Background:Although the health benefits of regular physical activity and exercise are well established and have been incorporated into national public health recommendations, there is a relative lack of understanding pertaining to the harmful effects of physical inactivity. Experimental paradigms including complete immobilization and bed rest are not physiologically representative of sedentary living. A useful ‘real-world’ approach to contextualize the physiology of societal downward shifts in physical activity patterns is that of short-term daily step reduction.Results:Step-reduction studies have largely focused on musculoskeletal and metabolic health parameters, providing relevant disease models for metabolic syndrome, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), sarcopenia and osteopenia/osteoporosis. In untrained individuals, even a short-term reduction in physical activity has a significant impact on skeletal muscle protein and carbohydrate metabolism, causing anabolic resistance and peripheral insulin resistance, respectively. From a metabolic perspective, short-term inactivity-induced peripheral insulin resistance in skeletal muscle and adipose tissue, with consequent liver triglyceride accumulation, leads to hepatic insulin resistance and a characteristic dyslipidaemia. Concomitantly, various inactivity-related factors contribute to a decline in function; a reduction in cardiorespiratory fitness, muscle mass and muscle strength.Conclusions:Physical inactivity maybe particularly deleterious in certain patient populations, such as those at high risk of T2D or in the elderly, considering concomitant sarcopenia or osteoporosis. The effects of short-term physical inactivity (with step reduction) are reversible on resumption of habitual physical activity in younger people, but less so in older adults. Nutritional interventions and resistance training offer potential strategies to prevent these deleterious metabolic and musculoskeletal effects.Impact:Individuals at high risk of/with cardiometabolic disease and older adults may be more prone to these acute periods of inactivity due to acute illness or hospitalization. Understanding the risks is paramount to implementing countermeasures.

Background Negative lifestyle behaviors are associated with an increased risk of adverse outcomes from coronavirus disease (COVID-19). This study aimed to assess lifestyle changes affecting weight, sleep, mental health, physical activity, and dietary habits prospectively from before COVID-19 to during lockdown. Methods A total of 297 Saudi women, aged 19–30 years (mean age, 20.7 ± 1.4 years), were interviewed at two time points, before and during the quarantine. The data collected included anthropometrics, sociodemographic data, clinical history, food frequency questionnaire responses, Pittsburgh Sleep Quality Index scores, Global Physical Activity Questionnaire (GPAQ) responses, and Perceived Stress Scale measures. In addition, during quarantine, COVID-19 and nutrition-related information and Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 scores were collected. Multivariate multinomial logistic regression analysis was used to examine the indicators of weight gain and loss from before COVID-19 (baseline) until during lockdown. Results Although approximately half of the participants did not report a weight change, 30% revealed weight loss and 18%, weight gain. The variables associated with increased weight gain were self-quarantine since COVID-19 started (OR: 5.17, 95% CI: 1.57–17.01, p = 0.007), age (OR: 1.53, 1.03–2.28, p = 0.04), and stress at baseline and during lockdown (OR: 1.15, 1.03–1.29, p = 0.01; OR: 1.10, 1.01–1.19, p = 0.03, respectively). The variables associated with a reduced risk of weight gain were the GPAQ score during lockdown (OR: 0.16, 0.04–0.66, p = 0.01), coffee consumption (OR: 0.36, 0.19–0.67, p = 0.01), and total sleep time (OR: 0.70, 0.51–0.97, p = 0.03). Conclusion While most young Saudi women experienced no weight change during the COVID-19 lockdown, one-third lost weight and a significant proportion gained weight. Factors associated with weight, such as stress, sleep hours, physical activity, and coffee consumption, highlight the need to carefully consider those at risk during future circumstances that may require lockdowns. These factors could also aid in implementing policies for future lockdowns and support those most at risk of gaining weight.

