Evaluation of teplizumab's efficacy and safety in treatment of type 1 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus (T1DM). Teplizumab, a humanized anti-CD3 monoclonal antibody, may help T1DM. Its long-term implications on clinical T1DM development, safety, and efficacy are unknown. AIM: To assess the effectiveness and safety of teplizumab as a therapeutic intervention for individuals with T1DM. METHODS: A systematic search was conducted using four electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals written in English. The odds ratio (OR) and risk ratio (RR) were calculated, along with their 95%CI. We assessed heterogeneity using Cochrane Q and I 2 statistics and the appropriate P value. RESULTS: There were 8 randomized controlled trials (RCTs) in the current meta-analysis with a total of 1908 T1DM patients from diverse age cohorts, with 1361 patients receiving Teplizumab and 547 patients receiving a placebo. Teplizumab was found to have a substantial link with a decrease in insulin consumption, with an OR of 4.13 (95%CI: 1.72 to 9.90). Teplizumab is associated with an improved C-peptide response (OR 2.49; 95%CI: 1.62 to 3.81) and a significant change in Glycated haemoglobin A1c (HbA1c) levels in people with type 1 diabetes [OR 1.75 (95%CI: 1.03 to 2.98)], and it has a RR of 0.71 (95%CI: 0.53 to 0.95). CONCLUSION: In type 1 diabetics, teplizumab decreased insulin consumption, improved C-peptide response, and significantly changed HbA1c levels with negligible side effects. Teplizumab appears to improve glycaemic control and diabetes management with good safety and efficacy.

Advances in electrochemical biosensors employing carbon-based electrodes for detection of biomarkers in diabetes mellitus.

Background and purpose: The increase in diabetes cases has become a major concern in the healthcare sector, necessitating the development of efficient and minimal diagnostic methods. This study aims to provide a comprehensive examination of electrochemical biosensors for detecting diabetes mellitus biomarkers, with a special focus on the utilization of carbon-based electrodes. Review approach: A detailed analysis of electrochemical biosensors incorporating various carbon electrodes, including screen-printed carbon electrodes, glassy carbon electrodes, and carbon paste electrodes, is presented. The advantages of carbon-based electrodes in biosensor design are highlighted. The review covers the detection of several key diabetes biomarkers, such as glucose, glycated hemoglobin (HbA1c), glycated human serum albumin (GHSA), insulin, and novel biomarkers. Key results: Recent developments in electrochemical biosensor technology over the last decade are summarized, emphasizing their potential in clinical applications, particularly in point-of-care settings. The utilization of carbon-based electrodes in biosensors is shown to offer significant advantages, including enhanced sensitivity, selectivity, and cost-effectiveness. Conclusion: This review underscores the importance of carbon-based electrodes in the design of electrochemical biosensors and raises awareness for the detection of novel biomarkers for more specific and personalized diabetes mellitus cases. The advancements in this field highlight the potential of these biosensors in future clinical applications, especially in point-of-care diagnostics.

A comparison of the safety and effectiveness of insulin aspart with other bolus insulins in women with pre-existing Type 1 diabetes during pregnancy: A post hoc analysis of a prospective cohort study.

AIMS: The safety and efficacy of insulin analogue insulin aspart (IAsp) have been demonstrated in a randomised clinical trial in pregnant women with Type 1 diabetes (T1D), and IAsp is widely used during pregnancy. The aim of this study was to assess glycaemic control and safety of IAsp versus other bolus insulins in Type 1 diabetic pregnancy in a real-world setting. METHODS: This was a post hoc analysis of a prospective cohort study of 1840 pregnant women with T1D, treated with IAsp (n = 1434) or other bolus insulins (n = 406) in the Diabetes Pregnancy Registry. The primary (composite) outcome was the proportion of pregnancies resulting in major congenital malformations or perinatal or neonatal death. Secondary outcomes included all HbA1c values measured immediately before and during pregnancy and major hypoglycaemia, as well as abortion, pre-eclampsia, pre-term delivery, large for gestational age at birth, stillbirth and fetal malformations. RESULTS: There were no significant differences found in any of the pregnancy outcomes between treatment with IAsp and other bolus insulins in either the crude or propensity score-adjusted analyses. However, maternal HbA1c was lower in the IAsp group at the end of the third trimester (adjusted difference, -0.16% point [95% CI -0.28;-0.05]; -1.8 mmol/mol [95% CI -3.1;-0.6]; p = 0.0046). CONCLUSIONS: No significant differences in safety or pregnancy outcomes were demonstrated when comparing treatment with IAsp versus other bolus insulins in women with T1D during pregnancy. The observed improvement in HbA1c with IAsp in late pregnancy should be confirmed in other studies.

Rural-Urban Differences in Risk Factors for Prediabetes and Undiagnosed Diabetes Among Adult Dwellers in Selected Yoruba-Speaking Parts of Nigeria: A Glycated Haemoglobin-Based Population Screening.

