Correction of Insulin Resistance in Obese Patients With Myocardial Infarction and Comorbid Metabolic Syndrome

Abstract

Objective. Insulin resistance (IR) is playing an essential role in the development of cardiovascular disease and has an adverse prognostic effect on the course of acute myocardial infarction (AMI) as a result of direct proatherogenic effects of IR and an adverse effect on myocardial contractility. The aim of the study was to evaluate the insulin resistance effects of multimodality therapy with dapagliflozin (Forxiga) and L-arginine/L-carnitine combination in overweight and obese patients with myocardial infarction.
 The aim of the study: to evaluate the insulin resistance effects of multimodality therapy with dapagliflozin (Forxiga) and L-arginine/L-carnitine combination in overweight and obese patients with myocardial infarction.
 Methods. The study enrolled 85 males with acute myocardial infarction with ST segment elevation; among these, there were 24 overweight patients (BMI within 25–29.9 kg/m2) and 36 patients with obesity (BMI >30 kg/m2). Normal body weight (BMI within 18–24.9 kg/m2) was documented in 25 study patients. The age of study subjects in the groups was 58.62±7.02 years on average. All patients were receiving standard of care treatment according to the protocols of the MoH of Ukraine [8]. Depending on the treatment program used, all patients were divided into three groups: Group 1 enrolled 25 patients who were receiving standard of care per-protocol treatment; Group 2 (test group) enrolled 28 patients where standard of care per-protocol treatment of MI was appended with L-arginine/L-carnitine combination (“TIVOR-L” by Yuria-Pharm Ltd.; marketing authorization No. UA/15067/01/01) as intravenous infusions for seven days at 100.0 ml once a day; Group 3 (test group) enrolled 32 patients who received dapagliflozin (10 mg/day) in addition to combination therapy (per-protocol treatment + L-arginine/L-carnitine combination). Control group enrolled 20 virtually healthy volunteers without cardiovascular disease.
 The presence of IR was assessed using HOMA-IR index. The severity of IR was determined based on the magnitude of the IR factor according to F. Caro. The patients were considered to have IR if the following criteria were met: HOMA > 2.77 and Caro index < 0.33; i.e. the higher the HOMA index and the lower the Caro index, the lower was the tissue sensitivity to insulin and the greater was the IR.
 Statistical analysis of study findings was performed using Statistica 10.0 package of statistical software and Microsoft Excel 2019.
 Results. Overweight and obese patients with MI + MS develop carbohydrate metabolism disorders, which are manifested by hyperglycemia, increased HOMA index and decreased Caro index. Insulin resistance is the main cause of the above disorders. The severity of insulin resistance was increasing in the presence of excessive body and obesity, as suggested by a significant reduction in Caro index. It is the presence of IR and carbohydrate metabolism disorders that contributed to the development of systolic-diastolic dysfunction of the myocardium in patients with ACS (MI).
 Conclusions. At baseline, overweight and obese patients with myocardial infarction develop a pronounced insulin resistance with carbohydrate metabolism disorders and reduced systolic-diastolic function of the heart. Multi-modality treatment with inclusion of L-carnitine/L-arginine combination and dapagliflozin in overweight and obese patients with myocardial infarction facilitated restoration of tissue sensitivity to insulin and improved carbohydrate metabolism and systolic-diastolic function of the heart in such comorbid patients.

The Effectiveness of L-arginine in Clinical Conditions Associated with Hypoxia

“…Improved myocardial infarction protocol treatment in therapy of cardiovascular diseases [38] Subjects with early diabetes forms; arginine, ornithine, and citrulline level Dipeptidylpeptidase-4 inhibitor linagliptin effects in subjects with coronary artery disease No significant improvements in the arginine bioavailability ratios [39] Review [45]…”

“…It is also responsible for such anti-inflammatory effects as the inhibition of the expression of cellular adhesion molecules [53]. Potential indications for the clinical use of L-arginine include spontaneous hypertension [27], pregnancy-induced hypertension [18,29,31], pulmonary hypertension [26,30,31], lower limb arteriosclerosis [32], Raynaud's phenomenon [34], hypercholesterolaemia [36,37], stable ischaemic heart disease [38], endothelial function [40,41], circulatory insufficiency in loss-and gain-of-function models for eNOS in Cre-induced gene inactivation [54], regulation of blood pressure and microcirculation [42], glaucoma [41], diabetes mellitus [39,42], aerobic training in chronic heart failure [45], chronic renal failure [55], prevention of coronary artery restenosis [49], and prevention of stroke and thrombotic vascular incidents [56].…”

The effectiveness of the physical therapy program for patients with metabolic syndrome based on the study of the dynamics of the functional state of the autonomic nervous system and hemodynamic parameters

“…According to statistics, more than half of the adult population of Ukraine is obese -20,4% of women and 11% of men (Virstiuk et al, 2020). Shved et al (2023) note that the problem of metabolic syndrome and type 2 diabetes mellitus in Ukraine is quite high and amounts to about 20% in the general population and more than 50% in certain social groups (physical inactivity, fast food lovers, smokers, etc.). At the same time, we note that according to the International Diabetes Federation (IDF), in people with metabolic syndrome, the total risk of developing MI in the next 8 years is 30%, mortality from coronary heart disease was 3 times higher and twice the mortality rate compared to patients without metabolic disorders.…”

“…Already, the following statistics can be observed: about 85 thousand people suffer from type 1 diabetes in Ukraine, and the rest (90%) are diagnosed with type 2 diabetes (Yuliya, K., & Sergey, K. 2018). According to the International Diabetes Federation, the prevalence of type 2 diabetes in 2019 is estimated at 9,3% (463 million), by 2030 it will grow to 10,2% (578 million), and in 2045 it will be 10,9% (700 million) (Shved et al, 2023).…”