Curing Necrotic Angiodermatitis with an Intact Fish Skin Graft in a Patient Living with Diabetes.

Background and Objectives: We describe a case of necrotic angiodermatitis. Materials and Methods: We used an intact fish skin graft to treat a patient living with diabetes, which was complicated by end-stage renal failure and arterial hypertension. The entire therapeutic procedure was carried out in ambulatory care without requiring the hospitalization of the patient. Results: The patient experienced a marked reduction in pain and complete epithelization of the lesion after 10 weeks of treatment. Conclusion: Our experience presents a new therapeutic approach to necrotic angiodermatitis.

Delayed Diagnosis of Bilateral Neuroarthropathy: Serious Impact on the Development of Charcot's Foot, a Case Report.

Charcot neuroarthropathy (CN) is a destructive complication of the joints in patients with diabetes and should be managed from the onset of the first symptoms to avoid joint deformity and the risk of amputating the affected joint. Here, we describe the case of a young 24-year-old patient living with type I diabetes who developed active bilateral CN in both tarsal joints. This case of neuroarthropathy was uncommon due to the bilateral presentation at the same level of the joint. Despite the patient consulting from the beginning of the symptoms, none of the physicians suspected or diagnosed CN, leading to a delay in management and the aggravation of bone destruction by CN. This highlights the importance of early management of CN with the need to refer people with suspected CN to specialised diabetic foot care centres.

Impact of the Rapid Normalization of Chronic Hyperglycemia on the Receptor Activator of Nuclear Factor-Kappa B Ligand and the Osteoprotegerin System in Patients Living with Type 2 Diabetes: RANKL-GLYC Study.

The RANKL-GLYC study aims to explore the impact of the rapid correction of chronic hyperglycemia on the receptor activator of nuclear factor-kappa B ligand (RANKL) and its antagonist osteoprotegerin (OPG). RANKL and OPG are considered the main factors in the pathophysiology of Charcot neuroarthropathy, a devastating complication of the joints that remains poorly understood. The study began recruiting patients in September 2021 and ends in June 2022; the final study results are scheduled for January 2023.

Intact Fish Skin Graft vs. Standard of Care in Patients with Neuroischaemic Diabetic Foot Ulcers (KereFish Study): An International, Multicentre, Double-Blind, Randomised, Controlled Trial Study Design and Rationale.

BACKGROUND: Cell and/or tissue-based wound care products have slowly advanced in the treatment of non-healing ulcers, however, few studies have evaluated the effectiveness of these devices in the management of severe diabetic foot ulcers. METHOD: This study (KereFish) is part of a multi-national, multi-centre, randomised, controlled clinical investigation (Odin) with patients suffering from deep diabetic wounds, allowing peripheral artery disease as evaluated by an ankle brachial index equal or higher than 0.6. The study has parallel treatment groups: Group 1 treatment with Kerecis® Omega3 Wound™ versus Group 2 treatment with standard of care. The primary objective is to test the hypothesis that a larger number of severe diabetic ulcers and amputation wounds, including those with moderate arterial disease, will heal in 16 weeks when treated with Kerecis® Omega3 Wound™ than with standard of care. CONCLUSION: This study has received the ethics committee approval of each participating country. Inclusion of participants began in March 2020 and ended in July 2022. The first results will be presented in March 2023. The study is registered in ClinicalTrials.gov as Identifier: NCT04537520.

Fracture of the Bone Inducing Its Necrosis as the End Point in the Evolution of Untreated Neuroarthropathy.

We describe here the case of a female patient with type I diabetes who developed active Charcot neuroarthropathy in the foot. Due to therapeutic noncompliance, talus necrosis was discovered 2 years after the presentation of neuroarthropathy. The impact of untreated neuroarthropathy on the bone is commonly described as fracture and joint dislocation, but we describe the complete disappearance of the bony structure and its necrosis associated with active neuroarthropathy in a patient who refused offloading.

Efficacy of two telemonitoring systems to improve glycaemic control during basal insulin initiation in patients with type 2 diabetes: The TeleDiab-2 randomized controlled trial.

