Apolipoprotein C3

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Robert J. Konrad - One of the best experts on this subject based on the ideXlab platform.

Karin E. Bornfeldt - One of the best experts on this subject based on the ideXlab platform.

  • Association of Apolipoprotein C3 with insulin resistance and coronary artery calcium in patients with type 1 diabetes
    Journal of clinical lipidology, 2020
    Co-Authors: Teresa Buckner, Baohai Shao, Robert H. Eckel, Jay W. Heinecke, Karin E. Bornfeldt, Janet K. Snell-bergeon
    Abstract:

    Abstract Background Apolipoprotein C3 (APOC3) is a risk factor for incident coronary artery disease in people with type 1 diabetes (T1D). The pathways that link elevated APOC3 levels to an increased risk of incident CVD in people with T1D are not understood. Objective To explore potential mechanisms, we investigated the association of APOC3 with insulin resistance and coronary artery calcium (CAC). Methods In a random sub-cohort of subjects with T1D from Coronary Artery Calcification in Type 1 Diabetes (CACTI) (n=134), serum APOC3, HDL-associated APOC3, and retinol binding protein 4 (RBP4; a potential marker of insulin resistance) were measured by targeted mass spectrometry. We used linear regression to evaluate associations of serum APOC3 and HDL-APOC3 with APOB, non-HDL cholesterol, serum- and HDL-associated RBP4, estimated insulin sensitivity (eIS), and logistic regression to evaluate association with presence of CAC, adjusted for age, sex, and diabetes duration. Results Serum APOC3 correlated positively with APOB and non-HDL cholesterol and was associated with increased odds of CAC (OR: 1.68, p=0.024). eIS was not associated with serum- or HDL-RBP4 but was negatively associated with serum APOC3 in males (s estimate: -0.318, p=0.0040) and decreased odds of CAC (OR: 0.434, p=0.0023). Conclusions Serum APOC3 associates with increased insulin resistance and CAC in T1D.

  • Emerging Targets for Cardiovascular Disease Prevention in Diabetes.
    Trends in molecular medicine, 2020
    Co-Authors: Nathan O. Stitziel, Jenny E. Kanter, Karin E. Bornfeldt
    Abstract:

    Type 1 and type 2 diabetes mellitus (T1DM and T2DM) increase the risk of atherosclerotic cardiovascular disease (CVD), resulting in acute cardiovascular events, such as heart attack and stroke. Recent clinical trials point toward new treatment and prevention strategies for cardiovascular complications of T2DM. New antidiabetic agents show unexpected cardioprotective benefits. Moreover, genetic and reverse translational strategies have revealed potential novel targets for CVD prevention in diabetes, including inhibition of Apolipoprotein C3 (APOC3). Modeling and pharmacology-based approaches to improve insulin action provide additional potential strategies to combat CVD. The development of new strategies for improved diabetes and lipid control fuels hope for future prevention of CVD associated with diabetes.

P. Lecomte - One of the best experts on this subject based on the ideXlab platform.

  • Triglycerides, apo C3 and Lp B:C3 and cardiovascular risk in Type II diabetes
    Diabetologia, 2000
    Co-Authors: N. Gervaise, M. A. Garrigue, G. Lasfargues, P. Lecomte
    Abstract:

    Aims/hypothesis. Cardiovascular complications and particularly coronary heart disease are the main causes of morbidity and mortality in Type II (non-insulin-dependent) diabetes mellitus. Some studies have shown that hypertriglyceridaemia in diabetes is an independent cardiovascular risk factor. In the ECTIM study high Apolipoprotein C3 and lipoprotein B:C3 concentrations (lipoparticles playing a role in triglyceride metabolism) were associated with myocardial infarction in non-diabetic subjects.¶Methods. We studied the relations between macroangiopathy and different cardiovascular risk factors and lipid variables in 188 Type II diabetic subjects.¶Results. Multivariate analysis showed that triglycerides, apo C3 and Lp B:C3, sex, duration of diabetes, microalbuminuria and age were independently associated with macroangiopathy. The study group was divided into quartiles according to apo C3 and Lp B:C3 concentrations: the prevalence of macroangiopathy and coronary heart disease were increased in upper quartiles.¶Conclusion/interpretation. Triglycerides apo C3 and Lp B:C3 were independent cardiovascular risk markers in our group of Type II diabetic patients. [Diabetologia (2000) 43: 703–708]

William E. Alborn - One of the best experts on this subject based on the ideXlab platform.

Per-henrik Groop - One of the best experts on this subject based on the ideXlab platform.

  • Apolipoprotein C3 and Cardiovascular Disease in Patients with Type 1 Diabetes and Diabetic Nephropathy
    Diabetes, 2018
    Co-Authors: Lars Stechemesser, Carol Forsblom, Raimund Weitgasser, Per-henrik Groop
    Abstract:

    Background and Aims: Apolipoprotein C3 (ApoC3) is a key regulator of triglyceride metabolism via its inhibitory effects on lipolysis and hepatic remnant uptake. Emerging evidence indicate that ApoC3 is an independent risk factor for cardiovascular events. The fact that glucose and insulin regulates ApoC3 expression raises the role of ApoC3 and cardiovascular risk in diabetes. We, therefore, investigated ApoC3 and its association with cardiovascular disease (CVD) in patients with and without diabetic nephropathy. Methods: This cross-sectional and prospective analysis was part of the prospective, ongoing Finnish Diabetic Nephropathy (FinnDiane) Study. Between 1994 and 2015 data were obtained from 3926 type 1 diabetes (T1D) patients at more than 80 hospitals or health centers across Finland. ApoC3 levels were explored by groups of albuminuria, CKD stages, presence of CVD as well as prediction of CVD and death. Survival curves were calculated by Cox regression analysis. Results: At baseline, normo-, micro- and macroalbuminuria were present in 71.7%, 13.8% and 14.5% of the population (n=3926, females 48%, age 37.8±12.2 years, diabetes duration 23.2±13 years, HbA1c 8.4±1.5%). CKD stage 3-5 was diagnosed in 14.3%. Coronary heart disease or stroke (CVD) were present in 5.5% at baseline, while 16.3% developed CVD during 15-year follow-up. Compared to normoalbuminuria ApoC3 was elevated in the presence of micro- (p=0.013) or macroalbumiuria (p Conclusions: Baseline ApoC3 levels were elevated in T1D patients with micro- and macroalbuminuria, with impaired renal function, and with CVD. ApoC3 also predicted the development of CVD and death during follow-up. Disclosure L. Stechemesser: None. C. Forsblom: None. R. Weitgasser: None. P. Groop: Other Relationship; Self; AstraZeneca, AbbVie Inc., Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Medscape, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi.