Abstract
It is an unexpected but pleasant surprise when new clinical relationships are identified, and one of the most interesting is the inverse association between LDL cholesterol (LDLc) and type 2 diabetes (T2D) risk. Evidence from both randomized clinical trials and genetic studies indicates that regulation of plasma lipids and glycemic control is more closely linked than previously assumed, yet in a counterintuitive, one could even say paradoxical, manner. Meta-analyses of randomized clinical trials have found that drugs designed to reduce LDLc, in addition to their hypolipidemic and cardioprotective effects, appear to also modestly increase T2D risk (1,2). Furthermore, naturally occurring genetic variation in molecular targets of LDLc-lowering therapy, such as genetic variants in or near HMGCR , NCP1L1 , and PCSK9 genes, have been found to be associated with impaired insulin sensitivity and new-onset T2D, particularly among people with impaired fasting glucose levels (3–6). Further supporting that this is a fundamental biologic relationship, individuals with familial hypercholesterolemia, a dominantly inherited disease characterized by high plasma levels of LDLc due to genetic mutations in LDLR or APOB genes, appear to have a lower prevalence of diabetes than unaffected relatives (7). However, not all genetic variants that raise LDLc have similar effects on glycemic control (8). This suggests that the mechanism by which LDLc is reduced might have relevant implications for glycemic deterioration and reveal potential important mechanisms for diabetogenesis in general. As reported in this issue of Diabetes , Klimentidis et al. (9) conducted a study to examine the phenotypic and genotypic relationships between LDLc …
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.