The impact of urbanisation on the cardiometabolic health of Indigenous Brazilian peoples: a systematic review and meta-analysis, and data from the Brazilian Health registry.

BACKGROUND: Indigenous Brazilian peoples have faced an unparalleled increase in the rate of cardiovascular diseases following rapid nutritional transition to more urban diets. We aimed to conduct a systematic review and meta-analysis to evaluate the association between urbanisation (including data from Amazon rainforest deforestation) and cardiometabolic risk factors and outcomes. METHODS: In this systematic review and meta-analysis, we searched Pubmed, Embase, Web of Science, and Scopus for articles published in any language between the year 1950 and March 10, 2022. Studies conducted in Indigenous Brazilian adults that evaluated metabolic health were included. Data for deforestation was obtained by the Amazon Deforestation Monitoring Project. Cardiovascular mortality was obtained from the Brazilian Health registry. Two independent reviewers evaluated studies for risk of bias, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. The main outcomes assessed were the prevalence of obesity and related cardiometabolic risk factors among Indigenous Brazilian peoples and its association with urbanisation. Summary data were extracted from published reports for the meta-analyses. We calculated pooled estimates of the prevalence of each cardiometabolic outcome by using a random-effects model (DerSimonian-Laird method). This study is registered with the International Prospective Register of Systematic Reviews, CRD42021285480. FINDINGS: 46 studies were identified, including a total of 20 574 adults from at least 33 Indigenous Brazilian ethnicities. Meta-analyses of the prevalence of obesity showed that there were higher rates of obesity (midwest region: 23% [95% CI 17-29]; and south region 23% [13-34]) and hypertension (south region: 30% [10-50]) in Indigenous peoples living in urban regions of Brazil, while the lowest rates of obesity (11% [95% CI 8-15]) and hypertension (1% [1-2]) were observed in those in the less urbanised (north) regions of Brazil. The prevalence of obesity was 3·5 times higher in participants living in urbanised Indigenous territories (28%) than in those living in lands with >80% native Amazon rainforest (8%). In meta-analyses that evaluated blood pressure level, there was no incremental change in blood pressure with ageing in Indigenous peoples who lived according to traditional lifestyle, in contrast to those living in urbanised regions. For Indigenous men with traditional lifestyles, systolic blood pressure changed from 109·8 mm Hg to 104·4 mm Hg between the youngest (<30 years) and the oldest (>60 years) age groups, and diastolic blood pressure changed from 69·8 mm Hg to 66·1 mm Hg. For Indigenous women with traditional lifestyles, systolic blood pressure was 100·0 mm Hg for the youngest age group with no changes for older age groups, and diastolic blood pressure was 62 mm Hg for the youngest age group with no changes for older age groups. For Indigenous men with urbanised lifestyles, systolic blood pressure changed from 117·3 mm Hg to 124·9 mm Hg between the youngest and the oldest age groups, and diastolic blood pressure changed from 72·7 mm Hg to 76·4 mm Hg. For Indigenous women with urbanised lifestyles, systolic blood pressure changed from 110·0 mm Hg to 116·0 mm Hg between the youngest and the oldest age groups, and diastolic blood pressure changed from 68·3 mm Hg to 74·0 mm Hg. For the years 1997 and 2019, the cardiovascular mortality rate in individuals living in the southeast region (the most urbanised) was 2·5 times greater than that observed in the north. Conversely, the incremental rise in cardiovascular mortality in the past two decades among Indigenous Brazilians living in the north or northeast (2·7 times increase) stands in stark contrast to the stable rates in those living in already urbanised regions. INTERPRETATION: The macrosocial changes of Indigenous peoples' traditional ways of living consequent to urbanisation are associated with an increased prevalence of adverse cardiometabolic outcomes. These data highlight the urgent need for environmental policies to ensure the conservation of the natural ecosystem within Indigenous territories, as well as the development of socio-health policies to improve the cardiovascular health of Indigenous Brazilians peoples living in urban areas. FUNDING: None.

