Diabetes-related Diseases Research Articles

The impact of diabetes mellitus on tendon pathology: a review

Diabetes is one of the most common metabolic diseases worldwide, leading to complications, mortality, and significant healthcare expenditures, which impose a substantial social and financial burden globally. A diabetic environment can induce metabolic changes, negatively affecting tendon homeostasis, leading to alterations in biomechanical properties and histopathology. Numerous studies have investigated the mechanisms through which diabetes exerts pathological effects on tendons, including increased free radical production, oxidative stress, inflammatory responses, deposition of advanced glycation end products (AGEs), and microvascular changes. These metabolic changes damages tendon structure, biomechanics, and tendon repair processes. The proliferation of tendon stem cells decreases, apoptosis increases, and abnormal differentiation, along with abnormal expression of myofibroblasts, ultimately lead to insufficient tendon repair, fibrosis, and remodeling. Although researches unveiling the effects of diabetes on tendinopathy, fibrosis or contracture, and tendon injury healing are growing, systematic understanding is still lacking. Therefore, this review summarizes the current research status and provides a comprehensive overview, offering theoretical guidance for future in-depth exploration of the impact of diabetes on tendons and the development of treatments for diabetes-related tendon diseases.

Paradigm shift from glucocentric to organ protection for the management of hyperglycemia in patients with type 2 diabetes

The UK Prospective Diabetes Study was the first study to investigate the effectiveness of glycemic control in patients with type 2 diabetes. Since then, many studies have evaluated the impact of intensive glycemic control on diabetes-related morbidities and mortality. The results of these studies were intended to change the paradigm for controlling glycated hemoglobin and preventing diabetes-related complications, but the beneficial outcomes were limited to microvascular diseases rather than diabetes-related cardiorenal diseases and deaths. This has emphasized the need for comprehensive management of other risk factors (hypertension, dyslipidemia, renal failure, etc.) in addition to hyperglycemia to prevent atherosclerotic cardiovascular diseases and end-stage renal disease in type 2 diabetes. Since 2008, clinical trials to demonstrate cardiovascular safety have shown a beneficial effect of sodium-glucose transporter 2 inhibitors or glucagon-like peptide-1 receptor agonists on macrovascular or renal complications in patients with type 2 diabetes. Recently, major societies around the world including the Korean Diabetes Association, have shifted the goals of diabetes management from the typical glucocentric view to cardiorenal outcome-oriented (organ protection) care, which has been widely accepted and is gradually applied to primary care.

Exploring Machine Learning Models for Predicting Diabetic Retinopathy: A Comprehensive Comparative Study of Logistic Regression an Advanced Technique

This research provides a comprehensive examination of machine learning models for predicting diabetes-related ocular diseases, with a focus on Logistic Regression versus more advanced approaches. A large dataset encompassing a variety of diabetes-related lifestyle and health factors is used in the study to extensively train and analyze multiple models in order to demonstrate their predictive utility. The thorough evaluation results illuminated the subtle differences in performance between Logistic Regression and other advanced algorithms, offering insightful information about the pros and cons of each in terms of predicting the risk of diabetic retinopathy and other complications relating to the eyes. The findings reveal crucial themes for additional research and advancement in the realm of predictive modeling for diabetic eye disorders, in the process of verifying that logistic regression works well in specific situations.

Impact of Socio-Demographics and Knowledge, Attitudes, and Practices (KAP) on Misconceptions of Metformin Use in Diabetes: A Potential Myth and Disbelief in South Asia.