Obesity is a chronic condition that requires long-term management and is associated with unprecedented stigma in different settings, including during interactions with the health care system. This stigma has a negative impact on the mental and physical health of people with obesity and can lead to avoidance of health care and disruption of the doctors-patient relationship. There is significant evidence that simply having a conversation about obesity can lead to weight loss which translates into health benefits, however, both health-care practitioners and people living with obesity alike report apprehension in initiating this conversation.We have gathered stakeholders from Obesity UK, physicians, dieticians, clinical psychologists, obesity researchers, conversation analysts, nurses, and representatives from NHS England Diabetes and Obesity. This group has contributed to production of this report on how people living with obesity wish to have their condition referred to, and provides practical guidance for health care professionals to facilitate collaborative and supportive discussions about obesity. The expert stakeholders consider that changes to language used at the point of care can act to alleviate the stigma of obesity within the health care system and support better outcomes for both people living with obesity and for the healthcare system.

Global rates of obesity and Type 2 diabetes mellitus (T2DM) are increasing globally concomitant with a rising prevalence of sleep deprivation and sleep disorders. Understanding the links between sleep, obesity and T2DM might offer an opportunity to develop better prevention and treatment strategies for these epidemics. Experimental studies have shown that sleep restriction is associated with changes in energy homeostasis, insulin resistance and β-cell function. Epidemiological cohort studies established short sleep duration as a risk factor for developing obesity and T2DM. In addition, small studies suggested that short sleep duration was associated less weight loss following lifestyle interventions or bariatric surgery. In this article, we review the epidemiological evidence linking sleep duration to obesity and T2DM and plausible mechanisms. In addition, we review the impact of changes in sleep duration on obesity and T2DM.

Background Chronic wounds (e.g. diabetic foot ulcers) reduce the quality of life, yet treatments remain limited. Glucocorticoids (activated by the enzyme 11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1) impair wound healing. Objectives Efficacy, safety, and feasibility of 11β-HSD1 inhibition for skin function and wound healing. Design Investigator-initiated, double-blind, randomized, placebo-controlled, parallel-group phase 2b pilot trial. Methods Single-center secondary care setting. Adults with type 2 diabetes mellitus without foot ulcers were administered 400 mg oral 11β-HSD1 inhibitor AZD4017 (n = 14) or placebo (n = 14) bi-daily for 35 days. Participants underwent 3-mm full-thickness punch skin biopsies at baseline and on day 28; wound healing was monitored after 2 and 7 days. Computer-generated 1:1 randomization was pharmacy-administered. Analysis was descriptive and focused on CI estimation. Of the 36 participants screened, 28 were randomized. Results Exploratory proof-of-concept efficacy analysis suggested AZD4017 did not inhibit 24-h ex vivoskin 11β-HSD1 activity (primary outcome; difference in percentage conversion per 24 h 1.1% (90% CI: −3.4 to 5.5) but reduced systemic 11β-HSD1 activity by 87% (69–104%). Wound diameter was 34% (7–63%) smaller with AZD4017 at day 2, and 48% (12–85%) smaller after repeat wounding at day 30. AZD4017 improved epidermal integrity but modestly impaired barrier function. Minimal adverse events were comparable to placebo. Recruitment rate, retention, and data completeness were 2.9/month, 27/28, and 95.3%, respectively. Conclusion A phase 2 trial is feasible, and preliminary proof-of-concept data suggests AZD4017 warrants further investigation in conditions of delayed healing, for example in diabetic foot ulcers. Significance statement Stress hormone activation by the enzyme 11β-HSD type 1 impairs skin function (e.g. integrity) and delays wound healing in animal models of diabetes, but effects in human skin were previously unknown. Skin function was evaluated in response to treatment with a 11β-HSD type 1 inhibitor (AZD4017), or placebo, in people with type 2 diabetes. Importantly, AZD4017 was safe and well tolerated. This first-in-human randomized, controlled, clinical trial found novel evidence that 11β-HSD type 1 regulates skin function in humans, including improved wound healing, epidermal integrity, and increased water loss. Results warrant further studies in conditions of impaired wound healing, for example, diabetic foot ulcers to evaluate 11β-HSD type 1 as a novel therapeutic target forchronic wounds.

