Abstracts of oral and poster presentations from the 5th Cardiovascular Outcome Trial (CVOT) Summit 2021, Munich, Germany, 18 – 19 November 2021.

Oral Presentations

OP 1: Healthy China program – early ­diabetic kidney disease screening

Gu WJ, Ma JH, Hong TP, Li XY, Shi LX, Wang YG, Xue YM, Yu XF, Zhu DL, Mu YM; Beijing, China

Background: To improve the prevention and treatment of diabetic kidney disease (DKD) in China, the Beijing Great Physician Commonweal Foundation launched the "Healthy China Program – Early Diabetic Kidney Disease Screening" in 2019. This project aims to evaluate the prevalence, awareness, and screening rate of albuminuria in adult type 2 diabetes mellitus (T2DM) patients in China.

Methods: Patients were eligible for inclusion in the study if they 1) had T2DM, 2) were 18 years old or older, and 3) received antidiabetic medication. Pregnant women with T2DM were excluded. A total of 50 general hospitals in 8 provinces were selected. 10 000 T2DM patients will be included in the database in 2021 – 2022. This database of T2DM patients includes basic information and biochemical blood results. The cohort will be followed up for 6 months.

The database includes two parts: demographic characteristics and laboratory measurements. A standard questionnaire was used in part one. In part two, routine blood and urine tests, HbA1c, fasting blood glucose, fasting C-peptide, fasting insulin, blood electrolytes, high sensitivity CRP (hsCRP), blood lipids, liver, kidney, and thyroid function were measured. All data were recorded at baseline and at 6-month follow-up.

Descriptive statistics are used to describe the weighted sample characteristics and the prevalence of albuminuria. The association between the prevalence of albuminuria and risk factors is performed using the chi square test. The statistical significance of differences is estimated by Student’s t-test and one-way ANOVA.

Results:This database will provide the following information: First, the changes in albuminuria and renal outcome in patients with T2DM; second, the relationship between albuminuria and other variables. The aim of this analysis is to identify clinical risk factors associated with the development of albuminuria and renal impairment in patients with T2DM. The change of HbA1c, fasting insulin, blood pressure, blood lipids, uric acid, and the development of albuminuria will be investigated. The use of different hypoglycaemic drugs and the status of standardised diagnosis and treatment will be also evaluated in this project. Third, the effects of different oral hypoglycaemic drugs on albuminuria will be studied. The effects of SGLT-2 inhibitors on the change in urine albumin-to-creatinine ratio (UACR) and in the estimated glomerular filtration rate (eGFR) from baseline to the end of follow-up will be evaluated. The safety of SGLT-2 inhibitors will also be evaluated in this project.

Conclusions: This project aims to evaluate the prevalence of albuminuria in adult patients with T2DM in China, improve the awareness rate of DKD and provide a data platform for future in-depth research.

OP 2: Impact on diagnosis and management of diabetic kidney disease in real life clinical practice

Schultes B, Emmerich S, Kistler AD, Mecheri B, Schnell O, Rudofsky G; St. Gallen, Switzerland

Background:Quantitative albuminuria measurement using the albumin-to-creatinine ratio (ACR) is recommended according to various guidelines for the diagnosis of diabetic kidney disease (DKD). Our observational study aims at evaluating the impact of point-of-care testing (POCT) of ACR on DKD diagnosis and treatment management for glycaemic control and blood pressure.

Methods:Data of 236 patients with type 1 diabetes, 463 with type 2 diabetes, and 18 with other types of diabetes deriving from 3 diabetes centers were analysed. The impact of ACR POCT on DKD diagnosis and treatment management was assessed by using a case report form. The ACR POCT utilisation purpose and relevance for physicians was assessed using a questionnaire that was filled in by 8 physicians.

Results: Of all included patients (n = 717), 39.1 % had a confirmed or suspected DKD diagnosis, of whom 8.6 % were newly diagnosed with DKD, and 9.9 % were suspected with DKD based on the actual ACR POCT measurement. In 46.1 % of the patients with confirmed/suspected DKD (n = 280) the treatment was modified during the same visit of the ACR assessment. Initiation of glucagon-like peptide-1 (GLP-1) receptor agonists or sodium/glucose cotransporter 2 (SGLT-2) inhibitors treatment were the most frequent intervention, i. e. in 11.1 % or 8.9 % of patients with confirmed/suspected DKD, respectively. All of the 8 participating physicians indicated that they used ACR POCT measurement to examine patients with diabetes regardless of the presence of arterial hypertension, and 6 considered the measurement very important for patients with diabetes.

Conclusions: Our real life clinical practice study indicates that the implementation of ACR POCT has a relevant impact on DKD diagnosis and therapeutic management of patients with diabetes.

OP 3: Cardiovascular pathology in patients with non-alcoholic fatty liver disease with overweight and obesity

Pivtorak K; Vinnytsia, Ukraine

Background: The most common type of lesion among all chronic liver diseases is the non-alcoholic fatty liver disease (NAFLD). It is closely linked to obesity, insulin resistance and cardiovascular pathology.

The aim of this study was to evaluate the relationship between markers of endothelial dysfunction, insulin resistance, adipokines, and cholesterol level in patients with both NAFLD and overweight/obesity.

Methods: 223 patients with NAFLD were examined. We determined the level of inflammatory mediators, endothelin (ET-1), the activity of the von Willebrand factor (vWF), the thickness of the intima-media complex, the presence of atherosclerotic plaque and stenosis of the carotid arteries, and the index HOMA-IR. The ratio between the content of adiponectin and leptin was represented as log A/L. In addition, an anthropometric survey, measurement of levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), the degree of liver fibrosis using elastography (FibroScan), ECG and echocardiography were conducted.

Results:Correlation analysis revealed a direct correlation between HOMA-IR and leptin (r = 0.8; p = 0.00166) and an inverse correlation between HOMA-IR and adiponectin (r = −0.66; p = 0.0033) (index log A/L [r = −0.71; p = 0.0000]). A comparative analysis of the level of C-reactive protein (CRP) inflammation marker in obese patients showed a direct relationship with HOMA-IR (r = 0.58; p = 0.05), glucose (r = 0.44; p = 0.0045) and insulin (r = 0.66; p = 0.0001) in the blood. The patients with NAFLD and obesity showed a reduction in endothelium-dependent vasodilation, indicating the presence of endothelial dysfunction. The concentration of proinflammatory cytokines such as TNF-α and IL-6 in patients with NAFLD was 3 – 7 times higher than similar parameters in patients with a similar degree of obesity but without an evident NAFLD. The concentration of ET-1 in the blood plasma of patients with NAFLD had a strong direct correlation with the degree of cardiovascular risk and cognitive deficit in the surveyed patients. It was found that many inflammatory mediators (TNF-α, IL-1, IL-6) and markers (C-reactive protein, fibrinogen) highly correlated with the degree of obesity, the concentration of ET-1, vWF and markers of insulin resistance, a predictor for cardiovascular risk.

Conclusions: The development of NAFLD is associated with the development of endothelial dysfunction, increased levels of leptin, and decreased levels of adiponectin in patients with NAFLD, overweight and obesity.

OP 4: Autonomic neuropathy: impact on carbohydrate metabolism and thera­peutical challenges

Kempler P; Budapest, Hungary

Cardiac autonomic neuropathy (CAN) represents a serious complication as it carries a fivefold risk of mortality in patients with diabetes. The high mortality rate may be related to silent myocardial infarction, cardiac arrhythmias, cardiovascular and cardiorespiratory instability and to other causes not explained yet. Usually, we consider autonomic neuropathy as a complication of diabetes. However, it is worth to evaluate this problem from the other side as well: Could autonomic neuropathy have an impact on carbohydrate metabolism? The answer is yes. On the one hand, autonomic neuropathy among patients with newly diagnosed type 2 diabetes mellitus is associated with postprandial hyperglycaemia. On the other hand, it is well known that autonomic neuropathy is associated with hypoglycaemia unawareness and a higher frequency of severe hypoglycaemia. If sympathetic autonomic failure is present, signs of adrenergic activation (tachycardia, hunger, sweating) are frequently absent. As a consequence, hypoglycaemia may occur as a sudden loss of consciousness. Postprandial hyperglycaemia, as well as hypoglycaemia may lead to increased glucose variability, being associated with poor prognosis.

