Glucose Control Research Articles

Time-Efficacy Relationship of Semaglutide in the Treatment of Type 2 Diabetes Mellitus: A Model-Based Meta-Analysis.

Our objective was to quantify the efficacy of subcutaneous once-weekly semaglutide in treating type 2 diabetes mellitus (T2DM) over time. Based on a literature search of the PubMed, Embase, Cochrane, and Web of Science databases, a modified maximum effect (Emax) model including rebound effects was built using model-based meta-analysis with change from baseline in glycated hemoglobin as the efficacy endpoint. This was combined with the covariate model to form a final model, and then theoretical values of Emax and time to reach 50% of Emax (ET50) were obtained for each dose. Model fit and prediction were assessed using goodness-of-fit plots and visual prediction checking. Emax and ET50 were influenced by the proportion of males and the baseline values, respectively. There was no evidence of a placebo effect with semaglutide. The efficacy of other doses became more significant over time, and a rebound effect was observed after maximum efficacy, at a rate of 0.018. Simulation of the typical efficacy at the different doses yielded a maximum efficacy of -1.58% with 0.5 mg and a maximum efficacy of -1.87% with 1 mg. In addition, the six simulated doses (0, 0.1, 0.2, 0.5, 1, and 2 mg) showed a dose-dependent relationship between dose and efficacy except for 0.4 mg and 0.8 mg. A higher dose would result in greater efficacy and a faster onset of action. The efficacy of semaglutide in glucose control was investigated using the model-based meta-analysis method, which yields new insights into the treatment of T2DM with semaglutide.

Determining how the gestational changes, including low hemoglobin influence the hba1c and estimated average glucose relationship

ABSTRACT Background: Gestational Diabetes Mellitus (GDM) affects up to 14% of pregnancies globally, with accurate glycemic control critical for preventing adverse outcomes. While HbA1c is a standard marker for long-term glucose control, its reliability in pregnant women with anemia is debated. This study explores the association between anemia and glycemic indicators (Glycosylated hemoglobin HbA1c, Random plasma glucose (rPG), and Estimated average glucose (eAG) in pregnant women with GDM. Additionally, it examined the correlation between average glucose levels or eAG, measured by random plasma glucose rPG, and HbA1C. Methods: A prospective case-control study was carried out over eight months at the Departments of Chemical Pathology and Obstetrics and Gynecology, Dow University of Health Sciences (DUHS). Pregnant women in their second trimester after being diagnosed for GDM through oral glucose tolerance test were classified into anemic (hemoglobin < 10.5 g/dL) and non-anemic groups. Blood samples were collected and analyzed for HbA1c, hemoglobin, and random plasma glucose levels. Data were processed using SPSS (version-26) different variables compared by using independent t-test and correlation analyses at a significance level of p < 0.05. Results: Mean values for eAG, HbA1C, and rPG were 174.22 ± 24.489 mg/dl, 8.342 ± 1.6152%, and 166.21 ± 21.478 mg/dl, respectively. Anemia was associated with significantly higher HbA1C (p < 0.001), eAG (p < 0.001), and rPG (p = 0.004). A strong positive correlation was observed between eAG and rPG (r = 0.958, p < 0.01), while eAG showed a moderate correlation with HbA1C (r = 0.501, p < 0.01). In contrast, the correlation between HbA1C and rPG was weaker (r = 0.331, p < 0.01). Conclusion: eAG proved to be a good indicator for assessing glycemic control in pregnant non-anemic women with GDM. Anemia significantly affected glycemic metrics, leading to higher HbA1C and glucose levels.

Protective Potential of Sodium-Glucose Cotransporter 2 Inhibitors in Internal Medicine (Part 1)

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a revolutionary class of drugs with far-reaching protective effects in multiple organs. The protective potential of SGLT2i is much broader than that of the classical concept of glucose control and consists of an entire conglomerate of associated pleiotropic effects. This study aims to provide a descriptive review of the pleiotropic therapeutic potential of SGLT2i. The first part of the literature review examined the use of SGLT2i in cardiology and nephrology. The use of SGLT2i represents an innovative approach to improving patients’ quality of life and course of heart failure and chronic kidney disease, regardless of left ventricular ejection fraction and type 2 diabetes.

