Type 2 Diabetes Research Articles

TGF-β-mediated crosstalk between TIGIT+ Tregs and CD226+CD8+ T cells in the progression and remission of type 1 diabetes

Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by hyperglycemia resulting from the destruction of insulin-producing β-cells that is traditionally deemed irreversible, but partial remission (PR) with temporary reversal of hyperglycemia is sometimes observed. Here we use single-cell RNA sequencing to delineate the immune cell landscape across patients in different T1D stages. Together with cohort validation and functional assays, we observe dynamic changes in TIGIT+CCR7− Tregs and CD226+CCR7−CD8+ cytotoxic T cells during the peri-remission phase. Machine learning algorithms further identify TIGIT+CCR7− Tregs and CD226+CD8+ T cells as biomarkers for β-cell function decline in a predictive model, while cell communication analysis and in vitro assays suggest that TIGIT+CCR7− Tregs may inhibit CD226+CCR7−CD8+ T cells via TGF-β signaling. Lastly, in both cyclophosphamide-induced and streptozotocin (STZ)-induced mouse diabetes models, CD226 inhibition postpones insulitis onset and reduces hyperglycemia severity. Our results thus identify two interrelated immune cell subsets that may serve as biomarkers for monitoring disease progression and targets for therapeutic intervention of T1D.

Microbiota Transplantation in Individuals with Type 2 Diabetes and a High Degree of Insulin Resistance.

The objective of this study was to determine the results of fecal microbiota transplantation (FMT) from healthy lean subjects in patients with type 2 diabetes (T2D); Methods: We designed a phase II, randomized, single-blind, parallel-arm clinical trial. Twenty-one subjects (12 men [57.1%] and 9 women [42.9%]), who had previously signed an informed consent were randomized to FMT from lean donors, a probiotic (Lactobacillus delbrueckii spp. bulgaricus LB-14), or placebo. Mean age at baseline was 62.5 ± 5.8 years and mean body mass index (BMI) at baseline was approximately 32.4 ± 2.4 kg/m2. Anthropometric measures, biochemical variables, oral glucose tolerance test (OGTT), and a stool microbiota analysis were performed (baseline, 4 and 12 weeks). The trial was conducted following the Declaration of Helsinki, Good Clinical Practice Guides (CPMP/ICH/135/95) and the current Spanish legislation regarding clinical trials (RD 223/2004).; Results: FMT changes occurred at the expense of the species found in the donor. No differences in weight, body mass index, HbA1c, or the results of the OGTT for glucose and insulin were found between groups after the intervention, although a decrease in uric acid was observed in the probiotic group (-0.5 mg/dL; p = 0.037) and a mild increase in HbA1c in the FMT group (+0.25%; p = 0.041); Conclusions: In our sample, neither FMT from healthy and lean donors nor a probiotic were effective in improving insulin sensitivity and HbA1c in patients with T2D.

Ketone Management in Pediatric Diabetes Centers in the USA: Current Practices and a Call for Improved Standardization

Introduction: Diabetic ketoacidosis (DKA) is the leading cause of mortality among youth with type 1 diabetes (T1D). Guidelines for DKA prevention exist; however, specific guidance about when to check ketones and how to manage youth using insulin pumps and automated insulin delivery (AID) systems is lacking. Methods: A 35-item online survey exploring clinical ketone management practices for youth with T1D in the USA was distributed to diabetes healthcare professionals (HCPs). Survey responses, including multiple-choice and Likert scale questions, were summarized and rates of agreement and disagreement (Likert scale 4, 5 vs. 1, 2, 3) are reported. Results: In total, 123 HCPs (51% physicians, 26% diabetes educators, 19% nurse practitioners) from 47 institutions completed the survey. Seventy percent worked at academic specialty centers. Ninety-seven percent reported >50% continuous glucose monitoring use in their clinic and 72% reported >50% insulin pump use. Although 79% reported having ketone management protocols, the level and duration of hyperglycemia at which ketone monitoring was advised ranged from >200 to 350 mg/dL and from 0 min to >6 h of duration. While 72% had distinct ketone management protocols for pump users, only 29% had specific protocols for AID. Sixty-two percent agreed that DKA due to infusion site failure was a significant problem in their practice, and 70% agreed there was a need to standardize ketone management guidelines. Conclusions: The preventable nature and high incidence of DKA highlight the need to build consensus for clinical ketone management and to develop tools to facilitate management, especially as the use of diabetes technologies continues to increase.

