Perceived weight stigma in healthcare settings among adults living with obesity: A cross-sectional investigation of the relationship with patient characteristics and person-centred care.

INTRODUCTION: Patients living with obesity often experience weight stigma in healthcare settings, which has worrying consequences for their healthcare experiences. This cross-sectional study aimed to: (1) provide an overview of stigmatising experiences in healthcare settings reported by adults living with varying classes of obesity, (2) identify associations among patient characteristics and perceived weight stigma and (3) investigate the association between perceived weight stigma and person-centred care (PCC). METHODS: Dutch adults living with obesity classes I (body mass index [BMI]: 30 to <35 kg/m2; n = 426), II (BMI: 35 to <40 kg/m2; n = 124) and III (BMI: ≥40 kg/m2; n = 40) completed measures of perceived weight stigma in healthcare settings and PCC. Descriptive, correlational and multivariate analyses were conducted. RESULTS: Of patients living with classes I, II and III obesity, 41%, 59% and 80%, respectively reported experiences of weight stigma in healthcare settings. Younger age, greater obesity severity and the presence of chronic illnesses were associated with greater perceived weight stigma. Greater perceived weight stigma was associated with lower PCC. CONCLUSION: The results of this study emphasise the significant role of weight stigma in the healthcare experiences of patients living with obesity. Reducing weight stigma is expected to improve PCC and the overall quality of care for these patients. Minimising weight stigma will require efforts across various healthcare domains, including increasing awareness among healthcare professionals about sensitive communication in weight-related discussions. PATIENT CONTRIBUTION: Our sample consisted of patients living with obesity. Additionally, patients were involved in the pilot testing and refinement of the PCC instrument.

The relationship between person-centred care and well-being and satisfaction with care of patients living with obesity.

Person-centred care (PCC) is associated with improved patient well-being and higher levels of satisfaction with care but its impact on individuals living with obesity is not well-established. The main aim of this study was to assess the relationship between PCC and the physical and social well-being of patients living with obesity, as well as their satisfaction with care. This study is based on a cross-sectional, web-based survey administered among a representative panel of Dutch individuals living with obesity. The primary outcomes were physical and social well-being and satisfaction with care. The primary exposure was a rating of overall PCC, encompassing its eight dimensions. In addition, covariates considered in the analyses included sex, age, marital status, education level, body mass index, and chronic illness. The data from a total of 590 participants were analysed using descriptive statistics, correlation analyses, and multiple regression analyses. Among PCC dimensions, participants rated 'access to care' the highest (M 4.1, SD 0.6), while 'coordination of care' (M 3.5, SD 0.8) was rated lower than all other dimensions. Participants' overall PCC ratings were positively correlated with their physical (r = 0.255, P < .001) and social well-being (r = 0.289, P < .001) and their satisfaction with care (r = 0.788, P < .001), as were the separate dimension scores. After controlling for sex, age, marital status, education level, body mass index, and chronic illness in the regression analyses, participants' overall PCC ratings were positively related to their physical (ß = 0.24, P < .001) and social well-being (ß = 0.26, P < .001), and satisfaction with care (ß = 0.79, P < .001). PCC holds promise for improved outcomes among patients living with obesity, both in terms of physical and social well-being, as well as satisfaction with care. This is an important finding, particularly when considering the profound physical, social, and psychological consequences associated with obesity. In addition to highlighting the potential benefits of PCC in the healthcare of individuals living with obesity, the findings offer valuable insights into strategies for further refining the provision of PCC to meet the specific needs of these patients.

Reversal of insulin resistance in people with obesity by lifestyle-induced weight loss does not impact the proportion of circulating 12α-hydroxylated bile acids.

