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Polymetabolic syndrome achieved pandemic proportions and dramatically influenced public health systems functioning worldwide. Chronic vascular complications are the major contributors to increased morbidity, disability, and mortality rates in diabetes patients. Nitric oxide (NO) is among the most important vascular bed function regulators. However, NO homeostasis is significantly deranged in pathological conditions. Additionally, different hormones directly or indirectly affect NO production and activity and subsequently act on vascular physiology. In this paper, we summarize the recent literature data related to the effects of insulin, estradiol, insulin-like growth factor-1, ghrelin, angiotensin II and irisin on the NO regulation in physiological and diabetes circumstances.

Introduction: The use of mHealth can improve adherence to self-monitoring blood Glucose (SMBG) in the transition from hospital to outpatient setting. Objective: To evaluate adherence to self-monitoring with GC in patients with type 2 diabetes (T2DM) linked to an mHealth user education program (ClouDi) compared with the usual face-to-face education and follow-up program. Materials and Methods: Prospective longitudinal study. Patients with T2D assessed by diabetes education counseling with an indication for insulin treatment at hospital discharge were analyzed. Two groups were analyzed: one with face-to-face follow-up and another linked to an educational program and use of ClouDi. Results: Of the 86 patients (44% female, 41 ClouDi users, mean age 58.8 ± 11.2 years, with a mean duration of diabetes of 7.8 ± 7.4 years), 53.6% were in stratum 2, 92.9% belonged to the contributory system, 42.9% with basic pri-mary education and 51.2% were employed. Compliance with the SMBG was considered if 3 or more measurements per day were taken and recorded, was higher in ClouDi patients com-pared to usual care patients (64.4% vs. 28.2%, p <0.001), independent of sociodemographic variables.Conclusions: The use of ClouDi was associated with greater adherence to SMBG compared to in-person follow-up, independent of sociodemographic variables. The use of this technology may be useful in monitoring insulin-using patients after hospital discharge, Introdução: A utilização do mHealth pode melhorar a adesão à automonitorização com glico-metria capilar (GC) na transição do hospital para o ambulatório. Objetivo: avaliar a adesão ao automonitoramento com GC de pacientes com Diabetes Tipo 2 (DM2) vinculados a um progra-ma de educação de usuários de mHealth (ClouDi) em comparação com o programa habitual de educação e acompanhamento presencial. Materiais e métodos: Estudo prospectivo longitudi-nal. Foram analisados pacientes com DM2 avaliados por consulta de educação em diabetes com indicação de tratamento insulínico na alta hospitalar. Foram analisados dois grupos: um com acompanhamento presencial e outro vinculado a um programa educativo e uso do ClouDi. Re-sultados: Dos 86 doentes (44% do sexo feminino, 41 utilizadores do ClouDi, idade média 58,8 ± 11,2 anos, com duração média da diabetes de 7,8 ± 7,4 anos), 53,6% encontravam-se no estra-to 2, 92,9% pertenciam ao regime contributivo, 42,9% com ensino fundamental básico e 51,2% empregados. A adesão ao GC foi considerada quando realizada e registrada 3 ou mais medidas por dia em pacientes ClouDi foi maior em comparação aos pacientes em cuidados habituais (64,4% vs 28,2%, p <0,001), independente das variáveis sociodemográficas. Conclusão: O uso do ClouDi esteve associado à maior adesão ao automonitoramento com GC em comparação ao acompanhamento presencial independente das variáveis sociodemográficas. O uso dessa tecnologia pode ser útil no monitoramento de pacientes usuários de insulina na alta hospitalar, Introducción: El uso de mHealth puede mejorar la adherencia a el automonitoreo con glu-cometría capilar (GC) en la transición del ámbito hospitalario al ambulatorio. Objetivo: evaluar la adherencia al automonitoreo con GC de los pacientes con Diabetes Tipo 2 (DM2) vinculados a un programa de educación usuarios de mHealth (ClouDi) comparado con el programa de educación y seguimiento presencial usual. Materiales y métodos: Estudio longitudinal pro-spectivo. Se analizaron pacientes con DM2 valorados por consulta de educación de diabetes con indicación de tratamiento con insulina al egreso hospitalario. Se analizaron dos grupos: uno con seguimiento presencial y otro vinculado a un programa educativo y uso de ClouDi. Resultados: De los 86 pacientes (44% de sexo femenino, 41 usuarios ClouDi, edad promedio 58.8 ± 11.2 años, con una media de duración de la diabetes de 7.8 ± 7.4 años), 53.6% se encontraban en estrato 2, el 92.9% pertenecían al régimen contributivo, el 42.9% con educación básica primaria y 51.2% empleados. Fue considerada la adherencia a la GC al realizar y registrar 3 o más medi-ciones por día en los pacientes de ClouDi fue mayor comparado con los pacientes en cuidado usual (64.4% vs 28.2%, p <0.001), independiente de las variables sociodemográficas. Con-clusión: El uso de ClouDi se asoció a mayor adherencia a automonitoreo con GC comparado con seguimiento presencial independiente de variables sociodemográficas. El uso de esta tec-nología podría ser útil en el seguimiento de pacientes usuarios de insulina al egreso hospitalario

Background/methods: The impact of clinical pharmacist on undiagnosed pregnancy hyperglycemia (PHG) in mid- and late- pregnancy as a major preventable cause of maternal and neonatal (M/N) complications is investigated. This longitudinal randomized controlled study of changes in plasma levels of predictive/prognostic/diagnostic biomarkers of oxytocin, thrombospondin, MCP1, IL6, MIF, insulin and LAR and undesirable M/N pregnancy outcomes in women with/out PHG (pregnancy normoglycemia; PNG) following the implementation of clinical pharmacist interventions were investigated. Results: A total of 68 PHG (36 intervention vs. 32 non-intervention) vs. 21 PNG participants were enrolled at 20–28 weeks and followed up till delivery. BMI of intervention PHG (unlike non-intervention) was greater (p=0.036) compared to PNG’s. LAR and insulin, oxytocin, thrombospondin1, adiponectin and MCP1 plasma levels and their differences between 2nd and 3rd pregnancy trimesters lacked discrepancies in participants. Both PHG groups in mid pregnancy had substantially greater HbA1c %, FPG and IL6 levels vs. PNG, while PHG non-intervention’ leptin was greater than PNG’s. In late pregnancy, greater SBP, IL6 and MIF levels between either PHG groups vs. PNG’s were observed. Unlike PHG non-intervention and PNG; IL6 level in PHG intervention group decreased (-2.54±6.61; vs. non-intervention PHG’s 4.26±5.28; p<0.001 and vs. PNG’s 2.30±4.27; p=0.023). None of the assessed M/N outcomes was found of differential significance between any of the three study groups. Conclusions: Proinflammatory IL6 as a robust and generalizable cardiometabolic risk-based and related pharmacotherapy biomarker in mid and late hyperglycemic pregnancy with likely implications of novel therapeutic targets was delineated by clinical pharmacist interventions.

Within the islets of Langerhans, beta cells orchestrate synchronized insulin secretion, a pivotal aspect of metabolic homeostasis. Despite the inherent heterogeneity and multimodal activity of individual cells, intercellular coupling acts as a homogenizing force, enabling coordinated responses through the propagation of intercellular waves. Disruptions in this coordination are implicated in irregular insulin secretion, a hallmark of diabetes. Recently, innovative approaches, such as integrating multicellular calcium imaging with network analysis, have emerged for a quantitative assessment of the cellular activity in islets. However, different groups use distinct experimental preparations, microscopic techniques, apply different methods to process the measured signals and use various methods to derive functional connectivity patterns. This makes comparisons between findings and their integration into a bigger picture difficult and has led to disputes in functional connectivity interpretations. To address these issues, we present here a systematic analysis of how different approaches influence the network representation of islet activity. Our findings show that the choice of methods used to construct networks is not crucial, although care is needed when combining data from different islets. Conversely, the conclusions drawn from network analysis can be heavily affected by the pre-processing of the time series, the type of the oscillatory component in the signals, and by the experimental preparation. Our tutorial-like investigation aims to resolve interpretational issues, reconcile conflicting views, advance functional implications, and encourage researchers to adopt connectivity analysis. As we conclude, we outline challenges for future research, emphasizing the broader applicability of our conclusions to other tissues exhibiting complex multicellular dynamics.

