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International Journal of Molecular... Aug 2022Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid... (Review)
Review
Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders' views on AI for therapy discovery in CDG.
Topics: Artificial Intelligence; Biomarkers; Congenital Disorders of Glycosylation; Drug Repositioning; Humans; Rare Diseases
PubMed: 35955863
DOI: 10.3390/ijms23158725 -
Journal of Pediatric Endocrinology &... Sep 2023Glycogen storage disease (GSD) type 1a is an inherited autosomal recessive metabolic disease caused by a deficiency in glucose-6-phosphatase activity. The objectives of... (Review)
Review
Glycogen storage disease (GSD) type 1a is an inherited autosomal recessive metabolic disease caused by a deficiency in glucose-6-phosphatase activity. The objectives of this research were to systematically review the published literature on the epidemiology of GSD 1a and to assess the performance of reported epidemiology measures in a simulation model. In this systematic literature review 2,539 record titles and abstracts were screened. Of these, only 11 studies contained relevant data on GSD 1a disease epidemiology. Reported disease frequency ranged from 0.085/100,000 to 10.3/100,000 newborns when considering all the GSD literature. When this was narrowed to GSD 1 and GSD 1a, the range was tightened to 0.25-3.02/100,000 and 0.085-4.9/100,000 newborns, respectively. Most of the identified studies counted the number of diagnoses in a defined period and related to the number of births in the same (Dx method) or different time period (DoB method). The simulation model results indicate that in most of the situations, the Dx method provides a closer estimate to the true disease incidence than the DoB method. Despite the scarcity of epidemiology data, the results of this systematic review strongly support that GSD 1a and its parent disease groups (GSD and GSD 1) are rare diseases.
Topics: Infant, Newborn; Humans; Pregnancy; Female; Glycogen Storage Disease Type I; Glucose-6-Phosphatase; Parents; Parturition
PubMed: 37615591
DOI: 10.1515/jpem-2023-0127 -
Psychoneuroendocrinology Jun 2023Parent-child separation has been associated with negative mental health across childhood and adulthood, yet little is known about the long-term impacts for... (Review)
Review
BACKGROUND
Parent-child separation has been associated with negative mental health across childhood and adulthood, yet little is known about the long-term impacts for cardiovascular health. This systematic review synthesized and evaluated the quality of the literature examining the association between exposures to parent-child separation and cardiometabolic outcomes in adulthood.
METHODS
Following a registered protocol, online databases (Pubmed, PsycInfo, and Web of Science) were searched for relevant studies. Studies were included if they (a) defined the exposure before age 18 as institutionalization, foster care placement, parental incarceration, separation due to parents migrating for economic reasons, or asylum and war; and (b) quantified the association between parent-child separation and cardiometabolic events and diagnoses (e.g., coronary heart disease, diabetes) and risk factors (e.g., body mass index, fat distribution, serum-based metabolic markers, inflammatory markers in adulthood (≥ age 18). Studies lacking an unexposed comparison group were excluded. The risk for bias in each study was assessed with a modified Newcastle-Ottawa Scale.
RESULTS
Of the 1938 studies identified, 13 met our inclusion criteria. Two of the four studies examining associations between parent-child separation and cardiometabolic events and diagnoses found positive associations with coronary heart disease and diabetes. Amongst the 13 studies examining associations with any type of adult cardiometabolic risk factors, eight studies reported at least one positive association. Sub-analyses considering separate reasons for parent-child separation provided clearer insights: War evacuation was associated with hypertension and high blood pressure across four studies from the same cohort; out-of home care experiences largely evidenced null results across five different studies, and two studies on parental incarceration suggested positive associations with elevated inflammation, BMI and blood pressure.
CONCLUSIONS
The connections between parent-child separation and adult cardiometabolic outcomes and risk factors are currently inconsistent. The results may depend on the reason for separation, age of assessment, analytic differences and other psychosocial variables that are often unmeasured in this literature.
