Intermittent-scanned continuous glucose monitoring with low glucose alarms decreases hypoglycemia incidence in middle-aged adults with type 1 diabetes in real-life setting

ObjectiveThere is limited real-life data demonstrating that hypo-/hyperglycemic alarms added to continuous glucose monitoring (CGM) improve metabolic control in adults with type 1 diabetes (T1D).We evaluated the usefulness of switching from a flash or intermittent-scanned continuous glucose monitoring (is-CGM) device without low or higher glucose alarms to a is-CGM device with alarms to prevent hypoglycemia in adults with T1D.MethodsIndividuals with T1D and fearful of hypoglycemia, prone to hypoglycemia unawareness, and/or experiencing severe hypoglycemia while using is-CGM Free Style Libre 1 (FSL1) were switched to FSL2 with individually-programmable low glucose alarms. The primary endpoint was the changes in % time below range (TBR%) <70 mg/dl [3.9 mmol/l] and <54 mg/dl [3.0 mmol/l] after 12 weeks on FSL2 compared with FSL1. Secondary endpoints were changes in % time in range (TIR% 70–180 mg/dl [3.9–10.0 mmol/l]), % time above range (TAR%) >180 [10.0 mmol/l], mean interstitial glucose, glycemic management indicator (GMI), interstitial glucose coefficient of variation (CV%), hemoglobin A1c, and sensor's scans/day.ResultsWe included 108 individuals (57.4 % men), aged 58.2 ± 17.3 [95 % CI: 55.0 to 61.5] years, with mean diabetes duration 25 ± 14.6 [95 % CI: 22.1 to 27.7] years. Among individuals, 40 (37.0 %) had hypoglycemia awareness with Clarke's score ≥4 and 19 (17.5 %) had a history of severe hypoglycemia. The median low glucose alarm threshold was 70 [IQR: 65–70] mg/dl (3.9 [IQR: 3.6–3.9] mmol/L). By comparison of first 12 weeks on FSL2 vs. last 12 weeks on FSL1, TBR% <70 mg/dl decreased from 4.5 ± 4.4 to 2.3 ± 2.8 % (p < 0.001), TBR% <54 mg/dl decreased from 1.4 ± 2.2 to 0.3 ± 0.9 % (p < 0.001). TIR% was not significantly different (51.5 ± 14.9 vs. 52.9 ± 16 % (p = 0.13)), nor was TAR% (43.8 ± 16.2 vs. 44.7 ± 16.5 % (p = 0.5)). CV% decreased from 39.4 ± 6.9 to 37.9 ± 6.1 % (p < 0.001). Those at risk for hypoglycemia (TBR >4 % and >1 %, respectively, at baseline) showed a significant decrease in the incidence of hypoglycemia <70 and <54 mg/dl (p < 0.0001). Patients' satisfaction with hypoglycemia alarms was high, since all individuals opted to pursue using individual alarm beyond the study period.ConclusionSwitching from FSL1 to FSL2 with low glucose alarms reduced the frequency of hypoglycemia in middle-age adults with T1D, particularly in those who were prone to hypoglycemia awareness or severe hypoglycemia.     

Effectiveness of flash glucose monitoring in patients with type 1 diabetes and recurrent hypoglycemia between early and late stages after flash glucose monitoring initiation

AimsEvaluate the effectiveness of reimbursed flash glucose monitoring with optional alarms (FGM) in preventing severe hypoglycemia (SH) and reducing hypoglycemia exposure in T1D patients prone to hypoglycemia.MethodsAmbispective study in T1D patients treated with multiple daily injections (MDI) and prone to hypoglycemia, initiating reimbursed FGM (FreeStyle Libre 2). The primary outcome was the number of SH events (requiring third party assistance) and main secondary outcomes were time below range < 70 (TBR < 70) and < 54 mg/dL (TBR < 54), impaired awareness of hypoglycemia (IAH) and quality of life (QoL). Logistic regression models were constructed to explore variables associated with success of the intervention.ResultsWe included 110 patients (52.7 % women, mean age 47.8 ± 17.0 years). SH events at 1-year follow-up decreased from 0.3 ± 0.6 to 0.03 ± 0.2 (p < 0.001). Significant reductions in patients presenting an SH (26.4 % vs. 2.9 %, p < 0.001) and IAH (47.1 % vs. 25.9 %, p = 0.002) were observed, as well as improvements in QoL. TBR < 70 and TBR < 54 were not significantly reduced. Baseline GMI was inversely associated with a decrease in TBR < 70 [OR 0.37 (0.15–0.93)] and directly with an increase in time in range 70–180 mg/dL [OR 2.10 (1.03–4.28)].ConclusionsFGM decreased SH and improved hypoglycemia awareness and QoL. Initial tight glycemic control was associated with a decrease in hypoglycemia, while patients with suboptimal control reduced hyperglycemia.     

