Diabetic wounds are characterized by incomplete healing and delayed healing, resulting in a considerable global health care burden. Exosomes are lipid bilayer structures secreted by nearly all cells and express characteristic conserved proteins and parent cell-associated proteins. Exosomes harbor a diverse range of biologically active macromolecules and small molecules that can act as messengers between different cells, triggering functional changes in recipient cells and thus endowing the ability to cure various diseases, including diabetic wounds. Exosomes accelerate diabetic wound healing by regulating cellular function, inhibiting oxidative stress damage, suppressing the inflammatory response, promoting vascular regeneration, accelerating epithelial regeneration, facilitating collagen remodeling, and reducing scarring. Exosomes from different tissues or cells potentially possess functions of varying levels and can promote wound healing. For example, mesenchymal stem cell-derived exosomes (MSC-exos) have favorable potential in the field of healing due to their superior stability, permeability, biocompatibility, and immunomodulatory properties. Exosomes, which are derived from skin cellular components, can modulate inflammation and promote the regeneration of key skin cells, which in turn promotes skin healing. Therefore, this review mainly emphasizes the roles and mechanisms of exosomes from different sources, represented by MSCs and skin sources, in improving diabetic wound healing. A deeper understanding of therapeutic exosomes will yield promising candidates and perspectives for diabetic wound healing management.

Diabetic osteoporosis (DO) presents significant clinical challenges. This study aimed to investigate the potential of magnetic nanoparticle-enhanced extracellular vesicles (GMNPE-EVs) derived from bone marrow mesenchymal stem cells (BMSCs) to deliver miR-15b-5p, thereby targeting and downregulating glial fibrillary acidic protein (GFAP) expression in rat DO models. Data was sourced from DO-related RNA-seq datasets combined with GEO and GeneCards databases. Rat primary BMSCs, bone marrow-derived macrophages (BMMs), and osteoclasts were isolated and cultured. EVs were separated, and GMNPE targeting EVs were synthesized. Bioinformatic analysis revealed a high GFAP expression in DO-related RNA-seq and GSE26168 datasets for disease models. Experimental results confirmed elevated GFAP in rat DO bone tissues, promoting osteoclast differentiation. miR-15b-5p was identified as a GFAP inhibitor, but was significantly downregulated in DO and enriched in BMSC-derived EVs. In vitro experiments showed that GMNPE-EVs could transfer miR-15b-5p to osteoclasts, downregulating GFAP and inhibiting osteoclast differentiation. In vivo tests confirmed the therapeutic potential of this approach in alleviating rat DO. Collectively, GMNPE-EVs can effectively deliver miR-15b-5p to osteoclasts, downregulating GFAP expression, and hence, offering a therapeutic strategy for rat DO.

OBJECTIVE: To evaluate the association between type 1 diabetes (T1D)/type 2 diabetes (T2D) and periodontitis and assess the influence of periodontitis on diabetes-related complications.
METHODS: Observational study; longitudinal analysis of register data.
METHODS: Swedish primary care centres, hospitals and dental clinics reporting to nationwide healthcare registers (2010-2020).
METHODS: 28 801 individuals with T1D (13 022 women; mean age 42 years) and 57 839 individuals without diabetes (non-T1D; 26 271 women; mean age 43 years). 251 645 individuals with T2D (110 627 women; mean age 61 years) and 539 805 individuals without diabetes (non-T2D; 235 533 women; mean age 60 years). Diabetes and non-diabetes groups were matched for age, gender and county of residence.
METHODS: Prevalent periodontitis, diabetes-related complications (retinopathy, albuminuria, stroke and ischaemic heart disease) and mortality.
RESULTS: Periodontitis was more common among T2D (22%) than non-T2D (17%). Differences were larger in younger age groups (adjusted RR at age 30-39 years 1.92; 95% CI 1.81 to 2.03) and exacerbated by poor glycaemic control. Periodontitis prevalence was 13% in T1D and 11% in non-T1D; only the subgroup with poor glycaemic control was at higher risk for periodontitis. Periodontitis was associated with a higher incidence of retinopathy (T1D: HR 1.08, 95% CI 1.02 to 1.14; T2D: HR 1.08, 95% CI 1.06 to 1.10) and albuminuria (T1D: HR 1.14, 95% CI 1.06 to 1.23; T2D: HR 1.09, 95% CI 1.07 to 1.11). Periodontitis was not associated with a higher risk for stroke, cardiovascular disease or higher mortality in T1D/T2D.
CONCLUSIONS: The association between T2D and periodontitis was strong and exacerbated by poor glycaemic control. For T1D, the association to periodontitis was limited to subgroups with poor glycaemic control. Periodontitis contributed to an increased risk for retinopathy and albuminuria in T1D and T2D.

