Research from the Department of Advanced Biomedical Sciences at Federico II University in Naples reveals a concerning link between lower plasma low-density lipoprotein (LDL) cholesterol levels and a higher risk of developing type 2 diabetes. This association appears to be independent of statin use, challenging existing perceptions regarding cholesterol management and diabetes risk.
The study, titled “A six-year longitudinal study identifies a statin-independent association between low LDL-cholesterol and risk of type 2 diabetes,” was published in Cardiovascular Diabetology. It highlights that while statin therapy is known to increase the incidence of new type 2 diabetes cases, the underlying mechanisms remain unclear. Genetic research has suggested that certain alleles related to LDL cholesterol-lowering pathways may also contribute to diabetes risk.
Genetic insights further complicate the narrative. For instance, individuals with familial hypercholesterolemia, characterized by elevated LDL cholesterol and a heightened risk of coronary artery disease, tend to have a lower incidence of type 2 diabetes. This paradox indicates that while lower LDL cholesterol is often seen as beneficial, it may also correlate with an increased diabetes risk when viewed through a genetic lens.
Over the course of the study, data was collected from a cooperative of 140 general practitioners who utilized a shared electronic medical record system. This comprehensive database included information from over 200,000 adults, reflecting the demographics of Naples. After applying specific inclusion and exclusion criteria, the study focused on a cohort of 13,674 adults aged between 19 and 90. Among these participants, slightly more than half were receiving statin therapy at the outset.
During a median follow-up period of 71.6 months, the study found that 1,819 participants, or 13%, developed type 2 diabetes. Of these, 1,424 were statin-treated, representing 20% of those on statins, compared to 395, or 6%, among nonusers. These figures underscore a notable correlation between statin use and diabetes risk across various LDL cholesterol categories.
The findings revealed that for each 10 mg/dl increase in LDL cholesterol, there was a corresponding 10% reduction in the hazard of developing diabetes (adjusted hazard ratio of 0.90). Incidence rates of diabetes varied significantly across different LDL cholesterol quartiles, with rates of 27.6, 17.4, 13.5, and 8.4 cases per 1,000 person-years observed in the low, medium, high, and very high LDL groups, respectively.
Statin therapy consistently correlated with increased diabetes risk across all LDL cholesterol categories. The most pronounced relative risk increase occurred among participants starting with very high LDL cholesterol levels, with an adjusted hazard ratio of 2.41. Overall, the research indicates that while statin use contributes to an increased risk of diabetes, lower LDL cholesterol values are also associated with a higher incidence of the disease.
The study’s authors, including Maria Lembo, conclude that the relationship between LDL cholesterol and type 2 diabetes is complex, with lower LDL cholesterol levels linked to a greater risk of diabetes, largely independent of statin therapy. Conversely, higher LDL cholesterol levels, particularly those at or above 131 mg/dl, were associated with the lowest observed risk of developing diabetes.
These findings have significant implications for clinical practice and public health, highlighting the need for a nuanced understanding of cholesterol management and its potential impact on diabetes risk. The research may prompt healthcare professionals to reevaluate treatment strategies, ensuring they consider both cholesterol levels and diabetes risk in patient care.
This article was authored by Justin Jackson, with editing by Gaby Clark and fact-checking by Robert Egan.