BackgroundType 2 diabetes (T2DM) is increasing in prevalence worldwide, and is closely linked to obesity. Binge Eating Disorder (BED) and Night Eating Syndrome (NES) are eating disorders that are common in obesity, and may affect the management as well as long term outcomes of T2DM. Therefore, the aim of this review was to assess the prevalence and associations of BED or NES in adults with T2DM.MethodsWe conducted a systematic review. The databases MEDLINE, CINAHL and AMED were searched for articles which met the inclusion criteria; including patients > 18 years old, with T2DM, and BED and/or NES. The reference lists of included studies were also searched. Meta-analysis was not attempted due to the limited number of studies that measured the outcomes of interest.ResultsA total of 10 studies (2 included NES) were included in this systematic review. The number screened for BED and NES were 6527 and 1039 participants, respectively. Point prevalence was 1.2–8.0% for BED and 3.8–8.4% for NES. Patients with T2DM and BED had higher BMI than patients with T2DM without BED in the two studies that reported BMI. There was no statistically significant difference in HbA1c between patients with and without BED in the two studies that measured HbA1c.ConclusionsBED and NES are common in adults with T2DM, and BED is associated with higher BMI in patients with T2DM. However, only two studies reported important outcomes measures such as BMI and HbA1c in patients with T2DM. Hence, further well-designed studies are needed to assess the impact of BED and NES in patients with T2DM. Health Care Professionals should consider the diagnosis of BED and NES in patients with T2DM.

We aimed to determine the prognostic association between cardiac autonomic neuropathy (CAN) and cardiovascular disease events (CVE) and mortality in type 1 and type 2 diabetes through a systematic review and meta-analysis. This systematic review and meta-analysis was registered with PROSPERO (CRD42020216305) and was conducted with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodological criteria. CAN was defined on the basis of 1 (early/possible CAN) or ≥2 (definite CAN) positive autonomic function tests as per the Toronto Consensus guidelines. Studies included those with prospective CVE or mortality data. Methodological variables/risk of bias were assessed using ROBINS-I (Risk Of Bias In Non-randomized Studies - of Interventions) and RoB-2 (Risk-Of-Bias tool for randomized trials) appraisal tools. Electronic database searches yielded 18 467 articles; 84 articles were screened full-text, 26 articles fulfilled the inclusion criteria for quantitative synthesis. Sixteen studies from patients with (n=2875) and without (n=11 722) CAN demonstrated a pooled relative risk (RR) of 3.16 (95%CI 2.42 to 4.13; p<0.0001) of future CVE in favour of CAN. Nineteen studies provided all-cause mortality data from patients with (n=3679) and without (n=12 420) CAN, with a pooled RR of 3.17 (95%CI 2.11 to 4.78; p<0.0001) in favour of CAN. The risk of both future CVE and mortality was higher in type 1 compared with type 2 diabetes and with a definite CAN (vs possible CAN) diagnosis. Three studies were considered to have risk of serious bias. This study confirms the significant association between CAN and CVE and all-cause mortality. The implementation of population-based CAN screening will identify a subgroup with disproportionately higher cardiovascular and mortality risk that will allow for earlier targeted intervention.

ObjectivesThis study explored the impact of COVID-19 on people identified as at high risk of severe illness by UK government, and in particular, the impact of lockdown on access to healthcare, medications and use of technological platforms.DesignOnline survey methodology.SettingUK.Participants1038 UK adults were recruited who were either identified by UK government as at high risk of severe illness from COVID-19 or self-identified as at high risk with acute or other chronic health conditions not included in the UK government list. Participants were recruited through social media advertisements, health charities and patient organisations.Main outcomes measuresThe awareness, attitudes and actions survey which explores the impact of COVID-19, on including access to healthcare, use of technology for health condition management, mental health, depression, well-being and lifestyle behaviours.ResultsNearly half of the sample (44.5%) reported that their mental health had worsened during the COVID-19 lockdown. Management of health conditions changed including access to medications (28.5%) and delayed surgery (11.9%), with nearly half of the sample using telephone care (45.5%). Artificial Intelligence identified that participants in the negative cluster had higher neuroticism, insecurity and negative sentiment. Participants in this cluster reported more negative impacts on lifestyle behaviours, higher depression and lower well-being, alongside lower satisfaction with platforms to deliver healthcare.ConclusionsThis study provides novel evidence of the impact of COVID-19 on people identified as at high risk of severe illness. These findings should be considered by policy-makers and healthcare professionals to avoid unintended consequences of continued restrictions and future pandemic responses.