Diabetes is a metabolic disorder characterized by elevated blood glucose levels that can lead to various complications. Exploring the physiological alterations in rabbits can provide valuable insights for the development of therapeutic interventions. This research delves into the impact of diabetes on the physiological and biochemical parameters of male rabbits. Objectives: To compare the physiological parameters like body temperature, heart rate, respiration rate, and oxygen saturation) and body weight and biochemical parameters, including blood glucose levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, lactate dehydrogenase (LDH), and total protein levels in diabetic and non-diabetic rabbits. Methods: An experiment on 30 male rabbits divided into diabetic and control groups measured physiological parameters like body temperature, heart rate, respiration rate, and oxygen saturation. Body weight and blood glucose levels were tracked, and blood samples were taken for ALT, AST, creatinine, LDH, cholesterol, triglycerides and total protein levels. Statistical analysis was conducted to compare the physiological and biochemical parameters between the diabetic and control groups. Results: The results showed that induced diabetes in male rabbits affects their physiological and biochemical parameters significantly. Diabetic rabbits had lower body temperature, heart rate, respiration rate, and oxygen saturation compared to the control group. They also had higher body weight and blood glucose levels. Biochemical analysis showed increased ALT, AST, and creatinine levels, and decreased LDH and total protein levels in diabetic rabbits. Conclusions: These results demonstrate the extensive impact of diabetes on rabbit physiology and biochemistry, offering insights for future diabetes research.

Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.

Fruits are rich in bioactive compounds, such as (poly)phenols, and their intake is associated with health benefits, although recent animal studies have suggested that the photoperiod of consumption influences their properties. Fruit loss and waste are critical issues that can be reduced by obtaining functional fruit extracts. Therefore, the aim of this study was to obtain phenolic-enriched extracts from eight seasonal fruits that can modulate blood biochemical parameters and to investigate whether their effects depend on the photoperiod of consumption. Eight ethanol-based extracts were obtained and characterized, and their effects were studied in F344 rats exposed to short (6 h light, L6) and long (18 h light) photoperiods. Cherry and apricot extracts decreased blood triacylglyceride levels only when consumed under the L6 photoperiod. Pomegranate, grape, and orange extracts reduced cholesterol and fasting glucose levels during the L6 photoperiod; however, plum extract reduced fasting glucose levels only during the L18 photoperiod. The results showed the importance of photoperiod consumption in the effectiveness of phenolic-enriched fruit extracts and promising evidence regarding the use of some of the developed fruit extracts as potential functional ingredients for the management of several blood biomarkers., Ministerio de Ciencia e Innovación (España), Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Veterinaria, TRUE, pub

Silibinin has considerable therapeutic potential for the treatment of diabetes through anti-inflammatory, antioxidant, and immunomodulatory properties. However, the therapeutic application of silibinin is quite limited due to its poor bioavailability. In the present study, an attempt was made to improve the antidiabetic efficacy of silibinin by its encapsulation in liposomal vesicles. The liposomes with a high encapsulation efficiency of silibinin (96%) and a zeta potential of −26.2 ± 0.6 mV were developed and studied using nicotinamide/streptozotocin-induced diabetic rats. Administration of silibinin-loaded liposomes to diabetic rats lowered glucose levels, increased insulin levels, and improved pancreatic islet architecture. The anti-inflammatory effect of silibinin-loaded liposomes was demonstrated by a decrease in serum C-reactive protein (CRP) levels and a reduced deposition of collagen fibers in the islets of diabetic rats. Furthermore, silibinin-loaded liposomes were more efficient in lowering glucose, alanine transaminase, triglyceride, and creatinine levels in diabetic rats than pure silibinin. In addition, silibinin-loaded liposomes had a significantly better effect on beta-cell mass and Glut2 glucose receptor distribution in diabetic islets than pure silibinin. The present results clearly show that liposome encapsulation of silibinin enhances its antidiabetic efficacy, which may contribute to the therapeutic benefit of silibinin in the treatment of diabetes and its complications.

Background: Fasting levels of glucagon are known to be elevated in youth and adults with type 2 diabetes mellitus (T2D). Children and adolescents with obesity were previously reported to show increasing fasting and post-glucose-challenge hyperglucagonemia across the spectrum of glucose tolerance, while no data are available in those with impaired fasting glucose (IFG). Materials and methods: Individuals from the Beta-JUDO study population (Uppsala and Salzburg 2010-2016) (n=101, age 13.3 +/- 2.8, m/f =50/51) were included (90 with overweight or obesity, 11 with normal weight). Standardized OGTT were performed and plasma glucose, glucagon and insulin concentrations assessed at baseline, 5, 10, 15, 30, 60, 90 and 120 minutes. Patients were grouped according to their glycemic state in six groups with normal glucose metabolism (NGM) and normal weight (NG-NW), NGM with obesity or overweight (NG-O), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IGT+IFG and T2D, and in two groups with NGM and impaired glucose metabolism (IGM), for statistical analysis. Results and conclusion: Glucagon concentrations were elevated in young normoglycemic individuals with overweight or obesity (NG-O) compared to normoglycemic individuals with normal weight. Glucagon levels, fasting and dynamic, increased with progressing glycemic deterioration, except in IFG, where levels were comparable to those in NG-O. All glycemic groups showed an overall suppression of glucagon during OGTT. An initial increase of glucagon could be observed in T2D. In T2D, glucagon showed a strong direct linear correlation with plasma glucose levels during OGTT. Glucagon in adolescents, as in adults, may play a role in the disease progression of T2D.

Background: Fasting levels of glucagon are known to be elevated in youth and adults with type 2 diabetes mellitus (T2D). Children and adolescents with obesity were previously reported to show increasing fasting and post-glucose-challenge hyperglucagonemia across the spectrum of glucose tolerance, while no data are available in those with impaired fasting glucose (IFG). Materials and methods: Individuals from the Beta-JUDO study population (Uppsala and Salzburg 2010-2016) (n=101, age 13.3 +/- 2.8, m/f =50/51) were included (90 with overweight or obesity, 11 with normal weight). Standardized OGTT were performed and plasma glucose, glucagon and insulin concentrations assessed at baseline, 5, 10, 15, 30, 60, 90 and 120 minutes. Patients were grouped according to their glycemic state in six groups with normal glucose metabolism (NGM) and normal weight (NG-NW), NGM with obesity or overweight (NG-O), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IGT+IFG and T2D, and in two groups with NGM and impaired glucose metabolism (IGM), for statistical analysis. Results and conclusion: Glucagon concentrations were elevated in young normoglycemic individuals with overweight or obesity (NG-O) compared to normoglycemic individuals with normal weight. Glucagon levels, fasting and dynamic, increased with progressing glycemic deterioration, except in IFG, where levels were comparable to those in NG-O. All glycemic groups showed an overall suppression of glucagon during OGTT. An initial increase of glucagon could be observed in T2D. In T2D, glucagon showed a strong direct linear correlation with plasma glucose levels during OGTT. Glucagon in adolescents, as in adults, may play a role in the disease progression of T2D.

Background: Fasting levels of glucagon are known to be elevated in youth and adults with type 2 diabetes mellitus (T2D). Children and adolescents with obesity were previously reported to show increasing fasting and post-glucose-challenge hyperglucagonemia across the spectrum of glucose tolerance, while no data are available in those with impaired fasting glucose (IFG). Materials and methods: Individuals from the Beta-JUDO study population (Uppsala and Salzburg 2010-2016) (n=101, age 13.3 +/- 2.8, m/f =50/51) were included (90 with overweight or obesity, 11 with normal weight). Standardized OGTT were performed and plasma glucose, glucagon and insulin concentrations assessed at baseline, 5, 10, 15, 30, 60, 90 and 120 minutes. Patients were grouped according to their glycemic state in six groups with normal glucose metabolism (NGM) and normal weight (NG-NW), NGM with obesity or overweight (NG-O), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IGT+IFG and T2D, and in two groups with NGM and impaired glucose metabolism (IGM), for statistical analysis. Results and conclusion: Glucagon concentrations were elevated in young normoglycemic individuals with overweight or obesity (NG-O) compared to normoglycemic individuals with normal weight. Glucagon levels, fasting and dynamic, increased with progressing glycemic deterioration, except in IFG, where levels were comparable to those in NG-O. All glycemic groups showed an overall suppression of glucagon during OGTT. An initial increase of glucagon could be observed in T2D. In T2D, glucagon showed a strong direct linear correlation with plasma glucose levels during OGTT. Glucagon in adolescents, as in adults, may play a role in the disease progression of T2D.

