Glucose Disorders.

Glucose disorders are the most common endocrine condition in the primary care setting. The conditions overlap and are better viewed as a spectrum rather than discrete entities. Multiple treatment agents are now available for diabetes mellitus which include long-acting and short-acting insulins and medications targeting the various pathways of diabetes including liver gluconeogenesis, increasing peripheral insulin sensitivity, stimulating pancreatic insulin production, eliminating glucose renally, decreasing carbohydrate gastrointestinal absorption, and targeting the body's incretin system. Various endocrine conditions can cause secondary hyperglycemia or hypoglycemia. Medications and physiologic stress can affect glucose levels. Genetic syndromes causing enzyme deficiencies underlie a small portion of glucose disorders.

Insulin-Mimetic Activity of Herbal Extracts Identified with Large-Scale Total Internal Reflection Fluorescence Microscopy.

Diabetes mellitus is a spreading global pandemic. Type 2 diabetes mellitus (T2DM) is the predominant form of diabetes, in which a reduction in blood glucose uptake is caused by impaired glucose transporter 4 (GLUT4) translocation to the plasma membrane in adipose and muscle cells. Antihyperglycemic drugs play a pivotal role in ameliorating diabetes symptoms but often are associated with side effects. Hence, novel antidiabetic compounds and nutraceutical candidates are urgently needed. Phytogenic therapy can support the prevention and amelioration of impaired glucose homeostasis. Using total internal reflection fluorescence microscopy (TIRFM), 772 plant extracts of an open-access plant extract library were screened for their GLUT4 translocation activation potential, resulting in 9% positive hits. Based on commercial interest and TIRFM assay-based GLUT4 translocation activation, some of these extracts were selected, and their blood glucose-reducing effects in ovo were investigated using a modified hen's egg test (Gluc-HET). To identify the active plant part, some of the available candidate plants were prepared in-house from blossoms, leaves, stems, or roots and tested. Acacia catechu (catechu), Pulmonaria officinalis (lungwort), Mentha spicata (spearmint), and Saponaria officinalis (common soapwort) revealed their potentials as antidiabetic nutraceuticals, with common soapwort containing GLUT4 translocation-activating saponarin.

Phytochemicals-linked food safety and human health protective benefits of the selected food-based botanicals.

Phytochemicals-rich food-based botanicals including traditional or under-utilized plant-based ingredients can serve a dual functional role to help counter food contamination of bacterial origin, while also addressing the rise of diet-linked non-communicable chronic diseases (NCDs) such as type 2 diabetes, chronic hypertension and the associated oxidative stress. Hence the screening of these food-based botanicals for their phenolic content and profile, as well as antimicrobial, antioxidant, anti-hyperglycemic and anti-hypertensive properties has relevant merit. Using in vitro assay models, hot water extracts of different forms (slice, pickle, or powder) of amla (Phyllanthus emblica), clove (Syzygium aromaticum), kokum (Garcinia indica), and garlic (Allium sativum) were analyzed for their total soluble phenolic content (TSP) and phenolic profile as well as antimicrobial activity against strains of Salmonella Enteritidis, Listeria monocytogenes, and Escherichia coli that are associated with food-borne disease outbreaks. In addition, the antioxidant, anti-hyperglycemic and anti-hypertensive activity of the extracts were also determined using in vitro assay models, with the goal of establishing a dual functional role of the food safety and health protective benefits of these botanicals. A high baseline TSP content was observed in all the extracts and the major phenolic phytochemicals detected were gallic, cinnamic, ellagic, benzoic, dihydroxybenzoic, protocatechuic, and p-coumaric acid along with catechin and rutin. All extracts displayed significant antimicrobial activity against most of the bacterial strains tested and the antimicrobial activity was specific for each strain targeted in this study. Furthermore, significant antioxidant, anti-hyperglycemic and antihypertensive activity were observed among the botanical extracts, especially among the amla and kokum extracts. These results indicate that phytochemicals enriched botanicals, including amla and kokum, can be integrated into modern-day food preservation and dietary support strategies aimed at improving the food safety and health protective benefits of the food matrix.

