Culturally adapted mobile application for optimizing metabolic control in type 1 diabetes: a pilot study / Aplicación móvil adaptada desde el punto de vista cultural para optimizar el control metabólico en la diabetes tipo 1: estudio piloto / Aplicativo móvel culturalmente adaptado para otimizar o controle metabólico do diabetes tipo 1: estudo-piloto

[ABSTRACT]. Objective. To evaluate whether use of a culturally adapted mobile application (app) for adolescents with type 1 diabetes is associated with improved metabolic control. Methods. The Dominican Republic’s National Institute of Diabetes, Endocrinology, and Nutrition and the Learning to Live clinic recruited 23 pediatric participants for the study. Blood tests were performed before and after use of the app for a period of 3 months. Based on the user profile, participants were encouraged to use the app’s bolus insulin calculator after each meal. The app included a list of regionally and culturally specific foods, color-coded to indicate a high glycemic index (GI) as red; medium GI as yellow; and low GI as green. The color-coding was designed to assist participants in making healthier eating choices. Results. There were statistically significant improvements in lipid profile. Mean high-density lipoprotein values rose to acceptable levels, while low-density lipoproteins and triglyceride levels fell to the recommended values. The overall quality of life increased, although glycated hemoglobin levels showed no statistically significant changes. Conclusion. The findings of this study suggest that using this culturally tailored app can help young patients with type 1 diabetes to improve metabolic health.

[RESUMEN]. Objetivo. Evaluar si el uso de una aplicación móvil (app) para adolescentes con diabetes tipo 1, adaptada desde el punto de vista cultural, se asocia a una mejora del control metabólico. Métodos. El Instituto Nacional de Diabetes, Endocrinología y Nutrición de República Dominicana y Learning to Live Clinic reclutaron a 23 participantes pediátricos para el estudio. Se realizaron análisis de sangre antes y después de utilizar la aplicación durante un período de 3 meses. En función del perfil de usuario, se alentó a los participantes a utilizar la calculadora del bolo de insulina de la aplicación después de cada comida. La aplicación incluía una lista de alimentos propios de la región y la cultura, codificados por colores para indicar un índice glucémico (IG) alto (rojo), medio (amarillo) o bajo (verde). El código de colores se diseñó para ayudar a los participantes a adoptar opciones de alimentación más saludables. Resultados. Se observaron mejoras estadísticamente significativas en el perfil lipídico. Los valores medios de las lipoproteínas de alta densidad aumentaron hasta niveles aceptables, mientras que los niveles de las lipoproteínas de baja densidad y los triglicéridos descendieron hasta los valores recomendados. Se observó una mejora en la calidad de vida general, si bien no se observaron cambios estadísticamente significativos en los niveles de hemoglobina glucosilada. Conclusiones. Los resultados de este estudio sugieren que el uso de esta aplicación adaptada desde el punto de vista cultural puede ayudar a los pacientes jóvenes con diabetes mellitus tipo 1 a mejorar su salud metabólica.

[RESUMO]. Objetivo. Avaliar se o uso de um aplicativo móvel culturalmente adaptado para adolescentes com diabetes tipo 1 está associado a um melhor controle metabólico. Métodos. O Instituto Nacional de Diabetes, Endocrinologia e Nutrição da República Dominicana e a clínica Learning to Live recrutaram 23 participantes pediátricos para o estudo. Foram realizados exames de sangue antes e depois do uso do aplicativo por um período de 3 meses. Com base no perfil de usuário, os participantes foram incentivados a usar a calculadora de bolus de insulina do aplicativo após cada refeição. O aplicativo incluía uma lista de alimentos específicos da região e da cultura, codificados por cores para indicar índices glicêmicos (IG) altos em vermelho; IG médios em amarelo; e IG baixos em verde. O código de cores foi criado para ajudar os participantes a fazer escolhas alimentares mais saudáveis. Resultados. Houve melhoras estatisticamente significantes no perfil lipídico. Os valores médios de lipoproteínas de alta densidade subiram para níveis aceitáveis, e os níveis de lipoproteínas de baixa densidade e de triglicerídeos caíram para os valores recomendados. A qualidade de vida geral aumentou, embora os níveis de hemoglobina glicada não tenham apresentado alterações estatisticamente significantes. Conclusão. Os resultados deste estudo sugerem que o uso desse aplicativo culturalmente adaptado pode ajudar pacientes jovens com diabetes tipo 1 a melhorar sua saúde metabólica.