OBJECTIVE: Dysglycaemia accelerates cognitive decline. Intensive glucose control may help delay or prevent cognitive function decline (CFD). We aimed to determine how patient characteristics influence the effect of intensive glucose control [glycated haemoglobin (HbA1c) <6.0%] on delaying CFD in people with type 2 diabetes.
METHODS: In this post-hoc analysis of 2977 type 2 diabetes participants from the ACCORD MIND trial, we applied the causal forest and causal tree algorithms to identify the effect modifier of intensive glucose control in delaying CFD from 68 variables (demographics, disease history, medications, vitals and baseline biomarkers). The exposure was intensive versus standard glucose control (HbA1c <6.0% vs. 7.0%-7.9%). The main outcome was cognitive function changes from baseline to the 40th month follow-up, which were evaluated using the digit symbol substitution test, Rey auditory verbal learning test, mini-mental state examination and Stroop test. We used Cohen\'s d, a measure of standardized difference, to quantify the effect size of intensive glucose control on delaying CFD.
RESULTS: Among all the baseline characteristics, renal function was the most significant effect modifier. Participants with urinary albumin levels <0.4 mg/dl [absolute function change (AFC): 0.51 in mini-mental state examination, 95% confidence interval (CI): 0.04, 0.98, Cohen\'s d: 0.25] had slower CFD with intensive glucose control. Patients with preserved renal function (estimated glomerular filtration rate between 60 and 90 ml/min/1.73 m2) were associated with small benefits (AFC: 1.28 in Stroop, 95% CI: 0.28, 2.27, Cohen\'s d: 0.12) when undergoing intensive glucose control. Conversely, participants with an estimated glomerular filtration rate <60 ml/min/1.73 m2 (AFC: -0.57 in the Rey auditory verbal learning test, 95% CI: -1.09, -0.05, Cohen\'s d: -0.30) exhibited faster CFD when undergoing intensive glucose control. Participants who were <60 years old showed a significant benefit from intensive glucose control in delaying CFD (AFC: 1.08 in the digit symbol substitution test, 95% CI: 0.06, 2.10, Cohen\'s d: 0.13). All p < .05.
CONCLUSIONS: Our findings linked renal function with the benefits of intensive glucose control in delaying CFD, informing personalized HbA1c goals for those with diabetes and at risk of CFD.

UNASSIGNED: Diabetic gastroparesis is a common complication in patient with diabetes. Dietary intervention has been widely used in the treatment of diabetic gastroparesis. The aim of this study is to evaluate the role of diet in the treatment of diabetic gastroparesis.
UNASSIGNED: This systematic review was conducted a comprehensive search of randomized controlled trials using dietary interventions for the treatment of diabetic gastroparesis up to 9 November 2023. The primary outcomes were gastric emptying time and clinical effect, while fasting blood glucose, 2-hour postprandial blood glucose and glycosylated hemoglobin were secondary outcomes. Data analysis was performed using RevMan 5.4 software, and publication bias test was performed using Stata 15.1 software.
UNASSIGNED: A total of 15 randomized controlled trials involving 1106 participants were included in this review. The results showed that patients with diabetic gastroparesis benefit from dietary interventions (whether personalized dietary care alone or personalized dietary care+routine dietary care). Compared with routine dietary care, personalized dietary care and personalized dietary care+routine dietary care can shorten the gastric emptying time, improve clinical efficacy, and reduce the level of fasting blood glucose, 2-hour postprandial blood glucose and glycosylated hemoglobin.
UNASSIGNED: Limited evidence suggests that dietary intervention can promote gastric emptying and stabilize blood glucose control in patients with diabetic gastroparesis. Dietary intervention has unique potential in the treatment of diabetic gastroparesis, and more high-quality randomized controlled trials are needed to further validate our research results.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42023481621.