Enhancing care in the initiation and management of insulin in older people with diabetes: A collaborative journey with older individuals and their caregivers using Experience-Based Co-Design.

INTRODUCTION: Initiating insulin therapy in older individuals with type 2 diabetes (T2DM) poses unique challenges and requires a nuanced understanding of the age-related factors that impact safety and efficacy. This study employed Experience-Based Co-Design (EBCD) to enhance the insulin initiation and management experience for this population, emphasising a collaborative approach involving patients, caregivers, and healthcare professionals. AIM: The primary aim of the research was to develop a tailored care pathway, utilising co-design and the Behaviour Change Wheel (BCW), which addressed issues specific to older adults on insulin therapy. The study sought to identify key challenges, propose practical interventions, and construct a logic model illustrating a pathway for enhanced insulin treatment experiences. METHODS: An adapted EBCD process was used which integrated the Medical Research Council (MRC) Framework and BCW. The study involved thematic synthesis, video interviews, and feedback focus groups with patients, caregivers, and healthcare professionals. The 'Crazy Eights' brainstorming method, as part of the co-design workshop, generated practical solutions which informed subsequent logic model development. RESULTS: Focus group findings revealed distressing insulin initiation experiences, inconsistent dietary advice, and perceived disparities in care between type 1 and type 2 diabetes. The co-design workshop identified eight key challenges, leading to proposed interventions aligned with the BCW. The logic model illustrates a pathway for older individuals undergoing insulin treatment, emphasising behaviour change among patients, caregivers, and healthcare professionals. CONCLUSION: The collaborative efforts of participants contributed valuable insights in terms of the unique educational and emotional needs of patients, the importance of care continuity and of improving access to specialist services. Findings from this study can be used to inform and enhance tailored support strategies for older adults with T2DM during their insulin transition and ongoing management.

Effects of Metformin on CIMT and FMD in PCOS patients: a systematic review and meta-analysis.

BACKGROUND: This study aims to analyze the efficacy of metformin on carotid intima media thickness (CIMT) and flow-mediated dilation (FMD) for patients with polycystic ovary syndrome (PCOS). METHODS: A literature search of PubMed, Embase, and the Cochrane Library from inception to December 2023 was conducted. Then, after studies selection and data extraction, the mean difference (MD) with a 95% confidence interval (CI) was used to evaluate metformin efficacy in CIMT and FMD for PCOS patients. Heterogeneity was investigated through subgroup and sensitivity analysis. The protocol of our study has been registered in PROSPERO (CRD42024497239). RESULTS: A total of 12 studies with 248 patients were included. CIMT was lower in the endpoint group (after metformin) compared with the baseline group (before metformin) (MD = -0.11, 95% CI = -0.21 to -0.01, p = 0.04). FMD was higher in the endpoint group compared with the baseline group (MD = 3.25, 95% CI = 1.85 to 4.66, p < 0.01). No statistically significant difference was observed in nitroglycerin-mediated dilation (NMD) between the two groups (MD = 0.65, p = 0.51). Subgroup analysis showed that a relatively lower MD of CIMT in PCOS patients from Europe in the endpoint group compared with the baseline group (MD = -0.09, 95% CI = -0.14 to -0.04, p < 0.001). However, the MD in CIMT was not significantly different between the endpoint group and baseline group in PCOS patients from Asia (p = 0.270). CONCLUSION: Metformin may have a beneficial effect on CIMT and FMD, but not on NMD, suggesting that metformin may help reduce cardiovascular events in PCOS patients. Notably, the clinical efficacy of metformin can be influenced by regional differences and study types.

Antioxidant, Anti-Inflammatory, Anti-Diabetic, and Pro-Osteogenic Activities of Polyphenols for the Treatment of Two Different Chronic Diseases: Type 2 Diabetes Mellitus and Osteoporosis.

