Recently, a study conducted by researchers from the US and Japan indicated that low-density lipoprotein cholesterol (LDL-C) levels are negatively correlated with the risk of type 2 diabetes, and this association is largely independent of the use of statin medications.
This population-based study included a total of 13,674 participants, with an average age of 62 years, 58% of whom were male, and none had type 2 diabetes or cardiovascular disease at baseline, with 52% receiving statin treatment.
The researchers categorized participants based on baseline LDL-C levels into four groups: low (< 84 mg/dl, n=3,798), medium (≥84 to < 107 mg/dl, n=3,596), high (≥107 to < 131 mg/dl, n=3,326), and very high (≥131 mg/dl, n=2,954). The usage of statin medications in these groups was 66%, 46%, 41%, and 56%, respectively.
During a median follow-up of 71.6 months, 1,819 participants (13%) developed type 2 diabetes, with the incidence rates for the low, medium, high, and very high LDL-C groups being 27.6/1,000 person-years, 17.4/1,000 person-years, 13.5/1,000 person-years, and 8.4/1,000 person-years, respectively. The incidence rate in the very high LDL-C group was significantly lower than in the other three groups (P all <0.001).
Further analysis revealed that low LDL-C levels are associated with a higher risk of type 2 diabetes, with the lowest LDL-C group (< 84 mg/dl) having the highest risk.
In this study, the incidence of type 2 diabetes was higher in patients taking statins compared to those not taking them (12% vs. 6%). However, after including statin use in a multivariable model analysis, it was found that only patients in the very high LDL-C group had a significantly increased risk of type 2 diabetes, while in the other LDL-C groups, the interaction between statin use and type 2 diabetes was not statistically significant.
In other words, although the risk of type 2 diabetes increases with statin use across different LDL-C levels, this risk varies, being significantly increased only at very high LDL-C levels.
Additionally, genetic studies have also indicated that low LDL-C is associated with a high risk of type 2 diabetes.
Genes associated with low LDL-C and high type 2 diabetes risk can influence LDL-C levels through various pathways, including cholesterol absorption (NPC1L1), endogenous cholesterol synthesis (HMGCR), and the internalization of cholesterol-rich particles into cells (PCSK9).
Alleles of HMGCR associated with reduced LDL-C are correlated with higher fasting insulin and body mass index levels, suggesting that insulin resistance mechanisms may influence the occurrence of type 2 diabetes.
Moreover, some research findings suggest that elevated intracellular cholesterol levels may impair pancreatic β-cell function.
Source:Lembo M, Trimarco V, Pacella D, et al. A six-year longitudinal study identifies a statin-independent association between low LDL-cholesterol and risk of type 2 diabetes. Cardiovasc Diabetol. 2025 Nov 11;24(1):429.
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