Evolution of Myocardial Dysfunction in Asymptomatic Patients at Risk of Heart Failure

ObjectivesThe determinants of changes in systolic and diastolic parameters in patients age >65 years, at risk of heart failure (HF), and with and without asymptomatic type 2 diabetes mellitus (T2DM) was assessed by echocardiography. The association between metformin and myocardial function was also assessed.BackgroundThe increasing prevalence of T2DM will likely further fuel the epidemic of HF. Understanding the development or progression of left ventricular (LV) dysfunction may inform effective measures for HF prevention.MethodsA total of 982 patients with at least one HF risk factor (hypertension, obesity, or T2DM) were recruited from 2 community-based populations and divided into 2 groups: T2DM (n = 431, age 71 ± 4 years) and non-T2DM (n = 551, age 71 ± 5 years). Associations of metformin therapy were evaluated in the T2DM group. All underwent a comprehensive echocardiogram, including global longitudinal strain (GLS) and diastolic function (transmitral flow [E], annular velocity [e’]) at baseline and follow-up (median 19 months [interquartile range: 17 to 26 months]). Comparisons were facilitated by propensity matching.ResultsA reduction in GLS was observed in the T2DM group (baseline ?17.8 ± 2.6% vs. follow-up ?17.4 ± 2.8%; p = 0.003), but not in the non-T2DM group (?18.7 ± 2.7% vs. ?18.6 ± 3.0%; p = 0.41). Estimated LV filling pressures increased in both the T2DM group (p = 0.001) and the non-T2DM group (p = 0.04). Metformin-treated patients with T2DM did not increase estimated LV filling pressure (E/e’ baseline 8.9 ± 2.7 vs. follow-up 9.1 ± 2.7; p = 0.485) or change e’ (7.6 ± 1.5 cm/s vs. 7.6 ± 1.8 cm/s; p = 0.88). After propensity matching, metformin was associated with a smaller change in e’ (β = 0.58 [95% CI: 0.13 to 1.03]; p = 0.013) and E/e’ (β = ?0.96 [95% CI: ?1.66 to ?0.26]; p = 0.007) but was not associated with a change in GLS (p = 0.46).ConclusionsOver 2 years, there is a worsening of GLS and LV filling pressures in asymptomatic diabetic patients with HF risk factors. Metformin use is associated with less deterioration of LV filling pressures and myocardial relaxation but had no association with systolic function.     

Type 1 diabetes outpatient care and treatment effectiveness during COVID-19: A single-center cohort study

PurposeCOVID-19 has brought many challenges for providing quality healthcare for type 1 diabetes (T1DM). We evaluated the impact of the COVID-19 pandemic on the medical care, glycemic control, and selected outcomes in T1DM patients.MethodsWe retrospectively analyzed medical records from 357 T1DM adults enrolled in the Program of Comprehensive Outpatient Specialist Care at the University Hospital in Krakow, and assessed differences in patient data from before the COVID-19 period (March 2019–February 2020) and after it started COVID-19 (March 2020–February 2021).ResultsThe median HbA1c levels and the percentage of patients within the HbA1c target of <7 % (53 mmol/mol) were similar in both periods: before and after the beginning of the pandemic (6.86 % [51.5 mmol/mol], IQR 6.23–7.58 % [44.6–59.3 mmol/mol] vs. 6.9 % [51.9 mmol/mol], IQR 6.2–7.61 % [44.3–59.7 mmol/mol]; p = 0.50 and 56.3 % vs. 57.1 %, p = 0.42, respectively). However, we observed a rise in BMI and body weight (median 24.25, IQR 21.97–27.05 vs. 24.82, IQR 22.17–27.87 and median weight 71.0 IQR 61–82 vs. 72.55, IQR 55–85; p < 0.001 for both comparisons). There was no reduction in the numbers of total diabetes-related visits (median 4, IQR 4–5 vs. 5, IQR 4–5; p = 0.065), but the frequency of other specialist consultations decreased (2, IQR 0–2 vs. 1, IQR 0–2). During the pandemic, telehealth visits constituted of 1191 out of 1609 (71.6 %) total visits.ConclusionsIn this single-center observation, the COVID-19 pandemic did not have a negative impact on glycemic control in T1DM patients, but the patients' weight did increase. Telemedicine proved to be a valuable tool for T1DM care.     