Polyphenols are natural bioactives occurring in medicinal and aromatic plants and food and beverages of plant origin. Compared with conventional therapies, plant-derived phytochemicals are more affordable and accessible and have no toxic side effects. Thus, pharmaceutical research is increasingly inclined to discover and study new and innovative natural molecules for the treatment of several chronic human diseases, like type 2 diabetes mellitus (T2DM) and osteoporosis. These pathological conditions are characterized by a chronic inflammatory state and persistent oxidative stress, which are interconnected and lead to the development and worsening of these two health disorders. Oral nano delivery strategies have been used to improve the bioavailability of polyphenols and to allow these natural molecules to exert their antioxidant, anti-inflammatory, anti-diabetic, and pro-osteogenic biological activities in in vivo experimental models and in patients. Polyphenols are commonly used in the formulations of nutraceuticals, which can counteract the detrimental effects of T2DM and osteoporosis pathologies. This review describes the polyphenols that can exert protective effects against T2DM and osteoporosis through the modulation of specific molecular markers and pathways. These bioactives could be used as adjuvants, in combination with synthetic drugs, in the future to develop innovative therapeutic strategies for the treatment of T2DM and osteoporosis.

A Review of Experimental Studies on Natural Chalcone-Based Therapeutic Targeting of Genes and Signaling Pathways in Type 2 Diabetes Complications.

Diabetes mellitus type 2 (T2DM) is a common chronic condition that presents as unsettled hyperglycemia (HG) and results from insulin resistance (IR) and ß-cell dysfunction. T2DM is marked by an increased risk of microvascular and macrovascular complications, all of which can be the cause of increasing mortality. Diabetic nephropathy (DNE), neuropathy (DNU), and retinopathy (DR) are the most common complications of diabetic microangiopathy, while diabetic cardiomyopathy (DCM) and peripheral vascular diseases are the major diabetic macroangiopathy complications. Chalcones (CHs) are in the flavonoid family and are commonly found in certain plant species as intermediate metabolites in the biosynthesis of flavonoids and their derivatives. Natural CHs with different substituents exert diverse therapeutic activities, including antidiabetic ones. However, the therapeutic mechanisms of natural CHs through influencing genes and/or signaling pathways in T2DM complications remain unknown. Therefore, this review summarizes the existing results from experimental models which highlight the mechanisms of natural CHs as therapeutic agents for T2DM complications.

Baltic herring hydrolysates: Identification of peptides, in silico DPP-4 prediction, and their effects on an in vivo mice model of obesity.

Baltic herring is the main catch in the Baltic Sea; however, its usage could be improved due to the low processing rate. Previously we have shown that whole Baltic herring hydrolysates (BHH) and herring byproducts hydrolysates (BHBH) by commercial enzymes consisted of bioactive peptides and had moderate bioactivity in in vitro dipeptidyl peptidase (DPP)-4 assay. In this study, we identified the hydrolysate peptides by LC-MS/MS and predicted the potential bioactive DPP-4 inhibitory peptides using in silico tools. Based on abundance, peptide length and stability, 86 peptides from BHBH and 80 peptides from BHH were proposed to be novel DPP-4 inhibitory peptides. BHH was fed to a mice intervention of a high-fat, high-fructose diet to validate the bioactivity. The results of the glucose tolerance and insulin tolerance improved. Plasma DPP-4 activities, C-peptide levels, and HOMA-IR scores significantly decreased, while plasma glucagon-like peptide-1 content increased. In conclusion, BHH is an inexpensive and sustainable source of functional antidiabetic ingredients.

Metformin Restrains the Proliferation of CD4+ T Lymphocytes by Inducing Cell Cycle Arrest in Normo- and Hyperglycemic Conditions.

