Chrysin-based supramolecular cyclodextrin-calixarene drug delivery system: a novel approach for attenuating cardiac fibrosis in chronic diabetes.

Introduction: Cardiac fibrosis is strongly induced by diabetic conditions. Both chrysin (CHR) and calixarene OTX008, a specific inhibitor of galectin 1 (Gal-1), seem able to reduce transforming growth factor beta (TGF-ß)/SMAD pro-fibrotic pathways, but their use is limited to their low solubility. Therefore, we formulated a dual-action supramolecular system, combining CHR with sulfobutylated ß-cyclodextrin (SBECD) and OTX008 (SBECD + OTX + CHR). Here we aimed to test the anti-fibrotic effects of SBECD + OTX + CHR in hyperglycemic H9c2 cardiomyocytes and in a mouse model of chronic diabetes. Methods: H9c2 cardiomyocytes were exposed to normal (NG, 5.5 mM) or high glucose (HG, 33 mM) for 48 h, then treated with SBECD + OTX + CHR (containing OTX008 0.75-1.25-2.5 µM) or the single compounds for 6 days. TGF-ß/SMAD pathways, Mitogen-Activated Protein Kinases (MAPKs) and Gal-1 levels were assayed by Enzyme-Linked Immunosorbent Assays (ELISAs) or Real-Time Quantitative Reverse Transcription Polymerase chain reaction (qRT-PCR). Adult CD1 male mice received a single intraperitoneal (i.p.) administration of streptozotocin (STZ) at a dosage of 102 mg/kg body weight. From the second week of diabetes, mice received 2 times/week the following i.p. treatments: OTX (5 mg/kg)-SBECD; OTX (5 mg/kg)-SBECD-CHR, SBECD-CHR, SBECD. After a 22-week period of diabetes, mice were euthanized and cardiac tissue used for tissue staining, ELISA, qRT-PCR aimed to analyse TGF-ß/SMAD, extracellular matrix (ECM) components and Gal-1. Results: In H9c2 cells exposed to HG, SBECD + OTX + CHR significantly ameliorated the damaged morphology and reduced TGF-ß1, its receptors (TGFßR1 and TGFßR2), SMAD2/4, MAPKs and Gal-1. Accordingly, these markers were reduced also in cardiac tissue from chronic diabetes, in which an amelioration of cardiac remodeling and ECM was evident. In both settings, SBECD + OTX + CHR was the most effective treatment compared to the other ones. Conclusion: The CHR-based supramolecular SBECD-calixarene drug delivery system, by enhancing the solubility and the bioavailability of both CHR and calixarene OTX008, and by combining their effects, showed a strong anti-fibrotic activity in rat cardiomyocytes and in cardiac tissue from mice with chronic diabetes. Also an improved cardiac tissue remodeling was evident. Therefore, new drug delivery system, which could be considered as a novel putative therapeutic strategy for the treatment of diabetes-induced cardiac fibrosis.

A comparison of rural-urban differences in out-of-pocket expenses among older Mexicans with diabetes.

Objective: To compare total out-of-pocket expenses for physician visits and medications among older adults living with diabetes in Mexico from urban, semi-urban, and rural areas. Methods: The sample included 2,398 Mexicans aged 65 years and older with self-reported diabetes from the 2018 Mexican Health and Aging Study. Out-of-pocket expenses for physician visits and medications were regressed on locality, controlling for several factors. Results: The profile of those with higher out-of-pocket medication expenditures included rural localities, higher education, unmarried, depressive symptoms, participation in Seguro Popular, and lacking insurance. In the multivariate analysis, rural older adults with diabetes paid a higher amount in medication expenditures compared with other localities. Conclusion: Differences in locality are closely tied to the effective implementation of Seguro Popular. Although this program has improved access to care, participants have higher out-of-pocket expenditures for medications than those on employer-based plans across all localities. Among all groups, the uninsured bare the highest burden of expenditures, highlighting a continued need to address health inequities for the most underserved populations.

Does concomitance of Hashimoto's disease and type 1 diabetes affect diabetes control and development of its complications?