Influence of sex on long-term prognosis in patients with atrial fibrillation treated with oral anticoagulants. Results from the prospective,nationwide FANTASIIA study

BackgroundWhile many risk factors for Atrial Fibrillation (AF) have been identified, there are important differences in their relative impact between sexes. The aim of our study was to investigate the influence of sex as a long-term predictor of adverse events in “real world” AF patients treated with direct oral anticoagulants.MethodsThe FANTASIIA registry is a prospective, national and multicentric study including outpatients with anticoagulated AF patients. Baseline characteristics and adverse events at 3 years of follow-up were collected and classified by sex. Cox multivariate analysis was performed to investigate the role of sex in major events and composite outcomes.ResultsA total of 1956 patients were included in the study. 43.9% of them were women, with a mean age of 73.8 ± 9.4 years (women were older 76.5 ± 7.9 vs 71.7 ± 10.1, p<0.001). Women had higher rate of cardiovascular risk factors and higher mean of CHA₂DS₂-VASc (4.4 ± 1.4 vs 3.7 ± 1.6, p<0.001) and HAS-BLED (2.1 ± 1.0 vs 1.9 ± 1.1, p<0.001) than men. After 3 years of follow-up, rates of major events were similar in both groups with limit difference for all-cause mortality (4.4%/year in women vs 5.6%/year in men; p = 0.056). However, all the composite events were more frequent in women. We observed in the non-adjusted adverse events lower rate of all-cause mortality (HR 0.62, 95%CI 0.47–0.81; p<0.001), composite 1 outcomes (HR 0.80, 95%CI 0.65–0.98; p = 0.029) and composite 2 (HR 0.77, 95%CI 0.64–0.94; p = 0.010) in women compared with men. In multivariate Cox regression analysis observed that female sex was an independently protector factor for all-cause mortality and for the composite outcomes 1 and 2.ConclusionsIn this “real world” study of anticoagulated AF patients, women could have a protective role against development of adverse events, mainly on all-cause mortality and combined events.     

Hypoglycemia- simplifying the ways to predict an old problem in the general ward

ObjectiveTo examine the association between hypoglycemic events and inpatient and outpatient mortality rates, and to characterize the profile of patients with diabetes who develop hypoglycemia during hospitalization in order to identify risk factors and potentially avoid it.Research design and methodsThis retrospective cohort study analyzed data of 3410 patients with diabetes hospitalized during 2012. The associations among biochemical measures, severity of hypoglycemia, inpatient length of stay, and mortality during hospitalization, one month and within one year after discharge were evaluated.ResultsHypoglycemia was observed in 18.5% (633/3410) of patients with diabetes, 83% (529/633) with mild/moderate hypoglycemic values. Adjusted for age and sex, the 30-day mortality rate after discharge was higher in the group with mild/moderate hypoglycemia (HR = 1.749, CI 1.288–2.374, p < 0.001) and in the group with severe hypoglycemia (HR = 3.390, CI 2.332–6.100, p < 0.001). The mortality rate at the one-year follow-up was higher in the group with mild/moderate hypoglycemia (HR = 1.749, CI 1.288–2.374, p < 0.001) and in the group with severe hypoglycemia (HR = 3.390, CI 2.332–6.100, p < 0.001).In multivariate analysis, hemoglobin and albumin below normal values, and creatinine values above the upper limit were strongly associated with hypoglycemia (OR 1.35, 95%CI 1.1–1.6, p < 0.03; OR 1.6, 95%CI 1.33–1.89, p < 0.001; OR 1.3, 95%CI 1.08–1.55, p < 0.04, respectively).ConclusionsHospitalized patients with diabetes and low hemoglobin, low albumin or high creatinine levels are at increased risk of developing significant hypoglycemia. Identifying accurate high-risk factors in order to intervene early and efficiently can prevent life-threatening complications.     

Impact of sensor-augmented pump therapy with predictive low-glucose management on hypoglycemia and glycemic control in patients with type 1 diabetes mellitus: 1-year follow-up

AimsTo describe real-life experience with sensor-augmented pump therapy with predictive low-glucose management (SAPT-PLGM), in terms of hypoglycemia and glycemic control after one year of follow-up in T1D patients with hypoglycemia as the main indication of therapy.MethodsRetrospective cohort study under real life conditions. Baseline and one-year follow-up variables of glycemic control, hypoglycemia and glycemic variability were compared.ResultsFifty patients were included, 31 on prior treatment with SAPT with low-glucose suspend (LGS) feature and 19 on multiple dose insulin injections (MDI). Mean HbA1c decreased in the MDI group (8.24%–7.08%; p = 0.0001). HbA1c change was not significant in the SAPT-LGS group. Area under the curve (AUC) below 70 mg/dl improved in both SAPT-LGS and MDI groups while AUC, %time and events below 54 mg/dl decreased in SAPT-LGS group. Glycemic variability improved in the MDI group. Less patients presented severe hypoglycemia with SAPT-PLGM in both groups, however the change was non-significant.ConclusionsUnder real life conditions, SAPT-PLGM reduced metrics of hypoglycemia in patients previously treaded with MDI and SAPT-LGS without deteriorating glycemic control in SAPT-LGS patients, while improving it in patients treated with MDI.     

