Suppression of the postprandial hyperglycemia in patients with type 2 diabetes by a raw medicinal herb powder is weakened when consumed in ordinary hard gelatin capsules: A randomized crossover clinical trial.

INTRODUCTION: Contradictory claims about the efficacy of several medicinal plants to promote glycemic control in patients with type 2 diabetes mellitus (T2DM) have been explained by divergences in the administration form and by extrapolation of data obtained from healthy individuals. It is not known whether the antidiabetic effects of traditional herbal medicines are influenced by gelatin capsules. This randomized crossover trial aimed to evaluate the acute effect of a single dose of raw cinnamon consumed orally either dissolved in water as a beverage or as ordinary hard gelatin capsules on postprandial hyperglycemia (>140 mg/dL; >7.8 mmol/L) in T2DM patients elicited by a nutritionally-balanced meal providing 50 g of complex carbohydrates. METHODS: Fasting T2DM patients (n = 19) randomly ingested a standardized meal in five experimental sessions, one alone (Control) and the other after prior intake of 3 or 6 g of crude cinnamon in the form of hard gelatin capsules or powder dissolved in water. Blood glucose was measured at fasting and at 0.25, 0.5, 0.75, 1, 1.5 and 2 hours postprandially. After each breakfast, its palatability scores for visual appeal, smell and pleasantness of taste were assessed, as well as the taste intensity sweetness, saltiness, bitterness, sourness and creaminess. RESULTS: The intake of raw cinnamon dissolved in water, independently of the dose, decreased the meal-induced large glucose spike (peak-rise of +87 mg/dL and Δ1-hour glycemia of +79 mg/dL) and the hyperglycemic blood glucose peak. When cinnamon was taken as capsules, these anti-hyperglycemic effects were lost or significantly diminished. Raw cinnamon intake did not change time-to-peak or the 2-h post-meal glycaemia, but flattened the glycemic curve (lower iAUC) without changing the shape that is typical of T2DM patients. CONCLUSIONS: This cinnamon's antihyperglycemic action confirms its acarbose-like property to inhibit the activities of the carbohydrate-digesting enzymes α-amylases/α-glucosidases, which is in accordance with its exceptionally high content of raw insoluble fiber. The efficacy of using raw cinnamon as a diabetes treatment strategy seems to require its intake at a specific time before/concomitantly the main hyperglycemic daily meals. Trial registration: Registro Brasileiro de Ensaios Clínicos (ReBEC), number RBR-98tx28b.

Cardioprotection of Canagliflozin, Dapagliflozin, and Empagliflozin: Lessons from preclinical studies.

Clinical and preclinical studies have elucidated the favorable effects of Inhibitors of Sodium-Glucose Cotransporter-2 (iSGLT2) in patients and animal models with type 2 diabetes. Notably, these inhibitors have shown significant benefits in reducing hospitalizations and mortality among patients with heart failure. However, despite their incorporation into clinical practice for indications beyond diabetes, the decision-making process regarding their use often lacks a systematic approach. The selection of iSGLT2 remains arbitrary, with only a limited number of studies simultaneously exploring the different classes of them. Currently, no unique guideline establishes their application in both clinical and basic research. This review delves into the prevalent use of iSGLT2 in animal models previously subjected to induced cardiac stress. We have compiled key findings related to cardioprotection across various animal models, encompassing diverse dosages and routes of administration. Beyond their established role in diabetes management, iSGLT2 has demonstrated utility as agents for safeguarding heart health and cardioprotection can be class-dependent among the iSGLT2. These findings may serve as valuable references for other researchers. Preclinical studies play a pivotal role in ensuring the safety of novel compounds or treatments for potential human use. By assessing side effects, toxicity, and optimal dosages, these studies offer a robust foundation for informed decisions, identifying interventions with the highest likelihood of success and minimal risk to patients. The insights gleaned from preclinical studies, which play a crucial role in highlighting areas of knowledge deficiency, can guide the exploration of novel mechanisms and strategies involving iSGLT2.

Giving a voice to "the silent killer": a knowledge, attitude and practice study of diabetes among French Guiana's Parikweneh people.

