Journal of Clinical and Translational Endocrinology最新文献

In recent years, the prevalence of diabetic wounds has significantly increased, posing a substantial medical challenge due to their propensity for infection and delayed healing. These wounds not only increase mortality rates but also lead to amputations and severe mobility issues. To address this, advancements in bioactive molecules such as genes, growth factors, proteins, peptides, stem cells, and exosomes into targeted gene therapies have emerged as a preferred strategy among researchers. Additionally, the integration of photothermal therapy (PTT), nucleic acid, and gene therapy, along with 3D printing technology and the layer-by-layer (LBL) self-assembly approach, shows promise in diabetic wound treatment. Effective delivery of small interfering RNA (siRNA) relies on gene vectors. This review provides an in-depth exploration of the pathophysiological characteristics observed in diabetic wounds, encompassing diminished angiogenesis, heightened levels of reactive oxygen species, and impaired immune function. It further examines advancements in nucleic acid delivery, targeted gene therapy, advanced drug delivery systems, layer-by-layer (LBL) techniques, negative pressure wound therapy (NPWT), 3D printing, hyperbaric oxygen therapy, and ongoing clinical trials. Through the integration of recent research insights, this review presents innovative strategies aimed at augmenting the multifaceted management of diabetic wounds, thus paving the way for enhanced therapeutic outcomes in the future.

Aims

The study aims were to determine autoantibodies associated with type 1 diabetes (T1D), celiac disease (CD) and autoimmune thyroid disease (AITD) in individuals living with type 2 diabetes (T2D) compared to T1D and matched controls.

Methods

Individuals with T1D and T2D were randomly identified in health-care registers. Blood was collected through home-capillary sampling and autoantibodies associated with either T1D against glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A), CD against tissue transglutaminase (tTGA) or AITD against thyroid peroxidase (TPOA) were determined in an automated, multiplex Antibody Detection by Agglutination-PCR (ADAP) assay.

Results

GADA were detected in 46 % (88/191) of T1D and increased to 6.2 % (23/372) in T2D compared to 2.6 % (7/259) of controls (p = 0.0367). tTGA was low (1.1–2.6 %) and not different in between the study cohorts, nonetheless, in T1D tTGA was associated to islet autoantibodies. TPOA was more frequent in T1D, 27.1 % (53/191), compared to either T2D, 14.8 % (55/372; p = 0.0002) or controls, 14.3 % (37/259) (p = 0.0004). Overall, TPOA was more frequent in GADA positive (34.8 %; 8/23) than negative (13.5 %; 47/349; p = 0.0053) T2D individuals.

Conclusion

It’s suggested that analyzing GADA and TPOA may refine the autoimmune landscape in individuals clinically classified as T2D.

Background

Patients newly diagnosed with diabetes mellitus (diabetes), who require insulin must acquire diabetes “survival” skills prior to discharge home. COVID-19 revealed considerable limitations of traditional in-person, time-intensive delivery of diabetes education and survival skills training (diabetes survival skills training). Furthermore, diabetes survival skills training has not been designed to meet the specific learning needs of patients with diabetes and their caregivers, particularly if delivered by telehealth. The objective of the study was to identify and understand the needs of users (patients newly prescribed insulin and their caregivers) to inform the design of a diabetes survival skills training, specifically for telehealth delivery, through the application of user-centered design and adult learning and education principles.

Methods

Users included patients newly prescribed insulin, their caregivers, and laypersons without diabetes. In semi-structured interviews, users were asked about experienced or perceived challenges in learning diabetes survival skills. Interviews were audio-recorded and transcribed. Investigators performed iterative rounds of coding of interview transcripts utilizing a constant comparative method to identify themes describing the dominant challenges users experienced. Themes were then mapped to adult learning and education principles to identify novel educational design solutions that can be applied to telehealth-based learning.

Results

We interviewed 18 users: patients (N = 6, 33 %), caregivers (N = 4, 22 %), and laypersons (N = 8, 44 %). Users consistently described challenges in understanding diabetes survival skills while hospitalized; in preparing needed supplies to execute diabetes survival skills; and in executing diabetes survival skills at home. The challenges mapped to three educational strategies: (1) spiral learning; (2) repetitive goal directed practice and feedback, which have the potential to translate into design solutions supporting remote/virtual learning; and (3) form fits function organizer, which supports safe organization and use of supplies to execute diabetes survival skills independently.