Surgical or medical treatment of obesity-associated type 2 diabetes-an increasing clinical conundrum

In this editorial, we comment on the article by He et al , specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy in the management of type 2 diabetes (T2D) associated with obesity. Bariatric surgery has now also been shown to be safe and effective in pre-teens and teenagers with obesity and T2D, but information on newer GLP-1RAs in these groups is predictably limited. In older individuals (age > 65 years), both bariatric surgery and GLP-1RA therapy improve cardiovascular outcomes. Bariatric surgery is not infrequently associated with post-operative postprandial hypoglycemia, which is not the case with GLP-1RAs and, paradoxically, there is evidence that GLP-1RAs may reduce both the frequency and severity of postprandial hypoglycemia. Comparative trials of the long-term efficacy of bariatric surgery and GLP-1RAs are indicated.

The effect of antidiabetic drugs on bone metabolism: a concise review.

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia, which derives from either insufficient insulin production [type 1 diabetes mellitus (T1DM)] or both impaired insulin sensitivity along with inadequate insulin production [type 2 diabetes mellitus (T2DM)] and affects millions of people worldwide. In addition to the adverse effects of DM on classical target organs and tissues, skeletal health can also be adversely affected. There is considerable evidence linking DM with osteoporosis. The fracture risk in patients with DM differs upon the type of diabetes, and it appears to be related to the type of anti-diabetic treatment. Antidiabetic drugs may have various effects on bone health. Most of them have neutral or even favorable effects on bone metabolism with the exception of thiazolidinediones (TZDs). Some studies suggest that TZDs may have negative impact on bone health by decreasing bone formation and increasing the fracture risk. There are also limited studies linking the use of canagliflozin, a Sodium-glucose contransporter-2 inhibitor (SGLT2i), with increased fracture risk. On the other hand, therapies that are based on incretin effect, like Dipeptidyl peptidase-4 inhibitors (DPP-4i) and Glucagon-like peptide-1 receptor agonizts (GLP-1RAs) might have positive effects on bone health by promoting bone formation. Herein we review the impact of antidiabetic drugs on bone health, highlighting the potential benefits and risks associated with these medications in an attempt to contribute to the development of personalized treatment strategies for individuals with DM.

Mapping the evolution and impact of ketogenic diet research on diabetes management: a comprehensive bibliometric analysis from 2005 to 2024

ObjectiveThe ketogenic diet (KD) has been explored for diabetes management; however, a quantitative synthesis of its specific effects on diabetes has not yet been conducted. This study aims to examine the current status and research hotspots of KD in diabetes management from 2005 to 2024, providing a reference for future research.MethodsWe retrieved articles published between 2005 and 2024 from the Web of Science database and analyzed them using R software, VOSviewer, and CiteSpace.ResultsThis study includes 432 relevant publications. From 2005 to 2024, the volume of literature in this field has shown a steady upward trend, with a notable increase from 2017 to 2021, and a slight decline observed from 2021 to 2023. The United States is the leading country in terms of the number of publications, followed by China, Australia, and Canada. The United States not only leads in publication volume but also maintains a broader international collaboration network. Nutrients and the American Journal of Clinical Nutrition are the most frequently published and cited journals. Current research hotspots primarily focus on the impact of KD on blood glucose control, insulin resistance, and lipid metabolism in diabetic patients. Mechanistic studies on KD in diabetes management concentrate on aspects such as the “regulation of genes by β-hydroxybutyrate,” “anti-inflammatory effects,” and “oxidative stress.” The role of the gut microbiome is also emerging as an important research area. Currently, exploring the application of KD in managing different age groups and types of diabetes has become a significant research trend.ConclusionAs an emerging dietary intervention, KD is gradually attracting widespread attention from researchers around the world and is expected to become a major research focus in the future for diabetes management and control. This paper provides a systematic review and analysis of the current research status and hotspots of KD in diabetes management, offering important references and insights for future research in related fields.

