Breast adiposity: Menopausal status impact and its influence on glycemic and anthropometric metabolic parameters.

CONTEXT: Ectopic fat depots are related to the deregulation of energy homeostasis, leading to diseases related to obesity and metabolic syndrome (MS). Despite significant changes in body composition over women's lifespan, little is known about the role of breast adipose tissue (BrAT) and its possible utilization as an ectopic fat depot in women of different menopausal statuses. OBJECTIVE: We aimed to assess the relationship between BrAT and metabolic glycemic and lipid profiles and body composition parameters in adult women. METHODS: In this cross-sectional study, we enrolled adult women undergoing routine mammograms to perform history and physical examination, body composition assessment, semi-automated assessment of breast adiposity (BA) from mammograms and fasting blood collection for biochemical analysis. Correlations and multivariate regression analysis were used to examine the associations of the BA with metabolic and body composition parameters. RESULTS: Of the 101 participants included in the final analysis, 76.2% were in menopause, and 23.8% were in premenopause. The BA was positively related with fasting plasma glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, body mass index, waist circumference, body fat percentage, abdominal visceral and subcutaneous fat when adjusted for age among women in postmenopause. Also, the BA was an independent predictor of hyperglycemia and metabolic syndrome. These associations were not present among women in premenopause. CONCLUSION: The BA was related to different adverse body composition and metabolic factors in women in postmenopause. The results suggest that there might be a relevant BrAT endocrine role during menopause, whose mechanisms are yet to be clarified, which thus opens up research perspectives on the subject as well as on clinical settings.

Long-term lifestyle intervention can reduce the development of type 2 diabetes mellitus in subjects with prediabetes: A systematic review and meta-analysis.

AIMS: To evaluate the effectiveness of intensive lifestyle intervention (ILI) on the risk of type 2 diabetes (T2D) in prediabetes (PD). METHODS: We searched the Cochrane Central, Embase, MEDLINE, and Web of Science (until February 2024) to include RCTs of adults with PD, comparing ILI vs. general advice on the incidence of T2D. Two authors extracted the data, applied the Cochrane Risk of Bias (RoB) 2.0 tool and the GRADE framework. Meta-analysis was performed using random effects models, estimating relative risk (RR) and the 95%CI. RESULTS: Fifteen studies (n = 8,563, 46.7 % female, 53.3 ± 8.7 years, BMI 26.7 ± 5.4 Kg/m2) were included. ILI reduced T2D risk by 22 % when compared with general advice (RR 0.78; 95 %CI 0.72-0.85; I2 = 40 %; low certainty of evidence). Most studies had high risk of bias or raised some concerns. Sensitivity analysis showed that studies with mostly female populations and those using the WHO 1985 criteria for T2D had lower risk of the disease and that the longer the follow-up, the lower the protection. CONCLUSION: ILI can prevent T2D in subjects with PD. Healthcare teams should aim for structured ILI to maintain long-term lifestyle improvements.

Does metformin reduce the risk of cancer in obesity and diabetes? A systematic review and meta-analysis.

AIM: To evaluate the effect of metformin on cancer incidence in subjects with overweight/obesity and/or prediabetes/diabetes. MATERIALS AND METHODS: We searched MEDLINE, Embase and CENTRAL for randomized controlled trials (RCTs) in adults with overweight/obesity and/or prediabetes/diabetes that compared metformin to other interventions for ≥24 weeks. Independent reviewers selected and extracted data including population and intervention characteristics and new diagnoses of cancer. We used the RoB 2.0 risk-of-bias tool and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework to assess risk of bias and certainty of evidence. RESULTS: From 14 895 records after removal of duplicates, 27 trials were included, providing a total of 10 717 subjects in the metformin group and 10 003 in the control group, with 170 and 208 new cases of cancer, respectively. Using a random-effects model, the relative risk was 1.07 (95% confidence interval 0.87-1.31), with similar results in subgroup analyses by study duration or effect of control intervention on weight. Risk of bias in most studies was low, and no evidence of publication bias was found. Trial sequential analysis provided evidence that the cumulative sample size was large enough to exclude a significant effect of metformin on cancer incidence. CONCLUSIONS: Metformin did not reduce cancer incidence in RCTs involving subjects with overweight/obesity and/or prediabetes/diabetes.

Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso).

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up,14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusion: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Diabetes associates with mortality in critically ill patients with SARS-CoV-2 pneumonia: No diabetes paradox in COVID-19.

Background: Diabetes mellitus (DM) is not associated with increased mortality in critically ill patients, a phenomenon known as the "diabetes paradox". However, DM is a risk factor for increased mortality in patients with COVID-19. This study aims to investigate the association of DM and stress-induced hyperglycemia at intensive care unit (ICU) with mortality in this population. Methods: This is a retrospective study. Electronic medical records from patients admitted from March 2020 to September 2020 were reviewed. Primary outcome was mortality. Secondary outcomes were ICU and hospital mortality and stay, and need for mechanical ventilation and renal replacement therapy. Results: 187 patients were included. Overall mortality was 43.2%, higher in patients with DM (55.7% vs. 34%; p = 0.007), even after adjustment for age, hypertension, and disease severity. When patients were separated into groups, named normoglycemia (without DM and glycemia ≤140 mg/dL), stress-induced hyperglycemia (without DM and glycemia >140 mg/dL), and DM (previous diagnosis or HbA1c ≥ 6.5%), the mortality rate was 25.8%, 37.3%, and 55.7%, respectively (p = 0.021). Mortality was higher in patients with higher glycemic variability. No statistical difference related to secondary outcomes was observed. Conclusions: DM, hyperglycemia, and glycemic variability associated with increased mortality in critically ill patients with severe COVID-19, but did not increase the rates of other clinical outcomes. More than stress-induced hyperglycemia, DM was associated with mortality.

The effect of lifestyle interventions on depressive symptom severity in individuals with type-2 diabetes: A meta-analysis of randomized controlled trials.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a severe metabolic condition which is commonly comorbid with depression. Lifestyle factors are involved in the pathophysiology of both conditions; however, the role of lifestyle interventions remains unclear. OBJECTIVE: The objective of this study is to systematically review the literature on randomized controlled trials evaluating the effect of lifestyle interventions on depressive scores in patients with T2DM. METHODS: A systematic search was conducted in computerized databases before October 2022. A random-effects model was used to investigate the effect of lifestyle interventions on depression scores and meta-regression was conducted to assess the influence of age and disease onset. RESULTS: Six trials met the eligibility criteria for inclusion. A statistically significant reduction in depression scores was found for groups receiving lifestyle interventions compared to controls (SMD = -0.49 [95%CI -0.89 to -0.08]; p = 0.0269]). Interventions increased in efficacy with the age of the participants but no significant correlation was found with years since disease onset. Participants in a control group receiving a less intense lifestyle intervention demonstrated improved depression scores when compared to those who received standard care or no intervention at all. Trial design and outcome measurement tools were heterogeneous between studies and limited data on antidepressant use was available which may introduce bias into the results. CONCLUSION: Lifestyle interventions were effective at improving depressive symptom severity in patients with T2DM.

Coconut oil: an overview of cardiometabolic effects and the public health burden of misinformation.

Recent data from meta-analyses of randomized clinical trials (RCTs) suggest that dietary intake of coconut oil, rich in saturated fatty acids, does not result in cardiometabolic benefits, nor in improvements in anthropometric, lipid, glycemic, and subclinical inflammation parameters. Nevertheless, its consumption has surged in recent years all over the world, a phenomenon which can possibly be explained by an increasing belief among health professionals that this oil is as healthy as, or perhaps even healthier than, other oils, in addition to social network misinformation spread. The objective of this review is to present nutritional and epidemiological aspects related to coconut oil, its relationship with metabolic and cardiovascular health, as well as possible hypotheses to explain its high rate of consumption, in spite of the most recent data regarding its actual effects.

Obesity, diabetes, and cancer: epidemiology, pathophysiology, and potential interventions.