The above mentioned aspects imply various therapeutical implications as well. On the one hand, especially among diabetic patients with autonomic neuropathy, the use of antidiabetic agents not being associated with hypoglycaemia should be preferred. Moreover, agents decreasing postprandial hyperglycaemia (DPP-4 inhibitors, GLP-1 receptor agonists, short acting insulin analogues) are suggested for use. Another important place for therapeutical intervention is neuropathy. In this respect, the use of pathogenetic-based, disease-modifying causal therapy should be used. Pathogenetic oriented treatment with benfotiamine and/or alpha-lipoic acid has an impact on neuropathic damage/deficit and disability, while, on the other hand, it has a documented effect on the improvement of neuropathic pain and quality of life as well. Benfotiamine is a transketolase activator and inhibits harmful alternative metabolic pathways such as the polyol pathway, the exosamin pathway, advanced glycation end product formation, as well as the protein kinase C pathway. Alpha-lipoic acid is considered nowadays the most potent antioxidant agent. Combination therapy with benfotiamine and alpha-lipoic acid is suggested for use more commonly.

OP 5: Effects of empagliflozin on lipo­protein subfractions in patients with type 2 diabetes – data from a randomized, placebo-controlled study

Rau M, Thiele K, Hartmann NUK, Möllmann J, Wied S, Böhm M, Scharnagl H, März W, Marx N, Lehrke M; Aachen, Germany

Background:Sodium-glucose cotransporter 2 inhibitors, as glucose-lowering drugs that increase urinary glucose excretion, have been shown to reduce cardiovascular (CV) events in patients with type 2 diabetes (T2D), although these agents increase blood levels of the proatherogenic low density lipoprotein cholesterol (LDL-C). It has been hypothesized that haemoconcentration due to osmotic diuresis, effects on calculated LDL particle size, or a modulation of lipoprotein subfractions may play a role in this context, but to date the underlying mechanisms remain largely unexplored. Therefore, the present study examined effects of empagliflozin on LDL-C and lipoprotein subfractions including calculated LDL particle size and composition.

Methods:In this placebo-controlled, randomized, double blind study, patients with T2D were randomized to empagliflozin 10 mg (n = 20) or placebo (n = 22). Composition of lipoprotein subfractions was assessed before and after 3 months of treatment. Lipoproteins were separated using a combined ultracentrifugation-precipitation method (β-quantification).

Results: Empagliflozin increased LDL-C after 3 months of treatment (from baseline: 103 ± 36 mg/dl to 112 ± 47 mg/dl; p < 0.001), while no difference was recorded after day 1 or day 3 of treatment. The increase of LDL-C was paralleled by an increase of total cholesterol (baseline: 169 ± 41 mg/dl, 3 months: 185 ± 48 mg/dl; p = 0.001). Analyses of lipoprotein subfractions revealed LDL phospholipids and LDL apolipoprotein B to be increased by empagliflozin after 3 months of treatment, while calculated LDL particle size was not affected. In addition, empagliflozin increased free fatty acid concentrations.

Conclusion: Empagliflozin treatment of patients with T2D increased LDL-C and LDL apolipoprotein B levels, but had no effect on calculated LDL particle size.

OP 6: Updated meta-analysis of cardiovascular outcome trials evaluating cardiovascular efficacy of glucagon-like peptide-1 receptor agonists

Patoulias D, Papadopoulos C, Kassimis G, Karagiannis A, Doumas M; Thessaloniki, Greece

Background: Type 2 diabetes mellitus (T2DM) has gradually evolved as a metabolic pandemic, while its prevalence is going to rise over the next decades. Notably, cardiovascular disease remains the greatest threat for those subjects suffering from T2DM, while a multilevel treatment strategy is required for risk reduction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have now been considered along with sodium-glucose co-transporter 2 (SGLT-2) inhibitors the optimal treatment options for diabetic patients with established atherosclerotic cardiovascular disease or for those with multiple risk factors.

Methods: We sought to update previous relevant meta-analyses, pooling data from the published cardiovascular outcome, placebo-controlled trials until 1st July 2020. We utilised data from published reports, also searching relevant supplementary appendices for any missing data. We evaluated the following outcomes of interest: major adverse cardiovascular event (MACE), cardiovascular death, all-cause death, hospitalisation for heart failure (HF), non-fatal myocardial infarction (MI) and non-fatal stroke.

Results: We pooled data from 8 trials in a total of 60 080 enrolled participants with T2DM assigned either to GLP-1RA treatment or placebo. GLP-1RA treatment resulted in a significant decrease in the risk for MACE by 12 % (RR = 0.88; 95 % CI: 0.82 – 0.94; I2 = 46 %). In addition, GLP-1RA treatment led to a significant decrease in the risk for cardiovascular death by 12 %, compared to placebo (RR = 0.88; 95 % CI: 0.81 – 0.95; I2 = 6 %). In terms of all-cause death, GLP-1RAs also decreased the corresponding risk by 11 % compared to placebo (RR = 0.89; 95 % CI: 0.83 – 0.94; I2 = 7 %). GLP-1RA treatment produced a significant reduction in the risk for non-fatal stroke by 15 % (RR = 0.85; 95 % CI: 0.76 – 0.95; I2 = 0 %); however, it did not significantly affect the risk for HF hospitalisation or non-fatal MI.

Conclusion:Herein we present the first updated meta-analysis of cardiovascular outcome trials with GLP-1RAs, after the publication of the AMPLITUDE-O trial, demonstrating that this drug class provides a significant reduction in the risk for MACE, cardiovascular and all-cause death and non-fatal stroke, along with a marginally non-significant reduction in the risk for hospitalisation for HF decompensation and non-fatal MI.

Poster Presentations – PS 1: Treatment of diabetes

P 01: Consensus to turn the contempo­rary evidence of dapagliflozin for better patient outcomes – insights from a multidisciplinary group of experts

Sethi B, Bajaj S, Hazra PK, Das S, Singh P, Ambulkar S, Nair T, Khan A, Sinha N, Chandra S, TURN Working Group; Hyderabad, India

Background: Dapagliflozin is the first sodium-glucose-linked transporter 2 inhibitor (SGLT2i) to be triple indicated for type 2 diabetes mellitus (T2DM), heart failure, and chronic kidney disease, by US FDA. The aim of this study was to determine the level of consensus among Indian thought leaders across multidiscipline.

Methods: 300 leading endocrinologists, diabetologists, and cardiologists, with individual clinical experience of at least two decades, across India, deliberated through a virtual model. The perception mapping questions were interspersed after each specific identified contemporary evidence published in the years 2020 and 2021 for dapagliflozin and SGLT2i that included 10 statements, of which 9 statements were as 5-point Likert scale (1: strongly disagree, 5: strongly agree). Responses were digitally captured and shared live to enable cross-learning and entered in the spreadsheet for percentage analysis. A consensus statement was defined if it was endorsed by 75 % or more of the respondents.

