EndoBridge 2023: highlights and pearls.

EndoBridge 2023 took place on October 20-22, 2023, in Antalya, Turkey. Accredited by the European Council, the 3-day scientific program of the 11th Annual Meeting of EndoBridge included state-of-the-art lectures and interactive small group discussion sessions incorporating interesting and challenging clinical cases led by globally recognized leaders in the field and was well attended by a highly diverse audience. Following its established format over the years, the program provided a comprehensive update across all aspects of endocrinology and metabolism, including topics in pituitary, thyroid, bone, and adrenal disorders, neuroendocrine tumors, diabetes mellitus, obesity, nutrition, and lipid disorders. As usual, the meeting was held in English with simultaneous translation into Russian, Arabic, and Turkish. The abstracts of clinical cases presented by the delegates during oral and poster sessions have been published in JCEM Case Reports. Herein, we provide a paper on highlights and pearls of the meeting sessions covering a wide range of subjects, from thyroid nodule stratification to secondary osteoporosis and from glycemic challenges in post-bariatric surgery to male hypogonadism. This report emphasizes the latest developments in the field, along with clinical approaches to common endocrine issues. The 12th annual meeting of EndoBridge will be held on October 17-20, 2024 in Antalya, Turkey.

Developing an intervention to support dietary change for shift workers living with type 2 diabetes: A stakeholder consultation.

BACKGROUND: Shift workers, compared to day workers, are more likely to be diagnosed with type 2 diabetes (T2D). Currently, there is no tailored programme of dietary support available to either shift workers living with T2D or employers. METHODS: An intervention development consultation workshop was convened in June 2023 with the aim of evaluating potential interventions to identify those with a potential to take forward for further development. Findings from prior formative research into factors influencing dietary behaviour in shift workers with T2D were mapped to potential interventions addressing the barriers and enablers to healthy eating reported by shift workers with T2D. The findings of the Shift-Diabetes Study were presented in the context of the COM-B (Capability, Opportunity, Motivation, Behaviour) theoretical framework of behaviour change. Three interventions in turn were presented to attendees: (1) Educational resources and structured education, (2) Increasing availability and accessibility of food on a night shift and (3) Biofeedback and tailored advice. Seven workshop attendees were invited to express their thoughts, using the APEASE criteria (Affordability, Practicability, Effectiveness, Acceptability, Side-effects/Safety, Equity) to guide the discussion. The workshop was conducted online and recorded, and transcripts were thematically coded to the APEASE framework. RESULTS/CONCLUSIONS: The workshop highlighted the importance of multilevel interventions to support dietary behaviour change in this occupational group. Priority actions identified include (i) understanding barriers to 24/7 food availability, (ii) including shift workers in clinical diabetes studies and (iii) research to understand the effectiveness of continuous glucose monitoring in shift workers with T2D.

Liraglutide 3.0 mg in the treatment of adults with obesity and prediabetes using real-world UK data: A clinical evaluation of a multi-ethnic population.

UK guidelines recommend liraglutide 3.0 mg in adults treated within specialist weight management services with BMI ≥35 kg/m2, prediabetes and high cardiovascular disease risk. We aimed to clinically evaluate liraglutide 3.0 mg in specialist weight management services. We evaluated liraglutide 3.0 mg in weight management services at Guys and St Thomas' NHS Foundation Trust. Objective body weight (BW) was measured at baseline and 4 months, allowing classification as 'responders' (≥5% BW reduction) and 'non-responders' (<5% BW reduction). One hundred and twenty-one patients were evaluated. At 4 months, 76.0% attended follow-up (82.6% responders, 17.4% non-responders); BW (-8.6 kg, 95%CI:-9.8, -7.4 kg), BMI (-3.2 kg/m2, 95%CI: -3.6, -2.8) and %-BW (-6.6%, IQR: -8.8%, -5.2%) significantly reduced. In responders, HbA1c reduced by -5.0 mmol/mol (IQR: -7.0. -4.0 mmol/mol). In responders BW continued to reduce up to 12 months (4 m: -10.2 kg, p < .0001; 6 m: -15.6 kg, p < .0001; 9 m: -16.5 kg, p < .0001; 12 m: -16.7 kg, p < .01). Those of Black African and Caribbean ethnicity experienced less BW loss than those of white ethnicity (4.12 kg, p = .017) and had a greater attrition rate. In adults with obesity and prediabetes who are treated within specialist weight management services, liraglutide 3.0 mg reduces BW and HbA1c. Those of Black African and Caribbean ethnicity experienced less BW reduction and greater attrition at 4 months. Further evaluation of the ethnic differences in response to obesity pharmacotherapy is required.

