Glycated Hemoglobin Levels Research Articles

PIONEER REAL Japan: Baseline characteristics of a multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in clinical practice in Japan.

PIONEER REAL Japan was a non-interventional, multicenter, prospective study investigating oral semaglutide in adults with type 2 diabetes in routine clinical practice. We report baseline characteristics of participants enrolled in this study. Adults aged ≥20 years with type 2 diabetes but no previous treatment with injectable glucose-lowering medication were enrolled. Participants initiated oral semaglutide at their treating physician's discretion and were followed for 34-44 weeks. Participants were stratified into <75-year-old and ≥75-year-old subgroups. A total of 624 participants initiated the study. The mean (standard deviation) age was 64.1 years (14.1), the mean (standard deviation) body weight was 72.4 kg (16.1), and the mean (standard deviation) body mass index was 27.5 kg/m2 (5.0). Participants had a median (interquartile range) type 2 diabetes duration of 9.3 years (4.2, 15.2) and mean (standard deviation) glycated hemoglobin 7.7% (1.1). Most (75.6%) participants were taking glucose-lowering medications at baseline; the most common was metformin (51.9%). The main reasons for initiating oral semaglutide were glycemic control and weight loss. Most (86.0%) participants had an individualized target for glycemic control of glycated hemoglobin ≤7%. The <75-year-old subgroup was heavier (mean [standard deviation] body mass index 28.6 kg/m2 [5.2] vs 25.1 kg/m2 [3.4]) but had comparable glycated hemoglobin levels (mean [standard deviation] 7.7% [1.2] vs 7.8% [1.0]) to the ≥75-year-old subgroup. PIONEER REAL Japan describes the characteristics of individuals with type 2 diabetes prescribed oral semaglutide. The baseline characteristics provide insights into Japanese individuals with type 2 diabetes prescribed oral semaglutide in clinical practice.

Impact of Glucocorticoid Replacement Therapy on Nocturnal Hypoglycemia in Adrenal Insufficiency: An Analysis of Multiple Case Studies.

Adrenal insufficiency (AI) is a hormonal disorder characterized by insufficient glucocorticoid production. Nocturnal hypoglycemia (NH) occurs in patients with AI. However,the effect of glucocorticoid replacement therapy (GCRT) on AI and NH remains unclear. This study aimed to investigate the relationship between AI and NH by evaluating the impact of GCRT on NH in patients newly diagnosed with AI. The present study was conducted between October 2018 and December 2022 at the Department of Diabetes, Metabolism and Endocrinology of the Tokyo Rosai Hospital, Japan. In total, 15 patients aged ≥18 years with newly diagnosed AI or NH were included in this study. The NH frequency was measured using continuous glucose monitoring (CGM). The primary outcome was the change in NH frequency before and after the GCRT intervention. GCRT significantly decreased NH frequency. Severe NH frequency and minimum nocturnal glucose levels changed significantly while fasting blood glucose and glycated hemoglobin levels did not change significantly. GCRT intervention improved CGM profiles' time below range, time in range, and average daily risk range. The present study suggests that GCRT can help newly diagnosed patients with AI manage NH. These findings show that CGM can detect NH in patients with newly diagnosed AI, determine the optimal GCRT dosage, and hence prevent an impaired quality of life and even serious adverse effects in these patients. Further large multicenter studies should validate these findings and delve deeper into the mechanistic link between AI and NH.