Efficacy and safety of lobeglitazone,a new Thiazolidinedione,as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis

AimThis systematic review and meta-analysis was conducted to evaluate the efficacy and safety of lobeglitazone as compared to the standard of care (SOC) in patients with type 2 diabetes mellitus (T2DM).MethodsDatabases were searched for relevant randomized controlled trials. The primary outcome was the comparison of the glycated hemoglobin (HbA1C) level after 24 weeks. Pooled mean differences and odds ratios were calculated using random-effects models.ResultsOf 267 studies that were screened, four were included. Treatment with adjunct lobeglitazone showed a reduction in the HbA1C level [mean difference: ?0.23% (95% CI: ?0.62 to 0.16); p = 0.24; i²: 87%; moderate GRADE (Grading of Recommendations Assessment, Development and. Evaluation) of evidence], fasting blood glucose level [mean difference: ?7.12 mg/dl (95% CI: ?20.09 to 5.85); p = 0.28; i²: 87%; moderate GRADE of evidence], and lipid profile as compared to those following treatment with the SOC; however, the changes were not statistically significant. The risk of hypoglycemia was significantly lower [odds ratio: 0.24 (95% CI: 0.08 to 0.70); p < 0.05; i²: 0%; moderate GRADE of evidence] without any significant difference in the risk of drug-related adverse events [odds ratio: 1.59 (95% CI: 0.87 to 2.93); p = 0.13; i²: 0%; moderate GRADE of evidence] following treatment with lobeglitazone as compared to those following treatment with the SOC.ConclusionTreatment with adjunct lobeglitazone showed changes in the blood glycemic status and lipid profile similar to SOC in patients with T2DM, and the results were not statistically significant. Lobeglitazone was well tolerated; its safety profile was comparable to SOC.     

Effect of glucagon-like peptide-1 (GLP-1) analogues on epicardial adipose tissue: A meta-analysis

Background and aimsGlucagon-like peptide-1 (GLP-1) analogues reduce body fat and cardiovascular events in patients with type 2 diabetes. Accumulation of epicardial adipose tissue (EAT) is associated with increased cardio-metabolic risks and coronary events in type 2 diabetes.MethodsA systematic review and meta-analysis were performed from Glucagon-like peptide-1 analogues therapy on type 2 diabetes patients, reporting data from changes in EAT, after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases.ResultsIt has been found a limited number of studies, a total of 4 studies (n = 160 patients with GLP-1 analogues therapy) were included in the final analysis. Pooled analysis revealed that GLP-1 analogues reduce EAT (MD: 1.83 mm [-2.50; ?1.10]; P < 0.01). Compared with the patients before the treatment, the patients after the treatment had a smaller HbA1c (MD -1.10%[-1.80; ?0.30]; p = 0.0143) and body mass index was reduced (MD -2.20 kg/m²[-3.70; ?0.60]; p = 0.0058), GLP-1 therapy reduced low-density lipoprotein levels (MD-13.53 mg/dL [-21.74; ?5.31]; p = 0.001) and reduced triglycerides levels significantly (MD -18.32 -28.20 mg/dL; ?8.50); p = 0.0003).ConclusionsThis meta-analysis suggests that the amount of EAT is significantly reduced in T2D patients with Glucagon-like peptide-1 analogues.     

Glycemic and cardiometabolic effects of exercise in South Asian Sri Lankans with type 2 diabetes mellitus: A randomized controlled trial Sri Lanka diabetes aerobic and resistance training study (SL-DARTS)