Society for Endocrinology guidelines for the diagnosis and management of post-bariatric hypoglycaemia.

Post bariatric hypoglycaemia (PBH) is typically a post-prandial hypoglycaemia occurring about 2-4 hours after eating in people who have undergone bariatric surgery. PBH develops relatively late after surgery and often after discharge from post-surgical follow-up by bariatric teams, leading to variability in diagnosis and management in non-specialist centres. AIM: to improve and standardise clinical practice in the diagnosis and management of PBH. OBJECTIVES: (1) to undertake an up-to-date review of the current literature; (2) to formulate practical and evidence-based guidance with regards on the diagnosis and treatment of PBH; (3) to recommend future avenues for research in this condition. METHOD: A scoping review was undertaken after an extensive literature search. A consensus on the guidance and confidence in the recommendations was reached by the steering group authors prior to review by key stakeholders. OUTCOME: We make pragmatic recommendations for the practical diagnosis and management of PBH including criteria for diagnosis and recognition, as well as recommendations for research areas that should be explored.

Real-world data of a digitally enabled, time-restricted eating weight management program in public sector workers living with overweight and obesity in the United Kingdom: A service evaluation of the Roczen program.

Introduction: The health of the United Kingdom workforce is key; approximately 186 million days are lost to sickness each year. Obesity and type 2 diabetes (T2D) remain major global health challenges. The aim of this retrospective service evaluation was to assess the impact of a digitally enabled, time-restricted eating (TRE) intervention (Roczen Program, Reset Health Ltd) on weight and other health-related outcomes. Methods: This service evaluation was conducted in people living with overweight/obesity, with 89% referred from public sector employers. Participants were placed on a TRE, low-carbohydrate, moderate protein plan delivered by clinicians and mentors with regular follow up, dietary guidance, goal setting, feedback, and social support. Results: A total of 660 members enrolled and retention was 41% at 12 months. The majority were female (73.2%), 58.9% were of White ethnicity, with a mean (SD) age of 47.5 years (10.1), and a body mass index of 35.0 kg/m2 (5.7). Data were available for 82 members at 12-month. At 12-month, members mean actual and percentage weight loss was -9.0 kg (7.0; p < 0.001) and -9.2% (6.7, p < 0.001) respectively and waist circumference reduced by -10.3 cm (10.7 p < 0.001), with 45.1% of members achieving ≥10% weight loss. Glycated hemoglobin was significantly improved at 6 months in people living with T2D (-11 mmol/mol [5.7] p = 0.012). Binge eating score significantly reduced (-4.4 [7.0] p = 0.006), despite cognitive restraint increasing (0.37 [0.6] p = 0.006). Conclusion: Our service evaluation showed that the Roczen program led to clinically meaningful improvements in body weight, health-related outcomes and eating behaviors that were sustained at 12-month.

Exploration of the individual, social and environmental factors influencing dietary behaviour in shift workers with type 2 diabetes working in UK healthcare-The Shift-Diabetes Study: A qualitative study using the theoretical domains framework.