Genetic and therapeutic for oral lichen planus and diabetes mellitus: a comprehensive study

BackgroundThis study employed a bidirectional Mendelian Randomization (MR) approach to explore the causal relationships between Oral Lichen Planus (OLP), diabetes mellitus (DM), and glycemic control. It also aims to identify potential pharmacological and herbal treatments that effectively address both OLP and the metabolic dysfunctions associated with DM.MethodsThis study employs a two-way MR approach to investigate the potential causal relationships between diabetes type and glycated hemoglobin (HbA1c) levels, and the risk of OLP. We analyzed differentially expressed genes from the OLP dataset in the Genomics Expression Omnibus (GEO) database, cross-referencing these with HbA1c-related genes for enrichment analysis. Additionally, the Drug-Gene Interaction Database (DGIdb) and Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) were utilized to assess the effectiveness of specific drugs, herbs, and ingredients in treating OLP while managing blood glucose levels.ResultsThe MR analysis revealed a significant association between Type 1 Diabetes mellitus (T1DM) and an increased risk of OLP, unlike Type 2 Diabetes mellitus (T2DM). This finding indicates a unique immunological interaction in T1DM that may predispose individuals to OLP. The drug prediction analysis focused on core targets linked to OLP and HbA1c, evaluating the therapeutic potential of retinoic acid, prednisone, and thalidomide for treating OLP and regulating blood glucose levels. Additionally, herbal medicines such as Ecliptae herbaand Amygdalus communis vas, along with herbal ingredients like quercetin, luteolin, and 17-beta-estradiol, were identified for their anti-inflammatory properties and potential to mitigate metabolic dysfunction in diabetes.ConclusionThe study highlighted a complex interplay between diabetes and OLP, underscoring the efficacy of integrated therapeutic strategies that target both conditions. The findings suggest that both pharmaceutical and herbal treatments can effectively manage the clinical manifestations of OLP and associated metabolic challenges. This holistic approach to treatment could significantly enhance patient outcomes by addressing the interconnected aspects of these chronic conditions.

Prognostic nutritional index as a predictor of mortality among patients admitted to ICU with acute exacerbation of chronic obstructive pulmonary disease

BackgroundThe PNI is a metric that may assess the combined impact of the inflammatory process and nutritional condition. It may be beneficial in evaluating the nutritional state of patients with AECOPD.In recent years, it has also been utilized for prognostic assessment of cases admitted to the critical care unit.Aim of the workThe objective of the research was to assess the relationship between PNI and the prognosis for ICU patients with AECOPD.Patients and methodsThis was a prospective cross-sectional observational research carried out in the RICU of Ain Shams University Hospitals from April 2023 to March 2024. The study included 161 AECOPD patients who were admitted to RICU. All patients underwent demographic data collection, special habits and comorbid conditions evaluations, and hematological indices with laboratory markers and ABG. ICU and hospital stay duration, SOFA score, and SAPS II were also documented. The PNI value was computed using the following equation: the formula to calculate the value is 10 times the serum albumin concentration in grams per deciliter plus 0.005 times the total lymphocyte count in cubic millimeters. The main measure of interest was the death rate within 30 days for all causes. Additional measures were the duration of stay in the ICU, the duration of hospitalization, and the rate of MV.ResultsThere was a significant relationship between PNI and type of respiratory failure, mechanical ventilation, fate, hypertension, and diabetes. One hundred five (65.2%) of the patients were extubated and discharged, while 56 (34.8%) of them died. The study also noted a significant positive relationship among PNI and HCT, lymphocytic %, HB, and albumin. However, there was a significant negative relationship between PNI and age, RDW, WBC, neutrophil count, neutrophil %, NLR, CRP, SAPSII, and SOFA. The SAPS II score (with SAPS II mortality) had greater AUROC in predicting mortality than PNI, NLR, and SOFA. The optimal cut-off value for PNI in this study was ≤ 29 with sensitivity 82.14% and specificity 56.19%.ConclusionThe study showed that PNI can be a useful biomarker for AECOPD. PNI with SAPS II scores on admission to ICU were closely correlated to adverse outcomes.

