Possibility of a New Therapeutic Strategy for Left Ventricular Dysfunction in Type 2 Diabetes

Abstract

Type 2 diabetes mellitus (T2DM) substantially increases the risk of cardiovascular events, including heart failure (HF), due to complications such as hypertension, obesity and dyslipidemia based on metabolic syndrome, which plays the central pathological role in HF. A reason is that T2DM causes left ventricular (LV) diastolic dysfunction beginning in the early phase of the disease, which in turn increases the risk of development of HF independently of the control of blood glucose levels, blood pressure or the presence of coronary artery diseases. Intracellular metabolic disorders and increased oxidative stress due to hyperglycemia, increased insulin resistance and chronic inflammation are pathogenic mechanisms involved in the LV diastolic dysfunction caused by T2DM. These mechanisms lead to structural changes in the heart such as LV hypertrophy and interstitial fibrosis, resulting in HF. The prevalence of HF with preserved ejection fraction (HFpEF), the major pathology of LV diastolic dysfunction, has been increasing recently, and a high incidence of HFpEF in patients with T2DM was reported. An effective therapy has not been established for HFpEF because multiple comorbidities such as advanced age, hypertension, obesity, dyslipidemia, chronic kidney disease and atrial fibrillation as well as diabetes are involved in its pathology. In the present review, we review the involvement of associated conditions such as hypertension, obesity and advanced age from the aspect of the T2DM and LV diastolic dysfunction and discuss the possibility of the development of a new therapeutic strategy for LV diastolic dysfunction and HFpEF.

Left Ventricular Diastolic Dysfunction in Type 2 Diabetes—Progress and Perspectives

“…Expert reviewers have noted that diabetes is capable of exerting a degree of influence on the pathological mechanisms leading to heart failure which, in its early stage, entails diastolic dysfunction. This relationship may explain why cardiac benefits were acknowledged in diabetic patients treated with novel antihyperglycemic medication such as sodium-glucose cotransporter-2 inhibitors and Glucagon-like peptide-1 receptor agonists [1,24,75,76,77,78,79]. Further studies are being undertaken with regard to maximizing therapeutic outcomes [80].…”

Insulin resistance contribution to pathogenesis of cardiac remodeling in patients with hypertension in combination with obesity and type 2 diabetes

“…Результаты исследования согласуются с данными Mancusi C, et al (2017), которые при проведении многомерного логистического анализа на выборке 8815 пациентов с АГ без распространенных сердечно-сосудистых заболеваний, разделенных по ИМТ, отметили, что ожирение было связано с более высокой распространенностью ГЛЖ в 6,9 раза (95% доверительный интервал 5,84-8,17, р=0,0001), независимо от значимых ассоциаций с женским полом, возрастом, СД, "офисным" САД, антигипертензивным и антиагрегантным лечением [9]. Согласно обзору литературы Sakamoto M, et al (2018) в основе нарушений структуры и функции сердца у больных АГ в сочетании с ожирением и/или СД 2 типа лежат следующие механизмы: хроническое воспаление, окислительный стресс в сердце и кровеносных сосудах, что в свою очередь приводит к повреждению эндотелия сосудов, ГЛЖ и интерстициальному фиброзу [10]. Частота выявления нами КГ ЛЖ была статистически значимо выше уже при присоединении к АГ или ожирения, или СД 2 типа и сопоставима с группой, где АГ сочеталась и с ожирением, и СД 2 типа.…”

“…Внутриклеточные метаболические нарушения и повышенный окислительный стресс из-за гипергликемии, инсулинорезистентности и хронического воспаления являются патогенетическими механизмами, вовлеченными в развитие ремоделирования ЛЖ, вызванного СД 2 типа [10,13]. Эти механизмы приводят к структурным изменениям в сердце, таким как ГЛЖ и интерстициальный фиброз вследствие чего в последующем развивается сердечная недостаточность.…”

Left ventricular diastolic dysfunction in diabetes mellitus and the therapeutic role of exercise training

“…Pharmacologic treatment includes antidiabetic drugs, blood pressure and lipid lowering medication, and metabolic modulators. Among antidiabetic drugs, metformin, thiazolidinedione, glucagon-like peptide, DPP-4, dipeptidyl peptidase and empagliflozin showed to have favorable effects on LV diastolic structure and/or function (49). Diabetes medication, along with diet, aimed at obtaining good glycemic control, is mandatory for all patients.…”

“…Novel medication includes antioxidants and cell-and genetic-based therapies. All these medications have been recently reviewed and are beyond the scope of this article (8,49,51). Exercise training in DM associated LVDD.…”