The proportion of deaths attributable to cancer is rising, and malignant neoplasms have become the leading cause of death in high-income countries. Obesity and diabetes are now recognized as risk factors for several types of malignancies, especially endometrial, colorectal, and postmenopausal breast cancers. Mechanisms implicated include disturbances in lipid-derived hormone secretion, sex steroids biosynthesis, hyperinsulinemia, and chronic inflammation. Intentional weight loss is associated with a mitigation of risk for obesity-related cancers, a phenomenon observed specially with bariatric surgery. The impact of pharmacological interventions for obesity and diabetes is not uniform: while metformin seems to protect against cancer, other agents such as lorcaserin may increase the risk of malignancies. However, these interpretations must be carefully considered, since most data stem from bias-prone observational studies, and high-quality randomized controlled trials with appropriate sample size and duration are needed to achieve definite conclusions. In this review, we outline epidemiological and pathophysiological aspects of the relationship between obesity, diabetes, and malignancies. We also highlight pieces of evidence regarding treatment effects on cancer incidence in these populations.

Cancer Outcomes Among Prediabetes and Type 2 Diabetes Populations With Dietary and Physical Activity-based Lifestyle Interventions.

CONTEXT: People with type 2 diabetes (T2D) have higher risks of cancer incidence and death. OBJECTIVE: We aimed to evaluate the relationship between dietary and physical activity-based lifestyle intervention and cancer outcomes among prediabetes and T2D populations. METHODS: We searched for randomized controlled trials with at least 24 months of lifestyle interventions in prediabetes or T2D populations. Data were extracted by pairs of reviewers and discrepancies were resolved by consensus. Descriptive syntheses were performed, and the risk of bias was assessed. Relative risks (RRs) and 95% CIs were estimated using a pairwise meta-analysis with both a random-effects model and a general linear mixed model (GLMM). Certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation framework, and trial sequential analysis (TSA) was conducted to assess if current information is enough for definitive conclusions. Subgroup analysis was performed by glycemic status. RESULTS: Six clinical trials were included. Among 12 841 participants, the combined RR for cancer mortality comparing lifestyle interventions with usual care was 0.94 (95% CI, 0.81-1.10 using GLMM and 0.82-1.09 using random-effects model). Most studies had a low risk of bias, and the certainty of evidence was moderate. TSA showed that the cumulative Z curve reached futility boundary while total number did not reach detection boundary. CONCLUSION: Based on the limited data available, dietary and physical activity-based lifestyle interventions had no superiority to usual care on reducing cancer risk in populations with prediabetes and T2D. Lifestyle interventions focused on cancer outcomes should be tested to better explore their effects.

Sodium-glucose cotransporter-2 inhibitors and cancer outcomes: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Concerns regarding breast and bladder cancer risk with Sodium-glucose cotransporter-2 (SGLT2) inhibitors remain controversial and its effect on cancer mortality is unknown. We aim to evaluate the association between SGLT2 inhibitors and the risk of cancer outcomes. METHODS: We searched PubMed, Embase and CENTRAL up to June 20th, 2022, for randomized controlled trials of SGLT2 inhibitors in adults, with a minimum follow-up of 48 weeks. Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with GRADE. We performed meta-analyses summarizing the relative risks (RRs) of cancer outcomes. RESULTS: Seventy-six trials encompassing 116,375 participants were selected. Overall risk of bias was low. SGLT2 inhibitors did not reduce/increase the overall risk of cancer (RR, 1.03; 95% confidence interval [CI], 0.96-1.10) and cancer mortality (RR, 0.99; 95% CI, 0.85-1.16). SGLT2 inhibitors likely result in little to no difference in the risk of breast (RR, 1.01; 95% CI 0.77-1.32) and bladder cancers (RR, 0.93; 95% CI 0.71-1.21). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. CONCLUSIONS: SGLT2 inhibitors are not associated with an increased risk of cancer outcomes, providing reassuring data regarding previous safety concerns.

Effects of nutritional interventions on the severity of depressive and anxiety symptoms of women in the menopausal transition and menopause: a systematic review, meta-analysis, and meta-regression.

