Changes in Symptoms and General Well-being After Reversal of Roux-en-Y Gastric Bypass: A Questionnaire Survey.

PURPOSE: After Roux-en-Y gastric bypass (RYGB), few patients develop severe complications, which ultimately may require reversal of RYGB. We aimed to examine the effect of reversal of RYGB on symptoms and well-being. MATERIALS AND METHODS: Via contact to medical and surgical departments treating patients with RYGB, we identified 18 patients, who had undergone reversal, 2009-2019. We conducted a Danish, nationwide questionnaire survey concerning symptoms before and after reversal of the RYGB including the patients' own perceptions of their well-being. RESULTS: Fourteen patients responded to the questionnaire (86% female; median age at RYGB, 36.2 years [IQR, 30.9-38.6 years]). The median time from RYGB to reversal was 5.8 years (IQR, 5.1-7.5 years). After RYGB, 13 patients (93%) reported abdominal pain, while 12 patients still had abdominal pain after reversal. Six out of 11 patients (45%) reported complete remission of dumping/post-bariatric hypoglycemia (PBH) after reversal. Malabsorption disappeared in 10 out of 11 patients (90%). Reversal had minor effect on neuropathy. The median weight loss from RYGB was 61 kg (IQR, 56-75 kg), while the median weight regain after reversal was 30 kg (IQR, 13-46 kg). Regarding the well-being, 72 of the patients felt better or much better after reversal. CONCLUSION: In total, 72% of the patients felt better or much better after reversal of RYGB, though some still had RYGB-related symptoms. The reversal relieved dumping/PBH and malabsorption, but not abdominal pain and neuropathy. Finally, half of the weight loss was regained after reversal. Reversal of RYGB may be an option in highly selected cases.

Effect of a higher protein diet and lifestyle camp intervention on childhood obesity (The COPE study): results from a nonrandomized controlled trail with 52-weeks follow-up.

PURPOSE: In adults, diets rich in protein seem beneficial in relation to satiety, weight loss, and weight management; however, studies investigating dietary protein and weight development in children are scarce and inconsistent. This nonrandomized controlled trial aimed to investigate the effect of a higher protein diet during lifestyle intervention on anthropometry and metabolic biomarkers in children with overweight and obesity. METHODS: Children (n:208) were recruited from two multicomponent lifestyle camps. One camp was assigned as the intervention group. In the intervention group, carbohydrates-rich foods at breakfast and two in-between-meals were replaced with protein-containing foods to increase the amount of protein from ~ 10-15 energy percent (E%) per day to ~ 25E% per day. Other components were similar between groups. Anthropometry and biochemical measurements were collected at baseline, 10 weeks (after camp) and 52 weeks. RESULTS: The intervention group had a non-significant improvement in BMI-SDS (- 0.07 SD (- 0.19; 0.05), p = 0.24) compared to the control group, but in general, there was no effect of a higher protein diet on anthropometry and metabolic biomarkers. Overall, 10 weeks at camp resulted in a more favorable body composition [- 6.50 kg (p < 0.00), - 0.58 BMI-SDS (p < 0.00), and - 5.92% body fat (p < 0.00)], and improved metabolic health, with most changes maintained at 52 weeks. CONCLUSION: A higher protein diet had no significant effect on body composition and metabolic health; however, these lifestyle camps are an efficiatious treatment strategy for childhood obesity. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov with ID: NCT04522921. Preregistered August 21st 2020.

Managing the new wave of weight loss medication in general practice: A qualitative study.

In early 2023, a new type of weight loss medication, Wegovy (semaglutide), was made available in Denmark. Both subsequent media coverage and public demand were huge. Wegovy is only available by prescription, primarily via general practitioners. However, there is very little knowledge about how healthcare professionals (HCPs) in general practice might deal with the great demand for and attention surrounding a new weight loss drug. The aim of this qualitative study was, therefore, to explore how Wegovy is managed and negotiated in general practice, particularly in terms of prescribing and follow-up. We conducted a focused ethnography study based on direct observation of consultations and both formal and informal interviews with seven doctors and four nurses from three general practices in Denmark. Using discourse analysis, we identified four central discourses revolving around trust in medicine, individual responsibility for health, the cost of weight loss medication, and the importance of shared decision-making. This study shows that the availability of a new, sought-after weight loss medication presents both opportunities and challenges for HCPs in general practice. The management of Wegovy involves numerous factors, including medical, economic, organizational, interpersonal and moral concerns.

