Dyslipidemia in diabetic kidney disease classified by proteinuria and renal dysfunction: A cross-sectional study from a regional diabetes cohort

J Diabetes Investig. 2022 Apr;13(4):657-667. doi: 10.1111/jdi.13697. Epub 2021 Nov 2.

Abstract

Aims/introduction: Diabetic kidney disease (DKD) exacerbates dyslipidemia and increases the incidence of atherosclerotic cardiovascular disease. DKD is a concept that includes typical diabetic nephropathy and an atypical phenotype without proteinuria. We investigated dyslipidemia in different DKD phenotypes that have not been fully studied.

Materials and methods: Fasting plasma was obtained from 1,073 diabetes patients enrolled in the regional diabetes cohort (ViNA cohort). Non-proteinuric and proteinuric DKD were defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 in the absence or presence of urinary albumin-to-creatinine ratio >300 mg/g. Novel lipid risk factors, low-density lipoprotein (LDL) triglyceride (TG) and small dense LDL cholesterol were measured using our established homologous assay.

Results: The proportion of atherosclerotic cardiovascular disease patients was higher in non-proteinuric DKD and even higher in proteinuric DKD than in non-DKD. Increased estimated glomerular filtration rate grade and albuminuric stage were independently correlated with higher TG, TG-rich lipoprotein cholesterol and apolipoprotein CIII. Therefore, proteinuric DKD had the highest of these levels. Small dense LDL cholesterol and LDL-TG were higher in the proteinuria without renal dysfunction group in the lipid-lowering drug-free subset. Lipoprotein(a) was higher in DKD regardless of proteinuria.

Conclusions: Proteinuria was associated with an atherogenic subspecies of LDL, whereas renal dysfunction was associated with increased lipoprotein(a). Proteinuria and renal dysfunction independently exacerbated TG-rich lipoprotein-related dyslipidemia. This is in good agreement with the results of large-scale clinical studies in which proteinuria and renal dysfunction synergistically increased the risk of atherosclerotic cardiovascular disease in populations with diabetes.

Keywords: Diabetic kidney disease; Low-density lipoprotein triglycerides; Small dense low-density lipoprotein cholesterol.

MeSH terms

  • Cardiovascular Diseases* / complications
  • Cholesterol, LDL
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2* / epidemiology
  • Diabetic Nephropathies* / complications
  • Diabetic Nephropathies* / epidemiology
  • Dyslipidemias* / complications
  • Female
  • Humans
  • Lipoprotein(a)
  • Male
  • Proteinuria / complications
  • Proteinuria / epidemiology

Substances

  • Cholesterol, LDL
  • Lipoprotein(a)