Referral pathway and competency profiles of primary care physiotherapists and kinesiologists for physical activity interventions for diabetes: a modified Delphi study

BackgroundHigh quality diabetes care is an essential service in primary care settings since the prevalence and associated complications of diabetes is increasing. Physical activity is effective for the prevention and management of diabetes yet is underutilized in diabetes care. Exercise professionals have specialized skills to deliver physical activity interventions, but effective interprofessional collaboration for diabetes care requires role clarity. This study established the competencies of entry-level physiotherapists and kinesiologists for physical activity interventions for diabetes care in primary care settings and used these competencies to develop clinical tools to promote role clarity in interprofessional care teams.MethodsWe used a modified Delphi process. Eleven physiotherapy and three kinesiology subject matter experts participated in two rounds of Delphi surveys to develop discipline and context specific competencies. These competencies were used to draft competency profiles and a referral pathway tool. Eleven of the participants then participated in a focus group for member-checking of the tools. Descriptive statistics and content analysis were used to analyze quantitative and qualitative data respectively.ResultsThe modified Delphi process resulted in 38 physiotherapy and 27 kinesiology competencies that identify the distinct roles of physiotherapists and kinesiologists in delivering physical activity interventions for diabetes care. The physiotherapy competencies describes their unique role in supporting people with all types of diabetes to engage in physical activity despite complex medical or physical barriers. The kinesiology competencies indicate where these professionals may require additional training, especially when working with people living with type 1 diabetes or who are pregnant. All developed tools had good face validity and were seen to be potentially useful tools by the subject matter experts.ConclusionsThe findings highlight that both physiotherapists and kinesiologists have fundamental skills and abilities to deliver physical activity interventions to people living with diabetes, but that different exercise professionals may be needed depending on the complexity of the clinical profile. The developed clinical tools support improved interprofessional collaboration by clarifying physiotherapy and kinesiology roles in delivering physical activity interventions for diabetes care and highlighting how the two distinct professions can contribute to addressing the growing diabetes epidemic in primary care.

Hypoglycemic Properties of Leccinum scabrum Extracts-An In Vitro Study on α-Glucosidase and α-Amylase Inhibition and Metabolic Profile Determination.

Type-2 diabetes affects an increasing percentage of the world's population and its control through dietary management, involving the consumption of health-promoting foods or their derived supplements, is a common strategy. Several mushroom species have been demonstrated to be endowed with antidiabetic properties, resulting from their ability in improving insulin sensitivity and production, or inhibiting the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase. This study aimed to investigate for the first time the hypoglycemic properties of the edible mushroom Leccinum scabrum (Bull.) Gray. Mushroom extracts were prepared through the microwave-assisted extraction (MAE) technique using green solvents with different polarity degrees. The inhibition activity of all the obtained extracts on both α-glucosidase and α-amylase was evaluated and the highest activity was observed for the EtOAc extract which showed an IC50 value about 60-fold lower than the reference compound 1-deoxynojirimycin (DNJ) on α-glucosidase (0.42 ± 0.02 and 25.4 ± 0.6 µg/mL, respectively). As expected on the basis of the literature data concerning both α-glucosidase and α-amylase inhibition, a milder inhibition activity on pancreatic α-amylase was observed. Preliminary in vivo tests on Drosophila melanogaster carried out on the most active obtained extract (EtOAc) confirmed the in vitro observed hypoglycemic activity. Finally, the EtOAc extract metabolic profile was determined through GC-MS and HRMS analyses.