BACKGROUND AND OBJECTIVES: Prevalence of prediabetes and undiagnosed diabetes are different in rural and urban dwellings, with varying driving factors. This study aimed to determine the differences in risk factors of prediabetes and undiagnosed diabetes among Yoruba speaking adult dwellers in selected rural and urban communities in Nigeria using haemoglobin A1c. METHODS: A cross-sectional study was conducted in five selected states in Southwestern Nigeria. Using a multistage sampling technique, 2,537 participants with no prior diagnosis of prediabetes or diabetes mellitus (DM) were enrolled and their glycated haemoglobin (HbA1c) determined. Descriptive statistics, univariate and multiple logistic regression analysis was used to determine the prevalence and risk factors of prediabetes and diabetes at 5% level of significance. RESULTS: Increased age, sex, family history of diabetes, being married, participants' history of hypertension, cardiovascular disease and Gestational Diabetes Mellitus (GDM) or delivery of big babies, BMI, systolic and diastolic blood pressure were significantly associated with prediabetes and diabetes in both urban and rural areas. However, adjusted odds ratio showed that family history of diabetes (2.14, 95% CI: 1.26-3.61 versus 1.36, 95% CI: 1.00-1.85) and past GDM among women (2.67, 95% CI: 0.62, 11.39 versus 1.32, 95% CI: 0.61, 2.89) clearly predict dysglycaemia in the rural compared to urban participants, respectively. CONCLUSIONS: Family history of diabetes and past GDM disproportionately predict dysglycaemia in rural compared to urban participants. Periodic screening for dysglycaemia and public health education, especially in child-bearing women, are necessary measures to reduce the burden of dysglycaemia in Nigeria.

CONTEXTE ET OBJECTIFS: La prévalence du prédiabète et du diabète non diagnostiqué diffère entre les zones rurales et urbaines, avec des facteurs déterminants variés. Cette étude visait à déterminer les différences dans les facteurs de risque du prédiabète et du diabète non diagnostiqué chez les adultes yoruba-parlants vivant dans des communautés rurales et urbaines sélectionnées au Nigeria, en utilisant l'hémoglobine A1c. MÉTHODES: Une étude transversale a été menée dans cinq États sélectionnés du sud-ouest du Nigeria. Utilisant une échantillonnage en plusieurs étapes, 2 537 participants sans diagnostic antérieur de prédiabète ou de diabète sucré (DS) ont été recrutés et leur hémoglobine glyquée (HbA1c) déterminée. Des statistiques descriptives, ainsi que des analyses de régression logistique univariée et multivariée, ont été utilisées pour déterminer la prévalence et les facteurs de risque du prédiabète et du diabète à un seuil de signification de 5 %. RÉSULTATS: L'augmentation de l'âge, le sexe, les antécédents familiaux de diabète, le mariage, les antécédents d'hypertension, de maladie cardiovasculaire et de diabète gestationnel (DG) ou l'accouchement de gros bébés, l'IMC, la pression artérielle systolique et diastolique étaient significativement associés au prédiabète et au diabète dans les zones urbaines et rurales. Cependant, les odds ratio ajustés ont montré que les antécédents familiaux de diabète (2,14, IC à 95 % : 1,26-3,61 contre 1,36, IC à 95 % : 1,00-1,85) et les antécédents de DG chez les femmes (2,67, IC à 95 %: 0,62, 11,39 contre 1,32, IC à 95 % : 0,61, 2,89) prédisent clairement la dysglycémie en milieu rural par rapport aux participants urbains, respectivement. CONCLUSIONS: Les antécédents familiaux de diabète et les antécédents de DG prédisent de manière disproportionnée la dysglycémie en milieu rural par rapport au milieu urbain. Un dépistage périodique de la dysglycémie et une éducation sanitaire, en particulier chez les femmes en âge de procréer, sont des mesures nécessaires pour réduire le fardeau de la dysglycémie au Nigeria. MOTS-CLÉS: Prédiabète, diabète non diagnostiqué, Facteurs de risque, Rural-urbain, Différences, Basé sur l'hémoglobine glyquée, Nigeria.

Analytical Performance Evaluation of the GreenCare A1c and Cera-Stat HbA1c Point-Of-Care Testing Assays.

