Research from the Department of Advanced Biomedical Sciences at Federico II University in Naples reveals a concerning link between lower plasma levels of LDL cholesterol and an increased risk of developing type 2 diabetes. This association is significant regardless of whether patients are taking statin medications.
Understanding the relationship between LDL cholesterol and diabetes risk has puzzled researchers for years. Statin therapy, commonly used to lower LDL cholesterol, has been associated with a higher incidence of type 2 diabetes, although the exact mechanisms remain unclear. A recent genetic study has added depth to this understanding, showing that specific genetic variants related to LDL cholesterol reduction are linked to a higher risk of diabetes. In contrast, individuals with familial hypercholesterolemia, a genetic condition characterized by high LDL cholesterol, appear less susceptible to type 2 diabetes.
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 aimed to determine whether plasma LDL cholesterol could predict the onset of type 2 diabetes over an extended period. Data collection involved a cooperative of 140 general practitioners, who contributed to a shared electronic medical record. This system follows over 200,000 adults in Naples, providing comprehensive data on patient visits, diagnoses, and treatment outcomes.
After applying inclusion and exclusion criteria, the study focused on a cohort of 13,674 adults aged between 19 and 90. Of these participants, slightly more than half were on statin therapy at the beginning of the study. Notably, statin users had a mean age of 70 years, while non-users averaged 54 years.
Throughout the median follow-up period of 71.6 months, 1,819 participants—approximately 13%—developed incident type 2 diabetes. The breakdown shows that 1,424 statin-treated participants (20%) were diagnosed compared to 395 non-users (6%).
The research identified a clear trend: for each 10 mg/dl increase in LDL cholesterol, there was a corresponding 10% decrease in the hazard of developing diabetes (adjusted hazard ratio of 0.90). This indicates that lower LDL cholesterol levels are linked to a higher risk of diabetes. The incidence rates of diabetes across different LDL cholesterol quartiles were 27.6, 17.4, 13.5, and 8.4 cases per 1,000 person-years for the low (<84 mg/dl), medium (84–<107 mg/dl), high (107–<131 mg/dl), and very high (≥131 mg/dl) groups, respectively. Additionally, the study found that statin therapy was associated with an increased risk of diabetes across all LDL cholesterol categories. The risk was most pronounced among those starting with very high LDL cholesterol levels, showing an adjusted hazard ratio of 2.41. Researchers concluded that while statin use increases diabetes risk at all levels of LDL cholesterol, the overarching pattern indicates that lower LDL cholesterol levels correlate with a greater risk of developing diabetes, largely independent of statin therapy. Conversely, LDL cholesterol levels at or above 131 mg/dl were associated with the lowest observed risk of diabetes. This research highlights the complex relationship between cholesterol management and diabetes risk, suggesting that clinicians should consider these dynamics when treating patients. The findings contribute to a growing body of evidence on the importance of personalized approaches to cholesterol management and diabetes prevention. For further reading, refer to the study by Maria Lembo et al., published in Cardiovascular Diabetology in 2025.