CD4+ T lymphocytes play a key role in the modulation of the immune response by orchestrating both effector and regulatory functions. The effect of metformin on the immunometabolism of CD4+ T lymphocytes has been scarcely studied, and its impact under high glucose conditions, particularly concerning effector responses and glucose metabolism, remains unknown. This study aims to evaluate the effect of metformin on the modulation of the effector functions and glucose metabolism of CD4+ T lymphocytes under normo- and hyperglycemic conditions. CD4+ T lymphocytes, obtained from peripheral blood from healthy volunteers, were anti-CD3/CD28-activated and cultured for 4 days with three concentrations of metformin (0.1 mM, 1 mM, and 5 mM) under normoglycemic (5.5 mM) and hyperglycemic (25 mM) conditions. Effector functions such as proliferation, cell count, cell cycle analysis, activation markers and cytokine secretion were analyzed by flow cytometry. Glucose uptake was determined using the 2-NBDG assay, and levels of glucose, lactate, and phosphofructokinase (PFK) activity were assessed by colorimetric assays. Metformin at 5 mM restrained the cell counts and proliferation of CD4+ T lymphocytes by arresting the cell cycle in the S/G2 phase at the beginning of the cell culture, without affecting cell activation, cytokine production, and glucose metabolism. In fact, CD69 expression and IL4 secretion by CD4+ T lymphocytes was higher in the presence of 5 mM than the untreated cells in both glucose conditions. Overall, metformin inhibited proliferation through mechanisms associated with cell cycle arrest, leading to an increase in the S/G2 phases at the expense of G1 in activated CD4+ T lymphocytes in normo- and hyperglycemic conditions. Despite the cell cycle arrest, activated CD4+ T lymphocytes remained metabolically, functionally, and phenotypically activated.

Methodology of clinical trials on sodium-glucose cotransporter 2 inhibitors registered on ClinicalTrials.gov: a cross-sectional study.

BACKGROUND/OBJECTIVE: The research on sodium-glucose cotransporter 2 (SGLT2) inhibitors has been increasing rapidly in the last decade, as well as indications for their use. This study aimed to analyze the methodological characteristics of clinical trials on SGLT2 inhibitors registered on ClinicalTrials.gov. DESIGN: We conducted a cross-sectional study of trials on SGLT2 inhibitors registered on ClinicalTrials.gov up to November 11, 2022. We included clinical trials that tested SGLT2 inhibitors for any clinical condition, as a single or combined SGLT2 therapy, compared to any other medication or placebo and mapped their characteristics. RESULTS: We identified 1102 eligible trials on 14 different SGLT2 inhibitors. The first trial registration was in 2005. There were 993 (90%) interventional and 109 (10%) observational trials. Most trials were in Phase 1 (29%), Phase 3 (23%), or Phase 4 (24%). Interventional trials were mostly randomized (85%); almost half of them did not use masking (44%). Trials on empagliflozin, dapagliflozin, and canagliflozin accounted for 75% of all trials. More than 60% of trials included patients with diabetes mellitus, 13% included only healthy subjects, and 12% included patients with heart diseases. Overall, these trials included more than 9.5 million participants (~ 312,000 of which in interventional studies). Almost 65% of all clinical trials were industry-funded. Most trials were completed (60%) and 35% of those reported results. For trials that are obligated to report results by the Food and Drugs Administration (FDA), 88% of them did so. Trials fully or partially funded by industry more frequently published results compared to non-industry funded trials (46.1% vs. 11.2%; p < 0.001). CONCLUSIONS: The number of registered trials on SGLT2 inhibitors is increasing progressively along with expanding indications for its use, shifting from diabetes mellitus to cardiovascular and renal diseases. Public reporting of trial results improved with time but remains suboptimal.

Mortality and cardiovascular events in diabetes mellitus patients at dialysis initiation treated with glucagon-like peptide-1 receptor agonists.