Age-related differences in fluctuations in insulin resistance evaluated with HOMA-IR and triglyceride and glucose-based indices during the menstrual cycle, as determined using the NHANES cross-sectional dataset.

OBJECTIVES: To determine how age affects insulin resistance during the menstrual cycle and insulin resistance-associated indices: the Triglyceride-glucose and Triglyceride-glucose-BMI indexes. METHODS: This prospective observational study used fasting plasma glucose, fasting insulin, triglycerides, body mass index (BMI), and days since the start of the menstrual period collected from the NHANES dataset (1999-2006). Insulin resistance was determined using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The participants were categorized as young (16-34 years) or older (>35 years). Rhythmicity during the menstrual cycle was analyzed using the Cosinor and Cosinor2 packages for R. MAIN OUTCOME MEASURES: Cosine fit curves for insulin resistance during the menstrual cycle and age-associated effects on rhythmicity. RESULTS: Using 1256 participants, rhythmicity was observed for fasting insulin and HOMA-IR (p < 0.05) but not for fasting plasma glucose, the Triglyceride-glucose index, or the Triglyceride-glucose-BMI index. Significant amplitudes for fasting insulin and HOMA-IR were observed when age was considered. Acrophases for fasting insulin and HOMA-IR were significant only for the younger group, and the differences between these groups were significant, suggesting that the changes in scores for insulin resistance for the younger and older groups occur at different times of their menstrual cycle. CONCLUSIONS: Insulin resistance does fluctuate during the menstrual cycle, and it is at a maximum at different times for younger and older women. Since these results are unadjusted, this study is preliminary and further investigation is required.

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.

Proteins and Peptides Studied In Silico and In Vivo for the Treatment of Diabetes Mellitus: A Systematic Review.

Bioinformatics has expedited the screening of new efficient therapeutic agents for diseases such as diabetes mellitus (DM). The objective of this systematic review (SR) was to understand naturally occurring proteins and peptides studied in silico and subsequently reevaluated in vivo for treating DM, guided by the question: which peptides or proteins have been studied in silico for the treatment of diabetes mellitus? The RS protocol was registered in the International Prospective Register of Systematic Reviews database. Articles meeting the eligibility criteria were selected from the PubMed, ScienceDirect, Scopus, Web of Science, Virtual Health Library (VHL), and EMBASE databases. Five studies that investigated peptides or proteins analyzed in silico and in vivo were selected. Risk of bias assessment was conducted using the adapted Strengthening the Reporting of Empirical Simulation Studies (STRESS) tool. A diverse range of assessed proteins and/or peptides that had a natural origin were investigated in silico and corresponding in vivo reevaluation demonstrated reductions in glycemia and/or insulin, morphological enhancements in pancreatic ß cells, and alterations in the gene expression of markers associated with DM. The in silico studies outlined offer crucial insights into therapeutic strategies for DM, along with promising leads for screening novel therapeutic agents in future trials.

Acute Effects of Dietary Protein Consumption on the Postprandial Metabolic Response, Amino Acid Levels and Circulating MicroRNAs in Patients with Obesity and Insulin Resistance.

The post-nutritional intervention modulation of miRNA expression has been previously investigated; however, post-acute dietary-ingestion-related miRNA expression dynamics in individuals with obesity and insulin resistance (IR) are unknown. We aimed to determine the acute effects of protein ingestion from different dietary sources on the postprandial metabolic response, amino acid levels, and circulating miRNA expression in adults with obesity and IR. This clinical trial included adults with obesity and IR who consumed (1) animal-source protein (AP; calcium caseinate) or (2) vegetable-source protein (VP; soy protein isolate). Glycaemic, insulinaemic, and glucagon responses, amino acid levels, and exosomal microRNAs isolated from plasma were analysed. Post-AP ingestion, the area under the curve (AUC) of insulin (p = 0.04) and the plasma concentrations of branched-chain (p = 0.007) and gluconeogenic (p = 0.01) amino acids increased. The effects of different types of proteins on the concentration of miRNAs were evaluated by measuring their plasma circulating levels. Compared with the baseline, the AP group presented increased circulating levels of miR-27a-3p, miR-29b-3p, and miR-122-5p (p < 0.05). Subsequent analysis over time at 0, 30, and 60 min revealed the same pattern and differences between treatments. We demonstrated that a single dose of dietary protein has acute effects on hormonal and metabolic regulation and increases exosomal miRNA expression in individuals with obesity and IR.