The influence of misconceptions and related socio-demographics on metformin use could hamper adherence to medications. This study aimed to assess the rates and causes of metformin non-adherence and to investigate knowledge, attitudes, and practices (KAP) on misconceptions of metformin use including the association with socio-demographic variables. An observational analytical cross-sectional study was conducted at the diabetes clinic of Karapitiya Teaching Hospital in Galle, Sri Lanka. Causes of metformin non-adherence, associations with socio-demographics, and KAP on misconceptions on metformin use were assessed using the chi-squared test, t-tests, and ANOVA using IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States) (p<0.05). Metformin non-adherence was reported as 55%. Use of complementary and alternative therapies was 14.7%. Fear of major organ failure was the commonest (20.5%) reason quoted within the non-adherence group (N=223). Socio-demographic factors like ethnicity, lower education, unemployment, use of complementary and alternative therapies, and obtaining medications for other diabetes-related diseases significantly influenced adherence to the metformin-prescribed doses (p<0.05). Among all participants (N=400), the most common misconception was that long-term use of metformin caused organ damage (kidney 72.5%, liver 64.3%, and heart 34.8%), while 44% believed higher doses (two tablets or more for a day) caused organ damage. The KAP scores were reported as 24.5% with low, 52.7% moderate, and 22.7% satisfactory levels. Significantly lower KAP scores were associated with lower education levels and patients obtaining complementary and alternative therapies (p<0.05). Misconceptions are not merely kept in mind but lead to non-adherence with metformin doses prescribed and warrant evidence-based educational interventions with the high-risk groups.

Counting the Cost of Cellular and/or Tissue-Based Products in Diabetic Foot Ulcers: Is There a Justifiable Price Limit per Square Centimeter?

Objective: To identify how cellular and/or tissue-based products (CTPs) relate to value in terms of cost per quality-adjusted life years (QALYs) in wound care in comparison with treatments in other medical fields. Approach: This is a cross-sectional study and a cost-effectiveness analysis. Payment limits for each CTP were obtained via the Healthcare Common Procedure Coding System Q codes and formulated as cost inputs into a cost-utility model published for treatment of Wagner 1 diabetic foot ulcers using dehydrated human amnion and chorion allograft versus standard of care (SOC). Additional changes to cap the number of CTP applications and adjustments for recent inflation were made. The literature was searched for other cost-utility models in other diabetes-related diseases as a comparison. Results: When the payment limit was ≤$140 per square centimeter, interventions were dominant (less costly, better outcomes) compared with SOC. When the limit exceeded $430 per square centimeter, the cost-effectiveness threshold of $100,000/QALY was exceeded. Newer Q codes are generally much more expensive and likely to not be cost-effective, similar to the results for many other chronic diabetes-related diseases . Innovation: This study presents decision makers with tools, by which they can determine as to whether a given CTP is likely to be cost-effective for patients. Conclusion: Over a third of all CTPs will very likely result in noncost-effective interventions. This number is likely to be higher when wounds are larger or used in other wound types where they are less efficacious. The recent trend in much higher costs for CTPs is worrisome.

Position paper: Open-source technology in the treatment of people living with diabetes mellitus-an Austrian perspective : Technology Committee of the Austrian Diabetes Association

People living with diabetes mellitus can be supported in the daily management by diabetes technology with automated insulin delivery (AID) systems to reduce the risk of hypoglycemia and improve glycemic control as well as the quality of life. Due to barriers in the availability of AID-systems, the use and development of open-source AID-systems have internationally increased. This technology provides a necessary alternative to commercially available products, especially when approved systems are inaccessible or insufficiently adapted to the specific needs of the users. Open-source technology is characterized by worldwide free availability of codes on the internet, is not officially approved and therefore the use is on the individual's own responsibility. In the clinical practice a lack of expertise with open-source AID technology and concerns about legal consequences, lead to conflict situations for health-care professionals (HCP), sometimes resulting in the refusal of care of people living with diabetes mellitus. This position paper provides an overview of the available evidence and practical guidance for HCP to minimize uncertainties and barriers. People living with diabetes mellitus must continue to be supported in education and diabetes management, independent of the chosen diabetes technology including open-source technology. Check-ups of the metabolic control, acute and chronic complications and screening for diabetes-related diseases are necessary and should be regularly carried out, regardless of the chosen AID-system and by a multidisciplinary team with appropriate expertise.

