Research from the Department of Advanced Biomedical Sciences at Federico II University in Naples indicates that lower levels of plasma LDL cholesterol are associated with a higher risk of developing type 2 diabetes, irrespective of statin use. The findings suggest that the relationship between cholesterol levels and diabetes is more complex than previously understood.
The study, titled “A six-year longitudinal study identifies a statin-independent association between low LDL-cholesterol and risk of type 2 diabetes,” is scheduled for publication in Cardiovascular Diabetology. Researchers explored whether plasma LDL cholesterol levels could predict the onset of type 2 diabetes over an extended follow-up period, specifically examining the influence of statin therapy on this relationship.
Researchers have observed that statin therapy, which lowers LDL cholesterol, tends to increase the incidence of type 2 diabetes in a dose-dependent manner. This has led to questions about the underlying mechanisms. The study introduces genetic evidence linking LDL cholesterol-lowering alleles in genes such as HMGCR and NPC1L1 to an increased risk of diabetes, suggesting a potential connection between lowering LDL cholesterol and diabetes risk.
The analysis involved a cohort of 13,674 adults aged between 19 and 90 years after applying specific inclusion and exclusion criteria. Within this group, slightly more than half were receiving statin therapy at the start of the study. Participants who were on statins had a mean age of 70 years, while nonusers had a mean age of 54 years.
During the median follow-up of 71.6 months, 1,819 participants—approximately 13%—developed incident type 2 diabetes. Notably, the incidence was significantly higher among those on statin therapy, with 1,424 cases (20%) compared to 395 cases (6%) among nonusers.
Higher LDL cholesterol levels correlated with a decreased risk of developing diabetes. Specifically, each 10 mg/dl increase in LDL cholesterol was linked to a 10% reduction in the hazard of diabetes (adjusted hazard ratio of 0.90). The incidence rates of type 2 diabetes across LDL cholesterol quartiles were as follows: 27.6 cases per 1,000 person-years in the low group (LDL < 84 mg/dl), dropping to 8.4 cases per 1,000 person-years in the very high group (LDL ≥ 131 mg/dl). The study also highlighted that statin therapy was associated with increased diabetes risk across all LDL cholesterol levels. In particular, the greatest relative risk increase was observed in individuals starting with very high LDL cholesterol levels, showing an adjusted hazard ratio of 2.41. Overall, the research concludes that while statin use contributes to an increased risk of diabetes across all LDL cholesterol categories, lower LDL cholesterol levels are primarily linked to higher diabetes incidence, largely independent of statin therapy. This presents a paradox where lower LDL values correlate with greater diabetes risk, contrasting with the observation that very high LDL cholesterol levels are associated with a lower risk of developing diabetes. The comprehensive findings of this study underscore the need for further research to unravel the complexities of cholesterol management and diabetes risk. Such insights could lead to improved clinical strategies for managing cardiovascular health without inadvertently increasing diabetes risk. This article is based on research conducted by Maria Lembo and colleagues, supported by a collaborative effort among 140 general practitioners who contributed to a shared electronic medical record system. As the study progresses, it aims to refine the understanding of cholesterol’s role in diabetes development.