A literature review of evidence for primary prevention of overweight and obesity in healthy weight children and adolescents: A report produced by a working group of the Danish Council on Health and Disease Prevention.

Primary prevention targets development of overweight in individuals with healthy weight and is a great challenge. This paper summarizes the main findings of a working group of the Danish Council on Health and Disease Prevention that reviewed the literature on primary prevention of overweight and obesity among children and adolescents. The results were presented in a Danish report, in which a 2019 Cochrane review on childhood obesity prevention was complemented by searches in PubMed to include all relevant subsequent studies published from January 2018 until March 2020. In this paper, the review was updated until June 2023. Numerous childhood overweight prevention interventions have been developed during the past decades, primarily targeting diet and/or physical activity. Several of these interventions showed positive effects on diet and physical activity level but did not show effects on risk of developing overweight. The evidence foundation is inconsistent as four out of five interventions did not show positive effects. Previously observed intervention effects may not reflect excessive weight gain prevention among children with healthy weight but rather bodyweight reduction among those with overweight or obesity. We do not have sufficient knowledge about how to prevent children with healthy weight from developing overweight, and creative solutions are urgently needed.

Diagnostic Impact of Hs-CRP and IL-6 for Acute Coronary Syndrome in Patients Admitted to the ED with Chest Pain: Added Value to the HEART Score?

Objective: To investigate whether hs-CRP and IL-6 provide additional diagnostic value beyond that achieved by the HEART score in patients with chest pain suggestive of acute coronary syndrome (ACS) admitted to the emergency department (ED). Methods: This was a post hoc analysis using data from the RACING-MI study. Baseline data, including hs-CRP and IL-6 levels, were analyzed using the plasma from the biobank. A total of 818 patients with chest pain suggestive of ACS were included in this analysis. Of these, 98 were diagnosed with ACS (12%). Logistic regression was used to identify the independent predictors of ACS development in patients with chest pain. Results: hs-CRP levels >2 mg/L were observed in 50% of all ACS cases. IL-6 levels >1.3 pg/mL were observed in 71% of all ACS cases. hs-CRP had a sensitivity of 50% and specificity of 51% for the diagnosis of ACS, whereas IL-6 had a sensitivity of 71% and specificity of 29%. The diagnostic likelihood ratios for ACS was 1.0 for hs-CRP>2 mg/L and IL-6 > 1.3 pg/mL, respectively. Logistic regression analysis revealed that age, male gender, and ongoing smoking were associated with ACS in patients with acute chest pain. No association was found between IL-6 or hs-CRP level and ACS. This was observed for both IL-6 and hs-CRP, whether assessed on a continuous scale or using prespecified cut-off values. Conclusion: Among the 818 patients admitted to the ED with chest pain suggestive of ACS, neither hs-CRP nor IL-6 provided an independent added diagnostic value. Our results suggest that inflammatory markers have limited diagnostic value in detecting patients with ACS in the ED.

The association between sleep duration and detailed measures of obesity: A cross sectional analysis in the ADDITION-PRO study.

Background: Sleep duration is associated with BMI and waist circumference. However, less is known about whether sleep duration affects different measurements of obesity differently. Objective: To investigate the association between sleep duration and different measures of obesity. Methods: In this cross-sectional analysis 1309, Danish, older adults (55% men) completed at least 3 days of wearing a combined accelerometer and heart rate-monitor for assessing sleep duration (hours/night) within self-reported usual bedtime. Participants underwent anthropometry and ultrasonography to assess BMI, waist circumference, visceral fat, subcutaneous fat, and fat percentage. Linear regression analyses examined the associations between sleep duration and obesity-related outcomes. Results: Sleep duration was inversely associated with all obesity-related outcomes, except visceral-/subcutaneous-fat-ratio. After multivariate adjustment the magnitude of associations became stronger and statistically significant for all outcomes except visceral-/subcutaneous-fat-ratio, and subcutaneous fat in women. The associations with BMI and waist circumference demonstrated the strongest associations, when comparing standardized regression coefficients. Conclusions: Shorter sleep duration were associated with higher obesity across all outcomes except visceral-/subcutaneous-fat-ratio. No specifically salient associations with local or central obesity were observed. Results suggest that poor sleep duration and obesity correlate, however, further research is needed to conclude on beneficial effects of sleep duration regarding health and weight loss.

