Diabetes mellitus promotes susceptibility to periodontitis-novel insight into the molecular mechanisms.

Diabetes mellitus is a main risk factor for periodontitis, but until now, the underlying molecular mechanisms remain unclear. Diabetes can increase the pathogenicity of the periodontal microbiota and the inflammatory/host immune response of the periodontium. Hyperglycemia induces reactive oxygen species (ROS) production and enhances oxidative stress (OS), exacerbating periodontal tissue destruction. Furthermore, the alveolar bone resorption damage and the epigenetic changes in periodontal tissue induced by diabetes may also contribute to periodontitis. We will review the latest clinical data on the evidence of diabetes promoting the susceptibility of periodontitis from epidemiological, molecular mechanistic, and potential therapeutic targets and discuss the possible molecular mechanistic targets, focusing in particular on novel data on inflammatory/host immune response and OS. Understanding the intertwined pathogenesis of diabetes mellitus and periodontitis can explain the cross-interference between endocrine metabolic and inflammatory diseases better, provide a theoretical basis for new systemic holistic treatment, and promote interprofessional collaboration between endocrine physicians and dentists.

Chronic pancreatitis and nutritional support.

Malnutrition in patients with chronic pancreatitis is common, but its evaluation is often missed in clinical practice. Pancreatic exocrine insufficiency is the single most important cause of malnutrition; therefore, it needs to be screened for and treated appropriately. Specific diet regimens in patients suffering from chronic pancreatitis are rarely reported in the literature. Patients suffering from chronic pancreatitis have a higher demand for energy but a lower caloric intake secondary to pancreatic exocrine insufficiency, combined with the malabsorption of liposoluble vitamin and micronutrients, which needs be corrected by appropriate dietary counselling. Diabetes is frequently observed in chronic pancreatitis and classified as type 3c, which is characterized by low levels of both serum insulin and glucagon; therefore, there is a tendency towards hypoglycaemia in patients treated with insulin. Diabetes contributes to malnutrition in chronic pancreatitis. Strategies to treat exocrine and endocrine insufficiency are important to achieve better control of the disease.

Risk Factors of New-onset Diabetes After Renal Transplantation and Prognostic Analysis.

Context: New-onset diabetes after transplantation (NODAT) is one of the most common complications after renal transplantation and in kidney-transplant recipients is closely related to long-term adverse outcomes for recipients and transplants. The risk factors for NODAT still require exploration. Objectives: The study intended to explore the risk factors for new-onset diabetes after transplantation (NODAT) for patients receiving a renal transplantation, to provide a theoretical basis for reducing the incidence rate of NODAT and promoting a better outcome for patients. Design: The research team designed a retrospective study using clinical data of patients receiving renal transplantation at a hospital. Setting: The study took place in the Department of Urology at Xuanwu Hospital at Capital Medical University in Beijing, China. Participants: Participants were 396 patients who had undergone renal transplantation at the hospital, of whom 28 had NODAT syndrome, the NODAT group, and 368 didn't meet the diagnostic criteria for NODAT, the N-NODAT group. Outcome Measures: The research team calculated the incidence rate of NODAT and determined the causes of the disease, evaluated participants' preoperative risk factors-gender, preoperative systolic blood pressure (SBP), preoperative diastolic blood pressure (DBP), height, family history of diabetes, weight, smoking habits, age, drinking habits, pretransplant body mass index (BMI), preoperative fasting blood glucose, triglycerides (TG), total cholesterol (TC)-and their postoperative risk factors-acute rejection, use of immunosuppressive agents, blood CsA concentration, blood FK506 concentration, and renal function. Additionally, the team subjected the data in the two groups to univariate, logistic regression analysis and to multivariate, unconditional, logistic regression analysis to discover risk factors for NODAT. Results: Among the 396 participants, 28 had NODAT (7.1%), and 368 didn't suffer NODAT (92.9%). Statistically significant differences existed between the groups in participants' ages (0.013), weights (P = .032), smoking habits (P = .034), drinking habits (P = .034), BMIs (P = .023), preoperative fasting blood glucose (P < .05), preoperative TG (P < .05), and preoperative TC (P < .01). In the univariate logistic regression analysis, significant associations existed between age (P = .016), weight (P = .033), BMI (P = .025), smoking habits (P = .035), drinking habits (P = .043), preoperative fasting blood glucose (P = .048), preoperative TG (P = .049), preoperative TC (P = .009), acute rejection (P = .009), and immunosuppressive agents (P = .012) and the occurrence of NODAT (P < .05). In the multivariate unconditional logistic stepwise regression analysis, acute rejection (P = .011) and use of FK506 in immunotherapy (P = .013) were independent risk factors for NODAT. Conclusions: The risk factors of NODAT include age, weight, BMI, smoking habits, drinking habits, preoperative fasting blood glucose, preoperative TG, preoperative TC, acute rejection and exposure to immunosuppressive agents. Among them, only acute rejection and immunosuppressive agents are modifiable factors. The application of CsA as an immunosuppressive agent after surgery may decrease the incidence rate of NODAT and prolong the longevity of patients receiving renal transplantation.