Results:The mean cumulative responses per statement was 103 (SD ± 8.2; range 92 – 115; 95 % CI: 97 – 108). Cumulatively, there were 1026 responses (34.2 % responder rate). The mean duration of the meeting was 143 minutes (SD ± 18; range 123 – 184; 95 % CI: 132 – 154). The consensus was agreed/strongly agreed for dapagliflozin, for initial publications established the strong foundations (81 %, n = 81/100), is efficacious, irrespective when used as monotherapy or add-on (82.6 %, n = 76/92), is efficacious in enabling bodyweight reduction (90.4 %, n = 104/115), is durable for glycaemic control (87.8 %, n = 87/99), in real-world, is as effective as demonstrated in clinical trials (88.8 %, n = 96/108). Dapagliflozin was perceived to have maximal benefits in patients with heart failure per se, followed by benefits in obese T2DM and patients with high cardiovascular risk by 52 % (48/92), 16.3 % (15/92), and 13 % (12/92) responders, respectively. It was agreed that guidelines for SGLT2i have been keeping pace with the emerging evidence, and usage of SGLT2i has postponed insulin initiation/increasing the dose of insulin.

Conclusions: The results highlight the potential impact of the contemporary evidence for the utilisation of dapagliflozin and SGLT2i in the Indian setting. Landmark trials of dapagliflozin for glycaemic and extra-glycaemic benefits are influential to build the consensus for metabolic modulation and translate benefits in the real-world setting.

P 02: Effects of excessive insulin doses replacement with oral drugs in patients with diabetes type 2

Lomtadze I, Khutsishvili T, Eloshvili N; Tbilisi, Georgia

Background: The chronic overdose of insulin is a widespread problem in Georgia and beyond. The goal of our research was to study the effects of excessive insulin doses reduction and replacement with oral drugs in patients with type 2 diabetes (T2D).

Methods: We selected 39 T2D patients with similar data (HbA1c, body mass index [BMI], C-peptide). Patients were divided into three groups. In all groups insulin doses were reduced. In the first group we added sulfonylurea (SU) (glimepiride, gliclazide), in the second group metformin and in the third group dapagliflozin, while the fourth group was a control one, where no insulin dose correction was made. We estimated parameters change after 6 months of treatment correction.

Results: 1) Due to insulin dose reduction (29 ± 11 U) and SU addition, we got a significant reduction of some parameters compared to control group: HbA1c (9.3 ± 2.1 vs. 7.4 ± 1.0, p < 0.001), BMI (36.7 ± 3.7 vs. 35.2 ± 3.6 kg/m², p = 0.005). 2) In the second group, where metformin was added, insulin dose was decreased by 15 ± 7 U. Compared to control group, here we got the statistically significant reduction of the following parameters: HbA1c (9.0 ± 1.9 vs. 7.5 ± 1.1 %, p < 0.001), BMI (34.7 ± 4.4 vs. 32.8 ± 4.3 kg/m², p = 0.04). 3) Due to insulin doses reduction (11 ± 5 U) and addition of dapagliflozin, in the third group the following parameters improvements were statistically significant: HbA1c (8.9 ± 1.4 vs. 7.4 ± 1.1 %, p < 0.001), BMI (36.6 ± 4.6 vs. 34.4 ± 4.1 kg/m², p < 0.001).

In all three groups, we got statistically significant reduction of blood pressure, especially in the dapagliflozin group. In this group we removed one antihypertensive component or reduced the combined antihypertensive drug doses.

Conclusions: Substantial insulin doses reduction and replacement with certain oral drugs caused the significant improvement of BMI, HbA1c, blood pressure; blood pressure reduction effect was the most evident in the dapagliflozin group.

P 03: Rational use of novel oral anti­coagulants and anti platelet agents for better cardiovascular outcomes: Delphi consensus from experts at the forefront of cardiology in India

Pinto B, Mullasari A, Gambhir DS, Mehta A, Khan A, Mahala BK, Sahoo PK, Kumar AS, Sethi R, Makkar JS, CLOT Consensus Group; Mumbai, India

Background: Consistent progress of clinical trials has transformed the evidence-based medicine for the usage of novel oral anticoagulants (NOACs) and antiplatelet agents. At times, guidelines reflect the gaps with the rapidly evolving evidence. Therefore, we realised the need for a consensus through a voluntary, interactive, evidence-based continuing medical education programme.

Methods: In-person scientific discussion was conducted encompassing the use of NOACs in atrial fibrillation, contemporary evidence for antiplatelets, thrombotic complications of COVID-19, thrombosis due to COVID-19 vaccine, and post COVID-19 cardiology. 21 questions (13 Likert-based) with 95 response items, were executed through a two-round modified Delphi approach, with no time lag between pre- and post-lecture. There were 40 Indian cardiologists as participants, for cluster opinion and therapeutic consensus, with cumulative clinical experience of 1200 man years. The statement with significant change post-lecture, with the agreement (A) and strong agreement (SA), were considered for consensus. GraphPad version 9.3.0 for Chi-square and Fisher’s exact test were used for statistical analysis.

Results:There was enhanced consensus that Asian patients were limited and rarely incorporated into major international guidelines (203 % increase SA, p = 0.0008); in patients with STEMI 12-month therapy for ticagrelor (180 mg loading and 90 mg twice-daily maintenance dose) was recommended in patients undergoing primary PCI (151 % increase in SA, p = 0.011); demonstration of the bioequivalence for ticagrelor was considered as the first step towards therapeutic equivalence (125 % increase in A, p = 0.009). In COVID-19 anti-inflammatory effects were also contributed by anticoagulants and antiplatelet therapies (23.7 % increase in A, p = 0.031); current societal recommendations that NOACs were useful for the treatment of confirmed or suspected vaccine-induced immune thrombotic thrombocytopenia (33.2 % increase in SA, p = 0.0032). COVID-19 was unanimously, considered as an acute manageable immunogenic thrombogenic inflammatory viral notifiable disease. COVID-19 vaccines-induced thrombosis was considered as a roadblock, rather than a dead-end street (50 – 83.3 %, p < 0.0001). Post COVID-19 syndrome was considered as a chronic reactive endotheliitis and disseminated vascular disease. 50 % agreed that alterations of left ventricular function were commonly observed in post-acute COVID-19 in patients with known cardiovascular pathology. The systemic inflammatory response was considered as the most important suspected mechanism, for the association between vascular thrombosis in the convalescent period by 72.7 % of respondents.

Conclusions: Our study emphasises that there are several clinical circumstances in cardiology practice, beyond the guidelines, where NOACs and antiplatelet agents are useful to facilitate complex decisions. Bioequivalent affordable ticagrelor has the potential to enhance access and aid quality care.

P 04: The influence of physical activity level on symptoms of depression in patients with diabetes mellitus type 1

Fedulovs A, Sokolovska J; Riga, Latvia

Background:Depression is one of the most common comorbidities of type 1 diabetes (T1D). Manifestations of depression reduce patient compliance and self-care level, which are among the most important aspects of successful T1D control. Aim is to find out the association of physical activity level of T1D patients with depressive symptoms.

Methods:The study method was secondary data analysis and included data from 346 patients with T1D. Data for the study were obtained from LatDiane ‘Latvian Diabetic Nephropathy Study’ research questionnaires. Data on depression symptoms were obtained from Beck Depression Inventory (BDI) from 2013 to 2020 with the following interpreted thresholds: scores from 0 to 9 indicated no or minimal depression, 10 to 18 indicated mild to moderate depression, 19 to 29 indicated moderate or severe depression. Questionnaire of physical activities included questions on frequency (times/week) and intensity of physical activity evaluated by questions on breathing, perspiration and effort. Total amount of leisure time physical activity in metabolic units/week was interpreted as follows: inactive (< 10 metabolic equivalent of task [MET] h/week), moderately active (10 – 40 MET h/week), active (> 40 MET h/week). In addition, data on biochemical analysis (HbA1c), anthropometric measures (weight, height), gender, age and duration of diabetes were analysed.

