Insulin resistance-associated genetic variants in type 1 diabetes.
Genetics
Glycemic control
Insulin resistance
Intensive insulin therapy
Type 1 diabetes
Journal
Journal of diabetes and its complications
ISSN: 1873-460X
Titre abrégé: J Diabetes Complications
Pays: United States
ID NLM: 9204583
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
12
10
2020
revised:
16
12
2020
accepted:
24
12
2020
pubmed:
21
1
2021
medline:
31
12
2021
entrez:
20
1
2021
Statut:
ppublish
Résumé
To examine candidate insulin resistance single nucleotide polymorphisms (SNPs) for associations with glycemic control, insulin resistance, BMI, and complications in an observational type 1 diabetes (T1D) cohort: the Pittsburgh Epidemiology of Diabetes Complications (EDC) study. In 422 European-ancestry participants, we assessed associations using additive models between 15 candidate SNPs and 25-year mortality, cardiovascular disease, microalbuminuria, overt nephropathy and proliferative retinopathy, and 25-year mean HbA1c, estimated glucose disposal rate (eGDR, inverse measure of insulin resistance), and BMI. The A allele of rs12970134 was associated with higher mean HbA1c (β = +0.34 ± 0.09, p = 0.00009) and nominally associated with worse eGDR (p = 0.02). Further analyses suggest the HbA1c association may be modified by diabetes therapy regimen: rs12970134 AA genotype was associated with higher HbA1c under non-intensive therapy conditions (<3 insulin injections/day or monitoring blood glucose<3 times/day [p = 0.004]), but not under intensive therapy (≥3 injections/day or insulin pump and monitoring glucose≥3 times/day [p = 0.71]). There were no significant associations between any SNPs and BMI or complications. rs12970134, near MC4R, is strongly associated with HbA1c in this cohort. Further exploration of this genomic region is warranted, as it may hold promise for discovering new therapeutic targets to improve glycemic control in T1D.
Identifiants
pubmed: 33468396
pii: S1056-8727(20)30643-7
doi: 10.1016/j.jdiacomp.2020.107842
pmc: PMC7936951
mid: NIHMS1661600
pii:
doi:
Substances chimiques
Blood Glucose
0
Glycated Hemoglobin A
0
Insulin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107842Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK034818
Pays : United States
Organisme : Chief Scientist Office
ID : ETM/47
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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