Effects of acute consumption of a beverage based on extruded whole-grain pearl millet flour on glycemic and insulinemic control, food intake, and appetite sensation in eutrophic adults: A randomized cross-over clinical trial.

OBJECTIVES: Whole-grain pearl millet is a nutritious cereal source of dietary fiber, vitamins, minerals, and bioactive compounds. It offers health benefits such as glycemic control and satiety. Extrusion cooking for diverse formulations, including beverages, can alter its chemical composition, impacting the nutritional value. This study aimed to evaluate the sensory acceptability of an extruded millet flour beverage and its acute effects on glycemic index (GI), glycemic and insulinemic response, food intake, and subjective appetite sensations in euglycemic and eutrophic adults. METHODS: This is an acute, single-blind, randomized, controlled, cross-over clinical study comprising 14 euglycemic and eutrophic adults. Initially, beverages based on whole extruded millet flour were developed, and sensorially and chemically analyzed. Next, a clinical trial was conducted with participants undergoing four sessions and consuming one of the following options: extruded millet beverage, a maltodextrin control beverage, or a glucose solution administered in two separate sessions. Blood glucose, insulin, and appetite responses were assessed over a 2-h period, in addition to determining the GI of the beverages and analyzing food intake in the 24 h following each session. RESULTS: The extruded millet flour strawberry-flavored beverage had the best sensory acceptance and was classified as having as high GI. Consumption of the extruded millet beverage showed similar glycemic and insulinemic responses, as well as appetite control and food intake of the subjects, when compared with consumption of the maltodextrin control beverage. CONCLUSIONS: Intake of the extruded millet beverage maintained glycemic and insulinemic responses, appetite control, and food intake in euglycemic and eutrophic subjects.

Effects of topical insulin on second-degree burn wound healing: brief report.

BACKGROUND: Burns are classified according to their mechanism of injury, depth, affected body area, affected region or part of the body, and extent of the lesions. Topical insulin modulates the healing process. However, studies evaluating the effects of topical insulin treatment on burns in human patients are lacking. PURPOSE: The purpose of this study was to investigate the effects of topical insulin on healing time of second-degree burns. METHODS: In this nonrandomized clinical trial, patients with second-degree burns were allocated to a control group (CG) or an intervention group (IG) in which wounds were treated with 1% silver sulfadiazine and topical insulin, respectively. RESULTS: Healing time was significantly shorter in the IG relative to the CG (9.1 ± 1.9 days and 12.7 ± 3.3 days, respectively; P < .05). The estimated burn area was similar in both groups (CG 1.44 ± 1.0%; IG 1.42 ± 0.53%). CONCLUSION: In this study, topical insulin reduced healing time in second-degree burns. Further investigation is warranted to support wider use in clinical practice.

Acute Consumption of Cooked Green Banana Pulp Beverage (Musa cavendishii) Decreases Plasma Glucose in Healthy Women: A Cross-Sectional Controlled Study.

This study aimed at comparing the carbohydrate composition of three banana varieties (cv. Nanica, Nanicão, and Prata) and investigating the effect of a single dose of cooked green banana pulp beverage (GBPd) on plasma glycemic homeostasis indexes (glucose, PYY, GIP, insulin) and hunger and satiety sensation (visual analog scale-VAS). The bananas were classified according to the color scale. The fiber, total carbohydrate, and resistant starch (RS) were determined using validated methods. Glucose homeostasis indexes and hunger/satiety sensation were determined in ten healthy women in two stages before and after intake: (1) glucose solution (250 g/L); (2) one week later, consumption of the glucose solution plus 75 g/L of GBPd. Blood samples were collected twice in stage-1 and every 15 min for 2 h in stage-2. Cv. Nanicão was selected, because it presented a higher content in RS and dietary fiber on dry base than the other cultivars. Thus, it was used to test glycemic response. After 2 h of GBPd intake, no difference was observed in hunger/satiety sensation and plasma glycemic homeostasis indexes, except for a decrease in plasma glucose concentration (-15%, p = 0.0232) compared to stage-1. These results suggest that cv. Nanicão has a higher potential as a functional ingredient and can influence the reduction in the glycemic index of a meal compared to other cultivars. However, it had not a short-term effect on hormones GIP and PYY in healthy women. Further research is needed to understand the long-term effects and mechanisms of green banana on glycemic control and satiety.