AIM: To identify factors influencing dietary behaviour in shift workers with type 2 diabetes (T2D) working in UK healthcare settings. METHODS: Semi-structured qualitative interviews based on the theoretical domains framework (TDF) were conducted with a convenience sample (n = 15) of shift workers (32-59 years) diagnosed with T2D who worked night shifts as part of a mixed shift schedule. The TDF was applied to analyse transcripts using a combined deductive framework and inductive thematic analysis approach. Identified influences were mapped to the behaviour change technique taxonomy to identify potential strategies to change dietary behaviour in this context. RESULTS: Key barriers to healthy dietary behaviours were access and cost of food available during night work (TDF domain: Environment Context and Resources). Factors identified as both enablers and barriers included: availability of staff facilities and time to take a break, (Environment Context and Resources), the physical impact of night work (Beliefs About Consequences), eating in response to stress or tiredness (Emotion), advance planning of meals/food and taking own food to work (Behavioural Regulation). Potential techniques to address these influences and improve dietary behaviour in this context include: meal planning templates, self-monitoring and biofeedback, and increasing accessibility and availability of healthier food choices during night shifts. CONCLUSIONS: The dietary behaviour of shift workers with T2D is influenced by interacting individual, socio-cultural and environmental factors. Intervention should focus on environmental restructuring and strategies that enable monitoring and meal planning.

Efficacy and safety of semaglutide 2.4 mg according to antidepressant use at baseline: A post hoc subgroup analysis.

OBJECTIVE: To explore the efficacy and safety of semaglutide 2.4 mg in people with overweight/obesity who were also being treated with antidepressants (ADs). METHODS: Across the Semaglutide Treatment Effect for People with obesity (STEP) 1-3 and 5 trials, adults with overweight/obesity and type 2 diabetes (STEP 2 only) were enrolled. People with severe major depressive disorder within 2 years prior to screening or with a patient health questionnaire-9 score ≥15 at screening were excluded. Participants were categorized into subgroups according to baseline AD status (on/off ADs) in this post hoc exploratory analysis of the STEP trials. RESULTS: Of 3683 participants randomized, 539 were on ADs at baseline. Mean body weight change from baseline to week 68 was greater for semaglutide versus placebo, regardless of baseline AD use. In STEP 1, for participants on ADs at baseline, mean change from baseline was -15.7% with semaglutide versus -0.2% with placebo and -14.7% versus -2.8% for those not on ADs at baseline. Similar patterns were seen in STEP 2, 3, and 5. The prevalence of adverse events (AEs) was generally similar between semaglutide and placebo in participants on ADs at baseline. CONCLUSIONS: In adults with overweight/obesity, semaglutide provided clinically meaningful weight loss regardless of baseline AD use, with an AE profile consistent with previous studies.

Laparoscopic adjustable gastric banding with liraglutide in adults with obesity and type 2 diabetes (GLIDE): a pilot randomised placebo controlled trial.

INTRODUCTION: Obesity drives type 2 diabetes (T2DM) development. Laparoscopic adjustable gastric banding (LAGB) has lower weight reduction than other bariatric procedures. Liraglutide, a GLP-1 receptor agonist, improves weight and glycaemic control in patients with T2DM. This study aimed to determine the efficacy and safety of liraglutide 1.8 mg in participants undergoing LAGB. METHODS: GLIDE, a pilot randomised, double-blind, placebo-controlled trial, evaluated LAGB with either liraglutide 1.8 mg or placebo in participants with T2DM and obesity. Participants were randomised (1:1) to 6-months therapy post-LAGB, with further 6 months off-treatment follow-up. The primary outcome was change in HbA1c from randomisation to the end of treatment, secondary outcomes included body weight change. A sample size of 58 (29 per group) had 80% power to detect a 0.6% difference in HbA1c between groups. RESULTS: Twenty-seven participants were randomised to liraglutide (n = 13) or placebo (n = 14). Multivariate analysis showed no difference between placebo and liraglutide arms in HbA1c at 6 months (HbA1c:0.2 mmol/mol, -11.3, 11.6, p = 0.98) however, at 12 months HbA1c was significantly higher in the liraglutide arm (HbA1c:10.9 mmol/mol, 1.1, 20.6, p = 0.032). There was no difference between arms in weight at 6 months (BW:2.0 kg, -4.2, 8.1, p = 0.50), however, at 12 months weight was significantly higher in the liraglutide arm (BW:8.2 kg, 1.6, 14.9, p = 0.02). There were no significant differences in adverse events between groups. CONCLUSIONS: Our pilot data suggest no additional improvement in glycaemic control or BW with LAGB and liraglutide therapy. However, this trial was significantly underpowered to detect a significant change in the primary or secondary outcomes. Further trials are needed to investigate whether GLP-1 agonists, and particularly with more effective weekly agents (i.e. semaglutide or tirzepatide), are of benefit following metabolic surgery. CLINICAL TRIAL REGISTRATION: EudraCT number 2015-005402-11.