Severe hypoglycemia and ketoacidosis over one year in Italian pediatric population with type 1 diabetes mellitus: A multicenter retrospective observational study

Background and aimsEvaluation of incidence and correlates of severe hypoglycemia (SH) and diabetes ketoacidosis (DKA) in children and adolescents with T1DM.Methods and resultsRetrospective study conducted in 29 diabetes centers from November 2011 to April 2012. The incidence of SH and DKA episodes and their correlates were assessed through a questionnaire administered to parents of patients aged 0–18 years. Incidence rates and incident rate ratios (IRRs) were estimated through multivariate Poisson regression analysis and multilevel analysis. Overall, 2025 patients were included (age 12.4 ± 3.8 years; 53% males; diabetes duration 5.6 ± 3.5 years; HbA1c 7.9 ± 1.1%). The incidence of SH and DKA were of 7.7 and 2.4 events/100 py, respectively. The risk of SH was higher in females (IRR = 1.44; 95%CI 1.04–1.99), in patients using rapid acting analogues as compared to regular insulin (IRR = 1.48; 95%CI 0.97–2.26) and lower for patients using long acting analogues as compared to NPH insulin (IRR = 0.40; 95%CI 0.19–0.85). No correlations were found between SH and HbA1c levels. The risk of DKA was higher in patients using rapid acting analogues (IRR = 4.25; 95%CI 1.01–17.86) and increased with insulin units needed (IRR = 7.66; 95%CI 2.83–20.74) and HbA1c levels (IRR = 1.63; 95%CI 1.36–1.95). Mother's age was inversely associated with the risk of both SH (IRR = 0.95; 95%CI 0.92–0.98) and DKA (IRR = 0.94; 95%CI 0.88–0.99). When accounting for center effect, the risk of SH associated with the use of rapid acting insulin analogues was attenuated (IRR = 1.48; 95%CI 0.97–2.26); 33% and 16% of the residual variance in SH and DKA risk was explained by center effect.ConclusionThe risk of SH and DKA is mainly associated with treatment modalities and strongly depends on the practice of specialist centers.     

Impact of semaglutide on biochemical and radiologic measures of metabolic-dysfunction associated fatty liver disease across the spectrum of glycaemia: A meta-analysis

Background and aimsNo meta-analysis has analysed efficacy and safety of semaglutide in metabolic-dysfunction associated fatty-liver disease (MAFLD).MethodsElectronic databases were searched for RCTs involving people with MAFLD and/or type-2 diabetes (T2DM) receiving semaglutide. Primary outcome was to evaluate changes in alanine aminotransferase (ALT). Secondary outcomes were to evaluate alterations in other measures of NAFLD, glycaemia, lipids and adverse-events.ResultsData from 4 RCTs (2115 patients) was analysed. A greater lowering with injectable semaglutide 0.4mg/0.5 mg once weekly was seen with regards to ALT [MD -3.89U/L (95%CI: ?5.41 to ?2.36); P < 0.01; I² = 0%; 2050 patients], liver stiffness (fibroscan®) [MD -3.19 kPa (95%CI: ?3.26 to ?3.12); P < 0.01; 162 patients], steatosis [MD -13.40 dB/m (95%CI: 20.56 to ?6.24); P < 0.01; 162 patients], triglycerides [MD -21.43 mg/dl (95% CI: 41.63 to ?1.23); P = 0.04; I² = 99%; 2050 patients], total cholesterol [MD -5.53 mg/dl (95% CI: ?8.45 to ?2.61); P < 0.01; I² = 0%; 1888 patients], LDL-cholesterol [MD -3.55 mg/dl (95% CI: ?5.87 to ?1.23); P < 0.01; I² = 0%; 1888 patients], percent-weight [MD -8.99% (95%CI: ?14.64 to ?3.34); P = 0.002; I² = 100%; 2115 patient] and HbA1c [MD -0.77% (95%CI: 1.10 to ?0.45); P = 0.002; I² = 100%; 2115 patients]. Number of patients inadequate to comment on histopathologic measures of MAFLD. Occurrence of treatment-emergent adverse-events [RR 2.31 (95% CI: 0.76–7.06); P = 0.14; I² = 82%] and severe adverse events [RR 1.07 (95%CI: 0.69–1.65); P = 0.77; I² = 33%] were comparable. Adverse-events leading to trial discontinuation [RR 2.37 (95% CI: 1.33–4.22); P = 0.003; I² = 24%], diarrhea [RR 2.05 (95%CI: 1.17–3.60); P = 0.01; I² = 66%], nausea [RR 4.98 (95%CI: 3.23–7.67); P < 0.001; I² = 0%] and vomiting [RR 3.90 (95%CI: 1.75–8.68); P < 0.01; I² = 54%] were higher with semaglutide.ConclusionThis meta-analysis provides reassuring data on efficacy of low dose semaglutide injections in improving ALT and certain radiologic features in MAFLD. Current conclusions are limited by small number of patients evaluated. Urgent need remains for larger studies focussing on liver biopsy.     