Effect of Early Time-Restricted Eating on Metabolic Markers and Body Composition in Individuals with Overweight or Obesity.

This study aimed to evaluate the effect of early time-restricted eating (eTRE) on metabolic markers and body composition in individuals with overweight or obesity. Seventeen subjects completed a randomized, crossover, and controlled clinical trial. Twelve women and five men participated, with a mean age of 25.8 ± 10.0 years and a BMI of 32.0 ± 6.3 kg/m2. The eTRE intervention included 16 h of fasting (3:00 pm to 7:00 am) and 8 h of ad libitum eating (7:00 am to 03:00 pm) (16:8). The trial included four weeks of interventions followed by a four-week washout period. Body weight, waist and hip circumferences, and body composition measurements were taken. Additionally, a venous blood sample was collected for biochemical determinations. In a before-after analysis, eTRE induced a reduction in BW and BMI in women but this was not significant when compared to the control group. eTRE did not modify any other anthropometric measurements, fasting biochemical parameters, glycemic and insulinemic responses, blood pressure, or subjective appetite. In conclusion, eTRE did not induce beneficial effects on the glycemic and lipid metabolisms, body composition, subjective appetite, or blood pressure. These findings may be attributed to the special characteristics of the population and the short intervention period.

The effect of serum biochemical parameters on clinical prognosis in children presenting with diabetic ketoacidosis.

OBJECTIVE: The aim of this study was to determine whether diabetes mellitus has a high risk of diabetic ketoacidosis-related complications. Biochemical parameters affect the resolution time of diabetic ketoacidosis. METHODS: The present study is based on a retrospective evaluation of the records of patients who presented to the Pediatrics Clinic of Adiyaman University Hospital between January 1, 2017, and October 1, 2022, with a diagnosis ofdiabetic ketoacidosis. The demographic characteristics, serum biochemical parameters, blood gas results, and time to transition to subcutaneous insulin therapy were all recorded. RESULTS: This study included 49 (49%) female and 51 (51%) male patients aged 1-17 years (mean age: 9.05±4.33 years). The average time to clinical improvement of the sample, that is, transition to subcutaneous insulin therapy, was 21.04±7.8 h. An evaluation of the presence of acute kidney injury based on serum urea and creatinine levels and eGFR values revealed no significant effect on the rate of clinical recovery (respective p-values: p=0.076, p=0.494, and p=0.884). A univariate analysis identified blood glucose (p=0.025), blood gas pH (p<0.001), and blood bicarbonate (p=0.004) values as prognostic factors, while a multivariate analysis revealed pH values had an independent and significant effect on the resolution time of diabetic ketoacidosis. CONCLUSION: Serum glucose, pH, and bicarbonate levels are the most important determinants of clinical prognosis in patients with diabetic ketoacidosis. These findings can serve as a guide for clinicians in the follow-up and treatment of such patients.

Exploring the Therapeutic Potential of Benfotiamine in a Sporadic Alzheimer's-Like Disease Rat Model: Insights into Insulin Signaling and Cognitive function.

Alzheimer's disease (AD) is a complex neurodegenerative process, also considered a metabolic condition due to alterations in glucose metabolism and insulin signaling pathways in the brain, which share similarities with diabetes. This study aimed to investigate the therapeutic effects of benfotiamine (BFT), a vitamin B1 analog, in the early stages of the neurodegenerative process in a sporadic model of Alzheimer's-like disease induced by intracerebroventricular injection of streptozotocin (STZ). Supplementation with 150 mg/kg of BFT for 7 days reversed the cognitive impairment in short- and long-term memories caused by STZ in rodents. We attribute these effects to BFT's ability to modulate glucose transporters type 1 and 3 (GLUT1 and GLUT3) in the hippocampus, inhibit GSK3 activity in the hippocampus, and modulate the insulin signaling in the hippocampus and entorhinal cortex, as well as reduce the activation of apoptotic pathways (BAX) in the hippocampus. Therefore, BFT emerges as a promising and accessible intervention in the initial treatment of conditions similar to AD.

