Bone marrow mesenchymal stem cell and mononuclear cell combination therapy in patients with type 2 diabetes mellitus: a randomized controlled study with 8-year follow-up.

BACKGROUND: To investigate the long-term effects of combining bone marrow mesenchymal stem cells (MSCs) with mononuclear cells (MCs) in the treatment of type 2 diabetes mellitus (T2DM). METHODS: T2DM patients were divided into the combination group (Dual MSC + MC, n = 33), the mononuclear cell group (MC-Only, n = 32) and the control group (Control, n = 31). All groups were treated with insulin and metformin. The Dual MSC + MC group additionally received MSC and MC infusion and the MC-Only group additionally received MC infusion. The patients were followed up for 8 years. The primary endpoint was the C-peptide area under the curve (C-p AUC) at 1 year. This study was registered with clinicaltrial.gov (NCT01719640). RESULTS: A total of 97 patients were included and 89 completed the follow-up. The area under the curve of C-peptide of the Dual MSC + MC group and the MC-Only group was significantly increased (50.6% and 32.8%, respectively) at 1 year. After eight years of follow-up, the incidence of macrovascular complications was 13.8% (p = 0.009) in the Dual MSC + MC group and 21.4% (p = 0.061) in the MC-Only group, while it was 44.8% in the Control group. The incidence of diabetic peripheral neuropathy (DPN) was 10.3% (p = 0.0015) in the Dual MSC + MC group, 17.9% (p = 0.015) in the MC-Only group, and 48.3% in the Control group. CONCLUSIONS: The combination of MSC and MC therapy can reduce the incidence of chronic diabetes complications and improves metabolic control with mild side effects in T2DM patients.

Lower extremity amputation rates in patients with chronic kidney disease: A database study comparing patients with and without diabetes mellitus.

Lower extremity amputation (LEA) is one of the most feared consequences of diabetes mellitus (DM). The purpose of this study was to evaluate the impact of DM on LEA rates in patients at various stages of chronic kidney disease (CKD). A commercially available de-identified database was searched for patients undergoing LEA and for CKD patients, from 2010 to 2023. Patients with DM and patients without DM who were followed for at least 5 years were included. LEA rates were then compared for patients at all 5 CKD stages in patients with and without diabetes. Rates of all LEA were found to be significantly higher at all CKD stages for patients with diabetes (overall, minor and major LEA). Compared to patients without DM who have CKD stage 5 (end stage renal disease), patients with DM and CKD stage 5 have a 30 fold increased likelihood of undergoing overall LEA [OR 30.2 (24.48-37.19), p < 0.001], 29 fold increased likelihood of undergoing minor LEA [28.9i (22.91-36.35), p < 0.001] and 40 times fold increased likelihood of undergoing major LEA [40.1 (26.59-60.42), p < 0.001]. For all stages of CKD, independent of diabetes status, minor LEA were performed with greater frequency than major LEA. In patients with DM, LEA rates significantly increased with CKD progression between stages 2-5 with a substantial jump between stages 4 and 5 [OR 2.6 (CI 2.49-2.74), p < 0.001]. However, CKD progression between stages 1 and 2 was not significantly associated with increased LEA rates (OR 1.1 (CI 0.92-1.21), p = 0.24) in patients with diabetes. Patients with comorbid diabetes have elevated risk for LEA at all stages of CKD compared to those without diabetes.

Diabetic Charcot neuroarthropathy: A threat to both limb and life.

