bluuebunny/crossref_metadata_2025 huggingface dataset:
LOW MOLECULAR WEIGHT HEPARIN AT HIGH DOSE IMPACTS ON OUTCOME OF COVID-19 HOSPITALIZED PATIENTS, WHILE STANDARD DOSE DOESN’T
Authors: Bonetti Silvia , Boari Gianluca E.M. , Chiarini Giulia , Faustini Cristina , Bianco Gianluca , Braglia-Orlandini Federico , Malerba Paolo , Rizzoni Damiano
Published: April 2021

Objective:

COVID-19 is a new disease caused by pandemic SARS-CoV-2, that involves multiple organs and can cause a potentially fatal respiratory distress syndrome. Accumulating evidence point out that an “endothelitis” due to a cytokines storm causes intravascular thrombosis, especially in the lungs, and is related to the poor outcome.

We tested possible relationships between anticoagulant treatment and/or administration of low molecular weight heparin (LMWH) at different doses and outcome in a population of 258 COVID-19 patients admitted from February 28th to April 30th, 2020 to General Medicine ward of the Hospital of Montichiari (Brixia, Italy).

Design and method:

A group of 258 consecutive patients (174 males and 84 females, mean age 71 years +/- 14) was included in the present study. In 168 patients, high-flow oxygen was required (Venturi mask), 6 patients needed orotracheal intubation and 20 were given continuous positive pressure oxygen therapy (CPAP). Patient were treated (unless a pulmonary embolism was detected) with different doses of prophylactic LMWH, according to emerging evidence during pandemic period. As of June 10th, 65 deaths had been observed. Survival curves were calculated according to Kaplan-Meier method. Comparison between groups was performed with Breslow and Mantel-Cox test.

Results:

LMWH at standard dose (4000 IU once daily) didn’t reduce mortality compared to no treatment (p = ns), while LMWH at a higher dose than usual prophylactic dose (enoxaparin 6000 IU once daily or 4000 IU bid) was associated with better outcome (p < 0.001 vs untreated and treated with standard dose). Significance was confirmed adding patients treated with oral anti-coagulant (OAC)for any reason. None of the patients treated with LMWH at higher doses or OAC died.

Conclusions:

The administration of subcutaneous LMWH at a higher dose than indicated for deep vein thrombosis prophylaxis is associated with a better outcome in patients with SARS-CoV-2 pneumonia, confirming some emerging evidence.
EFFECT OF ONGOING TREATMENT AND DIFFERENT THERAPIES ON PROGNOSIS IN COVID-19 PATIENTS IN AN HOSPITAL SETTING
Authors: Bianco Gianluca , Boari Gianluca E.M. , Bonetti Silvia , Chiarini Giulia , Orlandini Federico Braglia , Faustini Cristina , Malerba Paolo , Rizzoni Damiano
Published: April 2021

Objective:

Patients affected by novel pandemic SARS-CoV-2 may develop COVID-19 related pneumonia, which is potentially fatal. To date, the role of ongoing treatments for different conditions (such as hypertension) has been clarified in terms of their impact on survival and there is no established specific therapy for the disease, although many molecules are under investigation. Aim of the present study was testing those two issues in a population of 258 consecutive patients admitted from 29 February to 30 April 2020 to General Medicine ward of the Hospital of Montichiari (Brixia).

Design and method:

A group of 258 patients (173 males and 85 females, aged 71 ± 14) was enrolled. Their medical record and ongoing treatment were assessed. Patients were treated according to emerging information with oxygen, anti-malarian agents, anti-viral drugs, different antibiotics (azithromycin and others), tocilizumab and low molecular weight heparin (LMWH) at different doses. As of June 10th, 65 deaths had been observed. Survival curves were calculated according to Kaplan-Meier method. Comparison between groups was performed with Breslow and Mantel-Cox test

Results:

Ongoing therapy with ACE-inhibitors at the time of admission was associated with a worse prognosis (p = 0.004), while no difference in survival was observed in patients under treatment with ARBs (p = 0.68). Ongoing treatment with statins (p < 0.001), low-dose aspirin (p < 0.001) and steroids (p < 0.001) was associated with a poorer outcome as well

Administration during hospitalization of LMWH (p < 0.001), steroids (p < 0.001), anti-viral drugs (p = 0.002), anti-malarian drugs (p < 0.001) and tocilizumab (p < 0.001), improved prognosis, while antibiotics (azithromycin and other) didn’t have any impact.

Conclusions:

our experience confirms most findings in ongoing trials. Surprisingly, treatment with ACE-inhibitors seems to impact negatively on survival in patients affected by SARS-CoV-2 pneumonia. A possible explanation may be that patients treated with certain drugs are more comorbid and due to this, more fragile.
THE INFLUENCE OF LIRAGLUTIDE ON THE LEVEL OF BLOOD PRESSURE IN PATIENTS WITH ARTERIAL HYPERTENSION AGAINST THE BACKGROUND OF OBESITY AND TYPE 2 DIABETES MELLITUS
Authors: Zhuravlyova Larysa , Rogachova Tetyana , Sokolnikova Nelya , Filonenko Maryna
Published: April 2021

Objective:

To assess the effect of liraglutide (L) on the level of blood pressure (BP) in patients with arterial hypertension (AH) and obesity against the background of type 2 diabetes mellitus (T2DM).

Design and method:

A total of 55 patients with stage II AH and concomitant non-severe T2DM were examined (fasting plasma glucose <12 mmol/L, glycosylated hemoglobin (HbA1c) - 8.75 ± 1.4%, disease duration 6.4 ± 1.8 years, mean age 51.4 ± 2.7, BMI 35.2 ± 2.6 kg/m2, mean BP 165/103 ± 3.4/2.2 mm Hg). Patients were distributed into 2 groups: the comparison group consisted of 22 patients who received metformin 850 mg 2/day, lisinopril 10 mg 1/day and amlodipine 10 mg 1/day. Patients of the main group (L-group, n = 23), received liraglutide 1.8 mg in addition to similar therapy.