Different Dietary Patterns and New-Onset Diabetes Mellitus After Kidney Transplantation: A Cross-Sectional Study.

OBJECTIVE: To verify the association of dietary patterns and dietary components with new-onset diabetes mellitus after transplantation (NODAT). DESIGN: Cross-sectional study. SUBJECTS: Adult kidney transplant recipients, without history of diabetes before transplantation, who received a kidney transplant and were followed up for at least 1 year. One hundred and sixteen subjects recruited between January 2013 and August 2014. Diagnosis of NODAT was established according to the American Diabetes Association criteria for type 2 diabetes. METHODS: Demographic, clinical, and anthropometric data were collected. Dietary intake was assessed by food frequency questionnaire, administered by a registered dietitian. Dietary patterns were identified by cluster analysis. Chi-square test was used to verify the association between dietary patterns and NODAT. Total energy, fiber, and cholesterol intake were calculated. Consumption of macronutrients, carbohydrates, proteins, and fats (total fats and saturated, monounsaturated, polyunsaturated and trans fatty acids), were expressed in percentage of total energy intake. RESULTS: Twenty-eight patients developed NODAT in the follow-up period. They presented higher body mass index and body fat percentage, as well as higher levels of triglycerides and urinary protein/creatinine ratio than the non-NODAT group. Two dietary patterns, I and II, were identified. Pattern II was characterized by higher intake of total, saturated, monounsaturated, and trans fats than pattern I. No association between the dietary patterns and NODAT was identified (P = .905), and there was no difference in the distribution of macronutrients, dietary fiber, and dietary cholesterol between the groups with and without NODAT. CONCLUSION: Posttransplant dietary patterns were not different between patients with and without NODAT. Further larger and prospective studies are needed to evaluate a possible relationship between dietary components and NODAT incidence in kidney transplant recipients.

Effects of metabolic syndrome on kidney transplantation outcomes: a systematic review and meta-analysis.

Metabolic syndrome (MS) has been associated with proteinuria and reduced glomerular filtration rate. Immunosuppressive agents increase the incidence of traditional risk factors for cardiovascular disease (CVD) and have known effects on MS components after kidney transplantation. The purpose of this meta-analysis was to evaluate the impact of MS on relevant outcomes after kidney transplantation. MEDLINE, EMBASE, and Cochrane Library were searched up to November 7, 2015. Papers that compared patients with and without MS and assessed one of the following outcomes, graft loss, death by cardiovascular disease, and all-cause mortality, were included. Of 585 studies identified, five studies including 1269 patients were evaluated. MS was identified as a risk factor for graft loss [relative risk, 3.06; 95% confidence interval (CI), 2.17, 4.32; I² = 0%; P heterogeneity = 0.72] and death by CVD (relative risk, 3.53; 95% CI, 1.27, 9.85; I² = 0%; P heterogeneity = 0.40). Results on the association between MS and all-cause mortality were inconclusive (relative risk, 2.61; 95% CI, 0.70, 9.81; I² = 58%; P heterogeneity = 0.09). Graft loss and death by CVD were associated with the presence of MS after transplantation. Randomized clinical trials should be conducted to define whether interventions on each MS component would result in better outcomes after transplantation.

Exendin-4 attenuates brain death-induced liver damage in the rat.

