Apolipoprotein C3 and Cardiovascular Disease in Patients with Type 1 Diabetes and Diabetic Nephropathy

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<0.001). Increasing ApoC3 levels were observed alongside progression of CKD stage (p<0.001). Notably, higher baseline ApoC3 correlated with presence of CVD at baseline, development of CVD during follow-up and death. Differences in survival of those with the highest quartile of ApoC3 were independent of eGFR, triglycerides or HbA1c. 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.