Association between the rs1800624 and rs80096349 SNPs and diabetic retinopathy: a pilot study

ABSTRACT Background One of the conditions that might harm your eyesight is diabetic retinopathy (DR), DR may set in slowly but surely for those with long-term diabetes and poor glucose control. ‎ Objective To establish a connection between the various genotypes of the rs1800624 SNP and the rs80096349 SNP located in the AGER gene and DR patients. ‎ Methods The current case-control research examined one hundred thirty-four individuals diagnosed with type 2 diabetes and thirty-six healthy individuals who did not have DM. These samples were obtained from Amir Al-Muminin, a private hospital in Najaf, Iraq. The tetra primers ARMS-PCR method was utilized to determine the genotype of rs1800624 SNP of the AGER gene. Results A significant association was found between genotypes (AA, AG, and GG) and DR subgroups (NPDR & PDR) in patients (p = 0.001). The AG genotype of rs1800624 SNP is associated with a lowering the risk of developing NPDR (OR = 0.30; 95% CI = 0.12-0.74; p = 0.009 between controls and NPDR, OR = 0.36; 95% CI = 0.14-0.90; p = 0.029 between NDR and NPDR). HRM analysis verified the presence of only two genotypes in the samples: wild type (GG) and a heterozygous mutant (GA). However, a significant association between genotypes was observed when comparing DR status with controls and NDR (p = 0.031). Conclusion The rs1800624 SNP of the AGER gene is associated with the risk of NPDR and PDR in T2DM, and the polymorphism of the rs80096349 may be associated with retinopathy in the Iraqi population.

Relationship between diabetes-related clinical characteristics and preserved ratio impaired spirometry (PRISm): findings from NHANES 2007–2012

IntroductionTo analyse the relationship between diabetes, its severity (including blood glucose levels, disease duration, antidiabetic drug use and number of comorbidities) and preserved ratio impaired spirometry (PRISm) using data from...

NK2R control of energy expenditure and feeding to treat metabolic diseases.

The combination of decreasing food intake and increasing energy expenditure represents a powerful strategy for counteracting cardiometabolic diseases such as obesity and type 2 diabetes1. Yet current pharmacologicalapproaches require conjugation of multiple receptor agonists to achieve both effects2-4, and so far, no safe energy-expending option has reached the clinic. Here we show that activation of neurokinin 2 receptor (NK2R) is sufficient to suppress appetite centrally and increase energy expenditure peripherally. We focused on NK2R after revealing its genetic links to obesity and glucose control. However, therapeutically exploiting NK2R signalling has previously been unattainable because its endogenous ligand, neurokinin A, is short-lived and lacks receptor specificity5,6. Therefore, we developed selective, long-acting NK2R agonists with potential for once-weekly administration in humans. In mice, these agonists elicit weight loss by inducing energy expenditure and non-aversive appetite suppression that circumvents canonical leptin signalling. Additionally, a hyperinsulinaemic-euglycaemic clamp reveals that NK2R agonism acutely enhances insulin sensitization. In diabetic, obese macaques, NK2R activation significantly decreases body weight, blood glucose, triglycerides and cholesterol, and ameliorates insulin resistance. These findings identify a single receptor target that leverages both energy-expending and appetite-suppressing programmes to improve energy homeostasis and reverse cardiometabolic dysfunction across species.