Immunomodulatory and immunosuppressive therapies in cardiovascular disease and type 2 diabetes mellitus: A bedside-to-bench approach.

OBJECTIVE: To assess which immunosuppressive drugs have been investigated and proven efficacious in patients with cardiovascular disease (CVD) or type 2 diabetes (T2D) without preexisting immune mediated disorders to validate in vitro and animal model findings on low grade inflammation (bedside-to-bench). METHODS: Clinical trials on immunosuppressive drugs in CVD or T2D were found in PubMed. Studies on patients with preexisting immune mediated inflammatory disease were excluded. A total of 19 clinical trials testing canakinumab, anakinra, methotrexate, colchicine, hydroxychloroquine, etanercept and sulfasalazine were found. RESULTS: Canakinumab and colchicine significantly reduced the risk of CVD, whereas methotrexate did not. Sulfasalazine showed no effect on vascular function. Anakinra and hydroxychloroquine had a positive effect on glycemic control and ß-cell function in T2D. Etanercept had no effect in patients with T2D. CONCLUSION: The observed results indicate that immunosuppressive drugs specifically targeting IL-1ß hold promise for dampening CVD and T2D. These findings validate in vitro and animal models showing involvement of the IL-1-axis in the pathogenesis of CVD and T2D. The use of immunosuppressive drugs targeting the chronic inflammation in these diseases could be a possible future treatment strategy as an add-on to the existing pharmacological treatment of CVD and T2D. However, potential treatment effects, adverse events and cost-effectiveness should be carefully considered with importance for drug development.

Obesity augments the disease burden in COVID-19: Updated data from an umbrella review.

The ongoing coronavirus disease 2019 (COVID-19) pandemic calls for identification of risk factors, which may help to identify people at enhanced risk for severe disease outcomes to improve treatment and, if possible, establish prophylactic measures. This study aimed to determine whether individuals with obesity compared to individuals with normal weight have an increased risk for severe COVID-19. We conducted a systematic literature search of PubMed, Embase and Cochrane Library and critically reviewed the secondary literature using AMSTAR-2. We explored 27 studies. Findings indicate that individuals with obesity (body mass index ≥ 30 kg/m2 ), as compared to individuals without obesity, experience an increased risk for hospitalization (odds ratio [OR]: 1.40-2.45), admission to the intensive care unit (OR: 1.30-2.32), invasive mechanical ventilation (OR: 1.47-2.63), and the composite outcome 'severe outcome' (OR or risk ratio: 1.62-4.31). We found diverging results concerning death to COVID-19, but data trended towards increased mortality. Comparing individuals with obesity to individuals without obesity, findings suggested younger individuals (<60 years) experience a higher risk of severe disease compared to older individuals (≥60 years). Obesity augments the severity of COVID-19 including a tendency to increased mortality and, thus, contributes to an increased disease burden, especially among younger individuals.

Ambivalence and moral dilemmas in women's lived experiences of obesity and pregnancy: Qualitative insights for maternal lifestyle interventions.