Results:

6 months after the initiation of therapy, the following results were obtained: HbA1C in the L group was 6.35 ± 0.5%, and in the comparison group - 7.78 ± 0.45% (p < 0.05). BMI in the L-group was 30.28 ± 1.1 kg/m2, and in the comparison group - 32.5 ± 1.2 kg/m2. Systolic blood pressure (SBP) in the L-group was 132 ± 8.23 mm Hg., and in the comparison group - 143.5 ± 10.15 mm Hg., p < 0.05 of difference between groups. The diastolic blood pressure (DBP) in the L- group was 84.5 ± 3.7 mm Hg, and in the comparison group - 89 ± 5.5 mm Hg, significant differences were not identified.

Conclusions:

A significant decrease in SBP during treatment with liraglutide in patients with hypertension against the background of obesity and type 2 diabetes can be due to both significant loss of body weight and an improvement of metabolic control. The obtained data suggest that liraglutide has a potential to reduce cardiovascular risk in hypertensive patients with obesity and diabetes.
THE ASSOCIATION BETWEEN ARTERIAL STIFFNESS AND CIRCULATING ADIPOKINE IN PATIENTS WITH TYPE 2 DIABETES AND COMORBID OVERWEIGHT OR OBESITY
Authors: Varahabhatla Sai Krishna Ragh , Soloviuk Oleg Olegovich , Soloviuk Olena , Nazarenko Elena
Published: April 2021

Objective:

Omentin-1 is a circulating adipokine with anti-inflammatory, anti-atherosclerotic, cardioprotective effects. It is hypothesised that reduced levels of omentin-1 is connected with increase in arterial stiffness, thus leading to the rise in acute vascular events. A strong relationship between arterial stiffness and the levels of circulating omentin-1 in patients with diabetes mellitus type 2 (DM-2) and comorbid overweight or obesity was adapted from literature which necessitated for this study.

Design and method:

98 patients with diabetes mellitus type 2 were examined, of which 64 patients (34 women and 30 men) with comorbid overweight or obesity (BMI more than 25), included in the 1st group, 34 patients with normal body weight (19 women and 1 5 men) were in the 2nd group at the Regional Hospital, Zaporizhzhia. As a control, 28 practically healthy individuals were examined, comparable with the 1st and 2nd groups by age and sex. The levels of circulating Omentin-1 was determined by enzyme-linked immunosorbent assay and arterial stiffness was assessed by the pulse wave velocity (PWV) of the elastic and muscular arteries during rheovasography.

Results:

Results: In patients of the 1st group, the level of omentin-1 was 127.5% lower than in the 2nd group, with a longer duration of diabetes, the average values of omentin-1 were lower by 39.2% (p < 0.05) in Group 1 and 25.9% (p < 0.05) in group 2 compared with the control group. PWV in muscular arteries in the 2nd group was 15.7% higher than in the 2nd and 34.3% than in the control; Differences in elastic arteries were 10.6% and 30.5%, respectively. A relationship was established between the level of omentin-1, as well as PWV in the muscular (r = -0.56, p < 0.05) and elastic arteries (r = -0.47, p < 0.05).

Conclusions:

In patients with DM-2 and comorbid overweight or obesity, a decrease in the level of omentin-1 was noted, which was associated with high arterial stiffness leading to an increased cardiovascular mortality risk. Thus, omentin-1 is a potential biomarker and a new combined therapeutic target for metabolic and vascular diseases.
IS THERE A RELATIONSHIP BETWEEN NON-DIPPER PATTERN AND CARDIOVASCULAR EVENTS IN HYPERTENSIVE PATIENTS WITH DIABETES?
Authors: Stojanovic Milovan , Deljanin-Ilic Marina , Ilic Stevan , Stojanovic Sanja
Published: April 2021

Objective:

To determine the influence of diabetes mellitus (DM) on circadian blood pressure rhythm and to investigate is there a relationship between non-dipper pattern (ND) and cardiovascular events (coronary artery disease - CAD, stroke) in patients with DM and arterial hypertension.

Design and method:

184 consecutive hypertensive pts (92 men and 92 women, mean age 63.21 ± 12.62) were divided in two groups: 58 pts with type 2 diabetes mellitus (DM group) and 126 pts without diabetes (no-DM group). In all pts ambulatory blood pressure monitoring (AMBP) were performed. The values obtained by AMBP were compared between groups. ND pattern was defined as the absence of normal nocturnal fall of blood pressure (less than 10% and more than 20% compared to daily values).

Results:

Patients in DM group had higher systolic blood pressure (129.7 ± 17.4 vs 119.9 ± 11.5 mmHg, p = 0.001), higher values of the pulse pressure (58.7 ± 11.9 vs. 49.5 ± 9.0, p < 0.001) and larger burden of high blood pressure during AMBP (51.7% vs 22.2%, p = 0.001) in comparison to pts in no-DM group. Hyperlipidemia (84,5% vs. 70,6%; p < 0,05) and CAD (27,6% vs. 12,7%; p < 0,05) were more common in the DM than in no-DM group. Out of 184 hypertensive pts 129 pts were nod-dippers. There was borderline significant association between the ND pattern and CAD (20.9% vs. 9.1%, p = 0.058) but without significant association with stroke (6,2% vs 1,2%, p = 0.283). Prevalence of ND pattern was higher in DM group but without significant difference compared to no-DM group (75,9% vs 67,5%, ns). In patients with DM there was no significant association between ND pattern and CAD (31,8% vs 14,3%, p = 0,308) compared to dippers. Also, there was no significant association between ND pattern and stroke in pts with DM (6,8% vs 7,1%, ns).

