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Diabetes Care Aug 2022To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status.
OBJECTIVE
To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status.
RESEARCH DESIGN AND METHODS
We analyzed a nationwide sample of 111,576 adults without CVD at baseline, using data from the China Cardiometabolic Disease and Cancer Cohort Study. Insulin resistance was estimated by sex-specific HOMA of insulin resistance (HOMA-IR) quartiles for participants with normal glucose tolerance, prediabetes, or diabetes, separately, and by 1 SD of HOMA-IR for the overall study participants. We used Cox proportional hazards models to examine the association between insulin resistance and incident CVD according to glucose tolerance status and evaluate the CVD risk associated with the combined categories of insulin resistance and obesity in prediabetes and diabetes, as compared with normal glucose tolerance. Models were adjusted for age, sex, education attainment, alcohol drinking, smoking, physical activity, and diet quality.
RESULTS
In participants with normal glucose tolerance, prediabetes, and diabetes defined by three glucose parameters, multivariable-adjusted hazard ratios (95% CIs) for incident CVD associated with the highest versus the lowest quartile of HOMA-IR were 1.03 (0.82-1.30), 1.23 (1.07-1.42), and 1.61 (1.30-2.00), respectively; the corresponding values for CVD per 1-SD increase in HOMA-IR were 1.04 (0.92-1.18), 1.12 (1.06-1.18), and 1.15 (1.09-1.21), respectively (P for interaction = 0.011). Compared with participants with normal glucose tolerance, in participants with prediabetes, the combination of the highest HOMA-IR quartile and obesity showed 17% (95% CI 2-34%) higher risk of CVD, while the combination of the lowest two HOMA-IR quartiles and nonobesity showed 15-17% lower risk of CVD. In participants with diabetes, the upper two HOMA-IR quartiles exhibited 44-77% higher risk of CVD, regardless of obesity status. Consistent findings were observed for glucose tolerance status defined by different combinations of glycemic parameters.
CONCLUSIONS
Glucose intolerance status exacerbated the association between insulin resistance and CVD risk. Compared with adults with normal glucose tolerance, adults with prediabetes who were both insulin resistant and obese exhibited higher risks of CVD, while in adults with diabetes, the CVD risk related to insulin resistance remained, regardless of obesity.
Topics: Adult; Blood Glucose; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus; Female; Humans; Insulin Resistance; Male; Obesity; Prediabetic State; Prospective Studies; Risk Factors
PubMed: 35700159
DOI: 10.2337/dc22-0202 -
Cureus May 2022Lactose intolerance (LI) appears usually in later ages when the lactase enzyme becomes deficient or absent in the small intestine. Conflicting results have been reported...
BACKGROUND
Lactose intolerance (LI) appears usually in later ages when the lactase enzyme becomes deficient or absent in the small intestine. Conflicting results have been reported in the literature about the association of lactose intolerance with various gastrointestinal malignancies. Hence, our aim was to study the association between LI, colon cancer (CCa), and gastric cancer (GC) using a large database.
METHODS
A cross-sectional study was performed using the National Inpatient Sample (NIS) database between 2004 and 2014. We identified adult patients (18-90 years) who were diagnosed with LI (study group) using appropriate International Classification of Diseases, Ninth Revision (ICD-9) codes. The control group comprised patients who did not have a diagnosis of LI. We identified the diagnosis of CCa and GC in both study and control groups using the ICD-9 codes. Univariable and multivariable logistic regression analyses were performed to assess the association between LI, CCa, and GC.
RESULTS
The total population comprised 71,360,501 patients, of which 57,909 (0.08%) were diagnosed with LI. LI patients were older (62 vs 51 years) with more females (61.5% vs 60.1%) and less African American patients (11.8% vs 14.3%) (p <0.0001 for all). In addition, LI patients had more smoking (12.4% vs 12%) and obesity (15% vs 8.9%). On the other hand, patients in the LI group had less alcohol use (3.8% vs 4.2%) (p <0.0001). After adjusting for the age, gender, race, smoking, alcohol, obesity, and inflammatory bowel disease, the LI group had a slightly lower rate of CCa (OR 0 .974, 95%CI 0.906-1.048, p = 0.486) and a lower rate of GC (OR: 0.993, 95%CI 0.924-1.068, p =0.853); however, the results were not statistically significant.