Efficacy and Safety of Automated Insulin Delivery Systems in Patients with Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Automated insulin delivery (AID) systems studies are upsurging, half of which were published in the last 5 years. We aimed to evaluate the efficacy and safety of AID systems in patients with type 1 diabetes mellitus (T1DM). We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov until August 31, 2023. Randomized clinical trials that compared AID systems with other insulin-based treatments in patients with T1DM were considered eligible. Studies characteristics and glycemic metrics was extracted by three researchers independently. Sixty-five trials (3,623 patients) were included. The percentage of time in range (TIR) was 11.74% (95% confidence interval [CI], 9.37 to 14.12; P<0.001) higher with AID systems compared with control treatments. Patients on AID systems had more pronounced improvement of time below range when diabetes duration was more than 20 years (??.80% vs. ??.86%, P=0.031) and baseline glycosylated hemoglobin lower than 7.5% (??.93% vs. ??.87%, P=0.033). Dual-hormone full closed-loop systems revealed a greater improvement in TIR compared with hybrid closed-loop systems (??9.64% vs. ??0.87%). Notably, glycemia risk index (GRI) (??.74; 95% CI, ??.34 to ??.14; P<0.01) was also improved with AID therapy. AID systems showed significant advantages compared to other insulin-based treatments in improving glucose control represented by TIR and GRI in patients with T1DM, with more favorable effect in euglycemia by dual-hormone full closedloop systems as well as less hypoglycemia for patients who are within target for glycemic control and have longer diabetes duration.

Genus Stachys—Phytochemistry, Traditional Medicinal Uses, and Future Perspectives

The genus Stachys represents one of the most extensive genera within the subfamily Lamioideae and ranks as one of the largest genera in the Lamiaceae family. Many Stachys species are associated with a rich history in traditional medicine across various cultures, and their extracts and essential oils are rich in non-volatile and volatile compounds. Because of their complex profile of bioactive substances, Stachys members are considered to possess an extensive spectrum of therapeutic properties, including antioxidant, anti-inflammatory, analgesic, antibacterial, cytotoxic, and wound-healing effects, as well as benefits for memory enhancement, lipid profile regulation, blood glucose control, and weight management. Despite the wide distribution and chemical diversity of the genus, studies on its biological activities remain limited. The aim of this review is to summarize the most relevant data from studies on the bioactive compounds, traditional uses, and pharmacological properties of Stachys species found in databases such as Science Direct, PubMed, and Scopus. Specific keywords were used in the search strategy, including “bioactive compounds”, “Stachys”, “Lamiaceae”, “Stachys extract”, “Stachys essential oil”, “traditional uses”, “chemical composition”, “therapeutic potential”, “clinical trials”, “in vivo studies”, “in vitro studies”. The search strategy was performed according to the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data from 171 studies were included. The manuscript highlights the drug-discovery potential of Stachys species, emphasizing their potential applications in medicine, cosmetics, dietary supplements, and the food industry. Moreover, it provides important data that could assist Stachys research programs.

Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials.

Supplementation of nicotinamide mononucleotides (NMN) has been claimed to improve metabolic function. We reviewed human randomised controlled trials (RCTs) of NMN to evaluate its effect on markers of glucose and lipid metabolism. Eight RCTs on NMN (dosage ranged 250-2000mg/d for a duration of 14days to 12weeks) involving a total of 342 middle-age/older adults (49% females, mainly non-diabetic) reporting at least one outcome on glucose control or lipid profile published in 2021-2023 were reviewed. The random-effects meta-analyses indicated no significant benefit of NMN on fasting glucose, fasting insulin, glycated hemoglobin, homeostatic model assessment for insulin resistance and lipid profile. Based on the small number of RCTs involving mainly relatively healthy adults, short-term supplementation of NMN of 250-2000mg/d did not show significantly positive impacts on glucose control and lipid profile.

The whole-body and skeletal muscle metabolic response to 14 days of highly controlled low energy availability in endurance-trained females.