Background The escalating prevalence of diabetes underscores the need for precise diagnostic tools to facilitate effective management. Hemoglobin A1c (HbA1c) is a crucial biomarker for long-term glycemic control in diabetic patients. Point-of-care testing (POCT) for HbA1c offers rapid, accessible alternatives to conventional laboratory methods, but uncertainties persist regarding the accuracy and reliability of POCT assays. Methods This study evaluates the analytical performance of two boronate-affinity based HbA1c POCT assays, the GreenCare A1c and Cera-Stat HbA1c. Various analytical parameters including precision, linearity, comparison, accuracy are assessed following guidelines from Clinical and Laboratory Standards Institute (CLSI), with results applied to certification criteria from the National Glycohemoglobin Standardization Program (NGSP) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Furthermore, 52 and 13 frozen EDTA whole blood samples were respectively used for additional evaluation of accuracy and interference due to Hb variants for the GreenCare A1c assay. Results Both GreenCare and Cera-Stat demonstrated good precision (repeatability CV% 1.5-1.9 and total imprecision CV% 1.6-2.2), linearity (R2= 0.9996 & 0.9990), and correlation (r= 0.982 & 0.978) with an established HbA1c analyzer, the Bio-Rad D100. The GreenCare also exhibited good accuracy with frozen EDTA samples with known HbA1c values. Both assays met the certification criteria from NGSP and IFCC, classifying them as 'standard' according to IFCC model for quality targets for HbA1c. Conclusion This evaluation affirms the reliability of GreenCare and Cera-Stat POCT assays for HbA1c measurements, which can potentially reduce unnecessary referrals and enhance the overall quality of diabetes diagnosis and treatment.

The Impact of Hand Strength on HbA1c, Body Mass Index and Body Composition by Group According to Sedentary Behaviour: Cross-Sectional Study in Japanese Patients with Type 2 Diabetes Mellitus.

Background: The impact of hand strength in consideration of sedentary behaviour on diabetes management in patients with type 2 diabetes mellitus (T2DM) is unclear. The purpose of this study was to examine the impact of hand strength on HbA1c, body mass index (BMI) and body composition by group according to the duration of sedentary behaviour in Japanese patients with T2DM. Methods: In this retrospective, cross-sectional, single-centre study, hand strength standardised by bodyweight (GS) and sedentary time (ST), were obtained and analysed in a total of 270 Japanese T2DM outpatients in 2021. After dividing the patients into four categories of median values (high and low GS, and long and short ST), odds ratios (ORs) for good control of HbA1c, BMI, waist circumference (WC) and intra-abdominal fat (IAF) were investigated using logistic regression models. Results: The high GS/short ST group was found to have a significantly higher (OR = 2.01; 95% CI: 1.00, 4.03; P = 0.049) for controlled HbA1c compared with that of the low GS/long ST group. The high GS/short ST and the high GS/long ST groups had significantly higher ORs for controlled BMI, WC and IAF compared with the OR of the low GS/long ST group. In addition, the ORs were significantly increased with a positive trend in order from low GS/long ST, low GS/short ST, high GS/long ST, to high GS/short ST in all models (P < 0.001 for trend). Conclusion: Hand strength, with modest effects from sedentary behaviour, could be helpful for diabetes management in T2DM patients.

Impact of haemoglobin variants on the diagnostic sensitivity of glycated haemoglobin (HbA1c) assay methodologies in sub-Saharan Africa: a laboratory-based method validation study.

Introduction: the utility of glycated haemoglobin (HbA1c) for the diagnosis and monitoring of diabetes in sub-Saharan Africa is uncertain due to limited data on the performance of the available HbA1c assay methods in this population, which has a high prevalence of haemoglobin variants. We aimed to compare the diagnostic accuracy of the major HbA1c methodologies (Boronate Affinity, Capillary Electrophoresis, High Performance Liquid Chromatography, Immunoassay) in an African population, and assess the impact of the common haemoglobin variant HbAS (sickle cell trait). Methods: whole blood samples were obtained from 182 individuals living with type 2 diabetes in Uganda. HbA1c values for each method were compared to average glucose measured over 14 days by continuous glucose monitoring (CGM). To determine concordance, the three HbA1c assay methods were compared to the capillary electrophoresis method. Results: there was a strong correlation between CGM average glucose levels and all four HbA1c methodologies (r=0.81-0.89) which did not differ in those with and without HbAS (present in 37/182 participants). The presence of HbAS did not alter the relationship between HbA1c and CGM glucose for any assay (p for interaction >0.2 for all methods). Diagnostic accuracy for CGM average glucose thresholds of 7 and 10mmol/L was similar across methods (area under the receiver operating characteristic curve 0.80-0.84 and 0.76-0.84 respectively). The maximum bias between the HbA1c assay methodologies was 2 mmol/mol (2.07%). Conclusion: all major HbA1c technologies offer accurate and comparable HbA1c measurement even in this population with high prevalence of haemoglobin variants.

Effectiveness of switching from dipeptidyl peptidase-4 inhibitor to oral glucagon-like peptide-1 receptor agonist in Japanese participants with type 2 diabetes mellitus: Prospective observational study using propensity score matching.