THE UTILITY OF BODY INDICES FOR DIABETES PREDICTION IN PATIENTS WITH FASTING HYPERGLYCEMIA: A 10-YEAR FOLLOW-UP STUDY

Objective: We aimed to compare the new body indices against traditional body mass index in their ability to predict diabetes development in patients with fasting hyperglycemia. Design and method: Baseline examination of population-based cohort was performed 2012-2013 in the framework of epidemiological study ESSE-RF which included questionnaires, anthropometry (weight, height, waist and hip circumference), laboratory tests (fasting glucose, glycated hemoglobin, lipids) and target organ damage assessment. In 2022-2023 patients with fasting hyperglycemia at baseline visit were re-examined to register onset of diabetes mellitus (DM), glucose and glycated hemoglobin levels. Several anthropometric indices were calculated: body mass index (BMI), waist-to-height ratio (WHtR), body shape index (ABSI), body roundness index (BRI), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), and lipid accumulation product (LAP). Results: In total 72 participants were re-examined - 35 men and 37 women (mean age 43,6 years and 50,5 years, respectively). New onset of DM was confirmed in 15 patients (20,8%), in 6 men and 9 women. According to multiple regression analysis the most significant predictors of DM development were BRI (p=0,04, beta=-2,2) and WHTR (p=0,04, beta=2,94), but not BMI (p=0,42, beta=-0,22), model (R2 = 0.32; p=0,0014). After adjustment for traditional risk factors (sex, triglycerides, age, insulin, high density lipoproteins, waist circumference, glucose), the most significant diabetes predictors were the WHTR (p=0,01, beta=4,23) and VAI indices (p=0,04, beta=0,732), model (R2 = 0.547; p=1x10-4). We used individual body indices as predictors for the DM and estimated the area under the ROC curve (AUC). The AUC ROC for BRI, WHTR, CVAI and ABSI was greater than for traditional BMI, while for VAI and LAP indices performed worse than BMI (Table 1). Conclusions: New body composition indices involving advanced mathematical framework and including extended set of parameters - BRI, WHTR, CVAI and ABSI, are more reliable diabetes predictors than BMI in patients with fasting hyperglycemia after 10 years of follow-up. This work was supported by the Ministry of Science and Higher Education of the Russian Federation (Agreement # 075-15-2022-301) to A.Konradi.

Nomogram for Predicting Remission of Metabolic Syndrome 1 Year after Sleeve Gastrectomy Surgery in Chinese Patients with Obesity.

Sleeve gastrectomy (SG) is a widely used and effective treatment for patients with obesity and comorbid metabolic abnormalities. No specialized tool is available to predict metabolic syndrome (MS) remission after SG. We presented a nomogram that evaluated the probability of MS remission in obese patients 1year after SG. Patients with preoperative MS who underwent SG were enrolled in this retrospective study. They were divided into a training set and a validation set. Multivariate logistic regression analysis was performed to identify independent predictors of MS remission, and these predictors were included in the nomogram. Receiver operating characteristic curve was used to evaluate discrimination. Calibration was performed with the Hosmer-Lemeshow goodness-of-fit test. The net benefits of the nomogram were evaluated using decision curve analysis (DCA). Three hundred and eighteen patients with a median age of 34.0years were analyzed. A training set and a validation set with 159 individuals each were established. A combination of age, preoperative high-density lipoprotein cholesterol, elevated triglycerides and glycated hemoglobin level independently and accurately predicted MS remission. The nomogram included these factors. The discriminative ability was moderate in training and validation sets (Area under curve 0.800 and 0.727, respectively). The Hosmer-Lemeshow X2 value of the nomogram was 8.477 (P = 0.388) for the training set and 5.361 (P = 0.718) for the validation set, indicating good calibration. DCA showed the nomogram had clinical benefits in both datasets. Our nomogram could accurately predict MS remission in Chinese patients with obesity 1year after SG.

How effective are mobile apps in managing people with type 2 diabetes mellitus? A systematic literature review protocol.

The rise of new technologies in the field of health is yielding promising results. In certain chronic conditions such as type 2 diabetes mellitus, which ranks among the top five causes of global mortality, it could be useful in supporting patient management. A systematic review will be conducted on scientific publications from the last 5 years (January 2019 to October 2023) to describe the effect of mobile app usage on glycated hemoglobin for the management of adult patients with type 2 diabetes mellitus who participated in randomized controlled clinical trials. The search will be carried out in the databases of MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), CENTRAL, WoS, Scopus, Epistemonikos, and LILACS. The search strategy will be constructed using both controlled and natural language. Additionally, the Cochrane filter will be applied to identify randomized controlled trials. The review will include scientific articles reporting studies that present results from randomized controlled trials, with texts in Spanish, English, or French, utilizing mobile applications for the management of adult individuals (over 18 years) with type 2 diabetes mellitus, and whose outcomes report the effects on glycated hemoglobin. The Cochrane Risk of Bias Tool will be used to assess the quality of the studies, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology will be implemented to evaluate the certainty of the evidence. The analysis will be conducted by observing the value of the glycated hemoglobin levels of the participants. Given that this data is a quantitative and continuous value, it facilitates the identification of the effects of the mobile applications used for the management of type 2 diabetes mellitus (T2DM) in adults. Furthermore, if sufficient data are available, a meta-analysis will be conducted using IBM-SPSS. The effect of the intervention will be estimated by the mean difference. All point estimates will be accompanied by 95% confidence intervals. A random effects model will be used. The heterogeneity of the results will be assessed using Cochrane's Q and I2 statistics. Considering that the quality of content and functionality of certain applications in the healthcare field is highly variable, it is necessary to evaluate the scientific evidence reported on the effect of the use of this type of technology in people with T2DM.