The economic burden of type 2 diabetes on the public healthcare system in Kenya: a cost of illness study

BackgroundThe burden of chronic non-communicable diseases (NCDs) is a growing public health concern. The availability of cost-of-illness data, particularly public healthcare costs for NCDs, is limited in Sub-Saharan Africa (SSA), yet such data evidence is needed for policy action.ObjectiveThe objective of this study was to estimate the economic burden of type 2 diabetes (T2D) on Kenya’s public healthcare system in 2021 and project costs for 2045.MethodsThis was a cost-of-illness study using the prevalence-based bottom-up costing approach to estimate the economic burden of T2D in the year 2021. We further conducted projections on the estimated costs for the year 2045. The costs were estimated corresponding to the care, treatment, and management of diabetes and some diabetes complications based on the primary data collected from six healthcare facilities in Nairobi and secondary costing data from previous costing studies in low and middle-income countries (LMICs). The data capture and costing analysis were done in Microsoft Excel 16, and sensitivity analysis was conducted on all the parameters to estimate the cost changes.ResultsThe total cost of managing T2D for the healthcare system in Kenya was estimated to be US$ 635 million (KES 74,521 million) in 2021. This was an increase of US$ 2 million (KES 197 million) considering the screening costs of undiagnosed T2D in the country. The major cost driver representing 59% of the overall costs was attributed to T2D complications, with nephropathy having the highest estimated costs of care and management (US$ 332 million (KES 36, 457 million). The total cost for T2D was projected to rise to US$ 1.6 billion (KES 177 billion) in 2045.ConclusionThis study shows that T2D imposes a huge burden on Kenya’s healthcare system. There is a need for government and societal action to develop and implement policies that prevent T2D, and appropriately plan care for those diagnosed with T2D.

Tracing links between micronutrients and type 2 diabetes risk: the singular role of selenium.

Type 2 diabetes (T2D) is a growing global health concern. While micronutrients are crucial for physiological functions and metabolic balance, their precise links to T2D are not fully understood. We investigated the causal relationships between 15 key micronutrients and T2D risk using both univariate and multivariate Mendelian randomization (MR) methods. Our analysis leveraged data from a large prospective cohort genome-wide association study (GWAS) on these micronutrients and T2D. We employed MR techniques such as inverse variance weighting (IVW), MR Egger, weighted median, and simple models. Multivariate analysis adjusted for diabetes-related factors like body mass index (BMI) and hypertension to assess the independent effects of micronutrients, particularly selenium, on T2D risk. Selenium intake was associated with an increased risk of T2D, with an odds ratio (OR) of 1.045, a 95% confidence interval (CI) ranging from 1.009 to 1.082, and a P-value of 0.015. This association was consistent in multivariate analyses, suggesting an independent effect of selenium on T2D risk after adjusting for confounders. Our study presents novel evidence of a positive correlation between selenium intake and T2D risk, underscoring the importance of micronutrients in diabetes prevention and treatment strategies. Further research is necessary to confirm these findings and to clarify the specific biological mechanisms through which selenium influences diabetes risk.

Immunotherapy-Based Strategies for Treatment of Type 1 Diabetes.

Type 1 diabetes (T1D) is more than an insulin-deficiency disease-it is an autoimmune disease, and the field is moving towards adopting disease-modifying immunotherapy as part of clinical care during T1D development. Recent successful immunotherapies as well as therapies that missed the mark are reviewed. T cell-directed therapies may allow for the greatest preservation of β cell function but also come with more side effects. Anti-cytokine therapies are very promising but likely need chronic administration. Antigen-specific therapies while safe have not produced meaningful results. Most successful trials have been conducted in adolescents and adults with stage 3 T1D (clinical T1D) with preserved C-peptide (up to 60% more compared to placebo) demonstrated 1-2 years post treatment. HbA1c and total insulin dose are less likely to be significantly different between treated and placebo groups because most participants in studies are meeting glycemic targets and because of the heterogeneous nature of these measures. In the prevention space (delaying progression from stage 2 to stage 3 T1D) the outcome is more discrete, and a T cell-directed therapy, teplizumab, has received FDA approval. Even negative studies with promising mechanistic and safety profiles have added value. What is clear, a single administration or short course of an immunotherapy is unlikely to provide sustained freedom from exogenous insulin.

Cognitive disorders in type 1 diabetes: Role of brain glucose variation, insulin activity and glucocorticoid exposure.

