Long-term impact of the metabolic status on weight loss-induced health benefits

Background: While short-term effects of weight loss on quality of life and metabolic aspects appear to be different in metabolically healthy (MHO) and metabolically unhealthy obese (MUO), respective long-term data is still missing. Given the high relevance of long-term changes, we aimed to address these in this post-hoc analysis of the MAINTAIN trial. Methods: We analyzed 143 overweight/obese subjects (BMI >= 27 kg/m(2), age >= 18 years) before and after a 3-month weight loss program (>= 8% weight loss), after a 12-month period of a randomized weight maintenance intervention (n =121), and after another 6 months without intervention (n=112). Subjects were retrospectively grouped into MHO and MUO by the presence of metabolic syndrome and secondarily by estimates of insulin sensitivity (HOMA-IR and ISIclamp). Quality of life (QoL), blood pressure, lipids, HOMA-IR, and ISIclamp were assessed and evaluated using mixed model analyses. Results: Despite similar short- and long-term weight loss, weight loss-induced improvement of HOMA-IR was more pronounced in MUO than MHO after 3 months (MHO: 2.4[95%-CI: 1.9-2.9] vs. 1.6[1.1-2.1], p= 0.004; MUO: 3.6[3.2-4.0] vs. 2.0[1.6-2.4], p < 0.001; p= 0.03 for inter-group comparison). After 21 months, the beneficial effect was no longer seen in MHO (2.0[1.5-2.6], p= 1.0), while it remained partially preserved in MUO (2.9[2.4-3.3], p= 0.002). QueryShort-term improvements of lipid parameters were similar in both groups. However, long-term improvements of HDL-cholesterol and triglycerides were only seen in MUO (44.4[41.5-47.4] vs. 49.3[46.2, 52.3] mg/dl, p < 0.001; 176.8[158.9-194.8] vs. 138.8[119.4-158.3] mg/dl, p < 0.001, respectively) but not in MHO. Weight loss-induced improvements in the QoL and particularly the physical health status were maintained in MUO until the end of the trial, while benefits disappeared over time in MHO. Group allocation by HOMA-IR and ISIclamp revealed higher benefits for MUO mainly in parameters of the glucose metabolism and QoL. Conclusions: Our data demonstrates stronger and longer-lasting improvements of metabolism and QoL in MUO after weight loss

Incidental Detection of Internal Jugular Vein Thrombosis Secondary to Undiagnosed Benign Substernal Goiter

Internal jugular vein thrombosis is a serious event with potentially fatal outcome, where the clinical symptoms may be vague or absent. This paper refers to a rare case where routine carotid Doppler ultrasound prior to coronary artery bypass grafting (CABG) and aortic valve replacement (AVR) in a 76-year-old man, incidentally revealed thrombosis of the right internal jugular vein. Thoracic CT demonstrated an underlying, large, benign substernal multinodular goiter, mainly involving the right lobe, causing compression and displacement of the great vessels. A successful, one-stage operation including ligation of the internal jugular vein to avoid pulmonary embolism and hemithyroidectomy, combined with the scheduled CABG and AVR, was performed. This case illustrates that benign substernal goiter may be associated with asymptomatic internal jugular vein thrombosis. Carotid Doppler ultrasound should involve evaluation of the internal jugular vein concerning thrombosis as its presence may reveal space-occupying lesions in the thorax

Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans

Objective: To study the association of vaspin with glucose metabolism. Design: Cross-sectional and intervention study. Subjects and methods: The association of serum vaspin with metabolic and anthropometric characteristics was investigated in 108 volunteers. Euglycemic–hyperinsulinemic clamps (EHC) were performed in 83 of the participants. Changes of circulating vaspin levels were additionally studied in a crossover study using 300 min EHC with lipid versus saline infusion (n=10). Results: Neither glucose tolerance status nor insulin sensitivity, both as measured using EHCs and using homeostasis model assessment for insulin resistance (HOMA-IR), was significantly associated with serum vaspin in the cross-sectional study. Furthermore, there was no effect of short-term lipid-induced insulin resistance due to a 300 min intravenous lipid challenge on circulating vaspin. However, circulating vaspin levels were significantly elevated in women using oral contraceptives (OC), both compared to women without OC intake (1.17±0.26 vs 0.52±0.09 ng/ml, P=0.02) and males (1.17±0.26 vs 0.29±0.04 ng/ml, P=0.01). After exclusion of OC using females and stratification according to body mass index (BMI), a significant sexual dimorphism in subjects with a BMI <25 kg/m2 was observed (males 0.21±0.04 ng/ml versus females 0.70±0.16 ng/ml, P=0.009). Conclusion: Our results support the existence of a sexual dimorphism regarding circulating vaspin. The lack of an association of serum vaspin with HOMA-IR and M value indicates, however, no major role for vaspin concerning insulin sensitivity in nondiabetic humans