Conclusions:

Our study showed that hypertensive pts with DM have inadequate regulation of blood pressure which results in higher values of systolic and pulse pressure and higher prevalence of non-dipping pattern than in hypertensive pts without DM, but failed to prove that there is a relationship between non-dipping pattern and cardiovascular events in patients with DM.
ARTERIAL STIFFNESS AND ITS CORRELATION WITH LABORATORY PARAMETERS AND INDICATORS OF OBESITY IN DIABETIC HYPERTENSIVE PATIENTS
Authors: Novak Ivana , Milin Sara , Nenadic Dora Bucan , Radic Josipa
Published: April 2021

Objective:

Arterial stiffness can be assessed by a variety of non-invasive methods. One of the measures of arterial stiffness that has been used in clinic for some time now is pulse wave velocity (PWV). PWV can be measured with “Agedio B900” device which, in addition to measuring arterial pressure, gives information about arterial stiffness and cardiovascular age. The aim of this study was to evaluate correlations of PWV with age, laboratory parameters and indicators of obesity in Dalmatian diabetic hypertensive patients.

Design and method:

106 hypertensive diabetic patients, 66 (62.3 %) men and 40 (37.7%) women, aged 69.5 (range 36-94) years were included. For each patient data about age, gender, body weight and height were collected and BMI (body mass index), WC (waist circumference) and MUAC (mid-upper circumference) were calculated. Also, values of laboratory parameters such as haemoglobin (Hg), urea, creatinine, urate, albuminuria, cholesterol and triglycerides were taken for each patient. The Agedio B900 device was used for the measurement of arterial pressure and PWV calculation. Each study subject was measured with Tanita MC780 Multi Frequency segmental body composition analyser to record whole body and segmental measurements of body composition.

Results:

PWV was significantly higher in patients over 65 years old than those younger than 65. Among the laboratory parameters statistically significant correlation was found only between PWV and Hg (Rho= -0.365, p = 0.02). Among the indicators of obesity, only MUAC showed significant correlation (Rho = -0.316, p = 0.01). However, statistical significance was reached after making adjustments for age, eGFR, urea, creatinine and albuminuria. All of the variables of body composition affected PWV (p < 0.001, R2 = 0.28) but BMI (p < 0.001), fat mass (p < 0.001) and muscle mass (MM) of the trunk (p < 0.001) and skeletal MM to body fat ratio (p < 0.001) stood out.

Conclusions:

PWV was correlated to all the variables of body composition after making adjustments for age and markers of kidney function. Future studies with larger number of participants should evaluate correlation of PWV with the observed parameters in this population of patients.
EFFECTS OF ANGIOTENSIN RECEPTOR BLOCKER AZILSARTAN IN ARTERIAL HYPERTENSION COMBINED WITH TYPE II DIABETES MELLITUS
Authors: Musayev Zaur , Rasulova Gulshan , Dadasheva Antiga
Published: April 2021

Objective:

Arterial Hypertension (AH) with type II Diabetes Mellitus (DM II) is characterized by diminished myocardial compliance with diastolic dysfunction and impaired left ventricular filling. Angiotenzin receptors blocker (ARB) Azilsartan (Az) is antihypertensive drug in AH combined with DM II for good tolerance and metabolic neutrality. Az in AH patients with DM II is unexplored in view of influence on cardiac systolic and diastolic parameters. The interrelation between long-term Az treatment and basic metabolism lipid, carbohydrate indices alterations in AH coupled with DM II is disputable. The purpose of study was evaluation of ARB Az's antihypertensive, hemodynamic and metabolic actions in AH patients with DM II.

Design and method:

72 diagnosed I-II WHO classification AH patients without coronary artery disease and congestive heart failure signs with DM II were examined (46 male, 26 female, 42–63 aged, mean age 52+/-2,1 years old, body mass index 32+/-1,8 kg/m2, systolic and diastolic blood pressure (SBP,DBP) range 145/90-179,109 mm Hg, mean blood pressure (MBP) 120+/-3,1 mm Hg. Az was administered once daily 40–80 mg in addition to basic management of DM II.

Results:

Az significantly reduced SBP 169+/-5.3 vs 148+/-5.1 mm Hg, diminution -12.4% (p<0.02), DBP 104+/-2.6 mm Hg vs 91+/-2.8 mm Hg, diminution-12.6% (p < 0.02), MBP 120+/-3.1 mm Hg vs 106+/-4.4 mm Hg, diminution 11.7% (p < 0.02). Early diastolic filling flow velocity (Peak E) increased significantly 0.56+/-0.033 vs 0.79+/-0.048 m/sec, augmentation+28.9% (p < 0.02). After 4 weeks SBP, DBP, MBP significantly decreased (p < 0.02), 12-weeks management resulted in BP reduction (p < 0.01). No negative changes of carbohydrate, lipid metabolism indices and GFR observed, moreover 12-weeks Az treatment had a trend to some improvement of blood and urine glucose level, lipids and lipoprotein fractions.

Conclusions:

Az in I-II AH patients with DM II resulted in antihypertensive effect, left ventricular systolic and diastolic performance indices improved. Study didn’t reveal any negative changes of metabolism and GFR. Metabolism indices improvement was marked probably on account of Atherosclerosis prevention actions. Az improves systolic performance and diastolic compliance in AH with DM II, positively affects on metabolism indices. Long-term Az treatment in AH combined with DM II should explored further.
FRAGILITY INDEX OF VARIOUS GLP1 AGONISTS ON CARDIOVASCULAR OUTCOMES IN PLACEBO CONTROLLED TRIALS
Authors: Mourad Jean -Jacques , Voisin Olivier , Le Lorch Erwan , Hubert Sidonie , Menage Elodie , Mahe Anabelle , Borie Marie -Francoise , Azria Philippe , Antakly Yara
Published: April 2021

Objective:

Several well-designed randomized controlled trials (RCTs) have been conducted to evaluate the cardiovascular and renal effects of Glucagon-Like Peptide receptor agonists (GLP1) in type 2 diabetes. Their results have largely influenced the most recent dedicated therapeutic recommendations. Traditionally, p-values and confidence intervals have been used to denote the statistical significance of RCT results. However, even with a p-value and a confidence interval, the clinician cannot immediately discern how likely the study, if repeated, would yield a different and potentially conflicting result. The Fragility Index (FI) was developed as a novel metric to further assess the quality of statistically significant results and assist with the interpretation and clinical applicability of RCT findings, by providing the absolute number of patients or events from an RCT whose alternate outcome would have resulted in the study no longer being statistically significant. To date, there have been no studies evaluating the statistical fragility of GLP1 agonists RCTs.

