Back to Search
Start Over
A Polygenic Score for Type 2 Diabetes Risk Is Associated With Both the Acute and Sustained Response to Sulfonylureas
A Polygenic Score for Type 2 Diabetes Risk Is Associated With Both the Acute and Sustained Response to Sulfonylureas
- Source :
- Diabetes
- Publication Year :
- 2020
- Publisher :
- American Diabetes Association, 2020.
-
Abstract
- There is a limited understanding of how genetic loci associated with glycemic traits and type 2 diabetes (T2D) influence the response to antidiabetic medications. Polygenic scores provide increasing power to detect patterns of disease predisposition that might benefit from a targeted pharmacologic intervention. In the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH), we constructed weighted polygenic scores using known genome-wide significant associations for T2D, fasting glucose, and fasting insulin, comprising 65, 43, and 13 single nucleotide polymorphisms, respectively. Multiple linear regression tested for associations between scores and glycemic traits as well as pharmacodynamic end points, adjusting for age, sex, race, and BMI. A higher T2D score was nominally associated with a shorter time to insulin peak, greater glucose area over the curve, shorter time to glucose trough, and steeper slope to glucose trough after glipizide. In replication, a higher T2D score was associated with a greater 1-year hemoglobin A1c reduction to sulfonylureas in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) study (P = 0.02). Our findings suggest that individuals with a higher genetic burden for T2D experience a greater acute and sustained response to sulfonylureas.
- Subjects :
- Blood Glucose
Male
0301 basic medicine
medicine.medical_specialty
Genotype
endocrine system diseases
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
030209 endocrinology & metabolism
Genome-wide association study
Type 2 diabetes
Polymorphism, Single Nucleotide
03 medical and health sciences
0302 clinical medicine
Internal medicine
Diabetes mellitus
Internal Medicine
Humans
Hypoglycemic Agents
Medicine
Genetic Predisposition to Disease
Glycemic
Glycated Hemoglobin
business.industry
Insulin
nutritional and metabolic diseases
Genetics/Genomes/Proteomics/Metabolomics
medicine.disease
3. Good health
Metformin
Sulfonylurea Compounds
Treatment Outcome
030104 developmental biology
Diabetes Mellitus, Type 2
Pharmacogenetics
Female
business
Genome-Wide Association Study
Glipizide
medicine.drug
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 70
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....5f42d08d38146e4bceda77275033fc3b
- Full Text :
- https://doi.org/10.2337/db20-0530