Screening and treatment of pre-bariatric surgical patients with obesity related sleep disordered breathing.

Background: There is a significant burden of sleep disordered breathing (SDB) in patients living with severe and complex obesity undergoing pre-bariatric surgery assessment. This longitudinal observational study evaluated the burden of obesity hypoventilation syndrome (OHS) in this cohort of patients and the therapeutic compliance of patients commenced on positive airway pressure treatment. Methods: All pre-bariatric surgery patients referred to the sleep clinic for review after an abnormal screening study between 2018 and 2022 were included. We collected data on their sleep study results, anthropometrics, co-morbid medical conditions, clinical observations, spirometry and arterial blood gas (ABG). Patients commenced on therapy were followed-up longitudinally and compliance data collected via remote monitoring. Results: A total of 116 patients were included [age: mean ± standard deviation (SD) 48.8±10.8 years; body mass index (BMI) 49.2±8.5 kg/m2; Epworth Sleepiness Scale (ESS) 8.7±5.1 points]. Fifteen patients (12.9% of cohort) were diagnosed with hypercapnic respiratory failure (pH 7.40±0.02; pO2 11.00±1.04 kPa; pCO2 6.15±0.08 kPa). Compared to eucapnic obstructive sleep apnoea (OSA) patients, they were older (51.1 vs. 48.5 years; P=0.311), had a higher BMI (51.5 vs. 48.9 kg/m2; P=0.266), more likely to be female (66.7% vs. 53.5%; P=0.275) and had a higher ESS score (10.4 vs. 8.5 points; P=0.177). On binomial regression analysis insulin dependent diabetes was the only patient characteristic of significance with prevalence increased in patients with OHS (26.7% vs. 8.9%; P=0.042). Forced vital capacity (FVC) and oxygen saturation (SpO2) cut-offs demonstrated high specificity (96.8%) but low sensitivity (13.3%) to diagnosed hypercapnia. Fifty percent of the patients with hypercapnia required bi-level ventilation. On follow-up 44.9% of patients were compliant with therapy (>4 hours usage/night). Conclusions: In minimally symptomatic patients living with severe and complex obesity who have an abnormal overnight oximetry, over 1 in 10 demonstrated chronic respiratory failure. Clinic spirometry and daytime SpO2 excluded those with hypercapnia. Overall adherence to prescribed therapy is low. Screening, appropriate pre-operative optimisation and peri-operative planning are important in preventing complications in this patient cohort.

Individual, social and environmental factors influencing dietary behaviour in shift workers with type 2 diabetes working in UK healthcare: A cross-sectional survey.

BACKGROUND: The present study aimed to understand the individual, social and environmental factors influencing dietary behaviour in shift workers with type 2 diabetes (T2D) working in UK healthcare settings. METHODS: A cross-sectional study was conducted using data collected from an anonymous online survey. Participant agreement was measured using five-point Likert scale (strongly disagree to strongly agree) against 38 belief statements informed by the Theoretical Domains Framework (TDF) of behaviour change. RESULTS: From the complete responses (n = 119), 65% worked shifts without nights, 27% worked mixed shift rota including nights and 8% worked only night shifts. The statements ranked with the highest agreements were in the TDF domains: Environment Context/Resources (ECR) - mainly identified as a barrier to healthy eating, Behaviour Regulation (BR) and intention (IN) - identified as enablers to healthy eating. For the belief statement 'the available options for purchasing food are too expensive' (ECR), 80% of night workers and 75% non-night workers agreed/strongly agreed. Taking their own food to work to prevent making unhealthy food choices (BR) had agreement/strong agreement in 73% of non-night and 70% night workers; 74% non-night workers and 80% of night workers agreed/strongly agreed with the statement 'I would like to eat healthily at work' (IN). Mixed shift workers agreed that following dietary advice was easier when working a non-night compared to a night shift (p = 0.002). CONCLUSIONS: Access and affordability of food were identified as important determinants of dietary behaviour during shifts. The findings support interventions targeting the food environment for shift workers with T2D.