Association between area-level walkability and glycated haemoglobin: a Portuguese population-based study

Diabetes poses a substantial disease burden, prompting preventive interventions. Physical inactivity, a major risk factor for type 2 diabetes, can potentially be mitigated by enhancing area-level walkability. Despite this, limited population-based studies have investigated the link between walkability and objective diabetes measures. Our study aims to estimate the association between area-level walkability and individual glycated haemoglobin levels in the Portuguese adult population without the diagnosis of diabetes. Data from the 2011 census and an updated street map were obtained to construct a walkability index based on residential density, land-use mix, and street connectivity. Individual health data were sourced from The National Health Examination Survey (INSEF) 2015, a representative survey of the Portuguese adult population. Gamma regression was employed for estimation of the main associations, revealing that residing in moderately walkable areas significantly reduced average glycated haemoglobin levels (Exp(β) = 0.906; 95% CI: 0.821, 0.999) compared to the least walkable areas. The association was less pronounced and not statistically significant for the third tertile of walkability (Exp(β) = 0.919; 95% CI: 0.822, 1.028). Our findings highlight a nonlinear protective association between walkability and glycated haemoglobin, emphasizing the potential policy implications for urban planning, diabetes prevention, and health promotion.

Detection of significant liver fibrosis in Chinese psoriasis patients receiving methotrexate: a comparison between transient elastography and liver histology.

Methotrexate (MTX) is effective for treating psoriasis and psoriatic arthritis, but its potential hepatoxicity remains a concern. Liver biopsy, the gold standard for detecting MTX-induced liver injury, is invasive and carries considerable risk. Transient elastography (TE) offers a non-invasive alternative for detecting advanced liver fibrosis. This study investigated the performance of TE in detecting MTX-induced liver fibrosis among Chinese psoriasis patients, compared with liver biopsy. This study included adult patients with clinical psoriasis. Liver stiffness measurement using TE was performed in patients receiving MTX. Exclusion criteria were known liver cirrhosis, positive viral hepatitis carrier status, or conditions influencing TE performance. Liver biopsy was performed when liver stiffness was ≥7.1 kilopascals (kPa) or when the total cumulative dose (TCD) of MTX was ≥3.5 g. A total of 228 patients were screened; among 34 patients who met the inclusion criteria, nine (26.5%) had significant liver fibrosis (Roenigk grade ≥3a). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval=0.59-0.93; P=0.021), indicating that TE had satisfactory performance in detecting liver fibrosis. A cut-off value of 7.1 kPa of liver stiffness yielded 100% sensitivity and 68% specificity. Liver fibrosis was not correlated with the TCD of MTX or the duration of MTX use; it was significantly correlated with obesity and diabetes status (body mass index ≥30 kg/m2, waist circumference ≥138 cm, and glycated haemoglobin level ≥7.8%). Transient elastography is reliable and superior to the TCD for detecting liver fibrosis in Chinese psoriasis patients receiving MTX. Liver biopsy should be reserved for high-risk patients or patients with liver stiffness ≥11.7 kPa on TE.

Impact of Anemia on the Determination of Glycated Haemoglobin by High-Performance Liquid Chromatography in Diabetic Patients