Influence of Seropositivity against Adenovirus-36 on the Risk of Obesity and Insulin Resistance in the Child Population of Southern Chile.

Background: Previous infection with Adenovirus-36 (HAdv-D36) has been associated with adipogenesis and glycemic regulation in cell culture and animal models. In humans, HAdv-D36 antibodies correlate with increased obesity risk yet paradoxically enhance glycemic control across various demographics. This study assesses the association of HAdv-D36 seropositivity with obesity, lipid, and glycemic profiles among school-aged children. Methods: We evaluated 208 children aged 9-13, categorized by BMI z-scores into normal weight (-1 to +1), overweight (+1 to +2), and obese (>+3). Assessments included anthropometry, Tanner stage for pubertal development, and biochemical tests (relating to lipids, glucose, and insulin), alongside HAdv-D36 seropositivity checked via ELISA. Insulin resistance was gauged using Chilean pediatric criteria. Results: The cohort displayed a high prevalence of overweight/obesity. HAdv-D36 seropositivity was 5.4%, showing no correlation with nutritional status. Additionally, no link between HAdv-D36 seropositivity and lipid levels was observed. Notably, insulin levels and HOMA-RI were significantly lower in HAdv-D36 positive children (p < 0.001). No cases of insulin resistance were reported in the HAdv-D36 (+) group in our population. Conclusions: HAdv-D36 seropositivity appears to decrease insulin secretion and resistance, aligning with earlier findings. However, no association with obesity development was found in the child population of southern Chile.

NGF effects promote the maturation of rat pancreatic beta cells by regulating GLUT2 levels and distribution, and glucokinase activity.

The nerve growth factor (NGF) participates in cell survival and glucose-stimulated insulin secretion (GSIS) processes in rat adult beta cells. GSIS is a complex process in which metabolic events and ionic channel activity are finely coupled. GLUT2 and glucokinase (GK) play central roles in GSIS by regulating the rate of the glycolytic pathway. The biphasic release of insulin upon glucose stimulation characterizes mature adult beta cells. On the other hand, beta cells obtained from neonatal, suckling, and weaning rats are considered immature because they secrete low levels of insulin and do not increase insulin secretion in response to high glucose. The weaning of rats (at postnatal day 20 in laboratory conditions) involves a dietary transition from maternal milk to standard chow. It is characterized by increased basal plasma glucose levels and insulin levels, which we consider physiological insulin resistance. On the other hand, we have observed that incubating rat beta cells with NGF increases GSIS by increasing calcium currents in neonatal cells. In this work, we studied the effects of NGF on the regulation of cellular distribution and activity of GLUT2 and GK to explore its potential role in the maturation of GSIS in beta cells from P20 rats. Pancreatic islet cells from both adult and P20 rats were isolated and incubated with 5.6 mM or 15.6 mM glucose with and without NGF for 4 hours. Specific immunofluorescence assays were conducted following the incubation period to detect insulin and GLUT2. Additionally, we measured glucose uptake, glucokinase activity, and insulin secretion assays at 5.6 mM or 15.6 mM glucose concentrations. We observed an age-dependent variation in the distribution of GLUT2 in pancreatic beta cells and found that glucose plays a regulatory role in GLUT2 distribution independently of age. Moreover, NGF increases GLUT2 abundance, glucose uptake, and GSIS in P20 beta cells and GK activity in adult beta cells. Our results suggest that besides increasing calcium currents, NGF regulates metabolic components of the GSIS, thereby contributing to the maturation process of pancreatic beta cells.

An Observational Study Suggests That Natural HAdV-36 Infection Decreases Blood Glucose Levels without Affecting Insulin Levels in Obese Young Subjects.