Results: The study included data from 346 patients with T1D, of whom the majority were young with a mean age of 35.9 ± 13.5 years. Most patients (237) had a duration of diabetes > 5 years and a median of 15.5 ± 12.3 years. From 346 respondents, 50 were depressed and only one-third (16) used antidepressants. The prevalence of depression was more than twice higher in the female group than in the male group (36 vs. 14; p = 0.03; OR = 2.67). Patients with T1D > 5 years had a higher HbA1c level than those who had T1D < 5 years (p = 0.032). Patients with a higher BDI score had a higher HbA1c level than those who had a lower BDI score (p = 0.017). Those who had a higher BDI score, had an age statistically significant higher than those who had a lower BDI score (p = 0.045). No statistically significant correlation was found between leisure time physical activity and BDI (p = 0.58). The Mann-Whitney test revealed a statistically significant association between depression and the intensity of physical activity: the higher the intensity of physical activity, the lower the BDI level of depression (p = 0.001). Patients with different intensity of physical activity differed in their BDI scores statistically significant (p < 0.013).

Conclusions: Intense exercise in leisure time was associated with weaker depressive symptoms in this patient group. We also found that depressive symptoms were more present in the following T1D patient groups: women, patients with a longer T1D history, a higher age and inferior T1D metabolic compensation. It is important to educate patients about the importance of physical activity and depression screening.

Poster Presentations – PS 2: Diabetes, NAFLD and lipid disorders

P 05: The impact of NAFLD on cardio­vascular mortality in type 2 diabetes patients undergoing haemo­dialysis

Stoica RA, David T, Stefan SD, Bica C, Serafinceanu C, Pantea-Stoian A; Bucharest, Romania

Background: The relationship between non-alcoholic fatty liver disease (NAFLD), end stage renal disease (ESRD) and cardiovascular risk is multidirectional. The presence of NAFLD increases the cardiovascular risk three-fold in haemodialysis, and the cardiovascular disease (CVD) increases the risk for NAFLD. NAFLD is an interplay factor between CVD, malnutrition and inflammation in this fragile population.

Methods:We conducted an observational, prospective study lasting 12 months (June 2020 – June 2021). The study included all patients with diabetes and ESRD who underwent 3 haemodialysis sessions per week at the National Institute of Diabetes, Nutrition, and Metabolic Diseases (INDNBM) N. C. Paulescu. An abdominal ultrasound was performed for screening. To not include patients with alcoholic fatty liver disease, patients who self-reported alcohol consumption were excluded. At the first and second visits we collected biological samples and calculated the hepatic steatosis index (HSI) score. We used Mann-Whitney U test to analyse the differences between the two groups based on NAFLD diagnosis. The final data analysis was performed using SPSS Statistics 20.0.

Results: Our study included 26 type 2 diabetes patients with a mean disease duration of 19.81 ± 8.4 years complicated with ESRD (mean duration of dialysis 3.88 ± 2.78 years). 58 % of the patients were diagnosed with ultrasound hepatic steatosis. In the univariate analysis, the HSI score correlated positively with body mass index (BMI) (Spearman coefficient 0.824; p < 0.05), positively with the fat mass (Spearman coefficient 0.564; p = 0.03), and negatively with age (Spearman coefficient −0.400; p = 0.048). HSI also correlated with fasting glycaemia and HbA1c (Spearman coefficient 0.339 and 0.166, p = non-significant). There were significant differences at the first visit in terms of total cholesterol and HDL-C (p = 0.033 and 0.016, respectively). Regarding the causes of death, more than a quarter of the subjects, namely 27 % of them, died of COVID-19 before the 1-year follow-up. Cardiovascular causes represented 18 % of the total deaths. Survival analysis using the Kaplan Meier curve indicated a lower survival of patients with ultrasound-diagnosed hepatic steatosis.

Conclusions: The prevalence of NAFLD in type 2 diabetes and ESRD haemodialysis patients was 58 %, the majority of them having obesity class I. The HSI score correlated positively with BMI. Diabetic patients with ultrasound-diagnosed hepatic steatosis in haemodialysis had a lower survival rate.

P 06: Treatment of patients with NAFLD, type 2 diabetes mellitus and ­concomitant cardiac pathology

Pivtorak K, Yakovleva O, Kobirnichenko A, Krikus O; Vinnytsia, Ukraine

Background: The positive effect of glucose-lowering drugs on the course of non-alcoholic fatty liver disease (NAFLD) is known, as well as the positive results of many multicenter studies examining a new class of drugs of sodium-dependent glucose cotransporter type 2 (SGLT-2) inhibitors on cardiovascular complications. Since NAFLD is extremely often accompanied by diseases of the cardiovascular system, this class of drugs was used for patients with NAFLD.

The aim of this study was to investigate the effect of SGLT-2 inhibitors on the course of NAFLD in patients with type 2 diabetes mellitus with concomitant coronary heart disease (CHD) and arterial hypertension (AH) compared with patients taking other antidiabetic drugs.

Methods: During the study, 38 patients with NAFLD, type 2 diabetes mellitus and concomitant CHD and AH were monitored. 56 % of those surveyed were women and 44 % were men. The average age of the subjects was 52.3 years. Patients were divided into two representative groups. The first group received metformin and an SGLT-2 inhibitor (empagliflozin or dapagliflozin). The second group received any other combination of glucose-lowering drugs and metformin. In both groups, the effect of treatment on the degree of steatosis and liver fibrosis, blood glucose levels, cardiovascular status, and change in body weight were assessed.

Results: The study found that in the group of patients taking SGLT-2 inhibitors there was a tendency of decreasing in the degree of steatosis without worsening the degree of liver fibrosis. These patients had fewer angina attacks by 5.3 %, and had a better controlled blood pressure – a decrease in systolic blood pressure by 7 – 12 mmHg, in diastolic blood pressure by 3 – 5 mmHg – which is in contrast to group 2. There was also a tendency to reduce the body weight of patients in the first group by 7 – 8 %, which contrasted group 2. In both groups, there was a compensation of glucose metabolism when a second glucose-lowering drug was added to the treatment.

Conclusion: Given the results of the study, namely the achievement of normoglycaemia and a positive effect on modified risk factors for cardiac complications in patients with type 2 diabetes mellitus (overweight, hypertension and a positive effect on the course of NAFLD), we can conclude that SGLT-2 inhibitors should be the drugs of choice for enhancing antihyperglycaemic therapy in the treatment of patients with NAFLD, type 2 diabetes mellitus and concomitant cardiac pathology.

P 07: Pancreatic steatosis and athero­sclerotic process

Pivtorak K, Fedzhaga I, Pivtorak N; Vinnytsia, Ukraine

Background: The atherosclerotic process is closely related to steatosis of the liver and pancreas. The mechanisms by which this pathogenetic process occurs have not been studied. One of the hypotheses involves an increased synthesis of pro-inflammatory cytokines and the formation of a chronic inflammatory process in the tissue of the pancreas and blood vessels. The purpose of the study was to establish the features of lipid metabolism in patients with pancreatic steatosis.

Methods: 76 patients with pancreatic steatosis were examined. The criteria for the diagnosis of steatosis were a decrease in densitometric parameters of pancreatic tissue (< 30 HU), obtained by computed tomography of the abdominal cavity. Blood lipid profile of cholesterol and triglycerides, low-density lipoprotein cholesterol, very low density, high density and atherogenicity index were evaluated. The levels of glucose, insulin and C-peptide were assessed on an empty stomach and two hours after ingestion of 75 g glucose, dissolved in 250 – 300 ml of water, within 5 minutes. The presence of insulin resistance was determined by the level of the Homeostasis Model Assessment (HOMA) index. We determined the level of inflammatory mediators (TNF-α, IL-1, IL-6), markers (C-reactive protein, fibrinogen), the thickness of the intima-media complex, presence of atherosclerotic plaque and stenosis of the carotid arteries for all examined patients.