Incidence, Risk Factors, and Outcomes of COVID-19 Infection in a Large Cohort of Solid Organ Transplant Recipients.

BACKGROUND: Solid organ transplant recipients (SOTr) are at increased risk for severe disease from coronavirus disease 2019 (COVID-19) compared with non-SOTr. METHODS: We performed a retrospective cohort study between March 1, 2020, and March, 30, 2021, in an integrated healthcare system with 4.3 million members aged ≥18 y including 5126 SOTr. Comparisons in COVID-19 mortality, hospitalization, and incidence were made between SOTr and non-SOTr, and between different SOTr organs. Multivariate analysis was performed to identify risk factors for COVID-19 mortality and hospitalization. RESULTS: There were 600 SOTr (kidney, liver, heart, and lung) with COVID-19. Per person-year incidence of COVID-19 among SOTr was 10.0% versus 7.6% among non-SOTr (P < 0.0001). Compared with uninfected SOTr, infected SOTr were older (57.1 ± 14.0 versus 45.7 ± 17.9 y, P < 0.001), predominantly Hispanic/Latino (58.8% versus 38.6%, P < 0.0001), hypertensive (77.0% versus 23.8%; P < 0.0001), and diabetic (49.6% versus 13.0%; P = 0.0009). Compared with non-SOTr, infected SOTr had higher hospitalization (39.5% versus 6.0%; P < 0.0001), intensive care unit admission (29.1% versus 15.5%; P < 0.0001), and mortality (14.7% versus 1.8%; P < 0.0001) from COVID-19. Older age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.05-1.10), male gender (HR, 1.79; 95% CI, 1.11-2.86), and higher body mass index (HR, 1.04; 95% CI, 1.00-1.09; P = 0.047) were associated with increased mortality from COVID-19, whereas race, diabetes, and number/type of immunosuppressive medications were not. Among the different SOTr, COVID-19 mortality risk was lowest in liver recipients (HR, 0.34; 95% CI, 0.16-0.73) and highest in lung recipients (HR, 1.74; 95% CI, 0.68-4.42). CONCLUSIONS: SOTr have higher rates of hospitalization and mortality from COVID-19 compared with the general population. Among the SOTr, the incidence and outcomes were distinct among different transplantation types.

Diabetic retinopathy screening and treatment through the Brazilian National Health Insurance.

The current study aimed to investigate diabetic retinopathy (DR) screening and treatment coverages among diabetic patients evaluated through the Brazilian National Health Insurance from 2014 to 2019. The Brazilian Public Health System Information Database was used as the primary data source. DR screening coverage was calculated as the rate of procedures of clinical dilated fundus exam and color fundus photograph over the number of diabetic patients. DR treatment coverage was calculated as the rate of procedures of intravitreal injection, photocoagulation, and panretinal photocoagulation over the number of diabetic patients presumably in need of DR treatment. The overall screening coverage increased from 12.1% in 2014 to 21.2% in 2019 (p < 0.001) with substantial regional discrepancies so that North region was the only one with no changes along the period. The overall treatment coverage increased from 27.7% in 2014 to 44.1% in 2019, with Southeast and Midwest absorbing the demand for service from the North, Northeast and South. Despite an improvement along the past years, both screening and treatment coverages for DR in diabetes patients are ineffective in Brazil. Public health policies should address resources disparities throughout the country aiming to offer same healthcare conditions to patients regardless their geographic location.