AIM: Recently, the development of the oral glucagon-like peptide-1 receptor agonist semaglutide has drawn a great deal of attention. This study aimed to compare the effectiveness of oral glucagon-like peptide-1 receptor agonist semaglutide and dipeptidyl peptidase-4 (DPP-4) inhibitors on glycaemic control and several metabolic parameters in patients with type 2 diabetes mellitus over a 6-month period. METHODS: Fifty-nine participants were included, and we compared various clinical parameters between before and after switching from DPP-4 inhibitors to oral semaglutide in 'study 1' (pre-post comparison) and set the control group using the propensity score matching method in 'study 2'. RESULTS: In 'study 1', 6 months after the switching, the glycated haemoglobin value was significantly reduced from 7.5% to 7.0%, and the body mass index was also decreased from 29.7 kg/m2 to 28.8 kg/m2. Such effects were more clearly observed in participants whose glycaemic control was poor. In 'study 2', after 1:1 propensity score matching, 51 participants from each group were matched, and glycaemic control as well as body weight management were improved in the switching group compared with the DPP-4 inhibitor continuation group over the 6-month observation period. CONCLUSION: In this study, including obese participants with poor glycaemic control, switching DPP-4 inhibitors to oral semaglutide showed more beneficial effects on both glycaemic and weight control, irrespective of age, body weight and diabetes duration. Therefore, we should bear in mind that it would be better to start using an oral semaglutide in clinical practice, particularly in obese participants with poor glycaemic control with DPP-4 inhibitors.

Salivary fructosamine in diabetic and non-diabetic individuals with healthy and diseased periodontium and its changes after non-surgical periodontal therapy.

AIMS: A bidirectional relationship has been reported between diabetes mellitus and periodontitis. The present study aimed to estimate salivary fructosamine in diabetic and non-diabetic individuals with healthy and diseased periodontium and to measure its changes after non-surgical periodontal therapy. Another aim was to identify the cut-off value of salivary fructosamine to diagnose diabetes mellitus and to correlate it with glycated hemoglobin. METHODS: Salivary fructosamine and HbA1c were assessed in periodontally healthy individuals and periodontitis patients (n = 60 in each group). Both groups comprised of equal number of patients with and without diabetes mellitus. Salivary fructosamine estimation was repeated 4 weeks after non-surgical periodontal therapy in periodontitis patients. RESULTS: HbA1c and Salivary fructosamine were significantly higher in the periodontally diseased compared to the healthy group. Significantly higher values of these biomarkers were noticed in diabetic patients with periodontitis compared to the non-diabetic group. Periodontal therapy significantly reduced salivary fructosamine in both diabetic and nondiabetic periodontitis patients. A significant positive high correlation was noticed between salivary fructosamine and HbA1c (r = 0.76). The cut-off value of salivary fructosamine was found to be 68 µg/mL with 95% sensitivity, 81.67% specificity, 83.82% positive predictive value, and 94.23% negative predictive value. CONCLUSION: Periodontitis can contribute to glycemic control and periodontal therapy can bring about improvement in glycemic status. Salivary fructosamine could be used as an alternate glycemic biomarker and its advantages over HbA1c include simple and non-invasive collection of saliva and it can provide intermediate glycemic status. CLINICAL TRIAL REGISTRY OF INDIA: 2020/11/038496.

Inquiry of the Metabolic Traits in Relationship with Daily Magnesium Intake: Focus on Type 2 Diabetic Population.

Magnesium (Mg), an essential nutrient with a wide area of physiological roles, stands as a cofactor in over 600 enzymatic reactions involved in the synthesis of proteins and nucleic acids, DNA repair, neuromuscular functions, neuronal transmission, cardiac rhythm regulation, and the modulation of metabolic pathways, as well as acting as a natural blocker for the calcium channels. Our objective was to highlight the most recent clinical data with respect to daily Mg intake (DMI) and metabolic traits, particularly type 2 diabetes mellitus (DM). This was a PubMed-based review of the English-language medical papers across different key terms of search; the time frame was from January 2019 until April 2024. We included (clinically relevant) original studies and excluded cases reports, series, reviews, editorials, opinion, experimental studies, and non-human data as well as studies that did not specifically assessed DMI and only provided assays of serum Mg, studies on patients diagnosed with type 1 or secondary DM. A total of 30 studies were included and we organized the key findings into several sections as follows. Studies investigating DMI in relationship with the adherence to local recommendations in diabetic subjects (n = 2, one transversal and another retrospective cohort; N = 2823) found that most of them had lower DMI. Deficient DMI was correlated with the risk of developing/having DM across five studies (n = 5, one prospective and four of cross-sectional design; N = 47,166). An inverse correlation between DMI and DM prevalence was identified, but these data are presented amid a rather heterogeneous spectrum. Four novel studies (N = 7279) analysed the relationship between DMI and DM control according to various methods (HbA1c, fasting and postprandial glycaemia, and insulin); the association may be linear in diabetic subjects only at certain levels of DMI; additionally, the multifactorial influence on HBA1c should take into consideration this dietary determinant, as well, but there are no homogenous results. Three studies concerning DMI and diabetic complications (one cross-sectional, one prospective, and another case-control study) in terms of retinopathy (n = 1, N = 3794) and nephropathy (n = 2, N = 4805) suggested a lower DMI was associated with a higher risk of such complications. Additionally, two other studies (one prospective and one retrospective cohort) focused on mortality (N = 6744), which, taking only certain mortality indicators into consideration, might be decreased in the subgroups with a higher DMI. Seven studies (N = 30,610) analysed the perspective of DMI in the general population with the endpoint of different features amid glucose profile, particularly, insulin resistance. Concerning HOMA-IR, there were three confirmatory studies and one non-confirmatory, while fasting plasma glucose was highlighted as inversely correlated with a DMI (n = 1). The highest level of evidence regarding Mg supplementation effects on glucose metabolism stands on seven randomised controlled trials (N = 350). However, the sample size was reduced (from 14 to 86 individuals per study, either diabetic or pre-diabetic) and outcomes were rather discordant. These clinical aspects are essential from a multidisciplinary perspective and further trials are mandatory to address the current areas of discordant results.

