bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.