BACKGROUND: Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) have demonstrated efficacy in improving mortality and cardiovascular (CV) outcomes. However, the impact of GLP-1RAs therapy on cardiorenal outcomes of diabetic patients at the commencement of dialysis remains unexplored. PURPOSE: This study aimed to investigate the long-term benefits of GLP-1RAs in type 2 diabetic patients at dialysis commencement. METHODS: A cohort of type 2 diabetic patients initializing dialysis was identified from the TriNetX global database. Patients treated with GLP-1RAs and those treated with long-acting insulin (LAI) were matched by propensity score. We focused on all-cause mortality, four-point major adverse cardiovascular events (4p-MACE), and major adverse kidney events (MAKE). RESULTS: Among 82,041 type 2 diabetic patients initializing dialysis, 2.1% (n = 1685) patients were GLP-1RAs users (mean ages 59.3 years; 55.4% male). 1682 patients were included in the propensity-matched group, treated either with GLP-1RAs or LAI. The main causes of acute dialysis in this study were ischemic heart disease (17.2%), followed by heart failure (13.6%) and sepsis (6.5%). Following a median follow-up of 1.4 years, GLP-1RAs uses at dialysis commencement was associated with a reduced risk of mortality (hazard ratio [HR] = 0.63, p < 0.001), 4p-MACE (HR = 0.65, p < 0.001), and MAKE (HR = 0.75, p < 0.001). This association was particularly notable in long-acting GLP-1RAs users, with higher BMI, lower HbA1c, and those with eGFR > 15 ml/min/1.73m2. GLP-1RAs' new use at dialysis commencement was significantly associated with a lower risk of MACE (p = 0.047) and MAKE (p = 0.004). Additionally, GLP-1RAs use among those who could discontinue from acute dialysis or long-term RAs users was associated with a lower risk of mortality, 4p-MACE, and MAKE. CONCLUSION: Given to the limitations of this observational study, use of GLP-1RAs at the onset of dialysis was associated with a decreased risk of MACE, MAKE, and all-cause mortality. These findings show the lack of harm associated with the use of GLP-1RAs in diabetic patients at the initiation of acute dialysis.

Impact of Different Anti-Hyperglycaemic Treatments on Bone Turnover Markers and Bone Mineral Density in Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-Analysis.

Diabetic bone disease (DBD) is a frequent complication in patients with type 2 diabetes mellitus (T2DM), characterised by altered bone mineral density (BMD) and bone turnover marker (BTMs) levels. The impact of different anti-diabetic medications on the skeleton remains unclear, and studies have reported conflicting results; thus, the need for a comprehensive systematic review is of paramount importance. A systematic search was conducted in PubMed and the Cochrane Library. The primary outcomes assessed were changes in BMD in relation to different anatomical sites and BTMs, including mainly P1NP and CTX as well as OPG, OCN, B-ALP and RANK-L. Risk of bias was evaluated using the JADAD score. The meta-analysis of 19 randomised controlled trials comprising 4914 patients showed that anti-diabetic medications overall increased BMD at the lumbar spine (SMD: 0.93, 95% CI [0.13, 1.73], p = 0.02), femoral neck (SMD: 1.10, 95% CI [0.47, 1.74], p = 0.0007) and in total hip (SMD: 0.33, 95% CI [-0.25, 0.92], p = 0.27) in comparison with placebo, but when compared with metformin, the overall effect favoured metformin over other treatments (SMD: -0.23, 95% CI [-0.39, -0.07], p = 0.004). GLP-1 receptor agonists and insulin analogues seem to improve BMD compared to placebo, while SGLT2 inhibitors and thiazolidinediones (TZDs) showed no significant effect, although studies' number cannot lead to safe conclusions. For BTMs, TZDs significantly increased P1NP levels compared to placebo. However, no significant differences were observed for CTX, B-ALP, OCN, OPG, and RANK-L between anti-diabetic drugs and metformin or placebo. High heterogeneity and diverse follow-up durations among studies were evident, which obscures the validity of the results. This review highlights the variable effects of anti-diabetic drugs on DBD in T2DM patients, emphasising the need for long-term trials with robust designs to better understand these relationships and inform clinical decisions.

Assessing Carbohydrate Counting Accuracy: Current Limitations and Future Directions.

Diabetes mellitus is a prevalent chronic autoimmune disease with a high impact on global health, affecting millions of adults and resulting in significant morbidity and mortality. Achieving optimal blood glucose levels is crucial for diabetes management to prevent acute and long-term complications. Carbohydrate counting (CC) is widely used by patients with type 1 diabetes to adjust prandial insulin bolus doses based on estimated carbohydrate content, contributing to better glycemic control and improved quality of life. However, accurately estimating the carbohydrate content of meals remains challenging for patients, leading to errors in bolus insulin dosing. This review explores the current limitations and challenges in CC accuracy and emphasizes the importance of personalized educational programs to enhance patients' abilities in carbohydrate estimation. Existing tools for assessing patient learning outcomes in CC are discussed, highlighting the need for individualized approaches tailored to each patient's needs. A comprehensive review of the relevant literature was conducted to identify educational programs and assessment tools dedicated to training diabetes patients on carbohydrate counting. The research aims to provide insights into the benefits and limitations of existing tools and identifies future research directions to advance personalized CC training approaches. By adopting a personalized approach to CC education and assessment, healthcare professionals can empower patients to achieve better glycemic control and improve diabetes management. Moreover, this review identifies potential avenues for future research, paving the way for advancements in personalized CC training and assessment approaches and further enhancing diabetes management strategies.

