Abstract

BACKGROUND Chronic low-grade inflammatory profile (CLIP) is one of the pathways involved in type 2 diabetes (T2D). Currently, there is limited evidence for ameliorating effects of combined lifestyle interventions on CLIP in type 2 diabetes. We investigated whether a 13-week combined lifestyle intervention, using hypocaloric diet and resistance exercise plus high-intensity interval training with or without consumption of a protein drink, affected CLIP in older adults with T2D. METHODS In this post-hoc analysis of the PROBE study 114 adults (≥55 years) with obesity and type 2 (pre-)diabetes had measurements of C-reactive protein (CRP), pro-inflammatory cytokines interleukin (IL)-6, tumor-necrosis-factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1, anti-inflammatory cytokines IL-10, IL-1 receptor antagonist (RA), and soluble tumor-necrosis-factor receptor (sTNFR)1, adipokines leptin and adiponectin, and glycation biomarkers carboxymethyl-lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) from fasting blood samples. A linear mixed model was used to evaluate change in inflammatory biomarkers after lifestyle intervention and effect of the protein drink. Linear regression analysis was performed with parameters of body composition (by dual-energy X-ray absorptiometry) and parameters of insulin resistance (by oral glucose tolerance test). RESULTS There were no significant differences in CLIP responses between the protein and the control groups. For all participants combined, IL-1RA, leptin and adiponectin decreased after 13 weeks (p = 0.002, p < 0.001 and p < 0.001), while ratios TNF-α/IL-10 and TNF-α/IL-1RA increased (p = 0.003 and p = 0.035). CRP increased by 12 % in participants with low to average CLIP (pre 1.91 ± 0.39 mg/L, post 2.13 ± 1.16 mg/L, p = 0.006) and decreased by 36 % in those with high CLIP (pre 5.14 mg/L ± 1.20, post 3.30 ± 2.29 mg/L, p < 0.001). Change in leptin and IL-1RA was positively associated with change in fat mass (β = 0.133, p < 0.001; β = 0.017, p < 0.001) and insulin resistance (β = 0.095, p = 0.024; β = 0.020, p = 0.001). Change in lean mass was not associated with any of the biomarkers. CONCLUSION 13 weeks of combined lifestyle intervention, either with or without protein drink, reduced circulating adipokines and anti-inflammatory cytokine IL-1RA, and increased inflammatory ratios TNF-α/IL-10 and TNF-α/IL-1RA in older adults with obesity and T2D. Effect on CLIP was inversely related to baseline inflammatory status.

Abstract

Effect sizes from previously reported trials are often used to determine the meaningful change in weight in childhood obesity prevention interventions because information on clinically meaningful differences is lacking. Estimates from previous trials may be influenced by statistical significance; therefore, it is important that they have a low risk of type 1 error. A systematic review and meta-analysis were conducted to report on the design of child obesity prevention randomized controlled trials and effectiveness according to risk of type 1 error. Eighty-four randomized controlled trials were identified. A large range of assumptions were applied in the sample size calculations. The most common primary outcome was BMI, with detectable effect size differences used in sample size calculations ranging from 0.25 kg/m2 (followed up at 2 years) to 1.1 kg/m2 (at 9 months) and BMI z-score ranging from 0.1 (at 4 years) to 0.67 (at 3 years). There was no consistent relationship between low risk of type 1 error and reports of higher or lower effectiveness. Further clarity of the size of a meaningful difference in weight in childhood obesity prevention trials is required to support evaluation design and decision-making for intervention and policy. Type 1 error risk does not appear to impact effect sizes in a consistent direction.

