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1.
Article in English | MEDLINE | ID: mdl-39108088

ABSTRACT

CONTEXT: There are limited comparative studies between one anastomosis gastric bypass (OAGB) versus Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on body composition and musculoskeletal health. OBJECTIVE: To compare changes in body composition, areal bone mineral density (aBMD), muscle strength, and physical function in the first year following OAGB, RYGB and SG within a UK-based healthcare setting. METHODS: This is a secondary analysis of the BARI-LIFESTYLE trial in 119 adults (77% women; mean±SD, age: 45.9±10.3 years; BMI: 43.6±5.5 kg/m2) who underwent OAGB (n=19), RYGB (n=39) and SG (n=61). Body composition and aBMD by dual energy x-ray absorptiometry, handgrip strength, sit-to-stand (STS) test and 6-minute walking test (6MWT) were assessed pre-surgery and at 12 months post-surgery. RESULTS: OAGB, RYGB, and SG exhibited similar reductions in body weight, body fat and lean mass (within-group comparisons, p<0.001). All surgery types were associated with reductions in aBMD at the total hip, femoral neck, and lumbar spine, which were more pronounced after OAGB and RYGB compared to SG (all p<0.03), though no difference between OAGB and RYGB. Despite reductions in absolute handgrip strength, relative handgrip strength, STS test and 6MWT improved post-surgery (all p<0.02), with no differences by surgical procedure. CONCLUSION: OAGB, RYGB, and SG resulted in comparable weight loss, changes in body composition and improvements in relative muscle strength and physical function. OAGB and RYGB, compared with SG, led to greater BMD reductions at clinically relevant sites. Future long-term studies should explore whether these BMD reductions translate into a greater fracture risk.

2.
Mult Scler Relat Disord ; 90: 105808, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39128162

ABSTRACT

BACKGROUND: Environmental and lifestyle factors are associated with an increased risk of Multiple Sclerosis (MS). Metabolic syndrome (MetS) contributes to systemic inflammation, which is associated with poorer MS disease evolution. We compared persons with MS (PwMS) and controls to assess metabolic and lifestyle parameters associated with MS. METHODS: We pooled data from two prospective observational studies with the same eligibility criteria, matching PwMS and controls (1:2 ratio) by sex, age, and body mass index (BMI). We compared anthropometric, biological and lifestyle parameters, including sleep and physical activity. RESULTS: We included 53 PwMS and 106 controls with a median age of 35 years and 79% of women. PwMS had low Expanded Disability Status Scale (median 1.5). Compared to controls, PwMS had increased waist-to-hip (p<0.001) and waist-to-height (p=0.007) ratios, and practiced less physical activity (p=0.03). In regression models, lifestyle factors with the strongest factor loadings to predict central obesity were processed food consumption, and vigorous physical activity. DISCUSSION: Although both groups were matched by age, sex, and BMI, we found increased central obesity in PwMS. Even with minimal neurological impairment, PwMS practiced less physical activity. This suggests that improvement of lifestyle and metabolic parameters should be targeted in MS.

3.
Eur J Intern Med ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38987097

ABSTRACT

BACKGROUND: With increasing use of cannabis, we need to know if cannabis use and Body Mass Index (BMI) are associated. METHODS: The Coronary Artery Risk Development in Young Adults Study followed Black and White adults over 30 years with assessments every 2 to 5 years in four centers in the USA. We assessed self-reported current and computed cumulative cannabis exposure at every visit, and studied associations with BMI, adjusted for relevant covariables in mixed longitudinal models. We also applied marginal structural models (MSM) accounting for the probability of having stopped cannabis over the last 5 years. RESULTS: At the Year 30 visit, 1,912 (58 %) identified as women and 1,600 (48 %) as Black, mean age was 56 (SD 2) years. While 2,849 (85 %) had ever used cannabis, 479 (14 %) currently used cannabis. Overall, participants contributed to 35,882 individual visits over 30 years. In multivariable adjusted models, mean BMI was significantly lower in daily cannabis users (26.6 kg/m2, 95 %CI 26.3 to 27.0) than in participants without current use (27.7 kg/m2, 95 %CI 27.5 to 27.9, p < 0.001). Cumulative cannabis use was not associated with BMI. The MSM showed no change in BMI when stopping cannabis use over a 5-year period (ß=0.2 kg/m2 total, 95 %CI -0.2 to 0.6). CONCLUSIONS: Current cannabis use was associated with lower BMI, but cumulative cannabis use and cessation were not. This suggests that recreational cannabis use may not lead to clinically relevant changes in BMI and that the association between current cannabis use and lower BMI is likely due to residual confounding.

