Abstract
BackgroundType 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.ResultsOur 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.ConclusionsThis 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.
Highlights
Type II diabetes is an important health problem with a complex connection to obesity, leading to a broad range of cardiovascular complications
The aim of this study was to determine the association of catechol O-methyltransferase (COMT) Val108/158Met and DBH-1021C/T polymorphisms with effectiveness of insulin detemir in achieving glucose control as well as body weight control
Patients were treated with premix insulin analogues for a mean duration of 5.7 ± 2.8 years, and were on an average daily dose of 0.72 Units/ kg (Table 1)
Summary
Type II diabetes is an important health problem with a complex connection to obesity, leading to a broad range of cardiovascular complications. 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. Type II diabetes (T2DM) represents an important health problem, affecting a substantial percentage of the world population. It is designated by a chronic progressive course and a subsequent need for a long-term insulin therapy to achieve optimal glucose control. Plasma DBH activity is under the genetic control of a single-nucleotide polymorphism (SNP), DBH-1021C/T, in the 5′ flanking region of the DBH gene. It is known that DBH knock down mice are presenting with an impaired glucagon response to hypoglycemia and elevated insulin levels [14]
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