The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects.
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ABSTRACT:
SUBMITTER: Niemi M
PROVIDER: S-EPMC1727442 | biostudies-other | 1999 Apr
REPOSITORIES: biostudies-other
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Project description:BackgroundAlthough dietary selenium (Se) deficiency or excess induces type 2 diabetes-like symptoms in mice, suboptimal body Se status usually causes no symptoms but may promote age-related decline in overall health.ObjectivesWe sought to determine the dietary Se requirement for protection against type 2 diabetes-like symptoms in mice.MethodsThirty mature (aged 4 mo) male C57BL/6J mice were fed a Se-deficient torula yeast AIN-93M diet supplemented with Na2SeO4 in graded concentrations totaling 0.01 (basal), 0.04, 0.07, 0.10, and 0.13 (control) mg Se/kg for 4 mo (n = 6) until they were middle-aged (8 mo). Droplets of whole blood were used to determine glucose tolerance and insulin sensitivity in the mice from ages 5 to 8 mo. Postmortem serum, liver, and skeletal muscle were collected to assay for selenoprotein expression and markers of glucose metabolism. Data were analyzed by 1-way ANCOVA with or without random effects for time-repeated measurements using live mice or postmortem samples, respectively.ResultsCompared with control, the consumption of basal diet increased (P < 0.05) fasting serum insulin (95% CI: 52%, 182%) and leptin (95% CI: 103%, 118%) concentrations in middle-aged mice. Dietary Se insufficiency decreased (P < 0.05) 1) glucose tolerance (13-79%) and insulin sensitivity (15-65%) at ≤0.10 mg Se/kg; 2) baseline thymoma viral proto-oncogene phosphorylation on S473 (27-54%) and T308 (22-46%) at ≤0.10 and ≤0.07 mg Se/kg, respectively, in the muscle but not the liver; and 3) serum glutathione peroxidase 3 (51-83%), liver and muscle glutathione peroxidase 1 (32-84%), serum and liver selenoprotein P (28-42%), and liver and muscle selenoprotein H (39-48%) and selenoprotein W (16-73%) protein concentrations at ≤0.04, ≤0.10, ≤0.07, and ≤0.10 mg Se/kg, respectively.ConclusionsMice fed diets containing ≤0.10 mg Se/kg display impaired glucose tolerance and insulin sensitivity, suggesting increased susceptibility to type 2 diabetes by suboptimal Se status at levels ≤23% of nutritional needs.
| S-EPMC8502482 | biostudies-literature
Project description:BackgroundGallstone disease (GSD) is a common biliary tract disease worldwide. Previous studies have investigated the association of apolipoprotein E (APOE) E4 with GSD and reported inconsistent results.MethodsIn this paper, we conducted meta-analyses to examine whether APOE E4 is associated with the risk of GSD. A systematic literature search was performed in PubMed, Cochrane Library, EMBASE, and Google Scholar using the following inclusion criteria: 1) Studies on human subjects; 2) subjects in the control group must undergo ultrasound GSD screening, and presence of GSD in the experiment group can be clearly determined, e.g., diagnosis of GSD through ultrasound screening or a previous history of cholecystectomy or cholelithiasis; 3) the studies reported APOE genotype data (APOE E4+ vs. E4-) for subjects with and without GSD. In all the meta-analyses, we used random-effects models to calculate the odds ratios (ORs) as a measure of association as well as the corresponding confidence intervals (CIs).ResultsOur literature search found 13 publications with 14 studies, including a total of 1632 GSD patients and 5001 controls, that met the eligibility criteria and were included in the meta-analyses. We did not find a significant association between APOE E4 and risk of GSD (OR = 1.23, 95% CI: 0.89-1.68; p = 0.205). No significant associations were observed in subgroup analyses by gender and mean age. We obtained similar insignificant findings if an additive model was used, if subjects who had E2E4 genotype were excluded, or if low-quality studies were excluded.ConclusionOur meta-analysis found insufficient evidence for the effect of APOE E4 on GSD risk. Future studies with large sample sizes that control for important confounding/risk factors are needed to validate our findings and to explore other genetic loci that might affect GSD risk.
| S-EPMC6570961 | biostudies-literature
Project description:BackgroundPhocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE) have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life.MethodsCase control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment.ResultsClinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females) and 17 controls (37.9±9.0 years; 8 females) demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1), L5 radiculopathic sensory impairment (n = 1) and cervical myelopathy (n = 1). In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002) ([95% CI], p-value)) and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089)) in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232)) and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169)).ConclusionsWe found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation.