Background: Fasting levels of glucagon are known to be elevated in youth and adults with type 2 diabetes mellitus (T2D). Children and adolescents with obesity were previously reported to show increasing fasting and post-glucose-challenge hyperglucagonemia across the spectrum of glucose tolerance, while no data are available in those with impaired fasting glucose (IFG). Materials and methods: Individuals from the Beta-JUDO study population (Uppsala and Salzburg 2010-2016) (n=101, age 13.3 +/- 2.8, m/f =50/51) were included (90 with overweight or obesity, 11 with normal weight). Standardized OGTT were performed and plasma glucose, glucagon and insulin concentrations assessed at baseline, 5, 10, 15, 30, 60, 90 and 120 minutes. Patients were grouped according to their glycemic state in six groups with normal glucose metabolism (NGM) and normal weight (NG-NW), NGM with obesity or overweight (NG-O), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IGT+IFG and T2D, and in two groups with NGM and impaired glucose metabolism (IGM), for statistical analysis. Results and conclusion: Glucagon concentrations were elevated in young normoglycemic individuals with overweight or obesity (NG-O) compared to normoglycemic individuals with normal weight. Glucagon levels, fasting and dynamic, increased with progressing glycemic deterioration, except in IFG, where levels were comparable to those in NG-O. All glycemic groups showed an overall suppression of glucagon during OGTT. An initial increase of glucagon could be observed in T2D. In T2D, glucagon showed a strong direct linear correlation with plasma glucose levels during OGTT. Glucagon in adolescents, as in adults, may play a role in the disease progression of T2D.

Chronic use of nicotine is known to dysregulate metabolic signaling through altering circulating levels of feeding-related hormones, contributing to the onset of disorders like type 2 diabetes. However, little is known about the acute effects of nicotine on hormonal signaling. We previously identified an acute increase in food intake following acute nicotine, and we sought to determine whether this behavior was due to a change in hormone levels. We first identified that acute nicotine injection produces an increase in feeding behavior in dependent rats, but not nondependent rats. We confirmed that chronic nicotine use increases circulating levels of insulin, leptin, and ghrelin, and these correlate with rats' body weight and food intake. Acute nicotine injection in dependent animals decreased circulating GLP-1 and glucagon levels, and administration of glucagon prior to acute nicotine injection prevented the acute increase in feeding behavior. Thus, acute nicotine injection increases feeding behavior in dependent rats by decreasing glucagon signaling.

Background: Fasting levels of glucagon are known to be elevated in youth and adults with type 2 diabetes mellitus (T2D). Children and adolescents with obesity were previously reported to show increasing fasting and post-glucose-challenge hyperglucagonemia across the spectrum of glucose tolerance, while no data are available in those with impaired fasting glucose (IFG). Materials and methods: Individuals from the Beta-JUDO study population (Uppsala and Salzburg 2010-2016) (n=101, age 13.3 +/- 2.8, m/f =50/51) were included (90 with overweight or obesity, 11 with normal weight). Standardized OGTT were performed and plasma glucose, glucagon and insulin concentrations assessed at baseline, 5, 10, 15, 30, 60, 90 and 120 minutes. Patients were grouped according to their glycemic state in six groups with normal glucose metabolism (NGM) and normal weight (NG-NW), NGM with obesity or overweight (NG-O), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IGT+IFG and T2D, and in two groups with NGM and impaired glucose metabolism (IGM), for statistical analysis. Results and conclusion: Glucagon concentrations were elevated in young normoglycemic individuals with overweight or obesity (NG-O) compared to normoglycemic individuals with normal weight. Glucagon levels, fasting and dynamic, increased with progressing glycemic deterioration, except in IFG, where levels were comparable to those in NG-O. All glycemic groups showed an overall suppression of glucagon during OGTT. An initial increase of glucagon could be observed in T2D. In T2D, glucagon showed a strong direct linear correlation with plasma glucose levels during OGTT. Glucagon in adolescents, as in adults, may play a role in the disease progression of T2D.

Sodium nitrite and quercetin are frequently employed as protective agents on glucose levels, levels of thyroid hormones, and lipid profile. The present study aimed to see the quercetin effect on some biochemical parameters in adult rats treated with sodium nitrite. A total of twenty-one laboratory animals (Wistar albino rats) were used in this experiment, separated into three groups of seven animals each. During the trial, Group I was given water only to drink and Group II received sodium nitrite directly by oral feeding needle. The study used 80 mg.kg-1/body weight (BW) of sodium nitrite, while Group IIIreceived drinking water containing sodium nitrite orally in doses of up to 80 mg.kg-1 BW and quercetin with a (50 mg/kg ). After blood was drawn and serum extracted, the parameters determined were thyroid hormones, lipids, Homeostasis Model Evaluation for Insulin Resistance (HOMA-IR) and glucose level. The study observed that compared to the controls, the insulin (HOMA-IR) and sugar levels and lipid profile of the sodium-nitrite treated group were much higher. The sodium nitrite-treated group also had a substantial drop in thyroid hormone concentrations and a rise in Thyroid Stimulated Hormone (TSH), whereas the quercetin alleviated the harmful effects of sodium nitrate by lowering blood sugar, insulin, HOMA-IR,and improved the lipid profile. There was an improvement in glucose, insulin resistance, lipidemia, and TSH hormone levels, which increased as a result of exposure to nitrite. Thus, the present study demonstrated how quercetin protected against sodium nitrite-induced toxicity by improving several biochemical parameters in adult rats.

Diabetes mellitus (DM), an endocrine syndrome characterized by high blood glucose levels due to abrogated insulin activity. The existing treatments for DM have side effects and varying degrees of efficacy. Therefore, it is paramount that novel approaches be developed to enhance the management of DM. Therapeutic plants have been accredited as having comparatively high efficacy with fewer adverse effects. The current study aims to elucidate the phytochemical profile, anti-hyperlipidemic, and anti-diabetic effects of methanolic extract D. salicifolia (leaves) in Alloxan-induced diabetic mice. Alloxan was injected intraperitoneally (150 mg kg-1, b.w), to induced diabetes in mice. The mice were divided into three groups (n=10). Group 1 (normal control) received normal food and purified water, Group II (diabetic control) received regular feed and clean water and group III (diabetic treated) received a methanolic extract of the plant (300 mg kg-1) for 28 days with a typical diet and clean water throughout the experiment. Blood samples were collected to checked serum glucose and concentration of LDL, TC, TG. The extract demonstrated significant antihyperglycemic activity (P<0.05), whereas improvements in mice’s body weight and lipid profiles were observed after treatment with the extract. This study establishes that the extract has high efficacy with comparatively less toxicity that can be used for DM management. © 2024, Instituto Internacional de Ecologia. All rights reserved. Diabetes mellitus (DM) é uma síndrome endócrina caracterizada por níveis elevados de glicose no sangue devido à atividade anulada da insulina. Os tratamentos existentes para o DM têm efeitos colaterais e vários graus de eficácia. Portanto, é fundamental que novas abordagens sejam desenvolvidas para aprimorar o manejo do DM. As plantas terapêuticas foram acreditadas como tendo eficácia comparativamente alta com menos efeitos adversos. O presente estudo visa elucidar o perfil fitoquímico, efeitos anti

Oral antidiabetic drug (OAD) failure is an indication for starting insulin therapy, butthere is still a dilemma as to whether basal insulin or a premixed/co-formulation analog shouldbe the choice. Aim: To compare the safety and efficacy of once daily (OD) insulin degludec/insulin aspart (IDegAsp) to OD insulin glargine (IGlar U100) in insulin-naïve Indian subjectswith type 2 diabetes mellitus (T2DM), inadequately controlled with OADs alone. Setting anddesign: Retrospective study. Methods and material: Data was retrieved from the author’sclinic database of OAD failure patients (18-80 years), who were started either with (IGlar U100,n = 120) or IDegAsp (n = 89) OD over and above the standard of care. Data of fasting plasmaglucose (FPG), postprandial plasma glucose (PPG) and glycated hemoglobin (HbA1c) frombaseline and at last follow-up visits were collected. Statistical analysis used: Baselinecharacteristics and change in study parameters during the follow-up period were computedbetween two groups (IGlar U100 vs. IDegAsp) by unpaired t-test and paired t-test, respectively.ANCOVA test was used to compute percentage reduction in body weight, body mass index(BMI), FPG, PPG and HbA1c in between two groups (IGlar U100 vs. IDegAsp). Results:IDegAsp caused a significantly greater reduction in FPG, PPG and HbA1c as compared tothe IGlar U100 arm. There was no significant difference in the proportion of patients withhypoglycemia between IDegAsp and IGlar U100 groups (p = 0.208). No episodes of severehypoglycemia were reported. Conclusion: Comparison of IDegAsp and IGlar U100 OD inT2DM patients indicated that both were relatively safe but the former controlled FPG andPPG levels more effectively.