Introduction: Glycated haemoglobin is considered an objective element in monitoring glycaemic control in diabetic patients. High-performance liquid chromatography (HPLC) is the reference method for measuring HbA1c. However, even this method can be affected by certain conditions such as anemia. Purpose: To study the impact of anaemia on the measurement of glycated haemoglobin levels by HPLC in diabetic patients. Methodology: We conducted a prospective, descriptive and comprehensive study from November 2022 to April 2023, on 06 months at the Mali Hospital, measuring glycated haemoglobin, blood glucose and haematological parameters (CBC). Results: We included 71 diabetic patients, 42.3% were men and 57.7% women. In our study population, 33.8% were anaemic, among them 16.9% were women and 16.9% men. The age group [50-80] years constituted the majority (n = 14) of anaemic patients. The most common type of anaemia in our diabetic patients was normocytic anaemia. HbA1c &gt;7% was found in 91.6% (n=22) of our anaemic patients. The mean haemoglobin level was not statistically significantly different from the HbA1c level (P = 0.0595). There was a statistically significant difference between MCHC and HbA1c (P = 0.04). To our knowledge, we did not observe any significant impact of anaemia on the measurement of HbA1c by the HPLC method. Conclusion: Our study showed a high frequency of normocytic anaemia in diabetic patients. We also noted that the reliability of HPLC in measuring HbA1c was not affected by a minor decrease in total haemoglobin levels.

The Obese Taste Bud study: Objectives and study design.

Taste modifies eating behaviour, impacting body weight and potentially obesity development. The Obese Taste Bud (OTB) Study is a prospective cohort study launched in 2020 at the University of Leipzig Obesity Centre in cooperation with the HI-MAG Institute. OTB will test the hypothesis that taste cell homeostasis and taste perception are linked to obesity. Here, we provide the study design, data collection process and baseline characteristics. Participants presenting overweight, obesity or normal weight undergo taste and smell tests, anthropometric, and taste bud density (TBD) assessment on Day 1. Information on physical and mental health, eating behaviour, physical activity, and dental hygiene are obtained, while biomaterial (saliva, tongue swap, blood) is collected in the fasted state. Further blood samples are taken during a glucose tolerance test. A stool sample is collected at home prior to Day 2, on which a taste bud biopsy follows dental examination. A subsample undergoes functional magnetic resonance imaging while exposed to eating-related cognitive tasks. Follow-up investigations after conventional weight loss interventions and bariatric surgery will be included. Initial results show that glycated haemoglobin levels and age are negatively associated with TBD, while an unfavourable metabolic profile, current dieting, and vegan diet are related to taste perception. Olfactory function negatively correlates with age and high-density lipoprotein cholesterol. Initial findings suggest that metabolic alterations are relevant for taste and smell function and TBD. By combining omics data from collected biomaterial with physiological, metabolic and psychological data related to taste perception and eating behaviour, the OTB study aims to strengthen our understanding of taste perception in obesity.

Association between the response of intravitreal antivascular endothelial growth factor injection and systemic factors of diabetic macular edema

BackgroundThis study investigated the effects of systemic factors in response to intravitreal injections in patients with macular edema due to non-proliferative diabetic retinopathy (NPDR).MethodsWe retrospectively reviewed the medical records of patients treated with intravitreal injections for macular edema secondary to NPDR between January 2018 and January 2021. The patients were divided into three groups according to the injection response. When patients with diabetic macular edema showed 20µ or more reduction in central retinal thickness compared to baseline, they were classified as responsive group, and if not, they were classified as refractory group. The responsive group was further divided into the complete and incomplete response groups. Patients with complete disappearance of edema at seven months were classified as the complete response group, whereas those in which edema did not disappear were classified as the incomplete response group. The clinical characteristics of each group, including medical history, ophthalmic examination results, and laboratory examination results at the time of diagnosis, were analyzed.ResultsOf the 112 eyes (91 patients) that satisfied the inclusion criteria, 89 (77 patients) in the responsive group and 23 (14 patients) in the refractory group were included in the analysis. The responsive group was further divided into the complete (51 eyes) and incomplete (38 eyes) response groups. The refractory group had significantly higher glycated hemoglobin levels and significantly lower estimated glomerular filtration rates than the responsive group (p = 0.026 and p = 0.012, respectively). In the multivariate logistic regression analysis, both factors were found to be significant in predicting the degree of response (all p < 0.05). No factor showed a significant difference between the incomplete and complete response groups(all p > 0.05).ConclusionsIn macular edema caused by NPDR, low glomerular filtration rates and high glycated hemoglobin levels may be used as predictors of poor response to intravitreal injection therapy. In addition to blood glucose control, education should be provided regarding the need for the continuous monitoring of renal function.

Weight management with orlistat in type 2 diabetes: an electronic health records study.

