Cardiovascular autonomic neuropathy in diabetes: an update with a focus on management.

Cardiovascular autonomic neuropathy (CAN) is an under-recognised yet highly prevalent microvascular complication of diabetes. CAN affects approximately 20% of people with diabetes, with recent studies highlighting the presence of CAN in prediabetes (impaired glucose tolerance and/or impaired fasting glucose), indicating early involvement of the autonomic nervous system. Understanding of the pathophysiology of CAN continues to evolve, with emerging evidence supporting a potential link between lipid metabolites, mitochondrial dysfunction and genetics. Recent advancements, such as streamlining CAN detection through wearable devices and monitoring of heart rate variability, present simplified and cost-effective approaches for early CAN detection. Further research on the optimal use of the extensive data provided by such devices is required. Despite the lack of specific pharmacological interventions targeting the underlying pathophysiology of autonomic neuropathy, several studies have suggested a favourable impact of newer glucose-lowering agents, such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, where there is a wealth of clinical trial data on the prevention of cardiovascular events. This review delves into recent developments in the area of CAN, with emphasis on practical guidance to recognise and manage this underdiagnosed condition, which significantly increases the risk of cardiovascular events and mortality in diabetes.

Exploring the experiences of people with obesity and post-bariatric surgery patients after three months using the mindful eating reflective practice: An interpretative phenomenological analysis.

Background: Experiential dimensions of Mindful Eating Practices are scarce in the literature. Aim: The study focuses on thirteen individuals with clinical obesity and nine post-bariatric surgery patients who engaged in MERP over three months. Methods: The present research utilized Interpretative Phenomenological Analysis (IPA) as the analytical framework of interviews. Results: Four overarching themes emerged from the analysis: 1. "Enhanced Awareness of Eating": This theme underscores MERP's central emphasis on cultivating heightened mindfulness during food consumption, highlighting the importance of being present at the moment while eating; 2. "Facilitating the Transition to Healthier Eating Habits": This theme explores how MERP influences participants' dietary choices, eating pace, portion control, and overall enjoyment of meals. It reveals that MERP encourages individuals to reflect on their eating habits and transition towards healthier choices; 3. "Diverse Perspectives on Satisfaction with MERP": Within the context of MERP, participants held varied interpretations of satisfaction. Some encountered practical limitations or engaged in reflective self-examination, while others found sensory satisfaction, enhancing their overall eating experiences; and 4. "Utilization and Development of MERP": This theme delves into participants' patterns of using MERP. It reveals a tendency to avoid MERP in the morning, a gradual decline in its usage over time, and a preference for an electronic version of the practice. Conclusion: The MERP shows promise in improving overall eating habits by enhancing enjoyment of food, increasing awareness of body cues, promoting healthier choices, and encouraging mindful eating practices. These findings provide valuable insights for future research and the refinement of clinical tools aimed at effective weight management and the promotion of sustainable healthy eating practices by effectively addressing a significant gap in our understanding of the experiential facets of eating practices.

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.

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.

Global variations in preoperative practices concerning patients seeking primary bariatric and metabolic surgery (PACT Study): A survey of 634 bariatric healthcare professionals.

BACKGROUND: Bariatric and Metabolic Surgery (BMS) is a popular weight loss intervention worldwide, yet few scientific studies have examined variations in preoperative practices globally. This study aimed to capture global variations in preoperative practices concerning patients planned for BMS. METHODS: A 41-item questionnaire-based survey was designed and the survey link was freely distributed on social and scientific media platforms, email groups and circulated through personal connections of authors. The survey included eight parts: basic information; criteria for BMS; preoperative nutritional screening; preoperative weight loss; preoperative diets for liver size reduction; preoperative glycemic control; other laboratory investigations and preparations; decision making, education, and consents. Descriptive statistics were used to analyse data and graphs were used for representation where applicable. RESULTS: Six hundred thirty-four bariatric healthcare professionals from 76 countries/regions completed the survey. Of these, n = 310 (48.9%) were from public hospitals, n = 466 (73.5%) were surgeons, and the rest were multidisciplinary professionals. More than half of respondents reported using local society/association guidelines in their practice (n = 310, 61.6%). The great majority of respondents routinely recommend nutritional screening preoperatively (n = 385, 77.5%), mandatory preoperative diets for liver size reduction (n = 220, 53.1%), routine screening for T2DM (n = 371, 90.7%), and mandate a glycemic control target before BMS in patients with T2DM (n = 203, 55.6%). However, less than half (n = 183, 43.9%) recommend mandatory preoperative weight loss to all patients. Most respondents (n = 296, 77.1%) recommend psychological intervention before surgery for patients diagnosed with psychological conditions. Variations were also identified in laboratory investigations and optimisation; and in the aspects of decision making, education and consent. CONCLUSIONS: This survey identified significant global variations in preoperative practices concerning patients seeking primary BMS. Our findings could facilitate future research for the determination of best practice in these areas of variations, and consensus-building to guide clinical practice while we wait for that evidence to emerge.

