Data-driven identification of predictive risk biomarkers for subgroups of osteoarthritis using interpretable machine learning.

Osteoarthritis (OA) is increasing in prevalence and has a severe impact on patients' lives. However, our understanding of biomarkers driving OA risk remains limited. We developed a model predicting the five-year risk of OA diagnosis, integrating retrospective clinical, lifestyle and biomarker data from the UK Biobank (19,120 patients with OA, ROC-AUC: 0.72, 95%CI (0.71-0.73)). Higher age, BMI and prescription of non-steroidal anti-inflammatory drugs contributed most to increased OA risk prediction ahead of diagnosis. We identified 14 subgroups of OA risk profiles. These subgroups were validated in an independent set of patients evaluating the 11-year OA risk, with 88% of patients being uniquely assigned to one of the 14 subgroups. Individual OA risk profiles were characterised by personalised biomarkers. Omics integration demonstrated the predictive importance of key OA genes and pathways (e.g., GDF5 and TGF-ß signalling) and OA-specific biomarkers (e.g., CRTAC1 and COL9A1). In summary, this work identifies opportunities for personalised OA prevention and insights into its underlying pathogenesis.

The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased risk of diabetes-related complications. Hence, it is plausible that Continuous Positive Airway Pressure (CPAP) could have a favorable impact on these complications. To assess the feasibility of conducting a randomized control trial (RCT) in patients with type 2 diabetes (T2D) and OSA over 2 years. METHODS: An open-label multicenter feasibility RCT of CPAP vs no CPAP in patients with T2D and OSA. Patients with resting oxygen saturation <90%, central apnea index >15/hour or Epworth Sleepiness Scale (ESS) ≥11 were excluded. OSA was diagnosed using a multichannel portable device (ApneaLink Air, ResMed). The primary outcome measures were related to feasibility, and the secondary outcomes were changes in various clinical and biochemical parameters related to diabetes outcomes. RESULTS: Eighty-three (40 CPAP vs 43 no CPAP) patients were randomized, with a median (IQR) follow-up of 645 [545, 861] days. CPAP compliance was inadequate, with a median usage of approximately 3.5 hours/night. Early CPAP use predicted longer-term compliance. The adjusted analysis showed a possible favorable association between being randomized to CPAP and several diabetes-related endpoints (chronic kidney disease (CKD), neuropathy, and quality of life (QoL)). CONCLUSIONS: It was feasible to recruit, randomize, and achieve a high follow-up rate over 2 years in patients with OSA and T2D. CPAP compliance might improve by a run-in period before randomization. A full RCT is necessary to assess the observed favorable association between CPAP and CKD, neuropathy, and QoL in patients with T2D. CLINICAL TRIAL REGISTRATION: Registry: ISRCTN; URL: https://www.isrctn.com/ISRCTN12361838; Title: The impact of sleep disorders in patients with type 2 diabetes; Identifier: ISRCTN12361838.

'Surgery is my only hope': A qualitative study exploring perceptions of living with obesity and the prospect of having bariatric surgery.

The health benefits of bariatric surgery are well documented; however, the occurrence of weight-regain after surgery, along with the development of mental health difficulties poses a question of how contemporary psychology could assist to prepare people living with obesity prior to undergoing bariatric surgery. This research explored individuals' (in the immediate pre-operative and post-operative population) attitudes, beliefs and experiences towards obesity and their journey to bariatric surgery. Seventeen adult participants (males n = 4; age range: 26-64 years) were recruited and participated in a semi-structured interview. Twelve individuals participated prior to undergoing bariatric surgery. Five individuals participated in the early post-operative period (<3 months post-surgery). People living with obesity displayed high optimism for positive outcomes, with participants hoping that bariatric surgery would be different to previous attempts at weight regulation, with there being a clear shift in the locus of control for weight management from self to healthcare professionals. Whilst this is adaptive, there was the presence of seemingly unrealistic optimism, with many pre-surgery participants not relaying the realistic possibility of post-surgery weight-regain. Despite the optimism individuals feel about bariatric surgery, participants felt that the psychological factors influencing eating behaviours are not being addressed by healthcare. These findings suggest that mindfulness, mindful eating, and self-compassion approaches should be incorporated into clinical practice to support weight regulation and adaption to physiological changes after bariatric surgery.