[Efficacy of the Extract from Fermentation of Soybean and Rice Bran on Hyperglycemia].

In recent years, lifestyle-related diseases such as hypertension and diabetes have been on the rise. These conditions can cause serious conditions such as myocardial and cerebral infarctions. Therefore, proper control of blood pressure and blood glucose levels is important issues in preventive medicine. Traditional fermented foods have been shown to have various functions, and their effects on lifestyle-related diseases have attracted particular attention. In this study, we investigated the effects of fermented soybeans and rice bran (OE-1) and supplements containing OE-1 on blood glucose levels and weight changes. We identified an inhibitory effect on elevated blood glucose levels upon administration of OE-1, and this effect was thought to be due to digestive enzyme inhibition. These effects of foods containing OE-1 are expected to have a positive effect on the prevention and improvement of lifestyle-related diseases as health foods.

Association between antibiotics use and diabetes incidence in a nationally representative retrospective cohort among Koreans.

Numerous studies have reported that antibiotics could lead to diabetes, even after adjusting for confounding variables. This study aimed to determine the causal relationship between antibiotics use and diabetes in a nationally representative cohort. This retrospective cohort study included adults aged 40 years or older who were enrolled in the Korean National Health Insurance Service-Health Screening Cohort. Antibiotic exposure was assessed from 2002 to 2005 and newly diagnosed diabetes mellitus was determined based on diagnostic codes and history of antidiabetic medication use from 2006 to 2015. Multivariate Cox proportional hazards model was used to assess the association between antibiotic use and diabetes incidence. The mean age of the 201,459 study subjects was 53.2 years. People who used antibiotics for 90 or more days had a higher risk of diabetes (adjusted hazard ratio [aHR] 1.16, 95% confidence interval [CI] 1.07-1.26) compared to non-users. Those who used five or more classes of antibiotics had a higher risk of diabetes than those who used one antibiotic class (aHR 1.14; 95% CI 1.06-1.23). The clear dose-dependent association between antibiotics and diabetes incidence supports the judicious use of antibiotics in the future.

Experimental Animal Studies Support the Role of Dietary Advanced Glycation End Products in Health and Disease.

The increased incidence of obesity, diabetes mellitus, aging, and associated comorbidities indicates the interplay between genetic and environmental influences. Several dietary components have been identified to play a role in the pathogenesis of the so-called "modern diseases", and their complications including advanced glycation end products (AGEs), which are generated during the food preparation and processing. Diet-derived advanced glycation end products (dAGEs) can be absorbed in the gastrointestinal system and contribute to the total body AGEs' homeostasis, partially excreted in the urine, while a significant amount accumulates to various tissues. Various in vitro, in vivo, and clinical studies support that dAGEs play an important role in health and disease, in a similar way to those endogenously formed. Animal studies using wild type, as well as experimental, animal models have shown that dAGEs contribute significantly to the pathogenesis of various diseases and their complications, and are involved in the changes related to the aging process. In addition, they support that dAGEs' restriction reduces insulin resistance, oxidative stress, and inflammation; restores immune alterations; and prevents or delays the progression of aging, obesity, diabetes mellitus, and their complications. These data can be extrapolated in humans and strongly support that dAGEs' restriction should be considered as an alternative therapeutic intervention.

New Insights of SF1 Neurons in Hypothalamic Regulation of Obesity and Diabetes.