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.

Obesity Without Metabolic Abnormality and Incident CKD: A Population-Based British Cohort Study.

RATIONALE & OBJECTIVE: Metabolically healthy obesity (obesity without any metabolic abnormality) is not considered to be associated with increased risk of morbidity and mortality. We examined and quantified the association between metabolically healthy overweight/obesity and the risk of incident chronic kidney disease (CKD) in a British primary care population. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: 4,447,955 of the 5,182,908 adults in The Health Improvement Network (THIN) database (United Kingdom, 1995-2015) with a recorded body mass index (BMI) at the time of registration date who were free of CKD and cardiovascular disease. EXPOSURE: 11 body size phenotypes were created, defined by BMI categories (underweight, normal weight, overweight, and obesity) and 3 metabolic abnormalities (diabetes, hypertension, and dyslipidemia). OUTCOME: Incident CKD defined as a recorded code for kidney replacement therapy, a recorded diagnosis of CKD, or by an estimated glomerular filtration rate of<60mL/min/1.73m2 for≥90 days, or a urinary albumin-creatinine ratio>3mg/mmol for≥90 days. RESULTS: Of the 4.5 million individuals, 1,040,921 (23.4%) and 588,909 (13.2%) had metabolically healthy overweight and metabolically healthy obesity, respectively. During a mean follow-up interval of 5.4±4.3 (SD) years, compared with individuals with a metabolically healthy normal weight (n=1,656,231), there was a higher risk of incident CKD among those who had metabolically healthy overweight (adjusted HR, 1.30 [95% CI, 1.28-1.33]) and metabolically healthy obesity (adjusted HR, 1.66 [95% CI, 1.62-1.70]). The association was stronger in those younger than 65 years of age. In all BMI categories, there was greater risk of incident CKD with a greater number of metabolic abnormalities in a graded manner. LIMITATIONS: Potential misclassification of metabolic status due to delayed diagnosis and residual confounding due to unmeasured factors. CONCLUSIONS: Overweight and obesity without metabolic abnormality are associated with a higher risk of incident CKD compared with those with normal body weight and no metabolic abnormality.

How to manage weight loss in women with obesity and PCOS seeking fertility?

Obesity exacerbates the phenotype of polycystic ovarian syndrome (PCOS) including infertility as well as reducing the efficacy and access to fertility treatments. Weight management is, therefore, a key component of treatment for women with PCOS and coexistent obesity. Many women with PCOS describe significant difficulty losing weight and treatment options are limited. The first-line treatment is lifestyle interventions though the weight loss and any impact on fertility are limited. No one dietary strategy can be preferentially recommended based on current evidence. While very low energy diets can result in significant weight loss the evidence for impact on fertility is limited. Pharmacotherapy, including a range of treatments can result in marked weight loss and there is some evidence of improved rates of conception including spontaneous and in response to assisted reproduction treatment. As with pharmacotherapy, data regarding bariatric surgery is largely from nonrandomized studies and though the significant weight loss is anticipated to improve fertility the available data prevents firm conclusions. Clinicians and patients must consider the magnitude of weight loss to be targeted as well as the anticipated fertility treatment required and the timeline of treatment when deciding upon the personalized weight loss strategy. Clinicians and patients should be confident in targeting the most appropriate treatment early in the patient's management to avoid unnecessary delays.

Frequency Rhythmic Electrical Modulation System (FREMS) to alleviate painful diabetic peripheral neuropathy: A pilot, randomised controlled trial (The FREMSTOP study).