The causal relationship between anti-diabetic drugs and gastrointestinal disorders: a drug-targeted mendelian randomization study

BackgroundThe incidence of diabetic gastrointestinal diseases is increasing year by year. This study aimed to investigate the causal relationship between antidiabetic medications and gastrointestinal disorders, with the goal of reducing the incidence of diabetes-related gastrointestinal diseases and exploring the potential repurposing of antidiabetic drugs.MethodsWe employed a two-sample Mendelian randomization (TSMR) design to investigate the causal association between antidiabetic medications and gastrointestinal disorders, including gastroesophageal reflux disease (GERD), gastric ulcer (GU), chronic gastritis, acute gastritis, Helicobacter pylori infection, gastric cancer (GC), functional dyspepsia (FD), irritable bowel syndrome (IBS), ulcerative colitis (UC), Crohn’s disease (CD), diverticulosis, and colorectal cancer (CRC). To identify potential inhibitors of antidiabetic drug targets, we collected single-nucleotide polymorphisms (SNPs) associated with metformin, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, insulin, and its analogs, thiazolidinediones, sulfonylureas, and alpha-glucosidase inhibitors from published genome-wide association study statistics. We then conducted a drug-target Mendelian randomization (MR) analysis using inverse variance weighting (IVW) as the primary analytical method to assess the impact of these inhibitors on gastrointestinal disorders. Additionally, diabetes was selected as a positive control.ResultsSulfonylureas were found to significantly reduce the risk of CD (IVW: OR [95% CI] = 0.986 [0.978, 0.995], p = 1.99 × 10− 3), GERD (IVW: OR [95% CI] = 0.649 [0.452, 0.932], p = 1.90 × 10− 2), and chronic gastritis (IVW: OR [95% CI] = 0.991 [0.982, 0.999], p = 4.50 × 10− 2). However, they were associated with an increased risk of GU development (IVW: OR [95%CI] = 2 0.761 [1.259, 6.057], p = 1 0.12 × 10− 2).ConclusionsThe results indicated that sulfonylureas had a positive effect on the prevention of CD, GERD, and chronic gastritis but a negative effect on the development of gastric ulcers. However, our research found no causal evidence for the impact of metformin, GLP-1 agonists, SGLT2 inhibitors, DPP 4 inhibitors, insulin and its analogs, thiazolidinediones, or alpha-glucosidase inhibitors on gastrointestinal diseases.Graphical abstract

Undiagnosed and Untreated Peripheral Complications of Diabetes: Findings from a Pilot Study on Diabetes-Related Foot Diseases (DFD) in Patients with Glycemic Disorders.

BACKGROUND Diabetes-related foot disease (DFD) is a serious complication of diabetes, increasing the risk of amputation. Coimplications are preventable, but most diabetics do not receive proper screening and treatment, despite indications. This study was a pilot screening of diabetes-related foot disease in a group of people with glycemic disorders. MATERIAL AND METHODS We recruited 143 volunteers over 40 years of age. In the final analysis, we included 85 people diagnosed with glycemic disorders (diabetes or prediabetes), for whom we performed a total of 170 foot measurements. We screened for peripheral artery disease using: foot pulse, ankle-brachial index (manual and automatic), toe-brachial index, and transcutaneous oxygen pressure (TcPO2). To screen for diabetic peripheral neuropathy, we used indicators of loss of protective sensation: pressure perception and temperature perception, and plantar pressure distribution. RESULTS A history of diabetes was reported by 26 (30.6%) of the subjects. Disorders of at least 1 foot occurred in 20 (66.7%) subjects with diagnosed diabetes and in 10 (17%) subjects declaring no diabetes. Higher risk and DFD category were correlated with duration of diabetes (r=0.68, p=0.007), glycemic levels (r=0.56, p=0.001), age (r=0.57, p=0.007), and the presence of other diabetes complications. The best predictor of risk in DFD was manual ABI, p=0.001; followed by automatic ABI, p=0.006. CONCLUSIONS Our results showed that peripheral complications of diabetes, such as DFD, often remain undiagnosed and untreated despite the high risk of developing ulcers. There is a need for multi-center screening studies.

Population-based assessment of awareness of diabetes and diabetes related eye diseases in rural areas in Telangana, India – implications for eye health promotion

