PECULIARITIES OF THE CYTOKINE PROFILE OF PATIENTS WITH TYPE 2 DIABETES MELLITUS IN COMBINATION WITH AUTOIMMUNE THYROIDITIS

Study objective: study of the nature of changes in the immune system of patients with type 2 diabetes mellitus (DM) in combination with autoimmune thyroiditis (AIT) and without it; comparative analysis of similar indicators of patients with type 1 DM in combination with AIT and without it.

Materials and methods. 104 patients at the age of 22 to 62 y.o. (57 women and 47 men) took part in the study. They were divided into 4 groups (type 2 DM, type 2 DM and AIT, type 1 DM, type 1 DM and AIT). Groups of patients who were examined regarding the state of carbohydrate and lipid metabolism, indicators of the T-cell link of the immune system, concentration of interleukin 4 (IL-4), IL-6, interferon-gamma, and leptin level, were comparable regarding their sex, age, duration of disease.

Results. Unidirectional relationship between body mass index (BMI), amount of CD4 +-, CD8+- lymphocytes, level of leptin, IL-4, IL-6 concentrations and BMI and immunoregulatory index of patients with type 2 DM both with AIT and without it was determined. Patients with type 2 DM displayed decreasing activity of the T-cell link of the immune system and increasing of the concentration of pro-inflammatory cytokines irrespectively of the availability of accompanying AIT, which evidenced primary development of autoimmune processes. At the same time, positive
correlating relationship between the level of leptin and BMI and immunoregulatory index of patients with type 2 DM both with AIT and without it was revealed (r = 0.83; р < 0.005; r = 0.77; р < 0.01; r = 0.9; р < 0.001, and r = 0.53; р < 0.05 respectively), which demonstrates autoimmune directivity of immune system disorders in combination with metabolic shifts.

Conclusion. For the purpose of performance of simultaneous correction of metabolic and immunological disorders of patients with type 2 DM, it is necessary to determine immunological indicators (of the CD+- range of lymphocytes). The latter is caused with higher occurrence of AIT with patients with type 2 DM as compared to the general population.

1. Donath M.Y., Ehses J.A., Maedler K. et al. Mechanism of β-cell death in type 2 diabetes. Diabetes 2005;54 Suppl 2:S108–13.

2. Kohn L.D., Wallace B., Schwartz F., McCall K. Is type 2 diabetes an auto-immuneinflammatory disorder of the innate immune system? Endocrinology 2005;146(10):4189–91.

3. Gambelunghe G., Forini F., Laureti S. et al. Increased risk for endocrine autoimmunity in type 2 diabetic patients with GAD65 autoantibodies. Clin Endocrinol (Oxf) 2000;52(5):565–73.

4. Radaideh A.R., Nusier M.K., Amari F.L. et al. Thyroid dysfunction in patients with type 2 diabetes mellitus in Jordan. Saudi Med J 2004;25(8):1046–50.

5. Балаболкин М.И., Клебанова Е.М. Гормоны жировой ткани и их роль в патогенезе сахарного диабета 2-го типа. Лечащий врач 2010;(11):27–33. [Balabolkin M.I., Klebanova E.M. Adipose tissue hormones and their role in pathogenesis of type 2 diabetes mellitus. Lechashchiy Vrach = Attending Physician 2010;(11):27–33. (In Russ.)].

6. Coppack S.W. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc 2001;60(3): 349–56.

7. Анастасій Л.В., Малижев В.О., Карабун П.М. и др. Зв’язок цитокінів з метаболічними проявами цукрового діабету типу 2. Імунологія та алергологія 2002;(1):3–9. [Anastasiy L.V., Malizhev V.O., Karabun P.M. et al. Relationship between cytokines and metabolic effects of type 2 diabetes mellitus. Immunology and Allergology 2002;(1):3–9. (In Russ.)].

8. Быковская С.Н., Насонов Е.Л. Роль дефектов иммуносупрессии в развитии аутоиммунных заболеваний. Научно-практическая ревматология 2005;(4):81–4.

9. [Bykovskaya S.N., Nasonov E.L. The role of immunosuppression defects in development of autoimmune diseases. Nauchnopracticheskaya revmatologiya = Scientific and Practical Rheumatology 2005;(4):81–4. (In Russ.)].

10. Bastard J.P., Maachi M., Van Nhieu J.T. et al. Adipose tissue Il-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab 2002;87(5):2084–9.