4.
Nutrients ; 16(11)2024 May 23.
Article in English | MEDLINE | ID: mdl-38892522

ABSTRACT

Observational studies have shown a relationship between eating patterns and chronotypes with metabolic health in the general population and in healthy pregnancies. Data are lacking in the postpartum period, which is characterized by an externally driven misalignment of sleep and food intake. We investigated the associations between eating patterns, chronotypes, and metabolic health in the early postpartum period in women who had gestational diabetes mellitus (GDM). We prospectively included 313 women who completed their 6-8 weeks postpartum visit between January 2021 and March 2023 at the Lausanne University Hospital. Women filled questionnaires on the timing of food intake, sleep (a shortened Pittsburgh Sleep Quality Questionnaire), and the chronotype (the Morningness-Eveningness Questionnaire) and underwent HbA1c and fasting plasma glucose measurements. After adjustments for weight, sleep quality, or breastfeeding, the later timing of the first and last food intake were associated with higher fasting plasma glucose and HbA1c levels 6-8 weeks postpartum (all p ≤ 0.046). A higher number of breakfasts per week and longer eating durations were associated with lower fasting plasma glucose levels (all p ≤ 0.028). The chronotype was not associated with metabolic health outcomes. Eating patterns, but not the chronotype, were associated with worsened metabolic health in the early postpartum period in women with previous GDM.


Subject(s)
Blood Glucose , Diabetes, Gestational , Feeding Behavior , Glycated Hemoglobin , Postpartum Period , Humans , Female , Pregnancy , Adult , Blood Glucose/metabolism , Feeding Behavior/physiology , Prospective Studies , Glycated Hemoglobin/metabolism , Glycated Hemoglobin/analysis , Surveys and Questionnaires , Circadian Rhythm/physiology , Fasting , Eating/physiology , Sleep Quality , Sleep/physiology , Chronotype
5.
J Clin Endocrinol Metab ; 109(3): e1167-e1174, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-37862463

ABSTRACT

CONTEXT: With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown. OBJECTIVE: To investigate incidence and determinants of spontaneous normalization of TSH levels in older adults with subclinical hypothyroidism. DESIGN: Pooled data were used from the (1) pretrial population and (2) in-trial placebo group from 2 randomized, double-blind, placebo-controlled trials (Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism Trial and Institute for Evidence-Based Medicine in Old Age thyroid 80-plus thyroid trial). SETTING: Community-dwelling 65+ adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom. PARTICIPANTS: The pretrial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free T4 within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included. MAIN OUTCOME MEASURES: Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization. RESULTS: In the pretrial phase, TSH levels normalized in 60.8% of participants in a median follow-up of 1 year. In the in-trial phase, levels normalized in 39.9% of participants after 1 year of follow-up. Younger age, female sex, lower initial TSH level, higher initial free T4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization. CONCLUSION: Because TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01660126 and Netherlands Trial Register, NTR3851.


Subject(s)
Hypothyroidism , Thyrotropin , Humans , Female , Aged , Thyrotropin/therapeutic use , Incidence , Hypothyroidism/drug therapy , Hypothyroidism/epidemiology , Thyroxine/therapeutic use
6.
Cell Rep Methods ; 3(8): 100545, 2023 08 28.
Article in English | MEDLINE | ID: mdl-37671030

ABSTRACT

Wearable biosensors and smartphone applications can measure physiological variables over multiple days in free-living conditions. We measure food and drink ingestion, glucose dynamics, physical activity, heart rate (HR), and heart rate variability (HRV) in 25 healthy participants over 14 days. We develop a Bayesian inference framework to learn personal parameters that quantify circadian rhythms and physiological responses to external stressors. Modeling the effects of ingestion events on glucose levels reveals that slower glucose decay kinetics elicit larger postprandial glucose spikes, and we uncover a circadian baseline rhythm for glucose with high amplitudes in some individuals. Physical activity and circadian rhythms explain as much as 40%-65% of the HR variance, whereas the variance explained for HRV is more heterogeneous across individuals. A more complex model incorporating activity, HR, and HRV explains up to 15% of additional glucose variability, highlighting the relevance of integrating multiple biosensors to better predict glucose dynamics.