Determining the role of novel metabolic pathways in driving intracranial pressure reduction after weight loss.

Idiopathic intracranial hypertension, a disease classically occurring in women with obesity, is characterized by raised intracranial pressure. Weight loss leads to the reduction in intracranial pressure. Additionally, pharmacological glucagon-like peptide-1 agonism reduces cerebrospinal fluid secretion and intracranial pressure. The potential mechanisms by which weight loss reduces intracranial pressure are unknown and were the focus of this study. Meal stimulation tests (fasted plasma sample, then samples at 15, 30, 60, 90 and 120 min following a standardized meal) were conducted pre- and post-bariatric surgery [early (2 weeks) and late (12 months)] in patients with active idiopathic intracranial hypertension. Dynamic changes in gut neuropeptides (glucagon-like peptide-1, gastric inhibitory polypeptide and ghrelin) and metabolites (untargeted ultra-high performance liquid chromatography-mass spectrometry) were evaluated. We determined the relationship between gut neuropeptides, metabolites and intracranial pressure. Eighteen idiopathic intracranial hypertension patients were included [Roux-en-Y gastric bypass (RYGB) n = 7, gastric banding n = 6 or sleeve gastrectomy n = 5]. At 2 weeks post-bariatric surgery, despite similar weight loss, RYGB had a 2-fold (50%) greater reduction in intracranial pressure compared to sleeve. Increased meal-stimulated glucagon-like peptide-1 secretion was observed after RYGB (+600%) compared to sleeve (+319%). There was no change in gastric inhibitory polypeptide and ghrelin. Dynamic changes in meal-stimulated metabolites after bariatric surgery consistently identified changes in lipid metabolites, predominantly ceramides, glycerophospholipids and lysoglycerophospholipids, which correlated with intracranial pressure. A greater number of differential lipid metabolites were observed in the RYGB cohort at 2 weeks, and these also correlated with intracranial pressure. In idiopathic intracranial hypertension, we identified novel changes in lipid metabolites and meal-stimulated glucagon-like peptide-1 levels following bariatric surgery which were associated with changes in intracranial pressure. RYGB was most effective at reducing intracranial pressure despite analogous weight loss to gastric sleeve at 2 weeks post-surgery and was associated with more pronounced changes in these metabolite pathways. We suggest that these novel perturbations in lipid metabolism and glucagon-like peptide-1 secretion are mechanistically important in driving a reduction in intracranial pressure following weight loss in patients with idiopathic intracranial hypertension. Therapeutic targeting of these pathways, for example with glucagon-like peptide-1 agonist infusion, could represent a therapeutic strategy.

Stratification of obesity phenotypes to optimize future therapy (SOPHIA).

INTRODUCTION: Obesity is considered a poor lifestyle choice. 'Obesity' is not a sufficient definition for patients, any more than 'cancer' or 'arthritis' would be. A major obstacle is the lack of understanding of pathogenesis. The disease of obesity is considered homogenous, while response to treatment is thought of as heterogeneous. This can change if pathogenesis, risk profiles for complications, and treatment responses are viewed within the context of obesity consisting of several subsets of disease. AREAS COVERED: The European Union-funded Innovative Medicine Initiative project Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy is part of a momentum shift. Operational variables are being used to develop tests and therapies which may allow the prediction of risk of obesities and the prediction of response to obesity treatments. However, changing stakeholder perspectives on obesity may require more than high-quality data and analysis. EXPERT OPINION: For patients to benefit, clinicians need to integrate evidence-based treatments and payers need to reimburse the management of the disease of obesity. This will generate commercial opportunities for industry. We need to involve stakeholders (patients, clinicians, regulators, payer, patient organisations) to create a shared value for mutual gain.

Weight Management Interventions for Adults With Idiopathic Intracranial Hypertension: A Systematic Review and Practice Recommendations.