Despite the substantial role played by the hypothalamus in the regulation of energy balance and glucose homeostasis, the exact mechanisms and neuronal circuits underlying this regulation remain poorly understood. In the last 15 years, investigations using transgenic models, optogenetic, and chemogenetic approaches have revealed that SF1 neurons in the ventromedial hypothalamus are a specific lead in the brain's ability to sense glucose levels and conduct insulin and leptin signaling in energy expenditure and glucose homeostasis, with minor feeding control. Deletion of hormonal receptors, nutritional sensors, or synaptic receptors in SF1 neurons triggers metabolic alterations mostly appreciated under high-fat feeding, indicating that SF1 neurons are particularly important for metabolic adaptation in the early stages of obesity. Although these studies have provided exciting insight into the implications of hypothalamic SF1 neurons on whole-body energy homeostasis, new questions have arisen from these results. Particularly, the existence of neuronal sub-populations of SF1 neurons and the intricate neurocircuitry linking these neurons with other nuclei and with the periphery. In this review, we address the most relevant studies carried out in SF1 neurons to date, to provide a global view of the central role played by these neurons in the pathogenesis of obesity and diabetes.

Moringa oleifera: un producto natural con posibilidades para ser usado en pacientes con diabetes mellitus / Moringa oleifera: a natural product with chances of being used in patients with diabetes mellitus

Introducción: La búsqueda de nuevos fármacos o de productos naturales que mejoren la calidad de la atención y los resultados en el tratamiento de la diabetes mellitus continúan. La Moringa oleifera tiene variados usos y es uno de los productos naturales que desde hace años se evalúa con este fin, por sus sustanciales propiedades curativas. Objetivo: Evaluar los efectos de la Moringa oleifera como un producto natural con posibilidades de ser usado en pacientes con diabetes mellitus. Método: Se utilizaron como buscadores de información científica a SciELO, PubMed, Google y a Google Académico. La estrategia de búsqueda incluyó los siguientes términos como palabras claves: Moringa oleifera, diabetes mellitus, propiedades antidiabéticas, reacciones adversas. Se evaluaron artículos de revisión, de investigación y páginas Web que, en general, tenían menos de 10 años de publicados, en idioma español, portugués e inglés, y que hicieran referencia específicamente al tema de estudio a través del título. Esto permitió evaluar 120 artículos, de los cuales 64 fueron referenciados. Conclusiones: La Moringa oleifera es una planta que constituye un producto natural con propiedades nutracéuticas y funcionales. Puede usarse como un coadyuvante en los tratamientos convencionales indicados para el tratamiento de la diabetes mellitus, lo cual dependería de los resultados de ensayos clínicos rigurosos, que permitan dilucidar si realmente es capaz de contribuir a lograr en el humano, un control glucémico eficaz, sin efectos secundarios importantes e incluso ayudar a mejorar algunas de las complicaciones y comorbilidades que habitualmente acompañan a la diabetes mellitus(AU)

Introduction: The search of new drugs or natural products that improve the quality of care and the results of diabetes mellitus treatment continue. Moringa oleifera has different uses and is one of the natural products that have been assessed through the years with that purpose, due to its considerable curative properties. Objective: Assess the effects of Moringa oleifera as a natural product with chances of being used in patients with diabetes mellitus. Methods: There were used as scientific information searchers ScieELO, PubMed, Google and Google Scholar. The search strategy included the following terms as keywords: Moringa oleifera, diabetes mellitus, anti-diabetic properties, adverse reactions. Review articles, research articles and web pages were assessed; in general terms, those had less than 10 years of being published, were in Spanish, Portuguese and English languages, and were making specific reference in the title to the studied subject. This allowed assessing 120 articles, of which 64 were quoted. Conclusions: Moringa oleifera is a plant that constitutes a natural product with nutraceutical and functional properties. It can be used as a contributory agent in conventional treatments indicated for diabetes mellitus, which will depend on the results of strict clinical trials that allow to clarify if it is actually capable of contributing to achieve an efficient glycemic control in humans, without relevant side effects, or even to help improving some of the complications and comorbidities that usually accompany diabetes mellitus(AU)

The Edible Brown Seaweed Sargassum horneri (Turner) C. Agardh Ameliorates High-Fat Diet-Induced Obesity, Diabetes, and Hepatic Steatosis in Mice.

