Very low low-density lipoprotein cholesterol (LDL-C) concentrations occurring in the absence of statin treatment were significantly associated with type 2 diabetes mellitus (T2DM) risk, according to a recent study. Researchers used electronic health records (EHRs) to compare the risk of T2DM in a cross-sectional study among individuals with very low (≤60 mg/dl, n= 8,943) and normal (90–130 mg/dl, n=71,343) LDL-C levels. They used a 2-phase approach: In 1/3 of the sample (discovery) they used T2DM phenome-wide association study codes (phecodes) to identify cases and controls, and in the remaining 2/3 (validation) they identified T2DM cases and controls using a validated algorithm. They found:

• In the discovery cohort, phecodes related to T2DM were significantly more frequent in the very low LDL-C group.
• In the validation cohort (n=33,039), the risk of T2DM was increased in the very low compared to normal LDL-C group.
• The association between low LDL-C levels and T2DM was significant in males and females; in normal weight, overweight, and obese categories; and in individuals with LDL-C < 40 mg/dl and LDL-C 40–60 mg/dl.