BACKGROUND: The prevalence of type 2 diabetes (T2D) in the French overseas department of French Guiana, South America, nearly doubles that in its European counterpart, Metropolitan France. This region is demographically diverse and includes several populations of Indigenous Peoples. Although such populations are at particular risk of developing T2D across the Americas, very little is known about their health status in French Guiana, and accurate numbers of diabetic patients do not exist. METHODS: In light of a potential public health crisis, an ethnomedicinal study of diabetes experienced by Indigenous Parikweneh was conducted to provide better insight into the knowledge, attitudes and practices (KAP) related to this quickly emerging disease in French Guiana. Altogether, 75 interviews were conducted with community members and Elders, as well as healthcare professionals and administrators providing services to the Parikweneh population of Macouria and Saint-Georges de l'Oyapock. RESULTS: Interviews suggest a high incidence of T2D in this population, with cases that have risen quickly since the mid-twentieth century. Parikweneh participants linked the development of the illness to dietary changes, notably through the introduction of new and sweet foods. Recognizing the complexity of diabetes and its symptoms, diabetic patients highlighted the importance of biomedical treatments and follow-ups, though they frequently alternated or used them concomitantly with Parikweneh medicines. With the help of biomedical tools (i.e. glucometer), local medicinal practices mirrored biomedical approaches through dietary adaptation and the use of medicinal animals and plants for glycaemic control and the treatment of complications from the disease. CONCLUSION: Parikweneh are appropriating T2D into their knowledge system and adapting their health system in response to this relatively new health concern. A greater understanding of local practices and perceptions relating to T2D among medical staff may therefore be beneficial for meeting patients' needs, providing greater autonomy in their health path, and improving treatment outcomes.

TNFα and IL-8 vitreous concentrations variations with two antidiabetic therapies in patients with proliferative diabetic retinopathy: an observational study.

BACKGROUND: Antidiabetic therapies are effective, but could indirectly modify the inflammatory response in the ocular microenvironment; therefore, a study was developed to evaluate the inflammatory cytokine profile in the vitreous humor of diabetic patients with retinopathy under treatment with antidiabetic drugs. METHODS: Observational, comparative, retrospective, cross-sectional study. Interleukins 1ß, 6, 8, 10, and tumor necrosis factor-alpha (TNFα) were evaluated in the vitreous humor obtained from patients with type 2 diabetes mellitus, proliferative diabetic retinopathy, and concomitant retinal detachment or vitreous hemorrhage, and who were already on antidiabetic treatment with insulin or metformin + glibenclamide. The quantification analysis of each cytokine was performed by the cytometric bead array (CBA) technique; medians and interquartile ranges were obtained, and the results were compared between groups using the Mann-Whitney U test, where a p-value < 0.05 was considered significant. RESULTS: Thirty-eight samples; quantification of TNFα concentrations was higher in the group of patients administered insulin, while interleukin-8 was lower; in the metformin + glibenclamide combination therapy group, it occurred inversely. In the stratified analysis, the highest concentrations of interleukin-8 and TNFα occurred in patients with vitreous hemorrhage; however, the only statistical difference existed in patients with retinal detachment, whose TNFα concentration in the combined therapy group was the lowest value found (53.50 (33.03-86.66), p = 0.03). Interleukins 1ß, 6, and 10 were not detected. CONCLUSION: Interleukin-8 and TNFα concentrations are opposite between treatment groups; this change is more accentuated in patients with proliferative diabetic retinopathy and vitreous hemorrhage, where the highest concentrations of both cytokines are found, although only TNFα have statistical difference.

[Access to medicines for the treatment of systemic arterial hypertension and type 2 diabetes mellitus in the Brazilian population: data from the 2019 Brazilian National Health Survey]. / Acesso a medicamentos para o tratamento de hipertensão arterial sistêmica e diabetes mellitus tipo 2 na população brasileira: dados da Pesquisa Nacional de Saúde de 2019.

This study aimed to measure access to medicines for the treatment of systemic arterial hypertension and type 2 diabetes mellitus in Brazil according to the mode of acquisition, as well as to analyze the factors associated with this access, based on data from the 2019 Brazilian National Survey of Health (PNS, acronym in Portuguese). Socioeconomic data and data related to the use of medicines by people aged 15 and over were analyzed in relation to access via the Brazilian Popular Pharmacy Program (PFPB, acronym in Portuguese) and via public services. The majority of Brazilians who took part in the PNS reported using medication to control hypertension in the previous 15 days (91.5%) and using oral medication for diabetes (95.2%) and/or insulin (70%). Most participants obtained oral medication for hypertension and type 2 diabetes mellitus via PFPB (45.2% and 53.6%, respectively), and the factors that most negatively influenced this access were older age, lower income, lower schooling, very poor self-rated health and not having private health insurance. Access to insulin, on the other hand, was most often via the public health service (69.7%), and the factors that most negatively influenced this access were black/mixed-race skin color, lower income, very poor self-rated health and not having private health insurance. Generally, the importance of the PFPB as a policy to increase access to essential medicines in Brazil was highlighted, considering the free supply of antihypertensive and antidiabetic drugs.