Topics: Adult; Humans; Child; Adolescent; Risk Factors; Parents; Hypertension; Diabetes Mellitus; Biomarkers; Parent-Child Relations
PubMed: 36996574
DOI: 10.1016/j.psyneuen.2023.106084 -
International Journal of Environmental... Sep 2023Previous studies consistently report a high prevalence of cardiovascular disease (CVD) risk factors among firefighters. However, the clustering of CVD risk factors,... (Meta-Analysis)
Meta-Analysis Review
Previous studies consistently report a high prevalence of cardiovascular disease (CVD) risk factors among firefighters. However, the clustering of CVD risk factors, defined as metabolic syndrome (MetSyn), has received little attention by comparison. Therefore, the aim of this study was to estimate the pooled prevalence of MetSyn among firefighters. Using combinations of free text for 'firefighter' and 'metabolic syndrome', databases were searched for eligible studies. Meta-analyses calculated weighted pooled prevalence estimates with 95% confidence intervals (CI) for MetSyn, its components and overweight/obesity. Univariate meta-regression was performed to explore sources of heterogeneity. Of 1440 articles screened, 25 studies were included in the final analysis. The pooled prevalence of MetSyn in 31,309 firefighters was 22.3% (95% CI: 17.7-27.0%). The prevalences of MetSyn components were hypertension: 39.1%; abdominal obesity: 37.9%; hypertriglyceridemia: 30.2%; dyslipidemia: 30.1%; and hyperglycemia: 21.1%. Overweight and obesity prevalence rates in firefighters were 44.1% and 35.6%, respectively. Meta-regression revealed that decreased risk of bias (RoB) score and increased body mass index (BMI) were positively associated with an increase in MetSyn prevalence. Since one in five firefighters may meet the criteria for MetSyn, novel interventions should be explored to both prevent MetSyn and reduce the onset of CVD risk factors.
Topics: Humans; Metabolic Syndrome; Prevalence; Overweight; Firefighters; Cardiovascular Diseases; Obesity; Risk Factors
PubMed: 37835084
DOI: 10.3390/ijerph20196814 -
Lipids in Health and Disease Jul 2017Fish oil supplementation has been shown to be associated with a lower risk of metabolic syndrome and benefit a wide range of chronic diseases, such as cardiovascular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fish oil supplementation has been shown to be associated with a lower risk of metabolic syndrome and benefit a wide range of chronic diseases, such as cardiovascular disease, type 2 diabetes and several types of cancers. However, the evidence of fish oil supplementation on glucose metabolism and insulin sensitivity is still controversial. This meta-analysis summarized the exist evidence of the relationship between fish oil supplementation and insulin sensitivity and aimed to evaluate whether fish oil supplementation could improve insulin sensitivity.
METHODS
We searched the Cochrane Library, PubMed, Embase database for the relevant studies update to Dec 2016. Two researchers screened the literature independently by the selection and exclusion criteria. Studies were pooled using random effect models to estimate a pooled SMD and corresponding 95% CI. This meta-analysis was performed by Stata 13.1 software.
RESULTS
A total of 17 studies with 672 participants were included in this meta-analysis study after screening from 498 published articles found after the initial search. In a pooled analysis, fish oil supplementation had no effects on insulin sensitivity compared with the placebo (SMD 0.17, 95%CI -0.15 to 0.48, p = 0.292). In subgroup analysis, fish oil supplementation could benefit insulin sensitivity among people who were experiencing at least one symptom of metabolic disorders (SMD 0.53, 95% CI 0.17 to 0.88, p < 0.001). Similarly, there were no significant differences between subgroups of methods of insulin sensitivity, doses of omega-3 polyunsaturated fatty acids (n-3 PUFA) of fish oil supplementation or duration of the intervention. The sensitivity analysis indicated that the results were robust.
CONCLUSIONS
Short-term fish oil supplementation is associated with increasing the insulin sensitivity among those people with metabolic disorders.
Topics: Animals; Databases, Factual; Fatty Acids, Omega-3; Fish Oils; Humans; Insulin Resistance; Metabolic Syndrome
PubMed: 28673352
DOI: 10.1186/s12944-017-0528-0 -
BMC Endocrine Disorders Apr 2019Previous studies have suggested that metabolic syndrome (MetS) and its component conditions are linked to the development of many benign or malignant diseases. Some... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies have suggested that metabolic syndrome (MetS) and its component conditions are linked to the development of many benign or malignant diseases. Some studies have described relationships among metabolic syndrome or diabetes and liver cancer, but not many articles described the relationships between MetS and cirrhosis, acute hepatic failure, end-stage liver disease, and even death. However, liver cancers, cirrhosis, acute hepatic failure, end-stage liver disease, and liver-related mortality-collectively described as liver-related events (LREs)-may have different relationships with MetS. We undertook this meta-analysis to examine the association between MetS and LREs, and to determine whether geographic region or hepatitis B virus (HBV) positivity might influence the association.