Background and aimsTo examine the effects of aerobic training (AT) and resistance training (RT) compared to standard care on glycemic control in South Asian Sri Lankan adults with Type 2 Diabetes Mellitus (T2DM).MethodsRandomized controlled trial (RCT) with parallel-group design recruited 86 sedentary Sri Lankans (aged 35–65 years) with T2DM into aerobic training (AT, n = 28), resistance training (RT, n = 28) and control (CN, n = 30) groups. Supervised progressive exercise training consisting of 75 min per session, 2 days per week for 12 weeks was conducted. The primary outcome was pre- and post-intervention absolute change in hemoglobin A1c (HBA1c). Secondary outcomes were serum lipids, liver enzymes, chronic inflammatory status, anthropometry, body composition and blood pressure.ResultsThe absolute change in HbA1c of RT vs. CN was ?0.08% (95% CI, 0.8% to ?0.7%, p = 0.8) and AT vs. CN was ?0.22% (95% CI, 0.95% to ?0.5%). Subgroup analysis (n = 49) with a high baseline HbA1c (>7.5%), absolute reduction in HbA1c in exercise groups were statistically significant (RT vs. CN was ?0.37%; 95% CI 1.3% to ?0.6%, p = 0.04 and AT vs. CN was ?0.57%; 95% CI 1.7% to ?0.6%, p = 0.03). The effect sizes (total and subgroup HbA1c >7.5%) ranged from 0.7 to 1.0 in AT, 0.4 to 1.1 in RT compared to 0.35 to 0.6 for the CN. Secondary outcomes did not significantly differ among groups.ConclusionsExercise training 2 days/week improved glycemic control in Sri Lankan adults with T2DM and the effects were significant in high baseline HbA1c (>7.5%) groups (RT > AT).     

The role of Intestinal-Fatty Acid Binding Proteins and Chitinase-3-Like Protein 1 across the spectrum of dysglycemia

Background and aimsRecent studies underlie the importance of intestinal permeability and chronic inflammation in the pathogenesis of T2DM. Our study compared the concentrations of FABP2 and YKL40 as markers of intestinal permeability and inflammation among normoglycemia, prediabetes and T2DM.MethodsWe recruited 122 participants (45 normoglycemic, 26 prediabetes, and 51 T2DM) of whom we measured the fasting serum levels of FABP2 and YKL-40 using ELISA method.ResultsThe levels of FABP2 were significantly higher in the T2DM group [2.890 (1.880–4.070)] in comparison to both prediabetes [2.025 (1.145–2.343), p = 0.0085] and normoglycemia group [1.72 (1.250–2.645), p = 0.011]. The levels of YKL-40 were also significantly higher in the T2DM group [68.70 (44.61–166.6)] in comparison to both prediabetes [28.85 (20.64–41.53), p < 0.0001] and normoglycemia group [28.64 (19.25–43.87), p < 0.001].ConclusionsOur study observed that the levels of FABP2 and YKL-40 were highest in the T2DM group supporting the available evidences on the role of intestinal permeability disruption and chronic low-grade inflammation in the pathogenesis of T2DM.     

Comparative efficacy of diabetes medications on liver enzymes and fat fraction in patients with nonalcoholic fatty liver disease: A network meta-analysis,,

ObjectivesThis network meta-analysis (NMA) aimed to evaluate the relative rank-order of existing diabetes medications in patients with nonalcoholic fatty liver disease (NAFLD) with or without type 2 diabetes mellitus (T2DM).MethodsA systematic literature search was conducted using the Medline, Embase and Cochrane databases. Clinical trials comparing the efficacy of diabetes medications with other interventions, including lifestyle modification and placebo, in patients with NAFLD were included. The results from the NMA are presented as the weighted mean difference (WMD) of the continuous results and the corresponding 95% confidence intervals (95% CIs).ResultsThe articles presented the results of 49 trials involving 3,836 subjects published between 2013 and 2021. According to our results, thiazolidinedione (TZD) was ranked as the best diabetes medication in the reduction of alanine aminotransferase (ALT) (WMD = -10.10, 95% CI: -15.18, -5.01), followed by dipeptidyl peptidase-4 inhibitor (DPP4i) (WMD = -8.90, 95% CI: -14.41, -3.40). DPP4i also resulted in the greatest reduction in aspartate aminotransferase (AST) (WMD = -6.89, 95% CI: -11.72, -2.07). γ-Glutamyl transferase (γ-GT) reduction was highest in patients treated with glucagon-like peptide 1 receptor agonists (GLP1RAs) (WMD = -15.48, 95% CI: -30.93, -0.02). Ultimately, SGLT2is and GLP1RAs were superior to other diabetes medications or placebo in reducing liver fat fraction (LFF) (WMD = -6.09, 95% CI: -10.50, -1.68; WMD = -5.55, 95% CI: -10.40, -0.69, respectively).ConclusionDiabetes medications, including TZD, DPP4i and GLP1RAs, were found to be suitable alternatives for liver enzyme reduction in the treatment of NAFLD patients. SGLT2is are considered the most effective therapies for lipid modulation in these patients.     

