Summary Type 1 diabetes is a chronic autoimmune disease characterised by insulin deficiency and resultant hyperglycaemia. Knowledge of type 1 diabetes has rapidly increased over the past 25 years, resulting in a broad understanding about many aspects of the disease, including its genetics, epidemiology, immune and β-cell phenotypes, and disease burden. Interventions to preserve β cells have been tested, and several methods to improve clinical disease management have been assessed. However, wide gaps still exist in our understanding of type 1 diabetes and our ability to standardise clinical care and decrease disease-associated complications and burden. This Seminar gives an overview of the current understanding of the disease and potential future directions for research and care.

Type 1 diabetes

Diabetic foot ulcers (DFU) are a major source of preventable morbidity in adults with diabetes. Consequences of foot ulcers include decline in functional status, infection, hospitalization, lower-extremity amputation, and death. The lifetime risk of foot ulcer is 19% to 34%, and this number is rising with increased longevity and medical complexity of people with diabetes. Morbidity following incident ulceration is high, with recurrence rates of 65% at 3-5 years, lifetime lower-extremity amputation incidence of 20%, and 5-year mortality of 50-70%. New data suggest overall amputation incidence has increased by as much as 50% in some regions over the past several years after a long period of decline, especially in young and racial and ethnic minority populations. DFU are a common and highly morbid complication of diabetes. The pathway to ulceration, involving loss of sensation, ischemia, and minor trauma, is well established. Amputation and mortality after DFU represent late-stage complications and are strongly linked to poor diabetes management. Current efforts to improve care of patients with DFU have not resulted in consistently lower amputation rates, with evidence of widening disparities and implications for equity in diabetes care. Prevention and early detection of DFU through guideline-directed multidisciplinary care is critical to decrease the morbidity and disparities associated with DFU. This review describes the epidemiology, presentation, and sequelae of DFU, summarizes current evidence-based recommendations for screening and prevention, and highlights disparities in care and outcomes.

/pdf/etiology-epidemiology-and-disparities-in-the-burden-of-63kackph.pdf

Etiology, Epidemiology, and Disparities in the Burden of Diabetic Foot Ulcers.

Diabetic foot ulcers (DFU) are one of the most challenging complications of diabetes. Up to one-third of patients with diabetes mellitus (DM) may suffer from DFUs during their life. DFU is one of the leading causes of morbidity in patients with DM. The treatment period is challenging, and the recurrence rate of DFUs is high. Hence, establishing prevention strategies is the most important point to be emphasized. A multidisciplinary approach is necessary in the prevention and treatment of DFUs. Patients at risk should be identified, and prevention measures should be taken based on the risk category. Once a DFU is formed, the appropriate classification and evidence-based treatment interventions should be executed. Glycemic control, diagnosis and treatment of vascular disease, local wound care, diagnosis, and treatment of infection should be addressed along with the proper evaluation and management of general health status.

Management of diabetic foot ulcers and the challenging points: An endocrine view

Fast healing of diabetic wounds remains a major clinical challenge. Herein, this study reports a strategy to combine nanofiber aerogels containing precision macrochannels and the LL‐37‐mimic peptide W379 for rapid diabetic wound healing. Nanofiber aerogels consisting of poly(glycolide‐co‐lactide) (PGLA 90:10)/gelatin and poly‐p‐dioxanone (PDO)/gelatin short electrospun fiber segments are prepared by partially anisotropic freeze‐drying, cross‐linking, and sacrificial templating with 3D printed meshes, exhibiting nanofibrous architecture and precision micro‐/macrochannels. Like human cathelicidin LL‐37, W379 peptide at a concentration of 3 µg mL−1 enhances the migration and proliferation of keratinocytes and dermal fibroblasts in a cell scratch assay and a proliferation assay. In vivo studies show that nanofiber aerogels with precision macrochannels can greatly promote cell penetration compared to aerogels without macrochannels. Relative to control and aerogels with and without macrochannels, adding W379 peptides to aerogels with precision macrochannels shows the best efficacy in healing diabetic wounds in mice in terms of cell infiltration, neovascularization, and re‐epithelialization. The fast re‐epithelization could be due to the upregulation of phospho‐extracellular signal‐regulated kinase (p38 mitogen‐activated protein kinase) after treatment with W379. Together, the approach developed in this study could be promising for the treatment of diabetic wounds and other chronic wounds.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/adfm.202206936

Nanofiber Aerogels with Precision Macrochannels and LL‐37‐Mimic Peptides Synergistically Promote Diabetic Wound Healing

The role of CXCL8 in chronic nonhealing diabetic foot ulcers and phenotypic changes in fibroblasts: a molecular perspective

Purpose A considerable number of diabetic foot ulcer (DFU) patients require amputation every year, which worsens their quality of life, aggravates the social burden, and shortens their life expectancy. Considering these negative effects, it is important to explore the relative risk factors affecting amputation in DFU patients. Methods The PubMed, SCIE and Embase databases were comprehensively searched for prospective or retrospective studies published before October 31, 2019. All English language studies involving DFU patients were included, and RevMan 5.3 software was used to analyse the data. Results This meta-analysis includes 21 studies involving 6505 participants, including 2006 patients who required a lower limb amputation. The following variables were associated with an increased risk of amputation: male sex (odds ratios (OR) = 1.30, 95% confidence interval (CI) = 1.16~1.46, P<0.00001), smoking history (OR = 1.19, 95% CI = 1.04~1.35, P = 0.009), a history of foot ulcers (OR = 2.48, 95% CI = 2.00~3.07, P<0.00001), osteomyelitis (OR = 3.70, 95% CI = 3.02~4.53, P<0.00001), gangrene (OR = 10.90, 95% CI = 5.73~20.8, P<0.00001), a lower body mass index (mean difference IV (MD) = -0.88, 95% CI = -1.30~-0.47, P<0.0001), and a higher white blood cell count (MD = 2.42, 95% CI = 2.02~2.82, P<0.00001). However, age (MD = 1.24, 95% CI = -0.45~2.93, P = 0.15), type of diabetes (OR = 0.96, 95% CI = 0.61~1.52, P = 0.86), hypertension (OR = 1.19, 95% CI = 0.96~1.47, P = 0.12), and HbA1c level (MD = 0.02, 95% CI = -0.28~0.33, P = 0.87) were not associated with amputation in patients with DFU. Conclusions Our meta-analysis identified several risk factors for amputation in DFU patients, including the male sex, a smoking history, a history of foot ulcers, osteomyelitis, gangrene, a lower body mass index, and a higher white blood cell count. Once gangrene occurs, the risk of amputation rapidly increases.

/pdf/risk-factors-for-lower-extremity-amputation-in-patients-with-2tmpgvjssm.pdf

Risk factors for lower extremity amputation in patients with diabetic foot ulcers: A meta-analysis

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Risk factors for lower extremity amputation in patients with diabetic foot ulcers: A meta-analysis