Results: An inverse correlation was found between BMI and densitometric parameters of pancreatic tissue. In pancreatic steatosis, patients with overweight and obesity had elevated (p < 0.05) levels of triglycerides (1.51 ± 1.26 mmol/l) and LDL cholesterol (1.48 ± 1.19 mmol/l). The level of total cholesterol was elevated in 22 patients. The average level of total cholesterol in the serum of patients was 5.2 ± 0.6 mmol/l. Most patients had a decrease in HDL cholesterol and an increase in LDL cholesterol. There was a frequent combination of pancreatic steatosis with hepatic steatosis, gallbladder cholesterol, gastroesophageal reflux disease and coronary heart disease. 21 patients were diagnosed with fasting hyperglycaemia and impaired glucose tolerance, and type 2 diabetes mellitus in 14 patients. Laboratory tests showed an increase in the HOMA index, the average values of which exceeded the norm by more than 2 times in 27 patients. In 38 patients there was an increase in insulin and C-peptide. The analysis of the quality of life of patients with pancreatic steatosis revealed a decrease in the levels of physical and psychological components.

Conclusions: Pancreatic steatosis was characterised by atherogenic disorders of lipid, mainly by type of hypertriglyceridaemia, and glucose metabolism in the form of type 2 diabetes, impaired glucose tolerance or hyperglycaemia on an empty stomach. The relationship between atherogenicity and signs of pancreatic lesions was established.

PS 3: COVID-19 and diabetes

P 08: Meta-analysis of the hallmark cardio­vascular and renal outcome trials addressing the risk for respiratory tract infections with sodium-­glucose co-transporter 2 inhibitors; implications for the COVID-19 pandemic

Patoulias D, Papadopoulos C, Boulmpou A, Doumas M; Thessaloniki, Greece

Background: Diabetes mellitus represents a global pandemic. Moreover, it has been recognised as an independent risk factor for severe acute respiratory syndrome when infected with coronavirus 2 (SARS-CoV-2) in the context of the coronavirus disease 19 (COVID-19) pandemic. Diabetic subjects feature a two-fold increase in the odds for severe disease by SARS-CoV-2 infection and a two- to three-fold increase in the odds for death due to the disease. Patients with diabetes mellitus experience a significant increase in the risk for in-hospital death due to SARS-CoV-2 infection. We sought to determine whether SGLT-2 inhibitors influence the risk for respiratory tract infections and acute respiratory distress syndrome (ARDS), pooling data from the published cardiovascular and renal outcome, placebo-controlled trials until November 2020.

Methods: We utilised data from published reports, also searching relevant supplementary appendices and ‘grey literature’ sources, namely clinicaltrials.gov. We evaluated the following primary outcomes of interest: upper respiratory tract infection, lower respiratory tract infection, viral infection, influenza and ARDS. We also assessed the following secondary outcomes: pharyngitis, bronchitis and pneumonia, as reported across the selected trials.

Results: We pooled data from 6 trials in a total with 47 728 enrolled participants assigned either to SGLT-2 inhibitor treatment or placebo. SGLT-2 inhibitor treatment compared to placebo resulted in a non-significant decrease in the risk for upper respiratory tract infection (RR = 0.95; 95 % CI: 0.48 – 1.88; I2 = 0 %) and for lower respiratory tract infection (RR = 0.66; 95 % CI: 0.39 – 1.13; I2 = 0 %). In addition, SGLT-2 inhibitor treatment produced a non-significant increase in the risk for viral infection (RR = 1.15; 95 % CI: 0.49 – 2.71; I2 = 0 %) and influenza (RR = 1.27; 95 % CI: 0.70 – 2.32; I2 = 0 %). We have also demonstrated that SGLT-2 inhibitor treatment led to a non-significant decrease in the risk for ARDS (RR = 0.68; 95 % CI: 0.24 – 1.96; I2 = 0 %). Of note, as far as the secondary safety outcomes are concerned, we showed that SGLT-2 inhibitor treatment compared to placebo resulted in a significant decrease in the risk for pneumonia by 15 % (RR = 0.85; 95 % CI: 0.75 – 0.97; I2 = 0 %).

Conclusions: Collectively, patients treated with SGLT-2 inhibitors do not have an increased risk for respiratory infection compared to diabetic subjects treated with other antidiabetic drug classes, while they might have decreased risk for pneumonia.

P 09: DPP-4 inhibitors and COVID-19-­related death among patients with type 2 diabetes mellitus: a meta-analysis of observational studies

Patoulias D, Doumas M; Thessaloniki, Greece

Background: Coronavirus disease 2019 (COVID-19) pandemic remains an unbeaten enemy, accounting for more than 4 million deaths worldwide until July 2021. Unfortunately, there is still no targeted treatment option available. Patients with type 2 diabetes mellitus (T2DM) feature increased odds for severe or fatal disease, as demonstrated in recent, large, observational studies. There is an ongoing discussion regarding the impact of different antidiabetic drug classes on outcomes of interest among affected subjects. Dipeptidylpeptidase-4 (DPP-4) inhibitors have been placed at the epicenter, since DPP-4 enzyme seems to be implicated at some extent into disease pathogenesis.

We sought to determine whether DPP-4 inhibitors influence the risk for COVID-19-related death, which corresponds to the ‘hardest’ outcome of the disease course.

Methods: We searched two major databases (PubMed and Cochrane Library) for published randomised controlled trials (RCTs) or observational studies enrolling adult patients with T2DM with prior use of DPP-4 inhibitors versus other antidiabetic drug classes with confirmed COVID-19 infection.

Results: Our search yielded a total of 77 reports. After deduplication and screening, we retrieved 17 reports for potential inclusion in our meta-analysis. We finally included in our quantitative synthesis 10 observational studies, published until 05/05/2021, while no relevant RCTs were identified. Use of DPP-4 inhibitors compared to other antidiabetic drug classes produced a non-significant decrease equal to 3 % in the risk for COVID-19-related death (95 % CI: 0.67 – 1.41; I2 = 83 %; p = 0.89). Of note, subgroup analyses according to the setting revealed that, when DPP-4 inhibitors were initiated in the inpatient setting, the result became significant (RR = 0.50; 95 % CI: 0.34 – 0.71; I2 = 0 %; p = 0.0001), while outpatient use of this antidiabetic drug class was not associated with a significant effect on the risk for COVID-19-related death (RR = 1.14; 95 % CI: 0.78 – 1.66; I2 = 81 %; p = 0.50).

Conclusions: Collectively, despite the fact that current evidence is based upon observational studies, prior use of DPP-4 inhibitors has a neutral effect against COVID-19-related death among patients with T2DM, while inpatient administration might contribute to decrease in the corresponding risk.

P 10: Effect of long-term administration of SGLT-2 inhibitors on ­ambulatory arterial stiffness in patients with type 2 diabetes mellitus: a pro­spec­tive, observational study in the context of the COVID-19 pandemic

Patoulias D, Papadopoulos C, Katsimardou A, Imprialos K, Stavropoulos K, Zografou I, Toumpourleka M, Tranidou A, Bakatselos S, Karagiannis A, Doumas M; Thessaloniki, Greece

Background: Patients with type 2 diabetes mellitus (T2DM) feature an excess risk for cardiovascular disease. Arterial stiffness represents an established, independent prognostic marker for cardiovascular disease development. Therefore, we sought to determine the effect of two different sodium-glucose co-transporter 2 (SGLT-2) inhibitors with proven cardiovascular efficacy, namely empagliflozin and dapagliflozin, on ambulatory arterial stiffness parameters in patients with T2DM.

Methods: In this single-center, single-arm, prospective study between January 2020 and August 2021, we enrolled 46 adult patients with established T2DM and stable antidiabetic and antihypertensive treatment, who were assigned either to empagliflozin or dapagliflozin for 6 months, according to treating physician’s clinical discretion. All patients underwent ambulatory blood pressure monitoring at two different time points. The primary efficacy outcome was the change in ambulatory pulse wave velocity (PWV) from baseline to week 24, while we also assessed several secondary outcomes of interest, including other markers of arterial stiffness and laboratory parameters.

