Vascular complications of diabetes mellitus worldwide and in Russia: The path of 100 years. A review

With the discovery and introduction of insulin, the "palette" of life-threatening conditions for patients with diabetes mellitus has changed dramatically: from diabetic coma of the "pre-insulin era" to severe vascular complications in the modern period. The key risk factors for diabetic angiopathies in diabetes mellitus are poor glycemic control in combination with a long course of the disease. Over the past 30 years, there has been a downward trend in the incidence of late vascular complications of diabetes both worldwide and in Russia. In particular, the frequency of cardiovascular events (myocardial infarctions, strokes, amputations) decreased, and the incidence of several other complications, such as diabetic retinopathy and neuropathy, stabilized. However, the incidence of chronic kidney disease and chronic heart failure is still increasing. The Joslin Medal, awarded to patients over 50, 75 and even 80 years of life with diabetes, reflects success in the fight against this disease

Сhronic kidney disease complications in patients with type 1 diabetes mellitus after simultaneous pancreas-kidney transplantation – potential role of oxidative stress and glycation end products

BACKGROUND: Normoglycaemia in patients with diabetes mellitus type 1 (T1DM) after simultaneous pancreas-kidney transplantation (SPKT) is very interesting in regards to chronic kidney disease (CKD) complications dynamics depending of posttransplantation period and possible targets of potential treatment from the point of view “metabolic memory” AIM: To evaluate the relationship between oxidative stress indicators and advanced glycation end products and complications of end-stage renal disease (ESRD) in patients with T1DM аnd a long-term history of diabetes decompensation, who reached stable euglycemia after SPKT. MATERIALS AND METHODS: The study included 20 patients with compensation of carbohydrate metabolism after SPKT performed from November 2011 to September 2018. Assessment included examination of complications of ESRD (arterial hypertension, dyslipidemia, anemia, mineral and bone disorder) and analysis of "metabolic memory" markers: 3-nitrothyrosine (3-NT), superoxide dismutase (SOD), advanced glycation end products (AGE) and AGE receptor (RAGE). We performed follow-up examination of patients included in the early postoperative period (1st day/week) in 6-12 months after SPKT. RESULTS: All patients with DM1 duration for 22 [19; 28] years, diabetic nephropathy (DN) 8 [6; 14] years and duration of renal replacement therapy (dialysis) for 3 [1.5; 4] years reached euglycemia (HbA1c 5,5 [5,1; 5,8] %; С-peptide 3,2 [2,45; 3,63] ng/ml) after 6 month of surgical treatment. Despite of stable graft function (estimated glomerular filtration rate (eGFR) CKD-EPI 84 [69; 95] ml/min/1.73m2) 35% of patients still needed antihypertensive therapy, 40% needed treatment with recombinant human erythropoietin (RHuEPO) and 15% – ferrotherapy. With vitamin D deficiency, observed in 80% of cases (13.3 [9.3; 18.5] ng/ml), 55% of patients had secondary hyperparathyroidism, 45% – osteoporosis. The results of the correlation analysis revealed the association of the state of ESRD target organs with the studied "metabolic memory" markers: oxidative stress and AGE-RAGE system. CONCLUSIONS: SPKT as the way to achieve compensation of carbohydrate metabolism and uremia does not provide regress of diabetes and complications of ESRD. Analysis of "metabolic memory" markers indicate their direct contribution to the persistence of metabolic consequences of diabetic nephropathy (DN). Found trends need more long-lasting observation and enlargement of study groups

Diabetes mellitus type 2 in adults

Public organization “Russian Association of Endocrinologists”. Clinical guidelines.&nbsp

Diabetes mellitus type 1 in adults

Public organization “Russian Association of Endocrinologists”. Clinical guidlines

Continuous Glucose Monitoring in Patients Following Simultaneous Pancreas–Kidney Transplantation: Time in Range and Glucose Variability

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

CCCP increases the SkQ-induced efflux of carboxyfluorescein from liposomes.

<p>Carboxyfluorescein (CF) efflux from DPhPC (diphytanoylphosphatidylcholine) liposomes (50 µg/ml), induced by 2.5 µM SkQ1 (panel A) or by 0.5 µM SkQR1 (panel B) was measured with or without CCCP. The efflux was accompanied by an increase in CF fluorescence due to dilution and a relief of CF self-quenching. In panel B, the CF efflux was measured 400 s after the addition of SkQR1. Incubation mixture, 10 mM Tris, 10 mM MES, 100 mM KCl, pH 7.</p

SkQ1 (10-(6-plastoquinonyl)decyl triphenylphosphonium) affects absorption spectra of CCCP in the presence of liposomes.

<p>Incubation mixture: 4 µM CCCP, 1 mM Tris, 1 mM MES, pH = 7.4, containing DPhPC (diphytanoylphosphatidylcholine) liposomes (20 µg/ml) in the absence (curve 1) and in the presence of 1 µM, 2 µM, 4 µM and 9 µM SkQ1 (panel A, curves 2–5, respectively) or in the presence of 1 µM, 2 µM, 4 µM and 9 µM SkQR4 (panel B, curves 2–5, respectively). Insert to panel B shows the dependence of λ_max on the concentration of the SkQ derivatives.</p

Comparison of SkQ1 and C₁₂TPP effects on the uncoupling activity of DNP and FCCP.

<p>Effects of 2 µM SkQ1, 2 µM C₁₂TPP or 200 µM TPP on the dependence of mitochondrial membrane potential on the concentration of DNP (panel A) or FCCP (panel B). The experiments were conducted in a way shown in Fig. 6. Shown are Mean±S.E. of 4–6 experiments.</p

C₁₂TPP enlarges the FCCP- and DNP-induced increase in respiration rates of intact yeast cells.

<p>The ordinate represents the ratio of the oxygen consumption rates after (V) and before (V₀) the addition of an uncoupler. (A) FCCP-mediated stimulation of yeast respiration in the absence (solid line) and in the presence (dotted line) of 1 µM C₁₂TPP. (B) DNP stimulation of yeast respiration in the absence (solid line) and in the presence of 0.5 µM (dotted line) or 1 µM (dot and dash line) C₁₂TPP. In the absence of the anionic uncoupler, C₁₂TPP did not increase the rate of oxygen consumption at concentrations below 2 µM (insert). Shown are Mean±S.E. of 4 experiments.</p

C₁₂R4 (rhodamine B dodecyl ester) strongly increases CCCP- (panel A) or DNP-mediated (panel B) electric current through bilayer lipid membrane (BLM).

<p>Where indicated, 0.1 µM CCCP or 1 µM DNP were added to both compartments prior to the measurements; incubation mixture, 0.1 M KCl, 10 mM Tris, 10 mM MES, pH 7.0; at t = 1.5 s, 100 mV voltage was applied to the BLM. Concentration of C₁₂R4 was 0.1 µM.</p