TeleDiab-2 was a 13-month randomized controlled trial evaluating the efficacy and safety of two telemonitoring systems to optimize basal insulin (BI) initiation in subjects with inadequately controlled type 2 diabetes (HbA1c, 7.5%-10%). A total of 191 participants (mean age 58.7 years, mean HbA1c 8.9%) were randomized into three groups: group 1(G1, standard care, n = 63), group 2 (G2, interactive voice response system, n = 64) and group 3 (G3, Diabeo-BI app software, n = 64). The two telemonitoring systems proposed daily adjustments of BI doses, in order to facilitate the achievement of fasting blood glucose (FBG) values targeted at ~100 mg/dL. At 4 months follow-up, HbA1c reduction was significantly higher in the telemonitoring groups (G2: -1.44% and G3: -1.48% vs. G1: -0.92%; P < 0.002). Moreover, target FBG was reached by twice as many patients in the telemonitoring groups as in the control group, and insulin doses were also titrated to higher levels. No severe hypoglycaemia was observed in the telemonitoring groups and mild hypoglycaemia frequency was similar in all groups. In conclusion, both telemonitoring systems improved glycaemic control to a similar extent, without increasing hypoglycaemic episodes.

Automated insulin delivery system: A solution for moderate to high-risk Ramadan fasting in people living with type 1 diabetes.

We investigated whether Ramadan, a yearly religious fasting lasting for one month, could challenge the metabolic control obtained under a hybrid closed-loop (HCL) therapy in patients living with type 1 diabetes (T1D). This real-life prospective study involved 20 patients with T1D and moderate to high-risk score of adverse events at baseline. We compared continuous glucose monitoring (CGM) parameters under HCL therapy one month before and during the Ramadan fasting month. The main outcome was the evolution of the percentage of time-in-range (TIR, 70-180 mg/dL) between the two time points, and secondary outcomes were the evolution of other CGM parameters and frequency of acute metabolic events. We observed no statistical difference regarding TIR (mean±SD) (63±11 % during fasting versus 62±12 % before) as well as for other parameters including time spent under 70 mg/dL (1.1±1.0% versus 1.5±1.3%) and percentage of HCL use (93±5% versus 94±5%). No acute metabolic event was observed during fasting under HCL. Results were homogenous across baseline risk score groups.

Trends in the pathophysiology of Charcot neuroarthropathy.

The pathophysiology of Charcot neuroarthropathy (CN) includes a number of gray areas, particularly regarding the onset of inflammation which induces the disruption of the bone remodeling factor responsible for the onset of bone lysis. This clinical insight highlights a potential link between this inflammation and the rapid correction of chronic hyperglycemia (Dardari et al., 2022), which is known to be responsible for a particular type of neuropathy known as treatment-induced neuropathy of diabetes (TIND). Our description makes an additional contribution to shed light on the mysterious physiopathology of CN.

Rapid correction of hyperglycemia: A necessity but at what price? A brief report of a patient living with type 1 diabetes.

BACKGROUND: The correction and control of chronic hyperglycemia are the management goals of patients living with diabetes. Chronic hyperglycemia is the main factor inducing diabetes-related complications. However, in certain situations, the rapid and intense correction of chronic hyperglycemia can paradoxically favor the onset of microvascular complications. CASE SUMMARY: In this case report, we describe the case of a 25-year-old woman living with type 1 diabetes since the age of 9 years. Her diabetes was chronic and unstable but without complications. During an unplanned pregnancy, her diabetes was intensely managed with the rapid correction of her hyperglycemia. However, over the following 2 years, she developed numerous degenerative microvascular complications: Charcot neuroarthropathy with multiple joint involvement, severe proliferative diabetic retinopathy, gastroparesis, bladder voiding disorders, and end-stage renal failure requiring hemodialysis. CONCLUSION: In the literature to date, the occurrence of multiple microvascular complications following the rapid correction of chronic hyperglycemia has been rarely described in the same individual.

Impact of Intensive Glycemic Treatment on Diabetes Complications-A Systematic Review.