Sargassum horneri (Turner) C. Agardh (S. horneri) is edible brown seaweed that grows along the coast of East Asia and has been traditionally used as a folk medicine and a local food. In this study, we evaluated the effects of S. horneri on the development of obesity and related metabolic disorders in C57BL/6J mice fed a high-fat diet. S. horneri was freeze-dried, fine-powdered, and mixed with a high-fat diet at a weight ratio of 2% or 6%. Feeding a high-fat diet to mice for 13 weeks induced obesity, diabetes, hepatic steatosis, and hypercholesterolemia. Supplementation of mice with S. horneri suppressed high-fat diet-induced body weight gain and the accumulation of fat in adipose tissue and liver, and the elevation of the serum glucose level. In addition, S. horneri improved insulin resistance. An analysis of the feces showed that S. horneri stimulated the fecal excretion of triglyceride, as well as increased the fecal polysaccharide content. Furthermore, extracts of S. horneri inhibited the activity of pancreatic lipase in vitro. These results showed that S. horneri can ameliorate diet-induced metabolic diseases, and the effect may be partly associated with the suppression of intestinal fat absorption.

Does the High Prevalence of Vitamin D Deficiency in African Americans Contribute to Health Disparities?

African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer's disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D3 supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.

Thiamine-Responsive Megaloblastic Anemia-Related Diabetes: Long-Term Clinical Outcomes in 23 Pediatric Patients From the DPV and SWEET Registries.

OBJECTIVES: To describe clinical presentation and long-term outcomes in a large cohort of children diagnosed with thiamine-responsive megaloblastic anemia (TRMA)-related diabetes. METHODS: Data from the Diabetes Patienten Verlaufsdokumentation (DPV) and Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference (SWEET) registries were used to identify cases. Complementary information was collected through a chart review of each case. Descriptive analyses with medians and interquartile ranges and numbers (proportions) were tabulated. RESULTS: We identified 23 cases (52% male) in the 2 registries. Eighteen (78%) had genetic confirmation of TRMA. Median age at diabetes onset was 1.4 (quartiles 0.8 to 3.6) years and median age at initiation of thiamine treatment was 5.9 (2.4 to 12.4) years. At their most recent visit, patients' median age was 14.3 (8.1 to 17.5) years, glycated hemoglobin level was 6.9% (6.1% to 7.9%), insulin dose was 0.9 (0.4 to 1.2) units/kg per day and thiamine dose was 200 (100 to 300) mg/day. Three patients were not treated with insulin or antidiabetic drugs. There was no difference in diabetes outcomes in patients with initiation of thiamine ≤1 year after diabetes onset compared to patients with initiation of thiamine >1 year after diabetes onset. CONCLUSIONS: This is the longest case series of pediatric TRMA-related diabetes reported to date. Diabetes onset often occurs several years before initiation of thiamine supplementation. Early initiation of thiamine (within 1 year of diabetes onset) was not linked to improved diabetes outcome. However, the role of thiamine in pancreatic function needs further assessment. Patients with TRMA-related diabetes maintained good glycemic control even after 9 years (median) of follow up.

In Vitro and In Vivo Antidiabetic Potential of Monoterpenoids: An Update.

Diabetes mellitus (DM) is a chronic metabolic condition characterized by persistent hyperglycemia due to insufficient insulin levels or insulin resistance. Despite the availability of several oral and injectable hypoglycemic agents, their use is associated with a wide range of side effects. Monoterpenes are compounds extracted from different plants including herbs, vegetables, and fruits and they contribute to their aroma and flavor. Based on their chemical structure, monoterpenes are classified into acyclic, monocyclic, and bicyclic monoterpenes. They have been found to exhibit numerous biological and medicinal effects such as antipruritic, antioxidant, anti-inflammatory, and analgesic activities. Therefore, monoterpenes emerged as promising molecules that can be used therapeutically to treat a vast range of diseases. Additionally, monoterpenes were found to modulate enzymes and proteins that contribute to insulin resistance and other pathological events caused by DM. In this review, we highlight the different mechanisms by which monoterpenes can be used in the pharmacological intervention of DM via the alteration of certain enzymes, proteins, and pathways involved in the pathophysiology of DM. Based on the fact that monoterpenes have multiple mechanisms of action on different targets in in vitro and in vivo studies, they can be considered as lead compounds for developing effective hypoglycemic agents. Incorporating these compounds in clinical trials is needed to investigate their actions in diabetic patients in order to confirm their ability in controlling hyperglycemia.