Design and method:

We performed a systematic review of GLP1 cardiovascular outcomes trials using the PubMed database and calculate the FI for the specified primary endpoint, non-fatal myocardial infarction, non-fatal stroke, cardiovascular and all-cause death and renal outcomes as defined for each trial. The larger the FI the better (more robust) a trial's data are. A FI index reported as ‘0’ clearly emphasizes the lack of robustness of the data.

Results:

Results: We identified and included 7 trials, that involved 6 different molecules. The results are depicted in the following figure.

Conclusions:

Conclusion: In trials reported to date, the CV and renal benefits of GLP-1 agonists are not consistent across this class of medications. The Fragility Index may help clinicians to identify how easily a particular RCTs statistical significance may be overturned and to choose the molecule with the more robust expected benefit.
HIGH NORMAL BLOOD PRESSURE CAN CAUSE DECLINE OF ATTENTION FUNCTION AMONG ELDERLY OUT-PATIENTS WITH DIABETES: SHIP-FD 5-YEAR FOLLOW-UP STUDY
Authors: Miyamatsu Naomi , Murata Shin , Okamoto Tomoko , Ichikawa Mizuki , Azuma Saori , Sumimoto Yuka , Tatsumi Yukako , Shima Azusa , Morino Katsutaro , Miyazawa Itsuko , Ugi Satoshi , Maegawa Hiroshi , Ogita Mihoko
Published: April 2021

Objective:

We evaluated which degree of increased BP would cause diminished attention function, one of the higher-order brain functions, among patients with diabetes.

Design and method:

We conducted a baseline survey regarding cognitive/physical function in diabetic out-patients in 2014 and its follow-up study in 2019. The decline of attention function was defined by the delta of the performance time of trail making test part A (TMT-A) at baseline and follow-up. Delta TMT-A was categorized into three levels; under 0 second as “not decline” (ND), 0–10 seconds as “slight decline” (SD), and 10 and over as “moderate decline” (MD). Office blood pressure level was categorized into normal, high-normal, elevated, grade I hypertension, and grade II and III hypertension according to JSH2019. Multinomial logistic regression analyses were performed adjusting for sex, age, HbA1c and usage of antihypertensives at baseline survey to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) of the decline of attention function by BP levels.

Results:

Among 157 participants (mean age: 65.0 years, 63.7% men) whose delta TMT-A was assessed, proportions of SD and MD were 23% and 20% in normal (n = 35), 23% and 51% in high-normal (n = 35), 24% and 36% in elevated (n = 42), 34% and 28% in grade I (n = 32), and 54% and 31% in grade II and III hypertension (n = 13). After excluded participants with TMT-A at baseline >=117.5 seconds or with missing values of co-variates, 142 remained for further analyses. Multivariate adjusted ORs (95% CIs) of MD, referring normal, were 8.60 (2.07–35.6) by high normal, 3.67 (0.99–13.5) by elevated, 2.78 (0.67–11.6) by grade I, and 6.95 (0.90–53.7) by grade II and III. Any significant increase in SD risk by BP categories was not observed. Even after adjusting TMT-A time and MMSE at baseline, results were similar. After stratified by age, this relationship was observed only in participants aged 65-year and older.

Conclusions:

The present study indicated that high-normal BP might promote the lowering of attention function in elderly patients with diabetes. Further study with a longer follow-up period is needed to assess the effect of BP on attention dysfunction in adult patients.
CAN WE IDENTIFY GLOMERULAR HYPERFILTRATION IN PATIENTS WITH TYPE 2 DIABETES BY CLINICAL PARAMETERS?
Authors: Kolwelter Julie , Striepe Kristina , Kannenkeril Dennis , Jung Suanne , Bosch Agnes , Ott Christian , Schmieder Roland E.
Published: April 2021

Objective:

In the early state of renal involvement in patients with type 2 diabetes (T2DM), glomerular hyperfiltration is often found, preceding the onset of albuminuria, leading to a slow decline of kidney function and finally to end-stage kidney disease. Our study goal was to identify the patients with glomerular hyperfiltration by clinical parameters.

Design and method:

In this cross-sectional study, we analyzed 192 patients with T2DM in the early stage of the disease having a normal renal function estimated by the CKD-EPI formula (eGFR). In each patient we measured glomerular filtration rate (mGFR) and renal plasma flow (RPF) by applying the constant infusion input clearance technique with inulin and sodium p-aminohippurate (PAH). In our study population, glomerular hyperfiltration was defined as mGFR >= 142 ml/min (>= 75th percentile). We assessed clinical and renal hemodynamic parameters. We also analysed the changes in renal function after medication.

Results:

Of all the patients with glomerular hyperfiltration (n = 50), only 12 patients had also an eGFR above the 75th percentile (eGFR >= 100 ml/min/1.73m2) and only 6 showed a microalbuminuria. Patients with glomerular hyperfiltration had significantly lower BMI, uric acid as well as cystatin C levels. BP, HbA1c, fasting plasma glucose or diabetes duration were not different between the two groups. Patients with glomerular hyperfiltration had significantly higher renal plasma flow, consequently higher renal blood flow and filtration fraction as well as intraglomerular pressure. The resistance in the vas afferens was significantly lower and in the vas efferens significantly higher than in patients with mGFR < 75th percentile.