Diabetic Charcot neuroarthropathy (DCN), first described in 1936, occurs in less than 1% of diabetic patients, but in those diabetic subjects with distal symmetrical polyneuropathy, the overall incidence increases to 30% and the risk is even greater in those with type 1 diabetes. Factors that precipitate DCN are trauma, ischaemia due to arterio-venous shunting, increased osteoclastic activity and inflammation. DCN usually presents with a painless swollen foot and/or ankle which is 'hot to the touch'. These clinical findings are soon followed by characteristic magnetic resonance imaging (MRI) abnormalities and later X-ray changes. The joints that are most typically involved in chronological order are the tarsometatarsals followed by the naviculocuniform, sub-tarsal, talonavicular and metatarsal and tarsophalangeal. The cornerstone of therapy is prolonged (3-12 months) offloading with immobilization. Bisphosphonates may possibly accelerate recovery, whereas other unproven possible therapies include rhPTH, 1-34, calcitonin and methylprednisolone, which are not only ineffective but in some cases may also prolong the time to healing. Denosumab is potentially an efficacious, if unproven, therapy to accelerate healing. The risk of amputation is high and increases in the presence of a foot ulcer. DCN is associated with manifestations of autonomic neuropathy, including cardiac denervation, so that the risks of a cardiac event and heart failure are increased with DCN. Mortality is also increased with DCN, especially in the presence of a foot ulcer. To avoid the recurrence of DCN and especially to lower the risk of the recurrence of a foot ulcer recurrence reconstructive, surgery may be needed.

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

BACKGROUND: The 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. OBJECTIVE: The 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. METHODS: This 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. RESULTS: The 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. CONCLUSION: This 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.

Slowing the progression of diabetic and non-diabetic kidney disease: A summary of the current evidence base for sodium-glucose co-transporter-2 inhibitors.

The global prevalence of chronic kidney disease (CKD) is approximately 9%. CKD is predicted to become the fifth largest global cause of death by 2040. Moreover, CKD causes disability, diminished quality of life and poses a high cost to healthcare systems. Delaying the development and progression of CKD is therefore of the utmost importance. Several kidney-specific outcome trials on sodium-glucose co-transporter-2 inhibitors (SGLT-2s) have recently provided a paradigm shift in the treatment of people with CKD, with or without diabetes, as these agents have been shown to reduce the progression of CKD on top of maximally tolerated renin-angiotensin-aldosterone system (RAAS) blockade. The relative benefit and safety of SGLT-2is seems to be consistent across ethnicities, ages and frailty categories; however, this needs to be tested in dedicated clinical trials. Guidelines make clear recommendations for the prescription of SGLT-2is and RAAS inhibitors as standard of care for people with CKD. Their combination with other newer antidiabetic agents may provide further benefits by targeting different components of CKD mechanisms. Dedicated randomized controlled trials are needed to test whether combination with other agents could extend the use of SGLT2is and identify people in whom a combination of drugs may be most effective. Increased efforts to implement the guidelines on treatment with SGLT-2is for people with CKD are needed, particularly in those at the highest risk of adverse outcomes and without type 2 diabetes. Moreover, strategies to target the equitable use of SGLT-2is are needed.

Effectiveness of Multifaceted Lifestyle Interventions in Prediabetic Adults: A Field Study in an Urban Slum Population of Pune, India.

Introduction Adults with diabetes have an increased risk of hypertension, heart attack, and stroke than those without diabetes. Diagnosing prediabetes at an early stage can significantly reduce the risk of diabetes through simple interventions such as lifestyle modifications. Lifestyle modifications such as weight loss combined with regular physical exercise and a healthy diet can help delay or prevent the progression of diabetes. This study aims to estimate the prevalence of prediabetes among the urban slum population and to assess the effect of lifestyle modifications on blood sugar levels, glycated hemoglobin (HbA1c), and lipid profile among the participants. Methods A quasi-experimental field study was conducted among the urban slum population. Participants were randomly selected from previous health screening data. Pre-intervention blood evaluations were performed, and those who fulfilled the criteria were enrolled for interventions. The follow-up period lasted three months and included telephonic and in-person meetings for support and motivation. All variables were reevaluated at the end of the follow-up period. Results Out of 34 participants included in the study, 20 completed the three-month follow-up. Statistically significant changes were observed after three months of intervention in weight, fasting blood sugar, HbA1c, BMI, triglycerides, and high-density lipoprotein (HDL) cholesterol levels. However, decreases in systolic blood pressure (BP), diastolic BP, total cholesterol, and low-density lipoprotein (LDL) cholesterol were not statistically significant. Conclusion The study revealed that lifestyle intervention programs promoting healthy diets, physical activity, and body weight reduction can prevent or delay the onset of diabetes among high-risk populations. The effectiveness of interventions across community settings depends on delivery formats, implementers, and the level of motivation of participants.

