Studying mechanisms of IR development in different pathologic conditions, including MI, is a relevant issue. According to P J Stubbs et al. (1999), IR in MI patients can help predict adverse disease outcome within 3 years of follow-up [10, 11]. IR manifestation in the early phase of MI is one of the typical body responses to catecholamine stress. In this study, new IR was diagnosed in 77% of MI patients during their hospital stay (Table 1) and was associated with a more severe disease course: higher incidences of large Q-wave MI and in-hospital complications.
In this study, IR was diagnosed using traditional markers, i.e., serum insulin and glucose levels as well as the IR index . Basal and postprandial hyperglycaemia, high postprandial insulin and C-peptide levels in the early recovery phase, and decreased QUICKI index were the markers of IR. The increase in glucose, insulin and C-peptide levels were associated with 2.8-, 3.65- and 2-fold higher risks of IR, respectively (Table 5). This can be regarded as a consequence of pancreatic dysfunction and impaired β-adrenergic glucose metabolism regulation in hepatocytes during catecholamine stress.
IR in MI patients was associated with a cluster of cardiovascular risk factors, including hypertension, obesity and dyslipidaemia, characterised by higher VLDL and TAG levels and lower HDL levels (Table 3). Moreover, IR patients had a sharp rise in plasma FFA, which might be a marker of excess lypolysis activation, impaired energy homeostasis in cardiomyocytes and IR manifestation in MI. This assumption is supported by the results of the logistic regression analysis: among all of the lipid profile markers, only FFA levels were closely associated with IR in MI (Table 5). Higher FFA levels in the acute phase of the disease were associated with a 3-fold increased IR risk. Measuring both FFA and insulin levels in the acute phase led to a better diagnostic value of FFAs, which is logical in terms of pathogenesis. FFAs are able to stimulate insulin secretion in pancreatic beta-cells, decrease insulin hepatic clearance, and impair receptor and postreceptor insulin signalling, which all result in postprandial hyperinsulinaemia and IR progression .
Adipokines, which are the essential regulators of energy metabolism that modulate insulin synthesis and secretion, play an important role in IR pathogenesis [13, 14]. To study the role of adipokine status, we chose markers with different mechanisms of action towards insulin: leptin and resistin are IR mediators and inductors, while adiponectin increases tissue sensitivity to insulin . Low adiponectin levels observed in diabetes, metabolic syndrome and coronary artery disease can lead to IR .
The study results showed the increased adipokine levels, which intensified IR (Table 4). High leptin and resistin levels were accompanied by a higher IR index during the entire hospital stay. Leptin in supraphysiological doses in vitro is known to block insulin interaction with its receptor on the cell membrane, which is associated with impaired insulin-mediated glucose transport, hyperglycaemia and more severe IR [15, 16]. Additionally, according to Opie et. al. (2008), high leptin levels intensify FFA oxidation and lead to diacylglyceride build-up, which, in turn, induces IR . Another adipokine, resistin, is an antagonist of insulin . Resistin inhibits insulin-mediated glucose uptake by the target tissues and decreases FFA consumption and their metabolism in the skeletal muscles through the activation of AMP-activated protein kinase . Generally, the increase in the above-mentioned adipokine levels can have a negative effect on insulin production, secretion and cell signalling, which may induce IR in MI.
Unlike leptin and resistin, the protective effects of adiponectin decreased during the hospital stay, especially in IR patients. Adiponectin is known to neutralise the lipotoxic effect of FFA, inducing endothelial dysfunction and IR . The decrease in adiponectin levels is likely to promote FFA lipotoxic effect, which certainly contributes to IR development and progression. This assumption is supported by the results of a correlation analysis showing a negative correlation between FFA and adiponectin levels.
The role of ghrelin, a gastrointestinal endocrine peptide and an important regulator of growth factor secretion, desire for food and energy homeostasis, in IR pathogenesis has been actively discussed recently [7, 21, 22]. It was found that cardiomyocytes are able to produce ghrelin, which has diverse protective effects, including the inhibition of cardiomyocyte and endothelial cell apoptosis and improved left ventricular function in ischaemia/reperfusion .
Ghrelin is known to modulate insulin secretion and, therefore, is regarded as a promising molecular IR marker. Ghrelin was shown to contribute to the expression of α- and β-insulin receptor subunits. At the same time, 1–10 nm/L of insulin inhibit basal and noradrenaline-stimulated ghrelin secretion but do not influence ghrelin mRNA expression . Obese children have lower ghrelin levels that those with normal metabolism; at the same time, ghrelin had a strong positive correlation with the HOMA-IR index irrespective of anthropometric and metabolic parameters of IR syndrome . Additionally, in diabetic patients, metformin therapy, which improves tissue sensitivity to insulin, was accompanied by higher ghrelin levels [26–28]. In this study, ghrelin levels were significantly decreased in MI patients during the entire hospital stay; in patients with IR, the changes were more pronounced. Previously, it was shown that MI patients have decreased ghrelin levels, which, in the authors’ opinion, is due to an enhanced binding of ghrelin with its receptor in ischaemia/reperfusion . We suggest that in MI, the inhibition of ghrelin secretion may also be due to the imbalance in the adipokine system accompanied by the dysfunction of insulin-secreting pancreatic cells, impaired lipid metabolism and IR manifestation. Our assumption is supported by the results of experimental studies that demonstrate the antagonistic relationship between leptin and ghrelin [30, 31] and the ability of high FFA levels to block ghrelin secretion  as well as by the result of a correlation analysis showing the negative correlation between leptin and ghrelin and between insulin and FFA in MI patients. Additionally, the ghrelin level appears to be a more informative IR marker than traditional markers and adipokine status parameters in both the acute and recovery MI phases (Table 5). Ghrelin, as a marker of IR in MI, has high diagnostic sensitivity and specificity (82-87%). Ghrelin has a better diagnostic value than insulin in the acute MI phase, and assessing both ghrelin and FFA levels increased the diagnostic significance of the latter with regard to IR.