Results: Due to the fact that the study was conducted in the context of the COVID-19 pandemic, mean (± standard deviation) follow-up was 9.97 (± 3.27) months. Mean age of enrolled subjects was 62.89 years, with a mean T2DM duration of 9.71 years. Regarding the primary efficacy outcome, we demonstrated that SGLT-2 inhibitor treatment resulted in a non-significant decrease in PWV (p = 0.65). More specifically, SGLT-2 inhibitor treatment produced a non-significant decrease in daytime PWV (p = 0.7) and a non-significant increase in nighttime PWV (p = 0.32). Notably, empagliflozin resulted in a non-significant increase in PWV (Δ = −0.16 m/s; p = 0.93), in daytime PWV (Δ = −0.17 m/s; p = 0.92) and in nighttime PWV (Δ = −0.14 m/s; p = 0.93), while dapagliflozin resulted in a non-significant increase in PWV (Δ = 0.18 m/s; p = 0.19), in daytime PWV (Δ = 0.04 m/s; p = 0.24), and in nighttime PWV (Δ = 0.12 m/s; p = 0.07). History of established cardiovascular disease at baseline did not significantly affect the observed effects.

Conclusions: SGLT-2 inhibitor treatment with empagliflozin or dapagliflozin in subjects with T2DM failed to improve ambulatory PWV over a mean follow-up of 10 months during the COVID-19 pandemic. Mechanisms other than improvement in arterial stiffness indices might be implicated into the long-term cardio-protection observed with this drug class.

P 11: Can COVID-19 trigger the development of diabetes mellitus?

Jashi L, Ketevan D, Kvanchakhadze R; Batumi, Georgia

Background: COVID-19 is a global challenge that particularly hurts patients with chronic diseases. In the fall of 2020, there was a strong third wave of infection in the Adjara region in Georgia. In the spring, the manifestation of diabetes increased, which patients associated with a transferred, diagnosed COVID-19.

The aim of the study was to investigate the possible association of newly diagnosed diabetes cases with SARS-CoV-2 infection in patients who did not have a proven SARS-CoV-2 infection history.

Methods: There were 22 cases of newly diagnosed diabetes mellitus in March 2020, 4 of which were associated with SARS-CoV-2 infection transmitted in November. 18 patients had no association with infection. The mean age of patients ranged from 39 to 67 years. 8 of them were women and 10 were men. All of them were tested for SARS-CoV-2 IgG antibodies. The assay was performed on SARS-CoV-2, IgG antibodies II Quant Abbott CMIA (normal range/negative < 50.0 AU/ml, positive ≥ 50.0 AU/ml).

Results: Antibodies were negative in 11 patients (61 % of cases) and ranged from < 5 ± 10 AU/ml. 2 patients had < 45 AU/ml, which was also assessed as being negative. 2 patients with > 55 ± 3.2 AU/ml and 4 patients with > 78 ± 4.7 AU/ml were positive. It was estimated that 6 patients, or 33 %, had the virus transmitted asymptomatically.

Conclusions: Based on the above data, we can assume that COVID-19 asymptomatic infection is also a risk factor for the manifestation of diabetes mellitus. The issue requires extensive research.

P 12: Impact of lockdown caused by the COVID-19 pandemic on glycaemic control in patients with diabetes

Sutkowska E, Marciniak D, Sutkowska K, Biernat K, Mazurek J, Kuciel N; Smolec, Poland

Background: The lockdown restrictions can impact lifestyle, which plays a crucial role in glycaemic control. The aim of this retrospective cohort study was to assess the impact of the lockdown due to COVID-19 on diabetes (DM) control.

Methods: The inclusion criteria for analysis of the patients’ records were presence of diabetes, age ≥ 18 years and 2 available HbA1c values from the period covered 3 – 5 months of treatment during the pandemic. The exclusion criterion was pregnancy. The HbA1c value from a pre-lockdown visit (V1) for patients from one diabetic center in Wrocław (Poland) was compared to the lockdown visit one (V2). Additional information on how the HbA1c changed and which variables can modify HbA1c during lockdown were also studied. To exclude the impact of seasons a similar analysis of HbA1c was performed for the previous year if data was available.

Results: During the defined period, 463 teleconsultations were recorded, but records from just 65 patients were eligible for the analysis (29 from women) due to the presence of gestational DM or lack of two visits with HbA1c information. The Caucasians (100 %) with DM type 2 predominated (96.92 %; women: 44.62 %) with a range of age typical for this population (mean age: 70.2 ± 5.48 years) and mean DM duration of 13.6 years. 20 % of the individuals declared previous macrovascular complications, 52.31 % had before-lockdown problems with glycaemic control, and 43.08 % had therapy modification before the lockdown. During the lockdown, 29.23 % of individuals declared weight gain, 93.85 % reported maintenance of physical activity, 7.69 % had acute disease, 20.00 % declared abandonment of the treatment. No patients suffered from COVID-19. At V1, the mean HbA1c was 7.5 % (58 mmol/mol) and at V2 7.2 % (55 mmol/mol), which corresponded to the value of the parameter decreased during the lockdown (assessed with the use of Wilcoxon’s test) (p = 0.0027). At V2 the HbA1c was within the target range in 60 % of the patients compared to only 40 % at V1 (p = 0.0033). The value of HbA1c normalised in 19 and worsened in 4 participants during the lockdown period (p = 0.0035). When the entire group of the patients was assessed, we detected no impact of sex, age, DM duration, type of therapy, declared change in body weight or in physical activity level during the lockdown period on the change in HbA1c. The history of macrovascular complications was the only variable that affected the increase in HbA1c during the lockdown period (p = 0.0072) with OR = 5.33.

Conclusions: The first months of lockdown due to the COVID-19 pandemic have not revealed worsened glycaemic control in patients with type 2 DM which was the most representative group of individuals in the studied group. However, a group of patients with DM and macrovascular complications was selected as turned out to be at risk of the harmful impact of the imposed restrictions on the level of HbA1c. These results may be useful in identifying patients who deserve closer attention in the case of a lockdown and are mostly interesting for being helped with their glycaemic control when behavioral intervention fails. It is also important to take into account the known impact of hyperglycaemia on vascular complications.

P 13: B12 Vitamin plasma levels in post COVID-19 patients with type 2 diabetes

Dundua K, Jashi L, Kvanchakhadze R, Peshkova T; Batumi, Georgia

Background: The link between immunity and nourishment is clearly known and special attention is being given to its role in COVID-19. Vitamin B12 is one of the dietary requirements necessary in the treatment of coronavirus patients. Coronavirus patients often show clinical symptoms, such as fever, cough, respiratory distress syndrome, gastrointestinal infection, and fatigue. It is sensible to suppose that COVID-19 affects cobalamin metabolism, impairs intestinal microbial proliferation, and contributes to symptoms of cobalamin deficiency. Such an assumption is based on the fact that there are signs and symptoms of vitamin B12 deficiency that are similar to those of a coronavirus infection. Based on these observations, it can be concluded that treatment with vitamin B12 can be useful in the recovery of COVID-19 patients (WHO recommendations).

The aim of the observational study was to identify vitamin B12 (cobalamin) plasma levels in the post COVID-19 patients with type 2 diabetes.

Methods: Approximately 43 diabetic patients aged 38 – 55 years were examined during a physician visit. The duration of diabetes in patients was about 3 – 5 years. COVID-19 was diagnosed about three months ago. Selected patients had a mild form of COVID-19 virus (i. e. did not require inpatient and oxygen), taking the tablets. All of them were tested for blood levels of vitamin B12 and glycated haemoglobin.