METHODS
Relevant studies were identified from PubMed, EMBASE, and the Cochrane database. Two reviewers independently searched records from January 1980 to December 2017. The search terms included 'metabolic syndrome', 'diabetes mellitus', 'insulin resistance syndrome', and 'metabolic abnormalities', combined with 'cirrhosis', 'hepatic fibrosis ', 'hepatocellular carcinoma', 'complication', 'LRE', 'HCC', 'liver-related events', and 'liver cancer'. No language restriction was applied to the search. We chose the studies reporting an association between MetS and LREs. We used Begg's and Egger's tests and visually examined a funnel plot to assess publication bias. All analyses were conducted in Stata 14.0 software.
RESULTS
There were 19 studies (18 cohort and 1 case-control) included in the analysis, with a total of 1,561,457 participants. The subjects' ages ranged from 18 to 84 years. The combined analysis showed an overall 86% increase risk of LREs in cases with MetS (RR: 1.86,95% CI: 1.56-2.23). The funnel plot was asymmetrical, and the Egger's test p values showed a publication bias in this meta analysis. However, through the trim and fill method, we obtained a new RR value for LREs with MetS of 1.49 (95% CI: 1.40-1.58, p = 0.000). There was no obvious difference with the two answers, so we concluded that the results were robust. For hepatitis B positive patients, the RR for MetS and LREs was 2.15 (95% CI:1.02-4.53, p = 0.038), but for the hepatitis B negative patients, the RR was 1.85 (95% CI:1.53-2.24, p = 0.000). And for non-Asians, the RR for MetS and LREs was 2.21 (95% CI: 1.66-2.69, p = 0.000), while for Asians, the RR was 1.73 (95% CI: 1.35-2.22, p = 0.000).
CONCLUSIONS
This meta-analysis showed that MetS is associated with a moderately increased risk of LREs prevalence. Patients with MetS together with hepatitis B are more likely to develop hepatic events. For non-Asians, MetS is more likely to increase the incidence of LREs.
Topics: Humans; Liver Diseases; Metabolic Syndrome; Prognosis; Risk Factors
PubMed: 31023282
DOI: 10.1186/s12902-019-0366-3 -
Nutrients Sep 2022: Exposure to maternal diabetes is considered one of the most common in utero insults that can result in an increased risk of complications later in life with a... (Review)
Review
: Exposure to maternal diabetes is considered one of the most common in utero insults that can result in an increased risk of complications later in life with a permanent effect on offspring health. In this study, we aim to assess the level of risk associated with each type of maternal diabetes on obesity, glucose intolerance, cardiovascular diseases (CVD), and neurodevelopmental disorders in offspring. : We conducted a systematic review of the literature utilizing PubMed for studies published between January 2007 and March 2022. Our search included human cohorts and case control studies following offspring exposed at least to two different types of maternal diabetes clearly identified during pregnancy. Collected outcomes included prevalence, incidence, odds ratio, hazard ratio and risk ratio. : Among 3579 published studies, 19 cohorts were eligible for inclusion in our review. The risks for overweight, obesity, type 2 diabetes (T2D), glucose intolerance, metabolic syndrome, and CVD were increased for all types of maternal diabetes during pregnancy. The risk of overweight or obesity in infancy and in young adults was similar between gestational diabetes mellitus (GDM) and type 1 diabetes (T1D). The risk for T2D or abnormal glucose tolerance was double for offspring from GDM mothers compared to offspring from T1D mothers. In contrast, the risk for T1D in offspring at any age until young adulthood was increased when mothers had T1D compared to GDM and T2D. The risk for CVD was similar for all types of maternal diabetes, but more significant results were seen in the occurrence of heart failure and hypertension among offspring from T2D mothers. The risk of autism spectrum disorders and attention deficit/hyperactivity disorders was mainly increased after in utero exposure to preexisting T1D, followed by T2D. : Offspring of diabetic mothers are at increased risk for multiple adverse outcomes with the highest risk detected among offspring from T2D mothers. Future work warrants large multiethnic prospective cohort studies that aim to identify the risks associated with each type of maternal diabetes separately.