BACKGROUND AND OBJECTIVES: Idiopathic intracranial hypertension (IIH) is associated with obesity; however, there is a lack of clinical consensus on how to manage weight in IIH. The aim of this systematic review was to evaluate weight loss interventions in people with IIH to determine which intervention is superior in terms of weight loss, reduction in intracranial pressure (ICP), benefit to visual and headache outcomes, quality of life, and mental health. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD42023339569). MEDLINE and CINAHL were searched for relevant literature published from inception until December 15, 2022. Screening and quality appraisal was conducted by 2 independent reviewers. Recommendations were graded using Scottish Intercollegiate Guidelines Network methodology. RESULTS: A total of 17 studies were included. Bariatric surgery resulted in 27.2-27.8 kg weight loss at 24 months (Level 1- to 1++). Lifestyle weight management interventions resulted in between 1.4 and 15.7 kg weight loss (Level 2+ to 1++). Bariatric surgery resulted in the greatest mean reduction in ICP (-11.9 cm H2O) at 24 months (Level 1++), followed by multicomponent lifestyle intervention + acetazolamide (-11.2 cm H2O) at 6 months (Level 1+) and then a very low-energy diet intervention (-8.0 cm H2O) at 3 months (Level 2++). The least ICP reduction was shown at 24 months after completing a 12-month multicomponent lifestyle intervention (-3.5 cm H2O) (Level 1++). Reduction in body weight was shown to be highly correlated with reduction in ICP (Level 2++ to 1++). DISCUSSION: Bariatric surgery should be considered for women with IIH and a body mass index (BMI) ≥35 kg/m2 since this had the most robust evidence for sustained weight management (grade A). A multicomponent lifestyle intervention (diet + physical activity + behavior) had the most robust evidence for modest weight loss with a BMI <35 kg/m2 (grade B). Longer-term outcomes for weight management interventions in people with IIH are required to determine whether there is a superior weight loss intervention for IIH.

Disease Burden and Health Status among People with Severe Obesity Who Do Not Receive Bariatric Surgery: A Retrospective Study.

INTRODUCTION: The aim of the study was to compare eligible individuals who were or were not treated with bariatric surgery and describe disease burden, treatment, and healthcare costs over 3 years in individuals who were not. METHODS: Adults with obesity class II and comorbidities, or obesity class III, were identified in IQVIA Ambulatory EMR - US and PharMetrics® Plus administrative claims databases (January 1, 2007-December 31, 2017). Outcomes included demographics, BMI, comorbidities, and per patient per year (PPPY) healthcare costs. RESULTS: Of 127,536 eligible individuals, 3,962 (3.1%) underwent surgery. The surgery group was younger, a greater proportion were women, and mean BMI and rates of some comorbidities (obstructive sleep apnea, gastroesophageal reflux disease, and depression) were higher than in the nonsurgery group. Mean healthcare costs PPPY in the baseline year were USD 13,981 in the surgery group and USD 12,024 in the nonsurgery group. In the nonsurgery group, incident comorbidities increased during follow-up. Mean total costs increased by 20.5% from baseline to year 3, mostly driven by an increase in pharmacy costs; however, fewer than 2% of these individuals initiated antiobesity medications. CONCLUSIONS: Individuals who did not undergo bariatric surgery showed a progressive worsening of health and increasing healthcare costs, indicating a large unmet need for access to clinically indicated obesity treatment.

Exploring the association between self-compassion, mindfulness and mindful eating with eating behaviours amongst patients with obesity.

Background: People who have obesity often experience problematic eating behaviours, contributing towards their excessive weight gain. Aims: Understanding problematic eating behaviours and their association to self-compassion, mindfulness and mindful eating is important for the development of future interventions that improve weight-loss and weight-regulation. Methods: One hundred and one participants attending their first session of a 6-session dietetic programme within a Tier 3 medical weight management service in the West Midlands, UK were recruited to complete questionnaires on self-compassion, mindfulness, mindful eating and eating behaviours, such as, emotional, restrained, external, fat and sugar consumption and grazing. Results: The findings suggested all three constructs, self-compassion, mindfulness and mindful eating were significantly and negatively associated with grazing and emotional eating, but mindful eating was the only construct that also displayed a significant and negative association with other eating behaviours that are often barriers to successful weight regulation, such as external eating and fat consumption. Further investigation suggested mindful eating had an indirect effect on fat consumption and grazing via external eating. Conclusion: Whilst, self-compassion, mindfulness and mindful eating displayed a negative relationship with grazing and emotional eating, mindful eating also displayed a negative relationship with fat consumption and external eating. Possible explanations and directions for future work are discussed with an emphasis on the need for more empirical work.