CONCLUSION
Patients with lactose intolerance may have a lower risk of colon and gastric cancer. However, these findings were not statistically significant. Further studies are needed to understand this association.
PubMed: 35676992
DOI: 10.7759/cureus.24713 -
Pediatric Pulmonology Oct 2022Cystic fibrosis (CF)-related diabetes (CFRD) affects 50% of CF adults. Gut microbial imbalance (dysbiosis) aggravates their inflammatory response and contributes to...
BACKGROUND AND OBJECTIVES
Cystic fibrosis (CF)-related diabetes (CFRD) affects 50% of CF adults. Gut microbial imbalance (dysbiosis) aggravates their inflammatory response and contributes to insulin resistance (IR). We hypothesized that probiotics may improve glucose tolerance by correcting dysbiosis.
METHODS
A single-center prospective pilot study assessing the effect of Vivomixx® probiotic (450 billion/sachet) on clinical status, spirometry, lung clearance index (LCI), and quality of life (QOL) questionnaires; inflammatory parameters (urine and stool metabolomics, blood cytokines); and glucose metabolism (oral glucose tolerance test [OGTT]), continuous glucose monitoring [CGM], and homeostasis model assessment of IR (HOMA-IR) in CF patients.
RESULTS
Twenty-three CF patients (six CFRD), mean age 17.7 ± 8.2 years. After 4 months of probiotic administration, urinary cysteine (p = 0.018), lactulose (p = 0.028), arabinose (p = 0.036), mannitol (p = 0.041), and indole 3-lactate (p = 0.046) significantly increased, while 3-methylhistidine (p = 0.046) and N-acetyl glutamine (p = 0.047) decreased. Stool 2-Hydroxyisobutyrate (p = 0.022) and 3-methyl-2-oxovalerate (p = 0.034) decreased. Principal component analysis, based on urine metabolites, found significant partitions between subjects at the end of treatment compared to baseline (p = 0.004). After 2 months of probiotics, the digestive symptoms domain of Cystic Fibrosis Questionnaire-Revised improved (p = 0.007). In the nondiabetic patients, a slight decrease in HOMA-IR, from 2.28 to 1.86, was observed. There was no significant change in spirometry results, LCI, blood cytokines and CGM.
CONCLUSIONS
Changes in urine and stool metabolic profiles, following the administration of probiotics, may suggest a positive effect on glucose metabolism in CF. Larger long-term studies are needed to confirm our findings. Understanding the interplay between dysbiosis, inflammation, and glucose metabolism may help preventing CFRD.
Topics: Adolescent; Adult; Arabinose; Blood Glucose; Blood Glucose Self-Monitoring; Child; Cysteine; Cystic Fibrosis; Cytokines; Diabetes Mellitus; Dysbiosis; Glucose Intolerance; Glutamine; Humans; Indoles; Insulin Resistance; Lactates; Lactulose; Mannitol; Pilot Projects; Probiotics; Prospective Studies; Quality of Life; Young Adult
PubMed: 35676769
DOI: 10.1002/ppul.26037 -
Biochimica Et Biophysica Acta.... Sep 2022Defects in cell membrane homeostasis are implicated in numerous disorders, including cancer, neurodegeneration and diabetes. There is therefore a need for a powerful...
