Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2022 Mar;291(3):338-349.
doi: 10.1111/joim.13412. Epub 2021 Nov 24.

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

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 Taskinen  7 , Per-Henrik Groop  1   2   3   8 ; FinnDiane Study Group  1
Affiliations
Observational Study

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

Fanny Jansson Sigfrids et al. J Intern Med. 2022 Mar.

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, HbA1c , 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.

PubMed Disclaimer

Conflict of interest statement

P‐HG has received lecture fees from Astellas, Astra Zeneca, Boehringer‐Ingelheim, Eli Lilly, Elo Water, Genzyme, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, Sanofi, and Sciarc. He is an advisory board member for AbbVie, Astellas, Astra Zeneca, Bayer, Boehringer‐Ingelheim, Eli Lilly, Janssen, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, and Sanofi. None of these entities participated in the design or interpretation of the study.

Figures

Fig. 1
Fig. 1
Forest plot illustrating sex‐ and diabetes duration–adjusted hazard ratios with 95% confidence intervals for apolipoprotein C‐III regarding separate components of the primary endpoints of interest; DKD, diabetic kidney disease; micro, microalbuminuria; macro, macroalbuminuria; MACE, major adverse cardiac event; AMI, acute myocardial infarction.
Fig. 2
Fig. 2
Kaplan–Meier curves stratified by quartiles of apolipoprotein C‐III (apoC‐III) concentration with respect to (a) the cumulative major adverse cardiac event (MACE) rate and (b) mortality; black solid line, quartile 1; red solid line, quartile 2; black dashed line, quartile 3; red dashed line, quartile 4. The two latter figures illustrate the relationship between apoC‐III and (c) the MACE/(d) mortality allowing for nonlinearity. In these models, apoC‐III was included as a restricted cubic spline using three knots. Reference hazard ratio = 1 was set to the median of apoC‐III in the studied populations. The analyses in (c) and (d) are adjusted for sex, diabetes duration, and the category of diabetic kidney disease at baseline.
See this image and copyright information in PMC

References

    1. Harjutsalo V, Forsblom C, Groop P‐H. Time trends in mortality in patients with type 1 diabetes: nationwide population based cohort study. BMJ. 2011;343:d5364. - PMC - PubMed
    1. Groop P‐H, Thomas MC, Moran JL, Wadén J, Thorn LM, Mäkinen V‐P, et al. The presence and severity of chronic kidney disease predicts all‐cause mortality in type 1 diabetes. Diabetes. 2009;58:1651–8. - PMC - PubMed
    1. Tolonen N, Forsblom C, Thorn L, Wadén J, Rosengård‐Bärlund M, Saraheimo M, et al. Lipid abnormalities predict progression of renal disease in patients with type 1 diabetes. Diabetologia. 2009;52:2522–30. - PubMed
    1. Mattock MB, Cronin N, Cavallo‐Perin P, Idzior‐Walus B, Penno G, Bandinelli S, et al. Plasma lipids and urinary albumin excretion rate in type 1 diabetes mellitus: the EURODIAB IDDM Complications Study. Diabet Med. 2001;18:59–67. - PubMed
    1. Tolonen N, Forsblom C, Mäkinen V‐P, Harjutsalo V, Gordin D, Feodoroff M, et al. Different lipid variables predict incident coronary artery disease in patients with type 1 diabetes with or without diabetic nephropathy: the FinnDiane study. Diabetes Care. 2014;37:2374–82. - PubMed

Publication types

Substances

LinkOut - more resources