Oral antidiabetic drug (OAD) failure is an indication for starting insulin therapy, butthere is still a dilemma as to whether basal insulin or a premixed/co-formulation analog shouldbe the choice. Aim: To compare the safety and efficacy of once daily (OD) insulin degludec/insulin aspart (IDegAsp) to OD insulin glargine (IGlar U100) in insulin-naïve Indian subjectswith type 2 diabetes mellitus (T2DM), inadequately controlled with OADs alone. Setting anddesign: Retrospective study. Methods and material: Data was retrieved from the author’sclinic database of OAD failure patients (18-80 years), who were started either with (IGlar U100,n = 120) or IDegAsp (n = 89) OD over and above the standard of care. Data of fasting plasmaglucose (FPG), postprandial plasma glucose (PPG) and glycated hemoglobin (HbA1c) frombaseline and at last follow-up visits were collected. Statistical analysis used: Baselinecharacteristics and change in study parameters during the follow-up period were computedbetween two groups (IGlar U100 vs. IDegAsp) by unpaired t-test and paired t-test, respectively.ANCOVA test was used to compute percentage reduction in body weight, body mass index(BMI), FPG, PPG and HbA1c in between two groups (IGlar U100 vs. IDegAsp). Results:IDegAsp caused a significantly greater reduction in FPG, PPG and HbA1c as compared tothe IGlar U100 arm. There was no significant difference in the proportion of patients withhypoglycemia between IDegAsp and IGlar U100 groups (p = 0.208). No episodes of severehypoglycemia were reported. Conclusion: Comparison of IDegAsp and IGlar U100 OD inT2DM patients indicated that both were relatively safe but the former controlled FPG andPPG levels more effectively.

OBJECTIVE: To study the impact of vigorous vs. moderate exercise on metabolic parameters in polycystic ovary syndrome (PCOS). DESIGN: Randomized controlled trial. SETTING: Unsupervised home-based exercise program. PATIENTS: Patients with PCOS on the basis of the Rotterdam criteria with insulin resistance. INTERVENTIONS: Participants were block randomized to a home-based exercise program of 75 minutes of vigorous exercise or 150 minutes of moderate exercise per week, for 8 weeks total. MAIN OUTCOME MEASURES: Changes in glucose, insulin, and insulin resistance. RESULTS: In total, 36 participants were randomized, of whom 20 completed the study. The percentage changes from baseline at 4 and 8 weeks for fasting glucose, insulin, and homeostatic model assessment for insulin resistance did not significantly differ between the groups, except for the change in the 8-week glucose level, which was more favorable in the moderate arm (8.06% [standard deviation, 6.44%] in the vigorous group compared with -0.32% [standard deviation, 4.91%] in the moderate group). The absolute values of the main outcomes (fasting glucose, insulin, and homeostatic model assessment for insulin resistance) at baseline and 4 and 8 weeks did not significantly differ between trial arms. When assessing the change from baseline at 4 and 8 weeks, overall and within each trial arm, only the 8-week fasting glucose level was significantly greater than the baseline value in the vigorous arm (93.5 [95% confidence interval, 88.7-98.3] vs. 86.8 [95% confidence interval, 81.1-92.4]). CONCLUSIONS: Unsupervised short-term exercise programs may not achieve significant metabolic improvements in patients with PCOS, regardless of vigorous vs. moderate intensity. Future studies should investigate this question in larger sample sizes and longer or structured exercise programs. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier, NCT02303470.

Insulin-mechanistic target of rapamycin (mTOR) signaling drives anabolic growth during organismal development; its late-life dysregulation contributes to aging and limits lifespans. Age-related regulatory mechanisms and functional consequences of insulin-mTOR remain incompletely understood. Here, we identify LPD-3 as a megaprotein that orchestrates the tempo of insulin-mTOR signaling during C. elegans aging. We find that an agonist insulin, INS-7, is drastically overproduced from early life and shortens lifespan in lpd-3 mutants. LPD-3 forms a bridge-like tunnel megaprotein to facilitate non-vesicular cellular lipid trafficking. Lipidomic profiling reveals increased hexaceramide species in lpd-3 mutants, accompanied by up-regulation of hexaceramide biosynthetic enzymes, including HYL-1. Reducing the abundance of HYL-1, insulin receptor/DAF-2 or mTOR/LET-363, normalizes INS-7 levels and rescues the lifespan of lpd-3 mutants. LPD-3 antagonizes SINH-1, a key mTORC2 component, and decreases expression with age. We propose that LPD-3 acts as a megaprotein brake for organismal aging and that its age-dependent decline restricts lifespan through the sphingolipid-hexaceramide and insulin-mTOR pathways.

Diabetes, a persistent metabolic challenge affecting various organs,are of three primary types—Type 1, Type 2, and Gestational—stemming from intricate interplays of genetics and environment. On a global scale, 537 million adults grapple with diabetes, with India experiencing a growing burden. The vital role of insulin in glucose regulation involves a complex biosynthesis process. Economic hurdles, compounded by soaring insulin prices, call for policy interventions to ensure accessible healthcare. Diverse insulin types cater to distinct patient needs, while biosimilars, like the FDA-approved Semglee, offer affordability. Economic analyses underscore the advantages of biosimilars, highlighting the dynamic landscape of diabetes management and treatment costs.

Diabetes, a persistent metabolic challenge affecting various organs,are of three primary types—Type 1, Type 2, and Gestational—stemming from intricate interplays of genetics and environment. On a global scale, 537 million adults grapple with diabetes, with India experiencing a growing burden. The vital role of insulin in glucose regulation involves a complex biosynthesis process. Economic hurdles, compounded by soaring insulin prices, call for policy interventions to ensure accessible healthcare. Diverse insulin types cater to distinct patient needs, while biosimilars, like the FDA-approved Semglee, offer affordability. Economic analyses underscore the advantages of biosimilars, highlighting the dynamic landscape of diabetes management and treatment costs.

Despite the availability of new classes of glucose-lowering drugs that improve glycaemic levels and minimise long-term complications, at least 20-25% of people with type 2 diabetes require insulin therapy. Moreover, a substantial proportion of these individuals do not achieve adequate metabolic control following insulin initiation. This is due to several factors: therapeutic inertia, fear of hypoglycaemia and/or weight gain, poor communication, complexity of insulin titration, and the number of injections needed, with the associated reduced adherence to insulin therapy. Once-weekly insulins provide a unique opportunity to simplify basal insulin therapy and to allow good glycaemic control with a low risk of hypoglycaemia. Several approaches to developing a stable and effective once-weekly insulin have been proposed, but, to date, insulin icodec and basal insulin Fc (insulin efsitora alfa) are the only two formulations for which clinical studies have been reported. The results of Phase I and II studies emphasise both efficacy (in term of glucose levels) and potential risks and adverse events. Phase III studies involving insulin icodec are reassuring regarding the risk of hypoglycaemia compared with daily basal insulin analogues. Despite some concerns raised in ongoing clinical trials, the available data suggest that weekly insulins may also be an option for individuals with type 1 diabetes, especially when adherence is suboptimal. For the first time there is an opportunity to make an important breakthrough in basal insulin therapy, particularly in people with type 2 diabetes, and to improve not only the quality of life of people with diabetes, but also the practice of diabetologists.