Orlistat is recommended as an adjunct to diet and exercise for weight loss in the treatment of type 2 diabetes mellitus (T2DM). To explore associations between patient characteristics and orlistat prescribing, and to determine associations of orlistat with weight loss in T2DM and prediabetes. Cohort study using anonymised health records from a UK database of general practice. The UK Clinical Practice Research Datalink (CPRD) Aurum database was searched to compile a cohort of patients aged ≥18 years, first diagnosed with T2DM or prediabetes in 2016 or 2017. Once the data had been collated, multivariable logistic regression models were used to determine associations with starting orlistat and stopping it early (<12 weeks of prescriptions) and orlistat's associations with weight loss in those who had not been prescribed second-line antidiabetic medications. Out of 100 552 patients with incident T2DM or prediabetes, 655 (0.8%) patients with T2DM and 128 (0.7%) patients with prediabetes were prescribed orlistat. Younger people, females, those in areas of deprivation, current smokers, those coprescribed metformin, and those recorded as having hypertension were statistically significantly more likely to be prescribed orlistat; higher baseline glycated haemoglobin levels were associated with early stopping. In comparison with patients not on orlistat, those who continued using it for ≥12 weeks were more likely to lose ≥5% weight (adjusted odds ratio [AOR] 1.69, 95% confidence interval [CI] = 1.07 to 2.67) but those who stopped orlistat early were less likely to lose ≥5% weight (AOR 0.56, 95% CI = 0.29 to 1.09). Orlistat was significantly associated with weight loss in patients with T2DM and prediabetes when taken for at least 12 weeks; however, it was infrequently prescribed and often taken for <12 weeks. Orlistat may be a useful adjunct to lifestyle modifications for patients with T2DM and prediabetes, but barriers to continued use means it may not be effective for everyone in managing weight loss.

Mendelian Randomization Analysis Identifies Inverse Causal Relationship between External Eating and Metabolic Phenotypes.

Disordered eating contributes to weight gain, obesity, and type 2 diabetes (T2D), but the precise mechanisms underlying the development of different eating patterns and connecting them to specific metabolic phenotypes remain unclear. We aimed to identify genetic variants linked to eating behaviour and investigate its causal relationships with metabolic traits using Mendelian randomization (MR). We tested associations between 30 genetic variants and eating patterns in individuals with T2D from the Volga-Ural region and investigated causal relationships between variants associated with eating patterns and various metabolic and anthropometric traits using data from the Volga-Ural population and large international consortia. We detected associations between HTR1D and CDKAL1 and external eating; between HTR2A and emotional eating; between HTR2A, NPY2R, HTR1F, HTR3A, HTR2C, CXCR2, and T2D. Further analyses in a separate group revealed significant associations between metabolic syndrome (MetS) and the loci in CRP, ADCY3, GHRL, CDKAL1, BDNF, CHRM4, CHRM1, HTR3A, and AKT1 genes. MR results demonstrated an inverse causal relationship between external eating and glycated haemoglobin levels in the Volga-Ural sample. External eating influenced anthropometric traits such as body mass index, height, hip circumference, waist circumference, and weight in GWAS cohorts. Our findings suggest that eating patterns impact both anthropometric and metabolic traits.

Glucose control during pregnancy in patients with type 1 diabetes correlates with fetal hemodynamics: a prospective longitudinal study