BACKGROUND: Maternal obesity is a global health concern that is associated with significant effects on both short- and long-term health of both mother and child. However, maternal lifestyle interventions tend to focus solely on diet and physical activity in ways that disembody and disengage the social context in which women live their lives. AIMS: The aim of this study was to explore the lived experiences of maternal obesity and delve into how experiences of the body and motherhood affect women's motivation for participating in a postpartum lifestyle intervention. METHOD: A qualitative study using in-depth semi-structured interviews based on participant-generated photographs was used to allow the women to openly express their lived experiences of maternal obesity. The study emanated from a gynaecological department of a major Danish hospital, and five pregnant or postpartum women living with obesity participated. Interviews were audio recorded, transcribed and analysed using an Interpretive Phenomenological Approach. RESULTS: The analysis identified an overall theme of ambivalence and four subthemes among the participating women. The themes reflected contrasting feelings where the obese body was simultaneously an arena for aesthetic failure, functional success and moral dilemmas. Experiences of weight stigma and moral accusations in healthcare settings further increased the women's sense of ambivalence and challenged their strong desire to lose weight. CONCLUSION: This study highlights an ambivalent and vulnerable situation of maternal obesity which makes moral sensitivity towards weight and body concerns crucial to consider in future maternal health interventions. Our data suggest that an emphasis on functionality and capability rather than aesthetics and measured ideals would be useful in providing care and support in postpartum lifestyle interventions for women living with obesity.

The quality of dietary carbohydrate and fat is associated with better metabolic control in persons with type 1 and type 2 diabetes.

BACKGROUND: Diet quality is generally poor in persons with diabetes and it is unknown whether this is associated with worse glycaemic control and atherogenic lipid profile. The aim was to examine diet quality in relation to important markers of metabolic control in adults with type 1 diabetes (T1D) and type 2 diabetes (T2D). METHODS: The study was cross-sectional and included 423 (49% females) persons with T1D and 339 (29% females) persons with T2D recruited from an outpatient diabetes clinic in Denmark. Data were collected from July 2014 to January 2015. Diet quality was assessed with a food frequency questionnaire to examine eight key dietary components (carbohydrates, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, added sugar, dietary fibre, fruit and vegetables). Clinical data assessing metabolic control (haemoglobin A1c (HbA1c), total cholesterol (total C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic and diastolic blood pressure and body mass index were extracted from the electronic medical records. RESULTS: In T1D, higher intake of carbohydrates and added sugar was associated with higher HbA1c; higher fruit intake was associated with lower total C and LDL-C; and higher intake of carbohydrates and dietary fibre was associated with lower HDL-C. In T2D, higher intake of saturated fat was associated with higher total C; higher intake of added sugar was associated with higher LDL-C; and higher intake of polyunsaturated fat was associated with higher diastolic blood pressure. CONCLUSIONS: In Danish adults with T1D and T2D, both the total intake and the quality of carbohydrates and fat were associated with an unfavourable glucose regulation and lipid profile. Thus, our findings support a constant focus on diet and emphasise the need for dietary support in people with diabetes to improve diet quality, metabolic control and possibly reduce cardiovascular risk.

A reliable and record-based frailty assessment method for older medical inpatients.

PURPOSE: The comprehensive geriatric assessment (CGA) including frailty assessment is considered the gold standard of assessment in geriatric patients. The Multidimensional Prognostic Index (MPI) is a CGA-based bedside assessment tool. Older medical inpatients' medical records comprehensively describe the MPI-featured components. Consequently, MPI-based frailty assessment may be accomplished retrospectively. We found no previous studies concerning record-based MPI. We studied the reproducibility and diagnostic accuracy of a record-based MPI. METHODS: The study was designed as a fully crossed, prospective, and cross-sectional study. A total of 50 inpatients aged ≥ 75 years were included from two medical wards. Record-based MPI was assessed by two independent raters in patients who required personal assistance on a daily basis or had a Charlson Comorbidity Index (CCI) ≥ 1. In the same patients, a bedside MPI rating was performed. Inter-rater and inter-method reproducibility and diagnostic accuracy measures were calculated. RESULTS: Evaluating the inter-rater reproducibility; the mean difference was -0.02 points [95% confidence interval (CI) - 0.06 to 0.01, p = 0.20]. Intraclass correlation coefficient (ICC) was 0.71. Evaluating inter-method reproducibility; the mean difference was -0.02 (95% CI - 0.04 to 0.01, p = 0.18); ICC = 0.83. Sensitivity was 100% and specificity 80%. The areas under the receiver operating curves (ROC) was 0.92 (95% CI 0.75-1.00) and 0.77 (95% CI 0.52-1.00). CONCLUSION: The record-based MPI rating method has an acceptable inter-rater reliability, good inter-method reliability, and high agreement as compared to the bedside-rated MPI. The diagnostic accuracy seems considerable. The record-based MPI seems useful in retrospective frailty assessment among older medical inpatients.