Introduction: Glucagon receptor agonism is currently explored for the treatment of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). The metabolic effects of glucagon receptor agonism may in part be mediated by increases in circulating levels of Fibroblast Growth Factor 21 (FGF21) and Growth Differentiation Factor 15 (GDF15). The effect of glucagon agonism on FGF21 and GDF15 levels remains uncertain, especially in the context of elevated insulin levels commonly observed in metabolic diseases. Methods: We investigated the effect of a single bolus of glucagon and a continuous infusion of glucagon on plasma concentrations of FGF21 and GDF15 in conditions of endogenous low or high insulin levels. The studies included individuals with overweight with and without MASLD, healthy controls (CON) and individuals with type 1 diabetes (T1D). The direct effect of glucagon on FGF21 and GDF15 was evaluated using our in-house developed isolated perfused mouse liver model. Results: FGF21 and GDF15 correlated with plasma levels of insulin, but not glucagon, and their secretion was highly increased in MASLD compared with CON and T1D. Furthermore, FGF21 levels in individuals with overweight with or without MASLD did not increase after glucagon stimulation when insulin levels were kept constant. FGF21 and GDF15 levels were unaffected by direct stimulation with glucagon in the isolated perfused mouse liver. Conclusion: The glucagon-induced secretion of FGF21 and GDF15 is augmented in MASLD and may depend on insulin. Thus, glucagon receptor agonism may augment its metabolic benefits in patients with MASLD through enhanced secretion of FGF21 and GDF15.

Background: Diabetes mellitus, a metabolic illness causing hyperglycemia, is primarily caused by insulin resistance. Melatonin, an indolamine, plays a role in the circadian cycle and affects hunger, fullness, and awareness. Melatonin treatment has shown positive effects on glycated hemoglobin, fasting plasma glucose, and insulin levels, but may increase insulin sensitivity and reduce fasting insulin levels. Methods: This systematic review focused on full-text English literature published between 2014 and 2024 using the PRISMA 2020 guidelines. Editorials and review pieces published in the same journal as the submission without a DOI were not accepted. The literature was compiled using PubMed, ScienceDirect, and SagePub, among other online venues. Result: Our study team initially collected more than 100,000 publications using reliable sources including Science Direct, PubMed, and SagePub. Just five publications were found to be directly related to our ongoing systematic examination after a rigorous three-level screening approach. Subsequently, a comprehensive analysis of the complete text was conducted, and additional scrutiny was given to these articles. To facilitate viewing, Table 1 gathers together the literature that was examined for this analysis. Conclusion: Melatonin, a hormone, can affect glycemic control, obesity control, and energy expenditure. It regulates insulin secretion and protects against reactive oxygen species and free radicals. However, high levels can negatively affect insulin sensitivity.

Background: Diabetes mellitus, a metabolic illness causing hyperglycemia, is primarily caused by insulin resistance. Melatonin, an indolamine, plays a role in the circadian cycle and affects hunger, fullness, and awareness. Melatonin treatment has shown positive effects on glycated hemoglobin, fasting plasma glucose, and insulin levels, but may increase insulin sensitivity and reduce fasting insulin levels. Methods: This systematic review focused on full-text English literature published between 2014 and 2024 using the PRISMA 2020 guidelines. Editorials and review pieces published in the same journal as the submission without a DOI were not accepted. The literature was compiled using PubMed, ScienceDirect, and SagePub, among other online venues. Result: Our study team initially collected more than 100,000 publications using reliable sources including Science Direct, PubMed, and SagePub. Just five publications were found to be directly related to our ongoing systematic examination after a rigorous three-level screening approach. Subsequently, a comprehensive analysis of the complete text was conducted, and additional scrutiny was given to these articles. To facilitate viewing, Table 1 gathers together the literature that was examined for this analysis. Conclusion: Melatonin, a hormone, can affect glycemic control, obesity control, and energy expenditure. It regulates insulin secretion and protects against reactive oxygen species and free radicals. However, high levels can negatively affect insulin sensitivity.

An intravenous glucose-infusion of 0.3 g glucose per Kg body weight was administered over 1 min in nine healthy males with simultaneous blood sampling from the hepatic vein, femoral artery and a peripheral vein. Insulin secretion rates (ISR) were determined by the Eaton method and the ISEC method using C-peptide concentrations from arterial and peripheral venous blood. First phase (0–10 min), second phase (10–60 min), and total insulin secretion (0–60 min) were calculated as the incremental areas (iAUC) above baseline. The primary endpoint was first phase insulin response. The first phase insulin response in artery and venous blood did not differ with the Eaton method (p = 0.25), but was significantly greater with the ISEC method in arterial compared with venous blood (p < 0.05). The first phase insulin responses did not differ between methods in artery (p = 0.73) or venous blood (p = 0.73). The first phase responses of insulin and C-peptide were significant higher in the hepatic vein compared with those in the artery (p < 0.05) and peripheral vein (p < 0.05) but did not differ significantly between the artery compared with the peripheral vein for insulin (p = 0.09) or C-peptide (p = 0.26). Prehepatic insulin secretion rates did not differ between the Eaton and ISEC methods, but with the ISEC method the first phase insulin response was significantly greater in arterial compared with venous blood. The first phase insulin response differs when calculated from plasma insulin or C-peptide and depends on sample sites., An intravenous glucose-infusion of 0.3 g glucose per Kg body weight was administered over 1 min in nine healthy males with simultaneous blood sampling from the hepatic vein, femoral artery and a peripheral vein. Insulin secretion rates (ISR) were determined by the Eaton method and the ISEC method using C-peptide concentrations from arterial and peripheral venous blood. First phase (0–10 min), second phase (10–60 min), and total insulin secretion (0–60 min) were calculated as the incremental areas (iAUC) above baseline. The primary endpoint was first phase insulin response. The first phase insulin response in artery and venous blood did not differ with the Eaton method (p = 0.25), but was significantly greater with the ISEC method in arterial compared with venous blood (p < 0.05). The first phase insulin responses did not differ between methods in artery (p = 0.73) or venous blood (p = 0.73). The first phase responses of insulin and C-peptide were significant higher in the hepatic vein compared with those in the artery (p < 0.05) and peripheral vein (p < 0.05) but did not differ significantly between the artery compared with the peripheral vein for insulin (p = 0.09) or C-peptide (p = 0.26). Prehepatic insulin secretion rates did not differ between the Eaton and ISEC methods, but with the ISEC method the first phase insulin response was significantly greater in arterial compared with venous blood. The first phase insulin response differs when calculated from plasma insulin or C-peptide and depends on sample sites.

Can the mere expectation of drinking a sweeter beverage induce changes in taste perception and blood metabolism? Recent evidence has shown that sweetness perception can be altered by other senses, such as vision, audition, and olfaction. However, it is still unclear whether such crossmodal influences have a physiological basis. The present study examined how subjective mental states, such as the expectation of drinking a sweeter beverage due to colour and odour associations, may influence taste perception and metabolism. Twenty-seven healthy participants consumed two beverages containing identical sucrose and citric acid concentrations but altered in colour and aroma, namely a green, lemon-flavoured beverage and a red, strawberry-flavoured beverage. On average, the strawberry manipulation resulted in significantly higher sweetness ratings and lower sourness ratings compared to the lemon manipulation, although there were clear individual differences in the direction of sweetness enhancement. Blood glucose and insulin levels measured at −15, 0, 10, 20, 30, 45, 60 and 90 min after consumption showed no direct difference between the two beverage conditions. However, we found a significant indirect effect of perceived sweetness on insulin release, whereby consuming the beverage perceived to be sweeter resulted in higher overall levels of insulin release compared to the beverage that was less sweet. These results show a partial role of subjective sweetness perception influencing metabolism in accordance with an anticipatory budging model, suggesting that psychological intervention programs may be important for diabetes and metabolic syndrome management.

CONTEXT: Gut hormones seem to play an important role in postprandial bone turnover, which also may be affected by postprandial plasma glucose excursions and insulin secretion.OBJECTIVE: To investigate the effect of an oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion (IIGI) on bone resorption and formation markers in individuals with type 1 diabetes and healthy controls.METHODS: This observational case-control study, conducted at the Center for Clinical Metabolic Research, Gentofte Hospital, Hellerup, Denmark, included 9 individuals with C-peptide negative type 1 diabetes and 8 healthy controls matched for gender, age, and body mass index. Subjects underwent an OGTT and a subsequent IIGI. We analyzed changes in bone resorption assessed by measurements of carboxy-terminal type I collagen crosslinks (CTX) and in bone formation as assessed by procollagen type I N-terminal propeptide (PINP) concentrations.RESULTS: Baseline CTX and PINP levels were similar in the 2 groups. Both groups exhibited significantly greater suppression of CTX during OGTT than IIGI. PINP levels were unaffected by OGTT and IIGI, respectively, in healthy controls. Participants with type 1 diabetes displayed impaired suppression of CTX-assessed bone resorption and inappropriate suppression of PINP-assessed bone formation during OGTT.CONCLUSION: Our data suggest the existence of a gut-bone axis reducing bone resorption in response to oral glucose independently of plasma glucose excursions and insulin secretion. Subjects with type 1 diabetes showed impaired suppression of bone resorption and reduced bone formation during OGTT, which may allude to the reduced bone mineral density and increased fracture risk characterizing these individuals.