BackgroundMaternal diabetes adversely affects fetal cardiovascular system development. Previous studies have reported that the fetuses of mothers with diabetes exhibit both structural and functional changes; nevertheless, prior studies have not examined the association between glucose control and fetal cardiac morphology and performance. Thus, the objective was to determine the association between fetal cardiac morphology and function and maternal glucose control in type 1 diabetes and to compare the differences in measured cardiac parameters between the fetuses of mothers with diabetes and healthy controls.MethodsIn this prospective, longitudinal case-control study — including 62 pregnant women with type 1 diabetes mellitus and 30 healthy pregnant women — fetal cardiac assessment using B-mode, M-mode, and spectral pulsed-wave Doppler was performed in the second and third trimesters. In women with T1DM, glycated hemoglobin and data obtained from glucose sensors — including the percentage of time in, below, and above the range (TIR, TBR, and TAR, respectively), and coefficient of variation (CV) — were analyzed across three time periods: the last menstrual period to 13 (V1), 14–22 (V2), and 23–32 weeks (V3) of gestation. Fetal cardiac indices were compared between groups, and the correlation between glucose control and fetal cardiac indices was assessed.ResultsAt 28–32 weeks, the fetuses of women with T1DM exhibited increased left ventricular end-diastolic length, relative interventricular septum thickness, right ventricular cardiac output, and pulmonary valve peak systolic velocity compared with healthy controls. At 18–22 weeks, pulmonary and aortic valve diameters, left and right ventricular stroke volumes, and left cardiac output inversely correlated with the CV and glycated hemoglobin levels at V1 and V2. Furthermore, at 28–32 weeks, pulmonary and aortic valve diameters, left ventricular stroke volume, cardiac output, and right/left atrioventricular valve ratio inversely correlated with the TBR at V1, V2, and V3. Moreover, diastolic functional parameters correlated with the TAR and glycated hemoglobin levels, particularly after the first trimester.ConclusionIn women with T1DM, maternal hyperglycemia during pregnancy correlates with fetal diastolic function, whereas glucose variability and hypoglycemia inversely correlate with fetal left ventricular systolic function in the second and third trimesters.

Associations of onset age, diabetes duration and glycated hemoglobin level with ischemic stroke risk in type 2 diabetes patients: a prospective cohort study

Objective: To investigate the associations of onset age, diabetes duration, and glycated hemoglobin (HbA1c) levels with ischemic stroke risk in type 2 diabetes patients. Methods: The participants were from Comprehensive Research on the Prevention and Control of the Diabetes in Jiangsu Province. The study used data from baseline survey from December 2013 to January 2014 and follow-up until December 31, 2021. After excluding the participants who had been diagnosed with stroke at baseline survey and those with incomplete information on onset age, diabetes duration, and HbA1c level, a total of 17 576 type 2 diabetes patients were included. Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95%CI of onset age, diabetes duration, and HbA1c level for ischemic stroke. Results: During the median follow-up time of 8.02 years, 2 622 ischemic stroke cases were registered. Multivariate Cox proportional risk regression model showed that a 5-year increase in type 2 diabetes onset age was significantly associated with a 5% decreased risk for ischemic stroke (HR=0.95, 95%CI: 0.92-0.99). A 5-year increase in diabetes duration was associated with a 5% increased risk for ischemic stroke (HR=1.05, 95%CI: 1.02-1.10). Higher HbA1c (per 1 standard deviation increase:HR=1.17, 95%CI: 1.13-1.21) was associated with an increased risk for ischemic stroke. Conclusion: The earlier onset age of diabetes, longer diabetes duration, and high levels of HbA1c are associated with an increased risk for ischemic stroke in type 2 diabetes patients.

Blood groups and Rhesus status as potential predictors of outcomes in patients with cardiac resynchronisation therapy

Cardiac resynchronisation therapy (CRT) improves prognosis in patients with heart failure (HF) however the role of ABO blood groups and Rhesus factor are poorly understood. We hypothesise that blood groups may influence clinical and survival outcomes in HF patients undergoing CRT. A total of 499 patients with HF who fulfilled the criteria for CRT implantation were included. Primary outcome of all-cause mortality and/or heart transplant/left ventricular assist device was assessed over a median follow-up of 4.6 years (IQR 2.3–7.5). Online repositories were searched to provide biological context to the identified associations. Patients were divided into blood (O, A, B, and AB) and Rhesus factor (Rh-positive and Rh-negative) groups. Mean patient age was 66.4 ± 12.8 years with a left ventricular ejection fraction of 29 ± 11%. There were no baseline differences in age, gender, and cardioprotective medication. In a Cox proportional hazard multivariate model, only Rh-negative blood group was associated with a significant survival benefit (HR 0.68 [0.47–0.98], p = 0.040). No association was observed for the ABO blood group (HR 0.97 [0.76–1.23], p = 0.778). No significant interaction was observed with prevention, disease aetiology, and presence of defibrillator. Rhesus-related genes were associated with erythrocyte and platelet function, and cholesterol and glycated haemoglobin levels. Four drugs under development targeting RHD were identified (Rozrolimupab, Roledumab, Atorolimumab, and Morolimumab). Rhesus blood type was associated with better survival in HF patients with CRT. Further research into Rhesus-associated pathways and related drugs, namely whether there is a cardiac signal, is required.