BACKGROUND: Frequency Rhythmic Electrical Modulated System (FREMS) is a non-invasive treatment for chronic pain conditions, but its place in the treatment algorithm for painful diabetic peripheral neuropathy (PDPN) is unknown. METHODS: A pilot, open-label, randomised controlled trial in individuals with PDPN inadequately controlled on at least dual neuropathic pain treatments recruited from primary and secondary care. Participants were randomised 1:1 to FREMS + usual care (n = 13) versus usual care (n = 12). Primary outcome was change from baseline in perceived pain (assessed by visual analogue scale) at 12 weeks between treatment groups. RESULTS: Of 25 participants, 14 (56%) were men, and 21 (84%) were White Europeans. Median (IQR) age and duration of diabetes were 64 (56, 68) and 14 (10, 20) years, respectively. At 12 weeks, FREMS showed improvements in perceived pain compared with baseline, although the change was not statistically significant from control group (-4.0[-5.0,0.4] vs. 0[-0.3,0.7], p = 0.087). There were significant improvements in pain with FREMS, assessed by McGill Pain questionnaire (p = 0.042) and Douleur neuropathique-4 questionnaire (p = 0.042). More participants on FREMS had greater than 30 percent reductions in perceived pain compared with controls [7/13(54%) vs 0/12(0%), p = 0.042] and significant improvements in Patient Global Impression of Change (p = 0.005). FREMS intervention had moderate benefits in quality of life, sleep, depression and pain medication use, but these were not statistically significant. CONCLUSIONS: FREMS might be used to treat individuals with PDPN inadequately controlled on two classes of neuropathic pain medications and is associated with improvements in pain severity and perceived impact of treatment. A larger, appropriately designed trial assessing its impact in this population is needed.

Managing idiopathic intracranial hypertension in pregnancy: practical advice.

Idiopathic intracranial hypertension (IIH) is more common in women of reproductive age who have obesity, yet there is little information on its management specifically in pregnancy. Women with IIH should plan their pregnancy including discussing contraception before pregnancy, recognising that hormonal contraceptives are not contraindicated. Potentially teratogenic medications including acetazolamide and topiramate are not recommended during pregnancy or in those with immediate plans to conceive; prescribing acetazolamide in pregnancy must only follow discussion with the patient and their obstetrician. Ideally, patients should aim to achieve disease remission or control before pregnancy, through optimising their weight. Although weight gain is expected in pregnancy, excessive weight gain may exacerbate IIH and increase maternal and fetal complications; evidence-based recommendations for non-IIH pregnancies may help in guiding optimal gestational weight gain. The vast majority of women with IIH can have a normal vaginal delivery, with spinal or epidural anaesthesia if needed, provided the papilloedema is stable or the IIH is in remission.

Metabolic surgery: A clinical update.

Metabolic and bariatric surgery has grown beyond 'experimental' weight-loss surgery. As techniques have advanced over the last few decades, so has the growing body of research and evidence, proving that both weight-loss and metabolic health improvement are induced. Metabolic surgery has become the more appropriate term for weight-loss surgery because of the altered gastrointestinal anatomy and subsequent beneficial metabolic effects. Although the tool of metabolic surgery has been well refined, a large portion of the global population does not have adequate access to it. This clinical update aims to (a) inform healthcare providers from all disciplines about the myriad of benefits of metabolic surgery and (b) equip them with the necessary knowledge to bridge the gap between patients in need of metabolic treatment and the therapies in metabolic surgery available to them.

Sodium-glucose co-transporter-2 inhibitors and susceptibility to COVID-19: A population-based retrospective cohort study.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID-19, when compared with an active comparator. We performed a propensity-score-matched cohort study with active comparators and a negative control outcome in a large UK-based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID-19. The incidence rate of COVID-19 was 19.7/1000 person-years among users of SGLT2 inhibitors and 24.7/1000 person-years among propensity-score-matched users of DPP-4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID-19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP-4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID-19 pandemic.

The association between overweight/obesity and double diabetes in adults with type 1 diabetes; a cross-sectional study.