Correction: Effect of high milk and sugar-sweetened and noncaloric soft drink intake on insulin sensitivity after 6 months in overweight and obese adults: a randomized controlled trial.

Since publication the authors noticed an error in Tables 2, 3, and 4 of the original article, where the pre-intervention values were presented by mean and SD instead of mean and SE as described in the table text. The correct tables are reproduced below where SD's are replaced by SE's.

Trends in antidiabetic drug utilization and expenditure in Denmark: A 22-year nationwide study.

AIMS: To examine the nationwide trends in antidiabetic drug utilization and expenditure in Denmark over the past 22 years. METHODS: Data on antidiabetic use and expenditure from 1996 to 2017 were retrieved from the Register of Medicinal Product Statistics. Antidiabetic drug use is reported as defined daily dose (DDD) in total counts and per 1000 inhabitants/d. Expenditure is reported as volume sold in total counts per 1000 inhabitants and as annual mean expenditure. RESULTS: Throughout the study period, the total use of antidiabetic drugs increased from 16.4 to 55.8 DDDs per 1000 inhabitants/d, while total expenditure increased from €59 to €286 m. The introduction of glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors has, since 2005, led to considerable variation in the proportional use of the different drug classes. Use of insulin and insulin analogues accounted for the majority of the cost of antidiabetic drugs, peaking at 75% in 2008; however, its proportional impact on overall antidiabetic drug expenditure decreased to ~44% in 2017. In contrast, a steep increase in GLP-1RA expenditure was observed from 2010 to 2017, reaching an annual cost of €85 m (~29% of all antidiabetic expenditure). CONCLUSION: Antidiabetic drug utilization and cost in Denmark has increased considerably over the last 22 years, in accordance with the increased incidence of type 2 diabetes and changes in treatment guidelines. The release of several novel antidiabetic drugs seems to be responsible for the increase in antidiabetic drug expenditure.

Effect of high milk and sugar-sweetened and non-caloric soft drink intake on insulin sensitivity after 6 months in overweight and obese adults: a randomized controlled trial.

BACKGROUND/OBJECTIVES: Milk contributes with saturated fat, but randomized controlled trials (RCT) on the effects of dairy on the risk of type 2 diabetes (T2D) where dairy is given as whole foods are scarce. The objective of our study was to investigate the long-term effects of semi-skimmed milk on insulin sensitivity and further to compare milk with sugar-sweetened soft drinks (SSSD). SUBJECTS/METHODS: A secondary analysis of a 6-month RCT with 60 overweight and obese subjects randomly assigned to 1 L/d of either milk (1.5 g fat/100 mL), SSSD, non-calorie soft drink (NCSD), or water was conducted. Insulin sensitivity was evaluated by oral glucose tolerance test (OGTT) and plasma free fatty acids. Second, fasting blood lipids, blood pressure, and concentration of plasminogen activator inhibitor-1 were assessed. RESULTS: There were no differences between milk, SSSD, NCSD, and water on insulin sensitivity assessed by OGTT (Matsuda Index, fasting, and area under the curve glucose, insulin and homeostasis model assessment values). SSSD increased total cholesterol compared to NCSD (P = 0.007), and triacylglycerol compared to NCSD and water (P = 0.045 and 0.045, respectively). None of the other parameters differed significantly between the groups. CONCLUSIONS: In conclusion, there were no differences in effect between intake of milk, SSSD, NCSD, and water (1 L/d) for 6-month on risk markers of T2D in overweight and obese adults. As a secondary analysis, these results need confirmation in future studies.

miRNAs in human subcutaneous adipose tissue: Effects of weight loss induced by hypocaloric diet and exercise.