Results: Patients were grouped according to glucose-lowering drugs. Group 1: 7 patients were on metformin alone; group 2: 8 patients on SGLT-2 inhibitors; group 3: 9 patients on DPP-4 inhibitors; group 4: 6 patients on sulfonylurea and metformin; group 5: 7 patients on DPP-4 inhibitors and metformin; group 6: 5 patients on a combination of SGLT-2 inhibitor and metformin. Vitamin B12 in group 1 was 105 ± 29.2 pg/ml (normal values are 160 – 950 pg/ml or 118 – 701 pmol/l. 2nd group – 198 ± 19.4 pg/ml; 3rd group – 478 ± 22.1 pg/ml; 4th group – 231 ± 10.2 pg/ml; 5th group – 324 ± 25.2 pg/ml; 6th group – 162 ± 19.5 pg/ml. It was found that in all groups, despite treatment, vitamin B12 deficiency was observed. In groups 1 to 3, vitamin B12 was prescribed according to the scheme of 1000 μg. The patients’ complaints improved significantly after 2 months of administration.

Conclusions: Thus, in middle-aged diabetic patients, despite the treatment, it is somewhat important to check the nutrients, as timely diagnosis and treatment of vitamin B12 deficiency improves the general condition and quality of life of patients.

PS 4: Neuropathy and cardiac complications

P 14: Markers of oxidative stress in patients with type 2 diabetes mellitus complicated by cardio­vascular autonomic neuropathy

Saienko YY, Gonchar O, Mankovsky B; Kyiv, Ukraine

Background: At present, the role of free radical oxidation in the development and progression of complications of diabetes mellitus remains fundamentally important. It is known that in various pathological conditions, proteins are the primary effective targets of reactive oxygen species (ROS), and their oxidative modification (OPM) is considered one of the reliable and sensitive markers of oxidative stress. Glutathione (GSH), a ubiquitous thiol tripeptide, provides the significant antioxidant protection and maintains cellular redox potential by keeping sulfhydryl proteins in a reduced state. Therefore, the aim of this study was to evaluate the severity of oxidative stress by measurement of protein biomarkers in patients with type 2 diabetes mellitus (T2DM) and cardiovascular autonomic neuropathy (CAN).

Methods: 10 healthy volunteers (aged 43.9 ± 1.7 years), 10 patients with T2DM without CAN (aged 45.4 ± 1.1 years) and 10 patients with T2DM and CAN (aged 43.9 ± 1.7 years) participated in the current study. HbA1c was 8.4 ± 1.3 %. Neuropathy was diagnosed using the following scales: NSS, TSS, NIS-LL, Toronto. The patients studied did not have a history of cerebrovascular diseases and did not take any medications affecting measured substances in blood. The levels of OPM and lipid peroxidation (LPO) in plasma as well as content of H2O2, reduced GSH and activity of GSH peroxidase in erythrocytes were measured.

Results: A significant increase in the content of OPM products (in 2.5 times, p < 0.05) was registered in T2DM patients with CAN in comparison with control healthy group and the degree of protein oxidative modification correlated with the severity of diabetes. Carbonyl modification of proteins in the examined patients was accompanied by significant LPO activation, as evidenced by excessive accumulation of secondary products of LPO (TBK-active products) and H2O2 in the blood by 61 and 41 % (p < 0.05), respectively, compared with control. A positive correlation (r = 0.55; p < 0.05) between the level of carbonyl groups and the content of TBK-active products indicated the relationship between oxidative modification of proteins and the intensity of LPO. We found that diabetic patients with and without CAN demonstrated significantly lower values of GSH (by 36 and 31 %, p < 0.05) and activity of glutathione peroxidase (by 25 and 16 %; p < 0.05) than control subjects. In these patients, the correlation analysis established the average degree of relationship between the duration of the disease and the content of H2O2 (r = 0.51; p < 0.05), TBA-AP (r = 0.61; p < 0.05). A positive linear relationship was observed between HbA1c levels and oxidative stress values (for TBA-AP r = 0.41; for H2O2 r = 0.49; p < 0.05). A weak relationship was observed between the severity of hyperglycaemia and the studied indicators of the state of the antioxidant system.

Conclusions: Our findings suggest that diabetic patients with CAN have more severe oxidative stress than diabetic patients without CAN. Thus, the accumulation of products of oxidative modification of proteins and a decrease in the redox potential of the glutathione system in erythrocytes reflect the intensity of free radical damage to macromolecules, which contributes to the development of neurological complications of T2DM.

P 15: Omega-3 polyunsaturated fatty acids: effects on the heart rate varia­bility and arterial stiffness para­meters in patients with diabetic cardiac autonomic neuro­pathy

Serhiyenko V, Hotsko M, Serhiyenko L, Serhiyenko A, Segin V; Lviv, Ukraine

Background: Cardiac autonomic neuropathy (CAN) in type 2 diabetes mellitus (T2DM) is one of the independent risk factors for cardiovascular mortality. We evaluated the effect of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) on the heart rate variability (HRV) and arterial stiffness indices in T2DM patients with confirmed CAN.

Methods: 36 patients with T2DM and confirmed CAN were involved. The study was carried out on two separate arms: traditional glucose-lowering therapy (n = 15, control) and one capsule/day omega-3 PUFAs (n = 21). The duration of the study was three months. We performed Holter-ECG (ECG ‘EC-3H’ [‘Labtech,’ Hungary]) analysis including measurement of 24-h ECG and HRV parameters. Artery stiffness parameters (aorta augmentation index [AIxao], brachial augmentation index [AIxbr] and pulse wave velocity [PWV]) were assessed using the device TensioMedTM Arteriograph. Statistics: ANOVA (MicroCal Origin v. 8.0).

Results: Prescription of omega-3 PUFAs promoted an increase in the time-domain HRV parameters, in low-frequency component (LF) (Δ = +30.2 ± 6.42 %; p < 0.01), in high-frequency (HF) (Δ = +18.1 ± 6.02 %; p < 0.05) and in LF/HF ratio (Δ = +14.42 ± 7.16 %; p < 0.05) during the active period of the day. Prescription of omega-3 PUFAs promoted an increase in LF (Δ = +30.8 ± 4.95 %; p < 0.01), in HF (Δ = +18.9 ± 4.72 %; p < 0.05), in LF/HF ratio (Δ = +10.5 ± 2.1 %; p < 0.05) and did not affect the very low-frequency component of HRV parameters during the passive period (compared to the control). Omega-3 PUFAs contributed to the decrease of the PWV by −11.6 ± 2.09 % (p < 0.05) and AIxao by −16.2 ± 3.12 % (p < 0.01) during the active period and to the decrease of the PWV by −18.9 ± 3.9 % (p < 0.01), AIxao by −11.2 ± 4.2 % (p < 0.05) and AIxbr by −98.0 ± 18.1 % (p < 0.05) during the passive period.

Conclusions: In patients with T2DM and confirmed CAN treatment with omega-3 PUFAs improved HRV and arterial stiffness parameters. However, further randomized, double-blind, placebo-controlled trials of larger scale, doses and duration may provide evidence for the hidden therapeutic capacity of omega-3 PUFAs therapy and its potential properties for diabetic CAN.

P 16: Vitamin D level and diabetic ­complications in adolescents with type 1 diabetes mellitus

Biliaieva K, Vlasenko MV; Vinnitsya, Ukraine

Background: Recent studies have shown that patients with type 1 diabetes mellitus (DM) have low vitamin D status. Vitamin D deficiency and insufficiency is associated with increased level of glycated haemoglobin (HbA1c) among diabetic patients. Vitamin D deficiency can have a possible connection with chronic diabetic complications. The purpose of the study was to evaluate the effect of vitamin D status on the development of diabetic complications in adolescents with type 1 diabetes mellitus.

Methods: The study involved 124 children aged 10 – 18 years (average age 14.38 ± 2.15 years), among them 61 girls, 63 boys. Participants were divided in 2 groups: 91 adolescents with type 1 DM (group 1), average age 14.43 ± 2.18 years, and 33 healthy children of the same age (group 2), average age 14.21 ± 2.07 years. Clinical evaluation of the patients, medical history, laboratory and statistical methods of research were used during the study. The level of 25(OH)D hydroxycholecalciferol in the blood serum was conducted using electrochemiluminescence method (Cobas analyzer). Vitamin D deficiency was diagnosed according to the Endocrine Practice Guidelines Committee and Institute of Medicine. The level of vitamin D: < 20 ng/ml (50 mmol/l) was marked as vitamin D deficiency, 21 – 29 ng/ml (50.1 – 74.9 nmol/l) – vitamin D insufficiency, > 30 ng/ml (75.0 nmol/l) was considered to be optimal.