Real-World Use of Hybrid Closed-Loop Systems during Diabetes Camp: A Preliminary Study for Secure Configuration Strategies in Children and Adolescents.

The introduction of closed-loop systems in the pediatric population has been a revolution in the management and evolution of diabetes. However, there are not many published studies in situations in which the feeding, schedules, and activities of the children deviate from the routine for which the systems were programmed, as in the case of a summer camp for children and adolescents with diabetes, where the specific programming of this device is not well known. It was a single-center prospective preliminary study. A total of twenty-seven patients (mean age 11.9 ± 1.9 years, 40% male, duration of diabetes 6.44 ± 2.83 years) were included (twenty with Medtronic MiniMed 780G system and seven with Tandem Control-IQ). Glucometric variables and pump functionality were monitored during the 7-day camp and in the following 3 weeks. There was no decrease from the objective TIR 70% at any moment. The worst results in Time Below Range were at 72 h from starting the camp, and the worst results in Time Above Range were in the first 24 h, with a progressive improvement after that. No episodes of level 3 hypoglycemia or ketoacidosis occurred. The use of specific programming in two integrated systems, with complex blood glucose regulation algorithms and not-prepared-for situations with increased levels of physical activity or abrupt changes in feeding routines, did not result in an increased risk of level 3 hypoglycemia and ketoacidosis for our pediatric type 1 diabetes (T1D) patients, regardless of the closed-loop device.

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a hepatic manifestation of the metabolic syndrome. It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries. MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma. Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis. The mechanisms involved in maintaining gut-liver axis homeostasis are complex. One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gut-liver axis functionality. An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis. Moreover, alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of drugs developed for the treatment of type 2 diabetes mellitus. They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis. The mechanisms reported to be involved in this effect include an improved regulation of glycemia, reduced lipid synthesis, ß-oxidation of free fatty acids, and induction of autophagy in hepatic cells. Recently, multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment. A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD. This review presents the current understanding of the role of the gut-liver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.

Trends in antidiabetes medication use among hospitalised patients with type 2 diabetes: a retrospective single-centre cohort study.

OBJECTIVES: Novel antidiabetes medications with proven cardiovascular or renal benefit, such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA), have been introduced to the market. This study explored the 4-year trends of antidiabetes medication use among medical hospitalisations with type 2 diabetes (T2D). DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital in Switzerland. PARTICIPANTS: 4695 adult hospitalisations with T2D and prevalent or incident use of one of the following antidiabetes medications (metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), sulfonylureas, GLP-1 RA, SGLT-2i, short-acting insulin or long-acting insulin), identified using electronic health record data. Quarterly trends in use of antidiabetes medications were plotted overall and stratified by cardiovascular disease (CVD) and chronic kidney disease (CKD). RESULTS: We observed a stable trend in the proportion of hospitalisations with T2D who received any antidiabetes medication (from 77.6% during 2019 to 78% in 2022; p for trend=0.97). In prevalent users, the largest increase in use was found for SGLT-2i (from 7.4% in 2019 to 21.8% in 2022; p for trend <0.01), the strongest decrease was observed for sulfonylureas (from 11.4% in 2019 to 7.2% in 2022; p for trend <0.01). Among incident users, SGLT-2i were the most frequently newly prescribed antidiabetes medication with an increase from 26% in 2019 to 56.1% in 2022 (p for trend <0.01). Between hospital admission and discharge, SGLT-2i also accounted for the largest increase in prescriptions (+5.1%; p<0.01). CONCLUSIONS: These real-world data from 2019 to 2022 demonstrate a significant shift in antidiabetes medications within the in-hospital setting, with decreased use of sulfonylureas and increased prescriptions of SGLT-2i, especially in hospitalisations with CVD or CKD. This trend aligns with international guidelines and indicates swift adaptation by healthcare providers, signalling a move towards more effective diabetes management.