This study investigated the effects of 14 days low energy availability (LEA) versus optimal energy availability (OEA) in endurance-trained females on substrate utilization, insulin sensitivity, and skeletal muscle mitochondrial oxidative capacity; and the impact of metabolic changes on exercise performance. Twelve endurance-trained females (V̇O2max 55.2 ± 5.1 mL × min-1 × kg-1) completed two 14-day randomized, blinded, cross-over, controlled dietary interventions: (1) OEA (51.9 ± 2.0 kcal × kg fat-free mass (FFM)-1 × day-1) and (2) LEA (22.3 ± 1.5 kcal × kg FFM-1 × day-1), followed by 3 days OEA. Participants maintained their exercise training volume during both interventions (approx. 8 h × week-1 at 79% heart rate max). Skeletal muscle mitochondrial respiratory capacity, glycogen, and maximal activity of CS, HAD, and PFK were unaltered with LEA. 20-min time trial endurance performance was impaired by 7.8% (Δ -16.8 W, 95% CI: -23.3 to -10.4, p < .001) which persisted following 3 days refueling post-LEA (p < .001). Fat utilization was increased post-LEA as evidenced by: (1) 99.4% (p < .001) increase in resting plasma free fatty acids (FFA); (2) 270% (p = .007) larger reduction in FFA in response to acute exercise; and (3) 28.2% (p = .015) increase in resting fat oxidation which persisted during submaximal exercise (p < .001). These responses were reversed with 3 days refueling. Daily glucose control (via CGM), HOMA-IR, HOMA-β, were unaffected by LEA. Skeletal muscle O2 utilization and carbohydrate availability were not limiting factors for aerobic exercise capacity and performance; therefore, whether LEA per se affects aspects of training quality/recovery requires investigation.

Time in tight range: A key metric for optimal glucose control in the era of advanced diabetes technologies and therapeutics.

Compared to glycated haemoglobin A1c (HbA1c), the rapidly developing continuous glucose monitoring (CGM) technology provides more detailed information about glycemic control. Amongst the new glucose metrics derived from CGM, time in target range of 3.9-10.0 mmol/L (time in range, TIR) has been widely used for the assessment of glucose control. In recent years, the rise of new technologies and therapies including advanced hybrid closed-loop automated insulin delivery systems and new hypoglycemic drugs has made it possible to achieve better glycemic control. In this context, the concept of time in tight range (TITR), defined as the percentage of time spent in target glucose range of 3.9-7.8 mmol/L, has gained increasing attention. Whilst TITR is highly correlated with TIR, there are still differences between the two metrics. These differences make TITR a more appropriate indicator in certain situations, such as when glucose levels are close to normal or when tighter glycemic control is required. This review summarizes recent studies related to TITR.

NCMP-30. GLUCOCORTICOID-INDUCED HYPERGLYCEMIA IN BRAIN TUMOR PATIENTS: A SINGLE CENTER RETROSPECTIVE STUDY

Abstract BACKGROUND Glucocorticoid (GC) therapies are integral in managing brain tumor-associated cerebral edema and neurological deficits in the neuro-oncology perioperative setting. Despite their effectiveness, GCs can induce significant morbidity, including hyperglycemia. METHODS This single-center retrospective study at the University of North Carolina neurological surgery department examines the incidence and risk factors for glucocorticoid-induced hyperglycemia in brain tumor patients treated with high-dose GCs. Data from clinical databases, electronic medical records, laboratory systems, and pathology information banks will be utilized. Documented glucose measurements, glycated hemoglobin test (HbA1c) and clinical outcomes (mortality, infection, hypoglycemia) in brain cancer patients treated with Glucocorticoid (GC) that developed hyperglycemia will be compared with brain tumor patient with normoglycemia. RESULTS We will document the total number of brain tumor patients referred over the study period, eligibility rates, and the percentage that developed glucocorticoid-induced diabetes (defined as two glucose measurements ≥200 mg/dL within the first week of treatment). Timing of hyperglycemia onset, treatments received, and risk factors for developing glucocorticoid-induced diabetes will also be analyzed. CONCLUSIONS The findings could underscore the necessity for proactive screening for glucocorticoid-induced diabetes in brain tumor patients to mitigate the associated morbidity. This study may guide future research on the benefits of optimized glucose control on clinical outcomes in patients with GC-induced hyperglycemia. Keywords: brain tumor, steroid-induced hyperglycemia, glucocorticoid-induced diabetes, dysglycemia, risk factors, outcomes.