The number of patients with type 2 diabetes (T2D) and type 1 diabetes (T1D) is on the rise, partly due to a global increase in new T1D cases among children. Beyond the well-documented microvascular and macrovascular complications, there is now substantial evidence indicating that diabetes also impacts the brain, leading to neuropsychological impairments. The risk of developing neuropsychiatric symptoms is notably higher in childhood due to the ongoing maturation of the brain, which makes it more susceptible to damage. Despite this awareness, the specific effects of diabetes on cognitive function remain poorly understood. This review synthesizes literature on the impact of diabetes on cognition and its relationship with brain structural changes. It presents data and hypotheses to explain how T1D contributes to cognitive dysfunction, with a particular focus on children and adolescents. The emphasis on the pediatric population is intentional, as young diabetic patients typically have fewer comorbidities, reducing confounding factors and simplifying the investigation of cognitive alterations. We examine the roles of hypo- and hyperglycemia, as well as the emerging role of glucocorticoids in the development of neuropsychological disorders. When specific mechanisms related to T1D are available, they are highlighted; otherwise, data and hypotheses applicable to both T1D and T2D are discussed.

SARS-CoV-2 Infection and New-Onset Type 2 Diabetes Among Pediatric Patients, 2020 to 2022

In adults, diagnoses of new-onset type 2 diabetes (T2D) have increased following diagnosis with COVID-19, but whether this occurs in children is unclear. To determine whether risk of incident T2D diagnosis is increased during the 6 months after SARS-CoV-2 infection among children. This retrospective cohort study used electronic health records from the TriNetX analytics platforms between January 1, 2020, and December 31, 2022. Pediatric patients aged 10 to 19 years without preexisting diabetes were eligible for inclusion. Data were analyzed from August 15 to September 15, 2023, with supplemental analyses January 20 and August 8 to 13, 2024. Diagnosis of COVID-19 or a non-COVID-19 respiratory infection. New diagnosis of T2D compared by risk ratios (RRs) and 95% CIs at 1, 3, and 6 months after index infection. The main study population included 613 602 patients, consisting of 306 801 with COVID-19 (mean [SD] age at index, 14.9 [2.9] years; 52.8% female) and 306 801 with other respiratory infections (ORIs) but no documented COVID-19 (mean [SD] age at index, 14.9 [2.9] years; 52.6% female) after propensity score matching. Risk of a new diagnosis of T2D was significantly increased from day of infection to 1, 3, and 6 months after COVID-19 diagnosis compared with the matched cohort with ORIs (RR at 1 month, 1.55 [95% CI, 1.28-1.89]; RR at 3 months: 1.48 [95% CI, 1.24-1.76]; RR at 6 months: 1.58 [95% CI, 1.35-1.85]). Similar results were found in the subpopulation classified as having overweight or obesity (RR at 1 month: 2.07 [95% CI, 1.12-3.83]; RR at 3 months: 2.00 [95% CI, 1.15-3.47]; RR at 6 months: 2.27 [95% CI, 1.38-3.75]) and the hospitalized subpopulation (RR at 1 month: 3.10 [95% CI, 2.04-4.71]; RR at 3 months: 2.74 [95% CI, 1.90-3.96]; RR at 6 months: 2.62 [95% CI, 1.87-3.66]). Similar elevation in risk was found at 3 and 6 months when excluding patients diagnosed during the interval from the index date to 1 month after infection. In this retrospective cohort study of children and adolescents aged 10 to 19 years, the risk of an incident diagnosis of T2D was greater following a COVID-19 diagnosis than in children diagnosed with ORIs. Further study is required to determine whether diabetes persists or reverses later in life.

MiR-210 as a therapeutic target in diabetes-associated endothelial dysfunction.

