Lviv clinical bulletin 2017, 2(18)-3(19): 32-38

https://doi.org/10.25040/lkv2017.023.032

Content of Some Pro- and Anti-inflammatory Factors, Insulin Resistance Parameters in Patients with Type 2 Diabetes Mellitus and Cardiovascular Autonomic Neuropathy, Influence of Omega-3 Polyunsaturated Fatty Acids on These Parameters

V. Serhiyenko, О. Serhiyenko

Danylo Halytsky Lviv National Medical University

Introduction. Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus (DM), that is strongly associated with increased risk of cardiovascular mortality. CAN among type 2 DM (T2DM) patients, is characterized by lesion of nerve fibers in the sympathetic and parasympathetic divisions of the autonomic nervous system, is diagnosed unsatisfactorily and 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 (MI), sudden death syndrome. CAN manifests in a spectrum of things, ranging from resting tachycardia and fixed heard rate to development of ″silent″ MI. Although it is a common complication, the significance of CAN has not been fully appreciated and there are no unified treatment algorithms for today. The pathogenetic treatment of CAN include lifestyle modification, intensive glycemic control, treatment of dyslipoproteinemia (DLP), correction of metabolic abnormalities in the myocardium, thrombosis prevention, prescription of α-lipoic acid, aldose reductase inhibitors; γ-linoleic acid, acetyl-L-carnitine, antioxidants, long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFAs), vasodilators, vitamin B1 and some other substances. American Diabetes Association (2016) recommend the prescription of ω-3 PUFAs in algorithms of DLP treatment among patients with T2DM and cardiovascular diseases. However, the data about the ω-3 PUFAs effectiveness are incomplete, the future investigation are needed.

The aim of the study was to investigate the content of some pro- and anti-inflammatory factors, insulin resistance parameters in patients with T2DM and CAN, influence of ω-3 PUFAs on these parameters.

Materials and methods. The study involved 48 patients with T2DM (16 women, 32 men, patients were aged between 50-59 years), among them: 1) 12 patients with T2DM without CAN; 2) 36 (aged 50-59 years, disease duration 1-6 years, glycated haemoglobin (HbA1c) level (7,1 ± 0,6) %) – with functional CAN stage. Control group – 15 healthy people of median age (51,9 ± 3,2) years.

The concentration of glucose, immunoreactive insulin (IRI), high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8 and IL-10 in the blood were determinate; insulin resistance index (HOMA-IR) and TNF-α/IL-10 ratio were calculated.

Patients with T2DM and functional stage of CAN were divided into 2 groups: patients of 1nd group (n = 21) received one capsule/day of the ω-3 PUFAs in addition to standard treatment, each one gram capsule of the ω-3 PUFA contains approximately 465 mg of eicosapentaenoic and 375 mg of docosahexaenoic acid and 4,0 g of tocopferol acetate; patients of 2nd group (n = 15) received standard glucose lowering therapy (control group). The duration of the study was 3 months.

Results. According to the results of our study there can be seen the increase of IRI, HOMA-IR levels are accom- panied with increase of hsCRP, TNF-α, IL-6, IL-8 and IL-10 (compared to the control). The development of func- tional stage of CAN was accompanied with statistically significant increase of IRI, hsCRP, TNF-α, IL-6, IL-8, IL-10 and TNF-α/IL-10 levels (compared to patients with T2DM without CAN). Obtained results could witness about the violation of cytokines dysbalance, development of compensative type of cytokine dysbalance.

The administration of ω-3 PUFAs to patients with T2DM and CAN promoted to the statistically significant decrease in hsCRP, TNF-α, IL-6 and IL-8 levels and TNF-α/IL-10 ratio; but no statistically significant changes of IL-10, HbA1c, IRI and HOMA-IR was found.

Conclusions. Obtained results could witness, that prescription of ω-3 polyunsaturated fatty acids leads to decrease of the proinflammatory immune response activity and allows to consider ω-3 polyunsaturated fatty acids as a promising medicine in the treatment of cardiac autonomic neuropathy in patients with type 2 diabetes mellitus.

References

  1. Vrjesinskaya OA, Beketova NA, Kodentsova VM et al. Effect of diet en- riched with vitamin deficient rats polyunsaturated fatty acids ω-3 family on biomarkers of vitamin and antioxidant status. Vopr Pitan. 2013;82(1):45-52. (Russian)
  2. Korkushko OV, Shatilo VB, Ishchuk VA. The use of omega-3 polyunsaturated fatty acids for the normalization of endothelial function and blood clotting in the pathology of the cardiovascular system. Ukr Med J. 2010;2(76):46-49. (Ukrainian)
  3. Kryzhanovsky SA, Vititnova MB. Omega-3 polyunsaturated fatty acids and the cardiovascular system. Human Physiol. 2009;35(4):110-123. (Russian)
  4. Lapach SN. Statistical methods in biomedical research using Excel. Кyiv: Moryon, 2000. 320 p. (Russian)
  5. Semenchenko IY, Sharafetdinov KK, Plotnikova OA et al. Markers of immune inflammation in patients with type 2 diabetes and obesity. Vopr Pitan. 2013;82(5):46-50. (Russian)
  6. Serhiyenko VA, Serhiyenko AA, Efimov AS. Long-chain ω-3 polyunsaturated fatty acids: cardiovascular diseases and type 2 diabetes mellitus (review of literature and own data). J NAMS Ukraine. 2011;17(4):353-367. (Ukrainian)
  7. Serik SA, Chenchik TA, Serdobinskaya-Kanivets EN, Bondar TN. Interleukin-10 and the pro-/anti-inflammatory cytokine balance in heart failure patients with type 2 diabetes mellitus. Ukr Ther J. 2012;3-4:58-63. (Russian)
  8. American Diabetes Association. Standards of medical care in diabetes-2016. Diabetes Care. 2016;39(1 Suppl):14-80.
  9. Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol. 2013;75(is 3):645-662.
  10. de Roos B, Mavrommatis Y, Brouwer IA. Long-chain n-3 polyunsaturated fatty acids: new insights into mechanisms relating to inflammation and coronary heart disease. Br J Pharmacol. 2009;158(2):413-428. https://doi.org/10.1111/j.1476-5381.2009.00189.x
  11. Figueras M, Olivan M, Busquets S, López-Soriano FJ, Argilés JM. Effects of eicosapentaenoic acid (EPA) treatment on insulin sensitivity in an animal model of diabetes: improvement of the inflammatory status. Obesity. 2010;19(1):362-369.
  12. Gazem RAA, Chandrashekariah SA. Omega fatty acids in health and disease: A review. J Pharmacy Res. 2014;8(8):1027- 1044.
  13. Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998;21(10):2191-2192. https://doi.org/10.2337/diacare.21.12.2191
  14. Mirza S, Hossain M, Mathews C, Martinez P, Pino P, Gay JL et al. Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: a cross-sectional study. Cytokine. 2012;57(1):136-142. https://doi.org/10.1016/j.cyto.2011.09.029
  15. N-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. The ORIGIN Trial Investigators. N Engl J Med. 2012;367(7):309-318.
  16. Serhiyenko VA, Serhiyenko AA. Diabetic cardiac autonomic neuropathy: Do we have any treatment perspectives? World J Diabetes. 2015;6(2):245-258. https://doi.org/10.4239/wjd.v6.i2.245
  17. Spallone V, Ziegler D, Freeman R, Bernardi L, Frontoni S, Pop-Busui R et al. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011;27(7):639-653. https://doi.org/10.1002/dmrr.1239