Apolipoprotein C-III predicts cardiovascular events and mortality in individuals with type 1 diabetes and albuminuria

Fanny Jansson Sigfrids; Lars Stechemesser; Emma H Dahlström; Carol M Forsblom; Valma Harjutsalo; Raimund Weitgasser; Marja-Riitta Taskinen; Per-Henrik Groop; FinnDiane Study Group

doi:10.1111/joim.13412

Apolipoprotein C-III predicts cardiovascular events and mortality in individuals with type 1 diabetes and albuminuria

J Intern Med. 2022 Mar;291(3):338-349. doi: 10.1111/joim.13412. Epub 2021 Nov 24.

Authors

Fanny Jansson Sigfrids^{1

2

3}, Lars Stechemesser^{1

4}, Emma H Dahlström^{1

2

3}, Carol M Forsblom^{1

2

3}, Valma Harjutsalo^{1

2

3

5}, Raimund Weitgasser^{4

6}, Marja-Riitta Taskinen⁷, Per-Henrik Groop^{1

2

3

8}; FinnDiane Study Group¹

Affiliations

¹ Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
² Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
³ Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁴ First Department of Medicine, Paracelsus Medical University, Salzburg, Austria.
⁵ National Institute for Health and Welfare, Helsinki, Finland.
⁶ Department of Medicine, Diabetology, Wehrle-Diakonissen Hospital, Salzburg, Austria.
⁷ Heart and Lung Centre, University of Helsinki, Helsinki, Finland.
⁸ Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.

Abstract

Objectives: We studied apolipoprotein C-III (apoC-III) in relation to diabetic kidney disease (DKD), cardiovascular outcomes, and mortality in type 1 diabetes.

Methods: The cohort comprised 3966 participants from the prospective observational Finnish Diabetic Nephropathy Study. Progression of DKD was determined from medical records. A major adverse cardiac event (MACE) was defined as acute myocardial infarction, coronary revascularization, stroke, or cardiovascular mortality through 2017. Cardiovascular and mortality data were retrieved from national registries.

Results: ApoC-III predicted DKD progression independent of sex, diabetes duration, blood pressure, HbA_1c , smoking, LDL-cholesterol, lipid-lowering medication, DKD category, and remnant cholesterol (hazard ratio [HR] 1.43 [95% confidence interval 1.05-1.94], p = 0.02). ApoC-III also predicted the MACE in a multivariable regression analysis; however, it was not independent of remnant cholesterol (HR 1.05 [0.81-1.36, p = 0.71] with remnant cholesterol; 1.30 [1.03-1.64, p = 0.03] without). DKD-specific analyses revealed that the association was driven by individuals with albuminuria, as no link between apoC-III and the outcome was observed in the normal albumin excretion or kidney failure categories. The same was observed for mortality: Individuals with albuminuria had an adjusted HR of 1.49 (1.03-2.16, p = 0.03) for premature death, while no association was found in the other groups. The highest apoC-III quartile displayed a markedly higher risk of MACE and death than the lower quartiles; however, this nonlinear relationship flattened after adjustment.

Conclusions: The impact of apoC-III on MACE risk and mortality is restricted to those with albuminuria among individuals with type 1 diabetes. This study also revealed that apoC-III predicts DKD progression, independent of the initial DKD category.

Keywords: apolipoprotein C-III; cardiovascular disease; diabetes mellitus; diabetic nephropathy; dyslipidemia; mortality; type 1.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Albuminuria
Apolipoprotein C-III*
Cardiovascular Diseases*
Diabetes Mellitus, Type 1* / complications
Diabetic Nephropathies*
Finland
Humans

Substances

Apolipoprotein C-III