MicroRNA (miR)-210 function in endothelial cells and its role in diabetes-associated endothelial dysfunction are not fully understood. We aimed to characterize the miR-210 function in endothelial cells and study its therapeutic potential in diabetes. Two different diabetic mouse models (db/db and Western diet-induced), miR-210 knockout and transgenic mice, isolated vessels and human endothelial cells were used. miR-210 levels were lower in aortas isolated from db/db than in control mice. Endothelium-dependent relaxation (EDR) was impaired in aortas from miR-210 knockout mice, and this was restored by inhibiting miR-210 downstream protein tyrosine phosphatase 1B (PTP1B), mitochondrial glycerol-3-phosphate dehydrogenase 2 (GPD2), and mitochondrial oxidative stress. Inhibition of these pathways also improved EDR in both diabetic mouse models. High glucose reduced miR-210 levels in endothelial cells and impaired EDR in mouse aortas, effects that were reversed by overexpressing miR-210. However, plasma miR-210 levels were not affected in individuals with type 2 diabetes (T2D) following improved glycaemic status. Of note, genetic overexpression using miR-210 transgenic mice and pharmacological overexpression using miR-210 mimic in vivo ameliorated endothelial dysfunction in both diabetic mouse models by decreasing PTP1B, GPD2 and oxidative stress. Genetic overexpression of miR-210 altered the aortic transcriptome, decreasing genes in pathways involved in oxidative stress. miR-210 mimic restored decreased nitric oxide production by high glucose in endothelial cells. This study unravels the mechanisms by which down-regulated miR-210 by high glucose induces endothelial dysfunction in T2D and demonstrates that miR-210 serves as a novel therapeutic target.

Mitochondrial proteins as therapeutic targets in diabetic ketoacidosis: evidence from Mendelian randomization analysis.

Diabetic ketoacidosis (DKA) is a severe and potentially fatal acute complication in diabetic patients, commonly occurring in type 1 diabetes (T1D) but also seen in type 2 diabetes (T2D). The pathogenesis of DKA involves complex physiological processes that are not fully understood, especially the role of mitochondria. Mitochondria, known as the powerhouse of cells, plays a crucial role in oxidative phosphorylation and ATP production, which is vital in various metabolic diseases, including diabetes. However, the exact causal relationship between mitochondrial dysfunction and DKA remains unclear. This study employed Mendelian randomization (MR) analysis and protein-protein interaction (PPI) networks to systematically explore the causal relationships between mitochondrial DNA copy number (mtDNA-CN) and specific mitochondrial proteins with DKA. We used bidirectional MR analysis and genome-wide association study (GWAS) data from openGWAS database to investigate the causal effects of mtDNA-CN and 64 mitochondrial-related proteins on DKA and its subtypes (T1DKA, T2DKA, unspecified-DKA). The study revealed that increased mtDNA-CN significantly reduces the risk of DKA, whereas the effect of DKA on mtDNA-CN was not significant. Mitochondrial-related proteins such as MRPL32, MRPL33, COX5B, DNAJC19, and NDUFB8 showed a negative causal relationship with DKA, indicating their potential protective roles. Conversely, ATP5F1B and COX4I2 have a positive causal relationship with DKA, indicating that excessive ATP production in diabetic patients may be detrimental to health and increase the risk of severe complications such as DKA. The results emphasize the necessity of protecting mitochondrial function in order to reduce the risk of DKA. The study offers novel perspectives on the molecular pathways involved in DKA, emphasizing the critical functions of mt-DNA and distinct proteins. These evidences not only enhance our comprehension of the implications of mitochondrial dysfunction in diabetes-related complications but also identify potential therapeutic targets for individualized treatment approaches, thereby making a substantial contribution to clinical care and public health initiatives.

Facilitators and barriers to implementing the Diabetes Prevention Program in rural church settings: A qualitative study using the Consolidated Framework for Implementation Research.

The CDC's Diabetes Prevention Program (DPP) is an effective lifestyle intervention to prevent type 2 diabetes (T2D). However, DPP implementation in rural areas is limited. This study sought to address this gap by implementing DPP in rural church settings through a community-academic partnership and identifying implementation facilitators and barriers. This was a cross-sectional qualitative study. Semistructured interviews guided by the Consolidated Framework for Implementation Research (CFIR) assessed church leaders' and lifestyle coaches' perceptions of implementing DPP in rural churches. Thematic analysis was used to identify key themes through an inductive approach; then, these emergent themes were deductively linked to CFIR constructs. COREQ guidelines were used to report study findings. Twenty-five stakeholders participated. Facilitators to implementing DPP included its evidence-based effectiveness in preventing T2D, as well as support from the academic partner in terms of funding, training, and communication. Additionally, DPP's alignment with community needs, along with the active engagement of pastors in participant recruitment, supported implementation. Several barriers hindered DPP implementation, including transportation and childcare issues, as well as program participants' medical conditions/disabilities limiting their participation. Furthermore, rural residents' reluctance to adopt lifestyle changes and loyalty to family churches posed challenges to their engagement in DPP. This study identified contextual factors influencing DPP implementation in rural communities. Findings highlight the importance of tailored strategies that leverage facilitators while proactively addressing barriers, including rural residents' reluctance to attend programs outside their church, resistance to lifestyle changes, and transportation issues to ensure successful DPP implementation in rural areas.