Depression and Anxiety Screening of Patients With Type II Diabetes Mellitus Attending Primary Healthcare Centers in Saudi Arabia.

BACKGROUND: Diabetes mellitus is a chronic condition affecting both physical and mental health. High blood sugar levels can lead to serious complications if not managed properly. Individuals with diabetes are also at a higher risk of developing mental health disorders like depression and anxiety. OBJECTIVE: The objective was to assess the prevalence of depression and anxiety among patients with type II diabetes attending primary healthcare centers in Makkah, Saudi Arabia. METHODS: An analytical cross-sectional study design was employed, targeting adults with type II diabetes attending primary healthcare centers in Makkah. A total sample size of 412 participants was selected through systematic random sampling. Data were collected using validated Arabic versions of the patient health questionnaire (PHQ-9) and the general anxiety disorder (GAD-7) questionnaire, along with demographic information. Statistical analysis was conducted with non-parametric tests used to evaluate the significance of outcome variables. RESULTS: The median age of participants was 47 years, with 237 (57.5%) being male and 373 (90.5%) Saudi nationals. Neuropathy was the most prevalent complication, affecting 181 (43.9%) of participants. The median GAD-7 score was 5, and the median PHQ-9 score was 7. Mild to moderate depression was observed in 224 (54.4%), and 194 (47%) had mild-to-moderate anxiety. Significant associations were found between mental health outcomes and several factors: nationality (non-Saudis showed higher depression and anxiety scores, p = 0.010 and p = 0.020, respectively), marital status (divorced participants had the highest mean ranks for both conditions, p = 0.003 for depression and p < 0.001 for anxiety), and monthly income (p = 0.007 for depression and p = 0.008 for anxiety). Additionally, the presence of diabetes complications was strongly associated with higher depression and anxiety scores (p < 0.001 for both). CONCLUSION: The findings indicate a high prevalence of depression and anxiety among patients with type II diabetes in Makkah. These mental health issues are significantly associated with socio-demographic factors and diabetes complications. Integrated medical and psychological care is needed to improve the quality of life and treatment outcomes for diabetic patients.

Cardiovascular autonomic neuropathy and the risk of diabetic kidney disease.

Background: Cardiovascular autonomic neuropathy (CAN) is known to affect patients with diabetes mellitus (DM) and cause adverse renal outcomes. We aimed to analyze the association between CAN and diabetic kidney disease (DKD). Method: We enrolled 254 DM patients (mean age, 56.7 ± 15.2 years; male: female ratio, 1.17:1) with 19 (7.5%) type 1 DM patients and 235 (92.5%) type 2 DM patients. All patients had undergone cardiovascular autonomic function tests between January 2019 and December 2021 in a tertiary hospital in Korea. Cardiovascular autonomic neuropathy was categorized as normal, early, or definite after measuring three heart rate variability parameters. Diabetic kidney disease refers to a persistently elevated urinary albumin-creatinine ratio (uACR ≥30 mg/g) or reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m2). Logistic and Cox regression analyses were performed. Results: Patients with elevated uACR (n=107) and reduced eGFR (n=32) had a higher rate of definite CAN. After adjusting for covariates, definite CAN was associated with elevated uACR (OR=2.4, 95% CI 1.07-5.36) but not with reduced eGFR (OR=3.43, 95% CI 0.62-18.90). A total of 94 patients repeated uACR measurements within 2 years (mean follow-up, 586.3 ± 116.8 days). Both definite and early CAN were independent risk factors for elevated uACR (HR=8.61 and 8.35, respectively; both p<0.05). In addition, high-density lipoprotein cholesterol, ACE inhibitors/angiotensin receptor blockers and glucagon-like peptide-1 receptor agonists were independent protective factors for elevated uACR (HR=0.96, 0.25, and 0.07, respectively; all p<0.05). Conclusion: Cardiovascular autonomic neuropathy is a potential indicator of DKD. Comprehensive management of DKD in the early stages of CAN may prevent microalbuminuria.

Identifying subtypes of Type 2 diabetes mellitus based on real-world electronic medical record data in China.