Clinical evaluation of patients living with obesity.

Obesity is a significant public health concern which is implicated in cardiometabolic disease, mechanical complications and psychiatric sequelae. BMI is currently used for diagnosis; however, it has limited sensitivity for adiposity in certain circumstances. This has led to the development of risk stratification tools like the Edmonton Staging criteria and the Kings Obesity Staging Criteria: these facilitate and guide comprehensive obesity-related complication assessment. Healthcare professionals working within obesity clinics should adopt evidence-based communication strategies, including shared decision-making, motivational interviewing, and realistic goal setting. It is also vital to avoid weight-stigmatising terminology in all aspects of care, as this can negatively impact patients. Primary care plays an essential part in obesity care and should work to promptly identify cases, initiate treatment and forward on to specialist services where appropriate. Clinical evaluation of the patient living with obesity should take a holistic approach and involve input from bariatric physicians, dietitians, psychologists, and bariatric surgeons, wider members of the multi-disciplinary team should be involved where needed. Clinicians should take a detailed history, examination and order laboratory tests to investigate for complications. Overall, with appropriate evaluation, these assessments can guide patient management and facilitate long-term improvement in health.

Impact of BMI and comorbidities on efficacy of once-weekly semaglutide: Post hoc analyses of the STEP 1 randomized trial.

OBJECTIVE: This study assessed the effects of semaglutide on body weight, cardiometabolic risk factors, and glycemic status in individuals categorized by baseline BMI with or without additional obesity-related comorbidities, including prediabetes and high risk of cardiovascular disease (CVD). METHODS: This was a post hoc exploratory subgroup analysis of the Semaglutide Treatment Effect in People with Obesity (STEP) 1 trial (NCT03548935), in which participants without diabetes and BMI ≥30 kg/m2 , or BMI ≥27 kg/m2 with ≥1 weight-related comorbidity, were randomized to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks. For this analysis, individuals were categorized into subgroups based on baseline BMI <35 versus ≥35 kg/m2 (with no additional criteria, with ≥1 comorbidity, with prediabetes, and with prediabetes and high risk of CVD). RESULTS: Mean changes in body weight from baseline to week 68 with semaglutide were -16.2% and -14.0% in the subgroups with baseline BMI <35 and ≥35 kg/m2 , respectively (both p < 0.0001 vs. placebo). Similar changes were observed in individuals with comorbidities, with prediabetes, and with prediabetes plus high CVD risk. The beneficial effects of semaglutide on cardiometabolic risk factors were consistent across all subgroups. CONCLUSIONS: This subgroup analysis confirms that semaglutide is effective in individuals with baseline BMI <35 and ≥35 kg/m2 , including in those with comorbidities.

Peri-operative outcomes of bariatric surgery in obstructive sleep apnoea: a single-centre cohort study.

Background: The prevalence of obstructive sleep apnoea (OSA) is increasing worldwide. Bariatric surgery is an option where conventional measures to achieve weight loss fail. We compared peri-operative outcomes in patients living with obesity with and without OSA undergoing bariatric surgery. Methods: Retrospective cohort study of consecutive patients undergoing bariatric surgery at a tertiary referral centre. Data were extracted from electronic patient records. Primary outcomes were the rate of peri-operative complications and level of respiratory support. Secondary outcomes were length of stay (LOS), and the highest level of care required. Results: A total of 302 patients underwent surgery [age 47 (±11.6) years, 238 (78.8%) female, body mass index (BMI) 48.1 (±7.8) kg/m2]. A total of 101 (33.4%) patients had moderate or severe OSA, or mild OSA with significant sleepiness, and were prescribed continuous positive airway pressure (CPAP), whilst 201 (66.6%) had mild OSA without symptoms or no OSA and weren't. Patients requiring CPAP were more obese (BMI 50.2 vs. 47.0 kg/m2, P=0.002). Complications were analysed individually and according to the Clavien-Dindo classification. The incidence of each individual complication did not differ between groups. When grouped into Clavien-Dindo grades, only grade I complications differed: CPAP 9% vs. non-CPAP 2.6%, P=0.02). LOS was longer in the CPAP group [3 (1.5) vs. 2 (1.0) days, P=0.002]. Conclusions: The rate of peri-operative complications in patients with OSA undergoing bariatric surgery is low and can be addressed by the provision of CPAP therapy in most cases. However, a longer LOS and more frequent Grade I complications requires selection of appropriate post-operative monitoring.