Topics: Adult; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose; Glucose Intolerance; Humans; Obesity; Overweight; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Young Adult
PubMed: 36145247
DOI: 10.3390/nu14183870 -
Revista Da Associacao Medica Brasileira... Mar 2018To identify the changes caused by dyslipidemia and obesity in pregnancy suggesting causes for premature birth, and the prognosis for the newborn. (Review)
Review
OBJECTIVE
To identify the changes caused by dyslipidemia and obesity in pregnancy suggesting causes for premature birth, and the prognosis for the newborn.
METHOD
Systematic review based on the Medline, Lilacs, Embase and Cochrane library databases between 1996 and 2016. The search for studies included the following keywords: "dyslipidemia, pregnancy, obesity, preterm birth." A protocol was programmed and a protocol for inclusion/exclusion of studies was implemented.
RESULTS
Of the 5,789 articles initially selected between March 1996 and July 2016, only 32 were in accordance with the established criteria. Of these, 28.12% discussed risk factors of prematurity; 37.50%, metabolic alterations and gestational dyslipidemia; 21.87%, dyslipidemic complications in preterm birth; and 12,50%, lipid metabolism, glycemic and placental transfer.
CONCLUSION
There is a reduced adaptation of obese pregnant women to the metabolic changes of gestation. This favors dyslipidemic intercurrences in the mother, which, directly or indirectly, suggests the occurrence of premature births and high lipid transfer to the fetus. Therefore, preterm newborns, whose mothers were dyslipidemic during pregnancy, have greater risk of epicardial fat, both in early (first year of life) and in later (adult) phases of life.
Topics: Dyslipidemias; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Obesity; Pregnancy; Premature Birth; Prognosis
PubMed: 29641774
DOI: 10.1590/1806-9282.64.03.264 -
Actas Dermo-sifiliograficas May 2017Meta-analyses have found evidence of a relationship between psoriasis and metabolic syndrome, but Latin American populations have not been included. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Meta-analyses have found evidence of a relationship between psoriasis and metabolic syndrome, but Latin American populations have not been included.
METHODOLOGY
We performed a systematic review and meta-analysis of observational studies including adults with psoriasis and metabolic syndrome indexed in Medline, Scopus, SciELO, Google Scholar, Science Direct, and LILACS between 1980 and 2016. We computed pooled odds ratios (OR) with a random effects model and analyzed subgroups according to patient variables used in the studies.
RESULTS
Five studies with a total of 241 patients with psoriasis were found; 46.5% of the patients also had metabolic syndrome (pooled OR, 2.63; 95% CI: 1.11-6.23; P=.03). In studies using the Adult Treatment Panel III (ATP-III) criteria for metabolic syndrome, the pooled OR was similar at 3.97 (95% CI: 1.27-21.42). Studies that included patients with chronic and severe disease detected higher risk for metabolic syndrome (pooled OR, 6.65; 95% CI: 3.32-13.31). Limitations are that few studies have been done in Latin America, heterogeneity was high, and inconsistency was found across studies.
CONCLUSION
The association between psoriasis and metabolic syndrome is high in Latin America. The association is stronger when psoriasis is chronic and severe and when the ATP-III criteria are used for diagnosis.
Topics: Adult; Causality; Comorbidity; Disease Susceptibility; Humans; Latin America; Metabolic Syndrome; Models, Theoretical; Observational Studies as Topic; Odds Ratio; Prevalence; Psoriasis; Research Design; Risk
PubMed: 28117050
DOI: 10.1016/j.ad.2016.11.009 -
The Cochrane Database of Systematic... May 2023The finding that exercise is inversely related to metabolic syndrome after transplantation is novel and suggests that exercise interventions might provide a means for... (Review)
Review
BACKGROUND
The finding that exercise is inversely related to metabolic syndrome after transplantation is novel and suggests that exercise interventions might provide a means for reducing metabolic syndrome complications in liver transplantation recipients. The use of exercise for increasing the physical activity daily levels by more frequent, higher intensity, and longer duration of training sessions, or the sum of these components may be necessary to counteract the effects of the pretransplant reduced activity, metabolic disturbances, and post-transplant immunosuppression, as well as improve physical function and aerobic capacity following liver transplantation. Regular physical activity has a long-term positive impact on recovery following various surgical procedures including transplantation, giving people the opportunity to return to an active life with their families, in society, and in their professional life. Likewise, specific muscle strength training may attenuate the loss of strength after liver transplantation.
