Patients with type 2 diabetes mellitus (DM) may develop cardiomyopathy independently of such risk factors as arterial hypertension and coronary heart disease. Myocardial dysfunction in diabetes mellitus may vary from subclinical forms of left ventricular dysfunction to heart failure. It was suggested that diastolic left ventricular dysfunction is one of the earliest signs of myocardial injury in diabetes mellitus and plays a key role in the formation of diabetic cardiomyopathy.
The aim of our study was to evaluate the effect of diabetes on the clinical and laboratory status of women with hypertension, obesity, and left ventricular diastolic dysfunction (LVDD).
Materials and methods. We examined 80 patients aged 40 to 60 years with stage 2, grade II and grade III hypertension, class I–III obesity, grade 1 LVDD and preserved ejection fraction. Depending on the presence or absence of diabetes, the cohort of patients was divided into two groups: patients with diabetes were assigned to group 1 and non-diabetes patients – to group 2. Statistical processing was performed using Statistica for Windows version 6.0.
Results. Patients had tendency to increased body mass index (BMI) in the DM group, but without significant differences. The results of the 6-minute walk test showed a tendency to decreased distance in the group of patients with diabetes. There was an increase in leptin levels and a decrease in adiponectin in patients with diabetes without significant differences. Levels of IL-6, glycosylated hemoglobin, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index were significantly higher in the cohort of patients with diabetes (p <0.05).
Conclusions. Women aged 40–60 years with LVDD with hypertension, class I–III obesity and type 2 diabetes mellitus differ from similar cohorts of patients without diabetes with a tendency to increased BMI levels, leptinemia, and decrease in distance of 6-minute walk test, LV ejection fraction and blood adiponectin level; they have significantly higher blood levels of interleukin-6, glycosylated hemoglobin (HbA1c) and HOMA-IR; indicators of diastolic function in the group of patients with diabetes tend to worsen the parameters of diastolic filling of the LV even in grade 1 DD.
2. Kane GC, Karon BL, Mahoney DW, et al. Progression of left ventricular diastolic dysfunction and risk of heart failure. JAMA. 2011;306:856–63. doi: 10.1001/jama.2011.1201.
3. Fontes-Carvalho, R, Ladeiras-Lopes, R, Bettencourt, P, et al. (2015). Diastolic dysfunction in the diabetic continuum: association with insulin resistance, metabolic syndrome and type 2 diabetes. Cardiovascular Diabetology, 14(1), 4. doi:10.1186/s12933-014-0168-x
4. Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010;56:1113–32. doi: 10.1016/j.jacc.2010.05.034
5. Seo JM, Park TH, Lee DY, et al. Subclinical Myocardial Dysfunction in Metabolic Syndrome Patients without Hypertension. J Cardiovasc Ultrasound. 2011;19:134–9. doi: 10.4250/jcu.2011.19.3.134
6. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal, Volume 34, Issue 28, 21 July 2013, Pages 2159–2219. doi.org/10.1093/eurheartj/ehy339
7. Kovalenko VM, Sychov OS, Dolzhenko MM ta in. Rekomendatsii z ekhokardiohrafichnoi otsinky diastolichnoi funktsii livoho shlunochka [Amosov Institute]. Режим доступу: http://amosovinstitute.org.ua/wp-content/uploads/2018/11/Rekomendatsiyi-diastola.pdf.
8. Nagueh SF, Smiseth OA, Appleton CP et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: An update from the American society of echocardiography and the European association of cardiovascular imaging. J Am Soc Echocardiogr. 2016. N 4, P. 277-314. doi: 10.1016/j.echo.2016.01.011.