AIMS: To replicate the European subtypes of type 2 diabetes mellitus (T2DM) in Chinese diabetes population, and investigate the risk of complications in different subtypes. METHODS: A diabetes cohort using real-world patient data was constructed and clustering was employed to subgroup the T2DM patients. Kaplan-Meier analysis and the Cox model were used to analyze the association between diabetes subtypes and the risk of complications. RESULTS: A total of 2,652 T2DM patients with complete clustering data were extracted. Among them, 466 (17.57 %) were classified as severe insulin-deficient diabetes (SIDD), 502 (18.93 %) as severe insulin-resistant diabetes (SIRD), 672 (25.34 %) as mild obesity-related diabetes (MOD), and 1,012 (38.16 %) as mild age-related diabetes (MARD). The risk of chronic kidney disease (CKD) and diabetic retinopathy (DR) were different in the four subtypes. Compared with MARD, SIRD had a higher risk of CKD (HR 2.01 [1.03, 3.91]), and SIDD had a higher risk of DR (HR 2.17 [1.12, 4.20]). The risk of stroke and coronary events had no difference. CONCLUSIONS: The European T2DM subtypes can be replicated in Chinese diabetes population. The risk of CKD and DR varied among different subtypes, indicating that proper interventions can be taken to prevent specific complications in different subtypes.

Building a multistate model from electronic health records data for modeling long-term diabetes complications.

Objective: The progression of long-term diabetes complications has led to a decreased quality of life. Our objective was to evaluate the adverse outcomes associated with diabetes based on a patient's clinical profile by utilizing a multistate modeling approach. Methods: This was a retrospective study of diabetes patients seen in primary care practices from 2013 to 2017. We implemented a five-state model to examine the progression of patients transitioning from one complication to having multiple complications. Our model incorporated high dimensional covariates from multisource data to investigate the possible effects of different types of factors that are associated with the progression of diabetes. Results: The cohort consisted of 10,596 patients diagnosed with diabetes and no previous complications associated with the disease. Most of the patients in our study were female, White, and had type 2 diabetes. During our study period, 5928 did not develop complications, 3323 developed microvascular complications, 1313 developed macrovascular complications, and 1129 developed both micro- and macrovascular complications. From our model, we determined that patients had a 0.1334 [0.1284, .1386] rate of developing a microvascular complication compared to 0.0508 [0.0479, .0540] rate of developing a macrovascular complication. The area deprivation index score we incorporated as a proxy for socioeconomic information indicated that patients who reside in more disadvantaged areas have a higher rate of developing a complication compared to those who reside in least disadvantaged areas. Conclusions: Our work demonstrates how a multistate modeling framework is a comprehensive approach to analyzing the progression of long-term complications associated with diabetes.

Predicting the risk of diabetes complications using machine learning and social administrative data in a country with ethnic inequities in health: Aotearoa New Zealand.

BACKGROUND: In the age of big data, linked social and administrative health data in combination with machine learning (ML) is being increasingly used to improve prediction in chronic disease, e.g., cardiovascular diseases (CVD). In this study we aimed to apply ML methods on extensive national-level health and social administrative datasets to assess the utility of these for predicting future diabetes complications, including by ethnicity. METHODS: Five ML models were used to predict CVD events among all people with known diabetes in the population of New Zealand, utilizing nationwide individual-level administrative data. RESULTS: The Xgboost ML model had the best predictive power for predicting CVD events three years into the future among the population with diabetes (N = 145,600). The optimization procedure also found limited improvement in prediction by ethnicity (using area under the receiver operating curve, [AUC]). The results indicated no trade-off between model predictive performance and equity gap of prediction by ethnicity (that is improving model prediction and reducing performance gaps by ethnicity can be achieved simultaneously). The list of variables of importance was different among different models/ethnic groups, for example: age, deprivation (neighborhood-level), having had a hospitalization event, and the number of years living with diabetes. DISCUSSION AND CONCLUSIONS: We provide further evidence that ML with administrative health data can be used for meaningful future prediction of health outcomes. As such, it could be utilized to inform health planning and healthcare resource allocation for diabetes management and the prevention of CVD events. Our results may suggest limited scope for developing prediction models by ethnic group and that the major ways to reduce inequitable health outcomes is probably via improved delivery of prevention and management to those groups with diabetes at highest need.

