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Phenotypic and Genetic Characterization of Lower LDL Cholesterol and Increased Type 2 Diabetes Risk in the UK Biobank
- Source :
- Diabetes
- Publication Year :
- 2020
- Publisher :
- American Diabetes Association, 2020.
-
Abstract
- Although hyperlipidemia is traditionally considered a risk factor for type 2 diabetes (T2D), evidence has emerged from statin trials and candidate gene investigations suggesting that lower LDL cholesterol (LDL-C) increases T2D risk. We thus sought to more comprehensively examine the phenotypic and genotypic relationships of LDL-C with T2D. Using data from the UK Biobank, we found that levels of circulating LDL-C were negatively associated with T2D prevalence (odds ratio 0.41 [95% CI 0.39, 0.43] per mmol/L unit of LDL-C), despite positive associations of circulating LDL-C with HbA1c and BMI. We then performed the first genome-wide exploration of variants simultaneously associated with lower circulating LDL-C and increased T2D risk, using data on LDL-C from the UK Biobank (n = 431,167) and the Global Lipids Genetics Consortium (n = 188,577), and data on T2D from the Diabetes Genetics Replication and Meta-Analysis consortium (n = 898,130). We identified 31 loci associated with lower circulating LDL-C and increased T2D, capturing several potential mechanisms. Seven of these loci have previously been identified for this dual phenotype, and nine have previously been implicated in nonalcoholic fatty liver disease. These findings extend our current understanding of the higher T2D risk among individuals with low circulating LDL-C and of the underlying mechanisms, including those responsible for the diabetogenic effect of LDL-C–lowering medications.
- Subjects :
- 0301 basic medicine
Oncology
Blood Glucose
medicine.medical_specialty
Candidate gene
Statin
endocrine system diseases
medicine.drug_class
Endocrinology, Diabetes and Metabolism
030209 endocrinology & metabolism
Type 2 diabetes
03 medical and health sciences
0302 clinical medicine
Internal medicine
Diabetes mellitus
Hyperlipidemia
Nonalcoholic fatty liver disease
Internal Medicine
medicine
Humans
Risk factor
Biological Specimen Banks
business.industry
nutritional and metabolic diseases
Genetics/Genomes/Proteomics/Metabolomics
Odds ratio
Cholesterol, LDL
medicine.disease
United Kingdom
030104 developmental biology
Diabetes Mellitus, Type 2
lipids (amino acids, peptides, and proteins)
business
Subjects
Details
- Language :
- English
- ISSN :
- 1939327X and 00121797
- Volume :
- 69
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....14e9cd5d55afc44ec1a1688fb2b969aa