Epidemiology of myosteatosis Miljkovic, Iva; Zmuda, Joseph M
Current opinion in clinical nutrition and metabolic care
13, Številka:
3
Journal Article
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PURPOSE OF REVIEWTo summarize the epidemiology of myosteatosis and its association with diabetes.
RECENT FINDINGSThe role of myosteatosis (fat infiltration in skeletal muscle) in diabetes has ...received considerable attention. There is reasonably consistent evidence that myosteatosis contributes to glucose and insulin abnormalities and diabetes, possibly even independent of overall obesity. Novel hypotheses that link myosteatosis with insulin resistance and type 2 diabetes have also recently been proposed. These hypotheses suggest that impaired secretion of adipokines, modulation of nutritive blood flow to skeletal muscle, or both may be of importance for the development of myosteatosis. Recent longitudinal data also suggest that myosteatosis increases with aging, regardless of changes in body weight.
SUMMARYFurther studies are needed to identify the specific physiological mechanisms that influence myosteatosis, and the mechanisms that link this fat depot with insulin resistance. Longitudinal studies are also needed to evaluate the remodeling of skeletal muscle fat with aging, across a wider age spectrum, and across different populations, especially those at high risk of developing diabetes. There is also a need to evaluate whether myosteatosis influences the incidence of type 2 diabetes independent of overall adiposity. A better understanding of the factors that regulate myosteatosis may lead to the development of novel therapies that influence a more metabolically ‘healthy’ skeletal muscle.
Genome‐wide association studies identified single‐nucleotide polymorphisms (SNPs) that are associated with increased hepatic fat or elevated liver enzymes, presumably reflecting nonalcoholic fatty ...liver disease (NAFLD). To investigate whether these SNPs are associated with histological severity of NAFLD, 1117 (894 adults/223 children) individuals enrolled in the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network and National Institutes of Health Clinical Center studies with histologically confirmed NAFLD were genotyped for six SNPs that are associated with hepatic fat or liver enzymes in genome‐wide association studies. In adults, three SNPs on chromosome 22 showed associations with histological parameters of NASH. After adjustment for age, sex, diabetes, and alcohol consumption, the minor allele of rs738409 C/G, a nonsynonymous coding SNP in the patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) (adiponutrin) gene encoding an Ile148Met change, was associated with steatosis (P = 0.03), portal inflammation (P = 2.5 × 10−4), lobular inflammation (P = 0.005), Mallory‐Denk bodies (P = 0.015), NAFLD activity score (NAS, P = 0.004), and fibrosis (P = 7.7 × 10−6). Two other SNPs in the same region demonstrated similar associations. Three SNPs on chromosome 10 near the CHUK (conserved helix‐loop‐helix ubiquitous kinase) gene were independently associated with fibrosis (P = 0.010). In children, no SNP was associated with histological severity. However, the rs738409 G allele was associated with younger age at the time of biopsy in multivariate analysis (P = 0.045). Conclusion: In this large cohort of histologically proven NAFLD, we confirm the association of the rs738409 G allele with steatosis and describe its association with histological severity. In pediatric patients, the high‐risk rs738409 G allele is associated with an earlier presentation of disease. We also describe a hitherto unknown association between SNPs at a chromosome 10 locus and the severity of NASH fibrosis. (Hepatology 2010)
Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. A single‐nucleotide polymorphism (SNP), rs6834314, was associated with serum liver enzymes in the general ...population, presumably reflecting liver fat or injury. We studied rs6834314 and its nearest gene, 17‐beta hydroxysteroid dehydrogenase 13 (HSD17B13), to identify associations with histological features of NAFLD and to characterize the functional role of HSD17B13 in NAFLD pathogenesis. The minor allele of rs6834314 was significantly associated with increased steatosis but decreased inflammation, ballooning, Mallory‐Denk bodies, and liver enzyme levels in 768 adult Caucasians with biopsy‐proven NAFLD and with cirrhosis in the general population. We found two plausible causative variants in the HSD17B13 gene. rs72613567, a splice‐site SNP in high linkage with rs6834314 (r2 = 0.94) generates splice variants and shows a similar pattern of association with NAFLD histology. Its minor allele generates simultaneous expression of exon 6‐skipping and G‐nucleotide insertion variants. Another SNP, rs62305723 (encoding a P260S mutation), is significantly associated with decreased ballooning and inflammation. Hepatic expression of HSD17B13 is 5.9‐fold higher (P = 0.003) in patients with NAFLD. HSD17B13 is targeted to lipid droplets, requiring the conserved amino acid 22‐28 sequence and amino acid 71‐106 region. The protein has retinol dehydrogenase (RDH) activity, with enzymatic activity dependent on lipid droplet targeting and cofactor binding site. The exon 6 deletion, G insertion, and naturally occurring P260S mutation all confer loss of enzymatic activity. Conclusion: We demonstrate the association of variants in HSD17B13 with specific features of NAFLD histology and identify the enzyme as a lipid droplet–associated RDH; our data suggest that HSD17B13 plays a role in NAFLD through its enzymatic activity.