BACKGROUND: Frailty has been identified as a risk factor for adverse outcomes in older adults with diabetes. This study aimed to investigate the impact of frailty on the prognosis of older adults with diabetes through a systematic review and meta-analysis, with the goal of offering insights for clinical decision-making.
METHODS: PubMed, Web of Science, Embase, Cochrane were systematically searched from inception to September 10th, 2023. Reviewers independently selected studies, extracted data and evaluated the quality of studies. Stata 15.1 Software was used to perform the meta-analysis. The primary outcomes of this study were mortality, hospitalization and disability, and the secondary outcomes were diabetes complications (including nephropathy, microvascular complications, macroangiopathy, cardiovascular events, hypoglycemia) and urolithiasis.
RESULTS: A total of 14 studies were included in this study, with low risk of bias and moderate to good quality. The results showed that frailty increased the risk of mortality (HR 1.91, 95% CI 1.55-2.35, P < .001), hospitalization (HR 2.19, 95% CI 1.53-3.13, P < .001), and disability in older adults with diabetes (HR 3.84, 95% CI 2.35-6.28, P < .001). In addition, frailty was associated with diabetes complications (including nephropathy, microvascular complications, macroangiopathy, cardiovascular events, hypoglycemia), urolithiasis.
CONCLUSIONS: Frailty is an important predictor of adverse outcomes, such as mortality, hospitalization, and disability in older adults with diabetes. Accurate assessment of the frailty in older adults with diabetes can help improve the adverse outcomes of patients.

BACKGROUND: We previously reported predictors of mortality in 1786 adults with diabetes or stress hyperglycemia (glucose>180 mg/dL twice in 24 hours) admitted with COVID-19 from March 2020 to February 2021 to five university hospitals. Here, we examine predictors of readmission.
METHODS: Data were collected locally through retrospective reviews of electronic medical records from 1786 adults with diabetes or stress hyperglycemia who had a hemoglobin A1c (HbA1c) test on initial admission with COVID-19 infection or within 3 months prior to initial admission. Data were entered into a Research Electronic Data Capture (REDCap) web-based repository, and de-identified. Descriptive data are shown as mean±SD, per cent (%) or median (IQR). Student\'s t-test was used for comparing continuous variables with normal distribution and Mann-Whitney U test was used for data not normally distributed. X2 test was used for categorical variable.
RESULTS: Of 1502 patients who were alive after initial hospitalization, 19.4% were readmitted; 90.3% within 30 days (median (IQR) 4 (0-14) days). Older age, lower estimated glomerular filtration rate (eGFR), comorbidities, intensive care unit (ICU) admission, mechanical ventilation, diabetic ketoacidosis (DKA), and longer length of stay (LOS) during the initial hospitalization were associated with readmission. Higher HbA1c, glycemic gap, or body mass index (BMI) were not associated with readmission. Mortality during readmission was 8.0% (n=23). Those who died were older than those who survived (74.9±9.5 vs 65.2±14.4 years, p=0.002) and more likely had DKA during the first hospitalization (p<0.001). Shorter LOS during the initial admission was associated with ICU stay during readmission, suggesting that a subset of patients may have been initially discharged prematurely.
CONCLUSIONS: Understanding predictors of readmission after initial hospitalization for COVID-19, including older age, lower eGFR, comorbidities, ICU admission, mechanical ventilation, statin use and DKA but not HbA1c, glycemic gap or BMI, can help guide treatment approaches and future research in adults with diabetes.