The majority of liver grafts destined for transplantation originate from brain dead donors. However, significantly better posttransplantation outcomes are achieved when organs from living donors are used, suggesting that brain death (BD) causes irreversible damage to the liver tissue. Recently, glucagon-like peptide-1 (GLP1) analogues were shown to possess interesting hepatic protection effects in different liver disease models. We hypothesized that donor treatment with the GLP1 analogue exendin-4 (Ex-4) could alleviate BD-induced liver damage. A rat model of BD was employed in order to estimate BD-induced liver damage and Ex-4's potential protective effects. Liver damage was assessed by biochemical determination of circulating hepatic markers. Apoptosis in the hepatic tissue was assessed by immunoblot and immunohistochemistry using an antibody that only recognizes the active form of caspase-3. Gene expression changes in inflammation and stress response genes were monitored by quantitative real-time polymerase chain reaction. Here, we show that Ex-4 administration to the brain dead liver donors significantly reduces levels of circulating aspartate aminotransferase and lactate dehydrogenase. This was accompanied by a remarkable reduction in hepatocyte apoptosis. In this model, BD caused up-regulation of tumor necrosis factor and stress-related genes, confirming previous findings in clinical and animal studies. In conclusion, treatment of brain dead rats with Ex-4 reduced BD-induced liver damage. Further investigation is needed to determine the molecular basis of the observed liver protection. After testing in a randomized clinical trial, the inclusion of GLP1 analogues in organ donor management might help to improve organ quality, maximize organ donation, and possibly increase liver transplantation success rates.

Effect of dietary lipids on circulating adiponectin: a systematic review with meta-analysis of randomised controlled trials.

Different dietary interventions have been identified as potential modifiers of adiponectin concentrations, and they may be influenced by lipid intake. We identified studies investigating the effect of dietary lipids (type/amount) on adiponectin concentrations in a systematic review with meta-analysis. A literature search was conducted until July 2013 using databases such as Medline, Embase and Scopus (MeSH terms: 'adiponectin', 'dietary lipid', 'randomized controlled trials (RCT)'). Inclusion criteria were RCT in adults analysing adiponectin concentrations with modification of dietary lipids. Among the 4930 studies retrieved, fifty-three fulfilled the inclusion criteria and were grouped as follows: (1) total dietary lipid intake; (2) dietary/supplementary n-3 PUFA; (3) conjugated linoleic acid (CLA) supplementation; (4) other dietary lipid interventions. Diets with a low fat content in comparison to diets with a high-fat content were not associated with positive changes in adiponectin concentrations (twelve studies; pooled estimate of the difference in means: -0·04 (95% CI -0·82, 0·74) µg/ml). A modest increase in adiponectin concentrations with n-3 PUFA supplementation was observed (thirteen studies; 0·27 (95% CI 0·07, 0·47) µg/ml). Publication bias was found by using Egger's test (P= 0·01) and funnel plot asymmetry. In contrast, CLA supplementation reduced the circulating concentrations of adiponectin compared with unsaturated fat supplementation (seven studies; -0·74 (95% CI -1·38, -0·10) µg/ml). However, important sources of heterogeneity were found as revealed by the meta-regression analyses of both n-3 PUFA and CLA supplementation. Results of new RCT would be necessary to confirm these findings.

Contraception in women with diabetes: adequacy of medical files registration and prescription - a cross-section study.

OBJECTIVE: To describe the adequacy of diabetes mellitus (DM) patient's files registry regarding contraception method (CM), factors associated with lack of registry, and if prescription is in accordance with World Health Organization (WHO) eligibility criteria. RESEARCH DESIGN AND METHODS: This cross-sectional study was developed in two phases: (1) electronic medical records of women with DM who attended the outpatient clinic of a university hospital were reviewed to identify women in reproductive age and to look for CM registration and (2) interviews regarding contraception use, comorbidities and chronic DM complications. RESULTS: Among 1069 files analyzed, 313 women with DM in childbearing age were identified. Out of those, 55.3% had a CM registered. Age >40 years, non-white skin color, and ≤11 years of education were associated with no registration. Of the 270 women interviewed, 201 (74.4%) were using CM. Out of the 69 patients not on CM, 51 fertile patients were at risk of an unplanned pregnancy (18.8% of the sample). The most frequently used method was oral hormonal (combined: 34.3%; progestin-only: 17.9%), and 67 (33.3%) were using an inadequate method (WHO eligibility category 3/4). CONCLUSION: One third of women with DM are in childbearing age. Older age, non-white skin color, and lower education level were associated with lack of CM registration. One-third of respondents were using CM inappropriate for their clinical condition and one-fifth were at risk for an unplanned pregnancy. So, improvements in family planning for women with DM should be instituted.