Diabetes complications can be related to the long duration of the disease or chronic hyperglycemia. The follow-up of diabetic patients is based on the control of chronic hyperglycemia, although this correction, if obtained rapidly in people living with severe chronic hyperglycemia, can paradoxically interfere with the disease or even induce complications. We reviewed the literature describing the impact of the rapid and intense treatment of hyperglycemia on diabetic complications. The literature review showed that worsening complications occurred significantly in diabetic microangiopathy with the onset of specific neuropathy induced by the correction of diabetes. The results for macroangiopathy were somewhat mixed with the intensive and rapid correction of chronic hyperglycemia having a neutral impact on stroke and myocardial infarction but a significant increase in cardiovascular mortality. The management of diabetes has now entered a new era with new therapeutic molecules, such as gliflozin for patients living with type 2 diabetes, or hybrid insulin delivery systems for patients with insulin-treated diabetes. Our manuscript provides evidence in support of these personalized and progressive algorithms for the control of chronic hyperglycemia.

Hospital stays and costs of telemedical monitoring versus standard follow-up for diabetic foot ulcer: an open-label randomised controlled study.

Background: Two randomised controlled trials (RCTs) have previously shown that telemedical monitoring of diabetic foot ulcer (DFU) reduces the number of visits to the outpatient clinic, without losing treatment efficacy or increasing costs. Here we present the results of an open-label, randomised controlled trial designed to investigate whether telemonitoring, provided by an expert nurse (with extensive experience in DFU and trained in remote monitoring), reduces the hospital stay and the associated costs for a patient with DFU (TELEPIED trial). Methods: Eligible patients (n = 180) were randomly allocated to: (i) a control group, in which they received standard care, and (ii) an intervention group, in which they received asynchronous telemedicine follow-up by the expert nurse. The primary outcome was the cumulative hospital days over 12 months. The main secondary outcomes were (i) direct healthcare costs (estimated in a collective perspective), (ii) wound healing and (iii) amputation rates. ITT (intention-to-treat) population was analysed. Findings: In the ITT population, cumulative hospital days were significantly higher in the control group (13.4 days [95% CI 9.0-17.8]) than in the intervention group (7.1 days [2.8-11.5]) (p = 0.0458, ANCOVA model). Cumulative direct costs over 12 months were 7185 € (95% CI 5144-9226) in the control group and 3471 € (95% CI 1430-5512) in the intervention group (p = 0.0120). The percentage of wounds healed and amputation rate were not significantly different between groups. Similar results were found with the PP population. Interpretation: The implementation of a telemedical intervention with an expert nurse could lead to a length of hospitalization and direct costs that were two times lower compared to conventional follow-up. This lower medical and economic burden was obtained without losing effectiveness on the rate of healing, nor increasing the amputation rate. Additional studies are required to confirm these findings. Funding: This study was designed, funded and conducted by CERITD (Study and Research Centre for Intensification of Diabetes Treatment, Evry, France), Genopole GIP, 20 rue Henri Desbruères, 91030 EVRY Cedex and Laboratoires URGO, 15 Avenue d'Iéna, 75116 Paris Cedex, France. The findings and conclusions in this study are those of the authors and do not necessarily represent the views of the sponsor. The corresponding author (DD) certify that authors were not precluded from accessing data in the study, and they accept responsibility to submit for publication.

Real-world treatment patterns and diagnosis of charcot foot in franco-belgian diabetic foot expert centers (The EPiChar Study).

AIM: To evaluate the real-life diagnosis and therapeutic means of Charcot Neuroosteoarthropathy (CN) in French-Belgian diabetic foot expert centers. METHODS: We collected clinical characteristics, results of exams and therapeutic pathways of consecutive adult patients with diabetic osteoarthropathy seen in consultation or hospitalization from January 1 to December 31, 2019 in 31 diabetic foot expert centers. The primary outcome was to describe the diagnostic and management methods for CN according to patient clinical characteristics, the clinical-radiological characteristics of acute and chronic CN and discharge means. RESULTS: 467 patients were included: 364 with chronic CN and 103 in the acute phase. 101 patients had bilateral chronic CN. Most patients were male (73.4%), treated with insulin (73.3%), and with multicomplicated diabetes. In the acute phase, edema and increased foot temperature were present in 75% and 58.3% of cases, respectively. Diagnosis confirmation was usually by MRI and the mode of discharge was variable. In the chronic phase, orthopedic shoes were prescribed in 81.5% of cases. CONCLUSIONS: This observational study highlights the diagnostic and therapeutic practices in 31 diabetic foot centers. Our results highlight that the use of MRI and the modalities of offloading, an essential treatment in the acute phase, need to be better standardized. Centers were highly encouraging about creating a patient registry.