Conclusion

Learning complex tasks, such as diabetes survival skills, requires time, repetition, and continued support. The combination of a user-centered design approach to uncover learning needs as well as identification of relevant adult learning and education principles could inform the design of more user-centered, feasible, effective, and sustainable diabetes survival skills training for telehealth delivery.

Background

Cystic fibrosis (CF) is a multi-organ disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Individuals with CF often have gastrointestinal (GI) dysbiosis due to chronic inflammation and antibiotic use. Previous studies suggested a role for vitamin D in reversing the GI dysbiosis found in CF.

Objective

To explore the potential role of a combination of high-dose oral cholecalciferol (vitamin D₃) and fermentable dietary fiber, inulin, to impact bacterial composition, richness, and diversity of intestinal and airway microbiota in adults with CF.

Methods

This was a 2 × 2 factorial, double-blinded, placebo-controlled, randomized, pilot clinical trial in which adults with CF received oral cholecalciferol (vitamin D₃) (50,000 IU/week) and/or inulin (12 g/day) for 12 weeks. Thus, there were 4 study groups (n = 10 subjects per group); 1) placebo 2) vitamin D₃ 3) inulin 4) vitamin D₃ plus inulin. Stool and sputum samples were collected at baseline (just before) and after the intervention and were analysed using 16S ribosomal RNA gene sequencing for gut and airway microbiota composition. Statistical analyses assessed alpha and beta diversity to evaluate microbial community changes.

Results

Of a total of 254 screened participants, 40 eligible participants were randomized to one of the 4 treatment arms. Participants receiving vitamin D₃ plus inulin exhibited greater changes in microbiome indexes in both intestinal and airway relative to those in the other study groups. Specific taxonomic changes supported the potential beneficial influence of this combination to mitigate both intestinal and airway dysbiosis in adults with CF.

Conclusion

This pilot study established that the combination of oral vitamin D₃ and the prebiotic inulin was well tolerated over 12 weeks in adults with CF and altered gut and airway bacterial communities. Future research appear warranted to define clinical outcomes and the role of microbiota changes therein with this approach.

Objective

To assess change in total daily dose (TDD) of insulin following a switch from subcutaneous (SC) injections to continuous subcutaneous insulin infusion (CSII) in pediatric patients with type 1 diabetes (T1D). Secondary objectives were to determine the change in %basal insulin, insulin to carbohydrate (I:C) ratios, insulin sensitivity factor (ISF), and HbA1c/IDAA1c.

Methods

A retrospective chart review of patients < 18 years of age who transitioned from SC to CSII at the Alberta Children’s Hospital (Calgary, Alberta, Canada) between January 2019 and March 2022.

Results

There was an increase of 0.04 units/kg/day in TDD from baseline vs 1–3 months later (p = 0.04, 95 % confidence interval (CI) [0.002, 0.072]). When stratified by age, a similar increase in TDD was observed in age 5–12 years only (p = 0.05, 95 % CI [0.0006, 0.8236]). There was a decrease in overall %basal insulin by 3 (44 % of TDD at baseline vs 41 % of TDD on CSII). (p = 0.02, 95 % CI [−5.5, −0.4]). No strengthening was seen in I:C ratios from baseline vs 1–3 months later. There was a significant strengthening of I:C ratios at all meals in the basal bolus group from 1–3 weeks to 1–3 months post-CSII; overall strengthening of ISF at both time points; and an overall HbA1c decrease −0.30 (p < 0.0001, CI [−0.45, −0.15]). Each extra year with diabetes was associated with a decrease in HbA1c by 0.07 % (p = 0.006).

Conclusions

TDD of insulin was not found to be decreased post CSII initiation and patient characteristics should be considered when changing from SC to CSII. HbA1c was significantly improved post CSII.

Background

Telemedicine has aided patients with diabetes during the COVID-19 pandemic in receiving better healthcare services. However, despite its numerous benefits, the use of this technology has faced several challenges. This study aimed to identify the challenges of using telemedicine for patients with diabetes during the COVID-19 pandemic.

Methods

This scoping review was conducted in 2024. Relevant articles published between 2020 and 2023 were searched in databases including PubMed, Scopus, Web of Science, ProQuest, and the Cochrane Library. Initially, 822 articles were retrieved, and after screening 21 articles were selected.