Handling of the Covid-19 Pandemic and Its Effects on Bariatric Surgical Practice: Analysis of GENEVA Study Database.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led to a worldwide suspension of bariatric and metabolic surgery (BMS) services. The current study analyses data on patterns of service delivery, recovery of practices, and protective measures taken during the COVID-19 pandemic by bariatric teams. MATERIALS AND METHODS: The current study is a subset analysis of the GENEVA study which was an international cohort study between 01/05/2020 and 31/10/2020. Data were specifically analysed regarding the timing of BMS suspension, patterns of service recovery, and precautionary measures deployed. RESULTS: A total of 527 surgeons from 439 hospitals in 64 countries submitted data regarding their practices and handling of the pandemic. Smaller hospitals (with less than 200 beds) were able to restart BMS programmes more rapidly (time to BMS restart 60.8 ± 38.9 days) than larger institutions (over 2000 beds) (81.3 ± 30.5 days) (p = 0.032). There was a significant difference in the time interval between cessation/reduction and restart of bariatric services between government-funded practices (97.1 ± 76.2 days), combination practices (84.4 ± 47.9 days), and private practices (58.5 ± 38.3 days) (p < 0.001). Precautionary measures adopted included patient segregation, utilisation of personal protective equipment, and preoperative testing. Following service recovery, 40% of the surgeons operated with a reduced capacity. Twenty-two percent gave priority to long waiters, 15.4% gave priority to uncontrolled diabetics, and 7.6% prioritised patients requiring organ transplantation. CONCLUSION: This study provides global, real-world data regarding the recovery of BMS services following the COVID-19 pandemic.

Glycemic outcomes in patients with type 2 diabetes after bariatric surgery compared with routine care: a population-based, real-world cohort study in the United Kingdom.

BACKGROUND: Clinical trials have shown that bariatric surgery (BS) is associated with better glycemic control and diabetes remission in patients with type 2 diabetes (T2D) compared with routine care. OBJECTIVE: We conducted a real-world population-based study examining the impact of BS on glycemic control and medications in patients with T2D. SETTING AND METHODS: This was a retrospective, matched, controlled cohort study conducted between January 1, 1990, and January 31, 2018, using IQVIA Medical Research Data, a primary care electronic records database. Adults with body mass index (BMI) ≥30 kg/m2 and T2D who had BS (surgical) were matched for age, sex, BMI, and diabetes duration to two controls (with T2D and no BS). RESULTS: A total of 1126 patients in the surgical group and 2219 patients in the control group were analyzed. Mean (standard deviation) age was 50.0 (9.3) years, 67.6% were women, baseline glycocylated hemoglobin (HbA1C) was 7.8% (1.7 mmol/mol), and diabetes duration was 4.7 years (range, 2.0-8.4 years). Over a median (interquartile range) follow-up of 3.6 years (1.7-5.9 years), a higher proportion of patients in the surgical group achieved an HbA1C of ≤6.0% than the control group (65.8% versus 22.8%). The surgical group showed a decrease in mean HbA1C of 1.5% (95% confidence interval [CI]: 1.4%-1.7%), 1.4% (1.2%-1.5%), and 1.3% (1.1%-1.5%) at 1-, 2-, and 3-year follow-up, respectively, whereas HbA1C increased in the control group. The proportion of patients receiving glucose-lowering medications decreased in the surgical group (92.2% to 66.5%) but increased in the control group (85.3% to 90.2%). CONCLUSION: BS is associated with significant improvement in glycemic control, achievement of normal HbA1C levels, and reduced need for glucose-lowering therapy in patients with T2D.