Background: Wholegrain intake is associated with lower risk of cardiometabolic diseases in adults, potentially via changes in the gut microbiota. Although cardiometabolic prevention should start early, we lack evidence on the effects in children. Objectives: This study investigated the effects of wholegrain oats and rye intake on serum low-density lipoprotein (LDL) cholesterol and plasma insulin (coprimary outcomes), other cardiometabolic markers, body composition, gut microbiota composition and metabolites, and gastrointestinal symptoms in children with high body mass index (BMI). Methods: In a randomized crossover trial, 55 healthy Danish 8- to 13-y-olds received wholegrain oats and rye (“WG”) or refined grain (“RG”) products ad libitum for 8 wk in random order. At 0, 8, and 16 wk, we measured anthropometry, body composition by dual-energy absorptiometry, and blood pressure. Fasting blood and fecal samples were collected for analysis of blood lipids, glucose homeostasis markers, gut microbiota, and short-chain fatty acids. Gut symptoms and stool characteristics were determined by questionnaires. Diet was assessed by 4-d dietary records and compliance by plasma alkylresorcinols (ARs). Results: Fifty-two children (95%) with a BMI z-score of 1.5 ± 0.6 (mean ± standard deviation) completed the study. They consumed 108 ± 38 and 3 ± 2 g/d wholegrain in the WG and RG period, which was verified by a profound difference in ARs (P < 0.001). Compared with RG, WG reduced LDL cholesterol by 0.14 (95% confidence interval: −0.24, −0.04) mmol/L (P = 0.009) and reduced total:high-density lipoprotein cholesterol (P < 0.001) and triacylglycerol (P = 0.048) without altering body composition or other cardiometabolic markers. WG also modulated the abundance of specific bacterial taxa, increased plasma acetate, propionate, and butyrate and fecal butyrate and reduced fatigue with no other effects on gut symptoms. Conclusion: High intake of wholegrain oats and rye reduced LDL cho

Introduction: Glucagon receptor agonism is currently explored for the treatment of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). The metabolic effects of glucagon receptor agonism may in part be mediated by increases in circulating levels of Fibroblast Growth Factor 21 (FGF21) and Growth Differentiation Factor 15 (GDF15). The effect of glucagon agonism on FGF21 and GDF15 levels remains uncertain, especially in the context of elevated insulin levels commonly observed in metabolic diseases. Methods: We investigated the effect of a single bolus of glucagon and a continuous infusion of glucagon on plasma concentrations of FGF21 and GDF15 in conditions of endogenous low or high insulin levels. The studies included individuals with overweight with and without MASLD, healthy controls (CON) and individuals with type 1 diabetes (T1D). The direct effect of glucagon on FGF21 and GDF15 was evaluated using our in-house developed isolated perfused mouse liver model. Results: FGF21 and GDF15 correlated with plasma levels of insulin, but not glucagon, and their secretion was highly increased in MASLD compared with CON and T1D. Furthermore, FGF21 levels in individuals with overweight with or without MASLD did not increase after glucagon stimulation when insulin levels were kept constant. FGF21 and GDF15 levels were unaffected by direct stimulation with glucagon in the isolated perfused mouse liver. Conclusion: The glucagon-induced secretion of FGF21 and GDF15 is augmented in MASLD and may depend on insulin. Thus, glucagon receptor agonism may augment its metabolic benefits in patients with MASLD through enhanced secretion of FGF21 and GDF15.

Efficient drug delivery remains a critical challenge for treating neurodegenerative diseases, such as Alzheimer's disease (AD). Using innovative nanomaterials, delivering current medications like acetylcholinesterase inhibitors to the brain through the intranasal route is a promising strategy for managing AD. Here, we developed a unique combinational drug delivery system based on N,N,N-trimethyl chitosan nanoparticles (NPs). These NPs encapsulate rivastigmine, the most potent acetylcholinesterase inhibitor, along with insulin, a complementary therapeutic agent. The spherical NPs exhibited a zeta potential of 17.6 mV, a size of 187.00 nm, and a polydispersity index (PDI) of 0.29. Our findings demonstrate significantly improved drug transport efficiency through sheep nasal mucosa using the NPs compared to drug solutions. The NPs exhibited transport efficiencies of 73.3% for rivastigmine and 96.9% for insulin, surpassing the efficiencies of the drug solutions, which showed transport efficiencies of 52% for rivastigmine and 21% for insulin ex vivo. These results highlight the potential of a new drug delivery system as a promising approach for enhancing nasal transport efficiency. These combinational mucoadhesive NPs offer a novel strategy for the simultaneous cerebral delivery of rivastigmine and insulin, which could prove helpful in developing effective treatments of AD and other neurodegenerative conditions.

Can the mere expectation of drinking a sweeter beverage induce changes in taste perception and blood metabolism? Recent evidence has shown that sweetness perception can be altered by other senses, such as vision, audition, and olfaction. However, it is still unclear whether such crossmodal influences have a physiological basis. The present study examined how subjective mental states, such as the expectation of drinking a sweeter beverage due to colour and odour associations, may influence taste perception and metabolism. Twenty-seven healthy participants consumed two beverages containing identical sucrose and citric acid concentrations but altered in colour and aroma, namely a green, lemon-flavoured beverage and a red, strawberry-flavoured beverage. On average, the strawberry manipulation resulted in significantly higher sweetness ratings and lower sourness ratings compared to the lemon manipulation, although there were clear individual differences in the direction of sweetness enhancement. Blood glucose and insulin levels measured at −15, 0, 10, 20, 30, 45, 60 and 90 min after consumption showed no direct difference between the two beverage conditions. However, we found a significant indirect effect of perceived sweetness on insulin release, whereby consuming the beverage perceived to be sweeter resulted in higher overall levels of insulin release compared to the beverage that was less sweet. These results show a partial role of subjective sweetness perception influencing metabolism in accordance with an anticipatory budging model, suggesting that psychological intervention programs may be important for diabetes and metabolic syndrome management.

Background: Wholegrain intake is associated with lower risk of cardiometabolic diseases in adults, potentially via changes in the gut microbiota. Although cardiometabolic prevention should start early, we lack evidence on the effects in children. Objectives: This study investigated the effects of wholegrain oats and rye intake on serum low-density lipoprotein (LDL) cholesterol and plasma insulin (coprimary outcomes), other cardiometabolic markers, body composition, gut microbiota composition and metabolites, and gastrointestinal symptoms in children with high body mass index (BMI). Methods: In a randomized crossover trial, 55 healthy Danish 8- to 13-y-olds received wholegrain oats and rye (“WG”) or refined grain (“RG”) products ad libitum for 8 wk in random order. At 0, 8, and 16 wk, we measured anthropometry, body composition by dual-energy absorptiometry, and blood pressure. Fasting blood and fecal samples were collected for analysis of blood lipids, glucose homeostasis markers, gut microbiota, and short-chain fatty acids. Gut symptoms and stool characteristics were determined by questionnaires. Diet was assessed by 4-d dietary records and compliance by plasma alkylresorcinols (ARs). Results: Fifty-two children (95%) with a BMI z-score of 1.5 ± 0.6 (mean ± standard deviation) completed the study. They consumed 108 ± 38 and 3 ± 2 g/d wholegrain in the WG and RG period, which was verified by a profound difference in ARs (P < 0.001). Compared with RG, WG reduced LDL cholesterol by 0.14 (95% confidence interval: −0.24, −0.04) mmol/L (P = 0.009) and reduced total:high-density lipoprotein cholesterol (P < 0.001) and triacylglycerol (P = 0.048) without altering body composition or other cardiometabolic markers. WG also modulated the abundance of specific bacterial taxa, increased plasma acetate, propionate, and butyrate and fecal butyrate and reduced fatigue with no other effects on gut symptoms. Conclusion: High intake of wholegrain oats and rye reduced LDL cho

Diabetes, a persistent metabolic challenge affecting various organs,are of three primary types—Type 1, Type 2, and Gestational—stemming from intricate interplays of genetics and environment. On a global scale, 537 million adults grapple with diabetes, with India experiencing a growing burden. The vital role of insulin in glucose regulation involves a complex biosynthesis process. Economic hurdles, compounded by soaring insulin prices, call for policy interventions to ensure accessible healthcare. Diverse insulin types cater to distinct patient needs, while biosimilars, like the FDA-approved Semglee, offer affordability. Economic analyses underscore the advantages of biosimilars, highlighting the dynamic landscape of diabetes management and treatment costs.