Results

The challenges of using telemedicine for patients with diabetes during the COVID-19 pandemic were categorized into the clinical, individual, organizational, and technical challenges. The clinical challenges included the lack of physical examinations and unavailability of patients’ medical history. The individual challenges contained difficulties in using smart phones by patients and their low level of literacy. The organizational challenges were related to insufficient laws about obtaining patient consent and limited reimbursement for telemedicine services, and the technical challenges included limited access to the high-speed Internet services and inadequate technical infrastructure for telemedicine services. Most studies highlighted the role of individual and organizational challenges in using this technology.

Conclusions

Considering the numerous challenges experienced in using telemedicine for patients with diabetes during the COVID-19 pandemic, it seems that more attention should be paid to address each of these challenges to improve the actual usage, service quality, and user acceptance of telemedicine technology. This, in turn, can lead to saving costs and improving the health status and quality of life of patients with diabetes.

There are several key points clinicians should consider when managing patients with overlapping thyroid and renal disease. Patients who are euthyroid and have chronic kidney disease (CKD) may physiologically have normal-high thyroid stimulating hormone (TSH), low free thyroxine (FT4), low free triiodothyronine (FT3) and normal-low reverse triiodothyronine (rT3). Untreated subclinical and primary hypothyroidism among patients with (CKD) is associated with reversible progression of renal failure. Supplementing these (CKD) patientswith levothyroxine can delay the progression of renal failure and prevent end stage renal disease (ESRD). Untreated hyperthyroidism increases the glomerular filtration rate (GFR) by 18 to 25%. Thus, the management of hyperthyroidism may unmask patients with undiagnosed CKD. There is no dosage adjustment required for methimazole among patients with CKD. However, methimazole may be eliminated during hemodialysis (HD) by around 30 to 40%. Patients with papillary thyroid cancer and ESRD may have higher rates of aggressive characteristics. Patients with CKD and ESRD undergoing radioiodine I-131 treatment for thyroid cancer are at increased risk of prolonged radiation transmission risk due to decreased iodine urinary excretion. Additionally, the optimal dosing and timing of radioiodine I-131 therapy amongst patients with ESRD and thyroid cancer requires further research. The use dosimetry studies and multidisciplinary coordination among nuclear medicine, nephrology and endocrinology is recommended for these patients.

Background and aim

Gut microbiota influences energy homeostasis in part through circulating hormones. Insulin-like growth factor-binding protein (IGFBP)-2 is a biomarker whose increase in systemic circulation is associated with positive effects on body weight and metabolism. In a recent clinical trial, probiotic Lacticaseibacillus rhamnosus HA-114 supplementation showed positive effects on eating behaviors and insulin resistance in overweight participants undergoing a weight-loss intervention. In this context, this ancillary study aimed at assessing the impact of L. rhamnosus HA-114 supplementation on plasma IGFBP-2 levels in these individuals, and whether this modulation correlated with changes in fat mass, energy metabolism, and eating behaviors.

Methods

Fasting plasma IGFBP-2 concentrations were quantified in 100 overweight or obese men and women enrolled in a 12-week diet-based weight reduction program (−500 kcal/day), in combination with probiotic L. rhamnosus HA-114 or placebo supplementation. Baseline and changes in circulating IGFBP-2 concentrations were correlated with anthropometric parameter, glucose and lipid metabolism, cardiorespiratory function and eating behaviors.

Results

On average, the intervention reduced BMI by 4.6 % and increased IGFBP-2 by 13 %, regardless of supplementation group. Individuals who presented an increase in IGFBP-2 levels had significantly greater reductions in BMI. Changes in IGFBP-2 levels were correlated with loss in fat mass (r = 0.2, p < 0.001) in the probiotic-supplemented group, but not with other metabolic parameters or eating behaviors. Baseline IGFBP-2 levels were not associated with weight loss or improvements in cardiometabolic parameters.

Conclusion

Probiotic supplementation with L. rhamnosus HA-114 did not modulate plasma IGFBP-2 levels. Changes in IGFBP-2 levels were correlated with greater reductions in BMI, but not with other metabolic parameters or eating behaviors, indicating that the benefits of HA-114 on eating behaviors are likely independent of IGFBP-2. Additional changes in microbiota might be required to modulate IGFBP-2 and observe its associations with eating behaviors and cardiometabolic improvements.