Beneficial effect of oral semaglutide for type 2 diabetes mellitus in patients with metabolic dysfunction-associated steatotic liver disease: A prospective, multicentre, observational study.

AIMS: To evaluate the efficacy and safety of oral semaglutide for type 2 diabetes mellitus (T2DM) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: This was a single-arm, multicentre, prospective study. Among 80 consecutive patients with MASLD and T2DM who newly received oral semaglutide, 70 completed 48-week oral semaglutide treatment as scheduled and were included in an efficacy analysis. Dose adjustments of oral semaglutide were determined by each physician while monitoring efficacy and adverse events. RESULTS: Significant improvements in body weight, liver enzymes, lipid profile, and glycaemic control were found at 48 weeks compared with baseline values (all p < 0.01). Controlled attenuation parameter values significantly decreased from baseline to 48 weeks (p < 0.01). Changes in alanine aminotransferase concentrations (r = 0.37, p < 0.01) and controlled attenuation parameter values (r = 0.44, p < 0.01) were significantly correlated with changes in body weight. Liver fibrosis markers, such as type IV collagen 7S, Wisteria floribunda agglutinin-positive Mac-2-binding protein, fibrosis-4 index, and liver stiffness measurement, significantly decreased from baseline to 48 weeks (all p < 0.01). The most common adverse events were Grades 1-2 transient gastrointestinal symptoms, such as nausea (23 patients, 28.8%), dyspepsia (12, 15.0%) and appetite loss (4, 5.0%). CONCLUSIONS: Oral semaglutide treatment for T2DM in patients with MASLD leads to an improvement in liver steatosis and injury, surrogate markers of fibrosis, diabetic status, and lipid profile, and reduces body weight.

The association of type 2 diabetes-related characteristics with fracture risk at different sites.

AIM: To determine the association of diabetes-related characteristics with fractures at different sites in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: We conducted a cohort study using the Clinical Practice Research Datalink (CPRD) GOLD. Patients aged over 30 years with T2D were identified within the CPRD. Patients were followed from the start of diabetes treatment until the end of data collection, death, or the occurrence of a fracture. Cox proportional hazards models were used to estimate the hazard ratios for the association of the individual characteristics (diabetes duration, glycated haemoglobin [HbA1c] level, and microvascular complications) with fracture risk, adjusted for demographics, comorbidities and comedication. RESULTS: A diabetes duration of >10 years was associated with an increased risk of any fracture and major osteoporotic fractures (MOFs), while a diabetes duration of >8 years was associated with an increased hip fracture risk, compared to a duration <2 years. An HbA1c level <6% was associated with an increased fracture risk compared to HbA1c values of 6% to <7%. The presence of one or two microvascular complications was associated with an increased risk of any fracture and MOFs and the presence of two microvascular complications was associated with an increased hip fracture risk, compared to no microvascular complications. CONCLUSION: In conclusion, our study shows that a diabetes duration of 10 years or more, strict glycaemic control resulting in HbA1c levels below 6%, and/or the presence of at least one microvascular complication increased the risk of any fracture, hip fractures, MOFs, and humerus fractures, but not ankle, scapula or skull fractures.

Fracture risk revisited: Bone mineral density T-score and fracture risk in type 2 diabetes.

AIM: To study the association between femoral neck (FN) bone mineral density (BMD) T-score and fracture risk in individuals with and without type 2 diabetes (T2D). MATERIALS AND METHODS: We performed a single-centre retrospective cohort study using the Danish National Health Service. BMD of the FN was measured by dual-energy X-ray absorptiometry. Cox proportional hazards regression models were used to study the association between FN BMD T-score and fractures in individuals with and without T2D separately, adjusted for age, comorbidities and comedication. The results from this analysis were used to estimate the 10-year absolute fracture risk. RESULTS: In total, there were 35,129 women (2362 with T2D) and 7069 men (758 with T2D). The FN BMD T-score was significantly associated with risk of any, hip and major osteoporotic fracture in men and women with [adjusted hazard risk ratios (aHR) women, hip: 1.57; 95% confidence interval (CI) 1.24-2.00, incidence rate (IR) 8.7; aHR men, hip: 1.55; 95% CI 1.01-2.36, IR 4.6] and without T2D (aHR women, hip: 1.75; 95% CI 1.64-1.87, IR 7.0; aHR men, hip: 1.97, 95% CI 1.73-2.25, IR 6.3), and its ability to predict fracture risk was similar. Fracture IRs were not significantly different for individuals with or without T2D, nor was the estimated cumulative 10-year fracture risk. CONCLUSIONS: The FN BMD T-score was significantly associated with hip, non-spine and major osteoporotic fracture risk in men and women with and without T2D. Fracture risk for a given T-score and age was equal in individuals with and without T2D, as was the ability of the FN BMD T-score to predict fracture risk.