| S-EPMC4839770 | biostudies-literature
Project description:BackgroundOur aim was to investigate the association between XbaI gene polymorphisms in the apolipoprotein B (APOB) gene and gallstone disease (GD) risk through a comparison of the allele and genotype distribution frequencies at this site using meta-analysis.MethodsA literature search was performed using PubMed and Wanfang through Jun 1, 2020. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of associations.ResultsAfter a comprehensive search, 14 different articles that met the inclusion criteria were selected, with 1583 cases and 1794 controls. Individuals carrying the A-allele or AA genotype of the rs693 polymorphism were determined to possibly have an increased risk of GD. For example, there was a significant relationship between the rs693 polymorphism and increased GD risk in the whole group (OR: 1.40, 95 % CI: 1.05-1.87 in the allelic contrast model), the Asian population (OR: 1.58, 95 % CI: 1.48-2.84 in the heterozygote model), and the hospital-based source of the control (OR: 1.79, 95 % CI: 1.13-2.84 in the dominant model).ConclusionsThis study suggests that the APOB rs693 polymorphism is potentially associated with GD susceptibility, which might offer a detection marker for use in future large scale clinic research.
| S-EPMC8091557 | biostudies-literature
Project description:Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased ?2-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2>1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation.
| S-EPMC4343260 | biostudies-literature
Project description:In obese male subjects, visceral adiposity has been associated with obstructive sleep apnoea (OSA), while studies in overweight males and females are limited. Our goal was to examine the association between OSA and visceral fat in a relatively nonobese population and assess the effects of 2 months placebo-controlled continuous positive airway pressure (CPAP) use on abdominal fat. 81 subjects, 22 middle-aged males and 20 post-menopausal females with OSA, and 19 male and 20 female controls were studied in the sleep laboratory for four nights. Abdominal (visceral (VAT) and subcutaneous (SAT) adipose tissue) and liver fat were assessed with computed tomography. OSA patients were re-assessed post-CPAP and post sham-CPAP. Apnoeic males had significantly higher VAT than controls, while apnoeic females had higher SAT than controls. In both sexes, OSA was associated with increased liver fat. In males, apnoea was associated with VAT whereas in females it was associated with subcutaneous, visceral and total fat. CPAP did not affect abdominal and liver fat. In overweight males, visceral adiposity is associated with OSA whereas in females it is associated with global adiposity. In overweight males, our therapeutic goal should be the reduction of visceral adiposity and its metabolic correlates, whereas, in females, weight loss may be sufficient. Short-term CPAP treatment does not affect general, abdominal or intra-hepatic adiposity.
| S-EPMC7091531 | biostudies-literature
Project description:ObjectiveTo examine in vivo amyloid burden in relation to APOEε4 genotype in middle-aged Hispanics. We hypothesize higher amyloid levels among APOE ε4 carriers vs APOE ε4 noncarriers.MethodsThis is a cross-sectional study in a community-based sample of 249 middle-aged Hispanics in New York City who underwent a 3T brain MRI and PET with the amyloid radioligand 18F-florbetaben. APOE genotype was the primary exposure. The primary outcome was amyloid positivity. The secondary outcome was subthreshold amyloid levels examined as a continuous variable.ResultsAPOE ε4 carriers (n = 85) had a higher frequency (15.3%) of amyloid positivity compared to APOE ε4 noncarriers (n = 164, 1.8%). In the subthreshold group of amyloid-negative participants (n = 233), APOE ε4 carriers (n = 72) had a 0.02 (95% confidence interval [CI] 0.01-0.04) higher global brain amyloid standardized uptake value ratio (SUVR) compared to APOE ε4 noncarriers (n = 161). Compared to participants with the ε3/ε3 genotype, participants with ε4/ε4 had the highest frequency of amyloid positivity (28.6%), followed by those with ε3/ε4 (11%). Among amyloid-negative participants (n = 233), compared to participants with ε3/ε3 (n = 134), those with ε4/ε4 (n = 5) had a 0.12 (95% CI 0.07-0.17) higher global brain amyloid SUVR, and those with ε3/ε4 had a 0.02 higher SUVR (95% CI 0.003-0.04). Results were similar when a median split was used for elevated amyloid, when continuous amyloid SUVR was analyzed in all participants, and in nonparametric Mann-Whitney comparisons.ConclusionMiddle-aged Hispanic APOE ε4 carriers have higher in vivo brain amyloid burden compared with noncarriers, as reported in non-Hispanics.