AIM: Bile acids (BAs) are implicated in the pathogenesis of several metabolic syndrome-related diseases, including insulin resistance (IR) and type 2 diabetes (T2D). It has been reported that IR and T2D are associated with an increased ratio of 12α/non-12α-hydroxylated BAs in the circulating BA pool. It is, however, unknown whether the improvement of insulin sensitivity inversely affects BA composition in humans. Therefore, we assessed whether lifestyle-induced weight loss induces changes in BA metabolism in people with obesity, with or without T2D, and if these changes are associated with metabolic parameters. MATERIALS AND METHODS: Individual BAs and C4 were quantified by ultra-high-performance liquid chromatography-tandem mass spectrometry in plasma samples collected from two cohorts of people with obesity (OB) and with T2D and obesity (T2D), before and after a lifestyle intervention. RESULTS: Lifestyle-induced weight loss improved glycaemic control in both cohorts, with plasma BA concentrations not affected by the lifestyle interventions. The ratio of 12α/non-12α-hydroxylated BAs remained unchanged in OB (p = .178) and even slightly increased upon intervention in T2D (p = .0147). Plasma C4 levels were unaffected in OB participants (p = .20) but significantly reduced in T2D after intervention (p = .0003). There were no significant correlations between the ratio of 12α/non-12α-hydroxylated BAs and glucose, insulin, or homeostatic model assessment-IR, nor in plasma triglycerides, low-density lipoprotein cholesterol, lipoprotein (a) in the T2D cohort. CONCLUSIONS: Lifestyle-induced weight loss did improve glycaemic control but did not affect BA concentrations. Improvements in insulin sensitivity were not associated with changes in BA parameters in people with obesity, with or without T2D.

Treatment with liraglutide or naltrexone-bupropion in patients with genetic obesity: a real-world study.

Background: Rare genetic obesity commonly features early-onset obesity, hyperphagia, and therapy-resistance to lifestyle interventions. Pharmacotherapy is often required to treat hyperphagia and induce weight loss. We describe clinical outcomes of glucagon-like peptide-1 analogue liraglutide or naltrexone-bupropion treatment in adults with molecularly confirmed genetic obesity (MCGO) or highly suspected for genetic obesity without definite diagnosis (HSGO). Methods: We conducted a real-world cohort study at the Obesity Center CGG at Erasmus University Center, Rotterdam, Netherlands, between March 19, 2019, and August 14, 2023. All patients with MCGO and HSGO who were treated with either liraglutide or naltrexone-bupropion were included. Liraglutide 3 mg and naltrexone-bupropion were administered according to the manufacturer's protocol. Treatment evaluation occurred short-term, after 12 weeks on maximum or highest-tolerated dose, preceded by the 4-5 week dose escalation phase. Differences in anthropometrics, body composition, metabolic markers, self-reported appetite, eating behaviour, and quality of life (QoL) were evaluated. Findings: Ninety-eight adults were included in the analysis: 23 patients with MCGO and 75 patients with HSGO, with median BMI of 42.0 kg/m2 (IQR 38.7-48.2) and 43.7 kg/m2 (IQR 38.0-48.7), respectively. After liraglutide treatment, median weight at evaluation significantly decreased compared to baseline in both groups: -4.7% (IQR -6.0 to -1.5) in patients with MCGO and -5.2% (IQR -8.1 to -3.5) in patients with HSGO. Additionally, improvements were observed in appetite, fat mass, fasting glucose, and HbA1c in both patients with MCGO and with HSGO. Patients with HSGO also reported significant improvements in several domains of QoL and eating behaviour. In patients with MCGO and HSGO treated with naltrexone-bupropion, mean weight at evaluation significantly differed from baseline: -5.2% ± 5.8 in patients with MCGO and -4.4% ± 4.7 in patients with HSGO. Appetite, fat mass, and waist circumference significantly decreased in both groups. Obesity-related comorbidities improved in significant proportions of patients treated with liraglutide or naltrexone-bupropion. Interpretation: In conclusion, our short-term findings show potential of liraglutide and naltrexone-bupropion as treatment options for adults with (a clinical phenotype of) genetic obesity. Funding: MB, EvdA, and EvR are supported by the Elisabeth Foundation, a non-profit foundation supporting academic obesity research.

