Rationale and protocol for the After Diabetes Diagnosis REsearch Support System (ADDRESS): an incident and high risk type 1 diabetes UK cohort study

INTRODUCTION: Type 1 diabetes is heterogeneous in its presentation and progression. Variations in clinical presentation between children and adults, and with ethnic group warrant further study in the UK to improve understanding of this heterogeneity. Early interventions to limit beta cell damage in type 1 diabetes are undergoing evaluation, but recruitment is challenging. The protocol presented describes recruitment of people with clinician-assigned, new-onset type 1 diabetes to understand the variation in their manner of clinical presentation, to facilitate recruitment into intervention studies and to create an open-access resource of data and biological samples for future type 1 diabetes research. METHODS AND ANALYSIS: Using the National Institute for Health Research Clinical Research Network, patients >5 years of age diagnosed clinically with type 1 diabetes (and their siblings) are recruited within 6 months of diagnosis. Participants agree to have their clinical, laboratory and demographic data stored on a secure database, for their clinical progress to be monitored using information held by NHS Digital, and to be contacted about additional research, in particular immunotherapy and other interventions. An optional blood sample is taken for islet autoantibody measurement and storage of blood and DNA for future analyses. Data will be analysed statistically to describe the presentation of incident type 1 diabetes in a contemporary UK population. ETHICS AND DISSEMINATION: Ethical approval was obtained from the independent NHS Research Ethics Service. Results will be presented at national and international meetings and submitted for publication to peer-reviewed journals.This work was supported by Diabetes UK grant number 09/0003919 and the Juvenile Diabetes Research Foundation grant number 9-2010-407. Recruitment is supported by staff at the National Institute for Health Research Clinical Research Network

Reversing painful and non-painful diabetic neuropathy with the capsaicin 8% patch: Clinical evidence for pain relief and restoration of function via nerve fiber regeneration

Introduction: Current oral treatments for pain in diabetic peripheral neuropathy (DPN) do not affect the progression of DPN i.e. “disease modification”. We assessed whether Capsaicin 8% patch treatment can provide pain relief and also restore nerve density and function via nerve regeneration, in both painful (PDPN) and non-painful (NPDPN) diabetic peripheral neuropathy. Methods: 50 participants with PDPN were randomized to receive Capsaicin 8% patch Qutenza with Standard of Care (SOC) (PDPN Q+SOC group), or SOC alone (PDPN SOC group). Pain symptoms were assessed with a diary (Numerical Pain Rating Scale, NRPS) and questionnaires. Investigations included quantitative sensory testing (QST) and distal calf skin biopsies, at baseline and 3 months after baseline visit; subsequent options were 3-monthly visits over 1 year. 25 participants with NPDPN had tests at baseline, and 3 months after all received Capsaicin 8% patch treatment. Results: At 3 months after baseline, PDPN Q+SOC group had reduction in NPRS score (p=0.0001), but not PDPN SOC group. Short-Form McGill Pain Questionnaire (SF-MPQ) showed significant reductions in scores for overall and other pain descriptors only in the PDPN Q+SOC group. Warm perception thresholds were significantly improved only in the PDPN Q+SOC group (p=0.02), and correlated with reduction in SF-MPQ overall pain score (p=0.04). NPDPN Q+SOC group did not report pain during the entire study. Density of intra-epidermal nerve fibres (IENF) with PGP9.5 was increased at 3 months in PDPN Q+SOC (p=0.0002) and NPDPN Q+SOC (p=0.002) groups, but not in the PDPN SOC group. Increased sub-epidermal nerve fibres (SENF) were observed with GAP43 (marker of regenerating nerve fibres) only in PDPN Q+SOC (p=0.003) and NPDPN Q+SOC (p=0.0005) groups. Pain relief in the PDPN Q+SOC group was correlated with the increased PGP9.5 IENF (p=0.0008) and GAP43 (p=0.004), whereas those with lack of pain relief showed no such increase; in some subjects pain relief and increased nerve fibres persisted over months. PGP9.5 IENF increase correlated with axon-reflex vasodilatation in a NPDPN Q+SOC subset (p=0.006). Conclusions: Capsaicin 8% patch can provide pain relief via nerve regeneration and restoration of function in DPN (disease modification). It may thereby potentially prevent diabetic foot complications, including ulcers