IMPORTANCE: Depression and anxiety may significantly affect women during the menopausal transition. In addition to traditional treatment strategies such as hormone therapy, antidepressants, and psychotherapy, nutritional interventions have been increasingly studied, but there is no consensus about their role in this patient population. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effect of nutritional interventions on the severity of depressive (DS) and anxiety (AS) symptoms in women during the menopausal transition or menopausal years. EVIDENCE REVIEW: Electronic search using databases PubMed, Cochrane, and Embase to identify articles indexed until January 31, 2021, focusing on randomized placebo-controlled trials documenting the effect of diet, food supplements, and nutraceuticals on DS and AS. FINDINGS: Thirty-two studies were included (DS, n = 15; AS, n = 1; DS and AS combined, n = 16). We found two studies that demonstrated data combined with other interventions: one with lifestyle interventions (vitamin D plus lifestyle-based weight-loss program) and another with exercise (omega 3 plus exercise). The pooled effect size favored the intervention group over placebo for both DS and AS (DS: standardized mean difference, -0.35 [95% confidence interval, -0.68 to -0.03; P = 0.0351]; AS: standardized mean difference, -0.74 [95% CI, -1.37 to -0.11; P = 0.0229]). There was significant heterogeneity in the pooled results, which can be attributed to differences in assessment tools for depression and anxiety as well as the variety of nutritional interventions studied. The subgroup analysis showed a statistically significant effect of menopausal status (perimenopausal or menopausal) but not the type or duration of nutritional intervention. Older age was the only significant predictor of the effect size of nutritional interventions in the meta-regression. CONCLUSIONS AND RELEVANCE: Nutritional interventions are promising tools for the management of mood/anxiety symptoms in women during the menopausal transition and in postmenopausal years. Because of significant heterogeneity and risk of bias among studies, the actual effect of different approaches is still unclear.

Effect of periodontal treatment on glycated haemoglobin and metabolic syndrome parameters: A randomized clinical trial.

AIM: To assess the effect of periodontal treatment on HbA1c and diagnostic parameters of patients with metabolic syndrome (MetS). MATERIALS AND METHODS: One hundred and fifty-eight patients with MetS and moderate and severe periodontitis were included. They were randomized into a test group (n = 79), which received non-surgical periodontal treatment, and a control group (n = 79), which received no treatment. Medical treatment was delivered to both groups. Clinical periodontal, anthropometric and serological parameters were assessed at baseline, 3 and 6 months. The main outcome was glycated haemoglobin (HbA1c) levels, and the secondary outcomes were changes in the MetS parameters, C-reactive protein (CRP) and HOMA indexes. RESULTS: Significant reductions in all periodontal parameters were observed in the test group, compared with the control group, at 3 and 6 months (p < .001). HbA1c levels, MetS parameters, CRP and HOMA indexes showed no significant differences between the test group and the control group at 3 and 6 months. CONCLUSIONS: Periodontal treatment led to a substantial reduction in periodontal inflammation, although there was no significant effect on the parameters used for MetS diagnosis in patients with early diagnosed and well-controlled MetS.

Coconut oil: an overview of cardiometabolic effects and the public health burden of misinformation

ABSTRACT Recent data from meta-analyses of randomized clinical trials (RCTs) suggest that dietary intake of coconut oil, rich in saturated fatty acids, does not result in cardiometabolic benefits, nor in improvements in anthropometric, lipid, glycemic, and subclinical inflammation parameters. Nevertheless, its consumption has surged in recent years all over the world, a phenomenon which can possibly be explained by an increasing belief among health professionals that this oil is as healthy as, or perhaps even healthier than, other oils, in addition to social network misinformation spread. The objective of this review is to present nutritional and epidemiological aspects related to coconut oil, its relationship with metabolic and cardiovascular health, as well as possible hypotheses to explain its high rate of consumption, in spite of the most recent data regarding its actual effects.

Obesity, diabetes, and cancer: epidemiology, pathophysiology, and potential interventions

ABSTRACT The proportion of deaths attributable to cancer is rising, and malignant neoplasms have become the leading cause of death in high-income countries. Obesity and diabetes are now recognized as risk factors for several types of malignancies, especially endometrial, colorectal, and postmenopausal breast cancers. Mechanisms implicated include disturbances in lipid-derived hormone secretion, sex steroids biosynthesis, hyperinsulinemia, and chronic inflammation. Intentional weight loss is associated with a mitigation of risk for obesity-related cancers, a phenomenon observed specially with bariatric surgery. The impact of pharmacological interventions for obesity and diabetes is not uniform: while metformin seems to protect against cancer, other agents such as lorcaserin may increase the risk of malignancies. However, these interpretations must be carefully considered, since most data stem from bias-prone observational studies, and high-quality randomized controlled trials with appropriate sample size and duration are needed to achieve definite conclusions. In this review, we outline epidemiological and pathophysiological aspects of the relationship between obesity, diabetes, and malignancies. We also highlight pieces of evidence regarding treatment effects on cancer incidence in these populations.

Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso)

ABSTRACT Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up, 14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusions: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Long-term Effect of Lifestyle Interventions on the Cardiovascular and All-Cause Mortality of Subjects With Prediabetes and Type 2 Diabetes: A Systematic Review and Meta-analysis.

BACKGROUND: Lifestyle interventions improve the metabolic control of individuals with hyperglycemia. PURPOSE: We aimed to determine the effect of lifestyle interventions on cardiovascular and all-cause mortality in this population. DATA SOURCES: Searches were made through MEDLINE, Cochrane CENTRAL, Embase, and Web of Science (no date/language restriction, until 15 May 2022). STUDY SELECTION: We included randomized clinical trials (RCTs) of subjects with prediabetes and type 2 diabetes, comparing intensive lifestyle interventions with usual care, with a minimum of 2 years of active intervention. DATA EXTRACTION: Data from the 11 RCTs selected were extracted in duplicate. A frequentist and arm-based meta-analysis was performed with random-effects models to estimate relative risk (RR) for mortality, and heterogeneity was assessed through I2 metrics. A generalized linear mixed model (GLMM) was used to confirm the findings. DATA SYNTHESIS: Lifestyle interventions were not superior to usual care in reducing cardiovascular (RR 0.99; 95% CI 0.79-1.23) or all-cause (RR 0.93; 95% CI 0.85-1.03) mortality. Subgroup, sensitivity, and meta-regression analyses showed no influence of type of intervention, mean follow-up, age, glycemic status, geographical location, risk of bias, or weight change. All of these results were confirmed with the GLMM. Most studies had a low risk of bias according to the RoB 2.0 tool and the certainty of evidence was moderate for both outcomes. LIMITATIONS: Most studies had a low risk of bias according to the RoB 2.0 tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach resulted in moderate certainty of evidence for both outcomes. Differences in lifestyle programs and in usual care between the studies should be considered in the interpretation of our results. CONCLUSIONS: Intensive lifestyle interventions implemented so far did not show superiority to usual care in reducing cardiovascular or all-cause mortality for subjects with prediabetes and type 2 diabetes.

Effects of transcranial direct current stimulation associated with hypocaloric diet on glucose homeostasis in obesity.

OBJECTIVE: The aim of this study was to test the effects of repetitive active transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex (rDLPFC) associated with a hypocaloric diet on glucose homeostasis in people with excessive weight. METHODS: Adults with overweight or obesity were selected in a randomized, double-blind pilot study to complete 4 weeks (20 sessions) of fixed-dose tDCS (2 mA, 20 minutes) delivered over the rDLPFC and associated with a standard hypocaloric diet. Participants were randomly assigned (1:1) and stratified by sex to the active tDCS group (active) or the sham tDCS group (sham). Changes in glucose homeostasis were assessed in a 4-hour liquid meal tolerance test, performed before and after the intervention. RESULTS: Twenty-eight participants were randomized (79% with obesity; mean [SD] age 37.6 [5.8] years). After the intervention, fasting plasma glucose (mean [95% CI], -7.8 mg/dL [-14.0 to -1.6]) and insulin levels (-7.7 µIU/mL [-13.9 to -1.6]) decreased in the active compared with the sham. Similarly, the Matsuda insulin sensitivity index increase in the active (4.7 pmol-1  × mmol-1 [1.6 to 7.8]) compared with the sham (0.6 pmol-1  × mmol-1 [-1.4 to 3.2]). CONCLUSIONS: Repetitive, active tDCS over the rDLPFC could be a promising noninvasive technique to improve glucose homeostasis in individuals with overweight or obesity on a low-calorie diet, highlighting the importance of investigating this intervention modality in individuals with type 2 diabetes mellitus.