Diabetic Cardiomiopathy Progression is Triggered by miR122-5p and Involves Extracellular Matrix: A 5-Year Prospective Study

ObjectivesThe purpose of this study was to follow the long-term progression of diabetic cardiomyopathy by combining cardiac magnetic resonance (CMR) and molecular analysis.BackgroundThe evolution of diabetic cardiomyopathy to heart failure affects patients’morbidity and mortality. CMR is the gold standard to assess cardiac remodeling, but there is a lack of markers linked to the mechanism of diabetic cardiomyopathy progression.MethodsFive-year longitudinal study on patients with type 2 diabetes mellitus (T2DM) enrolled in the CECSID (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes) trial compared with nondiabetic age-matched controls. CMR with tagging together with metabolic and molecular assessments were performed at baseline and 5-year follow-up.ResultsA total of 79 men (age 64 ± 8 years) enrolled, comprising 59 men with T2DM compared with 20 nondiabetic age-matched controls. Longitudinal CMR with tagging showed an increase in ventricular mass (ΔLVMi = 13.47 ± 29.66 g/m²; p = 0.014) and a borderline increase in end-diastolic volume (ΔEDVi = 5.16 ± 14.71 ml/m²; p = 0.056) in men with T2DM. Cardiac strain worsened (Δσ = 1.52 ± 3.85%; p = 0.033) whereas torsion was unchanged (Δθ = 0.24 ± 4.04°; p = 0.737), revealing a loss of the adaptive equilibrium between strain and torsion. Contraction dynamics showed a decrease in the systolic time-to-peak (ΔTtP = ?35.18 ± 28.81 ms; p < 0.001) and diastolic early recoil-rate (ΔRR = ?20.01 ± 19.07 s^-1; p < 0.001). The ejection fraction and metabolic parameters were unchanged. Circulating miR microarray revealed an up-regulation of miR122-5p. Network analysis predicted the matrix metalloproteinases (MMPs) MMP-16 and MMP-2 and their regulator (tissue inhibitors of metalloproteinases) as targets. In db/db mice we demonstrated that miR122-5p expression is associated with diabetic cardiomyopathy, that in the diabetic heart is overexpressed, and that, in vitro, it regulates MMP-2. Finally, we demonstrated that miR122-5p overexpression affects the extracellular matrix through MMP-2 modulation.ConclusionsWithin 5 years of diabetic cardiomyopathy onset, increasing cardiac hypertrophy is associated with progressive impairment in strain, depletion of the compensatory role of torsion, and changes in viscoelastic contraction dynamics. These changes are independent of glycemic control and paralleled by the up-regulation of specific microRNAs targeting the extracellular matrix. (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes [CECSID]; NCT00692237)     

Altered adipocytokine profile predicts early stage of left ventricular remodeling in hypertensive patients with type 2 diabetes mellitus