OBJECTIVES
To evaluate the benefits and harms of exercise-based interventions in adults after liver transplantation compared to no exercise, sham interventions, or another type of exercise.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 2 September 2022.
SELECTION CRITERIA
We included randomised clinical trials in liver transplantation recipients comparing any type of exercise with no exercise, sham interventions, or another type of exercise.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality; 2. serious adverse events; and 3. health-related quality of life. Our secondary outcomes were 4. a composite of cardiovascular mortality and cardiac disease; 5. aerobic capacity; 6. muscle strength; 7. morbidity; 8. non-serious adverse events; and 9. cardiovascular disease post-transplantation. We assessed risk of bias of the individual trials using RoB 1, described the interventions using the TIDieR checklist, and used GRADE to assess certainty of evidence.
MAIN RESULTS
We included three randomised clinical trials. The trials randomised 241 adults with liver transplantation, of which 199 participants completed the trials. The trials were conducted in the USA, Spain, and Turkey. They compared exercise versus usual care. The duration of the interventions ranged from two to 10 months. One trial reported that 69% of participants who received the exercise intervention were adherent to the exercise prescription. A second trial reported a 94% adherence to the exercise programme, with participants attending 45/48 sessions. The remaining trial reported a 96.8% adherence to the exercise intervention during the hospitalisation period. Two trials received funding; one from the National Center for Research Resources (US) and the other from Instituto de Salud Carlos III (Spain). The remaining trial did not receive funding. All trials were at an overall high risk of bias, derived from high risk of selective reporting bias and attrition bias in two trials. The results on all-cause mortality showed a higher risk of death in the exercise group versus the control group, but these results are very uncertain (risk ratio (RR) 3.14, 95% confidence interval (CI) 0.74 to 13.37; 2 trials, 165 participants; I² = 0%; very low-certainty evidence). The trials did not report data on serious adverse events excluding mortality or non-serious adverse events. However, all trials reported that there were no adverse effects associated with exercise. We are very uncertain on whether exercise compared with usual care has a beneficial or harmful effect on health-related quality of life assessed using the 36-item Short Form Physical Functioning subscale at the end of the intervention (mean difference (MD) 10.56, 95% CI -0.12 to 21.24; 2 trials, 169 participants; I² = 71%; very low-certainty evidence). None of the trials reported data on composite of cardiovascular mortality and cardiovascular disease, and cardiovascular disease post-transplantation. We are very uncertain if there are differences in aerobic capacity in terms of VO at the end of the intervention between groups (MD 0.80, 95% CI -0.80 to 2.39; 3 trials, 199 participants; I² = 0%; very low-certainty evidence). We are very uncertain if there are differences in muscle strength at end of the intervention between groups (MD 9.91, 95% CI -3.68 to 23.50; 3 trials, 199 participants; I² = 44%; very low-certainty evidence). One trial measured perceived fatigue using the Checklist Individual Strength (CIST). Participants in the exercise group showed a clinically important lower degree of fatigue perception than participants in the control group, with a mean reduction of 40 points in the CIST (95% CI 15.62 to 64.38; 1 trial, 30 participants). We identified three ongoing studies.
AUTHORS' CONCLUSIONS
Based on very low-certainty evidence in our systematic review, we are very uncertain of the role of exercise training (aerobic, resistance-based exercises, or both) in affecting mortality, health-related quality of life, and physical function (i.e. aerobic capacity and muscle strength) in liver transplant recipients. There were few data on the composite of cardiovascular mortality and cardiovascular disease, cardiovascular disease post-transplantation, and adverse event outcomes. We lack larger trials with blinded outcome assessment, designed according to the SPIRIT statement and reported according to the CONSORT statement.
Topics: Humans; Adult; Liver Transplantation; Quality of Life; Cardiovascular Diseases; Metabolic Syndrome; Exercise Therapy; Fatigue
PubMed: 37204002
DOI: 10.1002/14651858.CD013204.pub2