Defects in cell membrane homeostasis are implicated in numerous disorders, including cancer, neurodegeneration and diabetes. There is therefore a need for a powerful model to study membrane homeostasis and to identify eventual therapeutic routes. The C. elegans gene paqr-2 encodes a homolog of the mammalian AdipoR1 and AdipoR2 proteins that, when mutated, causes a membrane homeostasis defect accompanied by multiple phenotypes such as intolerance to dietary saturated fatty acids, intolerance to cold and a characteristic tail tip morphology defect. We screened a compound library to identify molecules that can suppress the paqr-2 phenotypes. A single positive hit, Tyloxapol, was found that very effectively suppresses multiple paqr-2 phenotypes. Tyloxapol is a non-ionic detergent currently in use clinically as an expectorant. Importantly, we examined the potential of Tyloxapol as a fluidizer in human cells and found that it improves the viability and membrane fluidity of AdipoR2-deficient human cells challenged with palmitic acid, a membrane-rigidifying saturated fatty acid.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Fatty Acids; Mammals; Membrane Proteins; Polyethylene Glycols; Receptors, Adiponectin
PubMed: 35588889
DOI: 10.1016/j.bbamem.2022.183959 -
Nutrients Apr 2022Dietary supplements for weight management include myriad ingredients with thermogenic, lipotropic, satiety, and other metabolic effects. Recently, the safety of this... (Review)
Review
Dietary supplements for weight management include myriad ingredients with thermogenic, lipotropic, satiety, and other metabolic effects. Recently, the safety of this product category has been questioned. In this review, we summarize the safety evidence as well as relevant clinical findings on weight management and metabolic effects of six representative dietary supplement ingredients: caffeine, green tea extract (GTE), green coffee bean extract (GCBE), choline, glucomannan, and capsaicinoids and capsinoids. Of these, caffeine, GTE (specifically epigallocatechin gallate [EGCG]), and choline have recommended intake limits, which appear not to be exceeded when used according to manufacturers' instructions. Serious adverse events from supplements with these ingredients are rare and typically involve unusually high intakes. As with any dietary component, the potential for gastrointestinal intolerance, as well as possible interactions with concomitant medications/supplements exist, and the health status of the consumer should be considered when consuming these components. Most of the ingredients reviewed also improved markers of metabolic health, such as glucose, lipids, and blood pressure, although the data are limited for some. In summary, weight management supplements containing caffeine, GTE, GCBE, choline, glucomannan, and capsaicinoids and capsinoids are generally safe when taken as directed and demonstrate metabolic health benefits for overweight and obese people.
Topics: Antioxidants; Caffeine; Catechin; Choline; Dietary Supplements; Humans; Overweight; Plant Extracts; Tea
PubMed: 35565754
DOI: 10.3390/nu14091787 -
Microbial Biotechnology Aug 2022Non-wine yeasts could enhance the aroma and organoleptic profile of wines. However, compared to wine strains, they have specific intolerances to winemaking conditions....
Non-wine yeasts could enhance the aroma and organoleptic profile of wines. However, compared to wine strains, they have specific intolerances to winemaking conditions. To solve this problem, we generated intra- and interspecific hybrids using a non-GMO technique (rare-mating) in which non-wine strains of S. uvarum, S. kudriavzevii and S. cerevisiae species were crossed with a wine S. cerevisiae yeast. The hybrid that inherited the wine yeast mitochondrial showed better fermentation capacities, whereas hybrids carrying the non-wine strain mitotype reduced ethanol levels and increased glycerol, 2,3-butanediol and organic acid production. Moreover, all the hybrids produced several fruity and floral aromas compared to the wine yeast: β-phenylethyl acetate, isobutyl acetate, γ-octalactone, ethyl cinnamate in both varietal wines. Sc × Sk crosses produced three- to sixfold higher polyfunctional mercaptans, 4-mercapto-4-methylpentan-2-one (4MMP) and 3-mercaptohexanol (3MH). We proposed that the exceptional 3MH release observed in an S. cerevisiae × S. kudriavzevii hybrid was due to the cleavage of the non-volatile glutathione precursor (Glt-3MH) to detoxify the cell from the presence of methylglyoxal, a compound related to the high glycerol yield reached by this hybrid. In conclusion, hybrid generation allows us to obtain aromatically improved yeasts concerning their wine parent. In addition, they reduced ethanol and increased organic acids yields, which counteracts climate change effect on grapes.