Evaluation of Iodine Supplementation in Pregnant Women with Gestational Diabetes: IODIAB Study.

BACKGROUND: Iodine supplementation is indicated by the French National Authority for Health (HAS) and the World Health Organization (WHO) during pregnancy. This study investigates whether this supplementation is consistently prescribed in line with WHO recommendations in pregnant women diagnosed with gestational diabetes mellitus. METHOD: A total of 99 women with a diagnosis of gestational diabetes were included in the study and were all closely monitored. RESULTS: Only 17 (17.2%) patients received the recommended iodine supplementation. The follow-up, whether conducted by a gynecologist or midwife, did not influence the prescription of iodine supplements. By contrast, 72 (72.7%) of patients received folic acid supplementation. CONCLUSIONS: The prescription of iodine supplementation for the pregnant women included in our study is insufficient. Few practitioners seem aware of the recommendations, even when the pregnancy is complicated by gestational diabetes.

Post-healing follow-up study of patients in remission for diabetic foot ulcers Pied-REM study.

The rate of recurrence for diabetic foot ulcer (DFU) is 50% at 2 years Armstrong DG, 2017. International recommendations call for regular monitoring to prevent DFU recurrence. We aim to investigate the relation between post-healing follow-up and recurrence rates. The study will begin in November 2021 and end in April 2022; final study results are scheduled for December 2022. The purpose of the study is to evaluate the benefit of the multidisciplinary follow-up of healed DFU patients at the rate of two annual consultations and its impact on foot wound recurrence.

Trends in the relation between hyperglycemia correction and active Charcot neuroarthropathy: results from the EPICHAR study.

INTRODUCTION: The pathophysiology of Charcot neuroarthropathy (CN) remains unclear. There are a number of hypotheses but these are not exclusive. In its clinical presentation, this complication intersects with the semiology of diabetic-induced neuropathy, such as peripheral hypervascularization and the appearance of arteriovenous shunt. The EPICHAR study is as yet an unpublished cohort of people living with diabetes complicated by CN (in active or chronic phase). Based on the findings of the EPICHAR study, this study aimed to investigate whether a reduction in the rate of hyperglycemia accompanies the onset of an active phase of CN. RESEARCH DESIGN AND METHODS: Hemoglobin A1c (HbA1c) levels were assessed 3 months (M3) and 6 months (M6) before the diagnosis of active CN (M0). RESULTS: 103 patients living with diabetes and presenting active CN were included between January and December 2019 from the 31 centers participating in this study (30 in France and 1 in Belgium). The mean age of the participants was 60.2±12.2 years; the vast majority were men (71.8%) living with type 2 diabetes (75.5%). Mean HbA1c levels significantly declined between M6 (median 7.70; Q1, Q3: 7.00, 8.55) and M3 (median 7.65; Q1, Q3: 6.90, 8.50) (p=0.012), as well as between M6 and M0 (median 7.40; Q1, Q3: 6.50, 8.50) (p=0.014). No significant difference was found between M3 and M0 (p=0.072). CONCLUSIONS: A significant reduction in HbA1c levels seems to accompany the onset of the active phase of CN. TRIAL REGISTRATION NUMBER: NCM03744039.

Why the Risk of Developing Neuroarthropathy Is Higher After Simultaneous Kidney and Pancreatic Transplantation Compared to Kidney Transplantation Only: The Role of Euglycemia.

Charcot's neuroarthropathy is a destructive complication of the joint, which is often found in patients living with diabetes. Despite the fact that its description was published almost 100 years ago, its pathophysiology, diagnosis, and treatment remain areas that need to be updated. Its prevalence is low in patients living with diabetes, but this increases in particular situations such as peripheral neuropathy, as well as after simultaneous kidney-pancreas transplantation (SPKT) in patients living with type 1 diabetes. We suggest that the development of neuroarthropathy after SPK in not only due to glucocorticoid therapy, as described, but also to the rapid passage into euglycemia. The reduced prevalence of neuroarthropathy after only kidney transplantation compared to SPK seems to validate our hypothesis.