Skeletal Muscle 11beta-HSD1 Controls Glucocorticoid-Induced Proteolysis and Expression of E3 Ubiquitin Ligases Atrogin-1 and MuRF-1

Recent studies demonstrated expression and activity of the intracellular cortisone-cortisol shuttle 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in skeletal muscle and inhibition of 11beta-HSD1 in muscle cells improved insulin sensitivity. Glucocorticoids induce muscle atrophy via increased expression of the E3 ubiquitin ligases Atrogin-1 (Muscle Atrophy F-box (MAFbx)) and MuRF-1 (Muscle RING-Finger-1). We hypothesized that 11beta-HSD1 controls glucocorticoid-induced expression of atrophy E3 ubiquitin ligases in skeletal muscle. Primary human myoblasts were generated from healthy volunteers. 11beta-HSD1-dependent protein degradation was analyzed by [3H]-tyrosine release assay. RT-PCR was used to determine mRNA expression of E3 ubiquitin ligases and 11beta-HSD1 activity was measured by conversion of radioactively labeled [3H]-cortisone to [3H]-cortisol separated by thin-layer chromatography. We here demonstrate that 11beta-HSD1 is expressed and biologically active in interconverting cortisone to active cortisol in murine skeletal muscle cells (C2C12) as well as in primary human myotubes. 11beta-HSD1 expression increased during differentiation from myoblasts to mature myotubes (p<0.01), suggesting a role of 11beta-HSD1 in skeletal muscle growth and differentiation. Treatment with cortisone increased protein degradation by about 20% (p<0.001), which was paralleled by an elevation of Atrogin-1 and MuRF-1 mRNA expression (p<0.01, respectively). Notably, pre-treatment with the 11beta-HSD1 inhibitor carbenoxolone (Cbx) completely abolished the effect of cortisone on protein degradation as well as on Atrogin-1 and MuRF-1 expression. In summary, our data suggest that 11beta-HSD1 controls glucocorticoid-induced protein degradation in human and murine skeletal muscle via regulation of the E3 ubiquitin ligases Atrogin-1 and MuRF-1

Long-Term Followup with Evaluation of the Surgical and Functional Results of the Ileal Pouch Reservoir in Restorative Proctocolectomy for Ulcerative Colitis

Aims. Evaluate the early and long term surgical and functional results of the ileal pouch-reservoir (IPAA) in patients with intractable ulcerative colitis. Material and Methods. Followup of 134 consecutive patients with W-or J-ileal pouch by diseases-specific and general health (SF-36) questionnaire. In the first 44 patients, early and late followup was performed. Results. Followup was performed 7.4 years (0.5–17 years) after construction of W (n = 9) and J (n = 125) ileal pouch, which had similar results. There were 14.9% early and 43.6% late complications with 12.7% early and 19.5% late reoperations. Protecting loop-ileostomy used in 54 patients (43.9%), did not protect against complications. Thirteen reservoirs (9.8%) were resected (n = 8) or deactivated (n = 5) due to functional failure. Operation time, postoperative complications and pouchitis were determinators for reservoir failure and reduced quality of life. The functional results at followup of 44 patients at 2.5 years (0.8–6.7 years) and 11.5 years (8.2–19.2 years) were remarkably similar. Conclusions. IPAA is a good option for most patients when medication fails. 10% experience failure with inferior quality of life. Protective stoma will not reduce failure rates. After an initial time period, reservoir function will not change over time

Hepatic Energy Metabolism under the Local Control of the Thyroid Hormone System

The energy homeostasis of the organism is orchestrated by a complex interplay of energy substrate shuttling, breakdown, storage, and distribution. Many of these processes are interconnected via the liver. Thyroid hormones (TH) are well known to provide signals for the regulation of energy homeostasis through direct gene regulation via their nuclear receptors acting as transcription factors. In this comprehensive review, we summarize the effects of nutritional intervention like fasting and diets on the TH system. In parallel, we detail direct effects of TH in liver metabolic pathways with regards to glucose, lipid, and cholesterol metabolism. This overview on hepatic effects of TH provides the basis for understanding the complex regulatory network and its translational potential with regards to currently discussed treatment options of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) involving TH mimetics

Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)—study protocol for a randomized controlled trial