Hospitalization and Health Resource Utilization in Emergency Department Cases of Diabetic Foot Infections in the U.S. from 2012 to 2021: A Nationally Representative Analysis.

Objectives: The objective of this paper was to assess hospitalizations and health resource utilization associated with diabetic foot infection (DFI)-related visits within emergency departments (EDs) in the U.S. Methods: This nationally representative, cross-sectional historical cohort utilized the Centers for Disease Control and Prevention's (CDC's) National Hospital Ambulatory Medical Care Survey across a ten-year period from 2012 to 2021. Inclusion criteria were as follows: adults ≥18 years of age; a diagnosis of Type 1 or Type 2 diabetes mellitus; presence of a DFI. Comparisons were drawn relative to a cohort of patients with diabetes without foot complications. Study outcomes included 72-hour (72 h) ED revisit, hospitalization, and length of stay (LOS). Top diagnoses and medications were also reported. Multivariable, generalized, linear regression analyses were employed, controlling for key demographics, health system factors, clinical characteristics, and year. Results: An estimated 150.6 million ED visits included a diabetes diagnosis, with 2.4 million involving a DFI (1.6%). Approximately half of DFI cases were hospitalized (43.7%). Anti-infective medications were prescribed in 83.1% of DFI cases, including vancomycin in 28.1%. Multivariable analyses observed that DFIs were associated with a 3.002 times higher odds of hospital admissions (CI: 2.145-4.203, p < 0.001) and a 55.0% longer LOS (IR = 1.550, CI: 1.241-1.936, p < 0.001). DFIs were not significantly associated with a 72 h ED revisit. Conclusions: This nationally representative study of 2.4 million DFI-related ED visits in the U.S. observed higher odds of hospital admissions and a longer LOS for DFIs versus diabetes without foot complications. Continued research should seek to assess prevention and coordinated treatment interventions prior to the emergence of DFIs requiring ED care.

The role of high mobility group box-1 on the development of diabetes complications: A plausible pharmacological target.

BACKGROUND: Diabetes mellitus has emerged as a pressing global concern, with a notable increase in recent years. Despite advancements in treatment, existing medications struggle to halt the progression of diabetes and its associated complications. Increasing evidence underscores inflammation as a significant driver in the onset of diabetes mellitus. Therefore, perspectives on new therapies must consider shifting focus from metabolic stress to inflammation. High mobility group box (HMGB-1), a nuclear protein regulating gene expression, gained attention as an endogenous danger signal capable of sparking inflammatory responses upon release into the extracellular environment in the late 1990s. PURPOSE: Given the parallels between inflammatory responses and type 2 diabetes (T2D) development, this review paper explores HMGB-1's potential involvement in onset and progression of diabetes complications. Specifically, we will review and update the understanding of HMGB-1 and its inflammatory pathways in insulin resistance, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy. CONCLUSIONS: HMGB-1 and its receptors i.e. receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs) present promising targets for antidiabetic interventions. Ongoing and future projects in this realm hold promise for innovative approaches targeting HMGB-1-mediated inflammation to ameliorate diabetes and its complications.

Pathogenic mechanisms, diagnostic, and therapeutic potential of microvesicles in diabetes and its complications.