Este estudo objetivou mensurar o acesso aos medicamentos para o tratamento da hipertensão arterial sistêmica e diabetes mellitus tipo 2 no Brasil segundo a via de obtenção, bem como analisar os fatores associados a esse acesso, de acordo com os dados da Pesquisa Nacional de Saúde (PNS) de 2019. Foram analisados dados socioeconômicos e relacionados ao uso de medicamentos de pessoas de 15 anos ou mais, em relação ao acesso via Programa Farmácia Popular do Brasil (PFPB) e via serviço público. A maior parte dos brasileiros que participaram da PNS referiu fazer uso do medicamento para controle da hipertensão, nos últimos 15 dias (91,5%), assim como a maior parte referiu fazer uso de medicamento oral para diabetes (95,2%) e/ou uso da insulina (70%).Os medicamentos orais para hipertensão arterial sistêmica e diabetes mellitus tipo 2 foram obtidos majoritariamente via PFPB, sendo respectivamente (45,2% e 53,6%), e os fatores que mais influenciaram negativamente esse acesso foram maior faixa etária, menor renda, menor escolaridade, não ter plano de saúde e referir uma autoavaliação de saúde muito ruim. O acesso à insulina, por sua vez, se deu com maior frequência via serviço público de saúde (69,7%), e os fatores que mais influenciaram negativamente esse acesso foram raça preta/parda, menor renda, não ter plano de saúde e referir uma autoavaliação de saúde muito ruim. De forma geral, foi evidenciada a importância do PFPB como política de ampliação de acesso a medicamentos essenciais no Brasil, considerando a gratuidade dos anti-hipertensivos e antidiabéticos.

Este estudio tuvo como objetivo medir el acceso a los medicamentos para el tratamiento de la hipertensión arterial sistémica y de la diabetes mellitus tipo 2 en Brasil según la vía de obtención, además de analizar los factores asociados a este acceso, según datos de la Encuesta Nacional de Salud (PNS) de 2019. Se analizaron datos socioeconómicos y relacionados con el uso de medicamentos de personas de 15 años o más, con relación al acceso por medio del Programa Farmacia Popular de Brasil (PFPB) y por medio del servicio público. La mayor parte de los brasileños que participaron en la PNS refirió utilizar medicamentos para controlar la hipertensión, en los últimos 15 días (91,5%), así como la mayoría refirió el uso de medicamentos orales para la diabetes (95,2%) o uso de insulina (70%). Los medicamentos orales para hipertensión arterial sistémica y diabetes mellitus tipo 2 se obtuvieron en su mayoría por medio del PFPB, respectivamente (45,2% y 53,6%), y los factores que influyeron de forma más negativa en este acceso fueron mayor rango de edad, menores ingresos, menor escolaridad, no tener seguro de salud y reportar una autoevaluación de salud muy mala. El acceso a la insulina, a su vez, se produjo con mayor frecuencia por medio del servicio público de salud (69,7%), y los factores que influyeron de forma más negativa en este acceso fueron la raza negra/morena, menores ingresos, no tener plan de salud y reportar una autoevaluación de salud muy mala. En general, se destacó la importancia de la PFPB como política de ampliación del acceso a medicamentos esenciales en Brasil, considerando la gratuidad de los antihipertensivos y antidiabéticos.

Effect of sodium-glucose co-transporter-2 inhibitors on survival free of organ support in patients hospitalised for COVID-19 (ACTIV-4a): a pragmatic, multicentre, open-label, randomised, controlled, platform trial.

