Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors.
The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling.
- Strawbridge RJ, Silveira A, Hoed MD, Gustafsson S, Luan J, Rybin D, Dupuis J, Li-Gao R, Kavousi M, Dehghan A, Haljas K, Lahti J, Gådin JR, Bäcklund A, de Faire U, Gertow K, Giral P, Goel A, Humphries SE, Kurl S, Langenberg C, Lannfelt LL, Lind L, Lindgren CCM, Mannarino E, Mook-Kanamori DO, Morris AP, de Mutsert R, Rauramaa R, Saliba-Gustafsson P, Sennblad B, Smit AJ, Syvänen AC, Tremoli E, Veglia F, Zethelius B, Björck HM, Eriksson JG, Hofman A, Franco OH, Watkins H, Jukema JW, Florez JC, Wareham NJ, Meigs JB, Ingelsson E, Baldassarre D, Hamsten A; IMPROVE study group. Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation. Atherosclerosis 2017 Sep 28;266:196-204. Go to PubMed