NT-proBNP is a biomarker of cardiovascular disease (CVD). Little is known about the heritability and genetic variants associated with NT-proBNP. Therefore, we estimated the heritability of and ...examined genetic associations of SNPs in the BNP gene region with circulating NT-proBNP and prevalent CVD in 4,331 participants from the Long Life Family Study (LLFS).
Genotypes of 10 SNPs from the NPPB and NPPA regions that encode BNP and A-type natriuretic peptide, respectively, were tested for association with NT-proBNP and prevalent cardiovascular disease and risk factors. We performed analyses using the Sequential Oligogenic Linkage Analysis (SOLAR) program to account for family relatedness, and adjusted all models for age, sex, and field center. The mean age of the LLFS was 69.8 years (range 24-110) with 55.4% females. NT-proBNP was significantly heritable (h2 = 0.21; P = 4x10-14), and the minor alleles of rs632793 (p<0.001) and rs41300100 (p = 0.05) were independently associated with higher serum NT-proBNP levels. Additionally, the minor allele of rs632793 was significantly and consistently associated with lower prevalent CVD, including blood pressures, independent of NT-proBNP level (all P<0.05). Results for prevalent CVD, but not NT-proBNP levels, showed significant interaction by familial generation.
In this family-based study of subjects with exceptional longevity, we identified several allelic variants in the BNP gene region associated with NT-pro-BNP levels and prevalent CVD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Context:
Total 25-hydroxyvitamin D (25OHD) is a marker of vitamin D status and is lower in African Americans than in whites. Whether this difference holds for free 25OHOD (f25OHD) is unclear, ...considering reported genetic-racial differences in vitamin D binding protein (DBP) used to calculate f25OHD.
Objectives:
Our objective was to assess racial-geographic differences in f25OHD and to understand inconsistencies in racial associations with DBP and calculated f25OHD.
Design:
This study used a cross-sectional design.
Setting:
The general community in the United States, United Kingdom, and The Gambia were included in this study.
Participants:
Men in Osteoporotic Fractures in Men and Medical Research Council studies (N = 1057) were included.
Exposures:
Total 25OHD concentration, race, and DBP (GC) genotype exposures were included.
Outcome Measures:
Directly measured f25OHD, DBP assessed by proteomics, monoclonal and polyclonal immunoassays, and calculated f25OHD were the outcome measures.
Results:
Total 25OHD correlated strongly with directly measured f25OHD (Spearman r = 0.84). Measured by monoclonal assay, mean DBP in African-ancestry subjects was approximately 50% lower than in whites, whereas DBP measured by polyclonal DBP antibodies or proteomic methods was not lower in African-ancestry. Calculated f25OHD (using polyclonal DBP assays) correlated strongly with directly measured f25OHD (r = 0.80–0.83). Free 25OHD, measured or calculated from polyclonal DBP assays, reflected total 25OHD concentration irrespective of race and was lower in African Americans than in US whites.
Conclusions:
Previously reported racial differences in DBP concentration are likely from monoclonal assay bias, as there was no racial difference in DBP concentration by other methods. This confirms the poor vitamin D status of many African-Americans and the utility of total 25OHD in assessing vitamin D in the general population.
We found no racial or genetic differences in serum vitamin D binding protein. Free 25OHD, directly measured or calculated from DBP (using polyclonal antibodies), was low in Afro-Americans, compared to US whites or blacks from The Gambia.
BACKGROUND/OBJECTIVES
To investigate potential mechanisms underlying the well‐established relationship of diabetes and obesity with cognitive decline, among older adults participating in a ...population‐based study.
DESIGN/SETTING
Ten‐year population‐based cohort study.
PARTICIPANTS
A total of 478 individuals aged 65 years and older.
MEASUREMENTS
We assayed fasting blood for markers of glycemia (glucose and hemoglobin A1c HbA1c), insulin resistance (IR) (insulin and homeostatic model assessment of IR), obesity (resistin, adiponectin, and glucagon‐like peptide‐1), and inflammation (C‐reactive protein). We modeled these indices as predictors of the slope of decline in global cognition, adjusting for age, sex, education, APOE*4 genotype, depressive symptoms, waist‐hip ratio (WHR), and systolic blood pressure, in multivariable regression analyses of the entire sample and stratified by sex‐specific median WHR. We then conducted WHR‐stratified machine‐learning (Classification and Regression Tree CART) analyses of the same variables.
RESULTS
In multivariable regression analyses, in the entire sample, HbA1c was significantly associated with cognitive decline. After stratifying by median WHR, HbA1c remained associated with cognitive decline in those with higher WHR. No metabolic indices were associated with cognitive decline in those with lower WHR. Cross‐validated WHR‐stratified CART analyses selected no predictors in participants older than 87 to 88 years. Faster cognitive decline was associated, in lower WHR participants younger than 87 years, with adiponectin of 11 or greater; and in higher WHR participants younger than 88 years, with HbA1c of 6.2% or greater.