Obesity and diabetes in people of African ancestry with HIV.

Obesity is a chronic disease with multiple adverse effects on health. The prevalence of obesity is increasing worldwide, and people of African ancestry are disproportionally affected. Several widely used antiretrovirals have been associated with weight gain and contribute to the rising burden of obesity in people with HIV. Obesity and weight gain on antiretroviral therapy are risk factors for the development of type 2 diabetes mellitus, a condition which also disproportionally affects black populations. In this review, we discuss recent data on weight gain in relation to initiating or switching antiretroviral therapy and advances in the management of obesity. Availability of highly effective treatments for obesity have the potential to address, and potentially reverse, the epidemics of obesity and diabetes mellitus in people with HIV.

Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.

AIM: To explore changes in body weight and cardiometabolic risk factors after treatment withdrawal in the STEP 1 trial extension. MATERIALS AND METHODS: STEP 1 (NCT03548935) randomized 1961 adults with a body mass index ≥ 30 kg/m2 (or ≥ 27 kg/m2 with ≥ 1 weight-related co-morbidity) without diabetes to 68 weeks of once-weekly subcutaneous semaglutide 2.4 mg (including 16 weeks of dose escalation) or placebo, as an adjunct to lifestyle intervention. At week 68, treatments (including lifestyle intervention) were discontinued. An off-treatment extension assessed for a further year a representative subset of participants who had completed 68 weeks of treatment. This subset comprised all eligible participants from any site in Canada, Germany and the UK, and sites in the United States and Japan with the highest main phase recruitment. All analyses in the extension were exploratory. RESULTS: Extension analyses included 327 participants. From week 0 to week 68, mean weight loss was 17.3% (SD: 9.3%) with semaglutide and 2.0% (SD: 6.1%) with placebo. Following treatment withdrawal, semaglutide and placebo participants regained 11.6 (SD: 7.7) and 1.9 (SD: 4.8) percentage points of lost weight, respectively, by week 120, resulting in net losses of 5.6% (SD: 8.9%) and 0.1% (SD: 5.8%), respectively, from week 0 to week 120. Cardiometabolic improvements seen from week 0 to week 68 with semaglutide reverted towards baseline at week 120 for most variables. CONCLUSIONS: One year after withdrawal of once-weekly subcutaneous semaglutide 2.4 mg and lifestyle intervention, participants regained two-thirds of their prior weight loss, with similar changes in cardiometabolic variables. Findings confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health.

Tumour detection and outcomes of surveillance screening in SDHB and SDHD pathogenic variant carriers.

OBJECTIVE: Succinate dehydrogenase subunit (SDHx) pathogenic variants predispose to phaeochromocytoma and paraganglioma (PPGL). Lifelong surveillance is recommended for all patients to enable prompt detection and treatment. There is currently limited evidence for optimal surveillance strategies in hereditary PPGL. We aim to detail the clinical presentation of PPGL in our cohort of non-index SDHB and SDHD pathogenic variant carriers. METHODS: Retrospective analysis of medical and genetic records from a single tertiary referral centre identified SDHB or SDHD pathogenic variants in 74 non-index cases (56 SDHB and 18 SDHD). Surveillance screening for asymptomatic relatives consisted of annual plasma metanephrine measurement and whole-body MRI with contrast at 3-5 yearly intervals. RESULTS: Twenty-three out of 74 non-index patients (10 SDHB and 13 SDHD) were diagnosed with PPGL, 17 patients through surveillance screening (24 tumours in total) and 6 diagnosed prior to commencement of cascade screening with symptomatic presentation. MRI with contrast identified PPGL in 22/24 screen-detected tumours and 5/24 tumours had elevated plasma metanephrine levels. Penetrance in non-index family members was 15.2 and 47.2% for SDHB carriers and 71.6 and 78.7% for SDHD carriers at age of 50 and 70 years, respectively. CONCLUSION: Surveillance screening with combined biochemical testing and imaging enables early detection of PPGL in asymptomatic relatives with SDHx pathogenic variants. The presence of disease at first screen was significant in our cohort and hence further multi-centre long-term data are needed to inform counselling of family members undergoing lifelong surveillance.