The effect of the intercellular adhesion molecule-1 and glycated haemoglobin on the management of diabetic neovascular glaucoma.

Introduction: The study hypothesizes that some patients with diabetic neovascular glaucoma (NVG) do not fully respond to transscleral (TSC) cyclophotocoagulation (CPC) due to significant inflammation and insufficient glucose control. Objective: The study aimed to determine the effect of baseline blood levels of intercellular adhesion molecule-1 (ICAM-1) and glycated haemoglobin (HbA1c) on the management of patients with diabetic NVG by TSC CPC. Methods: This open prospective study included 70 diabetic patients (75 eyes; aged Ме 63.0 years) with painful NVG and 20 healthy individuals (aged Ме 61.5 years) as an immunological control. All patients underwent TSC СPC with a diode laser. Baseline HbA1c levels and ICAM-1 expression in blood samples were determined. Follow-up was 12 months. Results: One month after TSC CPC, IOP decreased by 28% compared to baseline. The effectiveness of laser treatment after 12 months of follow-up was 63% with IOP decrease by 46%. In patients with NVG, the initial level of ICAM-1 was 2.5 times higher than in the control group. Patients who did not fully respond to the first TSC CPC (30 eyes) and required additional laser procedure, had high initial HbA1c (9.5%) and high expression values of the ICAM-1 (609.0 cells/µL). Conclusions: Repeated procedures of TSC CPC at high IOP in diabetic patients with NVG are associated with high initial values of expression of ICAM-1 in peripheral blood and high HbA1c. The strategy of management of patients with diabetic NVG should be aimed at intensive glucose control and local anti-inflammatory treatment. Abbreviations: PDR = proliferative diabetic retinopathy, DR = diabetic retinopathy, NVG = neovascular glaucoma, TSC CPC = transscleral cyclophotocoagulation, ICAM-1 = intercellular adhesion molecule-1, HbA1c = glycated haemoglobin, IOP = intraocular pressure.

Cognitive dysfunction in diabetes-related foot complications: A cohort study.

Objective: Mild-moderate cognitive impairment has been identified in general diabetes, and early evidence indicates cognitive reductions may be more pronounced in those with diabetes-related foot complications (DRFC). Cognitive difficulties may impede treatment engagement and self-management. This requires further explication to optimise patient care and outcomes. The current study aimed to characterise cognitive function in people with DRFC using comprehensive cognitive measures. Method: This cross-sectional cohort study recruited 80 adult participants (M age = 63.38, SD = 11.40, range = 30 - 89) from the Royal Melbourne Hospital Diabetic Foot Unit in Victoria, Australia, all with DRFC. Each completed a comprehensive cognitive battery (memory, attention, executive functions) and scores were calculated using age-matched population norms, where available. Results: On the majority of tasks, DRFC participants performed significantly worse than age-matched norms, with the largest decrements seen in inhibition control, verbal memory, verbal abstract reasoning and working memory. Small to moderate reductions were also seen in visual learning, verbal fluency, processing speed and premorbid functioning. Demographic (lower education, male gender) and clinical factors (higher HbA1c, macrovascular and microvascular disease, longer diabetes duration) were associated with poorer cognitive functioning. Conclusions: Marked reductions in cognitive functioning were found in individuals with DRFC, predominantly in the domains of verbal memory and executive functioning. Lower education, male gender and indicators of diabetes severity, such as vascular disease, are associated with heightened risk for poorer cognitive functioning. As DRFCs are a serious complication with devastating outcomes if not successfully managed, cognitive barriers to self-management must be addressed to optimise treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01381-4.