CONCLUSIONS
Our population‐based data suggest that, in individuals younger than 88 years with central obesity, even modest degrees of hyperglycemia might independently predispose to faster cognitive decline. In contrast, among those younger than 87 years without central obesity, adiponectin may be a novel independent risk factor for cognitive decline. J Am Geriatr Soc 68:991–998, 2020
Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to ...identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P = 3.8 x 10(-5)), establishing a novel phenotype for this genetic variant.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Relationship Between Serum IGF-1 and BMI Differs by Age Sherlala, Rehab A; Kammerer, Candace M; Kuipers, Allison L ...
The journals of gerontology. Series A, Biological sciences and medical sciences,
06/2021, Letnik:
76, Številka:
7
Journal Article
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Abstract
Background
Serum levels of insulin-like growth factor 1 (IGF-1) and body mass index (BMI) are both associated with susceptibility to age-related diseases. Reports on the correlation between ...them have been conflicting, with both positive to negative correlations reported. However, the age ranges of the participants varied widely among these studies.
Methods
Using data on 4241 participants (aged 24–110) from the Long Life Family Study, we investigated the relationship between IGF-1 and BMI by age groups using regression analysis.
Results
When stratified by age quartile, the relationship between IGF-1 and BMI varied: in the first quartile (Q1, 20–58 years) the relationship was negative (β = −0.2, p = .002); in Q2 (58–66 years) and Q3 (67–86 years) the relationship was negative (β = −0.07, β = −0.01, respectively) but nonsignificant; and in Q4 (87–110 years) the relationship was positive (β = 0.31, p = .0002). This pattern did not differ by sex. We observed a similar age-related pattern between IGF-1 and BMI among participants in the third National Health and Nutritional Examination Survey.
Conclusions
Our results that the relationship between IGF-1 and BMI differs by age may explain some of the inconsistency in reports about their relationship and encourage additional studies to understand the mechanisms underlying it.
The epidemiologic information regarding international differences in bone mineral density (BMD) in women is currently insufficient. We compared BMD in older women across five racial/ethnic groups in ...four countries. The femoral neck, total hip, and lumbar spine BMD were measured in women (aged 65–74 years) from the Study of Osteoporotic Fractures (SOF) (5,035 Caucasian women and 256 African American women in the US), the Tobago Women’s Health Study (116 Afro-Caribbean women), the Ms Os Hong Kong Study (794 Hong Kong Chinese women) and the Namwon Study (1,377 South Korean women). BMD was corrected according to the cross-site calibration results for all scanners. When compared with US Caucasian women, the age adjusted mean BMD measurements at the hip sites were 21–31 % higher among Tobago Afro-Caribbean women and 13–23 % higher among African American women. The total hip and spine BMD values were 4–5 % lower among Hong Kong Chinese women and 4–7 % lower among South Korean women compared to US Caucasians. The femoral neck BMD was similar in Hong Kong Chinese women, but higher among South Korean women compared to US Caucasians. Current/past estrogen use was a significant contributing factor to the difference in BMD between US versus non-US women. Differences in body weight partially explained the difference in BMD between Asian versus non-Asian women. These findings show substantial racial/ethnic differences in BMD even within African or Asian origin individuals, and highlight the contributing role of body weight and estrogen use to the geographic and racial/ethnic variation in BMD.
While the gut microbiota is relatively stable through adulthood, its composition is influenced by various host and environmental factors, including changes in health, gastrointestinal processes ...(e.g., transit time, gastric acidity), medication use, and diet. The association of habitual diet, in the form of a posteriori–derived dietary patterns, and microbiota composition has not been adequately studied, particularly in older men.
The objective was to investigate the association of dietary patterns with the composition and diversity of the gut bacterial microbiota in community-dwelling, older men.
This cross-sectional study included 517 men who were participants in the Osteoporotic Fractures in Men (MrOS) Study (≥65 y of age at baseline in 2000–2002) and who provided a stool sample and completed an FFQ at MrOS Visit 4 in 2014–2016. Dietary patterns were derived by factor analysis. 16S ribosomal RNA target gene sequencing was performed and taxonomy assignments were derived using the Greengenes database. Linear regression and permutational multivariate analysis of variance (PERMANOVA) considered variations in alpha and beta diversity by dietary pattern, and a model that implements a 0-inflated Gaussian distribution of mean group abundance for each taxa (metagenomeSeq) assessed taxonomic variations by dietary pattern.
In multivariable-adjusted models, greater adherence to the Western pattern was positively associated with families Mogibacteriaceae and Veillonellaceae and genera Alistipes, Anaerotruncus, CC-115, Collinsella, Coprobacillus, Desulfovibrio, Dorea, Eubacterium, and Ruminococcus, while greater adherence to the prudent pattern was positively associated with order Streptophyta, family Victivallaceae, and genera Cetobacterium, Clostridium, Faecalibacterium, Lachnospira, Paraprevotella, and Veillonella. The relative abundance of the dominant gut bacterial phyla, Bacteroidetes and Firmicutes, did not differ between participants with greater adherence to the Western pattern, compared with those with greater adherence to the prudent pattern. Dietary patterns were not associated with measures of alpha diversity, but beta diversity measures were significantly associated with both Western and prudent patterns.
We observed significant associations between dietary patterns and measures of gut microbial composition in this sample of community-dwelling, older men.
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