BACKGROUND: Double Diabetes (DD), type 1 diabetes (T1DM) + insulin resistance (IR), is associated with increased risk of micro/macro-vascular complications and mortality. Obesity can contribute to the development of DD. This study explored the prevalence of overweight/obesity and their association with DD in adults with T1DM. METHODS: Cross-sectional study of consecutive adults with T1DM attending diabetes clinics in a secondary care hospital (January-November 2019). Estimated glucose disposal rate (eGDR) was used as a marker of IR, and an eGDR < 8 was used to identify individuals with DD. RESULTS: One hundred seven adults with T1DM were included; female/male: 51/56; age [median (inter-quartile range): 30.0 (23-51) years]; BMI 25.4 (22.8-30.0) kg/m2. Overweight/obesity prevalence was 57/107 (53.3 %) [overweight: 30/107 (28 %); obesity: 27/107 (25.2 %)]. Compared to those with normal BMI, individuals with T1DM and overweight/obesity had longer diabetes duration; higher total daily insulin dose; and higher DD prevalence: 48/57 (84.2 %) vs. 14/50 (28 %) (p < 0.01); with similar HbA1c. BMI correlated with total daily insulin dose (rho = 0.55; p < 0.01). Individuals with DD were older, had longer duration of diabetes, higher HbA1c, and more adverse lipid profile and microalbuminuria compared to those without DD. CONCLUSIONS: Overweight/obesity is very common in adults with T1DM, and is associated with double diabetes. BMI is positively associated with total insulin dose. Double diabetes is associated with adverse cardiovascular risk profile and is also common in lean individuals with T1DM. Further research is needed to examine the impact of overweight/obesity in people with T1DM and whether weight loss in this population can improve diabetes-related outcomes.

Obstructive sleep apnoea and 12-month weight loss in adults with class 3 obesity attending a multidisciplinary weight management program.

BACKGROUND: Although there is a strong association between obesity and obstructive sleep apnoea (OSA), the effects of OSA and CPAP therapy on weight loss are less well known. The aim of this study in adults with class 3 obesity attending a multidisciplinary weight management program was to assess the relationship between OSA and CPAP usage, and 12-month weight change. METHODS: A retrospective cohort study of all patients commencing an intensive multidisciplinary publicly funded weight management program in Sydney, Australia, between March 2018 and March 2019. OSA was diagnosed using laboratory overnight sleep studies. Demographic and clinical data, and use of CPAP therapy was collected at baseline and 12 months. CPAP use was confirmed if used ≥4 h on average per night on download. RESULTS: Of the 178 patients who joined the program, 111 (62.4 %) completed 12 months in the program. At baseline, 63.1 % (n=70) of patients had OSA, of whom 54.3 % (n=38) were using CPAP. The non-OSA group had more females compared to the OSA with CPAP group and OSA without CPAP group (90.2 % vs. 57.9 % and 62.5 %, respectively; p=0.003), but there were no significant baseline differences in BMI (50.4±9.3 vs. 52.1±8.7 and 50.3±9.5 kg/m2, respectively; p=0.636). There was significant weight loss across all three groups at 12 months. However, there were no statistically significant differences across groups in the percentage of body weight loss (OSA with CPAP: 6.3±5.6 %, OSA without CPAP: 6.8±6.9 %, non-OSA: 7.2±6.5 %; p=0.844), or the proportion of patients who achieved ≥5 % body weight loss (OSA with CPAP: 57.9 %, OSA without CPAP: 59.4 %, non-OSA: 65.9 %; p=0.743). In patients with T2DM, there was a significant reduction in HbA1c from baseline to 12 months (7.8±1.7 % to 7.3±1.4 %, p=0.03), with no difference between groups (p=0.997). CONCLUSIONS: This multidisciplinary weight management program resulted in significant weight loss at 12 months, regardless of OSA diagnosis or CPAP use in adults with class 3 obesity. Larger studies are needed to further investigate the effects of severity of OSA status and CPAP use in weight management programs. Until completed, this study suggests that the focus should remain on implementing lifestyle changes and weight management regardless of OSA status.

Cardio-metabolic outcomes in South Asians compared to White Europeans in the United Kingdom: a matched controlled population-based cohort study.

