Simultaneous pancreas–kidney transplantation (SPKT) can improve long-term patient survival and restore endogenous insulin secretion in recipients with type 1 diabetes (T1D). There are currently few data on glucose fluctuations assessed by continuous glucose monitoring (CGM) after SPKT. Aim: to evaluate CGM-derived time in range (TIR) and glucose variability (GV) in patients with T1D and functioning pancreatic grafts after SPKT. Fifty-four CGM recordings from 43 patients, 15 men and 28 women, aged 34 (31; 39) years were analyzed. Time since SKPT was up to 1 year (group 1, n = 13), from 1 to 5 years (group 2, n = 15), and from 5 to 12 years (group 3, n = 26). TIR (3.9–10 mmol/L), Time Above Range (TAR), Time Below Range (TBR), and GV parameters were estimated. There were no differences in mean glucose (5.5 [5.1; 6.2], 5.9 [5.4; 6.2], and 5.9 [5.6; 6.7] mmol/L), TIR (97.6 [92.8–99.1], 97.2 [93.2; 99.1], and 97.5 [93.4; 99]%); TAR (0, 1.8 [1.3; 3.7], and 2.5 [2; 5]%), TBR (5 [3.3; 12.7], 4.1 [2.2; 10.1], and 3.5 [1.3; 6.5]%) and GV parameters between three groups (all p > 0.05). Thus, recipients with functioning pancreatic grafts demonstrate remarkably high TIR and low GV after SPKT.
The study of diabetes mellitus (DM), its complications and related pathologies has been continuously performed for many years; however, despite the substantial work and outstanding achievements in studying the mechanisms of DM development and the success of new medicinal products for controlling glycaemia, the problems associated with the late complications of DM continue to increase. The importance of glycaemic control in the early stages of DM for the development of complications is seen only after a sufficiently long period of observation. Such a delayed effect of primary good or unsatisfactory metabolic control, which shapes the patients clinical fate to a greater extent, is termed metabolic memory. The disorders developed under the influence of hyperglycaemia persist for long periods after the normalisation of carbohydrate metabolism; moreover, the effect of previous hyperglycaemia extends over the next 20 and even 30 years. Current research is focused on the possible mechanisms of metabolic memory development, including oxidative stress, advanced glycation end products and epigenetic mechanisms. This research will provide insight into potential markers for the early development and progression of vascular complications and new therapeutic possibilities for the future. However, determining the probable point of no return is more important, which implies that a point exists; after this point is crossed, the progression of vascular complications associated with DM cannot be prevented or reversed. The results of numerous experimental studies demonstrate that the prerequisite components of metabolic memory can be used as potential markers of the progression of DM complications, and may be potential therapeutic targets.
Diabetes mellitus (DM) and chronic kidney disease are the diseases that have exceeded epidemic thresholds in terms of prevalence all over the world. That made it possible to classify them as non-communicable epidemics of the XXI century. Diabetic nephropathy (DN) is implicated with high levels of disablement and mortality. Advanced glycation end products (AGE) play a key role in the progression of DN. Increased formation of AGE occurs due to hyperglycemia under the conditions of diabetes. Moreover, there are additional factors in DN that increase the elaboration of AGE, such as high levels of oxidative stress and decreased renal clearance which slows down the AGE excretion. Both immediate effects of AGE and interaction of AGE with its cell-bound receptor (RAGE) result in a сascade of events that lead to further progression of DN. Thus, the research of the new therapeutic approaches targeted on the AGE-RAGE system is of great interest to slow progression of DN and improve the prognosis.
Diabetes mellitus type 2 (DM2) is socially important disease, becoming non-infectious epidemic due to increasing prevalence. Chronic kidney disease (CKD) is one of the most common diabetic complications. Kidney injury signs and/or estimated glomerular filtration rate (eGFR) decrease are seen in 40-50% of patients with DM2. Three groups of factors are considered to be the basis of CKD development and progression in DM2: metabolic, hemodynamic, inflammation and fibrosis. Existing drugs that are used in patients with CKD and DM2 first of all target hemodynamic and metabolic disturbances, but their action against inflammation and fibrosis is indirect. Hyperactivation of mineralocorticoid receptors (MR) is considered as one of the main trigger factors of end-organ damage in patients with DM2 due to inflammation and fibrosis. Development of selective nonsteroidal MR antagonists (MRA) as a new class of medications is directed to demonstrate positive effects from blocking this pathophysiological pathway of CKD development and overcome the steroidal MRAs’ shortcomings. Hence pathophysiological hyperactivation of MR with subsequent inflammation and fibrosis in patients with CKD in DM2 is considered a promising therapeutic target for the new drugs with cardionephroprotective effect.