Core Set of Patient-Reported Outcome Measures for Measuring Quality of Life in Clinical Obesity Care.

PURPOSE: The focus of measuring success in obesity treatment is shifting from weight loss to patients' health and quality of life. The objective of this study was to select a core set of patient-reported outcomes and patient-reported outcome measures to be used in clinical obesity care. MATERIALS AND METHODS: The Standardizing Quality of Life in Obesity Treatment III, face-to-face hybrid consensus meeting, including people living with obesity as well as healthcare providers, was held in Maastricht, the Netherlands, in 2022. It was preceded by two prior multinational consensus meetings and a systematic review. RESULTS: The meeting was attended by 27 participants, representing twelve countries from five continents. The participants included healthcare providers, such as surgeons, endocrinologists, dietitians, psychologists, researchers, and people living with obesity, most of whom were involved in patient representative networks. Three patient-reported outcome measures (patient-reported outcomes) were selected: the Impact of Weight on Quality of Life-Lite (self-esteem) measure, the BODY-Q (physical function, physical symptoms, psychological function, social function, eating behavior, and body image), and the Quality of Life for Obesity Surgery questionnaire (excess skin). No patient-reported outcome measure was selected for stigma. CONCLUSION: A core set of patient-reported outcomes and patient-reported outcome measures for measuring quality of life in clinical obesity care is established incorporating patients' and experts' opinions. This set should be used as a minimum for measuring quality of life in routine clinical practice. It is essential that individual patient-reported outcome measure scores are shared with people living with obesity in order to enhance patient engagement and shared decision-making.

Chronic Stress Related to Cancer Incidence, including the Role of Metabolic Syndrome Components.

Epidemiological results on the link between chronic stress and cancer initiation have been inconsistent. This study examined the relation between chronic biological stress, indicated as hair cortisol (HairF) and hair cortisone (HairE), and cancer incidence, adjusting for metabolic syndrome (MetS) components. We analyzed HairF and HairE samples from 6341 participants from the population-based cohort Lifelines in 2014. A linkage with the Dutch Nationwide Pathology Databank (Palga) provided the cancer incidence from 2015 to 2021. The association between dichotomized HairF and log-transformed HairE (LogHairE) and cancer incidence was estimated using Cox regression. MetS components were evaluated as confounders or moderators. Of the 2776 participants with known HairF levels and no cancer history, 238 developed cancer. The HairF level did not predict cancer incidence (HR: 0.993, 95%CI: 0.740-1.333). No confounders or moderators were identified. Among the 4699 participants with known HairE levels and no cancer history, 408 developed cancer. There was no association between LogHairE and cancer incidence (HR: 1.113, 95%CI: 0.738-1.678). When including age as a confounder and gender as a moderator, LogHairE was statistically significantly associated with cancer incidence (HR: 6.403, 95%CI: 1.110-36.92). In a population-based cohort, chronic biological stress, measured by HairE, was associated with cancer incidence, after controlling for age and gender.

Erasing stigmas through storytelling: why interactive storytelling environments could reduce health-related stigmas.

In this article we describe how designers can apply storytelling to reduce health-related stigmas. Stigma is a pervasive problem for people with illnesses, such as obesity, and it can persistently hinder coping, treatment, recovery, and prevention. Reducing health-related stigma is complex because it is multi-layered and self-perpetuating, leading to intertwined vicious circles. Interactive storytelling environments can break these vicious circles by delimiting the narrative freedom of stigma actors. We theoretically explain the potential of interactive storytelling environments to reduce stigma through the following seven functions: 1) expose participants to other perspectives, 2) provide a protective frame, 3) intervene in daily conversations, 4) persuade all stigma actors, 5) exchange alternative understandings, 6) elicit understanding and support for stigma victims, and 7) support stigma victims to cope with stigmatization. We elaborate on these functions through a demonstration of an interactive storytelling environment against weight stigma. In conclusion, this article is a call on designers for health and wellbeing, scientists, and practitioners from various disciplines to be sensitive to the pervasiveness of stigma and to collaboratively create destigmatizing storytelling environments.