OBJECTIVE: Obesity is central in the development of insulin resistance. However, the underlying mechanisms still need elucidation. Dysregulated microRNAs (miRNAs; post-transcriptional regulators) in adipose tissue may present an important link. METHODS: The miRNA expression in subcutaneous adipose tissue from 19 individuals with severe obesity (10 women and 9 men) before and after a 15-week weight loss intervention was studied using genome-wide microarray analysis. The microarray results were validated with RT-qPCR, and pathway enrichment analysis of in silico predicted targets was performed to elucidate the biological consequences of the miRNA dysregulation. Lastly, the messenger RNA (mRNA) and/or protein expression of multiple predicted targets as well as several proteins involved in lipolysis were investigated. RESULTS: The intervention led to upregulation of miR-29a-3p and miR-29a-5p and downregulation of miR-20b-5p. The mRNA and protein expression of predicted targets was not significantly affected by the intervention. However, negative correlations between miR-20b-5p and the protein levels of its predicted target, acyl-CoA synthetase long-chain family member 1, were observed. Several other miRNA-target relationships correlated negatively, indicating possible miRNA regulation, including miR-29a-3p and lipoprotein lipase mRNA levels. Proteins involved in lipolysis were not affected by the intervention. CONCLUSIONS: Weight loss influenced several miRNAs, some of which were negatively correlated with predicted targets. These dysregulated miRNAs may affect adipocytokine signaling and forkhead box protein O signaling.

Acute exercise increases circulating inflammatory markers in overweight and obese compared with lean subjects.

The primary aim of the present study was to investigate if overweight and obese compared to lean individuals displayed differences in levels of inflammatory markers in circulation, skeletal muscle (SM) and adipose tissue (AT) after acute exercise. Fifteen lean (BMI: 22.4 ± 2 kg/m(2)) and 16 overweight or obese (BMI 31.8 ± 3 kg/m(2)) individuals were included in the study. They completed 120 min of ergometer bicycling at 55-60 % of maximal heart rate. Blood samples were obtained at baseline (T = 0), after 60 (T = 60) and 120 min of exercise (T = 120), and analyzed using an ELISA method. SM and AT biopsies were obtained at T0 and T120, and mRNA expression was investigated using a Real-time RT-PCR method. Circulating IL-6, TNF-α, IL-8, and IL-15 all increased at T = 120 min (p < 0.01). Circulating IL-6 and IL-15 increased in all subjects at T = 120 min (p < 0.01), but only the increase of IL-6 was significantly higher in overweight and obese subjects (p < 0.05), and was positively correlated with body fat percentage (p < 0.01). Circulating IL-8 and TNF-α were increased in overweight and obese (p < 0.05) but not in lean subjects. Acute exercise induced an increase in IL-6 mRNA expression in SM biopsies (p < 0.05). IL-6 as well as adiponectin mRNA expression was increased in AT biopsies (p < 0.05); however, no effect of body weight was found. The findings suggest that the systemic inflammatory response to acute exercise is different in lean compared to overweight and obese subjects, with a more pronounced increase in inflammatory markers (e.g., IL-6, IL-8, and TNF-α) in overweight and obese individuals.

Increased lipolysis but diminished gene expression of lipases in subcutaneous adipose tissue of healthy young males with intrauterine growth retardation.

Intrauterine growth retardation (IUGR) is associated with a central fat distribution and risk of developing type 2 diabetes in adults when exposed to a sedentary Western lifestyle. Increased lipolysis is an early defect of metabolism in IUGR subjects, but the sites and molecular mechanisms involved are unknown. Twenty IUGR and 20 control (CON) subjects, aged 20-30 years, were studied before and after 10 days of bed rest using the glucose clamp technique combined with measurements of in vivo metabolism by microdialysis technique and blood flow by (133)Xe washout technique in subcutaneous abdominal (SCAAT) and femoral (SCFAT) adipose tissue. Additionally, mRNA expression of lipases was evaluated in biopsies from SCAAT. Lipolysis in SCAAT was substantially higher in IUGR than in CON subjects despite markedly lower mRNA expression of lipases. Blood flow was higher in IUGR compared with CON in both SCAAT and SCFAT. Whole body insulin sensitivity did not differ between groups and decreased after bed rest. After bed rest, SCAAT lipolysis remained higher in IUGR compared with CON, and SCFAT lipolysis decreased in CON but not in IUGR. Prior to the development of whole body insulin resistance, young men with IUGR are characterized by increased in vivo adipose tissue lipolysis and blood flow with a paradoxically decreased expression of lipases compared with CON, and 10 days of physical inactivity underlined the baseline findings. Subjects with IUGR exhibit primary defects in adipose tissue metabolism.