Base-editing corrects metabolic abnormalities in a humanized mouse model for glycogen storage disease type-Ia

Glycogen storage disease type-Ia patients, deficient in the G6PC1 gene encoding glucose-6-phosphatase-α, lack blood glucose control, resulting in life-threatening hypoglycemia. Here we show our humanized mouse model, huR83C, carrying the pathogenic G6PC1-R83C variant displays the phenotype of glycogen storage disease type-Ia and dies prematurely. We evaluate the efficacy of BEAM-301, a formulation of lipid nanoparticles containing a newly-engineered adenine base editor, to correct the G6PC1-R83C variant in huR83C mice and monitor phenotypic correction through one year. BEAM-301 can correct up to ~60% of the G6PC1-R83C variant in liver cells, restores blood glucose control, improves metabolic abnormalities of the disease, and confers long-term survival to the mice. Interestingly, just ~10% base correction is therapeutic. The durable pharmacological efficacy of base editing in huR83C mice supports the development of BEAM-301 as a potential therapeutic for homozygous and compound heterozygous glycogen storage disease type-Ia patients carrying the G6PC1-R83C variant.

Protocol for a randomized comparative effectiveness trial comparing a very low-carbohydrate diet to DASH diet for polycystic ovary syndrome: the SUPER (Supporting Understanding of PCOS Education and Research) trial

BackgroundPolycystic ovary syndrome (PCOS), the most common endocrine disorder for women of reproductive age, is associated with increased risk for insulin resistance and type 2 diabetes. Current PCOS treatments insufficiently address the spectrum and severity of the disorder, and there is little evidence-based guidance available for lifestyle management of PCOS, especially through nutritional approaches. Some evidence shows that a very low-carbohydrate diet can improve glucose control compared to low-fat or moderate-carbohydrate diets, leading to improved glucose control and insulin levels that may help to treat symptoms of PCOS. This research investigates whether a very low-carbohydrate diet is more effective in improving glucose control and decreasing symptoms of PCOS in comparison to a DASH diet.MethodsThe SUPER study aims to address the gap in knowledge about nutritional advice for people with PCOS through a randomized, comparative effectiveness trial comparing two approaches to glucose control: the dietary approaches to stopping hypertension (DASH) diet, and a very low-carbohydrate (VLC) diet. We will randomize 184 women with PCOS with body mass indexes (BMIs) between 25 and 50 kg/m2 to a VLC or DASH diet. All participants will follow a 24-session, 12-month, online diet, and lifestyle intervention that teaches their assigned diet. Participants will receive nutritional education, support from diet coaches, and education about behavioral strategies to improve dietary adherence. The primary outcome measure is HbA1c, and secondary outcomes include glucose variance, lipid and hormone levels (including total and free testosterone), PCOS symptoms, inflammation (measured by high-sensitivity C-reactive protein), body composition and weight, psychological well-being, and intervention feasibility and acceptability.DiscussionThe SUPER study is a randomized comparative effectiveness trial that compares two promising approaches to glucose control in people with PCOS. The study also aims to assess the effects of each diet on PCOS symptoms. The research addresses an important gap in knowledge regarding nutritional advice for people with PCOS.Trial registrationClinicalTrials.gov NCT05452642. Registered 6 July 2022.

Methylation Patterns of Diabetes and Obesity Susceptibility Genes in Gestational Diabetes Mellitus: A Cross-Sectional Analysis from Karachi, Pakistan.

