S. Azhmi, V. Serhiyenko
Danylo Halytsky Lviv National Medical University
Introduction. Cardiovascular autonomic neuropathy (CAN) is a serious and common complication of type 2 diabetes mellitus (T2DM). Despite its relationship to an increased risk of cardiovascular mortality and its association with multiple symptoms and impairments, the significance of CAN has not been fully appreciated. CAN among T2DM patients may be accompanied by severe postural hypotension, decreased tolerance to the physical loadings, and cause the cardiac arrhythmias, ischemia of coronary vessels, ″silent″ myocardial infarction, sudden death syndrome. Although it is a common complication, the significance of CAN has not been fully appreciated and there are no unified treatment algorithms for today. It is obvious that the foreground should be the therapy aimed at lifestyle modification, reducing insulin resistance (IR), correction of hyperglycemia, dyslipoproteinemia (DLP), symptomatic treatment of concomitant diseases and syndromes. For DLP pharmacotherapy using statins, fibrates, bile acid sequestrants, nicotinic acid and its derivatives, products of long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFAs), or as an alternative-their combination with cholesterol absorption inhibitors. Statins are widely accepted as the first-line therapy of the atherogenic DLP, the effectiveness of its prescription was proved in several studies. However, the data about the ω-3 PUFAs effectiveness are incomplete, the future investigation are needed.
The aim of this study was to investigate the blood lipid profile and IR parameters in patients with T2DM and CAN and the effects of simvastatin and ω-3 PUFAs prescription.
Materials and methods. The study involved 219 patients with T2DM (101 women and 118 men, patients were aged between 50-59 years), among them: 1) 19 patients without CAN; 2) 44 – with subclinical CAN; 3) 156 (aged 50-59 years, disease duration 1-6 years, glycated haemoglobin A1c (HbA1c) level (7,1 ± 0,4) %) – with functional CAN. Control group – 15 healthy people of median age (51,9 ± 3,2) years.
The concentration of glucose, HbA1c, immunoreactive insulin (IRI) in the blood were determinated, the insulin resistance index (HOMA-IR) was calculated. Lipid metabolism was assessed by the concentration of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) measurements and calculation of the atherogenic coefficient (AC).
Among 156 patients with T2DM and functional CAN stage, 76 patients were allocated into four treatment groups: 1st group – 22 patients received standard hypoglycemic therapy and simvastatin 20 mg/day; 2nd group – 21 patients received standard hypoglycemic therapy and one capsule/day of the ω-3 PUFAs; 3rd group – 18 patients received standard hypoglycemic therapy, one capsule of the ω-3 PUFAs and simvastatin 10 mg/day; 4th group – control group received standard hypoglycemic therapy (n = 15). The duration of the study was 3 month.
Results and discussion. Obtained results of our study could witness that the increase of IRI, HOMA-IR parameters in patients with T2DM and CAN was accompanied by growth of TC, TG, LDL-C, AC and decrease of HDL-C levels. The most pronounced changes were observed in patients with functional stage of CAN. The prescription of simvastatin was accompanied by a statistically significant decrease in TC, LDL-C, TG, IRI and increase in HDL-C levels (compared to control); statistically significant decrease in TC, LDL-C and IRI (compared to ω-3 PUFAs).
ω-3 PUFAs are not contributing to changes in HbA1c, preprandial glucose, IRI and HOMA-IR; statistically significant reduced TG, AC and increased HDL-C levels. The combined prescription of simvastatin and ω-3 PUFAs contributed to the most positive, statistically significant changes in hyperinsulinemia/IR parameters and lipid metabolism, allowing to reduce the daily dose of simvastatin.
Conclusions. Obtained results could witness that effects of combined simvastatin and omega-3 polyunsaturated fatty acids prescription are not connected with diabetes mellitus compensation state and are as a direct influence of this pharmacological agents on investigated parameters that justify the appropriateness of their prescription to patients with type 2 diabetes mellitus and functional stage of cardiovascular autonomic neuropathy.
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