Clinical phenotypes of adults with monogenic and syndromic genetic obesity.

OBJECTIVE: Considering limited evidence on diagnostics of genetic obesity in adults, we evaluated phenotypes of adults with genetic obesity. Additionally, we assessed the applicability of Endocrine Society (ES) recommendations for genetic testing in pediatric obesity. METHODS: We compared clinical features, including age of onset of obesity and appetite, between adults with non-syndromic monogenic obesity (MO), adults with syndromic obesity (SO), and adults with common obesity (CO) as control patients. RESULTS: A total of 79 adults with genetic obesity (32 with MO, 47 with SO) were compared with 186 control patients with CO. Median BMI was similar among the groups: 41.2, 39.5, and 38.7 kg/m2 for patients with MO, SO, and CO, respectively. Median age of onset of obesity was 3 (IQR: 1-6) years in patients with MO, 9 (IQR: 4-13) years in patients with SO, and 21 (IQR: 13-33) years in patients with CO (p < 0.001). Patients with genetic obesity more often reported increased appetite: 65.6%, 68.1%, and 33.9% in patients with MO, SO, and CO, respectively (p < 0.001). Intellectual deficit and autism spectrum disorder were more prevalent in patients with SO (53.2% and 21.3%) compared with those with MO (3.1% and 6.3%) and CO (both 0.0%). The ES recommendations were fulfilled in 56.3%, 29.8%, and 2.7% of patients with MO, SO, and CO, respectively (p < 0.001). CONCLUSIONS: We found distinct phenotypes in adult genetic obesity. Additionally, we demonstrated low sensitivity for detecting genetic obesity in adults using pediatric ES recommendations, necessitating specific genetic testing recommendations in adult obesity care.

GNB1 and obesity: Evidence for a correlation between haploinsufficiency and syndromic obesity.

Most patients with GNB1 encephalopathy have developmental delay and/or intellectual disability, brain anomalies and seizures. Recently, two cases with GNB1 encephalopathy caused by haploinsufficiency have been reported that also show a Prader-Willi-like phenotype of childhood hypotonia and severe obesity. Here we present three new cases from our expert centre for genetic obesity in which GNB1 truncating and splice variants, probably leading to haploinsufficiency, were identified. They all have obesity, hyperphagia and intellectual deficit. The clinical cases and their weight courses are presented, together with a review of all 68 published cases with GNB1 encephalopathy. Information on weight was not mentioned in most of these articles, so we contacted authors for additional clinical information on weight status and hyperphagia. Of the 42 patients whose weight status we could determine, obesity was present in 8 patients (19%). Obesity is significantly over-represented in the group with truncating and splicing variants. In this group, we see an obesity prevalence of 75%. Since GNB1 has been linked to several key genes in the hypothalamic leptin-melanocortin pathway, which regulates satiety and energy expenditure, our data support the potential association between GNB1 haploinsufficiency and genetic obesity. We also suggest GNB1 is a candidate gene for the known obesity phenotype of the 1p36 microdeletion syndrome given this chromosomal region includes the GNB1 gene. Knowledge of an additional obesity phenotype is important for prognosis, early interventions against obesity and awareness when prescribing weight-inducing medication.

Hypertension and diabetes, but not leptin and adiponectin, mediate the relationship between body fat and chronic kidney disease.