9. Dinh W, Lankisch M, Nickl W, et al. Insulin resistance and glycemic abnormalities are associated with deterioration of left ventricular diastolic function: a cross-sectional study. Cardiovasc Diabetol. 2010;9:63. doi: 10.1186/1475-2840-9-63
10. Utsunomiya H, Yamamoto H, Kunita E, et. al. Insulin resistance and subclinical abnormalities of global and regional left ventricular function in patients with aortic valve sclerosis. Cardiovasc Diabetol. 2014;13:86. doi: 10.1186/1475-2840-13-86
11. Bajraktari G, Koltai MS, Ademaj F, et al. Relationship between insulin resistance and left ventricular diastolic dysfunction in patients with impaired glucose tolerance and type 2 diabetes. Int J Cardiol. 2006; 110:206–11. doi: 10.1016/j.ijcard.2005.08.033
12. Abel ED, O'Shea KM, Ramasamy R. Insulin resistance: metabolic mechanisms and consequences in the heart. Arterioscler Thromb Vasc Biol. 2012;32:2068–76. 10.1161/ATVBAHA.111.241984
13. Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation. 2007;115:3213–23. doi: 10.1161/CIRCULATIONAHA.106.679597
14. Peterson LR, Herrero P, Schechtman KB, et al. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation. 2004;109:2191–6. doi: 10.1161/01.CIR.0000127959.28627.F8
15. Stratmann B, Tschoepe D. Heart in diabetes: not only a macrovascular disease. Diabetes Care. 2011;34 Suppl 2:S138–44. doi: 10.2337/dc11-s208
16. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114:597–605. doi: 10.1161/CIRCULATIONAHA.106.621854
17. Banerjee D, Biggs ML, Mercer L, et al. Insulin resistance and risk of incident heart failure: Cardiovascular Health Study. Circ Heart Fail. 2013;6:364–70. doi: 10.1161/CIRCHEARTFAILURE.112.000022
18. Vardeny O, Gupta DK, Claggett B, et al. Insulin resistance and incident heart failure the ARIC study (Atherosclerosis Risk in Communities). JACC Heart Fail. 2013;1:531–6. doi: 10.1016/j.jchf.2013.07.006
19. Russo C, Jin Z, Homma S, et al. Effect of obesity and overweight on left ventricular diastolic function: a communitybased study in an elderly cohort. J Am Coll Cardiol. 2011;57:1368–74. doi: 10.1016/j.jacc.2010.10.042.
20. Canepa M, Strait JB, Abramov D, et al. Contribution of central adiposity to left ventricular diastolic function (from the Baltimore Longitudinal Study of Aging). Am J Cardiol. 2012;109:1171–8. doi: 10.1016/j.amjcard.2011.11.054
21. Canepa M, Strait JB, Milaneschi Y, et al. The relationship between visceral adiposity and left ventricular diastolic function: Results from the Baltimore Longitudinal Study of Aging. Nutr Metab Cardiovasc Dis. 2013;23:1263–70. doi: 10.1016/j.numecd.2013.04.003
22. Ingelsson E, Sundstrom J, Arnlov J, et al. Insulin resistance and risk of congestive heart failure. JAMA. 2005;294:334–41. doi: 10.1001/jama.294.3.334
23. Horwich TB, Fonarow GC. Glucose, obesity, metabolic syndrome, and diabetes relevance to incidence of heart failure. J Am Coll Cardiol. 2010;55:283–93. doi: 10.1016/j.jacc.2009.07.029.
24. Qu D, Liu J, Lau CW, Huang Y (2014). IL-6 in diabetes and cardiovascular complications. British Journal of Pharmacology, 171(15), 3595–3603. doi:10.1111/bph.12713.
25. Rehman K, Akash MSH., Liaqat A, et al. (2017). Role of Interleukin-6 in Development of Insulin Resistance and Type 2 Diabetes Mellitus. Critical Reviews in Eukaryotic Gene Expression, 27(3), 229–236. doi:10.1615/critreveukaryotgeneexpr.2017019712
26. Akbari, M, Hassan-Zadeh V (2018). IL-6 signalling pathways and the development of type 2 diabetes. Inflammopharmacology, 26(3), 685–698. doi:10.1007/s10787-018-0458-0
27. Nazari A, Sardoo AM, Fard ET, et al. (2017) Is IL-6 Increased in Type 2 Diabetes Mellitus Patients Independent of Nephropathic Complication? J Endocrinol Diabetes Obes 5(2): 1102.
28. Spranger J, Kroke A, Mohlig M, et al. (2003). Inflammatory Cytokines and the Risk to Develop Type 2 Diabetes: Results of the Prospective Population-Based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes, 52(3), 812–817. doi:10.2337/diabetes.52.3.812
29. Wang Y, van Boxel-Dezaire AHH, Cheon H, Yang J, Stark GR (2013). STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor. Proceedings of the National Academy of Sciences, 110(42), 16975–16980. doi:10.1073/pnas.1315862110
30. Lowe G, Woodward M, Hillis G, et al. (2013). Circulating Inflammatory Markers and the Risk of Vascular Complications and Mortality in People With Type 2 Diabetes and Cardiovascular Disease or Risk Factors: The ADVANCE Study. Diabetes, 63(3), 1115–1123. doi:10.2337/db12-1625
31. Pradhan, A. D. (2001). C-Reactive Protein, Interleukin 6, and Risk of Developing Type 2 Diabetes Mellitus. JAMA, 286(3), 327. doi:10.1001/jama.286.3.327