Hypoglycemia symptoms are reduced in hospitalized patients with diabetes

AimsHospitalized patients with diabetes are have an impaired ability to detect hypoglycemia events. The purpose of this study was to compare hypoglycemia symptom scores (HSS) in hospitalized patients with diabetes after a documented blood glucose (BG) <70 mg/dl with recalled HSS with outpatient hypoglycemia events.MethodsNon-critically ill hospitalized patients with diabetes grouped as symptomatic (n = 23) or asymptomatic (n = 32) at time of index hypoglycemia completed a standardized HSS-Questionnaires (HSS-Q) related to the inpatient event and to recall of symptoms with outpatient hypoglycemia.ResultsAfter controlling for BG at time of index hypoglycemia (49.8 ± 11.4 vs. 57.4 ± 6.8 mg/dl, p = 0.02), symptomatic patients reported higher HSS than asymptomatic patients with the inpatient event (11.6 ± 7.3 vs. 1.5 ± 3.4, p < 0.001) and in the outpatient setting (13.9 ± 8.6 vs. 10.1 ± 10.6, p < 0.01). Recurrent hypoglycemia was more frequent in asymptomatic patients (13% vs. 44%, p = 0.015) during the hospitalization.ConclusionsCompared to symptomatic patients, asymptomatic patients had lower inpatient and outpatient HSS and more frequent recurrent hypoglycemia events. These results suggest modification of glycemic management strategies in high risk patients to reduce risk for hypoglycemia events.     

Concurrence of hyperinsulinemia and hyperuricemia significantly augmented all-cause mortality

Background and aimsHyperinsulinemia and hyperuricemia are known to increase the risk of mortality due to certain complications, such as Type 2 Diabetes and cardiovascular disease. However, despite their common comorbidities, their combined effect has not been evaluated. The study's aim was to evaluate the combine effect of hyperinsulinemia and hyperuricemia on all-cause mortality.Methods and resultsNHANES datasets (cycles 2003–2018) were examined. Differences between groups were evaluated using Rao-Scott Chi-square and General Linear Model for categorical and continuous data, respectively. Hazard Ratios (HR) were calculated using Cox regression with 95% confidence intervals (95%CI). There was significant difference (p < 0.05) in the mortality rate between the control group (2.3 ± 0.2%), the hyperinsulinemia only group (3.1 ± 0.3%), the hyperuricemia only group (4.0 ± 0.8%), and both conditions (5.1 ± 0.8%). Individually, when compared to the control group, there was a significant increase in mortality risk for hyperinsulinemia (HR: 1.50, 95%CI: 1.12–2.01, p = 0.007) and hyperuricemia (HR: 1.80, 95%CI:1.18–2.75, p = 0.006). However, when both conditions were present, there appeared an additive effect in the mortality risk (HR: 2.32, 95%CI: 1.66–3.25, p < 0.001). When stratified by BMI class, only normal weight participants presented with a significant risk (HR: 7.00, 95%CI: 2.50–20.30, p < 0.001). Also, when stratified by age, only participants older than 40 years presented a risk (HR: 2.22, 95%CI: 1.56–3.16, p < 0.001).ConclusionAlone, hyperuricemia and hyperinsulinemia significantly increased the mortality rate; however, the combined presence of both pathologies was associated with a significantly augmented mortality rate. Normal weight participant or that were >40 years old had a greater risk for mortality.     