Results: The results of the study clearly reflected the absolute prevalence of low vitamin D status among adolescents with type 1 diabetes mellitus: 70.33 % of the participants had vitamin D deficiency (n = 64), 23.08 % – insufficiency (n = 21), 6.59 % had optimal vitamin D levels (n = 6).

Chronic complications of type 1 diabetes (distal diabetic polyneuropathy, diabetic nephropathy) were present in 28.57 % (n = 26) of the participants. The majority of children with type 1 diabetes were diagnosed with diabetic distal polyneuropathy (77.42 %; n = 24) and 22.58 % (n = 7) had diabetic nephropathy.

Analysis of vitamin D status has shown that optimal levels of vitamin D were absent among adolescents with diabetic complications. Instead, the majority of participants had vitamin D deficiency (83.33 %, n = 20), 16.67 % of participants with diabetic polyneuropathy had insufficient levels of vitamin D. The average vitamin D level among children with distal diabetic neuropathy was 15.69 ± 1.69 ng/ml. The study showed that children with type 1 diabetes and vitamin D deficiency have a risk of developing diabetic neuropathy 2.9 times higher compared to adolescents with type 1 diabetes with sufficient vitamin D levels (RR = 2.84; 95 % CI: 1.04 – 6.98; χ2 = 3.5, p < 0.05). It should be noted that the average vitamin D levels in adolescents with diabetic complications were significantly lower than among adolescents with type 1 diabetes without complications (18.08 ± 0.43 ng/ml), p < 0.05.

Conclusions: Vitamin D deficiency is important among adolescents with type 1 diabetes mellitus. Children with type 1 diabetes and vitamin D deficiency have a higher risk of developing diabetic neuropathy compared to the patients with type 1 diabetes with sufficient vitamin D levels. The researchers should consider new possibilities for prevention of the development of diabetic complications.

PS 5: Brain injury, complications, vitamin D

P 17: Melatonin mitigates diabetes-­induced brain injury in experimental T2DM rat model

Amr Elmessiry M, Amer ME, Othamn AI; Mansoura, Egypt

Background: Diabetes mellitus (DM) has a variety of harmful effects on the brain and leads to a variety of neurodegenerative diseases. The brain is susceptible to oxidative stress due to high oxygen consumption, low antioxidants, and increased levels of redox-active transition metals.

Melatonin (MLT) is a neurohormone primarily synthesised in the pineal gland with multifunctional activity. Although several studies reported the beneficial effects of MLT on chronic brain injury in type 1 diabetes mellitus (T1DM), information on protective effect of MLT on T2DM-induced brain injury at early onset of T2DM are limited and incompletely clarified. Therefore, this study aimed to investigate the effect of MLT on T2DM-induced brain alterations including changes in redox state, neurotransmitters, and accumulation of amyloid-β, tau, homocysteine (Hcy), and apoptotic regulating proteins at early development of diabetes.

Methods: MLT (10 mg/kg) was administered daily for 15 days after diabetic induction by mixture of nicotinamide and streptozotocin (STZ) to induce T2DM rat model.

Results:MLT remarkably downregulated serum glucose levels. It also improved levels of the lipid peroxidation product 4-hydroxynonenal, improved levels of antioxidants including glutathione, glutathione peroxidase and glutathione reductase in the brains of the diabetic rats, and this is indicative of the antioxidant potential of MLT. MLT also prevented increase in homocysteine, amyloid-β42 and tau levels in diabetic rats. Treatment with MLT improved diabetes-induced structural alteration in the hippocampus and cerebral cortex. MLT significantly reduced caspase-3 and Bax as well as significantly increased Bcl-2 protein and GFAP-positive astrocytes indicating its anti-apoptotic effect.

Conclusions: This study shows that MLT remarkably protects the brain against DM-induced brain alteration and injury. The neuroprotective effect of MLT is confirmed by the decrease in glucose level, improvement in neurotransmitter levels, decrease in Aβ, tau and Hcy accumulation, amelioration of oxidative stress, and inhibition of apoptosis-activating proteins. The major advantages of melatonin are its low cost, safety over a very wide dose range, its long shelf-life and its ability to be self-administered. This study supports the recommendation that use of melatonin in clinical trials on diabetic human beings is feasible and important.

P 18: Cardiopulmonary resuscitation: knowledge and attitude of doctors from Lahore

Iqbal A; Lahore, Pakistan

Background: Cardiopulmonary resuscitation (CPR) is described by the American Heart Association (AHA) as a part of a ‘chain of survival’ that is an emergency medical procedure for the victims of sudden cardiac/respiratory arrest. Inadequacy in any step of CPR due to insufficient knowledge and attitude is associated with poor outcomes. There has not been any study done in Lahore (Pakistan) to evaluate the knowledge and attitude of doctors regarding CPR. Furthermore, it is the largest study done so far in Pakistan with regard to this topic.

Methods: A cross-sectional study has been conducted from March 2019 to March 2020 in six hospitals of Lahore. A structured questionnaire designed according to current AHA guidelines was used. Total respondents were 724. Data were analysed using statistical package for social sciences (SPSS) version 23. Knowledge was assessed based on the scores (good knowledge: score ≥ 10/15, poor knowledge: score < 10/15).

Results: Knowledge of 600 (83 %) respondents was poor and only 123 (17 %) doctors had good knowledge. The score increased with increase in years of experience, except for the unusually low score achieved by the consultants.

Conclusion: Doctors’ overall knowledge of CPR is not satisfactory. However, attitude of the doctors toward CPR is positive.

P 19: Prevalence of vitamin D deficiency in pregnant women: an Algerian cross-sectional study

Gouri A, Aoures H, Dekaken A, Gasmi R, Taamallah A, Benharkat S; Annaba, Algeria

Background: Vitamin D deficiency during pregnancy is associated with multiple adverse health outcomes in mothers and neonates. There are no representative data available on vitamin D status of pregnant women in Algeria. Thus, the main aim of this study was to estimate the prevalence of vitamin D deficiency among Algerian pregnant women.

Methods: Blood samples of 114 pregnant women living in three northern Algerian cities (Annaba, Guelma and El Taref) were collected and a questionnaire was completed face-to-face. Plasma 25-hydroxyvitamin D (25-OHD) was determined by a chemiluminescence immunoassay method.

Results: Plasma 25-OHD concentrations ranged from 3.02 to 51.41 nmol/l (median [IQR] 19.0 [14.8]). More than 94 % of the study population had 25-OHD levels below 30 ng/ml with 82.1 % of women having vitamin D deficiency (25-OHD < 20 ng/ml) and 31.4 % of women having severe vitamin D deficiency (25-OHD < 12 ng/ml).

Conclusion: For Algerian pregnant women, given the high prevalence and the severity of vitamin D deficiency, it would be important to introduce vitamin D supplementation to improve maternal and neonatal health.

9 European CME credits (EACCME)

The CVOT Summit 2021, Munich, Germany, 18/11/2021–19/11/2021 has been accredited by the European Accreditation Council for Continuing Medical Education (EACCME®) with 9 European CME credits (ECMEC®s). Each medical specialist should claim only those hours of credit that he/she actually spent in the educational activity.

Redaktion „Diabetes, Stoffwechsel und Herz“
Verlag Kirchheim & Co GmbH
Wilhelm-Theodor-Römheld-Str. 14, 55130 Mainz

Erschienen in: Diabetes, Stoffwechsel und Herz, 2021; 30 (6) Seite 407-422