PURPOSE: Obesity may promote kidney damage through hemodynamic and hormonal effects. We investigated the association between body mass index (BMI), total body fat (TBF) and chronic kidney disease (CKD) and whether hypertension, diabetes, leptin and adiponectin mediated these associations. METHODS: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, 6671 participants (45-65 y) were included. We defined CKD as eGFR <60 ml/min/1.73 m2 and/or moderately increased albuminuria. The percentage of mediation was calculated using general structural equation modeling, adjusted for potential confounding factors age, sex, smoking, ethnicity, physical activity and Dutch healthy diet index. RESULTS: At baseline mean (SD) age was 56 (6), BMI 26.3 (4.4), 44% men, and 4% had CKD. Higher BMI and TBF were associated with 1.08 (95%CI 1.05; 1.11) and 1.05-fold (95%CI 1.02; 1.08) increased odds of CKD, respectively. As adiponectin was not associated with any of the outcomes, it was not studied further as a mediating factor. The association between BMI and CKD was 8.5% (95%CI 0.5; 16.5) mediated by diabetes and 22.3% (95%CI 7.5; 37.2) by hypertension. In addition, the association between TBF and CKD was 9.6% (95%CI -0.4; 19.6) mediated by diabetes and 22.4% (95%CI 4.2; 40.6) by hypertension. We could not confirm mediation by leptin in the association between BMI and CKD (35.6% [95%CI -18.8; 90.3]), nor between TBF and CKD (59.7% [95%CI -7.1; 126.6]). CONCLUSION: Our results suggest that the relations between BMI, TBF and CKD are in part mediated by diabetes and hypertension.

MC4R variants modulate α-MSH and setmelanotide induced cellular signaling at multiple levels.

CONTEXT: Melanocortin-4 receptor (MC4R) plays an important role in body weight regulation. Pathogenic MC4R variants are the most common cause of monogenic obesity. OBJECTIVE: We have identified 17 MC4R variants in adult and pediatric patients with obesity. Here, we aimed to functionally characterize these variants by analyzing four different aspects of MC4R signaling. In addition, we aimed to analyze the effect of setmelanotide, a potent MC4R agonist, on these MC4R variants. MATERIALS AND METHODS: Cell surface expression and α-MSH- or setmelanotide-induced cAMP response, ß-arrestin-2 recruitment, and ERK activation were measured in cells expressing either wild type (WT) or variant MC4R. RESULTS: We found a large heterogeneity in the function of these variants. We identified variants with a loss of response for all studied MC4R signaling, variants with no cAMP accumulation or ERK activation but normal ß-arrestin-2 recruitment, and variants with normal cAMP accumulation and ERK activation but decreased ß-arrestin-2 recruitment, indicating disrupted desensitization and signaling mechanisms. Setmelanotide displayed a greater potency and similar efficacy as α-MSH, and induced significantly increased maximal cAMP responses of several variants compared to α-MSH. Despite the heterogeneity in functional response, there was no apparent difference in the obesity phenotype in our patients. DISCUSSION: We show that these obesity-associated MC4R variants affect MC4R signaling differently, yet leading to a comparable clinical phenotype. Our results demonstrate the clinical importance of assessing the effect of MC4R variants on a range of molecular signaling mechanisms to determine their association with obesity, which may aid in improving personalized treatment.

Long-term glucocorticoid exposure and incident cardiovascular diseases - the Lifelines cohort.

CONTEXT: Long-term glucocorticoid levels in scalp hair (HairGCs), including cortisol and the inactive form cortisone, represent the cumulative systemic exposure to glucocorticoids over months. HairGCs have repeatedly shown associations with cardiometabolic and immune parameters, but longitudinal data are lacking. DESIGN: We investigated 6341 hair samples of participants from the Lifelines cohort study for cortisol and cortisone levels, and associated these to incident cardiovascular diseases (CVD) during 5-7 years of follow-up. We computed the odds ratio (OR) of HairGC levels for incident CVD via logistic regression, adjusting for classical cardiovascular risk factors, and performed a sensitivity analysis in subcohorts of participants <60 years and >= 60 years. Also, we associated HairGC levels to immune parameters (total leukocytes and subtypes). RESULTS: Hair cortisone levels (available in n = 4701) were independently associated with incident CVD (p < 0.001), particularly in younger individuals (multivariate-adjusted OR 4.21, 95% confidence interval (CI) 1.91-9.07 per point increase in 10-log cortisone concentration (pg/mg), p < 0.001). All immune parameters except eosinophils were associated with hair cortisone (all multivariate-adjusted p < 0.05). CONCLUSIONS: In this large, prospective cohort study, we found that long-term cortisone levels, measured in scalp hair, represent a relevant and significant predictor for future cardiovascular diseases in younger individuals. These results highlight glucocorticoid action as possible treatment target for CVD prevention, where hair glucocorticoid measurements could help identify individuals that may benefit from such treatments.