BACKGROUND: Patients hospitalised for COVID-19 are at risk for multiorgan failure and death. Sodium-glucose co-transporter-2 (SGLT2) inhibitors provide cardiovascular and kidney protection in patients with cardiometabolic conditions and could provide organ protection during COVID-19. We aimed to investigate whether SGLT2 inhibitors can reduce the need for organ support in patients hospitalised for COVID-19. METHODS: This pragmatic, multicentre, open-label, randomised, controlled, platform trial was conducted across 63 sites in the USA, Spain, Brazil, Italy, and Mexico. Patients aged at least 18 years hospitalised for COVID-19 (moderate or severe illness) were randomly assigned (1:1), via an interactive voice system or web-response system, to receive locally available SGLT2 inhibitor (administered orally, once daily) plus standard-of-care or standard-of-care for 30 days. The primary outcome was organ support-free days evaluated through 21 days, assessed using intention-to-treat approach. This trial is registered on ClinicalTrials.gov, NCT04505774. FINDINGS: The first patient was randomly assigned to the SGLT2 inhibitor domain on Dec 3, 2021. On March 31, 2023, at the recommendation of the data and safety monitoring board, enrolment in the SGLT2 inhibitor domain for both moderately and severely ill hospitalised patients was stopped prematurely for futility due to a low likelihood of finding a treatment benefit. The final randomised population consisted of 575 patients (mean age 72 years [SD 13], 242 (42%) female and 154 (27%) Hispanic; 504 in the moderate illness group and 71 in the severe illness group). 573 patients had a known 21-day outcome; 215 (75%) of 285 patients in the SGLT2 inhibitor plus standard-of-care group did not require respiratory or cardiovascular organ support versus 231 (80%) of 288 patients in the standard-of-care group. The adjusted odds ratio (OR) for an SGLT2 inhibitor effect on organ support-free days was 0·74 (95% Credible Interval [CrI] 0·48-1·13; where OR higher than 1 indicated treatment benefit, yielding a posterior probability of futility P(OR <1·2) of 99% and a posterior probability of inferiority P(OR<1·0) of 91%). There were 37 deaths (13%) in the SGLT2 inhibitor plus standard-of-care group and 42 deaths (15%) in the standard-of-care group at 90 days (hazard ratio 0·91 [95% CrI 0·58-1·43], probability of hazard ratio <1 of 66%). No safety concerns were observed with SGLT2 inhibitors, including no cases of ketoacidosis. INTERPRETATION: SGLT2 inhibitors did not significantly increase days free of organ support or reduce mortality in patients hospitalised with COVID-19. SGLT2 inhibitors were well tolerated with no observed safety concerns. Overall, these findings do not support the use of SGLT2 inhibitors as standard care in patients hospitalised with COVID-19. FUNDING: National Institutes of Health.

SGLT2 Inhibitors and How They Work Beyond the Glucosuric Effect. State of the Art.

Type 2 diabetes mellitus (T2DM) is associated with a heightened risk of cardiovascular and renal complications. While glycemic control remains essential, newer therapeutic options, such as SGLT2 inhibitors, offer additional benefits beyond glucose reduction. This review delves into the mechanisms underlying the cardio-renal protective effects of SGLT2 inhibitors. By inducing relative hypoglycemia, these agents promote ketogenesis, optimize myocardial energy metabolism, and reduce lipotoxicity. Additionally, SGLT2 inhibitors exert renoprotective actions by enhancing renal perfusion, attenuating inflammation, and improving iron metabolism. These pleiotropic effects, including modulation of blood pressure, reduction of uric acid, and improved endothelial function, collectively contribute to the cardiovascular and renal benefits observed with SGLT2 inhibitor therapy. This review will provide clinicians with essential knowledge, understanding, and a clear recollection of this pharmacological group's mechanism of action.

The dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist tirzepatide effects on body weight evolution, adiponectin, insulin and leptin levels in the combination of obesity, type 2 diabetes and menopause in mice.

AIM: Tirzepatide (Tzp), a novel dual agonist glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1, is approved for treating insulin resistance and obesity, and menopausal women consuming a high-calorie diet are a target to study the Tzp effect. Therefore, we aimed to allometrically scale body weight (BW) in Tzp-treated obese diabetic menopausal mice. MATERIALS AND METHODS: Three-month-old C57BL/6 female mice had bilateral ovariectomy (Ovx) or a sham procedure and for 12 weeks were fed a control diet or a high-fat and high sucrose diet (n = 120/each group [control (C), obese diabetic (Od), Ovx (O), sham (S), Tzp (T)]). Tzp was subcutaneously administered (10 nmol/kg) or vehicle once a day for an additional 4 weeks. The analysis considered log-transformed data and the allometric equation log y = log a + b log x. RESULTS: Od and OdO showed more upward slopes than C and CO. In C, BW was non-allometric by T administration. Od and OdO showed slightly positive slopes (more prominent in OdO than Od). OdT and OdOT showed negative slopes, significant intercepts, and more robust Pearson coefficients than untreated ones. A potent drug effect was seen with BW allometric decline. Interactions between diet versus Ovx and diet versus Tzp affected weight gain. Diet versus Ovx versus Tzp affected food intake. CONCLUSIONS: A model was developed to show three usual factors observed in mature women. Notably, Tzp improved the metabolism and weight loss of OdO mice. Tzp-treated mice showed negative allometric BW across treatment time, which is a quantitative assessment that allows better comparison between results.

Liraglutide for the Treatment of Weight Regain After Bariatric Surgery: A Systematic Review and Meta-analysis.

