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  The influence of dopamine-beta-hydroxylase and catechol O-methyltransferase gene polymorphism on the efficacy of insulin detemir therapy in patients with type 2 diabetes mellitus

Bozek, T., Blazekovic, A., Nikolac Perkovic, M., Gotovac Jercic, K., Sustar, A., Smircic-Duvnjak, L., et al. (2017). The influence of dopamine-beta-hydroxylase and catechol O-methyltransferase gene polymorphism on the efficacy of insulin detemir therapy in patients with type 2 diabetes mellitus. Diabetology & Metabolic Syndrome, 9: 97. doi:10.1186/s13098-017-0295-0.

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 Creators:
Bozek, Tomislav, Author
Blazekovic, Antonela, Author
Nikolac Perkovic, Matea, Author
Gotovac Jercic, Kristina, Author
Sustar, Aleksandra, Author
Smircic-Duvnjak, Lea, Author
Outeiro, Tiago F.1, Author           
Pivac, Nela, Author
Borovecki, Fran, Author
Affiliations:
1Experimental Neurodegeneration, Max Planck Institute of Experimental Medicine, Max Planck Society, ou_3398149              

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Free keywords: Type 2 diabetes mellitus; Insulin detemir; COMTVal108/158Met polymorphism; DBH-1021C/T polymorphism; Hemoglobin A1c (HbA1c); BMI
 Abstract: Background:
Type II diabetes is an important health problem with a complex connection to obesity, leading to a broad range of cardiovascular complications. Insulin therapy often results in weight gain and does not always ensure adequate glycemic control. However, previous studies reported that insulin detemir is an efficient long-acting insulin with a weight sparing effect. The aim of this study was to determine the association of catechol O-methyltransferase (COMT) Val108/158Met and dopamine-beta-hydroxylase (DBH) 1021C/T polymorphisms with the effectiveness of insulin detemir in achieving glucose control and body weight control. Participants and methods: This 52-week observational study included 185 patients with inadequate glycemic control treated with premix insulin analogues, which were replaced with insulin aspart and insulin detemir, and 156 healthy controls. After DNA isolation from blood samples, genotyping of DBH-1021C/T polymorphism (rs1611115) and COMT Val108/158Met polymorphism (rs4680) was performed.

Results:
Our results confirmed that insulin detemir did not lead to weight gain. The most significant finding was that A carriers (the combined AG and AA genotype) of the COMT Val108/158Met achieved significantly better hemoglobin A1c (HbA1c) values compared to patients carrying GG genotype. No association between DBH-1021C/T genotypes and weight and/or glucose control was detected in diabetes patients or in healthy control subjects.

Conclusions:
This study showed that the presence of one or two A allele of the COMT Val108/158Met was associated with improved glycemic response, and with a better response to insulin detemir therapy in patients with type II diabetes, separating them as best candidates for detemir therapy.

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Language(s): eng - English
 Dates: 2017-11-222017-12-04
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1186/s13098-017-0295-0
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Title: Diabetology & Metabolic Syndrome
  Other : Diabetology and Metabolic Syndrome
Source Genre: Journal
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Publ. Info: London : BioMed Central
Pages: - Volume / Issue: 9 Sequence Number: 97 Start / End Page: - Identifier: Other: ISSN
CoNE: https://pure.mpg.de/cone/journals/resource/1758-5996