TOPLINE:
Lower baseline low-density lipoprotein cholesterol (LDL-C) levels were associated with a higher risk of developing type 2 diabetes (T2D) in individuals without a prior history of T2D and cardiovascular disease, and this association was largely independent of statin use.
METHODOLOGY:
- Researchers conducted a population-based study to assess whether baseline LDL‑C levels were associated with the risk for incident T2D and whether statin therapy modified that association.
- They analysed data of 13,674 participants who were free of T2D and cardiovascular diseases at baseline (mean age, 62 years; 58% men); 52% of participants were on statin therapy.
- Baseline LDL-C levels were measured on fasting blood samples at enrolment; participants were stratified into four groups on the basis of quartiles of LDL-C levels for analysis: low (< 84 mg/dL), medium (≥ 84 to < 107 mg/dL), high (≥ 107 to < 131 mg/dL), and very high (≥ 131 mg/dL).
- The primary outcome was incident T2D, requiring at least two fasting plasma glucose readings ≥ 126 mg/dL, at least one A1c value ≥ 6.5%, or the prescription of antidiabetic therapy for more than 30 days.
- The median follow-up duration was 71.6 months.
TAKEAWAY:
- Overall, 13% of participants developed incident T2D; the incidence was 20% among statin users and 6% among non‑users (P < .001).
- Lower LDL-C levels were associated with a higher risk for incident T2D (P < .001), with participants in the low LDL-C group (< 84 mg/dL) having the highest risk.
- The modifying effect of statin therapy on the risk for T2D was evident only in the very high LDL-C group (≥ 131 mg/dL), and statin users had a higher risk for incident T2D than non-users (P = .018).
- By contrast, the interaction between statin use and the risk for T2D was not statistically significant in the other LDL‑C groups.
IN PRACTICE:
“The lack of significant interaction of statin therapy on incident T2D for low LDL-C levels groups in the present study may imply that the reduction in plasma LDL-C concentration is accompanied by an increase in incident T2D largely independent on statin therapy,” the authors wrote.
SOURCE:
This study was led by Maria Lembo, Valentina Trimarco, Daniela Pacella, and Raffaele Izzo, “Federico II” University, Naples, Italy. It was published online on November 11, 2025, in Cardiovascular Diabetology.
LIMITATIONS:
The findings did not elucidate the underlying pathophysiologic mechanisms connecting low LDL-C levels to an increased risk for incident T2D. This study lacked data on statin potency and dosage at baseline. Additionally, genetic analysis was not included in the assessment, and information about lifestyle factors — such as physical activity and dietary patterns — that could have influenced the risk for T2D was unavailable.
DISCLOSURES:
This study was funded by multiple sources, including the National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; and National Center for Advancing Translational Sciences. The authors reported having no competing interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.