Diabetic neuropathies, including cardiovascular autonomic neuropathy (CAN), are a common chronic complications of Type 2 diabetes mellitus and confer high morbidity and mortality to diabetic patients. The present study has examined the metabolic effects of simvastatin (SIM), omega-3 polyunsaturated fatty acids (ω-3 PUFA) and their combinations in Type 2 diabetic patients with CAN.

76 Type 2 diabetic patients with CAN (54,7±3,6 years), BMI 27,8±2,3kg/m2, HbA1c 7,1±0,7 % and 15 age-matched controls were observed. Fasting blood glucose, HbA1c, lipid profile, immunoreactive insulin (IRI), C-peptide, N-terminal pro B-type natriuretic peptide (NT-proBNP), leptin, tumor necrosis factor-⍺ (TNF-⍺), high sensitivity C-rective protein (hs-CRP), interleukin-8 (IL-8), interleukin-18 (IL-18) were evaluated. HOMA-IR and HOMA-β-CF indexes were calculated. Heart rate variability (HRV) properties were assessed by Holter ECG. Patients with CAN were allocated to four groups: group A (n=15) received standart basic therapy; B (n=22) - SIM 20mg; C (n=21) - capsules of fish oil [1,0g (≈85% ω-3 PUFA)]; D (n=18) - SIM 10mg plus capsules of fish oil. All patients were on the same diet. The duration of the study was 3 months. Statistics: ANOVA (MicroCal Origin v. 8,2)].

Lipid disorders [high level of total cholesterol, low density lipoprotein-cholesterol (LDL-C), triglycerides (TG) (P<0,05) and decreased level of high density lipoprotein-cholesterol (HDL-C)] in patients with CAN are accompanied by the increase of IRI, C-peptide, leptin, hs-CRP, IL-8, IL-18, NT-proBNP, TNF-⍺ concentration in blood, increase of HOMA–IR and decrease of HOMA-β-CF parameters; correlation between leptin, TG concentration and parameters of insulin resistance were found. HRV properties are characterized by reduction of sympathetic, parasympathetic and humoral links tonus with predominance of sympathetic link of vegetative nervous system. After 3 months of treatment there was a more significant decrease in LDL-C (−42,9±2,25 %, p<0,001), TG (−44,1±3,15 %, p<0,001), increase of HDL-C (+15,8±1,35 %, p<0,001) concentration, positively influence on HRV, blood pressure in the 4-rd group. In particular, the decrease of IRI (−21,1±2,04 %, p<0,001), HOMA–IR (−25,3±3,18 %, p<0,001), leptin (−19,4±1,9 %, p<0,001), C-peptide (−16,2±2,25 %, p<0,01), hs-CRP (−18,3±2,04 %,p<0,001), IL-8 (−11,1±2,45 %, p<0,05), IL-18 (−10,0±1,74 %, p<0,05), NT-proBNP(−9,7±2,12%, p<0,05), TNF-⍺ (−16,4±2,27%, p<0,001), increase of root mean square successive difference, HOMA-β-CF parameters (P<0,05) were observed.

Usage of ω-3 PUFA in treatment of Type 2 diabetic patients with CAN improve the general condition of patients, contribute to clinical disease symptoms regression. By the evaluation of vegetative state the total score was significantly decreased (p<0,01). In addition, in most patients with CAN and peripheral polyneuropathy reduction of pain, paresthesias, frequency of muscles courts, improvement of tactile, vibration and temperature sensitivity, pulse flow performance and capillaroscopy was observed.

Positive impact of the combined administration of SIM and ω-3 PUFA on the lipid profile, concentration of IRI, hs-CRP, NT-proBNP, some adipokins in blood and reported before mild hypotensive and vegetomodulation effects allows to recommend their combination in the complex treatment of Type 2 diabetic patients with CAN.