Subject(s)
Circadian Rhythm , Wearable Electronic Devices , Humans , Bayes Theorem , Exercise , Glucose
7.
Rev Med Suisse ; 19(829): 1072-1077, 2023 May 31.
Article in French | MEDLINE | ID: mdl-37260202

ABSTRACT

The management of a patient with type 2 diabetes is well known and is the subject of numerous studies. Protein-calorie malnutrition, on the other hand, is an entity that is still under-diagnosed and under-treated. When artificial nutrition is introduced, glucose homeostasis can be disturbed in case of (pre-)diabetes. To date, few recommendations based on expert opinion exist on the management of diabetes after the introduction of enteral or parenteral nutrition. This article proposes an algorithm for the management of type 2 diabetes when oral nutritional supplements are introduced.


La prise en charge d'un patient diabétique de type 2 est bien connue et fait l'objet de nombreuses études. La dénutrition protéino-calorique quant à elle est une entité encore sous-diagnostiquée et sous-traitée. Lors de la mise en place d'une nutrition artificielle, l'équilibre glycémique peut être perturbé en cas de prédiabète ou de diabète. À ce jour, quelques recommandations basées sur des avis d'experts existent sur la prise en charge du diabète après la mise en place d'une nutrition entérale ou parentérale. Cet article propose un algorithme de prise en charge du diabète de type 2, lors de l'introduction de suppléments nutritifs oraux.


Subject(s)
Diabetes Mellitus, Type 2 , Malnutrition , Humans , Enteral Nutrition , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/therapy , Nutritional Status , Parenteral Nutrition , Malnutrition/therapy
8.
Rev Med Suisse ; 19(819): 576-580, 2023 Mar 22.
Article in French | MEDLINE | ID: mdl-36950789

ABSTRACT

The ketogenic diet, which consists of reduced carbohydrate intake and increased fat intake, is a recognized treatment option for children with intractable epilepsy. This diet is now receiving renewed interest from physicians and researchers because of its potential therapeutic effect in other diseases, such as neurodegenerative diseases, metabolic syndrome or cancer. Since cancer is one of the major public health challenges, complementary approaches to improve the efficacy of standard anti-cancer therapies are the subject of much research. This article reviews the place of the ketogenic diet as a complementary therapy in cancer, the scientific evidence and possible practical aspects of such an approach.


Le régime cétogène vise à réduire l'apport nutritionnel d'hydrates de carbone en augmentant les lipides. Ce régime est une option thérapeutique reconnue, en particulier chez les enfants souffrant d'épilepsie réfractaire. Il fait aujourd'hui l'objet d'un regain d'intérêt de la part des médecins et des chercheurs, en raison de son potentiel effet thérapeutique dans d'autres pathologies comme certaines maladies neurodégénératives, le syndrome métabolique ou même le cancer. Le cancer étant l'un des grands défis de santé publique, les approches complémentaires pour améliorer l'efficacité des thérapies anticancéreuses standards font l'objet de nombreuses recherches. Cet article fait le point sur la place du régime cétogène comme thérapie complémentaire dans le cancer, les évidences scientifiques et les éventuels aspects pratiques d'une telle approche.


Subject(s)
Complementary Therapies , Diet, Ketogenic , Metabolic Syndrome , Neoplasms , Child , Humans
9.
Cancers (Basel) ; 15(6)2023 Mar 21.
Article in English | MEDLINE | ID: mdl-36980767

ABSTRACT

The advantages of prehabilitation in surgical oncology are unclear. This systematic review aims to (1) evaluate the latest evidence of preoperative prehabilitation interventions on postoperative outcomes after gastrointestinal (GI) cancer surgery and (2) discuss new potential therapeutic targets as part of prehabilitation. Randomized controlled trials published between January 2017 and August 2022 were identified through Medline. The population of interest was oncological patients undergoing GI surgery. Trials were considered if they evaluated prehabilitation interventions (nutrition, physical activity, probiotics and symbiotics, fecal microbiota transplantation, and ghrelin receptor agonists), alone or combined, on postoperative outcomes. Out of 1180 records initially identified, 15 studies were retained. Evidence for the benefits of unimodal interventions was limited. Preoperative multimodal programs, including nutrition and physical activity with or without psychological support, showed improvement in postoperative physical performance, muscle strength, and quality of life in patients with esophagogastric and colorectal cancers. However, there was no benefit for postoperative complications, hospital length of stay, hospital readmissions, and mortality. No trial evaluated the impact of fecal microbiota transplantation or oral ghrelin receptor agonists. Further studies are needed to confirm our findings, identify patients who are more likely to benefit from surgical prehabilitation, and harmonize interventions.

