Analysis of the condition of the kallikrein-kinin system in the comorbid course of chronic pancreatitis and type 2 diabetes

Abstract

Background. According to evidence, within approximately 8 years, 50% of patients with chronic pancreatitis (CP) develop endocrine and exocrine insufficiency, which manifests itself as steatorrhea, weight loss, diabetes mellitus (DM), and nutritional disorders. Diabetes mellitus aggravates these phenomena, which deepens the disorder of metabolic processes in CP, including protein metabolism. Protein structures include components of the kallikrein-kinin system (KKS), which plays a role in the regulation of vascular tone, diuresis, inflammation, coagulation, and pain reception. Due to repeated exacerbations of pancreatitis, there is fibrosis of the pancreas, which increases the risk of insulin resistance and the formation of type 2 diabetes. Thus, disorders of the kallikrein-kinin system and the progression of CP are interrelated, which makes it important to study the state of KKS in CP, especially in combination with type 2 diabetes mellitus. The purpose is to investigate the state of the kallikrein-kinin system in chronic pancreatitis in outpatients, depending on the presence of concomitant type 2 diabetes. Material and methods. 137 outpatients with CP with concomitant diabetes mellitus and without diabetes were studied: the main group— 112 patients with CP without exacerbation in combination with diabetes mellitus in a state of complete or subcompensation, and the comparison group— 25 patients with isolated CP. Evaluation of general and specific proteolysis (α1-proteinase inhibitor, α2-macroglobulin, kallikrein, kininase II activity, prekallikrein, plasma proteolytic activity) was performed by the method analysis using standard kits from BIOSERV ELISA. Results. There was a 20.8% increase in the level of the total proteolytic activity of plasma in the group of patients with comorbidity of CP and diabetes mellitus compared with the group with isolated CP, 51.9% increase in specific proteolysis (or kininogenesis)— the level of kallikrein (proteolysis enzyme), p<0.05. At the same time, a decrease in prekallikrein (inactive precursor of kallikrein) was found in the group of patients with comorbidity by 19.4% compared to that in isolated CP (p < 0.05). The presence of dissociation of protective parameters of kallikrein-kinin system is proved; increase by 9.4% of α1-proteinase inhibitor content at comorbidity of CP and DM2 in relation to that in isolated CP; decrease in the content of α2-macroglobulin in CP relative to the control group (p<0.05), which showed a decrease in the body’s compensatory capacity in CP, at the same time found an increase in α2-macroglobulin in the comorbidity of CP with DM2 by 49.5% relative to isolated CP; reduction of kininase-II activity in CP and diabetes mellitus by 14.5% relative to that in CP. Conclusions. Activation of KKS with multidirectional changes in KKS parameters and general and specific proteolysis in CP was noted. In CP and in the comorbid course with diabetes mellitus, further activation of proteolysis took place with the simultaneous inclusion of protective mechanisms for resolving inflammation and detoxification. Excessive production of kinins in concomitant DM2 has been proven, which weakened the body’s protective response.