Retrospective Observational Study on Assessing Sitagliptin and Dapagliflozin as a Fixed-Dose Combination in the Indian Population With Type 2 Diabetes Mellitus: The SIDAXA Study.

Introduction Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, necessitates multifaceted treatment approaches. Emerging studies highlight the cardiovascular advantages of sodium-glucose transport protein 2 (SGLT2) and dipeptidyl peptidase 4 (DPP-4) inhibitors in T2DM. This investigation delves into the synergistic effects of the fixed-dose combination (FDC) of sitagliptin and dapagliflozin, offering insights into its safety and efficacy for the Indian population. Methods This real-world, retrospective, observational study spanned 328 cases across 111 Indian centres, evaluating the safety, efficacy, and clinical utilization of the sitagliptin and dapagliflozin FDC in T2DM patients after obtaining ethical approval. Assessments at baseline, week four, and week 12 encompassed hemoglobin A1C (HbA1C), fasting plasma glucose (FPG), postprandial blood glucose (PPBG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), and weight change. The statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 29.0.1.0(171) (IBM Corp., Armonk, NY, USA) with a significance level p<0.05. Results Study participants [mean age: 51.14±5.55 years, 77.74% (n=255) males, 22.26% (n=73) females] exhibited prevalent risk factors like sedentary lifestyle (n=167, 50.91%) and smoking (n=147, 44.82%). Comorbidities included hypertension (n=235, 71.65%) and dyslipidaemia (n=139, 42.38%). Metformin (n=282, 85.98%) and sulfonylurea (n=134, 40.85%) were commonly prescribed concomitant oral antidiabetic agents (OADs). FDC administration significantly reduced HbA1c by 1.05 ± 0.83% (p < 0.0001) at week 12. FPG and PPBG showed significant reductions of 22.98 ± 22.23 mg/dL (p < 0.0001), 165.50 ± 37.02 mg/dL and 40.94 ± 36.04 mg/dL (p < 0.0001) at four weeks respectively. By week 12, significant reductions were noted in SBP (14.61±13.98mmHg reduction, p-value <0.0001), DBP (7.80±8.45mmHg reduction, p-value <0.0001), and LDL-C levels (18.14±23.95 mg/dL reduction, p-value <0.0001). In patients with established cardiovascular disease, there was reduction in HbA1c levels by 1.02 ± 0.63% after 12 weeks, with FPG decreasing by 54.52 ± 32.67 mg/dL and PPBG decreasing by 88.73 ± 44.90 mg/dL. Treatment-emergent adverse events included headache, changes in micturition, genital mycotic infection, and nausea and diarrhoea which were mild, transient, and necessitated no treatment discontinuation. Conclusion The FDC of sitagliptin and dapagliflozin significantly improved glycaemic control and lipid profiles in T2DM patients, particularly those with coronary artery disease. It demonstrated a favourable safety profile in the Indian population, signifying its potential as an effective and well-tolerated therapeutic option in patients with established cardiovascular disease.

Impact of Self-Monitoring Blood Glucose on Glycaemic Control Among Insulin-Treated Patients With Diabetes Mellitus in Northeastern Tanzania: A Randomised Controlled Trial.

Introduction: Tracking of blood glucose levels by patients and care providers remains an integral component in the management of diabetes mellitus (DM). Evidence, primarily from high-income countries, has illustrated the effectiveness of self-monitoring of blood glucose (SMBG) in controlling DM. However, there is limited data on the feasibility and impact of SMBG among patients in the rural regions of sub-Saharan Africa. This study is aimed at assessing SMBG, its adherence, and associated factors on the effect of glycaemic control among insulin-treated patients with DM in northeastern Tanzania. Materials and Methods: This was a single-blinded, randomised clinical trial conducted from December 2022 to May 2023. The study included patients with DM who had already been on insulin treatment for at least 3 months. A total of 85 participants were recruited into the study and categorised into the intervention and control groups by a simple randomization method using numbered envelopes. The intervention group received glucose metres, test strips, logbooks, and extensive SMBG training. The control group received the usual care at the outpatient clinic. Each participant was followed for a period of 12 weeks, with glycated haemoglobin (HbA1c) and fasting blood glucose (FBG) being checked both at the beginning and at the end of the study follow-up. The primary and secondary outcomes were adherence to the SMBG schedule, barriers associated with the use of SMBG, and the ability to self-manage DM, logbook data recording, and change in HbA1c. The analysis included descriptive statistics, paired t-tests, and logistic regression. Results: Eighty participants were analysed: 39 in the intervention group and 41 in the control group. In the intervention group, 24 (61.5%) of patients displayed favourable adherence to SMBG, as evidenced by tests documented in the logbooks and glucometer readings. Education on SMBG was significantly associated with adherence. Structured SMBG improved glycaemic control with a HbA1c reduction of -1.01 (95% confidence interval (CI) -1.39, -0.63) in the intervention group within 3 months from baseline compared to controls of 0.18 (95% CI -0.07, 0.44) (p < 0.001). Conclusion: Structured SMBG positively impacted glycaemic control among insulin-treated patients with DM in the outpatient clinic. The results suggest that implementing a structured testing programme can lead to significant reductions in HbA1c and FBG levels. Trial Registration: Pan African Clinical Trials Registry identifier: PACTR202402642155729.