ABSTRACT Clinical relevance Understanding the awareness level of diabetes and diabetes-related eye diseases will help in developing better eye health education programmes and improve health-seeking behaviour in the community. Background Diabetes and diabetes related eye diseases are increasing in numbers both in urban and rural areas in India. There are limited data on awareness of diabetes and diabetes-related eye disease in rural communities of India. This study reports on awareness of diabetes and diabetes-related eye diseases in people aged ≥40 years from two rural districts of Telangana, India. Methods A structured questionnaire was used to determine the awareness of diabetes and diabetes-related eye diseases among participants aged ≥40 years in the Khammam and Warangal districts of Telangana, India. Social investigators visited the participant’s households and conducted the interviews. A positive response to a question on having heard about diabetes was considered as ‘awareness’. For those aware, follow-up questions were asked about the effect of diabetes on vision, frequency of eye examination and source of information. A positive response on a question that diabetes could cause loss of vision was considered as awareness of diabetic eye disease. Results A total of 3273 participants were interviewed. Among them, 56.2% (n = 1840) were women, 60.6% (n = 1985) had no formal education, and 50.2% (n = 1645) were from the Khammam district. The mean age of the participants was 55.3 years (standard deviation: 11.7 years). Awareness of diabetes was 52.5% (n = 1719). Among them, 1056 participants (61.4%) were aware that diabetes could affect vision. Conclusion Only half of the participants were aware of diabetes and of this substantial proportion of individuals was unaware of potential vision loss due to diabetes. Improving awareness about diabetes and its impact on vision is recommended to prevent potential vision loss in this population.

Dıabetic Foot: Wound Healing, Amputation Decision, and Innovative Developments

Aim: To review the effects of diabetes-related diseases on the healing process and amputation decision in diabetic foot ulcers (DFU), negative pressure wound therapy (NPWT) results, and current treatment approaches.&#x0D; Materials and Methods: The study was planned as retrospective and cross-sectional. Data of patients who were admitted to our clinic due to DFU and were treated were examined. A total of 38 patients were included in the study. The results of patients (n=19) who underwent periodic debridement and classic dressing were compared with the results of patients (n=19) who underwent NPWT. Healing in patients was achieved by amputation (n=8), repair with partial thickness grafts or flaps (n=10), and secondary epithelialization development (n=10). The effect of diabetes-related peripheral arterial disease (PAD), cardiovascular disease (CVD), chronic kidney disease (CKD), diabetic retinopathy (DRP), and previous amputation history (AH) on recovery time was examined. The predictive importance of diabetes-related diseases for amputation was investigated.&#x0D; Results: It was determined that diabetes-related diseases caused a delay in wound healing. [PAD (p

Gap analysis of diabetes-related foot disease management systems in Pacific Islands Countries and Territories

BackgroundPacific Island Countries and Territories (PICTs) are known to have high prevalence of Diabetes Mellitus and high incidence of diabetes-related foot disease. Diabetes-related foot disease can lead to lower limb amputation and is associated with poor outcomes, with increased morbidity and mortality. The purpose of this study was to gain a better understanding of diabetes-related foot disease management in selected countries in PICTs and to identify potential barriers in management of diabetes-related foot disease management in the region.MethodsA cross-sectional survey was sent to eleven hospitals across six selected PICTs. The survey instrument was designed to provide an overview of diabetes-related foot disease (number of admissions, and number of lower limb amputations over 12 months) and to identify clinical services available within each institution. Two open-ended questions (free text responses) were included in the instrument to explore initiatives that have helped to improve management and treatment of diabetes-related foot diseases, as well as obstacles that clinicians have encountered in management of diabetes-related foot disease. The survey was conducted over 6 weeks.ResultsSeven hospitals across four countries provided responses. Number of admissions and amputations related to diabetes-related foot disease were only reported as an estimate by clinicians. Diabetes-related foot disease was managed primarily by general medicine physician, general surgeon and/or orthopaedic surgeon in the hospitals surveyed, as there were no subspecialty services in the region. Only one hospital had access to outpatient podiatry. Common themes identified around barriers faced in management of diabetes-related foot disease by clinicians were broadly centred around resource availability, awareness and education, and professional development.ConclusionDespite the high prevalence of diabetes-related foot disease within PICTs, there appears to be a lack of functional multi-disciplinary foot services (MDFs). To improve the outcomes for diabetes-related foot disease patients in the region, there is a need to establish functional MDFs and engage international stakeholders to provide ongoing supports in the form of education, mentoring, as well as physical resources.

LncRNA PVT1 as a Novel Biomarker for Diabetes-related Complications.