INTRODUCTION: The efficacy of liraglutide for treating type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Library databases in January 2024. A random-effects model was employed to compute mean differences (MD) and events per 100 observations with 95% confidence intervals (CI) for continuous and binary endpoints. Statistical analysis was performed using R software. RESULTS: A total of 16 studies were included and 881 individuals. Patients were mostly female (50%), aged 36 to 55 years, with a mean body mass index (BMI) of 39.4 kg/m2, and had BS surgery 5 years prior. Over a mean follow-up time ranging from 3 months to 4 years, it was observed a statistically significant reduction in BMI (MD - 8.56 kg/m2; 95% CI 3.34 to 13.79; p < 0.01) and a mean reduction in total weight (MD - 16.03 kg; 95% CI 0.03 to 32.02; p = 0.05) after liraglutide use. Additionally, 65% of patients undertaking liraglutide showed total body weight loss (BWL) above 5% (65.8 events per 100 observations; 95% CI 54.96 to 75.20; p < 0.01), while 26% lost more than 10% of total BWL (26.77 events per 100 observations; 95% CI 19.17 to 36.02; p < 0.01). A limitation is a variability between the studies. CONCLUSIONS: Our findings support the use of liraglutide for weight management in patients who experience weight regain after BS. Liraglutide is well tolerated and promotes significant weight loss, providing clinicians with a therapeutic option for this clinical challenge.

Effectiveness and safety of once-weekly semaglutide: findings from the SEMACOL-REAL retrospective multicentric observational study in Colombia.

Introduction: Diabetes stands as one of the leading causes of death worldwide. Glucagon-like peptide-1 receptor agonists rank among the most effective medications for lowering blood glucose and body weight, as well as reducing cardiovascular risk in individuals with diabetes. Observational studies complement experimental evidence in new settings, different populations, and real-world healthcare practices. Methods: A multicentric observational study of adults with type 2 diabetes treated with once-weekly subcutaneous semaglutide in four health centers in Colombia was conducted. The protocol for the present study was not pre-registered. Results: Data from 186 patients were included. Most patients were women (57%) with a mean age of 62.8 ± 12.1 years. One year of once-weekly semaglutide usage was associated with a mean reduction in HbA1C of -1.47% (95% CI -1.76, -1.17), weight loss of -4.23 kg (95% CI -5.34, -3.12), and albumin/creatinine ratio of -18.6 mg/g (95% CI -60.2, -5.9). Approximately half the treated patients achieved a level of HbA1c ≤7% by the end of follow-up. Adverse events were rare and consistent with clinical trial safety profiles. Conclusion: In Colombia, administering semaglutide subcutaneously once a week over a 1-year period led to an average weight loss of 4.2 kg and a decrease of 1.4% in HbA1c.

Computational approaches for lead compound discovery in dipeptidyl peptidase-4 inhibition using machine learning and molecular dynamics techniques.

The prediction of possible lead compounds from already-known drugs that may present DPP-4 inhibition activity imply a advantage in the drug development in terms of time and cost to find alternative medicines for the treatment of Type 2 Diabetes Mellitus (T2DM). The inhibition of dipeptidyl peptidase-4 (DPP-4) has been one of the most explored strategies to develop potential drugs against this condition. A diverse dataset of molecules with known experimental inhibitory activity against DPP-4 was constructed and used to develop predictive models using different machine-learning algorithms. Model M36 is the most promising one based on the internal and external performance showing values of Q2CV = 0.813, and Q2EXT = 0.803. The applicability domain evaluation and Tropsha's analysis were conducted to validate M36, indicating its robustness and accuracy in predicting pIC50 values for organic molecules within the established domain. The physicochemical properties of the ligands, including electronegativity, polarizability, and van der Waals volume were relevant to predict the inhibition process. The model was then employed in the virtual screening of potential DPP4 inhibitors, finding 448 compounds from the DrugBank and 9 from DiaNat with potential inhibitory activity. Molecular docking and molecular dynamics simulations were used to get insight into the ligand-protein interaction. From the screening and the favorable molecular dynamic results, several compounds including Skimmin (pIC50 = 3.54, Binding energy = -8.86 kcal/mol), bergenin (pIC50 = 2.69, Binding energy = -13.90 kcal/mol), and DB07272 (pIC50 = 3.97, Binding energy = -25.28 kcal/mol) seem to be promising hits to be tested and optimized in the treatment of T2DM. This results imply a important reduction in cost and time on the application of this drugs because all the information about the its metabolism is already available.

Semaglutide Attenuates Anxious and Depressive-Like Behaviors and Reverses the Cognitive Impairment in a Type 2 Diabetes Mellitus Mouse Model Via the Microbiota-Gut-Brain Axis.