Pharmacological and Benefit-Risk Profile of Once-Weekly Basal Insulin Administration (Icodec): Addressing Patients' Unmet Needs and Exploring Future Applications.

Diabetes mellitus (DM) is a chronic metabolic disease affecting over 500 million people worldwide, which leads to severe complications and to millions of deaths yearly. When therapeutic goals are not reached with diet, physical activity, or non-insulin drugs, starting/adding insulin treatment is recommended by international guidelines. A novel recombinant insulin is icodec, a once-weekly insulin that successfully completed phase III trials and that has recently obtained the marketing authorization approval from the European Medicines Agency. This narrative review aims to assess icodec pharmacological and clinical features concerning evidence on benefit-risk profile, as compared to other basal insulins, addressing the potential impact on patients' unmet needs. Icodec is a full agonist, recombinant human insulin analogue characterized by an ultra-long half-life (196 h), enabling its use in once-weekly administration. Phase III randomized clinical trials involving more than 4000 diabetic patients, mostly type 2 DM, documented non-inferiority of icodec, as compared to currently available basal insulins, in terms of estimated mean reduction of glycated hemoglobin levels; a superiority of icodec, compared to control, was confirmed in insulin-naïve patients (ONWARDS 1, 3, and 5), and in patients previously treated with basal insulin (ONWARDS 2). Icodec safety profile was comparable to the currently available basal insulins. Once-weekly icodec has the potential to improve patients' adherence, thus positively influencing patients' treatment satisfaction as well as quality of life, especially in type 2 DM insulin-naïve patients. An improved adherence might positively influence glycemic target achievement, reduce overall healthcare costs and overcome some of the unmet patients' needs. Icodec has the potential to emerge as a landmark achievement in the evolution of insulin therapy, with a positive impact also for the National Health Services and the whole society.

Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study

BackgroundSodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF.MethodsA two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c.ResultsGenetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30–0.59], P < 0.0001). Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with both SGLT-2 inhibition and HF. Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224, FDR-adjusted P = 0.0844). The effect of SGLT-2 inhibition on HF was mediated by CXCL10 by 17.85% of the total effect (95% CI [3.03%–32.68%], P = 0.0183).ConclusionsThis study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.Graphical

Internet-Based Interventions for Preventing Premature Birth Among Pregnant Women: Systematic Review.

Premature birth rates have slightly increased globally, making its prevention critical for both short-term and long-term health outcomes. Various interventions have been developed in response to the multifaceted risk factors for premature birth, including internet-based programs. These programs offer accessibility and enhanced engagement; however, their overall efficacy in preventing premature births requires thorough evaluation. This systematic review aims to identify the study designs and assess the effectiveness of internet-based interventions in preventing premature birth among pregnant women. A comprehensive search of the MEDLINE, Embase, CINAHL, and Cochrane Library databases was conducted to identify randomized trials and quasi-experimental studies evaluating internet-based interventions for premature birth prevention in pregnant women. The search was inclusive, with no restrictions based on language or geographical location, allowing for a comprehensive global perspective. The time frame for the inclusion of studies extended until February 2023. The risk of bias (RoB) in each study was independently assessed by 3 authors forming pairs, using the revised Cochrane RoB tool (RoB 2) for randomized trials, as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Owing to heterogeneity in populations, measurements, and interventions, a meta-analysis was not conducted. This review included 26 articles, comprising 12 intention-to-treat and 14 per-protocol studies. The overall RoB was high in most intention-to-treat studies and of some concern in most per-protocol studies. The target populations varied, including nonspecific pregnant women, those with gestational diabetes mellitus (GDM) or those at risk of GDM, individuals with anxiety or depression, and those experiencing preterm labor. Psychosocial, physiological, and wellness health outcomes were evaluated. Internet-based interventions effectively reduced stress/distress in nonspecific pregnant women but not in those experiencing preterm labor. Their effectiveness in reducing anxiety and depression varied, with inconsistent results among different groups. In women with GDM or those at risk of GDM, interventions successfully controlled fasting plasma glucose and 2-hour postprandial plasma glucose levels but did not consistently manage glycated hemoglobin levels. These interventions did not reduce the incidence of premature births across the various populations studied. The effectiveness of these internet-based interventions in addressing substance or alcohol abuse and insomnia also varied. Internet-based interventions show promise in improving psychosocial health and managing blood sugar to prevent premature birth, highlighting variability in effectiveness across different risk factors. Further research, including clinical trials, is vital for developing, evaluating, and disseminating effective, safe internet-based interventions. Establishing standardized measurement tools and rigorous evaluation processes is crucial for enhancing these interventions' effectiveness and reliability in clinical practice, significantly contributing to preventing premature births and improving maternal health outcomes. PROSPERO CRD42021278847; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021278847.