10.
Age Ageing ; 52(1)2023 01 08.
Article in English | MEDLINE | ID: mdl-36721961

ABSTRACT

BACKGROUND: loss of skeletal muscle function, strength and mass is common in older adults, with important socioeconomic impacts. Subclinical hypothyroidism is common with increasing age and has been associated with reduced muscle strength. Yet, no randomized placebo-controlled trial (RCT) has investigated whether treatment of subclinical hypothyroidism affects muscle function and mass. METHODS: this is an ancillary study within two RCTs conducted among adults aged ≥65 years with persistent subclinical hypothyroidism (thyrotropin (TSH) 4.60-19.99 mIU/l, normal free thyroxine). Participants received daily levothyroxine with TSH-guided dose adjustment or placebo and mock titration. Primary outcome was gait speed at final visit (median 18 months). Secondary outcomes were handgrip strength at 1-year follow-up and yearly change in muscle mass. RESULTS: we included 267 participants from Switzerland and the Netherlands. Mean age was 77.5 years (range 65.1-97.1), 129 (48.3%) were women, and their mean baseline TSH was 6.36 mIU/l (standard deviation [SD] 1.9). At final visit, mean TSH was 3.8 mIU/l (SD 2.3) in the levothyroxine group and 5.1 mIU/l (SD 1.8, P < 0.05) in the placebo group. Compared to placebo, participants in the levothyroxine group had similar gait speed at final visit (adjusted between-group mean difference [MD] 0.01 m/s, 95% confidence interval [CI] -0.06 to 0.09), similar handgrip strength at one year (MD -1.22 kg, 95% CI -2.60 to 0.15) and similar yearly change in muscle mass (MD -0.15 m2, 95% CI -0.49 to 0.18). CONCLUSIONS: in this ancillary analysis of two RCTs, treatment of subclinical hypothyroidism did not affect muscle function, strength and mass in individuals 65 years and older.


Subject(s)
Hypothyroidism , Thyroid Hormones , Aged , Aged, 80 and over , Female , Humans , Male , Hypothyroidism/diagnosis , Hypothyroidism/drug therapy , Muscle, Skeletal , Thyroid Hormones/therapeutic use , Thyrotropin , Thyroxine/therapeutic use
11.
J Clin Endocrinol Metab ; 108(8): 2087-2098, 2023 Jul 14.
Article in English | MEDLINE | ID: mdl-36658456

ABSTRACT

CONTEXT: Humans respond profoundly to changes in diet, while nutrition and environment have a great impact on population health. It is therefore important to deeply characterize the human nutritional responses. OBJECTIVE: Endocrine parameters and the metabolome of human plasma are rapidly responding to acute nutritional interventions such as caloric restriction or a glucose challenge. It is less well understood whether the plasma proteome would be equally dynamic, and whether it could be a source of corresponding biomarkers. METHODS: We used high-throughput mass spectrometry to determine changes in the plasma proteome of i) 10 healthy, young, male individuals in response to 2 days of acute caloric restriction followed by refeeding; ii) 200 individuals of the Ely epidemiological study before and after a glucose tolerance test at 4 time points (0, 30, 60, 120 minutes); and iii) 200 random individuals from the Generation Scotland study. We compared the proteomic changes detected with metabolome data and endocrine parameters. RESULTS: Both caloric restriction and the glucose challenge substantially impacted the plasma proteome. Proteins responded across individuals or in an individual-specific manner. We identified nutrient-responsive plasma proteins that correlate with changes in the metabolome, as well as with endocrine parameters. In particular, our study highlights the role of apolipoprotein C1 (APOC1), a small, understudied apolipoprotein that was affected by caloric restriction and dominated the response to glucose consumption and differed in abundance between individuals with and without type 2 diabetes. CONCLUSION: Our study identifies APOC1 as a dominant nutritional responder in humans and highlights the interdependency of acute nutritional response proteins and the endocrine system.