Background: Women with gestational diabetes mellitus (GDM) and their offspring have an increased risk of adverse perinatal and long-term health outcomes, which may be attributable to epigenetic modification of diabetes and obesity susceptibility genes. We aimed to investigate the methylation patterns of eight genes in GDM and normoglycemic (NG) mothers, and their respective offspring. Methods: This cross-sectional study, conducted at Aga Khan University from August 2019 to December 2022, recruited pregnant women in the first trimester of gestation from the outpatient obstetrics clinic. Participants were classified as NG or GDM based on the Society of Obstetricians and Gynecologists Pakistan. Venous blood samples were collected from mothers and cord blood from neonates. Peripheral blood mononuclear cells were used for DNA extraction and methylation analysis using methylation-specific PCR. Maternal and neonatal clinical data were recorded. Statistical analysis was performed using R, including binary logistic regression to assess the association between various gene methylation levels and GDM. Results: The study found that GDM mothers had significantly higher fasting blood glucose, 2-hr OGTT, and serum carboxymethyl lysine (CML) levels compared to NG mothers, but no significant differences in neonatal birth weight or serum CML levels. Chemerin methylation was significantly lower in GDM mothers and their babies, while NAMPT, MTNR1B, FNDC5, FAT4, and FTO methylation levels were higher in GDM offspring compared to NG offspring. GDM mothers also had higher methylation levels of brain-derived neurotrophic factor gene (BDNF). Multivariable binary logistic regression identified methylation levels of maternal BDNF and neonatal MTNR1B to be independently associated with GDM. Conclusions: Our study shows a trend of epigenetic modifications in both GDM mothers and their offspring in various genes related to metabolism and inflammation, suggesting an intergenerational transmission of increased risk of developing metabolic disorders. These findings emphasize the need for high throughput studies, early screening, tight glucose control during pregnancy, and postnatal follow-up to mitigate long-term health risks.

Using continuous glucose monitoring (CGM) to understand glucose control in women with obesity during pregnancy.

In women with obesity but without diabetes, the factors driving poor pregnancy outcomes are inadequately understood. This study explores glucose as a potential mediator of adverse pregnancy outcomes in women with obesity. A two-arm observational study was conducted in a single maternity hospital in Melbourne, Australia. Thirty-eight women without diabetes, 20 of normal weight (BMI 20-24.9 kg/m2) and 18 with obesity (BMI ≥30 kg/m2), wore a continuous glucose monitor and had anthropometry and blood samples collected in early, mid and late pregnancy. Subjects who developed gestational diabetes were excluded prior to analysis. Groups were compared with respect to patient-day mean glucose, mean blood glucose, daytime and nighttime glucose AUC, post-prandial glucose AUC, HOMA-IR and QUICKI. Five subjects developed gestational diabetes and were excluded from the analysis. Compared to controls (n = 19), women with obesity (n = 14) had significantly higher PDMG (p < .001), daytime and nighttime glucose AUC (p < .01) and post-breakfast glucose AUC (p < .001 and p = .043) and post-dinner glucose AUC (p < .001) in early and mid-pregnancy. Mean plasma glucose and post-lunch glucose AUC were only higher in women with obesity in early pregnancy (p = .009 and p < .001, respectively). In mid and late pregnancy, HOMA-IR was significantly higher (p < .05) and QUICKI (p < .01) significantly lower in the women with obesity compared to controls. Most parameters that used to assess glycaemic control in pregnancy demonstrated significantly higher plasma glucose in women with obesity compared to controls. This supports the hypothesis that glucose is a mediator of adverse pregnancy outcomes in women with obesity.

Remote Foot Temperature Monitoring Among Veterans: Large Observational Study of Noncompliance and Its Correlates.

