complications had low serum lipids, less inflammation, and better glycemic control, whereas patients with advanced kidney disease had high serum cystatin-C and sphingomyelin. These phenotype extremes shared low unsaturated fatty acids (UFAs) and phospholipids. Prospectively, progressive albuminuria was associated with high UFAs, phospholipids, and IDL and LDL lipids. Progression at longer duration was associated with high HDL lipids, whereas earlier progression was associated with poor glycemic control, increased saturated fatty acids (SFAs), and inflammation. Diabetic kidney disease consists of diverse metabolic phenotypes: UFAs, phospholipids, IDL, and LDL may be important in the subclinical phase, high SFAs and low HDL suggest accelerated progression, and the sphingolipid pathway in advanced kidney injury deserves further research.
KW - NMR metabonomics
KW - fatty acids
KW - nephropathy
KW - phospholipids
KW - sphingomyelin
UR - http://www.scopus.com/inward/record.url?scp=84857883247&partnerID=8YFLogxK
U2 - 10.1021/pr201036j
DO - 10.1021/pr201036j
M3 - Article
C2 - 22204613
AN - SCOPUS:84857883247
VL - 11
SP - 1782
EP - 1790
JO - Journal of Proteome Research
JF - Journal of Proteome Research
SN - 1535-3893
IS - 3
ER -