Risk of diabetes in stroke patients who used Bu Yang Huan Wu Tang: A nationwide propensity-score matched study.

BACKGROUND: The utilization of traditional Chinese medicine is a common therapeutic approach for stroke patients in Chinese population, but little is known about the effect of Bu Yang Huan Wu Tang (BYHWT) on post-stroke diabetes. PURPOSE: We aimed to evaluate the risk of diabetes in stroke patients who used BYHWT. STUDY DESIGN: A retrospective cohort study based on a real-world database was conducted. METHODS: Newly diagnosed stroke patients receiving inpatient care from 2000 to 2004 were identified using a large-scale insurance database in Taiwan. Propensity score matching was used to select eligible stroke patients who did (n = 9849) and did not (n = 9849) receive BYHWT. These two groups were followed up until the end of 2009 to track incident diabetes. Cox proportional hazard models were used to calculate the adjusted hazard rations (HRs) and 95% confidence intervals (CIs) for post-stroke diabetes associated with BYHWT during the follow-up period. RESULTS: Stroke patients who used BYHWT had a reduced incidence of diabetes (14.1% vs. 19.0%, p < 0.0001) and reduced risk of diabetes (HR 0.77; 95% CI 0.72 to 0.83) compared with the control group. The association between BYHWT and reduced risk of post-stroke diabetes was significant across sexe, age group, and stroke subtype. Additionally, the use of BYHWT was associated with a reduced risk of post-stroke diabetes even after excluding the initial three months of diabetes cases in the sensitivity analysis. CONCLUSIONS: Stroke patients who received BYHWT therapy had a reduced risk of diabetes, and a positive effect was observed in various subgroups. However, future clinical trials will be necessary to validate the present findings and identify the biochemical mechanism involved.

Garcinia linii extracts exert the mediation of anti-diabetic molecular targets on anti-hyperglycemia.

Different portions (stem GIS and leaf GIL) of Garcinia linii were extracted by ethanol/water and crude extracts were employed to investigate the contents of total phenol and flavonoids, antioxidation activities, and inhibitory activities of α-amylase and α-glucosidase via enzymatic assay and OGTT and OSTT for lowering glucose levels. The data revealed that GlS and GlL contained different levels of flavonoids and total phenol. Furthermore, the results showed the extracts exhibited remarkable antioxidation activities and inhibitory activities of α-amylase and α-glucosidase. In silico docking studies were done using Gold software and the probable molecules retrieved from PubChem were docked with several anti-diabetic relate targets, the results showed several components of G. linii could potentially inhibit diabetic molecules when compared with clinic drugs. The cell glucose uptake data also confirmed that GlL and GlS could retain the active component in the regulation of insulin, AMPK, PPARγ, and DPP4. In vivo, the evidence showed G. linii extracts including syringaldehyde suppressed effect of hyperglycemia on OSTT and OGTT assays. These results suggest that G. linii extract has a potential therapeutic value for the treatment of diabetes in humans.

Molecular mechanism of down-regulating adipogenic transcription factors in 3T3-L1 adipocyte cells by bioactive anti-adipogenic compounds.

Obesity is growing at an alarming rate, which is characterized by increased adipose tissue. It increases the probability of many health complications, such as diabetes, arthritis, cardiac disease, and cancer. In modern society, with a growing population of obese patients, several individuals have increased insulin resistance. Herbal medicines are known as the oldest method of health care treatment for obesity-related secondary health issues. Several traditional medicinal plants and their effective phytoconstituents have shown anti-diabetic and anti-adipogenic activity. Adipose tissue is a major site for lipid accumulation as well as the whole-body insulin sensitivity region. 3T3-L1 cell line model can achieve adipogenesis. Adipocyte characteristics features such as expression of adipocyte markers and aggregation of lipids are chemically induced in the 3T3-L1 fibroblast cell line. Differentiation of 3T3-L1 is an efficient and convenient way to obtain adipocyte like cells in experimental studies. Peroxisome proliferation activated receptor γ (PPARγ) and Cytosine-Cytosine-Adenosine-Adenosine-Thymidine/Enhancer-binding protein α (CCAAT/Enhancer-binding protein α or C/EBPα) are considered to be regulating adipogenesis at the early stage, while adiponectin and fatty acid synthase (FAS) is responsible for the mature adipocyte formation. Excess accumulation of these adipose tissues and lipids leads to obesity. Thus, investigating adipose tissue development and the underlying molecular mechanism is important in the therapeutical approach. This review describes the cellular mechanism of 3T3-L1 fibroblast cells on potential anti-adipogenic herbal bioactive compounds.