SDHC phaeochromocytoma and paraganglioma: A UK-wide case series.

OBJECTIVE: Phaeochromocytomas and paragangliomas (PPGL) are rare, but strongly heritable tumours. Variants in succinate dehydrogenase (SDH) subunits are identified in approximately 25% of cases. However, clinical and genetic information of patients with SDHC variants are underreported. DESIGN: This retrospective case series collated data from 18 UK Genetics and Endocrinology departments. PATIENTS: Both asymptomatic and disease-affected patients with confirmed SDHC germline variants are included. MEASUREMENTS: Clinical data including tumour type and location, surveillance outcomes and interventions, SDHC genetic variant assessment, interpretation, and tumour risk calculation. RESULTS: We report 91 SDHC cases, 46 probands and 45 non-probands. Fifty-one cases were disease-affected. Median age at genetic diagnosis was 43 years (range: 11-79). Twenty-four SDHC germline variants were identified including six novel variants. Head and neck paraganglioma (HNPGL, n = 30, 65.2%), extra-adrenal paraganglioma (EAPGL, n = 13, 28.2%) and phaeochromocytomas (PCC) (n = 3, 6.5%) were present. One case had multiple PPGLs. Malignant disease was reported in 19.6% (9/46). Eight cases had non-PPGL SDHC-associated tumours, six gastrointestinal stromal tumours (GIST) and two renal cell cancers (RCC). Cumulative tumour risk (95% CI) at age 60 years was 0.94 (CI: 0.79-0.99) in probands, and 0.16 (CI: 0-0.31) in non-probands, respectively. CONCLUSIONS: This study describes the largest cohort of 91 SDHC patients worldwide. We confirm disease-affected SDHC variant cases develop isolated HNPGL disease in nearly 2/3 of patients, EAPGL and PCC in 1/3, with an increased risk of GIST and RCC. One fifth developed malignant disease, requiring comprehensive lifelong tumour screening and surveillance.

Towards targeted dietary support for shift workers with type 2 diabetes (Shift-Diabetes study): A mixed-methods case study protocol.

BACKGROUND: Blood glucose is higher in people working night shifts compared to day workers. Changes to eating behaviour, activity and sleep patterns in addition to circadian disruption are likely to impact glucose management in night-shift workers with type 2 diabetes. AIM: To investigate current dietary intake and glucose variability during night work, including barriers and facilitators to dietary behaviour in this context. METHODS: A mixed-methods case study will be conducted. Shift workers with type 2 diabetes working in a hospital setting will be recruited to this two-part study. Part 1: 70 participants will complete a 10-day observational study collecting data on continuous glucose, diet (self-report diary), sleep and physical activity during a period covering night work, rest days and non-night workdays. Mean glucose concentration and variability, and the mean healthy diet index score, will be compared between days of night work, non-night work and rest, after adjusting for other individual factors (sleep/physical activity/demographics). Part 2: A sample (n~13) will complete semi-structured interviews based on behavioural science frameworks to explore barriers/enablers to dietary behaviour when working night shifts. This will inform a quantitative survey to explore the generalisability of interview findings. DISCUSSION: Findings from Part 1 and 2 will be triangulated to identify potential intervention strategies to address key barriers and enablers to healthier eating, and in turn improved glucose control, in shift workers with type 2 diabetes. This will be facilitated through stakeholder consultation and application of behavioural science frameworks. Shift-Diabetes study registration: ISRCTN11764942.