Background and aimAdipocytokine dysfunction is considered as causative factor of target organ damage in metabolic disease. The aim of the study was to investigate whether altered adipocytokine profile predicts left ventricular (LV) remodeling in hypertensive patients with type 2 diabetes mellitus (T2DM).MethodsA total of 186 patients (125 hypertensive and 61 non-hypertensive individuals) with established T2DM and 20 healthy volunteers were enrolled in the study. LV remodeling was determined at baseline. Concentrations of adipocytokines were measured with ELISA at baseline.ResultsThe most important predictors of LV hypertrophy in T2DM patients were serum levels of omentin-1 (B-coefficient = −0.64, p = 0.001), Zinc-α2-glycoprotein [ZA2G] (B-coefficient = −0.57, p = 0.002), visfatin (B-coefficient = 0.26, p = 0.034), hs-CRP (B-coefficient = 0.38, p = 0.002), HOMA-IR (B-coefficient = 0.34, p = 0.001), age (B-coefficient = 0.31, p = 0.022), glypican-4 (B-coefficient = −0.23, p = 0.042), and male sex (B-coefficient = 0.11, p = 0.048). After entering combined depending variable (LV hypertrophy and LV diastolic dysfunction) to the model the significant predictors remained serum levels of omentin-1 (B-coefficient = −0.82, p = 0.001), ZA2G (B-coefficient = −0.54, p = 0.001) and HOMA-IR (B-coefficient = 0.44, p = 0.001). Regression analyses showed that the most influential determinants of depending variable (LV hypertrophy + LV diastolic dysfunction) in T2DM patients were omentin-1 (B-coefficient = −1.6, p = 0.001) and ZA2G (B-coefficient = −0.78, p = 0.044).ConclusionWe found that serum levels of omentin-1 and ZA2G were the most important predictors for LV hypertrophy + LV diastolic dysfunction in T2DM patients. Large clinical trials are required to confirm this assumption and get clear explanation of issues unveiled.     

Relationship between insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene and susceptibility to type 2 diabetes mellitus in the Middle East and North Africa Region: A meta-analysis

Background and aimsThe association between insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and the risk of type 2 diabetes mellitus (T2DM) remains controversial. This study aimed to assess the effect of the ACE I/D gene polymorphism on T2DM in the Middle East and North Africa region (MENA region).Material and methodsOur data was extracted from PubMed, Science Direct, and the Web of Science. The predefined inclusion criteria included only the human case-control studies of English Peer-reviewed papers containing the data on genotype distributions of ACE I/D polymorphism and the T2DM risk. Review articles, meeting abstracts, editorials, animal studies, and studies not providing genotype distribution data or without sufficient data were excluded from this work. Results of this meta-analysis were expressed using odds ratios (OR) and 95% confidence intervals (CI). Indeed, the potential sources of heterogeneity and bias were examined by the Egger regression.ResultsOf 2755 identified articles, 10 studies were selected, including 2710 patients with T2DM and 2504 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and the D allele of ACE I/D gene polymorphism (OR = 1.97; 95% CI = 1.33–2.93, p = 0.0007), recessive (OR = 2.16; 95% CI = 1.27–3.67; p = 0.004), dominant (OR = 2.45; 95% CI = 1.54–3.91; p = 0.0001), homozygote (OR = 3.35; 95% CI = 1.78–6.29; p = 0.0001) and heterozygote comparisons (OR = 1.76; 95% CI = 1.07–2.88; p = 0.024).ConclusionOur result suggests that this polymorphism may contribute to the development of T2DM in the MENA Region. This result needs to be confirmed by future well-designed studies with larger sample sizes in diverse populations and ethnicities.     

Comparative effectiveness of glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors on noninvasive indices of hepatic steatosis and fibrosis in patients with type 2 diabetes mellitus

Background and aimsNonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM). There is currently no approved treatment for NAFLD. The main aim was the evaluation of the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) vs. dipeptidyl peptidase-4 inhibitor (DPP-4i) treatment on noninvasive indices of hepatic steatosis and fibrosis in patients with T2DM.MethodsIn this retrospective study, three noninvasive indices of hepatic steatosis [HSI, NAFLD ridge score, and triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio] and five of fibrosis (APRI, FIB-4, NAFLD fibrosis score, BAAT and BARD) were calculated before and after (6–18 months) the addition of a DPP-4i (n = 152) or a GLP-1 RA (n = 37) in patients with T2DM.ResultsRegarding steatosis indices, NAFLD ridge score was significantly decreased in the GLP-1 RA group (baseline: 0.90 ± 0.34, follow-up: 0.67 ± 0.24; p = 0.001), but not in the DPP-4i group (p = 0.25); the difference for group1time interaction was significant (p = 0.02). HSI showed a trend between groups, being significantly different at baseline and follow-up (p < 0.001) with no significant difference in group1time interaction. Indices of fibrosis were not essentially changed within or between groups.ConclusionsNAFLD ridge score was significantly decreased after the addition of GLP-1 RA in patients with T2DM. This study warrants further prospective clinical trials.     