BACKGROUND: There appears to be an inequality in the risk of cardio-metabolic disease between those from a South Asian (SA) background when compared to those of White Europeans (WE) descendance, however, this association has not been explored in a large European cohort. This population-based open retrospective cohort explores the incidence of cardio-metabolic disease in those without pre-existing cardiometabolic disease taken from a large UK primary care database from 1st January 2007 to 31st December 2017. METHODS: A retrospective open cohort matched population-based study using The Health Improvement Network (THIN) database. The outcomes of this study were the incidences of cardio-metabolic events (type 2 diabetes mellitus, hypertension, ischemic heart disease, stroke, heart failure, and atrial fibrillation). RESULTS: A total of 94,870 SA patients were matched with 189,740 WE patients. SA were at an increased risk of developing: T2DM (adjusted hazard ratio (aHR) 3.1; 95% CI 2.97-3.23); HTN (1.34; 95% CI: 1.29-1.39); ischaemic heart disease (IHD) (1.81; 95% CI: 1.68-1.93) and heart failure (HF) (1.11; 95% CI: 1.003-1.24). However, they were at a lower risk of atrial fibrillation (AF) (0.53; 95% CI: 0.48-0.59) when compared to WE. Of those of SA origin, the Bangladeshi community were at the greatest risk of T2DM, HTN, IHD and HF, but were at the lowest risk of AF in when compared to Indians and Pakistanis. CONCLUSION: Considering the high risk of cardio-metabolic diseases in the SA cohort, differential public health measures should be considered in these patients to reduce their risk of disease, which may be furthered tailored depending on their country of origin.

Socio-demographic predictors of uptake of a virtual group weight management program during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has had a significant adverse impact on the delivery of weight management programmes (WMPs), in order to ensure the safety of patients and healthcare professionals. Videoconferencing could provide safe remote access to group WMPs during the COVID-19 pandemic. The objectives of this study were to determine the uptake of a virtual group WMP and its predictors. METHODS: All patients enrolled on a face-to-face group WMP, which constitutes part of a Tier 3 WMP delivered by the NHS, at the time of the COVID-19 pandemic lockdown were invited to transfer to a virtual format of the group WMP. Baseline data included weight, BMI, age, gender, ethnicity and Index of Multiple Deprivation (IMD) quintile score. The outcomes were accept/decline transfer to the virtual group WMP. Logistic regression was performed to assess for predictors of uptake. RESULTS: The 315 participants were included, of which 72.1% (n = 227) accepted. After adjusting for gender, deprivation and BMI; older patients (OR 0.966, [95% CI 0.944, 0.989]; p = 0.003) and Black, Asian and Minority Ethnicity (BAME) patients (OR 0.460 [95% 0.248, 0.851]; p = 0.023) were less likely to accept the virtual group WMP. CONCLUSION: Strategies aimed at improving uptake of group WMP among BAME and older adult groups are needed, particularly considering the increased risk of severe COVID-19 in these two groups, and the links between obesity and poor COVID-19 outcomes.

The prevalence of obstructive sleep apnoea in women with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Obesity is a common risk factor for polycystic ovary syndrome (PCOS) and obstructive sleep apnoea (OSA). Both PCOS and OSA are associated with increased risk of type 2 diabetes and cardiovascular disease. Hence, it is important to determine the burden of OSA in women with PCOS. METHODS: We searched electronic databases (MEDLINE, Embase, CINAHL, PsycINFO, Scopus, Web of Science, OpenGrey, CENTRAL), conference abstracts, and reference lists of relevant articles, up to January 2019. No restriction for language or publication status. Studies that examined the presence of OSA in women with PCOS using polysomnography and/or level III devices were eligible for inclusion. RESULTS: Seventeen studies involving 648 participants were included. Our meta-analysis showed that 35.0% (95% CI 22.2-48.9%) of women with PCOS had OSA. This prevalence was not affected by variation in PCOS definition between studies. Approximately one-tenth of the variation in OSA prevalence was related to differences in study population (higher in adults than adolescents and mixed populations), and around one-tenth was related to sample size (higher in smaller studies). OSA prevalence was markedly higher in obese versus lean women with PCOS, and in women with PCOS compared to controls (odds ratio = 3.83, 95% CI 1.43-10.24, eight studies, 957 participants (349 PCOS and 608 controls)). However, most of the studies were at high risk of selection bias, did not account for important confounders, included predominantly women with class II obesity, and were conducted in one country (USA). CONCLUSIONS: Future studies need to examine the true prevalence of OSA in a more representative sample of women with PCOS. Nevertheless, our results suggest that the prevalence of OSA in women with PCOS and obesity is high and clinicians should have a high index of suspicion of OSA in these women.

Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort.