Association between diabetes and stress-induced hyperglycemia with skeletal muscle gene expression of INSR in critically ill patients: A prospective cohort study.

This study aimed to investigate the association between diabetes and stress-induced hyperglycemia with skeletal muscle gene expression of INSR of critically ill patients. Skeletal muscle biopsies were prospectively taken from the vastus muscle, and the expression level of INSR was analyzed using RT-qPCR. Fifty patients were included from April 2018 to September 2018. No significant differences in skeletal muscle gene expression were found between patients with or without diabetes. Similarly, there were no differences in gene expression between groups according to the presence of hypoglycemia 〈 70 mg/dl or hyperglycemia 〉 140 mg/dl. Patients with glycemic variability ≥ 40 mg/dl exhibited a downregulation of INSR compared to those with glycemic variability < 40 mg/dl (1.3 [0.01-5] vs. 2.1 [0.7 - 3.4] fold-changes, P = 0.045). The same pattern was observed when glycemic gap threshold of 80 mg/dl was used (1.4 [0.25-5] vs 1 [0.01 - 2.3] fold-changes in patients with glycemic gap < 80 mg/dl and glycemic gap ≥ 80 mg/dl respectively, P = 0.015). In conclusion, INSR was downregulated in the skeletal muscle of critically ill patients with stress-induced hyperglycemia.

Association between neuromuscular blocking agents and the development of intensive care unit-acquired weakness (ICU-AW): A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: The present study aims to review the literature and synthesize evidence concerning the effects of the use of neuromuscular blocking agents (NMBA) regarding the development of intensive care unit-acquired weakness (ICU-AW). METHODS: This study was registered in the PROSPERO database CRD42020142916. Systematic review in PubMed, Embase, and the Cochrane Central, Randomized clinical trials (RCTs), and cohort studies with adults that reported the use of NMBA and the development of ICU-AW were included. Pre-specified subgroup analyses were performed for presence of sepsis and type of NMBA used. The quality of evidence for intervention effects was summarized. The certainty of evidence was assessed using the GRADE approach. RESULTS: We included 30 studies, four RCTs, 21 prospective and 5 retrospective cohorts, enrolling a total of 3839 patients. Most of the included studies were observational with high heterogeneity, whereas the RCTs had a high risk of bias. The use of NMBA increased the odds of developing ICU-AW (OR = 2.77 [95% CI 1.98-3.88], I2 = 62%), with low-quality of evidence. A trial sequential analysis showed the need to include 22,330 patients in order to provide evidence for either beneficial or harmful intervention effects. CONCLUSIONS: This meta-analysis suggests that the use of NMBA might be implicated in the development of ICU-AW. However, there is not enough evidence to definitively conclude about the association between the use of NMBA and the development of ICU-AW, as these results are based mostly on observational studies with high heterogeneity.

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.

Effect of antihyperglycemic agents added to metformin and a sulfonylurea on glycemic control and weight gain in type 2 diabetes: a network meta-analysis.