Long-term glucocorticoids in relation to the metabolic syndrome and cardiovascular disease: A systematic review and meta-analysis.

The striking link of Cushing's syndrome with the metabolic syndrome (MetS) and cardiovascular disease (CVD) suggests that long-term exposure to extremely high cortisol levels catalyzes cardiometabolic deterioration. However, it remained unclear whether the findings from the extreme glucocorticoid overabundance observed in Cushing's syndrome could be translated into more subtle variations in long-term glucocorticoid levels among the general population, for example, due to chronic stress. Here, we performed a systematic review (PROSPERO: CRD42023425541) of evidence regarding the role of subtle variations in long-term biological stress, measured as levels of scalp hair cortisol (HairF) and cortisone (HairE), in the context of MetS and CVD in adults. We also performed a meta-analysis on the cross-sectional difference in HairF levels between individuals with versus without CVD. Seven studies were included regarding MetS, sixteen regarding CVD, and one regarding both. Most articles indicated a strong, consistent cross-sectional association of higher HairF and HairE levels with CVD, which was confirmed by our meta-analysis for HairF (eight studies, SMD = 0.48, 95% confidence intervals [CIs]: 0.16-0.79, p = 0.0095). Moreover, these relationships appear largely independent of standard risk factors. Age seems relevant as the effect seems stronger in younger individuals. Results regarding the associations of HairF and HairE with MetS were inconsistent. Altogether, long-term biological stress, measured as HairF and HairE, is associated with the presence of CVD, and less consistently with MetS. Prospective studies need to evaluate the directionality of this relationship and determine whether HairF and HairE can be used in addition to standard risk factors in predicting future cardiometabolic deterioration.

Determination of cortisone and cortisol in human scalp hair using an improved LC-MS/MS-based method.

OBJECTIVES: Human scalp hair is an easily available but complex matrix for determination of cortisone and cortisol, and has been shown to reflect long-term glucocorticoid exposure. Hair glucocorticoid analysis has been used to detect hypo- and hypercortisolism. In this study, we describe the development and validation of a LC-MS/MS method for quantification of cortisone and cortisol in human scalp hair, and provide a novel approach for analysis and interpretation of the results. METHODS: Improved sample preparation using pulverization and solid phase extraction allowed for low sample volumes (10 mg). Baseline chromatographic separation without matrix interference was achieved by reversed phase chromatography and MRM measurement in negative ion mode. Run-to-run time was 8 min. Mixed model analyses were performed to create individual patterns of cortisone and cortisol concentrations. RESULTS: Matrix matched calibration curves showed excellent linearity up to 100 pg (analyte)/mg (hair) for both cortisone and cortisol (R2>0.995). LLOQ was 1.5 and 1.0 pg/mg for cortisone and cortisol, respectively. Matrix effect was negligible for hair color (recoveries 95-105 %). Cortisone and cortisol concentrations decreased from proximal to distal hair segments, following a predictable, but subject-specific pattern, with less individual variation for cortisone than for cortisol. CONCLUSIONS: This improved LC-MS/MS method is able to accurately quantify cortisone and cortisol in human hair with minimum matrix interference. This new way of data analysis and interpretation including individual patterns of cortisone and cortisol will be of help with detection of pathological concentrations in both the high - and the low ranges of glucocorticoids.

Neuropsychiatric adverse effects of synthetic glucocorticoids: A systematic review and meta-analysis.