This paper will review the effect of aging on glucose metabolism and insulin resistance in pancreas and in peripheral tissues and how melatonin administration could affect these parameters. In SAMP8 mice insulin levels in plasma were found to be increased together with enhanced HOMA-IR values, whereas insulin content in pancreas showed a decrease with aging. Aging in SAMP8 mice was also associated with a significant increase in the relative expression of both protein and mRNA of different pro-inflammatory mediators. Furthermore, aging was associated with a decrease in the expression of Pdx-1, FoxO 1 and FoxO 3A and Sirt 1 in pancreas SAMP8 samples. Melatonin administration was able to reduce these age-related alterations, decreasing plasma insulin levels and increasing its pancreatic content in SAMP8 mice. HOMA-IR was decreased with melatonin treatment in all animals. Conversely, in SAMP8 mice, melatonin treatment decreased the expression of glucagon, GLUT2, somatostatin and insulin. Furthermore it was also able to increase the expression of Sirt 1, Pdx-1 and FoxO 3A. The present study has shown that aging is associated with significant alterations in the relative expression of pancreatic genes involved in both insulin secretion and glucose metabolism and that these are associated with an increase in inflammation and oxidative stress. Melatonin administration was able to reduce oxidative stress and inflammation and thus to improve pancreatic function in old mice. By doing so, insulin resistance is diminished and plasma insulin is reduced, enhancing insulin pancreatic content and reducing plasma glucose levels and HOMA index., Instituto de Salud Carlos III, Junta de Andalucía, Fondo de Investigaciones Sanitarias de la Seguridad Social, Depto. de Fisiología, Fac. de Medicina, TRUE, pub

Digestible carbohydrates differ in glycaemic response, therewith having the potential to influence metabolic conditions such as insulin resistance and diabetes mellitus. Isomaltulose has been proven to lower the glycaemic response in humans, which to date has not been studied in dogs. Therefore, the aim of the present study was to characterise the digestibility, as well as the physiological effects of isomaltulose in dogs, in comparison to other saccharides. To this end, three studies were performed. Study 1 was an in vitro study, evaluating the small intestinal hydrolysis of isomaltulose compared to other relevant carbohydrate sources. Three of these saccharides, having close and low-moderate degrees of hydrolysis by brush border enzymes, were also evaluated in vivo for their glycaemic effects by measuring plasma levels of glucose, insulin and glucagon-like peptide 1 (GLP-1) 0-180 min after administration of a single dosage after an overnight fast (i.e., isomaltulose, sucrose and maltodextrin in a 3 × 3 Latin-square design, in 9 dogs, Study 2). To understand if digestive enzymes, underlying glycaemic responses for isomaltulose and sucrose can be upregulated, we exposed dogs to these saccharides for 2 weeks and repeated the measurements after an overnight fast in 18 dogs (Study 3). Isomaltulose was hydrolysed by intestinal enzyme preparation from all three dogs, but the degrading activity was low (e.g., 3.95 ± 1.03 times lower vs. sucrose), indicating a slower rate of hydrolysis. Isomaltulose had a low glycaemic response, in line with in vitro data. In vitro hydrolysis of sucrose was comparable or even higher than maltodextrin in contrast to the more pronounced glycaemic response to maltodextrin observed in vivo. The numerically higher blood glucose response to sucrose after continuous consumption, might indicate an adaptive response. In conclusion, the current work provides valuable insights into the digestion physiology of various saccharides in dogs. Further i

Fibroblast growth factors (FGFs) are involved in numerous metabolic processes. The endocrine subfamily of FGFs, consisting of FGF19, FGF21, and FGF23, might have beneficial effects in the treatment of diabetes mellitus (DM) and/or obesity. The analog with the greatest potential, FGF21, lowers blood glucose levels, improves insulin sensitivity, and induces weight loss in several animal models. In this review we summarize recent (pre)clinical findings with FGF21 analogs in animal models and men. Furthermore, possible applications of FGF21 analogs for pets with DM will be discussed. As currently, information about the use of FGF21 analogs in pet animals is scarce.

The liver circadian clock plays a pivotal role in driving metabolic rhythms, being primarily entrained by the feeding schedule, although the underlying mechanisms remain elusive. This study aimed to investigate the potential role of insulin as an intake signal mediating liver entrainment in fish. To achieve this, the expression of clock genes, which form the molecular basis of endogenous oscillators, was analyzed in goldfish liver explants treated with insulin. The presence of insulin directly increased the abundance of per1a and per2 transcripts in the liver. The dependency of protein translation for such insulin effects was evaluated using cycloheximide, which revealed that intermediate protein translation is seemingly unnecessary for the observed insulin actions. Furthermore, the putative interaction between insulin and glucocorticoid signaling in the liver was examined, with the results suggesting that both hormones exert their effects by independent mechanisms. Finally, to investigate the specific pathways involved in the insulin effects, inhibitors targeting PI3K/AKT and MEK/ERK were employed. Notably, inhibition of PI3K/AKT pathway prevented the induction of per genes by insulin, supporting its involvement in this process. Together, these findings suggest a role of insulin in fish as a key element of the multifactorial system that entrains the liver clock to the feeding schedule., Ministerio de Ciencia e Innovación (España), Xunta de Galicia, Universidad Complutense de Madrid, Depto. de Genética, Fisiología y Microbiología, Fac. de Ciencias Biológicas, TRUE, pub

Type 1 diabetes (T1D) is the most frequent form of diabetes in pediatric age, affecting more than 1.5 million people younger than age 20 years worldwide. Early and intensive control of diabetes provides continued protection against both microvascular and macrovascular complications, enhances growth, and ensures normal pubertal development. In the absence of definitive reversal therapy for this disease, achieving and maintaining the recommended glycemic targets is crucial. In the last 30 years, enormous progress has been made using technology to better treat T1D. In spite of this progress, the majority of children, adolescents and young adults do not reach the recommended targets for glycemic control and assume a considerable burden each day. The development of promising new therapeutic advances, such as more physiologic insulin analogues, pioneering diabetes technology including continuous glucose monitoring and closed loop systems as well as new adjuvant drugs, anticipate a new paradigm in T1D management over the next few years. This review presents insights into current management of T1D in youths.

OBJECTIVE: We evaluated the performance of the iLet bionic pancreas (BP) in non-Hispanic White individuals (here referred to as Whites) and in Black, Hispanic, and other individuals (here collectively referred to as Minorities). RESEARCH DESIGN AND METHODS: A multicenter, randomized controlled trial evaluated glycemic management with the BP versus standard of care (SC) in 161 adult and 165 pediatric participants with type 1 diabetes over 13 weeks. RESULTS: In Whites (n = 240), the mean baseline-adjusted difference in 13-week HbA1c between the BP and SC groups was -0.45% (95% CI -0.61 to -0.29 [-4.9 mmol/mol; -6.6 to -3.1]; P < 0.001), while this difference among Minorities (n = 84) was -0.53% (-0.83 to -0.24 [-6.0 mmol/mol; -9.2 to -2.8]; P < 0.001). In Whites, the mean baseline-adjusted difference in time in range between the BP and SC groups was 10% (95% CI 7-12; P < 0.001) and in Minorities was 14% (10-18; P < 0.001). CONCLUSIONS: The BP improves glycemic control in both Whites and Minorities and offers promise in decreasing health care disparities.