Subject(s)
Diabetes Mellitus, Type 2 , Proteome , Humans , Male , Proteomics , Glucose , Caloric Restriction
12.
Obesity (Silver Spring) ; 31 Suppl 1: 85-95, 2023 02.
Article in English | MEDLINE | ID: mdl-36239695

ABSTRACT

OBJECTIVE: This study explored the impact of time-restricted eating (TRE) versus standard dietary advice (SDA) on bone health. METHODS: Adults with ≥1 component of metabolic syndrome were randomized to TRE (ad libitum eating within 12 hours) or SDA (food pyramid brochure). Bone turnover markers and bone mineral content/density by dual energy x-ray absorptiometry were assessed at baseline and 6-month follow-up. Statistical analyses were performed in the total population and by weight loss response. RESULTS: In the total population (n = 42, 76% women, median age 47 years [IQR: 31-52]), there were no between-group differences (TRE vs. SDA) in any bone parameter. Among weight loss responders (≥0.6 kg weight loss), the bone resorption marker ß-carboxyterminal telopeptide of type I collagen tended to decrease after TRE but increase after SDA (between-group differences p = 0.041), whereas changes in the bone formation marker procollagen type I N-propeptide did not differ between groups. Total body bone mineral content decreased after SDA (p = 0.028) but remained unchanged after TRE (p = 0.31) in weight loss responders (between-group differences p = 0.028). Among nonresponders (<0.6 kg weight loss), there were no between-group differences in bone outcomes. CONCLUSIONS: TRE had no detrimental impact on bone health, whereas, when weight loss occurred, it was associated with some bone-sparing effects compared with SDA.


Subject(s)
Bone Density , Bone and Bones , Adult , Humans , Female , Middle Aged , Male , Bone Density/physiology , Absorptiometry, Photon , Weight Loss
13.
Obes Facts ; 15(6): 762-773, 2022.
Article in English | MEDLINE | ID: mdl-36310013

ABSTRACT

INTRODUCTION: Lipedema is a poorly known condition. Diagnosis is based almost exclusively on clinical criteria, which may be subjective and not always reliable. This study aimed to investigate regional body composition (BC) by dual-energy X-ray absorptiometry (DXA) in patients with lipedema and healthy controls and to determine cut-off values of fat mass (FM) indices to provide an additional tool for the diagnosis and staging of this condition. METHODS: This study is a single-center case-control study performed at Lausanne University Hospital, Switzerland. Women with clinically diagnosed lipedema underwent regional BC assessment by DXA. The control group without clinical lipedema was matched for age and body mass index (BMI) at a ratio of 1:2 and underwent similar examination. Regional FM (legs, arms, legs and arms, trunk, android and gynoid FM) was measured in (kg) and divided by FM index (FMI) (kg/m2) and total FM (kg). The trunk/legs and android/gynoid ratios were calculated. For all indices of FM distribution showing a significant difference between cases and controls, we defined the receiver operating characteristic (ROC) curves, calculating the area under the curve (AUC), sensitivity, specificity, and Youden's index. Types and stages of lipedema were compared in terms of FM indices. Correlation analyses between all FM distribution indices and lipedema stages were performed. RESULTS: We included 222 women (74 with lipedema and 148 controls). Overall, the mean age was 41 years (standard deviation [SD] 11), and mean BMI was 30.9 kg/m2 (SD 7.6). A statistically significant difference was observed for all DXA-derived indices of FM distribution between groups, except for arm FM indices. The ROC curve analysis of leg FM/total FM, as a potential indicator of lipedema, resulted in an AUC of 0.90 (95% confidence interval 0.86-0.94). According to Youden's index, optimal cut-off value identifying lipedema was 0.384. Sensitivity and specificity were 0.95 and 0.73, respectively. We found no significant differences between lipedema types and stages in terms of FM indices, nor significant correlations between the latter and lipedema stages. DISCUSSION/CONCLUSION: BC assessment by DXA, and particularly calculation of the leg FM/total FM index, is a simple tool that may help clinicians rule out lipedema in doubtful cases.


Subject(s)
Lipedema , Humans , Female , Adult , Absorptiometry, Photon , Lipedema/diagnostic imaging , Case-Control Studies , Body Composition , Body Mass Index
14.
Clin Nutr ; 41(11): 2455-2463, 2022 11.
Article in English | MEDLINE | ID: mdl-36215865