Background: Given the global increase in the aging population and age-related diseases, the promotion of healthy aging is one of the most crucial public health issues. This trial aims to contribute to the establishment of effective approaches to promote cognitive and brain health in older individuals with subjective cognitive decline (SCD). Presence of SCD is known to increase the risk of objective cognitive decline and progression to dementia due to Alzheimer’s disease. Therefore, it is our primary goal to determine whether spermidine supplementation has a positive impact on memory performance in this at-risk group, as compared with placebo. The secondary goal is to examine the effects of spermidine intake on other neuropsychological, behavioral, and physiological parameters. Methods: The SmartAge trial is a monocentric, randomized, double-blind, placebo-controlled phase IIb trial. The study will investigate 12 months of intervention with spermidine-based nutritional supplementation (target intervention) compared with 12months of placebo intake (control intervention). We plan to recruit 100 cognitively normal older individuals with SCD from memory clinics, neurologists and general practitioners in private practice, and the general population. Participants will be allocated to one of the two study arms using blockwise randomization stratified by age and sex with a 1:1 allocation ratio. The primary outcome is the change in memory performance between baseline and post-intervention visits (12 months after baseline). Secondary outcomes include the change in memory performance from baseline to follow-up assessment (18months after baseline), as well as changes in neurocognitive, behavioral, and physiological parameters (including blood and neuroimaging biomarkers), assessed at baseline and post-intervention. Discussion: The SmartAge trial aims to provide evidence of the impact of spermidine supplementation on memory performance in older individuals with SCD. In addition, we will identify possible neurophysiological mechanisms of action underlying the anticipated cognitive benefits. Overall, this trial will contribute to the establishment of nutrition intervention in the prevention of Alzheimer’s disease

safety, feasibility, and metabolic response

Background Intensive care unit (ICU)-acquired weakness in critically ill patients is a common and significant complication affecting the course of critical illness. Whole-body vibration is known to be effective muscle training and may be an option in diminishing weakness and muscle wasting. Especially, patients who are immobilized and not available for active physiotherapy may benefit. Until now whole-body vibration was not investigated in mechanically ventilated ICU patients. We investigated the safety, feasibility, and metabolic response of whole-body vibration in critically ill patients. Methods We investigated 19 mechanically ventilated, immobilized ICU patients. Passive range of motion was performed prior to whole-body vibration therapy held in the supine position for 15 minutes. Continuous monitoring of vital signs, hemodynamics, and energy metabolism, as well as intermittent blood sampling, took place from the start of baseline measurements up to 1 hour post intervention. We performed comparative longitudinal analysis of the phases before, during, and after intervention. Results Vital signs and hemodynamic parameters remained stable with only minor changes resulting from the intervention. No application had to be interrupted. We did not observe any adverse event. Whole-body vibration did not significantly and/or clinically change vital signs and hemodynamics. A significant increase in energy expenditure during whole-body vibration could be observed. Conclusions In our study the application of whole-body vibration was safe and feasible. The technique leads to increased energy expenditure. This may offer the chance to treat patients in the ICU with whole-body vibration. Further investigations should focus on the efficacy of whole-body vibration in the prevention of ICU- acquired weakness. Trial registration Applicability and Safety of Vibration Therapy in Intensive Care Unit (ICU) Patients. ClinicalTrials.gov NCT01286610. Registered 28 January 2011

Attachment style contributes to the outcome of a multimodal lifestyle intervention

<p>Abstract</p> <p>Background & Aims</p> <p>The long-term success of life-style interventions in the treatment of obesity is limited. Although psychological factors have been suggested to modify therapeutic effects, specifically the implications of attachment styles and the patient-therapist relationship have not been examined in detail yet.</p> <p>Methods</p> <p>This study included 44 obese patients who participated in a one-year multimodal weight-reduction program. Attachment style was analyzed by the Adult Attachment Prototype Rating (AAPR) inventory and its relation to a one-year weight reduction program was studied. The patient-therapist-relationship was assessed using the Helping Alliance Questionnaire.</p> <p>Results</p> <p>Attachment style was secure in 68% of participants and insecure (preoccupied and dismissing) in 32%. Interestingly a significantly higher weight-reduction was found in securely (SAI) compared to insecurely attached individuals (UAI; p < 0.05). This estimation correlated positively also to the quality of helping alliance (p = 0.004).</p> <p>Conclusions</p> <p>The frequency of insecure attachment in obese individuals was comparable to that of the normal population. Our data suggest a greater weight-reduction for SAI than for UAI, and the patient-therapist relationship was rated more positively. The conclusion can be drawn that a patient's attachment style plays a role in an interdisciplinary treatment program for obesity and has an influence on the effort to lose weight.</p