BACKGROUND: Few studies have examined the effect of adding a third antihyperglycemic drug when blood glucose control is not achieved by using metformin and a sulfonylurea. PURPOSE: To compare the efficacy of add-on antihyperglycemic drugs in patients with type 2 diabetes that is not controlled with metformin and a sulfonylurea. DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, LILACS, and ClinicalTrials.gov electronic databases. STUDY SELECTION: Randomized trials at least 24 weeks in duration. Studies evaluated the effects of adding a third antihyperglycemic drug to treatment of adults aged 18 years or older with type 2 diabetes and a hemoglobin A(1c) (HbA(1c)) level greater than 7.0% who were already receiving a combination of metformin and a sulfonylurea. DATA EXTRACTION: Primary end points were change in HbA(1c) level, change in weight, and frequency of severe hypoglycemia. DATA SYNTHESIS: Eighteen trials involving 4535 participants that lasted a mean of 31.3 weeks (24 to 52 weeks) were included. Compared with placebo, drug classes did not differ in effect on HbA(1c) level (reduction ranging from -0.70% [95% credible interval {CrI}, -1.33% to -0.08%] for acarbose to -1.08% [CrI, -1.41% to -0.77%] for insulin). Weight increase was seen with insulins (2.84 kg [CrI, 1.76 to 3.90 kg]) and thiazolidinediones (4.25 kg [CrI, 2.76 to 5.66 kg]), and weight loss was seen with glucagon-like peptide-1 agonists (-1.63 kg [CrI, -2.71 to -0.60 kg]). Insulins caused twice the absolute number of severe hypoglycemic episodes than noninsulin antihyperglycemic agents. LIMITATIONS: Most of the trials were short term, and trial quality varied. With so few trials relative to antihyperglycemic agents, investigators relied on indirect comparisons, which increased the uncertainty of the findings and conclusions. CONCLUSION: There is no clear difference in benefit between drug classes when adding a third agent to treatment of patients with type 2 diabetes who are already receiving metformin and a sulfonylurea. The most appropriate option should depend on each patient's clinical characteristics. PRIMARY FUNDING SOURCE: Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenacao de Aperfeicoamento de Pessoal de Nível Superior.

Dose-ranging effects of SGLT2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis.

The lowest dosage of empagliflozin (10 mg) showed similar benefits on glycated hemoglobin (HbA1c) level, body weight, blood pressure, and total and cardiovascular mortality in comparison with the highest available dose (25 mg) in the EMPAREG trial. These findings have not been clearly demonstrated for canagliflozin and dapagliflozin. The objective was to compare the effect of different doses of SGLT2 inhibitors commercially available in Brazil on HbA1c and body weight of patients with type 2 diabetes. MEDLINE, Cochrane and Embase databases were searched from inception until 11th October 2021 for randomized controlled trials of SGLT2 inhibitors in type 2 diabetes patients, lasting at least 12 weeks. HbA1c and body weight variations were described using standard mean difference. We performed direct and indirect meta-analysis, as well as a meta-regression with medication doses as covariates. Eighteen studies were included, comprising 16,095 patients. In the direct meta-analysis, SGLT2 inhibitors reduced HbA1c by 0.62% (95% CI -0.66 to -0.59) and body weight by 0.60 kg (95% CI -0.64 to -0.55). In the indirect meta-analysis, canagliflozin 300 mg ranked the highest regarding reductions in HbA1c and body weight. The remaining medications and dosages were clinically similar, despite some statistically significant differences among them. Canagliflozin 300 mg seems to be more potent in reducing HbA1c and body weight in patients with type 2 diabetes. The remaining SGLT2 inhibitors at different doses lead to similar effects for both outcomes. Whether these glycemic and weight effects are reflected in lower mortality and cardiovascular events is still uncertain and may be a topic for further studies.

Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis.