Abstract

BACKGROUND Autoimmune thyroid disease (AITD) ranks among the most prevalent thyroid diseases, with inflammatory cytokines playing a decisive role in its pathophysiological process. However, the causal relationship between the inflammatory cytokines and AITD remains elusive. METHODS A two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal connection between AITD and 41 inflammatory cytokines. Genetic variations associated with inflammatory cytokines were sourced from the FinnGen biobank, whereas a comprehensive meta-analysis of genome-wide association studies (GWASs) yielded data on Graves' disease (GD) and Hashimoto thyroiditis. Regarding the MR analysis, the inverse variance-weighted, MR-Egger, and weighted median methods were utilized. Additionally, sensitivity analysis was conducted using MR-Egger regression, MR-pleiotropy residual sum, and outliers. RESULTS Seven causal associations were identified between inflammatory cytokines and AITD. High levels of tumor necrosis factor-β and low levels of stem cell growth factor-β were indicative of a higher risk of GD. In contrast, high levels of interleukin-12p70 (IL-12p70), IL-13, and interferon-γ and low levels of monocyte chemotactic protein-1 (MCP-1) and TNF-α suggested a higher risk of HD. Moreover, 14 causal associations were detected between AITD and inflammatory cytokines. GD increases the levels of macrophage inflammatory protein-1β, MCP-1, monokine induced by interferon-γ (MIG), interferon γ-induced protein 10 (IP-10), stromal cell-derived factor-1α, platelet-derived growth factor BB, β-nerve growth factor, IL-2ra, IL-4, and IL-17 in blood, whereas HD increases the levels of MIG, IL-2ra, IP-10, and IL-16 levels. CONCLUSION Our bidirectional MR analysis revealed a causal relationship between inflammatory cytokines and AITD. These findings offer valuable insights into the pathophysiological mechanisms underlying AITD.

Abstract

BACKGROUND Thyroid hormones have been indicated to be associated with depression, but their relationship with poststroke depression (PSD) remains controversial. Therefore, we performed a meta-analysis to explore the correlation between thyroid hormone levels in acute stroke and PSD. METHODS We searched databases for eligible studies. Standard mean differences (SMD) and 95% confidence intervals (CI) were applied to evaluate the association among levels of thyroid hormones, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), in acute stroke patients and the risk of PSD. RESULTS A total of 13 studies were included in the analysis. Compared to non-PSD patients, PSD patients had remarkably lower serum TSH and FT3 levels (TSH: SMD = -0.59, 95%CI = -1.04 to -.15, p = .009; FT3: SMD = -0.40, 95%CI = -.51 to -.30, p = .000) and higher serum FT4 levels (SMD = 0.33, 95%CI = .07-.59, p = .013). Subgroup analysis showed that there may be a more statistically significant association between FT3 and the risk of PSD compared to TSH and FT4. CONCLUSIONS Our results suggested that patients with lower serum TSH and FT3 levels as well as higher serum FT4 levels in the acute stage of stroke may be more susceptible to PSD.

Abstract

BACKGROUND Selenium-dependent deiodinases play a central role in thyroid hormone regulation and metabolism. In many European countries, insufficient selenium intake may consequently lead to adverse effects on thyroid function. In this randomised placebo-controlled double-blind study, we examined the effect of supplementation with selenium and coenzyme Q10 on thyroid hormonal status, cardiovascular (CV) mortality and health-related quality of life (Hr-QoL). METHODS Free T3, free T4, reverse T3, and TSH were determined in 414 individuals at baseline, and the effect of selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) supplementation on hormone concentrations, CV mortality and Hr-QoL was evaluated after 48 months using Short Form 36 (SF-36). Pre-intervention plasma selenium was low, mean 67 µg/L, corresponding to an estimated intake of 35 µg/day. Changes in concentrations of thyroid hormones following the intervention were assessed using T-tests, repeated measures of variance, and ANCOVA analyses. RESULTS In the total population, the group with the lowest selenium concentration at baseline presented with significantly higher levels of TSH and lower levels of fT3 as compared to subjects with the highest selenium concentration. Supplementation with selenium and coenzyme Q10 for 4 years significantly increased fT3 and rT3, decreased fT4, and diminished the increase in TSH levels compared with placebo treatment (p = 0.03, all). In the placebo group, TSH and fT4 values above the median were associated with an increase in 10-year CV mortality, as compared with the mortality rate among those with TSH and fT4 below the median (p < 0.04, both), with no difference in mortality rate according to TSH and fT4 levels in the active intervention group. Similarly, TSH > median and fT3 < median were associated with a decline in mental Hr-QoL measures vs. TSH < and fT3 > median in the placebo group during 4 years of follow-up, but this was wiped out in the active group. CONCLUSIONS Supplementation with selenium and coenzyme Q10 had a beneficial effect on thyroid hormones with respect to CV mortality and Hr-QoL outcomes. The initial deficient selenium status was associated with an impaired thyroid function and the changes in thyroid hormone levels can be explained by increased activity of deiodinases. We conclude that a substantial part of the elderly study population might suffer from suboptimal thyroidal function with adverse clinical implications due to selenium deficiency. TRIAL REGISTRATION This study was registered at ClinicalTrials.gov and has the identifier NCT01443780. Since it was not mandatory to register at the time the study began, the study has been registered retrospectively.