Topics: Ethanol; Fermentation; Glycerol; Saccharomyces; Saccharomyces cerevisiae
PubMed: 35485391
DOI: 10.1111/1751-7915.14068 -
International Journal of Environmental... Apr 2022Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason...
Influence of (rs4680) and (rs1076560, rs1800497) Gene Polymorphisms on Safety and Efficacy of Methylphenidate Treatment in Children with Fetal Alcohol Spectrum Disorders.
Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason for pharmacological treatment of FASD children is attention deficit hyperactivity disorder (ADHD), and methylphenidate (MPH) is the drug of choice. The aim of the study was to assess whether children born of hPAE with ADHD, with or without morphological FASD, differ in terms of catechol-O-methyltransferase () and dopamine receptor D2 () gene polymorphisms, and if genetic predisposition affects response and safety of MPH treatment. The polymorphisms of (rs4680) and (rs1076560, rs1800497) were analyzed in DNA samples. A borderline significance was found for the correlation between MPH side effects and the G allele of (rs4680) ( = 0.04994) in all ADHD children. No effect of (rs4680) and (rs1076560, rs1800497) polymorphisms and the treatment efficacy was observed. The analyzed and gene polymorphisms seem to play no role in MPH efficacy in ADHD children with hPAE, while low-activity (Met158) variant carriers may be more intolerant to MPH. The MPH treatment is effective in ADHD independent of FASD, although the ADHD-FASD variant requires higher doses to be successful. These results may help in optimization and individualization in child psychiatry.
Topics: Attention Deficit Disorder with Hyperactivity; Catechol O-Methyltransferase; Child; Female; Fetal Alcohol Spectrum Disorders; Genotype; Humans; Methylphenidate; Polymorphism, Genetic; Pregnancy; Prenatal Exposure Delayed Effects; Receptors, Dopamine D2
PubMed: 35457347
DOI: 10.3390/ijerph19084479 -
Nutrients Mar 2022People that experience prenatal alcohol exposure (PAE) may have behavioral and metabolic impairments, and it is unclear whether these remain stable or change with age....
People that experience prenatal alcohol exposure (PAE) may have behavioral and metabolic impairments, and it is unclear whether these remain stable or change with age. We assessed behavioral and metabolic endpoints across the lifespan in a mouse model of fetal alcohol spectrum disorder (FASD). Pregnant C57BL/6J mice received alcohol (ALC; 3 g/kg) or maltose-dextrin (control, CON) daily from embryonic day 8.5 to 17.5. Offspring were tested on accelerating rotarod, Y-maze, novel object recognition, and fear conditioning at 6 weeks and 10 and 17 months; females were also tested at 24 months. Body composition, fasting glucose, and glucose clearance were assessed at 18 months. Female but not male ALC mice had greater adiposity than age-matched CON from 7 months onward. At 18 months, male but not female ALC mice had reduced glucose clearance and ALC mice were more likely to have elevated fasting glucose. In the rotarod training session, ALC females performed worse than CON. In the Y-maze, significant exposure-age interactions affected ALC performance in both sexes versus age-match CON. For fear conditioning, all animals acquired the task and froze more at older ages. In both the context and cued tasks, there were exposure-age interactions and ALC animals frozen less than CON at 10 months. Correlation analysis revealed that fasting glucose and glucose clearance correlated with % of body fat in ALC but not in CON mice. Additionally, glucose intolerance and % body fat negatively correlated with performance in the rotarod, context learning, and novel object recognition tasks in ALC but not CON mice. All mice exhibit worsening of behavioral performance as they age, and PAE did not further exacerbate this. ALC but not CON mice displayed adiposity and glucose intolerance that correlate with their cognitive impairments, suggesting that these may be mechanistically related in PAE. Findings emphasize that FASD should be considered a whole-body disorder.
