engleski

Efficacy of insulin detemir treatment in type 2 diabetes mellitus is associated with a allele od the catechol o-methyltransferase polymorphism

Introduction: Growing evidence suggests that nutrients and hormonal signals converge and directly act on brain centers, leading to changes in energy metabolism and stable body weight over time. Catechol O-methyltransferase (COMT) is one of the major enzymes involved in catecholamine and estrogen degradation. There is a well-established association between the COMT Val108/158Met polymorphism and abdominal obesity, blood pressure increase and T2DM. Basal insulin detemir besides a low pharmacodynamic coefficient of variability, exhibits anorexigenic features, probably through a complex interplay of its effects on the CNS and on the finely tuned efferent and afferent signals between muscle, brain, liver, renal and adipose tissues. Aims: To investigate the association of COMT Val108/158Met polymorphisms with effectiveness of insulin detemir in achieving glucose control and body weight control. Methods: Observational study included 185 T2DM patients inadequately controled with premix insulin analogues, which were replaced with three doses of insulin aspart at mealtime and insulin detemir at bedtime that were followed for 52 weeks. After DNA isolation from blood samples, genotyping of COMT Val108/158Met polymorphism (rs4680) was performed. Results: The mean age of participants was 67.1±8.01 years, with a mean duration of diabetes 16.1±5.9 years. HbA1c and fasting plasma glucose were significantly decreased after 52 weeks (8.58% vs 7.78%, 11.7 mmol/l vs 8.7 mmol/l, respectively, P< 0.001). At the end of the follow up period, 28.1% of patients achieved HbA1c<7.0%. Insulin detemir had a significant weight sparing effect in overweight patients. The most prominent finding was that A carriers (the combined AG and AA genotype) of the COMT Val108/158Met achieved significantly better HbA1c values compared to patients carrying GG genotype. Conclusions: Our results 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 T2DM patients.

insulin detemir, catechol o-methyltransferase polymorphism

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