BACKGROUND: Synthetic glucocorticoids are widely used among patients suffering from a wide range of diseases. Glucocorticoids are very efficacious, but can be accompanied by neuropsychiatric adverse effects. This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids. METHODS: Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and non-users were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model. RESULTS: We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95%CI 14%-33%), 11% for mania (95%CI 2%-46%), 8% for anxiety (95%CI 2%-25%), 16% for delirium (95%CI 6%-36%), and 52% for behavioural changes (95%CI 42%-61%). Questionnaire scores for depression (SMD of 0.80 (95%CI 0.35-1.26)), and mania (0.78 (95%CI 0.14-1.42)) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use. CONCLUSIONS: The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed.

The (cost) effectiveness of a very low-energy diet intervention with the use of eHealth in patients with type 2 diabetes and obesity: study protocol for a randomised controlled non-inferiority trial (E-diet trial).

BACKGROUND: Despite preventive measures, the number of people with type 2 diabetes and obesity is increasing. Obesity increases morbidity and mortality in people with type 2 diabetes, making weight loss a cornerstone of treatment. We previously developed a very low energy diet (VLED) intervention that effectively reduced weight in people with type 2 diabetes in the long term. However, this intervention requires considerable time and manpower, which reduces the number of people who can benefit from it. eHealth offers more efficient solutions but has proven to be less effective than face-to-face interventions. Therefore, we want to investigate whether a blended version of our VLED intervention (in which face-to-face contact is partly replaced by an eHealth (mobile) application (E-VLED)) would be more cost-effective than the current face-to-face intervention. METHODS: We will conduct a randomised, controlled trial with non-inferiority design in patients with type 2 diabetes and obesity (BMI > 30 kg/m2), aged 18-75 years. The control group will receive the usual care VLED intervention, while the intervention group will receive the E-VLED intervention for 1 year, where face-to-face contact will be partly replaced by an eHealth (mobile) application. The main study endpoint is the difference in weight (% change) between the control and intervention group after 1 year, plus the difference between the total costs (euro) of the treatment in the control and intervention groups. The secondary aims are to investigate the effectiveness of the E-VLED diet intervention regarding cardiovascular risk factors, quality of life, patient satisfaction, compliance, and to study whether there is a difference in effectiveness in pre-specified subgroups. General linear models for repeated measurements will be applied for the statistical analysis of the data. DISCUSSION: We hypothesise that the E-VLED intervention will be equally effective compared to the usual care VLED but lower in costs due to less time invested by the dietician. This will enable to help more people with type 2 diabetes and obesity to effectively lose weight and improve their health-related quality of life. TRIAL REGISTRATION: Netherlands Trial Register, NL7832, registered on 26 June 2019.

The Effect of Including eHealth in Dietary Interventions for Patients with Type 2 Diabetes with Overweight or Obesity: A Systematic Review.

eHealth has a growing impact on the delivery of healthcare, making health systems more efficient. This study examined the effect of dietary interventions using eHealth compared to face-to-face contact in patients with (pre-) type 2 diabetes (T2D) and who are overweight/obese. Literature databases were searched upon November 2022. Inclusion criteria: randomized controlled trial; duration ≥ 6 months; involving dietary interventions; performed in adults with (pre-) T2D and who are overweight/obese; using eHealth compared to face-to-face contact; and report outcomes on weight loss, glycemic regulation, and/or cost-effectiveness. Selection of articles was performed manually and using ASReviewLab. Fifteen studies were included for data extraction, investigating a wide variety of eHealth interventions. Seven studies reporting on weight loss showed a significant between-group difference (-1.18 to -5.5 kg); five studies showed a trend in favor of the eHealth programs. Eleven studies reported on HbA1c; three found a significant between-group difference (-0.23 to -0.70%) in favor of the eHealth programs and six studies showed non-significant improvements. Interaction with healthcare professionals led to better results of the dietary interventions. Two studies reported incomplete data on cost-effectiveness. In conclusion, eHealth shows better results of dietary interventions in (pre-) T2D patients compared to face-to-face, especially when combined with interaction with healthcare professionals.

Psychological, behavioural, and physical aspects of caregiver strain in autism-caregivers: a cohort study.