The role of plasma fibrinogen,D-dimer and fibrinogen degradation products in diagnosis and disease activity in patients with ankylosing spondylitis

Aim of the workTo evaluate the role of coagulation-related markers such as plasma fibrinogen, D-dimer and fibrinogen degradation product (FDP) in ankylosing spondylitis (AS) patients and their relationship with disease activity.Patients and methodsData were collected from 210 AS patients and 204 age and gender matched healthy controls. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to divide AS patients into active (≥4) and inactive (score < 4) groups.ResultsThe mean age of the patients was 35.3 ± 16.3 years. They were 156 males and 54 females (M:F 2.9:1) and had a disease duration of 9.4 ± 7.2 years. The mean fibrinogen, D-dimer and FDP were significantly increased in the patients (375.4 ± 125.01 mg/dl, 2874.8 ± 1884.6 ug/l and 18.3 ± 11.3 mg/l) compared to the control (276.7 ± 71.9 mg/dl, 913.3 ± 540.6 ug/l and 3.01 ± 1.2 mg/l respectively; p < 0.001 each). Plasma fibrinogen, D-dimer and FDP increased in active compared to inactive patients (p < 0.001) and were significantly associated with BASDAI (p < 0.001). The optimal cut-off value of plasma fibrinogen, D-dimer and FDP for the diagnosis of AS were >288 mg/dl, >472 ug/l and >1.44 mg/l while to discriminate active from inactive the values were 393 mg/dl, 1228 μg/L and 1.82 mg/L, respectively. Logistic regression analysis showed that D-dimer is an independent predictor for AS disease activity (OR = 2.85, 95%CI: (1.85--4.43), p < 0.001).ConclusionFibrinogen, D-dimer and FDP increased in AS patients and significantly correlated with disease activity. D-dimer may play a role as a novel inflammatory parameter to predict disease activity in AS patients.     

Malnutrition status in patients of very advanced age with nonvalvular atrial fibrillation and its impact on clinical outcomes

Background and aimsMalnutrition is associated with adverse outcomes in patients with chronic disease. We screened malnutrition among patients of very advanced age with nonvalvular atrial fibrillation (AF) by malnutrition scores and investigated the associations between malnutrition and clinical outcomes.Methods and resultsThis retrospective observational study included 461 patients aged ≥80 years with nonvalvular AF. Malnutrition was screened using the Controlling Nutritional Status (CONUT), Prognostic Nutritional Index (PNI), and Geriatric Nutritional Risk Index (GNRI) scores. The primary endpoints were composite events, including thromboembolic events and all-cause death. Malnutrition was present in 62.9%, 5.0%, and 21.9% of patients according to the CONUT, PNI, and GNRI scores, respectively. During a median 27-month follow-up, 130 (28.2%) patients had composite events. Kaplan−Meier curves revealed that patients with moderate to severe malnutrition had the worst clinical outcomes (log-rank P < 0.05 for all scores). Multivariate Cox proportional hazards analysis showed that moderate to severe malnutrition was an independent predictor of composite events [hazard ratio (HR): 2.051, 95% confidence interval (95%CI): 1.143–3.679, P = 0.016 for CONUT score; HR: 3.374, 95%CI: 1.898–5.998, P < 0.001 for PNI score; HR: 2.254, 95%CI: 1.381–3.679, P = 0.001 for GNRI score]. Addition of the CONUT or GNRI score to a baseline prediction model for composite events significantly improved the net reclassification improvement and integrated discrimination improvement (all P < 0.05).ConclusionModerate to severe malnutrition was an independent predictor of adverse outcomes among patients of very advanced age with nonvalvular AF. Screening for malnutrition might provide useful information regarding prognosis and risk stratification.     

Low serum albumin levels and in-hospital outcomes in patients with ST segment elevation myocardial infarction

Background and aimsLow serum albumin (SA) is associated with an increased risk of long-term adverse events (AEs) among patients with chronic coronary syndromes. Its prognostic role in patients with ST-elevation myocardial infarction (STEMI) is less clear. To investigate the association between low SA and in-hospital AEs in STEMI patients.Methods and resultsMulticenter retrospective cohort study of 220 STEMI patients undergoing primary percutaneous coronary intervention within 12 h from the onset of symptoms. Hypoalbuminemia was defined by serum SA <35 g/L. SA. In-hospital AEs were defined as cardiogenic shock, resuscitated cardiac arrest and death. Median SA was 38 (IQR 35.4–41.0) g/L and 37 (16.8%) patients showed hypoalbuminemia (<35 g/L) on admission. Patients with hypoalbuminemia were older, more frequently women and diabetics, prior CAD and HF. Furthermore, they showed lower hemoglobin levels and impaired renal function. At multivariable logistic regression analysis, diabetes (odds ratio [OR]:4.59, 95% confidence interval [CI] 1.71–12.28, p = 0.002) and haemoglobin (OR:0.52, 95%CI 0.37–0.72, p < 0.001) were associated with low SA. In a subgroup of 132 patients, SA inversely correlated with D-Dimer (rS −0.308, p < 0.001). Globally, twenty-eight (14.6%) AEs were recorded. Hypoalbuminemia (OR:3.43, 95%CI 1.30–9.07, p = 0.013), high-sensitive (HS)-Troponin peak above median (OR:5.41, 95%CI 1.99–14.7, p = 0.001), C-reactive protein (CRP) peak above median (OR:6.03, 95%CI 2.02–18.00, p = 0.001), and in-hospital infection (OR:3.61, 95%CI 1.21–10.80, p = 0.022) were associated with AEs.ConclusionLow SA levels are associated with worse in-hospital AEs in STEMI patients, irrespective of HS-troponin and CRP plasma levels. Our findings suggest that low SA may contribute to the pro-thrombotic phenotype of these patients.     