Topics: Adiposity; Aging; Animals; Female; Fetal Alcohol Spectrum Disorders; Glucose; Glucose Intolerance; Humans; Male; Mice; Mice, Inbred C57BL; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 35406051
DOI: 10.3390/nu14071438 -
PloS One 2022Two theoretical perspectives have been proffered to explain changes in alcohol use during the pandemic: the 'affordability-availability' mechanism (i.e., drinking...
Two theoretical perspectives have been proffered to explain changes in alcohol use during the pandemic: the 'affordability-availability' mechanism (i.e., drinking decreases due to changes in physical availability and/or reduced disposable income) and the 'psychological-coping' mechanism (i.e., drinking increases as adults attempt to cope with pandemic-related distress). We tested these alternative perspectives via longitudinal analyses of the COVID-19 Psychological Consortium (C19PRC) Study data (spanning three timepoints during March to July 2020). Respondents provided data on psychological measures (e.g., anxiety, depression, posttraumatic stress, paranoia, extraversion, neuroticism, death anxiety, COVID-19 anxiety, intolerance of uncertainty, resilience), changes in socio-economic circumstances (e.g., income loss, reduced working hours), drinking motives, solitary drinking, and 'at-risk' drinking (assessed using a modified version of the AUDIT-C). Structural equation modelling was used to determine (i) whether 'at-risk' drinking during the pandemic differed from that recalled before the pandemic, (ii) dimensions of drinking motives and the psychosocial correlates of these dimensions, (iii) if increased alcohol consumption was predicted by drinking motives, solitary drinking, and socio-economic changes. The proportion of adults who recalled engaging in 'at-risk' drinking decreased significantly from 35.9% pre-pandemic to 32.0% during the pandemic. Drinking to cope was uniquely predicted by experiences of anxiety and/or depression and low resilience levels. Income loss or reduced working hours were not associated with coping, social enhancement, or conformity drinking motives, nor changes in drinking during lockdown. In the earliest stage of the pandemic, psychological-coping mechanisms may have been a stronger driver to changes in adults' alcohol use than 'affordability-availability' alone.
Topics: Adaptation, Psychological; Adult; Alcohol Drinking; COVID-19; Communicable Disease Control; Costs and Cost Analysis; Humans; Motivation; Pandemics
PubMed: 35324964
DOI: 10.1371/journal.pone.0265145 -
Scientific Reports Mar 2022ALDH2 is a key enzyme in alcohol metabolism that protects cells from acetaldehyde toxicity. Using iHS, iSAFE and F statistics, we identified regulatory acting variants...
ALDH2 is a key enzyme in alcohol metabolism that protects cells from acetaldehyde toxicity. Using iHS, iSAFE and F statistics, we identified regulatory acting variants affecting ALDH2 gene expression under positive selection in populations of European ancestry. Several SNPs (rs3184504, rs4766578, rs10774625, rs597808, rs653178, rs847892, rs2013002) that function as eQTLs for ALDH2 in various tissues showed evidence of strong positive selection. Very large pairwise F values indicated high genetic differentiation at these loci between populations of European ancestry and populations of other global ancestries. Estimating the timing of positive selection on the beneficial alleles suggests that these variants were recently adapted approximately 3000-3700 years ago. The derived beneficial alleles are in complete linkage disequilibrium with the derived ALDH2 promoter variant rs886205, which is associated with higher transcriptional activity. The SNPs rs4766578 and rs847892 are located in binding sequences for the transcription factor HNF4A, which is an important regulatory element of ALDH2 gene expression. In contrast to the missense variant ALDH2 rs671 (ALDH2*2), which is common only in East Asian populations and is associated with greatly reduced enzyme activity and alcohol intolerance, the beneficial alleles of the regulatory variants identified in this study are associated with increased expression of ALDH2. This suggests adaptation of Europeans to higher alcohol consumption.
Topics: Alcohol Drinking; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Alleles; Asian People; Gene Expression; Humans; Polymorphism, Single Nucleotide
PubMed: 35296751
DOI: 10.1038/s41598-022-08588-0