Researchers at the Department of Advanced Biomedical Sciences at Federico II University in Naples have revealed a concerning link between lower levels of low-density lipoprotein (LDL) cholesterol and an increased risk of developing type 2 diabetes. This study suggests that the relationship exists independently of statin use, a common treatment for lowering cholesterol levels.
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 the journal Cardiovascular Diabetology. It highlights that while statin therapy is known to raise the incidence of new type 2 diabetes diagnoses, the exact reasons for this association have remained unclear.
Genetic research has added complexity to this relationship. Variants in genes such as HMGCR and NPC1L1, which are involved in cholesterol metabolism, have been linked to a higher risk of diabetes. This suggests that lowering LDL cholesterol through various biological pathways may correlate with diabetes risk. Conversely, individuals with familial hypercholesterolemia, a genetic disorder characterized by high LDL cholesterol, show a lower incidence of type 2 diabetes, indicating that the relationship between cholesterol and diabetes is multifaceted.
The research utilized data from a network of 140 general practitioners, which tracked more than 200,000 adults in Naples. After applying inclusion and exclusion criteria, the study analyzed a cohort of 13,674 adults aged between 19 and 90 years. Notably, over half of the participants were undergoing statin therapy at baseline.
During the median follow-up period of 71.6 months, a total of 1,819 participants, or 13%, developed incident type 2 diabetes. Among those treated with statins, 1,424 participants (20%) were diagnosed, compared to 395 participants (6%) who were not on statin therapy.
The findings revealed observable correlations between LDL cholesterol levels and diabetes risk. For every 10 mg/dl increase in LDL cholesterol, there was a corresponding 10% reduction in the hazard of developing diabetes, with an adjusted hazard ratio of 0.90. Incidence rates of type 2 diabetes varied significantly across LDL cholesterol quartiles: 27.6 cases per 1,000 person-years in the low (<84 mg/dl) group, 17.4 in the medium (84–<107 mg/dl), 13.5 in the high (107–<131 mg/dl), and 8.4 in the very high (≥131 mg/dl) group. Statin therapy was associated with an increased diabetes risk in every LDL cholesterol category. The relative risk was greatest among individuals starting with very high LDL cholesterol levels, showing an adjusted hazard ratio of 2.41. The researchers concluded that while statin use increases diabetes risk across all categories of LDL cholesterol, the overarching trend remains that lower LDL values correlate with a higher incidence of diabetes. The study emphasizes the importance of monitoring LDL cholesterol levels in clinical practice and raises questions about the implications for patient care. With lower LDL cholesterol values linked to a greater risk of diabetes, healthcare providers may need to reevaluate approaches to cholesterol management and diabetes prevention strategies. This research was conducted by Maria Lembo and her team, with findings verified by Robert Egan. To support independent scientific journalism, readers are encouraged to consider donations for continued reporting on health and medical research. More information on the study can be found in the publication in Cardiovascular Diabetology.