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.     

Prasugrel vs Ticagrelor for DAPT in Patients with ACS Undergoing PCI: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

IntroductionDual antiplatelet therapy (DAPT) with a P2Y12 inhibitor added to aspirin is considered the standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous intervention (PCI). Prasugrel and ticagrelor are commonly used P2Y12 inhibitors, and a few head-to-head randomized control trials (RCTs) have been performed. We performed a systematic review and meta-analysis of these RCTs to compare the efficacy and adverse effects between these two agents when used in patients with ACS undergoing PCI.MethodsWe searched PubMed/MEDLINE and Cochrane library for RCTs comparing prasugrel to ticagrelor in ACS. The primary endpoint was major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stent thrombosis, major bleeding, and all bleeding event. Estimates were calculated as random effects risk ratios (RRs) with 95% confidence intervals (CI).ResultsSix trials with 6807 patients were included. There were no significant difference of MACE (RR 0.93; 95% CI [0.72–1.20]; p = 0.59; I² = 26%), all-cause mortality (RR 0.92; 95% CI [0.73–1.17]; p = 0.51; I² = 0%), cardiovascular mortality (RR 0.99; 95% CI [0.75–1.31]; p = 0.96; I² = 0%), MI (RR 0.87; 95% CI [0.60–1.27]; p = 0.48; I² = 27%), stent thrombosis (RR 0.64; 95% CI [0.39–1.04]; p = 0.07; I² = 0%), major bleeding (RR 0.94; 95% CI [0.70–1.26]; p = 0.68; I² = 6%), and all bleeding event (RR 0.92; 95% CI [0.77–1.09]; p = 0.32; I² = 0%) for prasugrel compared with ticagrelor.ConclusionThere are no significant difference of MACE, all-cause mortality, cardiovascular mortality, MI, stent thrombosis, and bleeding between prasugrel and ticagrelor when added to aspirin among patients with ACS undergoing PCI.     

Frequency of iron deficiency anemia in type 2 diabetes - Insights from tertiary diabetes care centres across India

AimTo study the frequency of iron deficiency anemia (IDA) in individuals with type 2 diabetes mellitus (T2DM) seen at tertiary diabetes care centres across India.MethodsThis is a retrospective study (January 1, 2017–December 31, 2019), which included 1137 individuals with T2DM, aged ≥18 years, for whom data on glycemic, lipid and haematological parameters were available. Anthropometric measurements were done using standardized techniques. Biochemical investigations included fasting plasma glucose[FPG], post prandial plasma glucose, HbA1c, lipids and serum ferritin and iron wherever feasible.ResultsOf the 1137 individuals included for the study, 117 (10.3%) were categorized as no ‘iron deficiency’ (ID) group [normal hemoglobin: male ≥13 g/dl, female ≥12 g/dl and normal serum ferritin ≥70 μg/L], 123 (10.8%) as ID group [normal hemoglobin and low serum ferritin <70 μg/L)], 447 (39.3%) as IDA group [low haemoglobin: male <13 g/dl, female <12 g/dl and low serum ferritin] and 450 (39.6%) as ‘anemia of chronic disease’ (ACD) group [low hemoglobin and normal serum ferritin]. The percentage of women having ID (57.7%) and IDA (65.3%) was significantly higher than their male counterparts. ID was most prevalent (61.7%) in the individuals with duration of diabetes <5 years whereas ACD was most prevalent (50.5%) in individuals with long standing diabetes (>10 years). Independent risk factors for IDA were female gender (OR 3.3,95% CI:1.75–6.23, p < 0.001), duration of diabetes (OR 1.05, 95% CI 1.01–1.11, p = 0.028) and FPG (OR 1.01, 95% CI 0.99–1.00, p = 0.018).ConclusionsThere is a need of identifying and monitoring iron status and anemia in patients with T2DM.     

Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes

Background and aimsTo assess the safety and efficacy of semaglutide compared with placebo and other anti-hyperglycaemic agents in type 2 diabetes (T2DM).MethodsWe searched PubMed, Scopus, Web of Science, and Cochrane library for relevant randomized controlled trials (RCTs). A network meta-analysis was conducted to compare different doses, durations, and interventions in T2DM. We presented results as mean difference (MD) or relative risk (RR) and 95% confidence interval (CI).ResultsTwenty-six included RCTs studied different doses of subcutaneous (SC) and oral semaglutide, tirzepatide, liraglutide, sitagliptin, canagliflozin, and empagliflozin compared with placebo. Tirzepatide showed the highest efficacy, however, it was comparable to semaglutide. SC semaglutide 1 mg once-weekly showed higher reduction in HbA_1c (MD = ?1.72, 95% CI [-2.32; ?1.12]), and fasting blood glucose (MD = ?1.93, 95% CI [-2.81; ?1.04]) versus placebo at 30 weeks and other timepoints. Adverse events (ADs) were comparable to placebo with oral and SC semaglutide, oral sitagliptin, SC liraglutide, and oral empagliflozin at most timepoints. However, SC semaglutide 0.8 mg and tirzepatide 10 mg groups had the highest gastrointestinal adverse events.ConclusionTirzepatide, oral and SC semaglutide has a favourable efficacy in treating T2DM. The adverse events were comparable to placebo; however, gastrointestinal adverse events were highly recorded in tirzepatide, oral and SC semaglutide groups.     

Determinants of glycemic control in type 2 diabetes mellitus in Brazil: A sub-analysis of the longitudinal data from the BrazIian type 1 & 2 diabetes disease registry (BINDER)

BackgroundData on glycemic control and its determinants among Brazilian patients with type-2 diabetes (DM2) are scarce. The BrazIliaN Type 1 & 2 DiabetEs Disease Registry (BINDER) is a multicenter, longitudinal study, designed to investigate the glycemic control in a real-word scenario.Methods1142 patients participated in the five visits of the BINDER study between April/2017 and October/2019. For each visit, glycemic control was assessed using the last measure available for HbA1c. Sociodemographic and anthropometric characteristics were also analyzed.ResultsAt baseline, the median HbA1c level was 7.1% (4.1–15.0%); 259 (31.4%) participants had HbA1c ≤ 6.5% and 396 (48.2%) had HbA1c ≤ 7.0%. Younger age (p = 0.014), low educational level (p = 0.025) and the type of healthcare service (public sector; p = 0.0058) were independently associated with the elevated HbA1c. After 2 years, there were no statistically significant differences in HbA1c median values in relation to baseline.ConclusionsIn this sample of DM2 patients, younger age, low educational level and being treated at the public service were associated with worse glycemic control. Over a 2-year follow-up, there was no significant change in the median HbA1c. These findings suggest that strategies are needed to improve glycemic control, especially in those treated in the public service.     

Assessment of left ventricular global longitudinal strain in patients with type 2 diabetes: Relationship with microvascular damage and glycemic control

Background and aimsType 2 Diabetes mellitus (T2DM) is associated with a higher risk of Heart Failure; Left Ventricular (LV) diastolic dysfunction is often considered the first marker of Diabetic cardiomyopathy; however, early preclinical LV systolic dysfunction has also been observed by means of echocardiographic measurement of strain. This study is aimed at assessing determinants of impaired strain and diastolic ventricular dysfunction in patients with T2DM.Methods and resultsCross-sectional study, performed on a consecutive series of patients with T2DM aged 30–80 years, BMI<40 kg/m², free of cardiovascular disease, assessing metabolic control, microvascular complications, echocardiographic measures.Out of 206 patients, 19.6% had GLS lower than 18. GLS showed a significant inverse correlation with HBA1c, (p = 0.016), BMI (p = 0.002), waist (p < 0.0001), and mean L:H Ratio (p = 0.019). In a multivariate regression for LV GLS including HbA1c, age, sex, BMI and mean RR SDNN index, only HbA1c retained statistical significance: (B = ?0.050 [?0.091; ?0.009], p = 0.01. Among markers of LV diastolic function, only the E/E’ ratio was associated with HbA1c at a univariate analysis, and it retained statistical significance in a multivariate regression including HbA1c, age, sex and disease duration (B = 0.038 [0.03; ?0.073], p = 0.032). No significant difference in any parameter of systolic or diastolic function was observed between patients with or without microalbuminuria or diabetic retinopathy.ConclusionIn patients with T2DM, a reduced left ventricular global longitudinal strain appears to be independently associated with impaired glucose control and autonomic neuropathy, regardless of microvascular complications.     