Diabetes is now afflicting an expanding population, and it has become a major source of concern for human health. Diabetes affects several organs and causes chronic damage and dysfunction. It is one of the three major diseases that are harmful to human health. Plasmacytoma variant translocation 1 is a member of long non-coding RNA. PVT1 expression profile abnormalities have been reported in diabetes mellitus and its consequences in recent years, suggesting that it may contribute to the disease's progression. Relevant literature from the authoritative database "PubMed" are retrieved and summarized in detail. Mounting evidence reveals that PVT1 has multiple functions. Through sponge miRNA, it can participate in a wide variety of signal pathways and regulate the expression of a target gene. More importantly, PVT1 is crucially implicated in the regulation of apoptosis, inflammation, and so on in different types of diabetes-related complications. PVT1 regulates the occurrence and progression of diabetes-related diseases. Collectively, PVT1 has the potential to be a useful diagnostic and therapeutic target for diabetes and its consequences.

Transthyretin-Regulated Diabetic Retinopathy Through the VEGFA/PI3K/AKT Pathway.

Transthyretin (TTR) plays a regulatory role in a variety of diabetes-related diseases. The objective of this work was to probe whether TTR affects diabetic retinopathy (DR) through the VEGFA/PI3K/AKT pathway. High glucose (HG, 25mM) was used to treat human retinal microvascular endothelial cells (hRMECs) and C57BL/6J mice were intraperitoneally injected with STZ (50mg/kg) to construct a DR model. In vitro, the effect of TTR on DR was evaluated by measuring hRMEC proliferation, migration, and angiogenesis. The changes in retinal tissue were observed by hematoxylin and eosin staining in vivo. ELISA, immunohistochemistry, and immunofluorescence staining were used to measure VEGFA or CD31 levels. The levels of all proteins were evaluated through Western blot. The increase of proliferation, migration, and angiogenesis and decrease of apoptosis in hRMECs caused by HG were notably reversed by TTR. TTR greatly impeded HG-raised VEGFA, PI3K p-p85, and p-AKT in hRMECs. Inhibition of TTR further exacerbated the effect of HG-induced hRMECs. Inhibition of VEGFA reversed the effect of HG-induced hRMECs. VEGFA neutralized the function of TTR on cell proliferation, apoptosis, migration, and angiogenesis in HG-triggered hRMECs. It was further confirmed in vivo that TTR can alleviate the occurrence of DR in diabetic mice models. TTR significantly restrained the progression of DR via molecular modulation of the VEGFA/PI3K/AKT axis.

Knowledge, attitude, and practice of diabetes in patients with and without sight-threatening diabetic retinopathy from two secondary eye care centres in India.

Good knowledge, Attitude, and Practice (KAP) of diabetes influence its control and complications. We examined the KAP of diabetes in patients with sight-threatening diabetic retinopathy (STDR) and non-sight-threatening diabetic retinopathy (NSTDR) attending two different referral hospitals in India. 400 consecutive patients (mean age = 58.5years ± 10.3) with diabetic retinopathy attending retina referral clinics in Chennai (private) and Darjeeling (public) were recruited. A validated questionnaire on diabetic KAP was administered in English or the local language. Data were analysed using an established scalar-scoring method in which a score of 1 was assigned to the correct answer/healthy lifestyle and 0 to an incorrect answer/unhealthy lifestyle/practice. Clinical data included fasting blood sugar, blood pressure, retinopathy, and visual acuity. Retinopathy was graded as STDR/NSTDR from retinal images using Early Treatment of Diabetic Retinopathy Study criteria. Usable data from 383 participants (95.8%) were analysed. Of these, 83 (21.7%) had STDR, and 300 (78.3%) had NSTDR. The NSTDR group reported a significantly lower total KAP score (mean rank = 183.4) compared to the STDR group (mean rank = 233.1), z = -3.0, p < 0.001. A significantly greater percentage in the NSTDR group reported to being unaware that diabetes could affect eyes, did not know about possible treatment for DR, and checked their blood sugar less frequently than once a month. Patients who had not developed STDR had poorer KAP about diabetes and diabetes-related eye diseases. This is an important issue to address as the risk of their progressing to STDR is high unless appropriate steps to improve their knowledge/awareness and lifestyle practice are introduced early.

FNDC5/Irisin mitigates high glucose-induced neurotoxicity in HT22 cell via ferroptosis.

