Relationship between very low low-density lipoprotein cholesterol concentrations not due to statin therapy and risk of type 2 diabetes: A US-based cross-sectional observational study using electronic health records.

PLoS Medicine
QiPing FengC Michael Stein

Abstract

Observations from statin clinical trials and from Mendelian randomization studies suggest that low low-density lipoprotein cholesterol (LDL-C) concentrations may be associated with increased risk of type 2 diabetes mellitus (T2DM). Despite the findings from statin clinical trials and genetic studies, there is little direct evidence implicating low LDL-C concentrations in increased risk of T2DM. We used de-identified electronic health records (EHRs) at Vanderbilt University Medical Center 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 calculated using the Friedewald formula. LDL-C levels associated with statin use, hospitalization, or a serum albumin level < 3 g/dl were excluded. We used a 2-phase approach: in 1/3 of the sample (discovery) we used T2DM phenome-wide association study codes (phecodes) to identify cases and controls, and in the remaining 2/3 (validation) we identified T2DM cases and controls using a validated algorithm. The analysis plan for the validation phase was constructed at the time of the design of that component of the study. The prevalence of T2DM in the very low and normal LDL-C groups was co...Continue Reading

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Citations

Dec 20, 2018·Expert Review of Clinical Pharmacology·Uffe RavnskovRalf Sundberg
Dec 6, 2019·The Pharmacogenomics Journal·Roelof A J SmitUNKNOWN GIST consortium
May 22, 2020·Circulation Research·Mark O Goodarzi, Jerome I Rotter
Jan 20, 2021·European Heart Journal·Angelos D KaragiannisLaurence S Sperling
Jul 18, 2021·Journal of Medical Genetics·Lijuan WangXue Li

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Software Mentioned

STATA
PheWAS R package
MedEx
eMERGE
Synthetic
R

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