Long-term DHEA substitution in female adrenocortical failure, body composition, muscle function, and bone metabolism: a randomized trial.

CONTEXT: Adrenal derived androgens are low in women with adrenal failure. The physiological consequences of substitution therapy are uncertain. OBJECTIVE: To investigate the effects of DHEA substitution in women with adrenal failure on body composition, fuel metabolism, and inflammatory markers. DESIGN, PARTICIPANTS AND INTERVENTION: In this study, ten female patients (median age 38.5 years, range 28-52) with adrenal failure were treated with DHEA 50 mg for 6 months in a double-blind, randomized, placebo-controlled, and crossover study. The participants underwent dual-energy X-ray absorptiometry (DXA) scan, computed tomography scan of abdominal fat, indirect calorimetry, bicycle ergometry, muscle and fat biopsies, and blood samples. RESULTS: Baseline androgens were normalized to fertile range during active treatment. Anthropometric data were unaffected, but lean body mass (LBM) slightly increased compared with placebo (delta LBM (kg) placebo versus DHEA: -0.48±6.1 vs 1.6±3.4, P=0.02) with no alterations in total or abdominal fat mass. PTH increased with DHEA, but no significant changes were observed in other bone markers or in bone mineral content. The mRNA levels of markers of tissue inflammation (adiponectin, interleukin 6 (IL6), IL10, monocyte chemoattractant protein 1, and tumor necrosis factor α) in fat and muscle tissue were unaffected by DHEA treatment, as was indirect calorimetry and maximal oxygen uptake. A high proportion of self-reported seborrheic side effects were recorded (60%). CONCLUSION: In female adrenal failure, normalization of androgens with DHEA 50 mg for 6 months had no effects on muscle, fat, and bone tissue and on fuel metabolism in this small study. A small increase in LBM was observed. Treatment was associated with a high frequency of side effects.

Exercise training versus diet-induced weight-loss on metabolic risk factors and inflammatory markers in obese subjects: a 12-week randomized intervention study.

The purpose of this study was to investigate the effect of exercise training and diet-induced weight loss alone or in combination on inflammatory markers in circulation, in adipose tissue (AT) and in skeletal muscle (SM) in obese subjects. Seventy-nine obese subjects were randomized into a 12-wk intervention: 1) exercise only (EXO), 2) diet-induced weight loss using a very low energy diet (DIO), and 3) exercise and diet-induced weight-loss combined (DEX). Blood samples (metabolic and inflammatory markers) and AT and SM biopsies (mRNA expression) were collected at baseline and after 12 wk. In the EXO group the weight loss was 3.5 kg and in the DIO and DEX groups it was 12 kg in both. Vo(2max) was increased by 14-18% in the EXO and DEX groups with no changes in the DIO group. In the DIO and DEX groups, circulating levels of MCP-1, MIP-1alpha, IL-15, and IL-18 were decreased, and adiponectin was increased (P < 0.05 for all). In the EXO group, MCP-1 was decreased with 10% (P = 0.06). By combining the weight loss in all three groups, we found a correlation between the degree of weight loss and improvement in several of the inflammatory markers (P < 0.05). In AT biopsies, subjects in the DIO and DEX groups achieved a general beneficial but nonsignificant effect on the gene expression of inflammatory markers. In the EXO group, no changes in AT adipokine mRNA were found except for an increment of adiponectin (P < 0.05). In SM, the only observed change was that the gene expression of IL-6 was increased in all three groups (P < 0.05). In conclusion, rather large weight losses (>5-7%) were found to have beneficial effects on circulating inflammatory markers in these obese subjects. Aerobic exercise for 12 wk, which increased Vo(2max), was found to have no effects on circulating inflammatory markers in these obese patients. It is suggested that more intensive exercise may be necessary to affect systemic inflammation.