Diabetes-induced neuropathy represents a major etiology of dementia, highlighting an urgent need for the development of effective therapeutic interventions. In this study, we explored the role of fibronectin type III domain containing 5 (FNDC5)/Irisin in mitigating hyperglycemia-induced neurotoxicity in HT22 cells and investigated the underlying mechanisms. Our findings reveal that high glucose conditions are neurotoxic, leading to reduced viability of HT22 cells and increased apoptosis. Furthermore, the elevated expression of the intracellular ferroptosis marker Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), along with increased levels of ferrous ions and malondialdehyde (MDA), suggests that high glucose conditions may induce ferroptosis in HT22 cells. FNDC5/Irisin treatment effectively mitigates high glucose-induced neurotoxicity and ferroptosis in HT22 cells. Mechanistically, FNDC5/Irisin enhances cellular antioxidant capacity, regulates ACSL4 expression, and improves intracellular redox status, thereby inhibiting ferroptosis and increasing HT22 cell survival under high-glucose conditions. These results highlight the neuroprotective potential of FNDC5/Irisin in high glucose environments, offering a promising avenue for developing treatments for diabetes-related neurodegenerative diseases.

The Importance of Type 2 Diabetes and Physical Activity Research Beyond The Covid-19-Pandemia: A Letter to The Editor

Diabetes and diabetes-related diseases or health problems are global issues, and they cause human distress and great expenditures in a society. Therefore, diabetes and physical activity research is remarkable from a viewpoint of individual and public health especially during the COVID-19 pandemic and beyond. In a Corona-changing world it is important to prioritize physical activity in health promotion and strengthen scientific research to highlight the significance and the health benefits of physical activity for improving the management of diabetes (especially type 2), as well as to prevent the increase in global burden of diabetes, other non-communicable diseases and COVID-19. The new research findings could contribute solid scientific-based evidence to the international guidelines on physical activity in preventing and managing type 2 diabetes, and decreasing the diabetes-related risk of morbidity and mortality. Therefore, type 2 diabetes and physical activity research is timely and relevant, focusing on one of the leading health problems that our time is currently facing. Finally, in order to be successful, to change and save lives, the diabetes research requires more funding.

Nuclear Receptor PPARα as a Therapeutic Target in Diseases Associated with Lipid Metabolism Disorders.

Lipid metabolic diseases have substantial morbidity and mortality rates, posing a significant threat to human health. PPARα, a member of the peroxisome proliferator-activated receptors (PPARs), plays a crucial role in lipid metabolism and immune regulation. Recent studies have increasingly recognized the pivotal involvement of PPARα in diverse pathological conditions. This comprehensive review aims to elucidate the multifaceted role of PPARα in metabolic diseases including liver diseases, diabetes-related diseases, age-related diseases, and cancers, shedding light on the underlying molecular mechanisms and some regulatory effects of natural/synthetic ligands of PPARα. By summarizing the latest research findings on PPARα, we aim to provide a foundation for the possible therapeutic exploitation of PPARα in lipid metabolic diseases.

Single-cell RNA sequencing reveals a distinct profile of bone immune microenvironment and decreased osteoclast differentiation in type 2 diabetic mice

The pathogenic effects of type 2 diabetes on bone tissue are gaining attention, but the cellular and molecular mechanisms underlying osteoimmunology are still unclear in diabetes-related bone diseases. We delineated the single-cell transcriptome of bone marrow cells from both wide type and type 2 diabetes mice, which provided the first detailed global profile of bone marrow cells and revealed a distinct bone immune microenvironment at the genetic level under type 2 diabetic condition. It was observed that osteoclast activity was inhibited due to a dysregulated cytokine network, which ultimately led to decreased osteoclast formation and differentiation. In type 2 diabetes mice, a specific Cd36+ cluster (cluster 18, monocytes/macrophages 2) was identified as the precursor of osteoclasts with diminished differentiation potential. AP-1 was demonstrated to be the key transcription factor in the underlying mechanism.

IWGDF/IDSA Guidelines on the Diagnosis and Treatment of Diabetes-related Foot Infections (IWGDF/IDSA 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.

IWGDF/IDSA guidelines on the diagnosis and treatment of diabetes-related foot infections (IWGDF/IDSA 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.