Efficacy and safety of novel sodium glucose cotransporter-2 inhibitor remogliflozin in the management of type 2 diabetes mellitus: A systematic review and meta-analysis

Background and aimsNo meta-analysis has analysed efficacy and safety of remogliflozin. We undertook this meta-analysis to address this gap in knowledgeMethodsElectronic databases were searched for RCTs involving diabetes patients receiving remogliflozin as compared to controls. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glycaemia, lipids and adverse events.ResultsData from 3 RCTs involving 535 patients was analysed [2 having pioglitazone and 1 having dapagliflozin as active comparator]. Over 12–24 weeks use, Hba1c [mean difference (MD) −0.13% (95% CI: 0.35 – 0.09%); P = 0.24; I² = 99%] and fasting glucose [MD 3.67 mg/dl (95% CI: 0.53 – 7.88 mg/dl); P = 0.09; I² = 52%]. reduction with remogliflozin was not significantly different from controls. Remogliflozin was inferior to dapagliflozin with regards to reduction in post-prandial glucose [MD+12.17 mg/dl (95%CI:10.79–13.55 mg/dl); P < 0.001].Remogliflozin use was associated with a significantly greater decline in body weight [MD -2.79 kg (95% CI: 3.07 to −2.51 kg); P < 0.001; I² = 30%]. Total adverse events [Risk ratio (RR) 1.21 (95% CI: 0.62–2.64); P = 0.58; I² = 59%] were comparable among groups.ConclusionRemogliflozin had HbA1c and fasting glucose reduction comparable to pioglitazone and dapagliflozin. The paradox with regard to post-prandial glucose reduction needs further evaluation. The current analysis is limited by considerable data heterogeneity and low certainty of evidence for most primary and secondary outcomes. There remains urgent need for high quality RCTs evaluating long-term outcomes with remogliflozin.     

Rate of post-bariatric hypoglycemia using continuous glucose monitoring: A meta-analysis of literature studies

AimsHypoglycemia is a serious complication of bariatric surgery. The aim of the present meta-analysis was to evaluate the rate and the timing of post-bariatric hypoglycemia (PBH) with different bariatric procedures using reliable data from continuous glucose monitoring (CGM).Data synthesisStudies were systematically searched in the Web of Science, Scopus and PubMed databases according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The prevalence of PBH was expressed as weighted mean prevalence (WMP) with pertinent 95% confidence intervals (95%CI). A total of 8 studies (16 datasets) enrolling 280 bariatric subjects were identified. The total WMP of PBH was 54.3% (95%CI: 44.5%–63.8%) while the WMP of nocturnal PBH was 16.4% (95%CI: 7.0%–34%). We found a comparable rate of PBH after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) (OR 1.62, 95%CI: 0.71–3.7; P = 0.248); likewise, the percent time spent in hypoglycemia was similar with the two procedures (mean difference 5.3%, 95%CI: ?1.4%–12.0%; P = 0.122); however, RYGB was characterized by a higher glycemic variability than SG. Regression models showed that the time elapsed from surgical intervention was positively associated with a higher rate of both total PBH (Z-value: 3.32, P < 0.001) and nocturnal PBH (Z-value: 2.15, P = 0.013).ConclusionsPBH, both post-prandial and nocturnal, is more prevalent than currently believed. The rate of PBH increases at increasing time from surgery and is comparable after RYGB and SG with a higher glucose variability after RYGB.     