The sensitivity analysis (using the 70th, 80th and 90th percentile) did show similar results. Of the 192 patients, 6 patients showed an increase and 7 patients a decrease by 20% in mGFR. One of the 13 patients had a concordant increase or decrease, respectively, by 20% on the eGFR corrected for the actual body surface area.

Conclusions:

The data suggest that patients in the early stage of T2DM with glomerular hyperfiltration and thereby at risk for diabetic kidney disease are not identifiable by routinely used clinical parameters.
THE BODY MASS INDEX INFLUENCES THE ACHIEVEMENT RATIO OF TARGET BLOOD PRESSURE BY SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS IN JAPANESE TYPE 2 DIABETES PATIENTS WITH CKD
Authors: Kobayashi Kazuo , Tamura Kouichi , Toyoda Masao , Sakai Hiroyuki , Furuki Takayuki , Hatori Nobuo , Sato Kazuyoshi , Miyakawa Masaaki , Kanamori Akira
Published: April 2021

Objective:

Some large clinical trials using sodium-glucose cotransporter 2 inhibitor (SGLT2i) revealed the superiority in the renal outcome in type 2 diabetes mellitus (T2DM) patients. We already reported that the decrease in blood pressure (BP) was closely related to the renoprotective effects and SGLT2i was useful for the BP management in T2DM patients. The aim of this study is to clarify how body mass index (BMI; kg/m2) influence the achievement ratio of target BP by using SGLT2i in Japanese T2DM patients.

Design and method:

We retrospectively assessed 447 patients with Japanese T2DM patients with chronic kidney disease (CKD) who underwent SGLT2i treatment for more than 1 year and whose BP at office was uncontrolled (<130/80mmHg) before SGLT2i treatment. We set the endpoint that was the achievement of target BP at office (<130/80mmHg) after SGLT2i treatment. From ROC curve analysis, the estimated optimal cutoff value for BMI as a marker for the endpoint was 29.For comparative analyses, we performed the cohort model of patients with BMI > 29 at baseline or those with BMI <29, that was used propensity score–matching methods with the following algorithm: 1:1 nearest neighbor match with a ±0.047 caliper and no replacement.

Results:

The comparison of 130 propensity-matched patients in each group were performed. The incidence of the achievement of target BP after treatment was significantly higher in patients with BMI<29 at baseline than in those with BMI > 29 (n = 44 [33.8%] and n = 27 [20.8%], respectively, p = 0.018). The mean arterial pressure after SGLT2i treatment was significantly lower in patients with BMI<29, compared with those with BMI > 29 (94.5 ± 9.4 and 98.5 ± 10.0 mmHg, respectively, p = 0.002). From the analysis of mean prevalence of incidence of the endpoint depending on the quintiles of all patients, there was a significant difference between the two groups (p = 0.017) and the OR for the endpoint was 0.538 (95%CI,0.332, 0.873, p = 0.012, Mantel-Haenszel method) in patients with BMI<29.

Conclusions:

The BMI influenced the achievement ratio of target BP in Japanese T2DM patients with CKD. Further study should be performed to clarify the relation between obesity and BP lowering effects by SGLT2i treatment.
MAGNESIUM CITRATE IN UNTREATED PREDIABETICS AND TYPE II DIABETICS - A 12 WEEKS PLACEBO-CONTROLLED DB TRIAL
Authors: Werner Tanja , Kisters Klaus , Kisters Lukas , Vormann Jürgen
Published: April 2021

Objective:

In hypomagnesemic prediabetics and type II diabetics, Mg supplementation has beneficial effects on glycemic control and reduced diabetes medication. In addition, a positive effect of a magnesium therapy is known on blood pressure. This placebo-controlled double-blinded pilot trial was performed to evaluate the role of Mg supplementation in new-diagosed, untreated type II diabetics without hypomagnesemia.

Design and method:

50 subjects of age 64+/-13 years were randomly assigned to the Mg supplementation group receiving 400 mg Mg from Mg citrate daily for 12 weeks or placebo. Due to low numbers of untreated type II diabetics (inclusion criterium HbA1c >6%) within the pro-longed recruiting phase, untreated subjects with HbA1c >5.5% and high blood pressure were included (complete dataset for analysis included 18 for placebo and 19 for Mg). Blood parameters, blood pressure and body weight were determined before, after 6 and 12 weeks of supplementation.

Results:

Within the Mg group there was a highly significant decrease in blood pressure over supplementation period (144+/-10/86+/-4 vs 130+/-5/81+/-2 vs. 122+/-6/78+/-3 mmHg)(p<0.01).

Mg supplementation resulted in a significant decrease in HbA1c (6.24+/-0.62 vs. 6.05+/-0.5 vs. 6.0+/-0.46%)(p<0.01).

Mg therapy led to a significant increase in plasma Mg concentration (1.92+/-0.19 vs. 1.99+/-0.17 vs. 2.0+/-0.18 mg/dl)(p < 0.01).

Vitamin D Levels significantly increased in both groups.

There was no positive effect on cholesterol, triglycerides, CRP, IL-6, creatinine, calcium body weight or life quality questionnaire (SF-36)(ns).

Conclusions:

In untreated prediabetic patients with hypertension, oral Mg citrate supplementation improved glycemic control and reduced high blood pressure.
EFFECT OF A GLP-1 RECEPTOR AGONIST AND SGLT-2 INHIBITOR COMBINATION ON BLOOD PRESSURE LEVELS COMPARED TO SGLT-2 INHIBITOR ALONE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Patoulias Dimitrios , Imprialos Konstantinos , Stavropoulos Konstantinos , Katsimardou Alexandra , Kalogirou Maria , Manafis Alexandros , Lales Georgios , Sampanis Christos , Zografou Ioanna , Karagiannis Asterios , Doumas Michael
Published: April 2021

Objective:

Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now considered as key players in the treatment of type 2 diabetes mellitus (T2DM). We aimed at providing precise effect estimates regarding the effect of their combination on office blood pressure levels.