ABSTRACT

BACKGROUND & AIMS: The main source of error in body composition assessment of bedridden patients by bioelectrical impedance analysis (BIA) is the electrode inadequacy and placement. As electrocardiogram (ECG) electrodes are often used for BIA measurements, this study aimed to compare three of them with a reference BIA electrode. METHODS: BIA was performed sequentially on 24 healthy subjects in the supine position, using 3 different ECG electrodes (3M® Red Dot® 2330; Ambu® BlueSensor 2300; Ambu® BlueSensor SU-00-C) and the reference electrode (Bianostic AT®) for the BIA device (Nutriguard-M®, Data Input, Germany). Resistance (R), reactance (Xc), phase angle (PhA), appendicular skeletal muscle index (ASMI), fat-free mass index (FFMI) and fat mass percentage (FM%) obtained with the different electrodes were compared using Bland-Altman plots, repeated measures one-way ANOVA and paired t-test. Patient characteristics potentially involved in BIA measurement differences were assessed using linear regression analysis. RESULTS: The study population consisted of 9 men and 15 women, 33% and 47% of whom were overweight, respectively. The measured R was within the physiological range for all men (428-561 Ω) and women (472-678 Ω), regardless of the type of electrodes used. Compared to the reference electrode, the 3M® Red Dot® 2330 and Ambu® BlueSensor SU-00-C electrodes gave significantly different Xc and PhA values, but only the Ambu® BlueSensor SU-00-C gave significantly different ASMI, FFMI and FM% at 50 kHz, with biases of -0.2 kg/m2, -0.3 kg/m2 and +1.4%, respectively. The higher the current frequency, the lower was the Xc and PhA measured by the Ambu® BlueSensor SU-00-C compared to the reference electrode. These measurement differences seemed mainly due to the too small gel area of the Ambu® BlueSensor SU-00-C (154 mm2) compared to the reference electrode (1311 mm2). CONCLUSIONS: The use of electrodes with small gel area affects BIA measurement in the supine position, especially when PhA is used as an indicator of the nutritional status. Therefore, it is essential to specify the type of electrodes and carry out comparative tests before changing consumables for body composition assessment, to ensure BIA measurement reliability in clinical and research settings.


Subject(s)
Body Composition , Male , Humans , Female , Electric Impedance , Reproducibility of Results , Supine Position , Body Composition/physiology , Electrodes , Body Mass Index , Absorptiometry, Photon
15.
J Intern Med ; 292(6): 892-903, 2022 12.
Article in English | MEDLINE | ID: mdl-35894851

ABSTRACT

BACKGROUND: Antithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed whether older adults with subclinical hypothyroidism (SHypo) caused by autoimmune thyroid disease derive more benefits from levothyroxine treatment (LT4). OBJECTIVE: To determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies. METHODS: We pooled individual participant data from two RCTs, Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism and IEMO 80+. Participants with persistent SHypo were randomly assigned to receive LT4 or placebo. We compared the effects of LT4 versus placebo in participants with and without anti-thyroid peroxidase (TPO) at baseline. The two primary outcomes were 1-year change in Hypothyroid Symptoms and Tiredness scores on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire. RESULTS: Among 660 participants (54% women) ≥65 years, 188 (28.5%) had positive anti-TPO. LT4 versus placebo on Hypothyroid Symptoms lead to an adjusted between-group difference of -2.07 (95% confidence interval: -6.04 to 1.90) for positive antibodies versus 0.89 (-1.76 to 3.54) for negative antibodies (p for interaction = 0.31). Similarly, there was no treatment effect modification by baseline antibody status for Tiredness scores-adjusted between-group difference 1.75 (-3.60 to 7.09) for positive antibodies versus 1.14 (-1.90 to 4.19) for negative antibodies (p for interaction = 0.98). Positive anti-TPO were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment. CONCLUSIONS: Among older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4.


Subject(s)
Hypothyroidism , Thyroxine , Female , Humans , Aged , Male , Thyroxine/therapeutic use , Randomized Controlled Trials as Topic , Hypothyroidism/drug therapy , Hormone Replacement Therapy
16.
Clin Nutr ; 41(7): 1591-1599, 2022 07.
Article in English | MEDLINE | ID: mdl-35671611