Human adenovirus-36 (HAdV-36) infection has been linked to obesity, low lipid levels, and improvements in blood glucose levels and insulin sensitivity in animal models and humans, although epidemiological studies remain controversial. Therefore, this study investigated the relationship between HAdV-36 seropositivity and glycemic control in youths. This observational study examined 460 youths (246 with normal weight and 214 obese subjects). All participants underwent assessments for anthropometry, blood pressure, circulating fasting levels of glucose, lipids, insulin, and anti-HAdV-36 antibodies; additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. In all, 57.17% of the subjects were HAdV-36 seropositive. Moreover, HAdV-36 seroprevalence was higher in obese subjects compared to their normal weight counterparts (59% vs. 55%). BMI (33.1 vs. 32.3 kg/m2, p = 0.03), and waist circumference (107 vs. 104 cm, p = 0.02), insulin levels (21 vs. 16.3 µU/mL, p = 0.003), and HOMA-IR (4.6 vs. 3.9, p = 0.02) were higher in HAdV-36-positive subjects with obesity compared to seronegative subjects. In the obese group, HAdV-36 seropositivity was associated with a reducing effect in blood glucose levels in a model adjusted for total cholesterol, triglyceride levels, age and sex (ß = -10.44, p = 0.014). Furthermore, a statistically significant positive relationship was observed between HAdV-36 seropositivity and insulin levels in the obesity group. These findings suggest that natural HAdV-36 infection improves glycemic control but does not ameliorate hyperinsulinemia in obese subjects.

Lycopene in Combination with Insulin Triggers Antioxidant Defenses and Increases the Expression of Components That Detoxify Advanced Glycation Products in Kidneys of Diabetic Rats.

BACKGROUND: Biochemical events provoked by oxidative stress and advanced glycation may be inhibited by combining natural bioactives with classic therapeutic agents, which arise as strategies to mitigate diabetic complications. The aim of this study was to investigate whether lycopene combined with a reduced insulin dose is able to control glycemia and to oppose glycoxidative stress in kidneys of diabetic rats. METHODS: Streptozotocin-induced diabetic rats were treated with 45 mg/kg lycopene + 1 U/day insulin for 30 days. The study assessed glycemia, insulin sensitivity, lipid profile and paraoxonase 1 (PON-1) activity in plasma. Superoxide dismutase (SOD) and catalase (CAT) activities and the protein levels of advanced glycation end-product receptor 1 (AGE-R1) and glyoxalase-1 (GLO-1) in the kidneys were also investigated. RESULTS: An effective glycemic control was achieved with lycopene plus insulin, which may be attributed to improvements in insulin sensitivity. The combined therapy decreased the dyslipidemia and increased the PON-1 activity. In the kidneys, lycopene plus insulin increased the activities of SOD and CAT and the levels of AGE-R1 and GLO-1, which may be contributing to the antialbuminuric effect. CONCLUSIONS: These findings demonstrate that lycopene may aggregate favorable effects to insulin against diabetic complications resulting from glycoxidative stress.

Therapeutical Potential of T3 as Adjuvant Therapy in Male Alloxan-induced Diabetic Rats.

Alloxan-induced diabetic rats present with hypothyroidism. When treated with triiodothyronine (T3), glycemia and proinflammatory cytokine expression are downregulated, improving insulin sensitivity. The effectiveness of associating T3 with insulin (replacement dose [6 U] and [3 U]) in controlling glycemia was investigated in this experimental model. Male Wistar rats were made diabetic by alloxan injection and sorted into groups treated or not with insulin (3 or 6 U) associated or not with T3 (1.5 µg 100 g-1 BW) for 28 days. Nondiabetic rats constituted the control group. Fasting glycemia, glucose decay rate, and thyrotropin (TSH) were measured in the blood/serum of all animals. Immunoblotting was used to assess total GLUT4 expression in skeletal muscles and epididymal white adipose tissue. Cytokine and nuclear factor-κB (NF-κB) expression were measured in these tissues and liver. Diabetic rats presented with increased fasting glycemia, inflammatory cytokines, and NF-κB expression, TSH levels, and insulin resistance. In diabetic rats treated with T3 and/or insulin, these parameters were decreased, whereas GLUT4 and anti-inflammatory cytokine expression were increased. T3 combined with 3-U insulin restored the parameters to values of the control group and was more effective at controlling glycemia than 6-U insulin. Thus, a combination of T3 and insulin might represent a promising strategy for diabetes management since it reduces the insulin requirement by half and improves glycemic control of diabetic rats, which could postpone insulin resistance that develops with chronic insulin administration. These findings open a perspective for using thyroid analogues that provide tissue-specific effects, which might result in a potentially more effective treatment of diabetes.