CONTEXT: Regular exercise improves glucose control in diabetes, but the association of different exercise training interventions on glucose control is unclear. OBJECTIVE: To conduct a systematic review and meta-analysis of randomized controlled clinical trials (RCTs) assessing associations of structured exercise training regimens (aerobic, resistance, or both) and physical activity advice with or without dietary cointervention on change in hemoglobin A(1c) (HbA(1c)) in type 2 diabetes patients. DATA SOURCES: MEDLINE, Cochrane-CENTRAL, EMBASE, ClinicalTrials.gov, LILACS, and SPORTDiscus databases were searched from January 1980 through February 2011. STUDY SELECTION: RCTs of at least 12 weeks' duration that evaluated the ability of structured exercise training or physical activity advice to lower HbA(1c) levels as compared with a control group in patients with type 2 diabetes. DATA EXTRACTION: Two independent reviewers extracted data and assessed quality of the included studies. DATA SYNTHESIS: Of 4191 articles retrieved, 47 RCTs (8538 patients) were included. Pooled mean differences in HbA(1c) levels between intervention and control groups were calculated using a random-effects model. Overall, structured exercise training (23 studies) was associated with a decline in HbA(1c) level (-0.67%; 95% confidence interval [CI], -0.84% to -0.49%; I(2), 91.3%) compared with control participants. In addition, structured aerobic exercise (-0.73%; 95% CI, -1.06% to -0.40%; I(2), 92.8%), structured resistance training (-0.57%; 95% CI, -1.14% to -0.01%; I(2), 92.5%), and both combined (-0.51%; 95% CI, -0.79% to -0.23%; I(2), 67.5%) were each associated with declines in HbA(1C) levels compared with control participants. Structured exercise durations of more than 150 minutes per week were associated with HbA(1c) reductions of 0.89%, while structured exercise durations of 150 minutes or less per week were associated with HbA(1C) reductions of 0.36%. Overall, interventions of physical activity advice (24 studies) were associated with lower HbA(1c) levels (-0.43%; 95% CI, -0.59% to -0.28%; I(2), 62.9%) compared with control participants. Combined physical activity advice and dietary advice was associated with decreased HbA(1c) (-0.58%; 95% CI, -0.74% to -0.43%; I(2), 57.5%) as compared with control participants. Physical activity advice alone was not associated with HbA(1c) changes. CONCLUSIONS: Structured exercise training that consists of aerobic exercise, resistance training, or both combined is associated with HbA(1c) reduction in patients with type 2 diabetes. Structured exercise training of more than 150 minutes per week is associated with greater HbA(1c) declines than that of 150 minutes or less per week. Physical activity advice is associated with lower HbA(1c), but only when combined with dietary advice.

-866G/A and Ins/Del polymorphisms in UCP2 gene are associated with reduced short-term weight loss in patients who underwent Roux-en-Y gastric bypass.

BACKGROUND: Uncoupling protein 2 (UCP2) plays an important role in energy expenditure regulation. Previous studies have associated the common -866G/A (rs659366) and Ins/Del polymorphisms in the UCP2 gene with metabolic and obesity-related phenotypes. However, it is still unclear whether these polymorphisms influence weight loss after bariatric surgery. OBJECTIVES: To investigate whether UCP2 -866G/A and Ins/Del polymorphisms are associated with weight loss outcomes after bariatric surgery. SETTING: Longitudinal study in a university hospital. METHODS: We retrospectively evaluated 186 patients who underwent Roux-en-Y gastric bypass (RYGB) surgery for clinical and laboratory characteristics in the preoperative period, 6, 12, and 18 months after RYGB. The -866G/A (rs659366) polymorphism was genotyped using real-time PCR, while the Ins/Del polymorphism was genotyped by direct separation of PCR products in 2.5% agarose gels. RESULTS: Patients with the -866A/A genotype showed higher body mass index (BMI) after 6, 12, and 18 months of surgery and excess body weight after 6 and 12 months compared with G/G patients. They also showed lower excess weight loss (EWL%) after 6 and 12 months of surgery. Ins allele carriers (Ins/Ins + Ins/Del) had lower delta (Δ) BMI 12 months after surgery compared with Del/Del patients. Accordingly, patients carrying haplotypes with ≥2 risk alleles of these polymorphisms had higher BMI and excess weight and lower EWL% during follow-up. CONCLUSION: UCP2 -866A/A genotype is associated with higher BMI and excess weight and lower EWL% during an 18-month follow-up of patients who underwent RYGB, while the Ins allele seems to be associated with lower ΔBMI 12 months after surgery. Further studies are needed to confirm the associations of the -866G/A and Ins/Del polymorphisms with weight loss after bariatric surgery.