Efficacy and safety of novel dual glucokinase activator dorzagliatin in type-2 diabetes A meta-analysis

Background & aimsGlucokinase has a critical role in regulating glucose homeostasis in humans, and has been a target for diabetes drug development since 1990s. Dorzagliatin is a novel allosteric dual glucokinase activator targeting both pancreatic and hepatic glucokinase. No meta-analysis has analysed the efficacy and safety of dorzagliatin in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap.MethodsElectronic databases were searched for RCTs involving T2DM patients receiving dorzagliatin in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in blood glucose parameters, lipids, insulin-resistance and adverse events.ResultsFrom initially screened 17 articles, data from 3 RCTs (1333 patients) was analysed. Over 12–24 weeks use, dorzagliatin had significantly higher lowering of HbA1c [MD -0.66% (95%CI: ?0.74 to ?0.59); P < 0.01; I² = 99%], fasting glucose [MD -32.03 mg/dl (95%CI: 45.12 to ?18.94); P < 0.01; I² = 100%], 2-h post-prandial glucose [MD -43.49 mg/dl (95%CI: ?46.26 to ?40.72); P < 0.01; I² = 90%] along with greater number of patients achieving HbA1c<7% [OR 6.01 (95% CI: 2.50–14.46); P < 0.01; I² = 83%], as compared to placebo. Dorzagliatin was associated with significant elevation of triglycerides [MD 0.43 mmol/L (95%CI:0.30–0.56); P < 0.01; I² = 0%], greater occurrence of hyperlipidaemia [RR 1.52 (95% CI:1.05–2.18); P = 0.03; I² = 0%], and increase in body-weight [MD 0.40 kg (95%CI:0.06–0.75); P = 0.03; I² = 0%], compared to placebo. The occurrence of total-adverse-events [RR 1.43 (95%CI:1.11–1.83); P < 0.01; I² = 0%] but not severe adverse-events [RR 0.92 (95%CI:0.54–1.57); P = 0.76; I² = 0%] was significantly higher with dorzagliatin.ConclusionDorzagliatin has good glycaemic efficacy and well tolerated over 6-months use. Mild increase in body-weight, serum triglycerides and overall adverse events remain issues of concern warranting further evaluation in longer clinical trials with active controls.     

Dose-dependent efficacy and safety of licogliflozin on obese adults: A systematic review and meta-analysis of randomized controlled trials

Background and aimLicogliflozin is a dual SGLT1/2 inhibitor acting on the intestine and kidney by reducing glycemic and calorie content. We aimed to determine the efficacy and safety of licogliflozin on Anthropometric measurements and cardiometabolic parameters in obese participants.MethodsWe systematically searched the PubMed, Cochrane Library, Scopus, and Web of Science databases for randomized controlled trials (RCTs) relevant to our eligibility criteria. We performed a subgroup analysis based on licogliflozin doses and the diabetic state of participants. This meta-analysis was registered on PROSPERO (CRD42021286936).ResultsWe identified five RCTs with a total of 905 obese and overweight participants. All participants had a weight reduction of 2.43 kg (95% CI: ?3.17 to ?1.69, p < 0.00001) compared with placebo. The mean difference in HbA1c of obese diabetic patients was (MD: ?0.30%; 95% CI: ?0.45, ?0.16); I2 = 46% in favor of licogliflozin. The incidence of serious adverse events, all-cause mortality, headache, nausea, and vomiting were similar between licogliflozin and placebo (p = 0.72, 0.97, 0.09, 0.53, and 0.89, respectively). However, there was a higher incidence of diarrhea in the licogliflozin group.ConclusionWe found that licogliflozin was safe and tolerable. It reduces body weight significantly. Moreover, it improves glycemic control and other cardiometabolic parameters.