Effects of weight loss medications on mortality and cardiovascular events: A systematic review of randomized controlled trials in adults with overweight and obesity

AimsAdults affected by obesity are at higher risk of premature mortality. Medications can help to lose weight and to maintain weight loss. Aim of this meta-analysis was to assess whether anti-obesity medications affect all-cause mortality, mortality due to cardiovascular events, cardiovascular risk factors and body weight.Data synthesisA Medline search was performed to identify randomized controlled trials (RCTs) of anti-obesity medications in adults with overweight or obesity reporting data on all-cause mortality, cardiovascular mortality or non-fatal cardiovascular events, with a follow-up of at least 6 months. We identified 28 RCTs with 50,106 participants. The median follow-up was 52 weeks. Evidence did not show superiority of anti-obesity medications over placebo in reducing all-cause mortality (risk ratio 1.03, 95%Confidence Interval [CI] 0.87 to 1.21) or cardiovascular mortality (risk ratio 0.92, 95%CI 0.72 to 1.18). All-cause mortality rate was positively associated with weight loss (β = 0.0007; p = 0.045); hence, for each kg of body weight lost there was a 0.07% decrease of all-cause mortality. The pharmacological treatment reduced total-cholesterol (7.15 mg/dl; 95%CI 1.46–12.85), LDL-cholesterol (5.06 mg/dl; 95%CI 1.12–9.00), and triglycerides levels (9.88 mg/dl; 95%CI 5.02–14.75), while it increased HDL-cholesterol (1.37 mg/dl; 95%CI 0.17–2.57). Systolic blood pressure decreased (0.90 mmHg; 95%CI 0.15–1.64).ConclusionsAlthough we were unable to demonstrate a superiority of anti-obesity medications over placebo on mortality, metaregression showed that even a small weight reduction tends to reduce all-cause mortality in obesity. Our data support public health measures to reduce the obesity burden by including the use of anti-obesity medications.Registration number (PROSPERO)CRD42020210329.     

Comparing the accuracy of transcutaneous sensor and 90-day implantable glucose sensor

Background and aimsContinuous glucose monitoring improves glycemic control in diabetes. This study compared the accuracy of the Dexcom G5 Mobile (Dexcom, San Diego, CA) transcutaneous sensor (DG5) and the first version of Eversense (Senseonics,Inc., Germantown, MD) implantable sensor (EVS).Methods and resultsSubjects with type 1 diabetes (T1D) and using EVS wore simultaneously DG5 for seven days. At day 3, patients were admitted to a clinical research center (CRC) to receive breakfast with delayed and increased insulin bolus to induce glucose excursions. At CRC, venous glucose was monitored every 15 min (or 5 min during hypoglycemia) for 6 h by YSI 2300 STAT PLUS? glucose and lactate analyzer. At home patients were requested to perform 4 fingerstick glucose measurements per day.Eleven patients (9 males, age 47.4 ± 11.3 years, M±SD) were enrolled. During home-stay the median [25th-75th percentile] absolute relative difference (ARD) over all CGM-fingerstick matched-pairs was 11.64% [5.38–20.65]% for the DG5 and 10.75% [5.15–19.74]% for the EVS (p-value = 0.58). At CRC, considering all the CGM-YSI matched-pairs, the DG5 showed overall smaller median ARD than EVS, 7.91% [4.14–14.30]% vs 11.4% [5.04–18.54]% (p-value<0.001). Considering accuracy during blood glucose swings, DG5 performed better than EVS when glucose rate-of-change was ?0.5 to ?1.5 mg/dL/min, with median ARD of 7.34% [3.71–12.76]% vs 13.59% [4.53–20.78]% (p-value<0.001), and for rate-of-change < -1.5 mg/dl/min, with median ARD of 5.23% [2.09–15.29]% vs 12.73% [4.14–20.82]% (p-value = 0.02).ConclusionsDG5 was more accurate than EVS at CRC, especially when glucose decreased. No differences were found at home.     

Elevated serum uric acid is associated with a greater inflammatory response and with short- and long-term mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

Background and aimsDespite elevated serum uric acid (eSUA) has been identified as independent risk factor for cardiovascular diseases, its prognostic value in the setting of ST-segment elevation myocardial infarction (STEMI) is still controversial. Although the mechanisms of this possible relationship are unsettled it has been suggested that eSUA could trigger the inflammatory response. This study sought to investigate the association between eSUA with short- and long-term mortality and with inflammatory response in patients with STEMI treated with primary percutaneous coronary intervention (pPCI).Methods and resultsBlood samples were collected on admission and at 24 and 48 h after pPCI: the inflammatory biomarkers C-reactive protein (CRP), neutrophil count and neutrophil to lymphocytes ratio (NLR) were considered. Baseline eSUA was defined as ≥6.8 mg/dl. Cumulative 30-days and 1-year mortalities were estimated using the Kaplan-Meyer analysis. Multivariable analyses were performed by Cox proportional hazard models.In the 2369 patients with STEMI considered, 30-day mortality was 5.8% among patients with eSUA and 2% among patient with normal SUA level (p < 0.001); 1-year mortality was 8.5% vs 4%, respectively (p < 0.001). At multivariable analyses eSUA was an independent predictor of 30-day mortality (HR 1.196, 95%CI 1.006–1.321, p = 0.042) and 1-year mortality (HR 1.178, 95%CI 1.052–1.320, p = 0.005). eSUA patients presented higher values in on admission CRP (p < 0.001) and in neutrophil count and NLR at 24 h (respectively, p = 0.020 and p < 0.001) and at 48 h (p = 0.018 and p < 0.001) compared to patients with normal SUA levels.ConclusionsElevated serum uric acid is associated with higher short- and long-term mortality and with a greater inflammatory response after reperfusion in patients with STEMI treated with primary PCI.     