Extracellular vesicles (EVs), particularly microvesicles (MVs), have gained significant attention for their role as mediators of intercellular communication in both physiological and pathological contexts, including diabetes mellitus (DM) and its complications. This review provides a comprehensive analysis of the emerging roles of MVs in the pathogenesis of diabetes and associated complications such as nephropathy, retinopathy, cardiomyopathy, and neuropathy. MVs, through their cargo of proteins, lipids, mRNAs, and miRNAs, regulate critical processes like inflammation, oxidative stress, immune responses, and tissue remodeling, all of which contribute to the progression of diabetes and its complications. We examine the molecular mechanisms underlying MVs' involvement in these pathological processes and discuss their potential as biomarkers and therapeutic tools, particularly for drug delivery. Despite promising evidence, challenges remain in isolating and characterizing MVs, understanding their molecular mechanisms, and validating them for clinical use. Advanced techniques such as single-cell RNA sequencing and proteomics are required to gain deeper insights. Improved isolation and purification methods are essential for translating MVs into clinical applications, with potential to develop novel diagnostic and therapeutic strategies to improve patient outcomes in diabetes.

Effect of Diabetes Education on Complications and Diabetic Control Amongst Adult Patients with Diabetes in Madinah, Saudi Arabia.

BACKGROUND: Diabetes is a chronic condition that may become dangerous if there is insufficient insulin to help the body function properly. The proper care for diabetes depends on how well patients observe guidelines and prescriptions; consequently, patient education is critical. Poor learning may cause bad treatment and complications or other problems related to the disease. OBJECTIVES: This study aims to evaluate patients' knowledge of diabetes, assigning a knowledge (K) score out of 100, and investigate the possible impact of educating patients, through general means or via healthcare professionals, on patient knowledge of diabetes control demonstrated in the absence/presence of diabetic complications. METHODS: This multi-center interview-based cross-sectional study used a questionnaire in Madinah, Saudi Arabia. This study was conducted on adults with diabetes who were aged 15-80. We used the Michigan Diabetic Knowledge Test (MDKT) to assess the knowledge of patients with diabetes. RESULTS: This study included 364 participants. The gender distribution was 48.33% male and 51.67% female. Most of them had type 2 diabetes (T2DM) without insulin (48.63%), followed by those with T2DM on insulin (36.26%), and patients with type 1 diabetes (T1DM) (15.11%). Patients with T2DM had significantly higher K scores than patients with type 1. Additionally, T2DM non-insulin patients' k-scores significantly exceeded those with T1DM. General and healthcare education both helped increase patients' K-scores. Mostly, patients with diabetes without any complications had significantly higher knowledge compared to those having them. Lastly, regardless of whether the education was delivered by general or professional means, the effect on glycated hemoglobin (HbA1C) levels was not significant. CONCLUSIONS: Our study revealed that patients with T2DM exhibited higher knowledge than patients with T1DM. Furthermore, receiving education, whether by a healthcare professional or by general means, improved the knowledge levels of patients with T2DM but not patients with T1DM. Regarding diabetes complications, it was found that those with a higher level of knowledge had fewer complications. However, no evidence receiving education influenced the levels of HbA1C, neither in patients with T1DM nor T2DM.

Wound cleansing solutions versus normal saline in the treatment of diabetic foot ulcers - A systematic review.

Diabetic foot ulcers (DFUs) are a major complication of diabetes mellitus, defined as infection, ulceration and/or destruction of deep tissues and/or peripheral artery disease in the lower extremities. Efficient cleansing is essential for the treatment of wounds, as it removes debris and necrotic tissue and decreases the burden of wound-colonizing microorganisms. The objective was to conduct a systematic review of the literature to investigate the effects of wound cleansing agents commonly used in DFU care, compared to the use of normal saline for DFU management. This systematic review adhered to the PRISMA guidelines with additional guidance from the Cochrane Handbook for Systematic Reviews of Interventions and was registered in PROSPERO 2023. The included Randomized Controlled Trials compared various wound cleansing solutions to standard care practices recommended by the International Working Group on the Diabetic Foot. Findings indicate that Dakins solution and chloramines, as well as hypertonic saline, may improve ulcer healing compared to normal saline or standard treatment. However, we identified only three low-quality studies, each with a high risk of bias. Therefor, the certainty of the evidence is low, and we cannot conclusively determine the effectiveness of these cleansing agents in improving wound healing outcomes.