Diabetes relacionada con la fibrosis quística / Cystic fibrosis-related diabetes

Los avances en el campo de la fibrosis quística han aumentado la esperanza de vida de estos pacientes, por lo que cada vez es más prevalente la Diabetes Relacionada con la Fibrosis Quística (DRFQ) y sus complicaciones. La DRFQ se asocia a mayor morbimortalidad, deterioro de la función pulmonar y del estado nutricional. Por lo mismo, el manejo óptimo de esta patología depende de un diagnóstico precoz, tratamiento individualizado y vigilancia de las complicaciones diabéticas. El screening de DRFQ debe realizarse anualmente a partir de los 10 años, mediante una Prueba de Tolerancia a la Glucosa Oral (PTGO), lo cual permite el diagnóstico. El manejo de esta patología tiene por objetivo estabilizar y mejorar la función pulmonar y el estado nutricional y metabólico de los pacientes. Actualmente, la insulina es el tratamiento farmacológico de elección para controlar la hiperglicemia y el esquema de uso debe ser individualizado para cada persona. En caso de enfermedades agudas pueden existir mayores requerimientos de insulina. Además, se deben tener consideraciones especiales en cuanto a la dieta y la insuficiencia pancreática exocrina que presentan estos pacientes. Para la vigilancia de complicaciones microvasculares se debe realizar una monitorización anual a partir de los 5 años desde el diagnóstico de DRFQ. Debido a la complejidad de estos pacientes, para alcanzar el mejor cuidado posible se necesita un enfoque multidisciplinario con distintos profesionales de la salud coordinados, incluyendo en la toma de decisiones al paciente y su familia.

Advances made in the field of cystic fibrosis have increased the life expectancy of these patients, which is why Cystic Fibrosis-Related Diabetes (CFRD) and its complications are becoming more and more prevalent. CFRD is associated with increased morbidity and mortality, lower lung function and inadequate weight maintenance. Therefore, the optimal management of this pathology depends on an early diagnosis, individualized treatment and monitoring of diabetic complications. For CFRD, routine screening with an Oral Glucose Tolerance Test (OGTT) should be carried out yearly from the age of 10, which allows to diagnose it. The treatment goals in CFRD are to stabilize and improve lung function and obtain adequate weight gain. Currently, insulin is the pharmacological treatment of choice to control hyperglycemia and the insulin regimen must be personalized for each person. In acute illnesses, there may be higher insulin requirements. In addition, special considerations must be taken regarding diet and exocrine pancreatic insufficiency that these patients present. For the surveillance of microvascular complications, annual monitoring should be carried out 5 years after the diagnosis of CFRD. Due to the complexity of these patients, in order to achieve the best possible care, a multidisciplinary approach is needed with different coordinated health professionals, including the patients and their family in the decision-making process.

Pancreatitis, Pancreatic Cancer, and Their Metabolic Sequelae: Projected Burden to 2050.

INTRODUCTION: Future burden has been modeled from population-based data for several common gastrointestinal diseases. However, as we enter the third decade in the 21st century, there are no such data on diseases of the pancreas holistically. The study aimed to estimate future incidence of pancreatitis, pancreatic cancer, diabetes of the exocrine pancreas (DEP), and exocrine pancreatic dysfunction (EPD) as well as years of life lost (YLL) due to premature death in individuals with those diseases up to 2050. METHODS: Historical New Zealand nationwide data on hospital discharge, pharmaceutical dispensing, cancer, and mortality were obtained. Annual incidence of each disease and annual YLLs due to premature death in individuals with each disease were calculated. A time series analysis using the stepwise autoregressive method was conducted. RESULTS: Pancreatitis yielded the highest projected incidence (123.7 per 100,000; 95% confidence interval, 116.7-130.7) and YLL (14,709 years; 13,642-15,777) in 2050. The projected incidence and YLL of pancreatic cancer were 18.6 per 100,000 (95% confidence interval, 13.1-24.1) and 14,247 years (11,349-17,144) in 2050, respectively. Compared with pancreatitis and pancreatic cancer, DEP and EPD yielded lower but more steeply increasing projected incidence rates and YLLs. DISCUSSION: The findings suggest that the burden of pancreatitis, pancreatic cancer, DEP, and EPD will rise in the next 3 decades unless healthcare systems introduce effective prevention or early treatment strategies for diseases of the pancreas and their sequelae.