[Expert consensus on stroke prevention and blood glucose management in patients with type 2 diabetes].

Abnormal glucose metabolism is closely related to stroke and has adverse effects on the occurrence, development, and prognosis of stroke. Ideal glycemic control is of great significance in improving the prognosis of stroke. Some hypoglycemic drugs can reduce the risk of stroke occurrence and recurrence in patients with type 2 diabetes. Furthermore, such patients with stroke should strengthen their blood pressure and blood lipid control and use antiplatelet drugs reasonably. The expert consensus group finally established this consensus after discussions pertaining to evidence-based medicine and clinical practice, with the aim to provide a reference for clinical practice.

Nonpharmacological interventions on glycated haemoglobin in youth with type 1 diabetes: a Bayesian network meta-analysis.

The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine which interventions could provide the most significant benefits for the metabolic health of young individuals with type 1 diabetes mellitus. The aim of this study was to identify optimal nonpharmacological interventions on glycaemic control, measured by glycated haemoglobin (HbA1c), in children and adolescents with type 1 diabetes. Systematic searches were conducted in PubMed, Web of Science, Scopus, and SPORTDiscus from inception to July 1, 2023. Randomised clinical trials (RCT) investigating nonpharmacological interventions (e.g., physical activity, nutrition, and behavioural therapies) were included. Primary outcome was change in HbA1c levels. Secondary outcome was change in daily insulin dose requirement. Seventy-four RCT with 6,815 participants (49.43% girls) involving 20 interventions were analysed using a network meta-analysis. Most interventions showed greater efficacy than standard care. However, multicomponent exercise, which includes aerobic and strength training (n = 214, standardised mean difference [SMD] =- 0.63, 95% credible interval [95% CrI] - 1.09 to - 0.16) and nutritional supplements (n = 146, SMD =- 0.49, - 0 .92 to - 0.07) demonstrated the greatest HbA1c reductions. These interventions also led to the larger decreases in daily insulin needs (n = 119, SMD =- 0.79, 95% CrI -  1.19 to - 0.34) and (n = 57, SMD =- 0.62, 95% CrI -  1.18 to - 0.12, respectively). The current study underscores non-pharmacological options such as multicomponent exercise and nutritional supplements, showcasing their potential to significantly improve HbA1c in youth with type 1 diabetes. Although additional research to confirm their efficacy is required, these approaches could be considered as potential adjuvant therapeutic options in the management of type 1 diabetes among children and adolescents.

Clinical Pharmacokinetics of Semaglutide: A Systematic Review.

Purpose: The aim of this review was to provide all the pharmacokinetic data for semaglutide in humans concerning its pharmacokinetics after subcutaneously and oral applications in healthy and diseased populations, to provide recommendations for clinical use. Methodology: The PubMed and Embase databases were searched to screen studies associated with the pharmacokinetics of semaglutide. The pharmacokinetic parameters included area under the curve plasma concentrations (AUC), maximal plasma concentration (Cmax), time to Cmax, half-life (t1/2), and clearance. The systematic literature search retrieved 17 articles including data on pharmacokinetic profiles after subcutaneously and oral applications of semaglutide, and at least one of the above pharmacokinetic parameter was reported in all included studies. Results: Semaglutide has a predictable pharmacokinetic profile with a long t1/2 that allows for once-weekly subcutaneous administration. The AUC and Cmax of both oral and subcutaneous semaglutide increased with dose. Food and various dosing conditions including water volume and dosing schedules can affect the oral semaglutide exposure. There are limited drug-drug interactions and no dosing adjustments in patients with upper gastrointestinal disease, renal impairment or hepatic impairment. Body weight may affect semaglutide exposure, but further studies are needed to confirm this. Conclusion: This review encompasses all the pharmacokinetic data for subcutaneous and oral semaglutide in both healthy and diseased participants. The existing pharmacokinetic data can assist in developing and evaluating pharmacokinetic models of semaglutide and will help clinicians predict semaglutide dosages. In addition, it can also help optimize future clinical trials.