ABSTRACT

BACKGROUND & AIMS: The new indirect calorimeter developed in the framework of the ICALIC project was first evaluated in ventilation mode. This second phase aimed to compare its ease of use and precision with another commonly used device in spontaneously breathing adult patients using a canopy hood or a face mask. METHODS: The time required to measure resting energy expenditure (REE) with Q-NRG® in canopy and face mask mode was compared with Quark RMR® in canopy mode by sequential measurements in 45 and 40 spontaneously breathing adult patients, respectively. Their precision was assessed at different time intervals, using coefficients of variation (CV%) and repeated measures one-way ANOVA. Agreement between the two devices was evaluated by correlation coefficients, Bland-Altman plots, and paired t-test. Patients' characteristics potentially affecting the measurement were assessed using linear regression analysis. RESULTS: REE measurement with Q-NRG® was faster than Quark RMR® (19.7 ± 2.9 min vs 24.5 ± 4.3 min, P < 0.001). In canopy mode, Q-NRG® gave values similar to Quark RMR®, with 73% of patients achieving a steady state (CV% <10%) within the 5-15 min interval. In face mask mode, Q-NRG® was less stable than Quark RMR® in canopy mode, and steady state was achieved in only 40% of the patients within the 5-15 min interval. Correlation between the two devices was stronger when Q-NRG® was used in canopy than in face mask mode, with Pearson coefficients of 0.96 and 0.86, respectively. Compared to Quark RMR® in canopy mode, systematic bias±1.96∗SD with Q-NRG® was -14 ± 236 kcal/day in canopy and 73 ± 484 kcal/day in face mask mode. Q-NRG® in face mask mode overestimated REE by 150 ± 51 kcal/day in men compared to Quark RMR® in canopy mode. CONCLUSIONS: Q-NRG® in canopy mode made it possible to save at least 5 min compared to Quark RMR® while maintaining the same measurement precision. However, its use in face mask mode could lead to REE overestimation in men and, therefore, should not be recommended in the clinical setting. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT03947294.


Subject(s)
Energy Metabolism , Masks , Adult , Analysis of Variance , Basal Metabolism , Calorimetry, Indirect , Humans , Male , Reproducibility of Results , Rest
17.
Bone ; 161: 116404, 2022 08.
Article in English | MEDLINE | ID: mdl-35381390

ABSTRACT

The effect of levothyroxine (LT4) therapy for subclinical hypothyroidism (SHypo) on appendicular bone geometry and volumetric density has so far not been studied. In a nested study within the randomized, placebo-controlled Thyroid Hormone Replacement for Subclinical Hypothyroidism (TRUST) trial, we assessed the effect of LT4 therapy on bone geometry as measured by peripheral quantitative computed tomography (pQCT). In the TRUST trial, community-dwelling adults aged ≥65 years with SHypo were randomized to LT4 with dose titration vs. placebo with mock titration. We analyzed data from participants enrolled at the TRUST site in Bern, Switzerland who had bone pQCT measured at baseline and at 1 to 2 years follow-up. The primary outcomes were the annual percentage changes of radius and tibia epi- and diaphysis bone geometry (total and cortical cross-sectional area (CSA) and cortical thickness), and of volumetric bone mineral density (bone mineral content (BMC) and total, trabecular and cortical volumetric bone mineral density (vBMD)). We performed linear regression of the annual percentage changes adjusted for sex, LT4 dose at randomization and muscle cross-sectional area. The 98 included participants had a mean age of 73.9 (±SD 5.4) years, 45.9% were women, and 12% had osteoporosis. They were randomized to placebo (n = 48) or LT4 (n = 50). Annual changes in BMC and vBMD were similar between placebo and LT4-treated groups, without significant difference in bone geometry or volumetric bone mineral density changes, neither at the diaphysis, nor at the epiphysis. For example, in the placebo group, epiphyseal BMC (radius) decreased by a mean 0.2% per year, with a similar decrease of 0.5% per year in the LT4 group (between-group difference in %ΔBMC 0.3, 95% CI -0.70 to 1.21, p = 0.91). Compared to placebo, LT4 therapy for an average 14 months had no significant effect on bone mass, bone geometry and volumetric density in older adults with subclinical hypothyroidism. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov numbers NCT01660126 (TRUST Thyroid trial) and NCT02491008 (Skeletal outcomes).


Subject(s)
Hypothyroidism , Thyroxine , Aged , Bone Density/physiology , Bone and Bones , Female , Humans , Hypothyroidism/drug therapy , Male , Radius/physiology , Thyroxine/pharmacology , Thyroxine/therapeutic use , Tibia
18.
Rev Med Suisse ; 18(772): 445-452, 2022 Mar 09.
Article in French | MEDLINE | ID: mdl-35266345

ABSTRACT

Since their discovery more than a century ago to this day, vitamins went from misunderstood molecules with mysterious properties to fundamental components with undoubted clinical implications. Despite the scientific progresses in the understanding of their physiopathological role, vitamins raise to this day multiple interrogations in clinical practice. This article aims at answering questions that are frequently encountered in the outpatient setting regarding vitamin deficiencies: who to screen ? At what moment ? By which test ? How to interpret the results ? How to supplement ? By answering these questions, we hope to provide the general practitioners with a pragmatic tool to guide them in the management of issues related to vitamins.