Newly conducted research suggests that metabolic disorders, like diabetes and obesity, play a significant role as risk factors for psychiatric disorders. This connection presents a potential avenue for creating novel antidepressant medications by repurposing drugs originally developed to address antidiabetic conditions. Earlier investigations have shown that GLP-1 (Glucagon-like Peptide-1) analogs exhibit neuroprotective qualities in various models of neurological diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, and stroke. Moreover, GLP-1 analogs have demonstrated the capability to enhance neurogenesis, a process recognized for its significance in memory formation and the cognitive and emotional aspects of information processing. Nonetheless, whether semaglutide holds efficacy as both an antidepressant and anxiolytic agent remains uncertain. To address this, our study focused on a mouse model of depression linked to type 2 diabetes induced by a High Fat Diet (HFD). In this model, we administered semaglutide (0.05 mg/Kg intraperitoneally) on a weekly basis to evaluate its potential as a therapeutic option for depression and anxiety. Diabetic mice had higher blood glucose, lipidic profile, and insulin resistance. Moreover, mice fed HFD showed higher serum interleukin (IL)-1ß and lipopolysaccharide (LPS) associated with impaired humor and cognition. The analysis of behavioral responses revealed that the administration of semaglutide effectively mitigated depressive- and anxiety-like behaviors, concurrently demonstrating an enhancement in cognitive function. Additionally, semaglutide treatment protected synaptic plasticity and reversed the hippocampal neuroinflammation induced by HFD fed, improving activation of the insulin pathway, demonstrating the protective effects of semaglutide. We also found that semaglutide treatment decreased astrogliosis and microgliosis in the dentate gyrus region of the hippocampus. In addition, semaglutide prevented the DM2-induced impairments of pro-opiomelanocortin (POMC), and G-protein-coupled receptor 43 (GPR43) and simultaneously increased the NeuN + and Glucagon-like Peptide-1 receptor (GLP-1R+) neurons in the hippocampus. Our data also showed that semaglutide increased the serotonin (5-HT) and serotonin transporter (5-HTT) and glutamatergic receptors in the hippocampus. At last, semaglutide changed the gut microbiota profile (increasing Bacterioidetes, Bacteroides acidifaciens, and Blautia coccoides) and decreased leaky gut, improving the gut-brain axis. Taken together, semaglutide has the potential to act as a therapeutic tool for depression and anxiety.

The role of FGF19 in metabolic regulation: insights from preclinical models to clinical trials.

Fibroblast growth factor 19 (FGF19) is a hormone synthesized in enterocytes in response to bile acids. This review explores the pivotal role of FGF19 in metabolism, addressing the urgent global health concern of obesity and its associated pathologies, notably type 2 diabetes. The intriguing inverse correlation between FGF19 and body mass or visceral adiposity, as well as its rapid increase following bariatric surgery, emphasizes its potential as a therapeutic target. This article meticulously examines the impact of FGF19 on metabolism by gathering evidence primarily derived from studies conducted in animal models or cell lines, using both FGF19 treatment and genetic modifications. Overall, these studies demonstrate that FGF19 has antidiabetic and antiobesogenic effects. A thorough examination across metabolic tissues, including the liver, adipose tissue, skeletal muscle, and the central nervous system, is conducted, unraveling the intricate interplay of FGF19 across diverse organs. Moreover, we provide a comprehensive overview of clinical trials involving an FGF19 analog called aldafermin, emphasizing promising results in diseases such as nonalcoholic steatohepatitis and diabetes. Therefore, we aim to foster a deeper understanding of FGF19 role and encourage further exploration of its clinical applications, thereby advancing the field and offering innovative approaches to address the escalating global health challenge of obesity and related metabolic conditions.

The first report of leukocytoclastic vasculitis induced by once-weekly subcutaneous semaglutide.

INTRODUCTION: Leukocytoclastic vasculitis (LCV) is a small vessel vasculitis involving arterioles, capillaries and postcapillary venules. LCV is generally confined to the skin, with extracutaneous manifestations occurring less frequently. LCV has multiple potential etiologies. Indeed, histological LCV can be found in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, immune complex vasculitis, vasculitis associated with systemic diseases (i.e. sarcoidosis, Sjögren's syndrome, rheumatoid arthritis, and systemic lupus erythematosus), or in vasculitis associated with cancer, infections, sepsis and use of certain medications. LCV can also be idiopathic in up to 50% of cases. CASE REPORT: Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist used for management of type 2 diabetes mellitus (T2DM), obesity and overweight associated with one or more weight-related comorbidities. A case of drug-induced LCV has already been described with the use of once-daily oral semaglutide. Herein, we describe the first case of skin-limited LCV induced by once-weekly subcutaneous semaglutide in a 73-year-old man with T2DM, who experienced the complete resolution of the skin lesions shortly after the discontinuation of semaglutide therapy. CONCLUSION: Future prospective studies, adverse event reporting and post-marketing surveillance will certainly contribute to establishing if LCV represents a less rare than expected side effect of both oral and subcutaneous semaglutide formulations.