In-home remote foot temperature monitoring (RTM) holds promise as a method to reduce foot ulceration in high-risk patients with diabetes. Few studies have evaluated adherence to this method or evaluated the factors associated with noncompliance. The aims of this study were to estimate noncompliance in patients who were enrolled in RTM nationwide across Department of Veterans Affairs (VA) and to evaluate characteristics associated with noncompliance. We conducted an observational study including 1137 patients in the VA who were enrolled in RTM between January 2019 and June 2021, with follow-up through October 2021. Patient information was obtained from the VA's electronic health record and RTM use was obtained from the company. Noncompliance was defined as using the mat <2 days per week for ≥4 of the 12 months of follow-up. Using a multivariable model, we calculated odds ratios (ORs) and 95% CIs for associations between various factors and noncompliance and compared using Akaike information criterion statistics, a measure of model fit. The sample was predominantly male (n=1125, 98.94%) ; 21.1% (n=230) were Black and 75.7% (n=825) were White. Overall, 37.6% (428/1137) of patients were classified as noncompliant. In the multivariable model, an intermediate area deprivation index was statistically significantly and inversely associated with noncompliance (area deprivation index 50-74 vs 1-24; OR 0.56, 95% CI 0.35-0.89); factors significantly and positively associated with noncompliance included recent history of osteomyelitis (OR 1.44, 95% CI 1.06-1.97), Gagne comorbidity index score ≥4 (vs ≤0; OR 1.81, 95% CI 1.15-2.83), telehealth encounters (28+ vs <6; OR 1.70, 95% CI 1.02-2.84), hemoglobin A1c≥10 (vs <5.7; OR 2.67, 95% CI 1.27-5.58), and current smoking (OR 2.06, 95% CI 1.32-3.20). Based on Akaike information criterion differences, the strongest factors associated with noncompliance were behavioral factors (poor glucose control [as measured by hemoglobin A1c] and smoking), and to a lesser extent, factors such as a recent history of osteomyelitis and an elevated Gagne comorbidity index, indicating a high comorbidity burden. To reduce the risk of ulcer recurrence and amputation, proactively providing additional support for self-monitoring to patients with characteristics identified in this study (poor glucose control, current smoking, high comorbidity burden) may be helpful. Furthermore, research is needed to better understand barriers to use, and whether the addition of design features, reminders, or incentives may reduce noncompliance and the risk of foot ulcers.

Comprehensive Review of Pharmacological Therapies and Clinical Guidelines for Diabetes Mellitus: A Depth Study

Diabetes mellitus (DM) is a colossal burden in global health, its prevalence increases steadily throughout the world. This systematic review explores the pathophysiology and epidemiology of diabetes, which describes the interactions that implicate that is the result of the play between genetic, environmental, and lifestyle factors in the development and progression of the disease. The review also describes a plethora of pharmacological treatments available to manage diabetes, with the oral agent, insulin regimens, and new approaches to therapy. Integrating the wisdom of the best clinical guidelines, those are from American diabetes association (ADA), European association for the study of diabetes (EASD), and International Diabetes Federation (IDF). Since these reviews are consistent with normative standards for evidence-based recommendations of optimal care of diabetes. The review goes further to cover technological advances in the management of diabetes. They include Continuous Glucose Monitoring, advanced insulin delivery systems, and Artificial Pancreas Systems. Such technologies hold more promising routes to better glucose control and patient quality of life. All this comes along with challenges that their deployment and maintenance that run through economic, adherence issues, and unequal access to healthcare. The future research and innovation in the battle against DM will include the application of personalized medicine and the development of advanced digital health solutions. This article will become a treasure for health professionals, researchers, and policymakers who have dedicated themselves to battling the adversities of diabetes mellitus.

Association between Semaglutide and Non-Arteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Real-World Study