Association of Amount of Weight Lost After Bariatric Surgery With Intracranial Pressure in Women With Idiopathic Intracranial Hypertension.

BACKGROUND AND OBJECTIVES: The idiopathic intracranial hypertension randomized controlled weight trial (IIH:WT) established that weight loss through bariatric surgery significantly reduced intracranial pressure when compared with a community weight management intervention. This substudy aimed to evaluate the amount of weight loss required to reduce intracranial pressure and to explore the effect of different bariatric surgical approaches. METHODS: IIH:WT was a multicenter randomized controlled trial. Adult women with active idiopathic intracranial hypertension and a body mass index ≥35 kg/m2 were randomized to bariatric surgery or a community weight management intervention (1:1). This per-protocol analysis evaluated the relationship between intracranial pressure, weight loss, and the weight loss methods. A linear hierarchical regression model was used to fit the trial outcomes, adjusted for time, treatment arm, and weight. RESULTS: Sixty-six women were included, of whom 23 had received bariatric surgery by 12 months; the mean age was 31 (SD 8.7) years in the bariatric surgery group and 33.2 (SD 7.4) years in the dietary group. Baseline weight and intracranial pressure were similar in both groups with a mean weight of 119.5 (SD 24.1) and 117.9 (SD 19.5) kg and mean lumbar puncture opening pressure of 34.4 (SD 6.3) and 34.9 (SD 5.3) cmCSF in the bariatric surgery and dietary groups, respectively. Weight loss was significantly associated with reduction in intracranial pressure (R2 = 0.4734, p ≤ 0.0001). Twenty-four percentage of weight loss (weight loss of 13.3 kg [SD 1.76]) was associated with disease remission (intracranial pressure [ICP] ≤ 25 cmCSF). Roux-en-Y gastric bypass achieved greater, more rapid, and sustained ICP reduction compared with other methods. DISCUSSION: The greater the weight loss, the greater the reduction in ICP was documented. Twenty four percentage of weight loss was associated with disease remission. Such magnitude of weight loss was unlikely to be achieved without bariatric surgery, and hence, consideration of referral to a bariatric surgery program early for those with active idiopathic intracranial hypertension may be appropriate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02124486; ISRCTN registry number ISRCTN40152829; doi.org/10.1186/ISRCTN40152829. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that weight loss after bariatric surgery results in reduction in intracranial pressure in adult women with idiopathic intracranial hypertension. This study is Class II because of the use of a per-protocol analysis.

Diabetic Foot Risk Classification at the Time of Type 2 Diabetes Diagnosis and Subsequent Risk of Mortality: A Population-Based Cohort Study.

Aim: We aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem. Methods: This was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination. Results: Of 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30). Conclusion: Individuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.

Effect of BMI on safety of bariatric surgery during the COVID-19 pandemic, procedure choice, and safety protocols - An analysis from the GENEVA Study.

BACKGROUND: It has been suggested that patients with a Body Mass Index (BMI) of > 60 kg/m2 should be offered expedited Bariatric Surgery (BS) during the Coronavirus Disease-2019 (COVID-19) pandemic. The main objective of this study was to assess the safety of this approach. METHODS: We conducted a global study of patients who underwent BS between 1/05/2020 and 31/10/2020. Patients were divided into three groups according to their preoperative BMI - Group I (BMI<50 kg/m2), Group II (BMI 50-60 kg/m2), and Group III (BMI>60 kg/m2). The effect of preoperative BMI on 30-day morbidity and mortality, procedure choice, COVID-19 specific safety protocols, and comorbidities was assessed. RESULTS: This study included 7084 patients (5197;73.4 % females). The mean preoperative weight and BMI were 119.49 ± 24.4 Kgs and 43.03 ± 6.9 Kg/m2, respectively. Group I included 6024 (85 %) patients, whereas Groups II and III included 905 (13 %) and 155 (2 %) patients, respectively. The 30-day mortality rate was higher in Group III (p = 0.001). The complication rate and COVID-19 infection were not different. Comorbidities were significantly more likely in Group III (p = <0.001). A significantly higher proportion of patients in group III received Sleeve Gastrectomy or One Anastomosis Gastric Bypass compared to other groups. Patients with a BMI of > 70 kg/m2 had a 30-day mortality of 7.7 % (2/26). None of these patients underwent a Roux-en-Y Gastric Bypass. CONCLUSION: The 30-day mortality rate was significantly higher in patients with BMI > 60 kg/m2. There was, however, no significant difference in complications rates in different BMI groups, probably due to differences in procedure selection.