Functional chia (Salvia hispanica L.) co-product protein hydrolysate: An analysis of biochemical, antidiabetic, antioxidant potential and physicochemical properties.

Protein hydrolysates with antioxidant potential have been reported to act as adjuvants in preventing and treating type-2 diabetes (T2D). This work investigated the biochemical, antidiabetic, antioxidant potential, and physicochemical properties of chia meal protein hydrolysate (CMPH). Bands smaller than 14 kDa were observed in the electrophoretic profile. The predominant amino acids were hydrophobic and aromatic. CMPH had the potential to inhibit α-amylase (IC50: 1.76 ± 0.13 mg/mL), α-glucosidase (IC50: 0.42 ± 0.13 mg/mL), and DPP-IV (IC50: 0.46 ± 0.14 mg/mL). Antioxidant activity for ABTS (IC50: 0.236 mg/mL), DPPH (8.83 ± 0.52%), and ORAC (IC25: 0.115 mg/mL). Against chia meal protein isolate (CMPI), CMPH has a broad solubility (pH 2-12.46). Particle size (624.5 ± 247.3 nm), low PDI (0.22 ± 0.06), ζ-potential (-31.1 ± 2.5 mV), and surface hydrophobicity (11,183.33 ± 2024.11) and the intrinsic fluorescence peak of CMPH was lower than that of CMPI. CMPH represents an alternative to add value to the agri-food co-product of the chia seed oil industry, generating food ingredients with outstanding antidiabetic and antioxidant potential.

Iron chelation mitigates mitochondrial dysfunction and oxidative stress by enhancing nrf2-mediated antioxidant responses in the renal cortex of a murine model of type 2 diabetes.

Renal iron overload is a common complication of diabetes that leads to oxidative stress and mitochondrial dysfunction in the kidneys. This study investigated the effects of iron chelation using deferiprone on mitochondrial dysfunction and oxidative stress in the renal cortex of a murine model of type 2 diabetes. Diabetic rats were treated with deferiprone (50 mg/kg BW) for 16 weeks. Our results show that iron chelation with deferiprone significantly increased the nuclear accumulation of Nrf2, a transcription factor that regulates the expression of antioxidant enzymes. This led to enhanced antioxidant capacity, reduced production of reactive oxygen species, and improved mitochondrial bioenergetic function in diabetic rats. However, chronic iron chelation led to altered mitochondrial respiration and increased oxidative stress in non-diabetic rats. In conclusion, our findings suggest that iron chelation with deferiprone protects mitochondrial bioenergetics and mitigates oxidative stress in the renal cortex, involving the NRF2 pathway in type 2 diabetes.

Emerging role of Metformin in Alzheimer's disease: A translational view.

Alzheimer's disease (AD) constitutes a major public-health issue of our time. Regrettably, despite our considerable understanding of the pathophysiological aspects of this disease, current interventions lead to poor outcomes. Furthermore, experimentally promising compounds have continuously failed when translated to clinical trials. Along with increased population ageing, Type 2 Diabetes Mellitus (T2DM) has become an extremely common condition, mainly due to unbalanced dietary habits. Substantial epidemiological evidence correlates T2DM with cognitive impairment as well. Considering that brain insulin resistance, mitochondrial dysfunction, oxidative stress, and amyloidogenesis are common phenomena, further approaching the common features among these pathological conditions. Metformin constitutes the first-choice drug to preclude insulin resistance in T2DM clinical management. Experimental evidence suggests that its functions might include neuroprotective effects, in addition to its hypoglycemic activity. This review aims to summarize and discuss current knowledge of experimental data on metformin on this path towards translational medicine. Finally, we discuss the controversial data of responses to metformin in vitro, and in vivo, animal models and human studies.

Effects of vitamin D supplementation on metabolic syndrome parameters in patients with obesity or diabetes in Brazil, Europe, and the United States: A systematic review and meta-analysis.