Background: People who give care to autistic individuals (autism-caregivers) experience higher levels of caregiver strain than people who provide care for individuals with other chronic conditions (non-autism-caregivers). This places them at higher risk for psychological, behavioural and physical health concerns. The aim of this study is to delineate psychological, behavioural, and physical aspects of caregiver strain in autism-caregivers compared to non-autism-caregivers. Methods: We included 3354 adult caregivers from the general population in the Netherlands participating in the second assessment (January, 1, 2014-December, 31, 2017) of the Lifelines Cohort. In this cohort study, using multivariable regression adjusted for age, sex, and socioeconomic status, we analysed psychological (anxiety and depression based on a Mini International Neuropsychiatric Interview, and self-reported stress and perceived health), behavioural (questionnaire-assessed physical activity, alcohol use, and smoking), and physical aspects (body mass index, waist circumference, and leukocyte-counts) of caregiver strain in autism-caregivers (n = 722) compared with non-autism-caregivers (n = 2632). Findings: Autism-caregivers reported more stress (OR 3.61, 95% CI 2.60-4.99). Both anxiety (OR 1.85, 95% CI 1.37-2.49) and depressive disorders (OR 1.83, 95% CI 1.17-2.86) were more common in autism-caregivers than in non-autism-caregivers. Perceived health, physical activity, alcohol use, and smoking were not different between autism- and non-autism-caregivers. In autism-caregivers, lymphocyte- and monocyte-counts were lower than in non-autism-caregivers. Interpretation: In this large cohort, autism-caregivers had worse psychological health than non-autism-caregivers. Moreover, autism-caregiving might be associated with an altered immune balance. These findings underline the higher caregiver strain in autism-caregivers compared to other caregivers. This calls for increased support to autism-caregivers. Funding: Lifelines has been funded by the Dutch government.

Emerging diagnostic methods and imaging modalities in cushing's syndrome.

Endogenous Cushing's syndrome (CS) is a rare disease characterized by prolonged glucocorticoid excess. Timely diagnosis is critical to allow prompt treatment and limit long-term disease morbidity and risk for mortality. Traditional biochemical diagnostic modalities each have limitations and sensitivities and specificities that vary significantly with diagnostic cutoff values. Biochemical evaluation is particularly complex in patients whose hypercortisolemia fluctuates daily, often requiring repetition of tests to confirm or exclude disease, and when delineating CS from physiologic, nonneoplastic states of hypercortisolism. Lastly, traditional pituitary MRI may be negative in up to 60% of patients with adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (termed "Cushing's disease" [CD]) whereas false positive pituitary MRI findings may exist in patients with ectopic ACTH secretion. Thus, differentiating CD from ectopic ACTH secretion may necessitate dynamic testing or even invasive procedures such as bilateral inferior petrosal sinus sampling. Newer methods may relieve some of the diagnostic uncertainty in CS, providing a more definitive diagnosis prior to subjecting patients to additional imaging or invasive procedures. For example, a novel method of cortisol measurement in patients with CS is scalp hair analysis, a non-invasive method yielding cortisol and cortisone values representing long-term glucocorticoid exposure of the past months. Hair cortisol and cortisone have both shown to differentiate between CS patients and controls with a high sensitivity and specificity. Moreover, advances in imaging techniques may enhance detection of ACTH-secreting pituitary adenomas. While conventional pituitary MRI may fail to identify microadenomas in patients with CD, high-resolution 3T-MRI with 3D-spoiled gradient-echo sequence has thinner sections and superior soft-tissue contrast that can detect adenomas as small as 2 mm. Similarly, functional imaging may improve the identification of ACTH-secreting adenomas noninvasively; Gallium-68-tagged corticotropin-releasing hormone (CRH) combined with PET-CT can be used to detect CRH receptors, which are upregulated on corticotroph adenomas. This technique can delineate functionality of adenomas in patients with CD from patients with ectopic ACTH secretion and false positive pituitary lesions on MRI. Here, we review emerging methods and imaging modalities for the diagnosis of CS, discussing their diagnostic accuracy, strengths and limitations, and applicability to clinical practice.