Design and method:

PubMed and CENTRAL, along with grey literature sources, were searched from their inception to May 2019 for randomized controlled trials (RCTs) with a duration equal to or greater than 12 weeks, evaluating the safety and efficacy of addition of a GLP-1RA on a SGLT-2i compared to SGLT-2i alone in patients with T2DM.

Results:

We identified three eligible RCTs (namely, AWARD-10, DURATION-8 and SUSTAIN 9 trials), pooling data retrieved from 1,042 patients with T2DM in total. All studies were rated as low risk of bias. Administration of the maximum dose of a GLP-1RA on top of SGLT-2i treatment compared to SGLT-2i alone resulted in a significant decrease in systolic blood pressure levels by 3.64 mmHg (95% CI: -6.24 to -1.03, I^2 = 68%), although it did not have a significant impact on diastolic blood pressure levels (mean difference= -0.51, 95% CI: -1.51 to 0.49, I^2 = 0%).

Conclusions:

Both SGLT-2i and GLP-1Ras have provided remarkable results regarding their cardiovascular efficacy in hallmark cardiovascular outcome trials recently. However, there are no data regarding the cardiovascular efficacy of their combination, questioning whether those two drug classes exhibit additive cardioprotective effects. The present meta-analysis suggests a significant, additive effect on systolic blood pressure levels. Further RCTs are required in order to shed light on this hypothesis.
SHORT-TERM CRIZOTINIB TREATMENT REVERSES GLUT4 GLUCOSE TRANSPORTER DOWNREGULATION IN DIABETIC RAT HEART
Authors: Hadova Katarina , Mesarosova Lucia , Doka Gabriel , Pivackova Lenka Bies , Krenek Peter , Klimas Jan
Published: April 2021

Objective:

Crizotinib is a multitarget ALK/c-MET/ROS1/RON inhibitor that can potentially inhibit non-intended receptor tyrosine kinases (RTKs) which play a role in cardiac development, function and/or metabolism. Tyrosine kinase inhibitors (TKIs) studies in diabetic patients showed antidiabetic effects of some TKIs and several potential mechanisms were suggested including mechanisms via RTKs. We examined RTKs after short-term crizotinib treatment in diabetic heart.

Design and method:

To induce diabetes, male Wistar rats were injected with streptozotocin (STZ; 80 mg/kg, i.p.), controls received vehicle (CON). After 3 days, diabetic rats were treated with crizotinib in a dose 25 mg/kg/day p.o. (STZ+CRI) or vehicle p.o. for 7 days (STZ). mRNA expression of selected RTKs were assessed by RT-qPCR method in rat left ventricle samples. Blood glucose, c-peptide and glucagon in plasma samples and expression of cardiac glucose transporters Glut1 and Glut4 were assessed to determine impact on glucose homeostasis.

Results:

Intriguingly, crizotinib had a hypoglycaemic effect in diabetic animals (plasma glucose in STZ: 19.2 mmol/L vs. STZ+CRI: 14.5 mmol/L., P<0.05). STZ animals had lower c-peptide and unaltered glucagon plasma levels. However, plasma levels of c-peptide and glucagon were not changed after crizotinib treatment suggesting altered glucose utilization in tissues. In STZ rats, we detected downregulation of insulin dependent glucose transporter Glut4 (by 40% as compared to CON, P < 0.05). Interestingly, crizotinib prevented this downregulation. Insulin non-dependent Glut1 glucose transporter remained stable across all groups. Diabetes upregulated cardiac insulin receptor and Igf-1 receptor without significant crizotinib impact. Regarding RTKs, we observed unaltered c-Met, Flt1 and Erbb2 expressions in diabetic hearts without influence of crizotinib.

Conclusions:

Crizotinib had a hypoglycaemic effect in diabetic animals after short-term treatment. This was independent of insulin and glucagon levels. Crizotinib prevented cardiac insulin-dependent Glut4 decrease. Downregulation of cardiac insulin receptor family RTKs expression remains stable under crizotinib suggesting modulation of alternative pathways responsible for crizotinib action in diabetic rat heart.
IN TYPE 1 DIABETES MELLITUS, CAROTID INTIMA-MEDIA THICKNESS SHOWS DIFFERENCES BETWEEN GENDERS EARLY AFTER PUBERTY
Authors: Bortolotti Stefano , Tagetti Angela , Giontella Alice , Branz Lorella , Marcon Denise , Minuz Pietro , Antoniazzi Franco , Fava Cristiano
Published: April 2021

Objective:

Type 1 diabetes mellitus (T1DM) is characterized by the early development of macrovascular damages in both genders but could manifest earlier in males. Traditional risk factors, along with T1DM per se, are associated with this process in T1DM. If specific differences in early vascular damage are viewable even during childhood in T1DM is unknown.

Design and method:

Arterial structural changes (carotid intima-media thickness [cIMT]) and vascular elasticity (carotid coefficient of distensibility [cDC] and Pulse Wave Velocity [PWV]) were measured in 180 children and adolescents with T1DM by carotid ultrasonography and the SphygmoCor XCel device. Hemodynamic and metabolic risk factors (peripheral and central systolic/diastolic blood pressure [pSBP/pDBP; cSBP], body mass index (BMI), glycated haemoglobin, triglycerides, total cholesterol, nonHDL/HDL-cholesterol ratio were also assessed. The sample was divided according to Tunner's stages (pre-pubertal-pubertal vs. post-pubertal) and gender: seventy-four subjects were classified as pre-pubertal-pubertal (44 male, mean age±SD 12 ± 2 years: 30 females, 12 ± 1.5 years) and 106 as post-pubertal (43 males, 16 ± 1 years; 63 females; age: 15.5 ± 1.5 years). Sex-specific linear regression models, adjusted for the pubertal state, BMI, duration of diabetes, glycated haemoglobin, nonHDL/HDL-cholesterol ratio, were constructed to assess the relation between risk factors and the markers of early vascular damage.