ObjectiveChronic kidney disease (CKD) is associated with decreased anabolic response to insulin contributing to protein-energy wasting. Targeted metabolic profiling of oral glucose tolerance testing (OGTT) may help identify metabolic pathways contributing to disruptions to insulin response in CKD.MethodsUsing targeted metabolic profiling, we studied the plasma metabolome response in 41 moderate-to-severe nondiabetic CKD patients and 20 healthy controls at fasting and 2 hours after an oral glucose load. We used linear mixed modeling with random intercepts, adjusting for age, gender, race/ethnicity, body weight, and batch to assess heterogeneity in response to OGTT by CKD status.ResultsMean estimated glomerular filtration rate among CKD participants was 38.9 ± 12.7 mL/min per 1.73 m2 compared to 87.2 ± 17.7 mL/min per 1.73 m2 among controls. Glucose ingestion induced an anabolic response resulting in increased glycolysis products and a reduction in a wide range of metabolites including amino acids, tricarboxylic acid cycle intermediates, and purine nucleotides compared to fasting. Participants with CKD demonstrated a blunted anabolic response to OGTT evidenced by significant changes in 13 metabolites compared to controls. The attenuated metabolome response predominant involved mitochondrial energy metabolism, vitamin B family, and purine nucleotides. Compared to controls, CKD participants had elevated lactate:pyruvate (L:P) ratio and decreased guanosine diphosphate:guanosine triphosphate ratio during OGTT.ConclusionMetabolic profiling of OGTT response suggests a broad disruption of mitochondrial energy metabolism in CKD patients. These findings motivate further investigation into the impact of insulin sensitizers and mitochondrial targeted therapeutics on energy metabolism in patients with nondiabetic CKD.

The study was designed to determine whether urocortin 2 (Ucn2) gene transfer is as safe and effective as metformin in insulin-resistant mice. Four groups of insulin-resistant db/db mice and a nondiabetic group were studied: (1) metformin; (2) Ucn2 gene transfer; (3) metformin + Ucn2 gene transfer; (4) saline; and (5) nondiabetic mice. After completion of the 15-week protocol, glucose disposal was quantified, safety assessed, and gene expression documented. Ucn2 gene transfer was superior to metformin, providing reductions in fasting glucose and glycated hemoglobin and enhanced glucose tolerance. The combination of metformin + Ucn2 gene transfer provided no better glucose control than Ucn2 gene transfer alone and was not associated with hypoglycemia. Metformin alone, Ucn2 gene transfer alone, and metformin + Ucn2 gene transfer together reduced fatty infiltration of the liver. Serum alanine transaminase concentration was elevated in all db/db groups (vs. nondiabetic controls), but the metformin + Ucn2 gene transfer combined group had the lowest alanine transaminase levels. No group differences in fibrosis were detected. In a hepatoma cell line, activation of AMP kinase showed a rank order of combined metformin + Ucn2 peptide > Ucn2 peptide > metformin. We conclude (1) The combination of metformin + Ucn2 gene transfer does not result in hypoglycemia. (2) Ucn2 gene transfer alone provides superior glucose disposal versus metformin alone. (3) The combination of Ucn2 gene transfer and metformin is safe and has additive effects in reducing serum alanine transaminase concentration, activating AMP kinase activity, and increasing Ucn2 expression, but is no more efficacious than Ucn2 gene transfer alone in reducing hyperglycemia. These data indicate that Ucn2 gene transfer is more effective than metformin in the db/db model of insulin resistance and combined treatment with metformin + Ucn2 gene transfer appears to have favorable effects on liver function and Ucn2 express

Olahraga saat kehamilan diketahui dapat mengurangi kelelahan dan nyeri saat kontraksi persalinan karena adanya pelepasan β-endorfin yang berperan sebagai inhibitor respon nyeri (analgesik). β-endorfin juga terbukti mengurangi kelelahan pada otot dan meningkatkan uptake glucose. Sementara itu, insulin telah diketahui juga berperan dalam uptake glucose ke dalam sel. Penelitian experimental menggunakan uji insiliko ini bertujuan untuk mengetahui apakah kerja β-endorfin dalam hal ini melalui ikatan pada reseptor insulin dan untuk mengetahui nilai kekuatan dari ikatan β-endorfin pada reseptor insulin dibandingkan dengan ikatan insulin pada reseptor insulin, sehingga dapat mengetahui efek sinergitas ikatan β-endorfin pada reseptor insulin, dan perannya dalam meningkatkan uptake glucose. Hasil penelitian menunjukan terdapat dua model ikatan β-endorfin pada reseptor insulin dengan asam amino yang sama terlibat dalam ikatan insulin, dengan kekuatan ikatan β-endorfin dengan reseptor insulin yang lebih kuat dibandingkan ikatan antara insulin dengan reseptornya.

Mounting evidence links Type 1 diabetes (T1D) with cognitive dysfunction, psychiatric disorders, and synaptic alterations; however, the underlying mechanism remains unclear. Numerous synaptic proteins and synaptic adhesion molecules (SAMs) that orchestrate synaptic formation, restructuring, and elimination are essential for proper brain function. Currently, it is unclear whether the pathogenesis of T1D is related to the expression of synaptic proteins and SAMs. Here, we investigated whether T1D mice exhibited altered synaptic protein and SAM expression in the hippocampus and cortex. We discovered that T1D mice exhibited partially decreased levels of excitatory and inhibitory synapse proteins and SAMs, such as neurexins, neuroligins, and synaptic cell adhesion molecules. We also found that compared to control mice, T1D mice showed a marginal decrease in body weight and a significant increase in plasma glycoalbumin levels (a hyperglycemia marker). These results provide novel molecular-level insights into synaptic dysfunction in mice with T1D.

Background: To study and find the efficacy of circuit weight training on exercise tolerance in type 2 diabetes mellitus subjects. Methods: Ethical clearance was taken from the Institutional Ethical Committee. This study was carried out by analysing total 30 subjects with type 2 DM between the age group of 45 TO 55 years. The participants were divided into experimental and control group by random sampling. The experimental group was given circuit weight exercising for 8 weeks 3-4 times a week for 45-50 minutes. Borg’s scale was used to check the exercise tolerance before and after the intervention. Result: There was an observed increase in the mean exercise tolerance parameters of the exercise group at the end of the 8 weeks. Statically the patients who were given circuit weight training showed there was extremely significant difference (p<0.0002) whereas in the control group it was not significant (p value0.4716). There was a considerable decrease in the systolic blood pressure of the exercise group and the control group remained steady. There was a considerable decrease in the mean heart rate of the exercise group and the control group remained steady. Conclusion: This study concludes that circuit weight exercise 2-3 times a week is useful to improve the exercise tolerance. It also prevents further complications and helps improve the quality of life. It also reduces the risk of cardiovascular diseases.

Background: To study and find the efficacy of circuit weight training on exercise tolerance in type 2 diabetes mellitus subjects. Methods: Ethical clearance was taken from the Institutional Ethical Committee. This study was carried out by analysing total 30 subjects with type 2 DM between the age group of 45 TO 55 years. The participants were divided into experimental and control group by random sampling. The experimental group was given circuit weight exercising for 8 weeks 3-4 times a week for 45-50 minutes. Borg’s scale was used to check the exercise tolerance before and after the intervention. Result: There was an observed increase in the mean exercise tolerance parameters of the exercise group at the end of the 8 weeks. Statically the patients who were given circuit weight training showed there was extremely significant difference (p<0.0002) whereas in the control group it was not significant (p value0.4716). There was a considerable decrease in the systolic blood pressure of the exercise group and the control group remained steady. There was a considerable decrease in the mean heart rate of the exercise group and the control group remained steady. Conclusion: This study concludes that circuit weight exercise 2-3 times a week is useful to improve the exercise tolerance. It also prevents further complications and helps improve the quality of life. It also reduces the risk of cardiovascular diseases.

IntroductionInsulin is a high-risk medication, and errors can lead to patient morbidity and mortality. The American Board of Pediatrics recommends that all board-certified pediatricians be able to develop an insulin management plan for patients with diabetes. A needs assessment of pediatric residents revealed low self-efficacy at developing a new subcutaneous insulin plan despite didactic instruction on the topic.MethodsWe created a 90-minute interactive workshop that targeted resident skills in devising subcutaneous insulin plans. Learners engaged in small-group, problem-based learning and peer teaching to promote active learning and participation. We compared self-efficacy and knowledge before and after the intervention using paired t tests and evaluated learner satisfaction.ResultsTwenty-eight pediatric interns participated, with 25 completing both the pre- and postworkshop surveys. The primary outcome was self-efficacy (an individual's confidence in the ability to perform a specific task in a given domain). There was a statistically significant improvement in self-efficacy at creating a new subcutaneous insulin plan ( p < .001) as well as knowledge ( p < .001) after course completion. Learners were highly satisfied with the course, with a mean overall conference quality rating of 4.8 (SD = 0.4) based on a 5-point Likert scale (1 = poor, 5 = outstanding).DiscussionAn interactive workshop employing active learning methods resulted in improved self-efficacy and knowledge in first-year pediatric residents. Future work is needed to determine the impact of this workshop on patient care outcomes.