Interventions for the prevention of adrenal crisis in adults with primary adrenal insufficiency: a systematic review.

Objective: The incidence of adrenal crisis (AC) remains high, particularly for people with primary adrenal insufficiency, despite the introduction of behavioural interventions. The present study aimed to identify and evaluate available evidence of interventions aiming to prevent AC in primary adrenal insufficiency. Design: This study is a systematic review of the literature and theoretical mapping. Methods: MEDLINE, MEDLINE in Process, EMBASE, ERIC, Cochrane CENTRAL, CINAHL, PsycINFO, the Health Management Information Consortium and trial registries were searched from inception to November 2021. Three reviewers independently selected studies and extracted data. Two reviewers appraised the studies for the risk of bias. Results: Seven observational or mixed methods studies were identified where interventions were designed to prevent AC in adrenal insufficiency. Patient education was the focus of all interventions and utilised the same two behaviour change techniques, 'instruction on how to perform a behaviour' and 'pharmacological support'. Barrier and facilitator themes aiding or hindering the intervention included knowledge, behaviour, emotions, skills, social influences and environmental context and resources. Most studies did not measure effectiveness, and assessment of knowledge varied across studies. The study quality was moderate. Conclusion: This is an emerging field with limited studies available. Further research is required in relation to the development and assessment of different behaviour change interventions to prevent AC.

Safety of Bariatric Surgery in ≥ 65-Year-Old Patients During the COVID-19 Pandemic.

BACKGROUND: Age ≥ 65 years is regarded as a relative contraindication for bariatric surgery. Advanced age is also a recognised risk factor for adverse outcomes with Coronavirus Disease-2019 (COVID-19) which continues to wreak havoc on global populations. This study aimed to assess the safety of bariatric surgery (BS) in this particular age group during the COVID-19 pandemic in comparison with the younger cohort. METHODS: We conducted a prospective international study of patients who underwent BS between 1/05/2020 and 31/10/2020. Patients were divided into two groups - patients ≥ 65-years-old (Group I) and patients < 65-years-old (Group II). The two groups were compared for 30-day morbidity and mortality. RESULTS: There were 149 patients in Group 1 and 6923 patients in Group II. The mean age, preoperative weight, and BMI were 67.6 ± 2.5 years, 119.5 ± 24.5 kg, and 43 ± 7 in Group I and 39.8 ± 11.3 years, 117.7±20.4 kg, and 43.7 ± 7 in Group II, respectively. Approximately, 95% of patients in Group 1 had at least one co-morbidity compared to 68% of patients in Group 2 (p = < 0.001). The 30-day morbidity was significantly higher in Group I (11.4%) compared to Group II (6.6%) (p = 0.022). However, the 30-day mortality and COVID-19 infection rates were not significantly different between the two groups. CONCLUSIONS: Bariatric surgery during the COVID-19 pandemic is associated with a higher complication rate in those ≥ 65 years of age compared to those < 65 years old. However, the mortality and postoperative COVID-19 infection rates are not significantly different between the two groups.

Sleep behaviours and associated habits and the progression of pre-diabetes to type 2 diabetes mellitus in adults: A systematic review and meta-analysis.