The clinical efficacy, outcomes and quality of life of diabetic disease patients treated with dapagliflozin

Introduction: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease and a common serious complication that affects 1/3rd of type-1 and half of type-2 diabetes mellitus patients. In the early stages of DKD-RAAS blockades (angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers) and antihyperglycemic agents such as sodium-glucose transport protein (SGLT) 2 inhibitors, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors may help prevent DKD by lowering blood glucose levels and through intrinsic renal protection. SGLT2 inhibitors are a new class of oral antidiabetic drugs, which delay the progression of DKD. Dapagliflozin is a drug of choice when the estimated glomerular filtration rate (eGFR) is 25–75 mL/min/1.73 m2 and urine albumin–creatinine ratio ≥≥30 mg/mmol. Aim and Objectives: The aim of the study was to evaluate the clinical outcomes of dapagliflozin in DKD and to check the complications and quality of life of the patients after treatment. Methodology: It was a prospective observational study conducted for a period of 6 months in a tertiary care hospital. The data were collected from the 49 patients with DKD who underwent treatment with dapagliflozin, after approval of the protocol by the IEC. The statistical analysis was done using SPSS software, V.22.(1) 1. SPSS I. IBM SPSS Statistics Version 22 Statistical Software: Core System Users’ Guide. SPSS Inc. 2014. Results and Discussion: The majority of patients enrolled were males (81.63%) compared to females (18.36%) and most of them were geriatrics &gt; 60 years. The majority of patients received dapagliflozin 10 mg, followed by few patients with 5 mg. The effectiveness of dapagliflozin was observed by statistically significant improvement in serum creatinine (P &lt; 0.05), BUN (P &lt; 0.05), and blood urea (P ≤ 0.05). Clinically significant improvement was observed in eGFR, creatinine clearance, serum sodium, potassium, chlorides, glycated hemoglobin levels, and body mass index (P &gt; 0.05), which was statistically insignificant. Statistically significant improvement in the quality of life (P &lt; 0.001) of patients was observed. Out of 49, two patients reported with UTI which may be a suspected drug-related side effect. Conclusion: The study concludes that dapagliflozin has a positive impact on treating DKD. The overall quality of life of the patients was moderately improved. These outcomes suggest that dapagliflozin may become the main line therapy in patients suffering from DKD.

The Relationship Between Polychlorinated and Polybrominated Biphenyls and Glycated Hemoglobin among Electronics Workers.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants classified as endocrine disruptors related to prediabetes and diabetes. Polybrominated biphenyls are similar in structure to PCBs and are used as flame retardants. Due to the increased worldwide prevalence of diabetes, there is increased interest in understanding the role of environmental and occupational pollutants in its development. The study aims to assess the relation between PCBs and PBBs in the serum of electronic workers and glycated hemoglobin level as an early indicator of prediabetes and type 2 diabetes mellitus among occupationally exposed workers. Blood samples were collected from 152 workers to assess PCBs (by GCMS), random blood sugar (RBS), and glycated hemoglobin (HbA1c). Participants were classified into two groups according to the presence or absence of PCBs in their serum and were compared for RBS and HbA1c levels. Only two participants had detectable PCB derivate in their serum by GCMS, PCB 1 with methyl and benzole side chains. Regarding PBBs, 18 participants (12%) had detectable PBBs in their serum by GCMS. All participants had RBS and HbA1c levels within the normal range. No statistically significant difference was found between mean levels of RBS and HbA1c between participants with detected biphenyls and those without. The banning of PCB use in industry and modern automated techniques have prevented exposure to PCBs among electronics workers. However, exposure to PBBs continues in electronic industries, but it has no association with diabetes or prediabetes.