UCP2, IL18, and miR-133a-3p are dysregulated in subcutaneous adipose tissue of patients with obesity.

The aim of this study was to compare the expression of UCP2, NLRP3, IL1B, IL18, and miR-133a-3p in subcutaneous adipose tissue (SAT) of 61 patients divided according to BMI: Group 1 (n = 8; BMI<25.0 kg/m2), Group 2 (n = 24; BMI 30.0-39.9 kg/m2), and Group 3 (n = 29; BMI≥40.0 kg/m2). SAT biopsies were obtained from individuals who underwent bariatric surgery or elective abdominal surgery. Gene expressions were quantified using qPCR. Bioinformatics analyses were employed to investigate target genes and pathways related to miR-133a-3p. UCP2 and miR-133a-3p expressions were decreased in SAT of Groups 2 and 3 while IL18 was increased compared to Group 1. NLRP3 and IL1B expressions did not differ between groups; however, NLRP3 was positively correlated with waist circumference and excess weight. Bioinformatics analysis demonstrated that UCP2 and NLRP3 are targets of miR-133a-3p. In conclusion, UCP2 and miR-133a-3p expressions are downregulated in patients with obesity, while IL18 is upregulated. NRLP3 is correlated with waist circumference and weight excess.

Improvement of human pancreatic islet quality after co-culture with human adipose-derived stem cells.

The aim of this study was to investigate whether co-culture of human islets with adipose-derived stem cells (ASCs) can improve islet quality and to evaluate which factors play a role in the protective effect of ASCs against islet dysfunction. Islets and ASCs were cultured in three experimental groups for 24 h, 48 h, and 72 h: 1) indirect co-culture of islets with ASC monolayer (Islets/ASCs); 2) islets alone; and 3) ASCs alone. Co-culture with ASCs improved islet viability and function in all culture time-points analyzed. VEGFA, HGF, IL6, IL8, IL10, CCL2, IL1B, and TNF protein levels were increased in supernatants of islet/ASC group compared to islets alone, mainly after 24 h. Moreover, VEGFA, IL6, CCL2, HIF1A, XIAP, CHOP, and NFKBIA genes were differentially expressed in islets from the co-culture condition compared to islets alone. In conclusion, co-culture of islets with ASCs promotes improvements in islet quality.

Patient-centered Management of Type 2 Diabetes Mellitus Based on Specific Clinical Scenarios: Systematic Review, Meta-analysis and Trial Sequential Analysis.

INTRODUCTION: New antihyperglycemic medications have been proven to have cardiovascular (CV) and renal benefits in type 2 diabetes mellitus (T2DM); however, an evidence-based decision tree in specific clinical scenarios is lacking. MATERIALS AND METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs), with trial sequential analysis (TSA). Randomized controlled trial inclusion criteria were patients with T2DM from 1 of these subgroups: elderly, obese, previous atherosclerotic CV disease (ASCVD), previous coronary heart disease (CHD), previous heart failure (HF), or previous chronic kidney disease (CKD). Randomized controlled trials describing those subgroups with at least 48 weeks of follow-up were included. Outcomes: 3-point major adverse cardiovascular events (MACE), CV death, hospitalization due to HF, and renal outcomes. We performed direct meta-analysis with the number of events in the intervention and control groups in each subset, and the relative risk of the events was calculated. RESULTS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) were the only antihyperglycemic agents related to a reduction in CV events in different populations. For obese and elderly populations, GLP-1 RA were associated with benefits in 3-point MACE; for patients with ASCVD, both SGLT2i and GLP-1 RA had benefits in 3-point MACE, while for patients with CHD, only SGLT2i were beneficial. CONCLUSIONS: SGLT2i and GLP-1 RA reduced CV events in selected populations: SGLT2i led to a reduction in events in patients with previous CHD, ASCVD, and HF. GLP-1 RA led to a reduction in CV events in patients with ASCVD, elderly patients, and patients with obesity. Trial sequential analysis shows that these findings are conclusive. This review opens a pathway towards evidence-based, personalized treatment of T2DM. REGISTRATION: PROSPERO CRD42019132807.