11. Durinovic-Bello I. Autoimmune diabetes: the role of T cells, MHC molecules and autoantigens. Autoimmunity 1998;27(3): 159–77.

12. Herder C., Peltonen M., Koenig W. et al. Systemic immune mediators and lifestyle changes in the prevention of type 2 diabetes: results from the Finnish Diabetes Prevention Study. Diabetes 2006;55(8):2340–6.

13. Wang Z.W., Pan W.T., Lee Y. et al. The role of leptin resistance in the lipid abnormalities of ageing. FASEB J 2001;15(1):108–14.

14. Ceriello A., Quagliaro L., Piconi L. et al. Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes 2004;53(3):701–10.

15. Ляшенко А.А. Цитокины и молекулярные основы заболеваний старческого возраста. Клиническая геронтология 2003;9(3):45–54. [Lyashenko A.A. Cytokines and molecular basis of diseases of senior age. Klinicheskaya gerontologiya = Clinical Gerontology 2003;9(3):45–54. (In Russ.)].

16. Терешина Е.В. Возрастная дисфункция жировой ткани. Геронтология и гериатрия 2005;(5):98–101. [Tereshina E.V. Age-related dysfunction of adipose tissue. Gerontology and Geriatrics 2005;(5):98–101. (In Russ.)].

17. Poitout V., Robertson R.P. Minireview: Secondary beta-cell failure in type 2 diabetes – a convergence of glucotoxity and lipotoxity. Endocrinology 2002;143(2):339–42.

18. Bloomgarden Z.T. Developments in diabetes and insulin resistance. Diabetes Care 2006;29(1):161–7.

19. Дедов И.И., Абутова И.А., Шишко П.И. и др. Показатели клеточного и гуморального иммунитета у больных сахарным диабетом на ранних этапах его развития. Проблемы эндокринологии 1993;39(1):3–7. [Dedov I.I., Abutova I.A., Shishko P.I. et al. Indicators of cellular and humoral immunity of patients with diabetes in the early stages of its development. Problems of Endocrinology 1993;39(1):3–7. (In Russ.)].

20. Kohn L.D., Wallace B., Schwartz F., McCall K. Is type 2 diabetes an autoimmuneinflammatory disorder of the innate immune system? Endocrinology 2005;146(10):4189–91.

21. Kolb H., Mandrup-Poulsen T. An immune origin of type 2 diabetes? Diabetologia 2005;48(6):1038–50.

22. Lord G.M., Matarese G., Howard J.K. et al. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 1998;394(6696):897–901.

23. Johnson J.L. Diabetes Control in Thyroid Disease. Diabetes Spectrum 2006;19(3): 148–53.

24. Kasim S., Bessman A. Thyroid autoimmunity in type 2 (non-insulindependent) diabetic patients of Caucasoid, black and Mexican origin. Diabetologia 2004;27(1):59–61.

25. Akbar D.H., Ahmed M.M., Al-Mughales J. Thyroid dysfunction and thyroid autoimmunity in Saudi type 2 diabetics. Acta Diabetol 2006;43(1):14–8.

26. Smithson M.J. Screening for thyroid dysfunction in a community population of diabetic patients. Diabet Med 1998;15(2):148–50.

27. Kasuga A., Maruyama T., Ozawa Y. et al. Antibody to the M(r) 65,000 isoform of glutamic acid decarboxylase are detected in non-insulin-dependent diabetes in Japanese. J Autoimmun 1996;9(1):105–11.

28. Rezzonico J., Rezzonico M., Pusiol E. et al. Introducing the thyroid gland as another victim of the insulin resistance syndrome. Thyroid 2008;18(4):461–4.

29. Gambelunghe G., Forini F., Laureti S. et al. Increased risk for endocrine autoimmunity in Italian type 2 diabetic patients with GAD65 autoantibodies. Clin Endocrinol (Oxf) 2000;52(5):565–73.

30. Celani M.F., Bonati M.E., Stucci N. Prevalence of abnormal thyrotropin concentrations measured by a sensitive assay in patients with type 2 diabetes mellitus. Diabetes Res 1994;27(1):15–25.

31. Badman M.K., Chowdhury T.A. Should thyroid function tests be done annually in all patients with diabetes? Diabetic Med 2002;19 Suppl 3:7–9.