Depuis leur découverte il y a plus d'un siècle à aujourd'hui, les vitamines sont passées de molécules méconnues et aux propriétés mystérieuses à des composants primordiaux et aux implications cliniques certaines. Malgré les progrès scientifiques dans la compréhension de leur rôle physiopathologique, les vitamines suscitent encore de nombreuses interrogations en pratique clinique. Cet article s'efforce de répondre aux questions fréquem ment rencontrées en médecine ambulatoire portant sur les carences vitaminiques: qui dépister ? À quel moment ? Par quel test ? Comment interpréter les résultats ? Comment supplémenter ? En répondant à ces questions, nous espérons fournir au médecin de premier recours un outil pragmatique pour l'orienter dans la prise en charge des problématiques vitaminiques.


Subject(s)
Avitaminosis , General Practitioners , Adult , Avitaminosis/diagnosis , Avitaminosis/epidemiology , Avitaminosis/etiology , Dietary Supplements , Humans , Outpatients , Vitamins/therapeutic use
19.
J Clin Endocrinol Metab ; 107(6): e2339-e2347, 2022 05 17.
Article in English | MEDLINE | ID: mdl-35218666

ABSTRACT

CONTEXT: Subclinical thyroid dysfunction and anemia are common disorders, and both have increasing prevalence with advancing age. OBJECTIVE: The aim of this study was to assess whether levothyroxine treatment leads to a rise in hemoglobin levels in older persons with subclinical hypothyroidism. METHODS: This preplanned combined analysis of 2 randomized controlled trials included community-dwelling persons aged 65 years and older with subclinical hypothyroidism who were randomly assigned to levothyroxine or placebo treatment. The levothyroxine dose was periodically titrated aiming at thyroid stimulating hormone (TSH) level within the reference range, with mock titrations in the placebo group. The main outcome measure was the change in hemoglobin level after 12 months. RESULTS: Analyses included 669 participants (placebo n = 337, levothyroxine n = 332) with a median age of 75 years (range, 65-97) and mean baseline hemoglobin of 13.8 ±â€…1.3 g/dL. Although levothyroxine treatment resulted in a reduction in TSH from baseline after 12 months of follow-up compared with placebo, the change in hemoglobin level was not different between the levothyroxine and the placebo groups (-0.03 g/dL [95% CI, -0.16 to 0.11]). Similar results were found in stratified analyses including sex, age, or TSH levels. No difference in change of hemoglobin levels after 12 months was identified in 69 participants with anemia at baseline (-0.33 g/dL [95% CI, -0.87 to 0.21]). CONCLUSION: In persons aged 65 years and older with subclinical hypothyroidism, treatment with levothyroxine does not lead to a rise in hemoglobin levels, regardless of the presence of anemia.


Subject(s)
Hypothyroidism , Thyroxine , Aged , Aged, 80 and over , Double-Blind Method , Hemoglobins , Humans , Hypothyroidism/drug therapy , Randomized Controlled Trials as Topic , Thyrotropin/therapeutic use , Thyroxine/therapeutic use
20.
J Neuroinflammation ; 19(1): 42, 2022 Feb 07.
Article in English | MEDLINE | ID: mdl-35130916

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS) commonly affecting young adults. There is increasing evidence that environmental factors are important in the development and course of MS. The metabolic syndrome (MetS) which comprises dyslipidemia has been associated with a worse outcome in MS disease. Furthermore, the lipid-lowering drug class of statins has been proposed to improve MS disease course. However, cholesterol is also rate-limiting for myelin biogenesis and promotes remyelination in MS animal models. Thus, the impact of circulating blood cholesterol levels during the disease remains debated and controversial. METHODS: We assessed the role of circulating cholesterol on the murine model of MS, the experimental autoimmune encephalomyelitis (EAE) disease using two different approaches: (1) the mouse model of familial hypercholesterolemia induced by low-density lipoprotein receptor (LDLr) deficiency, and (2) the use of the monoclonal anti-PCSK9 neutralizing antibody alirocumab, which reduces LDLr degradation and consequently lowers blood levels of cholesterol. RESULTS: Elevated blood cholesterol levels induced by LDLr deficiency did not worsen clinical symptoms of mice during EAE. In addition, we observed that the anti-PCSK9 antibody alirocumab did not influence EAE disease course, nor modulate the immune response in EAE. CONCLUSIONS: These findings suggest that blood cholesterol level has no direct role in neuro-inflammatory diseases and that the previously shown protective effects of statins in MS are not related to circulating cholesterol.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypercholesterolemia , Multiple Sclerosis , Animals , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypercholesterolemia/metabolism , Mice , Neuroinflammatory Diseases
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