Comparative efficacy and safety of weekly tirzepatide versus weekly insulin in type 2 diabetes: A network meta-analysis of randomized clinical trials.

AIM: To compare the efficacy and safety profiles of recent innovations in type 2 diabetes mellitus (T2DM), which include once-weekly formulations such as tirzepatide, a dual glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor agonist, and once-weekly insulin options such as icodec and basal insulin Fc. METHODS: A systematic search of the PubMed, Scopus, Cochrane, and Web of Science databases was conducted. The network meta-analysis protocol was registered at OSF registries (https://osf.io/gd67x). The primary outcome of interest was change in glycated haemoglobin (HbA1c), with change in fasting plasma glucose (FPG), body weight, incidence of hypoglycaemia, and treatment discontinuation as secondary outcomes. RESULTS: Tirzepatide exhibited superior efficacy in reducing HbA1c levels compared with insulin therapies, with the 15-mg dose showing the most significant reduction (mean difference [MD] -1.27, 95% confidence interval [CI] -1.49; -1.0). In terms of FPG reduction, tirzepatide 15 mg ranked highest (MD -0.70, 95% CI -1.05; -0.34), followed by tirzepatide 10 mg and 5 mg. Additionally, tirzepatide led to substantial weight loss, with the 15-mg dose exhibiting the most pronounced effect (MD -12.13, 95% CI -13.98; -10.27). However, a higher incidence of adverse events (AEs) and treatment discontinuation were associated with tirzepatide, particularly at higher doses. CONCLUSION: Tirzepatide, particularly at higher doses, demonstrates superior efficacy in lowering HbA1c and reducing hypoglycaemia risk compared with weekly insulin. However, its use is also associated with a higher incidence of AEs and treatment discontinuation.

The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study.

Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806). Cross-trait linkage disequilibrium score regression was applied to determine genetic correlations across accelerometer-derived, self-reported sleep traits, and HbA1c/glucose. We found no causal effect of any accelerometer-derived sleep trait on HbA1c or glucose. Similar MR results for self-reported sleep traits in the UKB sub-sample with accelerometer-derived measures suggested our results were not explained by selection bias. Phenotypic and genetic correlation analyses suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different types of exposure. These findings suggested accelerometer-derived sleep traits do not affect HbA1c. Accelerometer-derived measures of sleep duration and quality might not simply be 'objective' measures of self-reported sleep duration and insomnia, but rather captured different sleep characteristics.

Lower achievement of guideline recommended care in Canadian adults with early-onset diabetes: A population-based cohort study.

AIMS: Adults with early-onset diabetes (age < 40 years) have an increased risk of complications, and it is unclear whether they are receiving guideline recommended care. We compared the frequency and results of haemoglobin A1c (HbA1c) testing in adults with early-onset and usual-onset diabetes and assessed factors related to guideline concordance. METHODS: Population-level databases from Alberta, Canada (∼4.5 million) were used to identify adults with incident diabetes. The cohort was stratified by age at diagnosis (< 40 vs. ≥ 40 years) and then followed for 365 days for HbA1c testing. Adjusted multivariable analyses were used to identify clinical and sociodemographic factors associated with guideline concordance. RESULTS: Among 23,643 adults with incident diabetes (mean age 54.1 ± 15.4 years; 42.1 % female), 18.9 % had early-onset diabetes. Early-onset diabetes was associated with lower frequency of testing (adjusted odds ratio (aOR), 0.80; 95 % CI 0.70-0.90) and above target glycaemic levels compared to usual-onset diabetes (aOR, 1.45; 95 % CI 1.29-1.64). Factors associated with guideline concordant frequency of HbA1c testing were rural residence and insulin use. CONCLUSIONS: In our universal care setting with premium-free health care, early-onset diabetes was associated with lower rates of HbA1c testing and sub-optimal glycaemic control compared to those with usual-onset diabetes.

Inflammatory and endothelial host responses in community-acquired pneumonia: exploring the relationships with HbA1c, admission plasma glucose, and glycaemic gap-a cross-sectional study.