Drug treatments for managing cystic fibrosis-related diabetes.

BACKGROUND: The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes (CFRD) has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/L (125 mg/dL); or oral glucose tolerance tests greater than 11.11 mmol/L (200 mg/dL) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/L (200 mg/dL); or glycated hemoglobin levels of at least 6.5%. This is an update of a previously published review. OBJECTIVES: To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences. Date of most recent register search: 10 September 2020. We searched online trials registries; date of most recent searches: 21 March 2020. SELECTION CRITERIA: Randomized controlled trials comparing all methods of pharmacological diabetes therapy in people with diagnosed CFRD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias in the included studies. Authors also used GRADE to assess the quality of the evidence. MAIN RESULTS: The searches identified 29 trials (45 references). Four included trials provide results: one short-term single-center cross-over trial (seven adults) comparing insulin with oral repaglinide and no medication in adults with CFRD and normal fasting glucose; one long-term multicenter trial (61 adults with CFRD) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (67 adults) comparing insulin with oral repaglinide; and one 12-week single-center cross-over trial (20 adults) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin. Two ongoing trials of newly approved incretin mimics have been noted for possible future inclusion. Downgrading of the quality of the evidence was mainly due to risks of bias across all domains, but particularly due to concerns surrounding allocation concealment and selective reporting. There were also some concerns due to imprecision from small sample sizes and low event rates. Finally, there may be some bias due to the amounts of insulin and repaglinide given not being comparable. Data from one trial comparing insulin to placebo (39 participants) did not show any difference between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) or nutritional status (low-quality evidence). Similarly, no differences between groups were seen for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or quality of life (QoL). These results were mirrored in the narrative reports for the second trial in this comparison (seven participants). Data from the one-year trial comparing repaglinide to placebo (38 participants), showed no differences between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) and nutritional status (low-quality evidence). Also, no differences were seen between groups for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or QoL. These findings were mirrored in the narrative reports for the second trial (n = 7) in this comparison. Three trials compared insulin to repaglinide (119 participants). Data from one trial (n = 67) showed no difference in blood glucose levels at either 12 months (high-quality evidence) or 24 months; narrative reports from one trial (45 participants) reported no difference between groups, but the second trial (7 participants) reported a beneficial effect of insulin over repaglinide. Two trials (112 participants) found no difference between insulin and repaglinide in lung function or nutritional status (moderate-quality evidence). Two trials (56 participants) reported no difference in the number of hypoglycemic episodes (low-quality evidence). One trial (45 participants) reported no difference between groups in secondary infections and cystic fibrosis QoL. The single trial comparing glargine to neutral protamine Hagedorn insulin did not report directly on the review's primary outcomes, but did report no differences between groups in post-prandial glucose values and weight; neither group reported infectious complications. There was no difference in episodes of hypoglycemia (very low-quality evidence) and while there was no difference reported in QoL, all participants opted to continue treatment with glargine after the trial was completed. Mortality was not reported by any trial in any comparison, but death was not given as a reason for withdrawal in any trial. AUTHORS' CONCLUSIONS: This review has not found any conclusive evidence that any agent has a distinct advantage over another in controlling hyperglycemia or the clinical outcomes associated with CFRD. Given the treatment burden already experienced by people with cystic fibrosis, oral therapy may be a viable treatment option. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes and its impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority. Specifically, investigators should evaluate adherence to different therapies and also whether there is benefit in using additional hypoglycemic agents as well as the newly approved incretin mimics. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should also be further investigated as adjuvant therapy to insulin.