The association of resilience with HbA1c and key psychosocial factors in emerging adults with type 1 diabetes.

Emerging adults (EAs) with type 1 diabetes (T1D) have difficulty meeting glycemic targets and have a high prevalence of mental health comorbidities. Resilience, the ability to harness resources needed to sustain one's emotional and physical well-being, may be a key factor impacting poor mental health and glycemic outcomes. We aimed to (a) evaluate the association between resilience, HbA1c, and key psychosocial factors and (b) explore whether resilience moderates the relationship between psychosocial factors (depression, diabetes-related distress, anxiety) and HbA1c in EAs with T1D. EAs with T1D (N = 233) (mean age = 19.9 years (SD = 1.6), range 16.8-24.7) seen at an EA-specific diabetes clinic completed resilience, diabetes-related distress, depression, and anxiety measures and had their HbA1c level evaluated. We used linear regression models and conducted moderation analyses for the resilience factor. Resilience was strongly associated with HbA1c, depression, diabetes-related distress, and anxiety in EAs with T1D. We did not find evidence that resilience moderates the relationship between depression, anxiety, or diabetes-related distress and HbA1c. This study found that resilience is a highly relevant psychological factor associated with HbA1c and a key mental health factor for EAs with T1D. Novel interventions are needed to ameliorate high diabetes-related distress and HbA1c, and bolstering resilience may be one avenue to explore. Future research on resilience should longitudinally characterize and evaluate whether resilience may be a mechanism underlying the relationship between poor psychosocial outcomes and not meeting glycemic targets in EAs with T1D.

Association between risk factors and bone mineral density and the development of a self-assessment tool for early osteoporosis screening in postmenopausal women with type 2 diabetes.

Both diabetes and osteoporosis have developed into major global public health problems due to the increasing aging population. It is crucial to screen populations at higher risk of developing osteoporosis for disease prevention and management in postmenopausal women with type 2 diabetes (T2D). This study aims to quantitatively investigate the association between risk factors and bone mineral density (BMD) and develop a self-assessment tool for early osteoporosis screening in postmenopausal women with T2D. We retrospectively enrolled 1,309 postmenopausal women with T2D. Linear regression methods were used to assess the association between risk factors and BMD. Additionally, a multivariate logistic regression analysis was performed to identify independent risk factors associated with osteoporosis. Utilizing the logistic regression machine learning algorithm, we developed an osteoporosis screening tool that categorizes the population into three risk regions based on age and body mass index (BMI), indicating low, moderate, and high prevalence of osteoporosis in the age-BMI plane. Older age and lower BMI were independently associated with decreased BMD. The BMD at the total hip, femur neck, and lumbar spine differed by 12.9, 10.9, and 15.5 mg/cm2 for each 1 unit increase in BMI, respectively. Both age and BMI were identified as independent predictors of osteoporosis. The osteoporosis screening tool was developed by using two straight lines with equations of BMI = 0.56 * age-4.12 and BMI = 0.56 * age-10.88; there were no significant differences in the prevalence of osteoporosis among the training, internal test, and external test datasets in the low-, moderate-, and high-risk regions. We have successfully developed and validated a self-assessment tool for early osteoporosis screening in postmenopausal women with T2D for the first time. BMI was identified as a significant modifiable risk factor. Our study may improve awareness of osteoporosis and is valuable for disease prevention and management for postmenopausal women with T2D.