INTRODUCTION: Autoimmune diseases concomitant with diabetes may complicate the treatment and adversely affect the prognosis. The most common is Hashimoto's disease (HD). We compared diabetes control and prevalence of chronic complications in type 1 diabetes patients differing in the coexistence of HD. MATERIAL AND METHODS: Medical records of 188 type 1 diabetics were analysed. Hashimoto's disease was diagnosed based on medical history, as well as determination of the levels of thyroid peroxidase antibodies, hormones and ultrasound examination. Statistical analysis was performed using Statistica 10PL. RESULTS: HD was diagnosed in 43 (23%) patients. The mean HbA1c was 8.8 ±1.5% in the group with HD, and 9 ±1.6% in the group without HD (ns). The prevalence of diabetes complications was similar in both groups: ischaemic heart disease was diagnosed in 19% of patients with HD and 19% without HD, cerebral vascular insufficiency - 8% and 7%, peripheral neuropathy - 14% and 12%, sensory polyneuropathy - 47% and 46%, diabetic foot - 7% and 8%, Charcot osteoarthropathy - 7% and 2%, cardiovascular neuropathy - 21% and 28%, neuropathy of the gastrointestinal tract - 5% and 6%, nephropathy - 12% and 19%, retinopathy - 42% and 43%, and cataract in 28% and 19%, respectively. Impaired hypoglycaemia perception was rarer in the group with HD: 9% vs. 25% (p ≈ 0.04). CONCLUSIONS: Hashimoto's disease does not significantly affect the level of type 1 diabetes control or the development of its complications. Only autonomic neuropathy in the form of impaired awareness of hypoglycaemia is rarer in patients with that thyroiditis.

Small bronchiolar histopathological changes related to prolonged diabetes / Pequeños cambios histopatológicos bronquiolares relacionados con la diabetes prolongada

SUMMARY: Diabetes mellitus increases the risk of developing chronic obstructive pulmonary disease (COPD). The small bronchiole is a prominent site of airflow obstruction that causes increased airway resistance in patients with the COPD. Therefore, the histological and ultrastructural changes in small bronchioles in streptozotocin (STZ)-induced chronic diabetes were determined. Twenty-four weeks after STZ induction, rats were sacrificed, and the right and left lungs were collected for examination by light and electron microscopy. The alterations to the small bronchioles were the same in both lungs of these diabetic rats. The bronchiolar epithelial cells, both ciliated and secretory club cells, showed pyknotic nuclei and damaged cytoplasmic organelles. Increased thickening of the bronchiolar wall occurred in diabetic rats due to smooth muscle layer thickening, inflammatory cell infiltration, and increased numbers of myofibroblasts with collagen deposition.These results indicated that chronic diabetes caused extreme damage to small bronchioles, which may lead to chronic small airway obstruction and ultimately increase the likelihood of COPD progression. This basic knowledge provides a better understanding of the progression of pathogenesis in the small airways of patients with prolonged diabetes.

RESUMEN: La diabetes mellitus aumenta el riesgo de desarrollar enfermedad pulmonar obstructiva crónica (EPOC). El bronquiolo es un sitio prominente de obstrucción del flujo de aire que causa una mayor resistencia de las vías respiratorias en pacientes con EPOC. Por lo tanto, se determinaron los cambios histológicos y ultraestructurales en los bronquiolos en la diabetes crónica inducida por estreptozotocina (STZ). 24 semanas después de la inducción de STZ, se sacrificaron las ratas y se analizaron los pulmones derecho e izquierdo por microscopía óptica y electrónica. Las alteraciones de los pequeños bronquiolos fueron las mismas en ambos pulmones de estas ratas diabéticas. Las células epiteliales bronquiolares, tanto ciliadas como secretoras, mostraban núcleos picnóticos y orgánelos citoplasmáticos dañados. Se produjo un aumento del engrosamiento de la pared bronquiolar en ratas diabéticas debido al engrosamiento de la capa de músculo liso, infiltración de células inflamatorias y un mayor número de miofibroblastos con colágeno. Estos resultados indicaron que la diabetes crónica causaba daño extremo a los pequeños bronquiolos, lo que puede conducir a una obstrucción crónica de las vías respiratorias pequeñas y además aumentar la probabilidad de progresión de la EPOC. Esta información proporcionará un mejor conocimiento de la patogénesis en las vías respiratorias pequeñas de los pacientes con diabetes prolongada.