INTRODUCTION: Certain sleep behaviours increase risk of type 2 diabetes mellitus (T2DM) in the general population, but whether they contribute to the progression from pre-diabetes to T2DM is uncertain. We conducted a systematic review to assess this. METHODS: Structured searches were performed on bibliographic databases (MEDLINE, EMBASE and CINAHL) from inception to 26/04/2021 for longitudinal studies/trials consisting of adults⩾18 years with pre-diabetes and sleep behaviours (short or long sleep duration (SD), late chronotype, insomnia, obstructive sleep apnoea, daytime napping and/or night-shift employment) that reported on incident T2DM or glycaemic changes. The Newcastle-Ottawa Scale was used for quality assessment. RESULTS: Six studies were included. Meta-analysis of three studies (n = 20,139) demonstrated that short SD was associated with greater risk of progression to T2DM, hazard ratio (HR) 1.59 (95% CI 1.29-1.97), I2 heterogeneity score 0%, p < 0.0001, but not for long SD, HR 1.50 (0.86-2.62), I2 heterogeneity 77%, p = 0.15. The systematic review showed insomnia and night-shift duty were associated with higher progression to T2DM. Studies were rated as moderate-to-high quality. CONCLUSIONS: Progression from pre-diabetes to T2DM increases with short SD, but only limited data exists for insomnia and night-shift duty. Whether manipulating sleep could reduce progression from pre-diabetes to T2DM needs to be examined.

Risk of incident obstructive sleep apnoea in patients with type 1 diabetes: a population-based retrospective cohort study.

AIMS/HYPOTHESIS: People with type 2 diabetes are at increased risk of developing obstructive sleep apnoea. However, it is not known whether people with type 1 diabetes are also at an increased risk of obstructive sleep apnoea. This study aimed to examine whether people with type 1 diabetes are at increased risk of incident obstructive sleep apnoea compared with a matched cohort without type 1 diabetes. METHODS: We used a UK primary care database, The Health Improvement Network (THIN), to perform a retrospective cohort study between January 1995 and January 2018 comparing sleep apnoea incidence between patients with type 1 diabetes (exposed) and without type 1 diabetes (unexposed) (matched for age, sex, BMI and general practice). The outcome was incidence of obstructive sleep apnoea. Baseline covariates and characteristics were assessed at the start of the study based on the most recent value recorded prior to the index date. The Cox proportional hazards regression model was used to estimate unadjusted and adjusted hazard ratios, based on a complete-case analysis. RESULTS: In total, 34,147 exposed and 129,500 matched unexposed patients were included. The median follow-up time was 5.43 years ((IQR 2.19-10.11), and the mean BMI was 25.82 kg/m2 (SD 4.33). The adjusted HR for incident obstructive sleep apnoea in patients with type 1 diabetes vs those without type 1 diabetes was 1.53 (95% CI 1.25, 1.86; p<0.001). Predictors of incident obstructive sleep apnoea in patients with type 1 diabetes were older age, male sex, obesity, being prescribed antihypertensive or lipid-lowering drugs, atrial fibrillation and depression. CONCLUSIONS/INTERPRETATION: Individuals with type 1 diabetes are at increased risk of obstructive sleep apnoea compared with people without diabetes. Clinicians should suspect obstructive sleep apnoea in patients with type 1 diabetes if they are old, have obesity, are male, have atrial fibrillation or depression, or if they are taking lipid-lowering or antihypertensive drugs.

The effect of intranasal insulin on appetite and mood in women with and without obesity: an experimental medicine study.

BACKGROUND/OBJECTIVES: Intranasal (IN) administration of insulin decreases appetite in humans, but the underlying mechanisms are unclear, and it is unknown whether IN insulin affects the food intake of women with obesity. SUBJECTS/METHODS: In a double-blind, placebo-controlled, crossover design, participants (35 lean women and 17 women with obesity) were randomized to receive 160 IU/1.6 mL of IN insulin or placebo in a counterbalanced order in the post prandial state. The effects of IN insulin on cookie intake, appetite, mood, food reward, cognition and neural activity were assessed. RESULTS: IN insulin in the post prandial state reduced cookie intake, appetite and food reward relative to placebo and these effects were more pronounced for women with obesity compared with lean women. IN insulin also improved mood in women with obesity. In both BMI groups, IN insulin increased neural activity in the insula when viewing food pictures. IN insulin did not affect cognitive function. CONCLUSIONS: These results suggest that IN insulin decreases palatable food intake when satiated by reducing food reward and that women with obesity may be more sensitive to this effect than lean women. Further investigation of the therapeutic potential of IN insulin for weight management in women with obesity is warranted.