Abstract

BACKGROUND Thyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age. However, as uniform serum TSH reference ranges are applied across the adult lifespan, subclinical hypothyroidism (SCH) diagnosis is more likely in older people, with some individuals also being commenced treatment with levothyroxine (LT4). It is unclear whether LT4 treatment in older people with SCH is associated with adverse cardiovascular or bone health outcomes. METHODS A systematic review and meta-analysis were performed to synthesise previous studies evaluating cardiovascular and bone health outcomes in older people with SCH, comparing LT4 treatment with no treatment. PubMed, Embase, Cochrane Library, MEDLINE, and Web of Science databases were searched from inception until March 13, 2023, and studies that evaluated cardiovascular and bone health events in people with SCH over 50 years old were selected. RESULTS Six articles that recruited 3853 participants were found, ranging from 185 to 1642 participants, with the proportion of females ranging from 45 to 80%. The paucity of data resulted in analysis for those aged over 65 years only. Additionally, a study with 12,212 participants aged 18 years and older was identified; however, only data relevant to patients aged 65 years and older were considered for inclusion in the systematic review. Of these 7 studies, 4 assessed cardiovascular outcomes, 1 assessed bone health outcomes, and 2 assessed both. A meta-analysis of cardiovascular outcomes revealed a pooled hazard ratio of 0.89 (95% CI 0.71-1.12), indicating no significant difference in cardiovascular risk between older individuals with SCH treated with LT4 compared to those without treatment. Due to overlapping sub-studies, meta-analysis for bone health outcomes was not possible. CONCLUSIONS This systematic review and meta-analysis found no significant association between LT4 use and cardiovascular and bone health outcomes in SCH participants over 65 years. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42022308006.

Abstract

Major Depressive Disorder in youth is associated with obesity and adult cardiovascular disease (CVD) risk. Eating in response to emotions (emotional eating) is a potential contributing factor to this association. Although emotional eating is associated with Major Depressive Disorder in adults, findings in children and adolescents are mixed. This systematic review and meta-analysis aims to determine the association between depression and emotional eating in children and adolescents. Systematic searches were conducted in seven databases. Studies were included if the study population had a mean age of ≤18 years and assessed both depression and emotional eating using validated measures. The search generated 12,241 unique studies, of which 37 met inclusion criteria. Random-effects meta-analyses of study outcomes were performed. Thirty-seven studies (26,026 participants; mean age = 12.4 years, SD = 3.1) were included. The mean effect size was significant for both cross-sectional and longitudinal data (Hedges' g = 0.48, p < 0.0001; g = 0.37, p = 0.002, respectively), revealing a positive moderately strong association between depressive symptoms and emotional eating in youth. Among longitudinal studies, the association was stronger when depressive symptoms and emotional eating were assessed using child and adolescent self-report versus parent-report. No studies examined youth with a clinical diagnosis of depression. Meta-analyses revealed that depressive symptoms and emotional eating are positively associated in children and adolescents. However, further research in clinical samples is needed. Results raise the possibility for the importance of emotional eating in the link between depression and early CVD risk, though further examination is required to determine whether emotional eating is a potential treatment target to decrease CVD risk among adolescents with increased depression symptoms.

