Naturally low LDL cholesterol levels linked to increased type 2 diabetes risk
medwireNews: Patients with very low low-density lipoprotein (LDL) cholesterol levels unrelated to statin use have double the risk for type 2 diabetes compared with those with normal cholesterol levels, an analysis of electronic health records shows.
“The findings suggest that special attention should be paid to risk of [type 2 diabetes] with therapies that lower LDL [cholesterol] markedly,” write QiPing Feng (Vanderbilt University Medical Center, Nashville, Tennessee, USA) and co-authors in PLOS Medicine.
Feng and team explain that low LDL cholesterol has previously been associated with an increased risk for type 2 diabetes in genetic studies and clinical trials of statin therapy, but the relationship “has not been tested in a clinical setting without statin treatment.”
To address this, they reviewed the electronic health records of over 80,000 patients at their institution, excluding patients with low LDL cholesterol levels associated with statin use, and those whose measurement was taken in hospital, or within 30 days of having a serum albumin level below 3 g/dL.
In the discovery phase of the study, the 2982 patients with very low (≤60 mg/dL) LDL cholesterol were significantly more likely to have groups of International Classification of Disease–9th revision codes (phecodes) related to type 2 diabetes than the 23,771 patients with normal LDL cholesterol (90–130 mg/dL).
These findings were then validated in a larger cohort identified using an algorithm that separates diabetes cases from controls with a higher degree of specificity than the phecodes.
In this analysis, patients with very low LDL cholesterol (n=5961) had a significant 2.1-fold increased risk for type 2 diabetes compared with those with normal LDL cholesterol (n=47,572), after adjustment for age, race, sex, BMI, high-density lipoprotein cholesterol, triglycerides, and duration of care.
Similar results were observed for both men and women, across BMI categories (normal weight, overweight, and obese), and when the low LDL cholesterol group was divided into those with a level below 40 mg/dL and those with a level between 40 and 60 mg/dL.
However, Feng and co-researchers identified a significant interaction between low LDL cholesterol and race, with the risk for type 2 diabetes significantly increased with low versus normal levels of cholesterol among individuals of European ancestry but not among those of African ancestry.
They say that this could be due to the fact that individuals of African ancestry had a higher risk for type 2 diabetes at normal LDL cholesterol levels.
The investigators remark that “the relationship between risk of [type 2 diabetes] and low LDL [cholesterol] concentrations is an important concern,” particularly with the “advent of powerful LDL [cholesterol]-lowering drugs.”
They add that the mechanism behind this relationship is currently unknown and longitudinal cohort studies in individuals with very low LDL cholesterol levels not associated with lipid-lowering therapy will therefore be important.
By Laura Cowen
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