Increased leukotriene B4 plasma concentration in type 2 diabetes individuals with cardiovascular autonomic neuropathy.

BACKGROUND AND AIM: A low-grade inflammation is associated with cardiac autonomic neuropathy (CAN) and increased concentration of leukotriene B4 (LTB4) was found in individuals with type 1 diabetes and definitive CAN. This cross-sectional study evaluated plasma concentration of LTB4 and of other inflammatory mediators, namely, tumor necrosis factor (TNF), interleukin (IL)1B, and IL10 in individuals with type 2 diabetes (T2D) and different degrees of CAN, and correlated these inflammatory mediators with the degree of glycemic control and with a surrogate marker of insulin resistance. METHODS: TNF, IL1B, IL10 and LTB4 plasma concentrations were measured in 129 T2D subjects (62% women with [median] age of 63 years, disease duration of 8 years and HbA1c of 7.3%) with or without CAN. The Lipid accumulation product index was used as a surrogate marker of insulin resistance. RESULTS: LTB4 concentration was significantly higher in those presenting incipient CAN (69.7 ± 16.6 pg mL-1) and definitive CAN (71.5 ± 15.7 pg mL-1) versus those without CAN (57.0 ± 13.9 pg mL-1). The groups without CAN and with incipient CAN were pooled (group without definitive CAN) and compared to those with definitive CAN. LTB4 concentration was higher in the latter group, as well as TNF concentration, while IL10 concentration was lower in this group. After adjustment for confounding variables, only LTB4 concentration remained significantly different between the groups with and without definitive CAN. Plasma concentration of LTB4 did not correlate with the degree of glycemic control. After sorting the participants by sex, a borderline weak correlation was found between LTB4 and the Lipid accumulation product index in women. CONCLUSION: In the T2D setting, circulating LTB4 concentration seems to be associated with cardiovascular dysautonomia.

Estilo de vida actual de los pacientes con diabetes mellitus tipo 2 / Current lifestyle of patients with diabetes mellitus type 2

Se realizó un estudio descriptivo transversal con el objetivo principal de determinar el estilo de vida actual de los pacientes con diabetes mellitus tipo 2. Para la recolección de la información se utilizó el cuestionario IMEVID . La población está conformada por 60 pacientes inscritos al programa de diabetes e hipertensión de una Institución Promotora de Salud (IPS) de I nivel; como muestra se tuvo en cuenta 30 pacientes que asistieron sin falta al control de la diabetes a los cuales se les aplicó el instrumento. Las variables utilizadas son nutrición, actividad física, consumo de tabaco, consumo de alcohol, información sobre la diabetes, emociones, adherencia terapéutica y estilos de vida. Se concluye que con relación a la edad de los pacientes encuestados se obtiene que estos se encuentran entre dos etapas muy importantes del ciclo vital humano, adultez media y adultez tardía; el 80% de los pacientes encuestados presentaron prácticas de estilos de vida saludables, el cual ayuda a prevenir complicaciones con relación a su patología obteniendo de esta manera un mejor bienestar durante su vida y la evolución de la enfermedad.

We performed a cross-sectional study with the primary objective of determining the current lifestyle of patients with diabetes mellitus type 2, for the data collection was used the IMEVID questionnaire. The population consists of 60 patients enrolled in the diabetes and hypertension program in a Health Promoting Institution (IPS) Level I, as a sample were taken into account 30 patients who attended every day to the diabetes control whose were applied the instrument. The variables used are nutrition, physical activity, tobacco consumption, alcohol consumption, diabetes information, emotions, therapeutic adherence and lifestyle. We conclude concerning to the age of the patients surveyed that they are in two important stages of the human life cycle, middle adulthood and late adulthood, 80% of patients surveyed had practice healthy lifestyles which helps to prevent complications related to their condition, thus obtaining a better life and welfare during the course of the disease.