Safety and efficacy of once weekly dipeptidyl-peptidase-4 inhibitor trelagliptin in type-2 diabetes: A meta-analysis

Background & aimsPooled systematic analysis of safety and efficacy data of trelagliptin in type-2 diabetes (T2DM) is lacking. We undertook this meta-analysis to address this issue.MethodsElectronic databases were searched for RCTs involving people with T2DM receiving trelagliptin in study arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in pre and post-meal glucose levels, glycaemic targets, lipid parameters and adverse events.ResultsFrom initially screened 63 articles, data from 6 RCTs involving 981 patients was analysed [3 in active control group (ACG) defined as having alogliptin, sitagliptin, linagliptin, teneligliptin, anagliptin or vildagliptin as active comparator; 2 in passive control group (PCG) defined as having placebo as controls; 1 study had both ACG and PCG]. HbA1c reduction by trelagliptin was comparable to ACG [MD 0.06% (95% CI: ?0.03 – 0.16); P = 0.20; I² = 0%], but superior to PCG [MD -0.54% (95% CI: ?0.64 to ?0.44); P < 0.01; I² = 22%]. Fasting blood glucose lowering with trelagliptin was inferior to ACG [MD +6.98 mg/dl (95%CI: 2.55–11.42); P = 0.002; I² = 0%], but superior to PCG [MD -6.11 mg/dl (95%CI: ?12.00 to ?0.23); P = 0.04; I² = 54%]. Glycated albumin lowering was similar to ACG [MD 0.03% (95%CI: ?0.47 – 0.53); P = 0.92; I² = 0%], but superior to PCG [MD -2.31% (95% CI: ?2.86 to ?1.76); P < 0.01; I² = 0%]. Treatment-emergent adverse events [Risk ratio (RR) 1.18 (95%CI:0.63–2.21); P = 0.59; I² = 19%] and severe adverse events [RR 1.75 (95%CI: 0.90–3.40); P = 0.10; I² = 0%] were comparable among groups.ConclusionOnce weekly trelagliptin has good glycaemic efficacy and well tolerated in people with T2DM.     

Effect of vitamin D receptor gene polymorphism on lipid profile in Egyptian children with juvenile idiopathic arthritis

Aim of the workTo assess the effect of vitamin D receptor (VDR) polymorphism on lipid profile in patients with juvenile idiopathic arthritis (JIA) and study its relation to disease characteristics.Patients and methodsThe study included 55 JIA children and 55 matched controls. The lipid profile including cholesterol, high and low-density lipoprotein (HDL and LDL), and triglycerides was assessed. The single nucleotide polymorphism (SNP) VDR gene (rs2228570) polymorphism was assayed by real-time polymerase chain reaction (PCR) in patients and control. Results:55 JIA patients were 36 girls and 19 boys (F:M 1.9:1) and with a mean of age 8.4 ± 3.1 years (3–13 years) and disease duration 1.8 ± 1.4 years (2 months ?8 years). Cholesterol, LDL, and triglycerides were significantly higher (175.4 ± 12.9 mg/dl vs 140.4 ± 7.3 mg/dl, 95.9 ± 9.3 mg/dl vs 71.4 ± 8.1 mg/dl, 95.4 ± 8.3 mg/dl vs 89.3 ± 9.1 mg/dl respectively) while the HDL was significantly lower (52.6 ± 4.5 mg/dl vs 54.9 ± 2.2 mg/dl)(p < 0.001) among JIA children as compared to control. The FF genotype was significantly more frequent in JIA (n = 35; 63.6%) than control(n = 19; 34.5%)(p < 0.001)(Odds ratio 3.3; CI 95% 1.5–7.2) while the Ff genotype was more in the control (n = 29; 52.7% vs n = 5; 9.1%)(p < 0.001). There were no significant variations in the lipid profile across VDR genotypes (p greater than 0.05).There was a significant association of FF genotype (n = 35; 100%) with the oligoarticular subtype of JIA and Ff (n = 3; 60%), ff (n = 9; 60%) with the polyarticular subtype of JIA (p < 0.001).ConclusionVDR FF genotype is associated with three folds risk for JIA and VDR polymorphism is not associated with dyslipidemia in JIA.