The effect of hydration in modulating metabolic disease risk is a comparatively recent concept. Diabetic patients are at increased risk of dehydration due to osmotic diuresis. Undiagnosed or undertreated hyperglycemia may lead to electrolyte imbalance and elevated renal burden of glucose excretion, which may alter fluid reabsorption in the kidney. Also, the presence of one or more contributory factors, such as inadequate fluid intake, strenuous exercise, high temperatures, alcohol consumption, diarrhea, acute illnesses, fever, nausea, and vomiting, may put diabetic patients at increased risk of dehydration and electrolyte imbalance. Certain antidiabetic agents used by diabetic patients may cause fluid retention/deficits and/or electrolyte abnormalities in a few patients. Thus, drinking ample amounts of water and fluids with appropriate electrolyte composition is important to prevent dehydration. Successful management of dehydration in patients with diabetes is an unmet need and can best be accomplished by maintaining adequate hydration status.

Currently, there is no known cure for diabetes. Different pharmaceutical therapies have been approved for the management of type 2 diabetes mellitus (T2DM), some are in clinical trials and they have been classified according to their route or mechanism of action. Insulin types, sulfonylureas, biguanides, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, sodium-glucose cotransporter type 2 inhibitors, and incretin-dependent therapies (glucagon-like peptide-1 receptor agonists: GLP-1R, and dipeptidyl peptidase 4 inhibitors: DPP-4). Although some of the currently available drugs are effective in the management of T2DM, the side effects resulting from prolonged use of these drugs remain a serious challenge. GLP-1R agonists are currently the preferred medications to include when oral metformin alone is insufficient to manage T2DM. Medicinal plants now play prominent roles in the management of various diseases globally because they are readily available and affordable as well as having limited and transient side effects. Recently, studies have reported the ability of phytochemicals to activate glucagon-like peptide-1 receptor (GLP-1R), acting as an agonist just like the GLP-1R agonist with beneficial effects in the management of T2DM. Consequently, we propose that careful exploration of phytochemicals for the development of novel therapeutic candidates as GLP-1R agonists will be a welcome breakthrough in the management of T2DM and the co-morbidities associated with T2DM.

Skin autofluorescence (sAF) measurement is a non-invasive method used to assess tissue advanced glycation end product (AGE) accumulation. This study aims to characterize sAF\'s association with (1) glycated hemoglobin (HbA1c) values, (2) cardiovascular risk markers, and (3) common comorbidities (autoimmune thyroiditis, celiac disease) in children with type 1 diabetes (T1D).
METHODS: A total of 348 children with T1D aged 3-18 years and 85 age- and gender-matched control subjects were enrolled. sAF was quantified using an AGE Reader (Diagnoptics BV, The Netherlands). The analysis covered HbA1c, blood lipid, and C-reactive protein (CRP) levels, ambulatory blood pressure monitoring records, and body composition parameters. The associations between variables and sAF were assessed using the Mann-Whitney U test and Spearman correlation.
RESULTS: We observed significantly higher sAF values in the T1D group compared to the control (1.40 [1.27-1.53] vs. 1.20 [1.07-1.30, AU]; p = 0.004), consistent across all tested age groups. In the T1D group, sAF was positively correlated with current HbA1c, mean of historical HbA1c values, and T1D duration (r values, respectively: 0.27, 0.22, 0.14, all p < 0.01). Percentage of body fat was positively correlated with sAF (r = 0.120; p = 0.044). No significant correlations were found between sAF and lipid fractions, Z-score of BMI, parameters from 24 h ambulatory blood pressure monitoring, or the amount of albumin excreted in urine. sAF was positively correlated with CRP (r = 0.17, p < 0.05). sAF was significantly higher in patients with concomitant celiac disease (1.53 [1.43-1.63] vs. 1.40 [1.27-1.53, AU], p = 0.001).
CONCLUSIONS: Among young T1D patients with relatively brief diabetes duration, sAF effectively mirrors prior glycemic control, as presented by historical average HbA1c. However, associations with conventional CV risk markers are not evident. The higher sAF values in patients with celiac disease warrant further exploration.