Introduction: Diabetes is associated with dysregulated immune function and impaired cytokine release, while transient acute hyperglycaemia has been shown to enhance inflammatory cytokine release in preclinical studies. Although diabetes and acute hyperglycaemia are common among patients with community-acquired pneumonia (CAP), the impact of chronic, acute, and acute-on-chronic hyperglycaemia on the host response within this population remains poorly understood. This study investigated whether chronic, acute, and acute-on- chronic hyperglycaemia are associated with distinct mediators of inflammatory, endothelial, and angiogenic host response pathways in patients with CAP. Methods: In a cross-sectional study of 555 patients with CAP, HbA1c, admission plasma (p)-glucose, and the glycaemic gap (admission p-glucose minus HbA1c- derived average p-glucose) were employed as measures of chronic, acute, and acute-on-chronic hyperglycaemia, respectively. Linear regression was used to model the associations between the hyperglycaemia measures and 47 proteins involved in inflammation, endothelial activation, and angiogenesis measured at admission. The models were adjusted for age, sex, CAP severity, pathogen, immunosuppression, comorbidity, and body mass index. Adjustments for multiple testing were performed with a false discovery rate threshold of less than 0.05. Results: The analyses showed that HbA1c levels were positively associated with IL-8, IL-15, IL-17A/F, IL-1RA, sFlt-1, and VEGF-C. Admission plasma glucose was also positively associated with these proteins and GM-CSF. The glycaemic gap was positively associated with IL-8, IL-15, IL-17A/F, IL-2, and VEGF-C. Conclusion: In conclusion, chronic, acute, and acute-on-chronic hyperglycaemia were positively associated with similar host response mediators. Furthermore, acute and acute-on-chronic hyperglycaemia had unique associations with the inflammatory pathways involving GM-CSF and IL-2, respectively.

Fructosamine and HbA1c: A Correlational Study in a Southeast Asian Population.

Objectives: Fructosamine correlates well with glycated haemoglobin (HbA1c) in Caucasians. This study investigates this correlation and whether fructosamine can reliably estimate glycated haemoglobin in Southeast Asians. Methods: We recruited 193 participants based on 4 HbA1c bands (<6.0%; 6.0 - 7.9%; 8.0- 9.9%; ≥10%) from a secondary hospital in Singapore between August 2017 and December 2021. Blood samples for fructosamine, glycated haemoglobin, albumin, haemoglobin, thyroid stimulating hormone and creatinine were drawn in a single setting for all participants. Scatter plot was used to explore correlation between fructosamine and glycated haemoglobin. Strength of linear correlation was reported using Pearson's correlation coefficient. Simple linear regression was used to examine the relationship between fructosamine and glycated haemoglobin. Results: We performed simple linear regression to study the relationship between fructosamine and HbA1c in the research participants (R2 = 0.756, p<0.01). Further analysis with natural logarithmic transformation of fructosamine demonstrated a stronger correlation between HbA1c and fructosamine (R2 = 0.792, p<0.01). Conclusions: Fructosamine is reliably correlated with HbA1c for the monitoring of glycaemic control in Southeast Asians.

Effect of COVID-19 lockdown on glycated haemoglobin testing and utilisation in KwaZulu-Natal, South Africa.

Background: Diabetic monitoring and treatment guidelines are easily accessible, but compliance is poor in KwaZulu-Natal. The coronavirus disease 2019 (COVID-19) pandemic had a devastating impact on diabetic healthcare, both directly and through public health interventions. Objective: This study aimed to close the gaps in knowledge concerning glycated haemoglobin (HbA1c) test utilisation and how this was affected by the COVID-19 lockdown in KwaZulu-Natal. Methods: We reviewed HbA1c test volumes and results from public health facilities in the 11 health districts in KwaZulu-Natal, South Africa. We compared testing trends and glycaemic control between two 10-month study periods before (March 2019 - December 2019) and during (March 2020 - December 2020) the COVID-19 pandemic. Results: The number of HbA1c tests performed decreased 6.1% during the pandemic period, with 173 760 HbA1c tests performed in 2019 and 163 236 HbA1c tests performed in 2020. There was a statistically significant increase in the average HbA1c level during the pandemic (mean HbA1c level in the pre-pandemic period: 70.5 mmol/mol [8.6%] versus mean HbA1c level in the pandemic period: 72.7 mmol/mol [8.8%]; p-value < 0.001). Of patients with suboptimal HbA1c results (83 421 in 2019, 83 259 in 2020), 11 656 (14.0%) in 2019 and 10 086 (12.1%) in 2020 had more than one HbA1c test performed during the study period. Conclusion: The COVID-19 pandemic impacted glycaemic monitoring in KwaZulu-Natal with lower HbA1c test volumes and worse glycaemic control seen during the pandemic. HbA1c testing practices are not in keeping with recommended guidelines. What this study adds: The study demonstrates that the COVID-19 pandemic impacted HbA1c utilisation in KwaZulu-Natal. Importantly, HbA1c testing practices in KwaZulu-Natal are not in keeping with Society for Endocrinology, Metabolism and Diabetes of South Africa guidelines regarding the monitoring of diabetic patients, and this requires more attention for future diabetic healthcare interventions.