Results:

No differences in cIMT, cDC, PWV and the respective z-score were found between males and females in the pre-pubertal-prepubertal sub-group. In the post-pubertal group, males had higher cIMT (0.05 ± 0.01 mm; p-value: 0.001) and Z-score cIMT (0.62 ± 0.02; p-value: 0.04) but no differences in cDC and PWV were found.

In linear regression models, the only risk factors independently associated with z-cIMT, were the nonHDL/HDL-cholesterol ratio (b ± SEM:0.267 ± 0.30; p-value:0.03) in males and z-cSBP in females (b ± SEM:0.286 ± 0.13; p-value:0.01). z-PWV and z-cDC showed associations with different types of BP values both in males and females.

Conclusions:

Gender-specific differences in cIMT are present early after puberty in adolescents with T1DM but seem associated with different risk factors in males and females. Different preventive strategies could be beneficial in males and females with T1DM, starting during adolescence.
EXAMINATION OF THE EFFECT OF LIRAGLUTIDE ON BLOOD PRESSURE AND URINARY SODIUM EXCRETION
Authors: Akasaka Hiroshi , Sugimoto Ken , Onishi Yuri , Fujimoto Taku , Yoshida Shino , Kurinami Hitomi , Rakugi Hiromi
Published: April 2021

Objective:

GLP-1 analog is suitable for use in obese diabetic patients as a drug having an effect of improving postprandial blood glucose and suppressing weight loss. Recently, it has been reported that the use of this drug causes hypotension, and its mechanism is to act on the GLP-1 receptor of the proximal tubule to promote sodium excretion and increase NO production of vascular endothelium. However, few clinical reports have examined the antihypertensive effects of GLP-1 analogs. We investigated the effects of liraglutide on blood pressure and urinary sodium excretion.

Design and method:

The subjects were ten patients with type 2 diabetes who admitted to our department for the adjustment of the antidiabetic treatment regimen (age 66.9 ± 11.7 years, male 40%). Before introduction of liraglutide and before discharge, various tests including blood pressure and blood glucose control index and measurement of urinary sodium excretion. The dose of liraglutide was 0.3 mg/day for the first week, then increased to 0.6 mg/day, up to a maximum of 0.9 mg/day.

Results:

Both BMI and HbA1c (NGSP) decreased with the administration of liraglutide (BMI from 28.1 ± 3.8 to 27.0 ± 3.7, p < 0.001, HbA1c from 8.7 ± 1.5% to 7.5 ± 1.1%, p < 0.001). Urinary Na excretion increased with administration of liraglutide (frome 135.7 ± 13.71 mEq/day to 155.2 ± 30.7 mEq/day, p < 0.05). Systolic blood pressure tended to decrease in patients with hypertension (from 130.9 ± 15.0 mmHg to 124.0 ± 11.5 mmHg, p = 0.06).

Conclusions:

Liraglutide, a GLP-1 analog, showed an improvement in glycemic control and a weight loss effect, as well as a decrease in urinary Na excretion. The drug was considered to exhibit antihypertensive effects, particularly in cases of hypertensive complications.
THE EFFECT OF ADD-ON THERAPY OF LIRAGLUTIDE AND EMPAGLIFLOZIN ON AMBULATORY BLOOD PRESSURE IN PATIENTS WITH POORLY CONTROLLED TYPE 2 DIABETES MELLITUS
Authors: Tzouganatou Eleni -Margarita , Papazafiropoulou Athanasia , Mpoumi Louisa , Rallatou Maria , Papantoniou Styliani , Kamaratos Alexandros , Melidonis Andreas , Antonopoulos Stavros
Published: April 2021

Objective:

It is known that both liraglutide and empagliflozin, except for their anti-hyperglycaemic effect, have a favorable effect on major cardiovascular outcomes. Furthermore, it has been shown that they reduce systolic (SBP) and to a lesser extent diastolic blood pressure (DBP). Therefore, the purpose of this study is to evaluate the effect of liraglutide and empagliflozin on ambulatory BP in patients with poorly controlled type 2 diabetes (T2D).

Design and method:

42 patients [20 men, mean age (± SD): 60.6 ± 9.4 years, were randomized to liraglutide therapy. 32 patients (16 men, mean age: 64.8 ± 7.1 years), were randomized to empagliflozin therapy. All patients underwent a complete clinical examination, laboratory testing, and ambulatory BP recording on baseline and three months after initiation of treatment with liraglutide and empagliflozin. Ambulatory BP was measured with the oscillometric Mobil-O-Graph NGW 24-hour ambulatory BP and PWA monitor (IEM; Stolberg, Germany).

Results:

In the liraglutide group, daytime SBP and DBP, mean change from baseline was –4.0 mmHg (P = 0.26) and –3.6 mmHg (P = 0.05). Nighttime SBP and DBP, mean change from baseline was –8.9 mmHg (P = 0.009) and –5.6 mmHg (P = 0.009). In the empagliflozin group, for daytime SBP and DBP, mean change from baseline was –1.4 mmHg (P = 0.61) and 0.2 mmHg (P = 0.91), respectively. For nighttime SBP and DBP, mean change from baseline were –8.9 mmHg (P = 0.03) and –4.5 mmHg (P = 0.02), respectively. Liraglutide caused higher daytime SBP and DBP decline from baseline than empagliflozin (P = 0.005). No statistically significant differences were observed for nighttime SBP and DBP between the two study groups.

Conclusions:

The results of the present study showed a favorable effect of 3-month therapy with liraglutide had a favorable effect on daily DBP and SBP and DBP during the night. A favorable effect of 3-month therapy with empagliflozin on nighttime SBP and DBP was also observed. Liraglutide caused higher daytime SBP and DBP decline from baseline than empagliflozin.
A STUDY OF THE EFFECT OF TIME RESTRICTED MEAL INTAKE ON ANTHROPOMETRIC AND BIOCHEMICAL PARAMETERS IN PATIENTS OF TYPE 2 DIABETES
Authors: Rastogi Smriti , Verma Narsingh
Published: April 2021

Objective:

1. To study effect of time restricted meal intake on anthropometric and biochemical parameters in Type 2 diabetes patients.