Plasma 25-dihydroxyvitamin D levels appear reduced in patients with obesity or type 2 diabetes, as reported in several observational studies. However, the association between these reduced hormone levels and metabolic parameters is unclear. In any case, vitamin D supplementation in patients with Metabolic Syndrome is standard. Still, the impacts of this supplementation on conditions such as glycemia, blood pressure, and lipidemia are debatable. Based on this question, we carried out a systematic review and meta-analysis of randomized clinical trials in Brazil, Europe, and the United States that analyzed the effects of vitamin D supplementation on Metabolic Syndrome parameters in patients with obesity or type 2 diabetes. Our search yielded 519 articles and included 12 randomized controlled trials in the meta-analysis. Vitamin D supplementation had no effect on any of the outcomes analyzed (fasting blood glucose and insulinemia, glycated hemoglobin, HOMA index, systolic and diastolic blood pressure, weight, waist circumference, total cholesterol, LDL and HDL, and triglycerides). However, subgroup analyses indicated that using vitamin D up to 2000 IU daily reduced participants' fasting blood glucose and glycated hemoglobin. Furthermore, the intervention reduced diastolic blood pressure only in participants with vitamin D deficiency. At least two studies showed a high risk of bias using the Rob2 protocol. According to the GRADE protocol, the evidence quality varied from moderate to very low. These results indicate that vitamin D supplementation does not improve patients' metabolic parameters and that the association between plasma 25-dihydroxyvitamin D levels and Metabolic Syndrome may not be causal but caused by other confounding characteristics. However, in any case, the quality of evidence is still low, and more randomized clinical trials are essential to clarify these relationships.

Prediction of pharmaceutical and non-pharmaceutical expenditures associated with Diabetes Mellitus type II based on clinical risk.

OBJECTIVE: To assess the effectiveness of different machine learning models in estimating the pharmaceutical and non-pharmaceutical expenditures associated with Diabetes Mellitus type II diagnosis, based on the clinical risk index determined by the analysis of comorbidities. MATERIALS AND METHODS: In this cross-sectional study, we have used data from 11,028 anonymized records of patients admitted to a high-complexity hospital in Bogota, Colombia between 2017-2019 with a primary diagnosis of Diabetes. These cases were classified according to Charlson's comorbidity index in several risk categories. The main variables analyzed in this study are hospitalization costs (which include pharmaceutical and non-pharmaceutical expenditures), age, gender, length of stay, medicines and services consumed, and comorbidities assessed by the Charlson's index. The model's dependent variable is expenditure (composed of pharmaceutical and non-pharmaceutical expenditures). Based on these variables, different machine learning models (Multivariate linear regression, Lasso model, and Neural Networks) were used to estimate the pharmaceutical and non-pharmaceutical expenditures associated with the clinical risk classification. To evaluate the performance of these models, different metrics were used: Mean Absolute Percentage Error (MAPE), Mean Squared Error (MSE), Root Mean Squared Error (RMSE), Mean Absolute Error (MAE), and Coefficient of Determination (R2). RESULTS: The results indicate that the Neural Networks model performed better in terms of accuracy in predicting pharmaceutical and non-pharmaceutical expenditures considering the clinical risk based on Charlson's comorbidity index. A deeper understanding and experimentation with Neural Networks can improve these preliminary results, therefore we can also conclude that the main variables used and those that were proposed can be used as predictors for the medical expenditures of patients with diabetes type-II. CONCLUSIONS: With the increase of technology elements and tools, it is possible to build models that allow decision-makers in hospitals to improve the resource planning process given the accuracy obtained with the different models tested.

Antidiabetic Effect of Passiflora ligularis Leaves in High Fat-Diet/Streptozotocin-Induced Diabetic Mice.

Type 2 diabetes mellitus (T2DM) is a major global public health concern, prompting the ongoing search for new treatment options. Medicinal plants have emerged as one such alternative. Our objective was to evaluate the antidiabetic effect of an extract from the leaves of Passiflora ligularis (P. ligularis). For this purpose, T2DM was first induced in mice using a high-fat diet and low doses of streptozotocin. Subsequently, an aqueous extract or an ethanolic extract of P. ligularis leaves was administered for 21 days. The following relevant results were found: fasting blood glucose levels were reduced by up to 41%, and by 29% after an oral glucose overload. The homeostasis model assessment of insulin resistance (HOMA-IR) was reduced by 59%. Histopathologically, better preservation of pancreatic tissue was observed. Regarding oxidative stress parameters, there was an increase of up to 48% in superoxide dismutase (SOD), an increase in catalase (CAT) activity by 35% to 80%, and a decrease in lipid peroxidation (MDA) by 35% to 80% in the liver, kidney, or pancreas. Lastly, regarding the lipid profile, triglycerides (TG) were reduced by up to 30%, total cholesterol (TC) by 35%, and low-density lipoproteins (LDL) by up to 32%, while treatments increased high-density lipoproteins (HDL) by up to 35%. With all the above, we can conclude that P. ligularis leaves showed antihyperglycemic, hypolipidemic, and antioxidant effects, making this species promising for the treatment of T2DM.