An overview of Charcot's neuroarthropathy.

Charcot's neuroarthropathy is a destructive complication of the joints, which is often found in people with diabetes with peripheral neuropathy. Despite the fact that its description was published almost 130 years ago, its pathophysiology, diagnosis, and treatment remain areas that need to be described. Thanks to the use of bone remodelling, new therapeutic classes have emerged, we hope that this review will shed light on the pathology from its discovery through to the current state of knowledge on its classification, diagnosis and treatment methods.

The onset of acute Charcot neuroarthropathy during pregnancy in patients with type 1 diabetes.

SUMMARY: We report the onset of acute Charcot neuroarthropathy during pregnancy in two patients with type 1 diabetes using retrospective review of case notes. We describe for the first time the onset of acute Charcot neuroarthropathy during pregnancy in two patients with type 1 diabetes. Pregnancy may promote the onset and worsening of a number of diabetic complications. A link between pregnancy and the onset of acute Charcot neuroarthropathy is demonstrated for the first time in this report. LEARNING POINTS: Patients with already diagnosed sensitive neuropathy can develop an active phase of Charcot neuroarthropathy during pregnancy. The rapid correction of hyperglycaemia may induce an active phase of Charcot neuroarthropathy during pregnancy.

Rapid glycemic regulation in poorly controlled patients living with diabetes, a new associated factor in the pathophysiology of Charcot's acute neuroarthropathy.

OBJECTIVE: Aggressive antidiabetic therapy and rapid glycemic control are associated with diabetic neuropathy. Here we investigated if this is also the case for Charcot neuroarthropathy. RESEARCH DESIGN AND METHODS: HbA1c levels and other relevant data were extracted from medical databases of 44 cases of acute Charcot neuroarthropathy. RESULTS: HbA1c levels significantly declined from 8.25% (67mmol/mol) [7.1%-9.4%](54-79mmol/mol), at -6 months (M-6), to 7.40%(54mmol/mol) [6.70%-8.03%] (50-64 mmol/mol) during the six months preceding the diagnosis of Charcot neuroarthropathy (P <0.001). CONCLUSIONS: HbA1c levels significantly declined during the six months preceding the onset of Charcot neuroarthropathy. This decline seems to be a associated factor with the appearance of an active phase of Charcot neuroarthropathy in poorly controlled patients with diabetic sensitive neuropathy.

Télépied Study: A Single-Centre Trial in Diabetic Subjects Comparing Total Duration of Hospitalization Over a 1-Year Period Required for Complete Healing of a Foot Ulcer Using Telemedicine Management and a Referral Nurse Versus the Standard Care Pathway.

PURPOSE: The aim of this study is to demonstrate that the total number of days in hospital required for healing of a de novo diabetes-related foot ulcer (DFU) is lower in patients followed up using a telemedicine platform (Télépied Follow-Up group [Group 2]) than in patients followed up using standard care (Standard Follow-Up control group [Group 1]). Patients are assigned to either Group 1 or Group 2 depending on whether their first inclusion visit is during an even or odd week. Patients included in Group 1 are to be followed at spaced intervals during day hospital visits by the investigator assisted by a specialized referral nurse as part of the regular follow-up procedure (dressing changes + ulcer monitoring). Between visits, an independent nurse (IN) provides local care on a daily basis. Patients included in Group 2 have their DFU treated by a referral nurse trained at the diabetic foot unit of the investigating centre, and they are also followed up by an IN under the supervision of a referral nurse. In Group 2, monitoring of lesions is performed weekly by the referral nurse using photos of the DFU with planimetry taken by the IN and sent to the referral nurse via telemedicine software. The referral nurse can, in turn, provide guidance to the IN on the care to be provided and/or decide that a further hospital visit is needed. Both treatment groups are to be followed for 12 months or until complete healing of the ulcer. RESULTS: Recruitment for the study began in March 2017 and ended in May 2019, with the final study visit scheduled for May 2020. CONCLUSION: The aim of the Télépied study is to assess the impact of ambulatory foot ulcer management in diabetics over a 1-year period by a non-specialized IN working under the supervision of a referral nurse via telemedicine follow-up versus standard follow-up by an IN alone. The primary endpoint is the total duration of hospitalization required until full healing of the ulcer.