Arterial spectral waveform analysis in the prediction of diabetic foot ulcer healing

Objective: We assessed the association between (1) severity of vessel wall calcification, (2) number of patent vessels at the ankle and (3) arterial spectral waveform features, as assessed on a focused ankle Duplex ultrasound (DUS), and healing at 12-months in a cohort of patients who had their diabetic foot ulcers conservatively managed. Research design and methods: Scans performed on 50 limbs in 48 patients were included for analysis. Patient health records were prospectively reviewed for 12-months to assess for the outcome of ulcer healing. Results: We identified that the number of waveform components, peak systolic velocity, systolic rise time and long forward flow as well as the number of vessels patent at the ankle on DUS, may be useful independent predictors of healing, as noted by the trend towards statistical significance. Conclusion: Arterial spectral waveform features may be useful in predicting the chance of diabetic foot ulcer healing

Fatal epidural abscess from diabetic foot disease

Summary Infection is a common complication of advanced diabetic foot disease, increasing the risk of acute admission and amputation. It is less well-known that foot ulceration and osteomyelitis may cause bacteraemia-associated hematogenous seeding and subsequent epidural abscess formation. Here we describe the case of a 57-year-old woman with known diabetic foot ulcer with underlying osteomyelitis admitted with backpain in the absence of trauma. Her condition deteriorated secondary to overwhelming sepsis. MRI of the spine confirmed spondylodiscitis and posterior epidural collection, not amenable to surgical intervention due to patient’s comorbidities and high surgical risk. Despite prolonged antibiotic therapy, the patient died following a hospital admission lasting 2.5 months. This case highlights the importance of regular contact with diabetes foot service for optimisation and prompt treatment of diabetic foot disease, which can be an underestimated potential source of remote site invasive systemic infection. Secondly, high clinical suspicion in admitting clinicians is imperative in ensuring timely diagnosis and early intervention to minimise fatal consequences

Ramadan-focused education and awareness in type 2 diabetes

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Association of other autoimmune diseases in thyroid eye disease

Background: Thyroid eye disease (TED) is a potentially disfiguring and sight-threatening autoimmune (AI) orbitopathy, affecting up to 400,000 people in the UK. There are no accurate early predictors of TED severity. Although polyautoimmunity has been shown to affect AI disease severity, its influence on TED severity has never been investigated. The prevalence of polyautoimmunity among TED patients is also unclear, with discordant results reported in the literature. This study evaluates the prevalence of non-thyroid/“other” AI (OAI) conditions in an ethnically diverse TED cohort and assesses how polyautoimmunity affects TED severity and activity. Methods: A retrospective study of patients presenting to multidisciplinary TED clinics across three North-West London hospitals between 2011 and 2019. Data collected included: 1) demographics; 2) OAI conditions and management; 3) endocrine management of thyroid dysfunction; 4) details of TED and clinical activity score at presentation. Results: Two hundred and sixty-seven patients with a median age of 46 (35–54) years were included, 79.4% were female and 55% were Black, Asian and minority ethnic (BAME). Thirty-seven patients (13.9%) had OAI conditions, with rheumatoid arthritis (3.7%), vitiligo (3.0%) and psoriasis (3.0%) among the most prevalent. Of patients with OAI conditions, 43.2% (16/37) required immunosuppression prior to TED onset. Non-immunosuppressed patients with OAI conditions had a significantly higher clinical activity score at presentation than TED-only and previously immunosuppressed patients (p=0.02). No significant differences were observed in thyroid receptor antibody titers between these groups. Conclusions: This study finds a 13.9% prevalence of OAI conditions among TED patients. Patients with OAI conditions overall have a tendency for more severe and significantly more clinically active TED than those without OAI conditions. Larger, prospective studies are warranted to further evaluate polyautoimmunity as an early predictor of TED severity