Assessment of Cardiometabolic Risk Factors and Insulin Sensitivity by Hyperinsulinemic-Euglycemic Clamp in Resistance to Thyroid Hormone ß Syndrome.

Background: Resistance to thyroid hormone beta (RTHß) is a rare disease resulting from mutations in the THRB gene, characterized by reduced T3 action in tissues with high thyroid hormone receptor ß expression. Thyroid hormones regulate body composition and metabolism in general, and increased or decreased hormone levels are associated with insulin resistance. This study evaluated the presence of cardiometabolic risk factors and insulin sensitivity in patients with RTHß. Methods: In all, 16 patients, 8 adults (52.3 ± 16.3 years of age) and 8 children (10.9 ± 3.9 years of age), were compared to 28 control individuals matched for age, sex, and body mass index (BMI). Anthropometry evaluation and blood samples were collected for glycemia, lipids, insulin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, adiponectin, ultrasensitive C-reactive protein (CRPus), free thyroxine, total triiodothyronine, thyrotropin, and anti-thyroid peroxidase measurements. Body composition was assessed using dual-emission X-ray absorptiometry and bioimpedance. Insulin sensitivity was evaluated in adult patients and controls using the hyperinsulinemic-euglycemic clamp (HEC), whereas homeostasis model assessment of insulin resistance (HOMA-IR) was calculated in all individuals studied. Results: Patients and controls presented similar weight, BMI, abdominal perimeter, and total fat body mass. Patients with RTHß demonstrated higher total cholesterol (TC), p = 0.04, and low-density lipoprotein cholesterol (LDL-C), p = 0.03, but no alteration was observed in other parameters associated with metabolic risk, such as leptin, TNF-α, and CRPus. Two adult patients met the criteria for metabolic syndrome. There was no evidence of insulin resistance assessed by HEC or HOMA-IR. Elevated IL-6 levels were observed in patients with RTHß. Conclusion: Using HEC as the gold standard method, no evidence of reduced insulin sensitivity in skeletal muscle was documented in RTHß adult patients; however, higher levels of TC and LDL-C were observed in these patients, which suggest the need for active monitoring of this abnormality to minimize cardiometabolic risk. In addition, we demonstrated, for the first time, that the increase in IL-6 levels in patients with RTHß is probably secondary to metabolic causes as they have normal levels of TNF-α and CRPus, which may contribute to an increase in cardiovascular risk. A larger number of patients must be studied to confirm these results.

Activation of the ROS/TXNIP/NLRP3 pathway disrupts insulin-dependent glucose uptake in skeletal muscle of insulin-resistant obese mice.

Oxidative stress and the activation of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain containing 3 (NLRP3) inflammasome have been linked to insulin resistance in skeletal muscle. In immune cells, the exacerbated generation of reactive oxygen species (ROS) activates the NLRP3 inflammasome, by facilitating the interaction between thioredoxin interacting protein (TXNIP) and NLRP3. However, the precise role of ROS/TXNIP-dependent NLRP3 inflammasome activation in skeletal muscle during obesity-induced insulin resistance remains undefined. Here, we induced insulin resistance in C57BL/6J mice by feeding them for 8 weeks with a high-fat diet (HFD) and explored whether the ROS/TXNIP/NLRP3 pathway was involved in the induction of insulin resistance in skeletal muscle. Skeletal muscle fibers from insulin-resistant mice exhibited increased oxidative stress, as evidenced by elevated malondialdehyde levels, and altered peroxiredoxin 2 dimerization. Additionally, these fibers displayed augmented activation of the NLRP3 inflammasome, accompanied by heightened ROS-dependent proximity between TXNIP and NLRP3, which was abolished by the antioxidant N-acetylcysteine (NAC). Inhibition of the NLRP3 inflammasome with MCC950 or suppressing the ROS/TXNIP/NLRP3 pathway with NAC restored insulin-dependent glucose uptake in muscle fibers from insulin-resistant mice. These findings provide insights into the mechanistic link between oxidative stress, NLRP3 inflammasome activation, and obesity-induced insulin resistance in skeletal muscle.

Correlation between islet α cell function and peripheral neuropathy in patients with type 2 diabetes mellitus.

BACKGROUND: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. RESULTS: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. CONCLUSION: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.