Type 2 diabetes mellitus characterized by chronic hyperglycaemia is caused by insulin resistance and β-cell dysfunction. Glycogen accumulation, due to impaired metabolism, contributes to this "glucotoxicity" via dysregulated biochemical pathways promoting β-cell dysfunction. Thus, long-term exposition of insulin-secreted cells or isolated islets together with increased free fatty acids (FFA) and glucose levels can cause insulin-induced glucose secretion depression, damage to insulin gene expression and apoptotic death of cells. It is known that, the main regulator of pancreatic β-cells functioning and regulator of insulin gene expression, synthesis and secretion of insulin is glucose. Glucose enters cells and progressively metabolizes, in particular, to pyruvate in a cycle of tricarboxylic acids, subjected to oxidative phosphorylation, during which formed adenosine triphosphate and reactive oxygen radicals (ROS). Although, when more glucose enters the cell, there are other ways in which extra glucose can be transferred to reserve and of the glucose molecules can form ROS. The release of excessive amounts of FFA leads to lipotoxicity, as lipids and metabolites produce ROS in the endoplasmic reticulum and mitochondria. This affects both adipose and non-fat tissue, making up its pathophysiology in many organs. This overview demonstrates that the insulin gene is expressed in pancreatic β-cells. Glucose is the main physiological regulator of insulin gene expression. It controls the effect of transcription factors, insulin mRNA stability, and transcription rate. Glucolipotoxicity mechanisms affect the transcription factors MafA and PDX-1. Important is the β-cells damaging, which is connected with the oxidative stress and the synthesis of ceramides.

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The prevalence of comorbidities has been growing for the last decades. Therefore, the detection of biomarkers for diagnostic and prognostic purposes is of great practical importance. The aim of this study was to assess the biomarkers of osteo-defficiency in the course of secondary osteoporosis in patients with comorbid chronic pancreatitis and arterial hypertension. We examined 110 patients with chronic pancreatitis: 70 of them had comorbid hypertension, and 40 patients were found as having no comorbidities. The age of patients ranged from 33.2 ± 2.1 (main group) and 32.9 ± 3.1 years (comparison group); women predominated (72.9% and 70%, respectively). The control group includes 78 healthy individuals of the same age and sex. Diagnostic investigation included studying clinical and anamnestic characteristics of patients (duration of the disease, manifestations of the course, frequency of recrudescence, fractures) and biochemical parameters of bone metabolism: osteocalcin, total bone phosphatase and tartrate-resistant acid phosphatase and the establishment of correlations between these parameters and incidence of complications. It was found that in the isolated course of chronic pancreatitis there is a high (R = 0.60) statistically significant (p <0.01) correlation between the levels of osteocalcin and pancreatic elastase-1. A negative statistically significant (p <0.01) mean correlation (R = -0.49) was found between the content of tartrate-resistant acid phosphatase and age of the patients having comorbidity of chronic pancreatitis and hypertension, as well as there is a moderate correlation between the content of tartrate-resistant acid phosphatase and the duration of hypertension, which is statistically significant (R = 0.36, p <0.01). The levels of total bone phosphatase and tartrate-resistant acid phosphatase in the main group exceeded the reference values in 2.5 and 1.9 times respectively (CMU; U = 866.0; p <0.01), while in the comparison group were 2 times (total bone phosphatase) and 1.3 times higher (tartrate-resistant acid phosphatase) times, respectively (CMU; U = 821.0; p <0.01) that enables to diagnose the development of osteopenic conditions. That is, the combined course of chronic pancreatitis and hypertension should be considered as unfavourable tandem in the development of secondary osteoporosis and requires early osteoporotic screening.