OBJECTIVE: Previous studies suggest that androgens have a sexually dimorphic impact on metabolic dysfunction. However, the sex-specific link between circulating androgens and risk of type 2 diabetes mellitus (T2DM) has not been examined in a large scale, longitudinal cohort, a task we undertook in this study. DESIGN: A retrospective cohort study in a UK primary care database. PATIENTS: We included men and women with available serum testosterone and sex hormone-binding globulin (SHBG) results. MEASUREMENTS: We categorized serum concentrations according to clinically relevant cut-off points and calculated crude and adjusted T2DM Incidence Rate Ratios (IRRs and aIRRs). RESULTS: Serum testosterone concentrations were available in 70 541 men and 81 889 women; serum SHBG was available in 15 907 men and 42 034 women. In comparison to a reference cohort with serum testosterone ≥20 nmol/L, men with lower serum testosterone had a significantly increased risk of T2DM, with the highest risk in those with serum testosterone <7 nmol/L (aIRR 2.71, 95% CI 2.34-3.14, P < 0.001). In women, the risk of T2DM started to increase significantly when serum testosterone concentrations exceeded 1.5 nmol/L, with the highest risk in women with serum testosterone ≥3.5 nmol/L (aIRR 1.98, 95% CI 1.55-2.52, P < 0.001). These observations were verified in a continuous rather than categorized analysis. The risk of T2DM increased in men and women with serum SHBG <40 and <50 nmol/L, respectively. CONCLUSIONS/INTERPRETATION: In this longitudinal study, we found sexually dimorphic associations between serum testosterone and risk of incident T2DM. Androgen deficiency and excess should be considered important risk factors for diabetes in men and women, respectively.

Preoperative weight loss with glucagon-like peptide-1 receptor agonist treatment predicts greater weight loss achieved by the combination of medical weight management and bariatric surgery in patients with type 2 diabetes: A longitudinal analysis.

We examined the relationship between weight changes after preoperative glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment and weight changes from the start of medical weight management (MWM) until 12 months after bariatric surgery in patients with type 2 diabetes in a retrospective cohort study. A total of 45 patients (64.4% women, median [interquartile range] age 49 [45-60] years) were included. The median (interquartile range) weight loss from start of MWM until 12 months post-surgery was 17.9% (13.0%-29.3%). GLP-1RA treatment during MWM resulted in 5.0% (1.9%-7.7%) weight loss. Weight loss during GLP-1RA treatment predicted weight loss from the start of MWM until 12 months post-surgery, but not postoperative weight loss after adjustment. The proportion of weight loss from start of MWM to 12 months post-surgery attributed to GLP-1RA treatment was negatively associated with that attributed to surgery, after adjustment. In conclusion, weight change after GLP-1RA treatment predicted the weight loss achieved by a combination of MWM and bariatric surgery, but not weight loss induced by surgery only. Failure to lose weight after GLP-1RA treatment should not be considered a barrier to undergoing bariatric surgery.

Initiation of dapagliflozin and treatment-emergent fractures.

An increase in fracture risk has been reported in patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin, possibly mediated by effects induced by all members of the sodium-glucose co-transporter-2 (SGLT2) inhibitor class. It is unclear whether initiation of dapagliflozin is followed by an increase in the risk of fracture; therefore, we performed a population-based, open cohort study (from January 2013 to January 2016) using The Health Improvement Network (THIN). A total of 22 618 people with T2DM (4548 exposed to dapagliflozin and 18 070 receiving standard antidiabetic treatment, matched for age, sex, body mass index and diabetes duration) with no history of fractures at baseline were included. The primary outcome was the occurrence of any fragility fracture (hip, spine, wrist) during the observation period. Risk of any fracture served as a secondary outcome. Adjusted hazard rate ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox regression. A total of 289 fractures (132 fragility fractures) were recorded. No difference in the risk of fragility fracture was detected between participants prescribed dapagliflozin and matched control participants (crude HR 0.90, 95% CI 0.59-1.39, P = .645; adjusted HR 0.87, 95% CI 0.56-1.35, P = .531). Similarly, no difference in the risk of any fracture was detected (adjusted HR 0.89, 95% CI 0.66-1.20; P = .427). Sensitivity analyses limited to the subset of the population at high risk of fracture produced similar results; thus, there was no evidence to suggest an increase in the risk of treatment-emergent fractures in patients with T2DM who initiated treatment with dapagliflozin.