Abstract

BACKGROUND Anxiety and depression can seriously undermine mental health and quality of life globally. The consumption of junk foods, including ultra-processed foods, fast foods, unhealthy snacks, and sugar-sweetened beverages, has been linked to mental health. The aim of this study is to use the published literature to evaluate how junk food consumption may be associated with mental health disorders in adults. METHODS A systematic search was conducted up to July 2023 across international databases including PubMed/Medline, ISI Web of Science, Scopus, Cochrane, Google Scholar, and EMBASE. Data extraction and quality assessment were performed by two independent reviewers. Heterogeneity across studies was assessed using the I2 statistic and chi-square-based Q-test. A random/fixed effect meta-analysis was conducted to pool odds ratios (ORs) and hazard ratios (HRs). RESULTS Of the 1745 retrieved articles, 17 studies with 159,885 participants were suitable for inclusion in the systematic review and meta-analysis (seven longitudinal, nine cross-sectional and one case-control studies). Quantitative synthesis based on cross-sectional studies showed that junk food consumption increases the odds of having stress and depression (OR = 1.15, 95% CI: 1.06 to 1.23). Moreover, pooling results of cohort studies showed that junk food consumption is associated with a 16% increment in the odds of developing mental health problems (OR = 1.16, 95% CI: 1.07 to 1.24). CONCLUSION Meta-analysis revealed that consumption of junk foods was associated with an increased hazard of developing depression. Increased consumption of junk food has heightened the odds of depression and psychological stress being experienced in adult populations.

Abstract

BACKGROUND Healthy Together Victoria (HTV) was a Victorian Government initiative that sought to reduce the prevalence of overweight and obesity through targeting chronic disease risk factors including physical activity, poor diet quality, smoking, and harmful alcohol use. The intervention involved a boosted workforce of > 170 local-level staff in 12 communities; employed to deliver system activation around health and wellbeing for individuals, families and communities. A cluster randomised trial (CRT) of a systems thinking approach to obesity prevention was embedded within HTV. We present the two-year changes in overweight and obesity and associated behaviours among secondary school students across Victoria, Australia. METHODS Twenty-three geographically bounded areas were randomised to intervention (12 communities) or comparison (11 communities). Randomly selected secondary schools within each community were invited to participate in the trial in 2014 and 2016. Students in Grade 8 (aged approximately 13-15 years) and Grade 10 (aged approximately 15-16 years) at participating schools were recruited using an opt-out approach across July-September 2014 and 2016. Primary outcomes were body mass index (BMI) and waist circumference. Secondary outcomes were physical activity, sedentary behaviour, diet quality, health-related quality of life, and depressive symptoms. Linear mixed models were fit to estimate the intervention effect adjusting for child/school characteristics. RESULTS There were 4242 intervention children and 2999 control children in the final analysis. For boys, the two-year change showed improvement in intervention versus control for waist circumference (difference in change: - 2.5 cm; 95% confidence interval [CI]: - 4.6, - 0.5) and consumption of sugar-sweetened beverages per day (< 1 serve: 8.5 percentage points; 95% CI: 0.6, 16.5). For girls, there were no statistically significant differences between conditions. CONCLUSIONS HTV seemed to produce favourable changes in waist circumference and sugar-sweetened beverage consumption for boys, however, no effect on BMI was observed. Although the HTV intervention was cut short, and the period between data collection points was relatively short, the changes observed in HTV contribute to the growing evidence of whole-of-community interventions targeting childhood obesity. TRIAL REGISTRATION This trial is unregistered. The intervention itself was a policy setting delivered by government and our role was the collection of data to evaluate the effect of this natural experiment. That is, this study was not a trial from the classical point of view and we were not responsible for the intervention.

Abstract

OBJECTIVE The objective of this study was to examine the chronic effects of a 20-week exercise training program on device-assessed sleep and sleep-disordered breathing; and to determine whether participating in a session of the exercise program had effects on device-assessed sleep the subsequent night in children with overweight/obesity. METHODS A randomized clinical trial was conducted from November 2014 to June 2016. A total of 109 children (age 8-11 years) with overweight/obesity were randomized into an exercise training or control group. The exercise program included aerobic and resistance training 3 to 5 days/week. The control group participants continued their usual lifestyle. Device-assessed sleep outcomes were measured using wrist-worn actigraphy at baseline, in the middle of the exercise program (10th week), and at postintervention for seven consecutive days (24 h/day), and sleep-disordered breathing was measured via the Pediatric Sleep Questionnaire. RESULTS The exercise training program had a statistically significant effect on wake after sleep onset time (-10.8 min/day, -0.5 SDs, p = 0.040). No other chronic or acute effects (i.e., the subsequent night of attending a session of the exercise training program) were observed on the remaining sleep outcomes. CONCLUSIONS A 20-week exercise training program reduced wake after sleep onset time in children with overweight/obesity. Future randomized trials that include a sample of children with poor sleep health at baseline are needed to better appreciate the role of exercise in sleep health.