2. To study if time restricted meal intake can act as an adjunct along with the standard conventional treatment of diabetes in patients of Type 2 diabetes mellitus.

Design and method:

384 Type 2 diabetes patients enrolled from OPD Endocrinology, King George's Medical University were randomly divided based on whether the patients consented to having early dinner TRM (time restricted meal) group (192 patients) or not (control group) (192 patients). Follow up was done at 6 and 12 months for anthropometric measurement, height, weight, waist hip ratio, neck size, fasting, post prandial blood sugar, HbA1c, serum urea, serum creatinine and lipid profile. The patient was given a clear understanding about chronomedicine. A single intervention was done - timing of dinner was at or around 7 pm in the evening for TRM group. Both groups were given standard conventional treatment of diabetes.

Result:

65% of TRM group, 40 % (non- TRM) had normal HbA1c after 12 months. BMI, Hip size, systolic blood pressure, HbA1c, blood sugar (fasting and post- prandial) were significantly different (p < 0.05) in TRM Group as compared to the p value of control group. p value <0.0167 observed in values of blood sugar (fasting) in TRM Group, p value < 0.8113 in control group. Blood sugar (post- prandial) in TRM Group a p value <0.0001 (highly significant), control group p value<0.6938. Hip size (TRM Group) p value < 0.0012 (Significant) (Difference between means=2.762 ± 1.261). BMI (TRM Group) p value = 0.0030, significant. Neck Size (TRM Group) p value= 0.9697, not significant. Waist Size (TRM Group)p value= 0.2832, not significant. Hip Size (TRM Group) p value = 0.0012, significant, correlation coefficient=0.8380. Systolic Blood Pressure (TRM Group) p value = 0.0211, significant. Diastolic Blood Pressure (TRM Group) p value = 0.536, not significant.

Results:

One of the first studies which has been undertaken in Indian diabetics, although the initial data obtained is encouraging yet further study is required to corroborate results.
MULTIMEDIA FOR DELIVERING PARTICIPANT INFORMED CONSENT IN CARDIOVASCULAR TRIALS
Authors: Chapman Niamh , Mcwhirter Rebekah , Armstrong Matthew , Fonseca Ricardo , Campbell Julie , Nelson Mark , Schultz Martin , Sharman James
Published: April 2021

Objective:

Obtaining informed consent is a cornerstone requirement of conducting ethical research. Traditional paper-based consent is often excessively lengthy, legalistic in character, and may fail to achieve desired participant understanding of study requirements. Multimedia tools including video and audio may be a useful alternative. This study aimed to determine the efficacy, usability and acceptability of stand-alone multimedia delivery of participant consent relating to a cardiovascular trial.

Design and method:

A total of 298 participants (63 ± 8 years; 51% female) were randomised to delivery of cardiovascular research study information and signed consent via multimedia (intervention; n = 146) compared with standard paper-based approach (control; n = 152) in a clinical research setting. Intervention was free of research staff and included short audio-visual explanations, with computer-based finger-signed consent. Efficacy, usability and acceptability were assessed by questionnaire.

Results:

All participants successfully completed allocated interventions. Efficacy parameters were significantly higher among intervention participants, including better understanding of study requirements compared with controls (P < 0.05 all). Intervention participants were also significantly more likely to engage with the study information and spend more time on the consent process and study questionnaire (P = 0.038 and P = 0.007, respectively). Both groups reported similar levels of acceptability of the consent process, although more control participants reported that the study information was too long (24% versus 14%; P = 0.020).

Conclusions:

A standalone multimedia consent process is effective for achieving participant understanding and obtaining consent on cardiovascular research in a clinical research setting free of research staff. Thus, multimedia represents a viable method to reduce the burden on researchers, meet participant needs, and achieve informed consent in clinical cardiovascular research.
COST-EFFECTIVENESS ANALYSIS FOR THE USE OF INTERVENTIONAL DECENTRALIZED TELEMONITORING (IDTM) IN HYPERTENSION THERAPY
Authors: Schmieschek Sebastian , Neumann Claas Lennart , Schulz Egbert G.
Published: April 2021

Objective:

We calculate quality-adjusted life years (QALY) and incremental cost-effectiveness ratio (ICER) for the use of interventional decentralized telemonitoring (idTM) in hypertension therapy. Both values are key performance indicators for cost-benefit and cost-effectiveness analysis of medical interventions.

The calculations compare blood pressure adjustment and the correlated reduction in risk of morbidity and mortality between idTM and standard therapy (ST).

Prior studies have shown idTM to significantly reduce the time required to reach blood pressure targets as well as to reduce the variability of blood pressure values. IdTM also allows maintaining blood pressure on target for a longer duration than ST.

Design and method:

Our QALY evaluation only takes myocardial infarction (MI) and stroke, the two most prominent comorbidities of hypertension, into account. Thus, the achievable QALY are likely to be underestimated by this analysis. We assume a linear correlation between elevated blood pressure and the risk of morbidity and mortality. Data on prevalence and morbidity have been included from statistical and medical publications on the German population while data on life quality come from an EQ-5D-based study performed in the US.

Results:

We calculate the ICER for both for the difference in QALY and blood pressure reduction in mmHg. The latter allows evaluating the cost-effectiveness of idTM independent of specific comorbidities.

Conclusions:

Even though idTM adds cost to the treatment of hypertension, we find that the resulting improvement of blood pressure significantly improves QALY and ICER over ST. Therefore, idTM in hypertension therapy is a promising concept both from a medical and cost-effectiveness point of view. Especially in the context of the upcoming evaluation of digital health applications (DiGA) by the German Federal Institute for Drugs and Medical Devices (BfArM), this is a crucial result. Furthermore, the results suggest idTM as a sensible candidate for addition as an element of standard care in Germany.