Clinical use of fructosamine in islet transplantation.

Many islet transplant recipients have medical conditions that could interfere with the accuracy of HbA1c measurements (e.g., anemia/dapsone use). Fructosamine is less prone to have clinical interferences and reflects glucose control in a shorter period of time than HbA1c. This study aimed to validate fructosamine use in islet transplant subjects and to evaluate its effectiveness as a predictor for islet graft dysfunction. Thirty-three islet transplant recipients who had concomitant fructosamine and HbA1c data available were retrospectively analyzed. HbA1c, fructosamine, mean capillary blood glucose, and islet graft function (fasting C-peptide/glucose ratio) were assessed. There was a significant and positive association between fructosamine and HbA1c (p < 0.0001). Both variables were also positively associated with mean overall and fasting capillary glucose. Neither fructosamine nor HbA1c was shown by ROC analysis to significantly discriminate between periods with and without subsequent graft dysfunction. HbA1c >6% was predictive of this outcome 1 month in advance (OR 2.95, p = 0.003). However, although significantly associated with graft dysfunction, use of this cutoff as a predictor of dysfunction has poor sensitivity (50%) and specificity (77.6%). Fructosamine above the normal range (>270 mumol/L Quest Diagnostics) was also predictive of ensuing dysfunction (OR 2.47, p = 0.03); however, it had similarly poor sensitivity (62%) and specificity (64%). Fructosamine can be used as an alternative to HbA1c for glycemic assessment in islet transplant recipients in situations with HbA1c assay interference. Neither HbA1c nor fructosamine are good predictors of islet graft dysfunction.

Intra- and interobserver reproducibility of pancreatic perfusion by computed tomography.

The aim of this study was to measure intra- and interobserver agreement among radiologists in the assessment of pancreatic perfusion by computed tomography (CT). Thirty-nine perfusion CT scans were analyzed. The following parameters were measured by three readers: blood flow (BF), blood volume (BV), mean transit time (MTT) and time to peak (TTP). Statistical analysis was performed using the Bland-Altman method, linear mixed model analysis, and intraclass correlation coefficient (ICC). There was no significant intraobserver variability for the readers regarding BF, BV or TTP. There were session effects for BF in the pancreatic body and MTT in the pancreatic tail and whole pancreas. There were reader effects for BV in the pancreatic head, pancreatic body and whole pancreas. There were no effects for the interaction between session and reader for any perfusion parameter. ICCs showed substantial agreement for the interobserver measurements and moderate to substantial agreement for the intraobserver measurements, with the exception of MTT. In conclusion, satisfactory reproducibility of measurements was observed for TTP in all pancreatic regions, for BF in the head and BV in the tail, and these parameters seem to ensure a reasonable estimation of pancreatic perfusion.

Glucagon-like peptide-1 receptor agonists and pancreatic cancer: a meta-analysis with trial sequential analysis.

We aimed to assess if GLP-1 agonists are associated with pancreatic cancer. Systematic review and meta-analysis of randomized trials with GLP-1 agonists as an intervention was performed. Trial sequential analysis (TSA) was performed to assess if the available information is sufficient to reject this association. Twelve trials met the study criteria, with a total of 36, 397 patients. GLP-1 analogues did not increase the risk for pancreatic cancer when compared to other treatments (OR 1.06; 95% CI 0.67 to 1.67; I2 14%). TSA confirmed that enough patients were randomized and again no association of the medications and pancreatic cancer was observed considering a NNH of 1000 and the short mean follow-up of the included trials (1.7 years). Larger studies with longer duration would be required to exclude a greater NNH and to aside concerns regarding possible influence of study duration and the outcome.