ObjectiveTo investigate whether semaglutide increases the risk of non-arteritic anterior ischemic optic neuropathy (NAION) in the general population. DesignThis retrospective cohort study utilized a de-identified global electronic medical records database. The enrollment period was extended from January 2017 to August 2023, with observations concluding in August 2024. ParticipantsThis study included individuals with type 2 diabetes mellitus (T2DM) or obesity. They were further categorized into T2DM-only, obesity-only, and T2DM with obesity groups to assess the differences among these subgroups. The effects of semaglutide were compared with those of glucose-lowering or weight loss medications other than glucagon-like peptide receptor agonists. MethodsPatient data were obtained from 160 healthcare organizations across 21 countries. Outcomes were evaluated at one, two, and three years of follow-up. A 1:1 propensity score matching was performed to balance age, sex, body mass index, hemoglobin A1C, medications, and underlying comorbidities. Cox regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI). Main Outcome MeasuresThe occurrence of NAION. ResultsThe final analysis included 37,245 participants with T2DM-only, 33,537 participants with obesity-only, and 64,989 participants with both T2DM and obesity. The results indicated that the administration of semaglutide was not associated with the development of NAION in the T2DM-only group (1 year follow-up: HR, 2.32; 95% CI, 0.60–8.97; 2 years: HR, 2.31; 95% CI, 0.86–6.17; 3 years: HR, 1.51; 95% CI, 0.71–3.25), the obesity-only group (1 year follow-up: HR, 0.25; 95% CI, 0.03–2.28; 2 years: HR, 0.44; 95% CI, 0.09–2.21; 3 years: HR, 0.44; 95% CI, 0.09–2.21), and the T2DM with obesity group (1 year follow-up: HR, 0.81; 95% CI, 0.42–1.57; 2 years: HR, 1.2; 95% CI, 0.74–1.94; 3 years: HR, 1.19; 95% CI, 0.78–1.82). ConclusionsThe findings suggest that semaglutide may not be associated with an increased risk of NAION in the general population. Therefore, avoidance of semaglutide based solely on concerns regarding the risk of NAION may not be warranted, as its potential benefits for blood glucose control and cardiovascular health likely outweigh its potential risks.

The novel lipid emulsion Vegaven is well tolerated and elicits distinct biological actions compared with a mixed-oil lipid emulsion containing fish oil:a parenteral nutrition trial in piglets

BackgroundVegaven is a novel lipid emulsion for parenteral nutrition (PN) based on 18-carbon n-3 fatty acids, which elicits liver protection via interleukin-10 (IL10) in the murine model of PN. ObjectiveIn a preclinical model of PN in neonatal piglets, Vegaven was tested for efficacy and safety and compared with a mixed-oil lipid emulsion containing fish-oil (SMOFlipid). Methods4-5-day-old male piglets were randomly allocated to isocaloric isonitrogenous PN for 14 days that varied only by the type of lipid emulsion (Vegaven, N=8; SMOFlipid, N=8). Hepatic IL10 tissue concentration served as primary outcome. Secondary outcomes were organ weights, bile flow, blood analyses, plasma insulin and glucagon concentrations, insulin signaling, proinflammatory cytokines, tissue lipopolysaccharide concentrations, and fatty acid composition of phospholipid fractions in plasma, liver, and brain. ResultsTotal weight gain on trial, organ weights, and bile flow were similar between the Vegaven and the SMOFlipid group. Vegaven elicited higher hepatic IL10 (Δ=148 pg/mg protein, p<0.001) and insulin receptor substrate-2 levels (Δ=0.08 O.D., p=0.012). Plasma insulin concentrations (Δ=1.46 mU/L, p=0.003) and fructosamine (glycated albumin, Δ=12.4 μmol/g protein, p=0.003) were increased in SMOFlipid as compared with Vegaven group, indicating insulin resistance. Higher hepatic injury markers were observed more frequently in the SMOFlipid group compared with the Vegaven group. Lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6 were increased in pancreatic and brain tissues of SMOFlipid- vs Vegaven-treated piglets. Insulin signaling was reduced in the brains of SMOFlipid-treated piglets. Vegaven and SMOFlipid elicited distinct fatty acid profiles in the phospholipid fractions of the rapidly growing brains, but showed similar accretion of docosahexaenoic acid and arachidonic acid after two weeks of PN. ConclusionsVegaven was well tolerated in this piglet model of PN and demonstrated distinct biological actions compared with SMOFlipid, namely lower liver, pancreas, and brain inflammation, enhanced insulin signaling, and improved whole-body glucose control.