Metabolic Diversity of Progressive Kidney Disease in 325 Patients with Type 1 Diabetes (the FinnDiane Study)

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.