HDL cholesterol efflux normalised to apoA-I is associated with future development of type 2 diabetes: from the CORDIOPREV trial
This prospective study evaluated whether baseline cholesterol efflux is associated with future development of type 2 diabetes (T2DM) in cardiovascular patients. We measured cholesterol efflux in all CORDIOPREV study (NCT00924937) participants free of T2DM at baseline (n = 462) and assessed its relationship with T2DM incidence during a 4.5 years of follow-up. Cholesterol efflux was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma. Disposition index was estimated as beta-cell function indicator. During follow-up 106 individuals progressed to T2DM. The cholesterol efflux/apoA-1 ratio was inversely associated with T2DM development independently of traditional risk factors (model-1, OR: 0.647, 95%CI: 0.495-0.846), and after additional adjustment for glycaemic parameters (model-2, OR: 0.670, 95%CI: 0.511-0.878). When cumulative incidence of diabetes was analysed by quartiles of cholesterol efflux/apoA-I, incidence of T2DM was reduced by 54% in subjects who were in the higher cholesterol efflux/apoA-I quartile compared to subjects in the lowest quartile (p = 0.018 and p = 0.042 for model-1 and 2). Moreover, participants who were in the higher cholesterol efflux/apoA-I presented significantly higher disposition index (β = 0.056, SE = 0.026; p = 0.035). In conclusion, HDL-cholesterol efflux normalised to apoA-I was inversely associated with T2DM development in cardiovascular patients. This association was independent of several T2DM risk factors, and may be related to a preserved beta-cell function. ; The authors would like to thank Veronica de Dios and Lorena Crespo of the Department of BiochemistryResearch, Hospital Universitario Ramon y Cajal, Instituto Ramon y Cajal de Investigacion Sanitaria (IRYCIS), for technical assistance. The authors also thank the volunteers who participated in the study. The present study was supported by the Ministerio de Economia y Competitividad, Spain (AGL2012/39615 and AGL2015-67896-P to J.L.-M.) and by the Ministerio de Ciencia e Innovacion, Spain (PI11/2077 to D.G.-C., PIE14/00005 to J.L.-M., PI13/00023 to J.D.-L. and PIE 14/00031 to CIBEROBN). It was also partly supported by a research grant from the European Commission (NUTRITECH European Integrated Project-289511). The CORDIOPREV study is supported by the Fundacion Patrimonio Comunal Olivarero. We also received additional funding from CITOLIVA, CEAS, Junta de Andalucia (Consejeria de Salud, Consejeria de Agricultura y Pesca, Consejeria de Innovacion, Ciencia y Empresa), Diputaciones de Jaen y Cordoba, Centro de Excelencia en Investigacion sobre Aceite de Oliva y Salud and Ministerio de Medio Ambiente, Medio Rural y Marino and the Spanish Government. The study was also co-financed by the Fondo Europeo de Desarrollo Regional (FEDER). The CIBEROBN is an initiative of the Instituto de Salud Carlos III, Madrid, Spain. The U.S. Department of Agriculture-Agricultural Research Service (ARS), under Agreement No. 58-1950-4-003 to J.M.O. The CNIC is supported by Ministerio de Economia y Competitividad, Spain, and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (Ministerio de Economia y Competitividad award SEV-2015-0505). R.B.-R. is supported by an ISCIII postdoctoral research contract (Sara Borrell). ; Sí