| S-EPMC7713748 | biostudies-literature
Project description:BackgroundLong chain omega-3 polyunsaturated fatty acids (ω-3PUFA) supplementation in animal models of diet-induced obesity has consistently shown to improve insulin sensitivity. The same is not always reported in human studies with insulin resistant (IR) subjects with obesity.ObjectiveWe studied whether high-dose ω-3PUFA supplementation for 3 months improves insulin sensitivity and adipose tissue (AT) inflammation in IR subjects with obesity.MethodsThirteen subjects (BMI = 39.3 ± 1.6 kg/m2) underwent 80 mU/m2·min euglycemic-hyperinsulinemic clamp with subcutaneous (Sc) AT biopsy before and after 3 months of ω-3PUFA (DHA and EPA, 4 g/daily) supplementation. Cytoadipokine plasma profiles were assessed before and after ω-3PUFA. AT-specific inflammatory gene expression was evaluated on Sc fat biopsies. Microarray analysis was performed on the fat biopsies collected during the program.ResultsPalmitic and stearic acid plasma levels were significantly reduced (P < 0.05) after ω-3PUFA. Gene expression of pro-inflammatory markers and adipokines were improved after ω-3PUFA (P < 0.05). Systemic inflammation was decreased after ω-3PUFA, as shown by cytokine assessment (P < 0.05). These changes were associated with a 25% increase in insulin-stimulated glucose disposal (4.7 ± 0.6 mg/kg ffm•min vs. 5.9 ± 0.9 mg/kg ffm•min) despite no change in body weight. Microarray analysis identified 53 probe sets significantly altered post- ω-3PUFA, with Apolipoprotein E (APOE) being one of the most upregulated genes.ConclusionHigh dose of long chain ω-3PUFA supplementation modulates significant changes in plasma fatty acid profile, AT, and systemic inflammation. These findings are associated with significant improvement of insulin-stimulated glucose disposal. Unbiased microarray analysis of Sc fat biopsy identified APOE as among the most differentially regulated gene after ω-3PUFA supplementation. We speculate that ω-3PUFA increases macrophage-derived APOE mRNA levels with anti-inflammatory properties.
| S-EPMC8159741 | biostudies-literature
Project description:Exercise intolerance among the clinical symptoms in patients with atrial fibrillation (AF) has usually been masked by their adjusted life style. We sought to assess the role of CHA2DS2-VASc score to predict exercise intolerance in asymptomatic AF patients, and further examine whether the relationship differs by age and gender. Among the 6,275 participants of the prospective Korean registry of the Comparison study of Drugs for symptom control and complication prevention of Atrial Fibrillation (CODE-AF), 1,080 AF patients who underwent exercise treadmill testing were studied. Exercise intolerance was defined as a peak exercise capacity of 7 metabolic equivalents (METs) or less, and the patients were divided into two groups for the analysis: ?7 METs (n?=?131) and >7 METs (n?=?949). Patients with exercise intolerance had a significantly higher CHA2DS2-VASc score than those without (3.1?±?1.3 vs. 2.0?±?1.5, p?<?0.0001). In the multivariate analysis, a higher CHA2DS2-VASc score (OR 1.54, 95% CI 1.31-1.81, p?<?0.0001), corrected QT interval (OR 1.01, 95% CI 1.00-1.02, p?=?0.026), and increased left atrial volume index (OR 1.02, 95% CI 1.01-1.03, p?=?0.001) were found to be independent predictors of exercise intolerance. The impact of the CHA2DS2-VASc score on exercise intolerance was significant only in male patients aged <65 years (OR 3.30, 95% CI 1.76-6.19, p?<?0.0001). The CHA2DS2-VASc score may be a feasible risk assessment tool to predict exercise intolerance, especially in young and middle-aged male patients with asymptomatic AF.
| S-EPMC6303333 | biostudies-literature
Project description:BACKGROUND:Transient cognitive impairment is common in adult patients of all ages following anaesthesia and surgery. Apolipoprotein E (APOE) ?4 carriers may have a larger deterioration in short-term cognitive function after major surgery compared with APOE ?4 noncarriers. OBJECTIVES:The aim was to examine the effect of APOE ?4 on the association between exposure to surgery and anaesthesia, and subsequent cognitive functioning. A more pronounced deterioration in cognitive function in APOE ?4 carriers was hypothesised. DESIGN:An observational cross-sectional and a 6 to 10 years longitudinal twin cohort design. SETTING:Survey and register study of 2936 Danish twins aged 45 to 92 years. MAIN OUTCOME MEASURES:Cognitive function was assessed using five age-sensitive cognitive tests. In the cross-sectional study, we compared twins exposed to surgery with a reference group (unexposed). Linear regression models were used adjusting for sex and age and stratified by APOE ?4 carrier status. In the longitudinal cognitive follow-up study 1671 twins participated. Intrapair analyses were also performed using 70 same-sexed twin pairs concordant for APOE ?4 carrier status, but discordant for major surgery. RESULTS:APOE ?4 carriers had lower cognitive scores compared with noncarriers, and this was statistically significant in elderly twins 70+ years of age (mean difference, -0.67; 95% CI, -1.14 to -0.17). There was no significant impact on cognitive function after surgery according to APOE ?4 carrier status in the cross-sectional study. Similarly, there was no APOE ?4 modification in the longitudinal study. Also, in the intrapair analyses no evidence was found of lower cognitive score after major surgery compared with the nonexposed cotwins among APOE ?4 carriers. CONCLUSION:No evidence was found of more pronounced long-term deterioration in cognitive function after surgery among APOE ?4 carriers, but elderly APOE ?4 carriers in general performed worse on the cognitive tests than noncarriers.
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