Exposure to Type 2 Diabetes Provokes Mitochondrial Impairment in Apparently Healthy Human Hearts.
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ABSTRACT:
SUBMITTER: Zweck E
PROVIDER: S-EPMC8132329 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeTo characterize accumulation of drug-modifiable cardiovascular (CV) risk factors in statin initiators who had no prior medication or hospitalizations for CV disease or diabetes.MethodsA cohort of 45-75-year-old statin initiators in Finland with no prior CV diseases, diabetes or medication for these conditions was followed up for 24 months after statin initiation for accumulation of CV and diabetes drugs. The number of drugs was measured semi-annually since the first statin purchase and analyzed by growth mixture modeling.ResultsOf the 11 948 apparently healthy statin initiators, 34% purchased at least one additional CV or diabetes drug during the subsequent 24 months. Of those, 20% redeemed no other CV or diabetes drugs at statin initiation but started to accumulate them after 18 months of follow-up, receiving on average 1.3 other drugs at 24 months. The majority, 59%, redeemed on average 0.5 drugs at statin initiation and accumulated 1.5 drugs by the end of 24-month follow-up. Seventeen percent received 1 additional drug at statin initiation, accumulating on average 3 drugs. The remaining 4% with an average of 2 CV or diabetes drugs at statin initiation redeemed 3.5 additional drugs during the follow-up.ConclusionsTwo years after statin initiation, 2 in 3 apparently healthy initiators could still be defined as such as reflected by CV and diabetes medication use.
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Project description:BACKGROUND:Mild cognitive impairment (MCI) is a stage between the expected cognitive decline of normal ageing and the serious decline of dementia. AIM:To identify risk factors and role of miRNAs associated with mild cognitive impairment (MCI) among employees. SUBJECTS AND METHOD:A cross-sectional study was carried out on 186 employees aged between 40 and 65 years. Cognitive function was evaluated using ACEIII, MoCA, and Quick cognitive tests. Medical history and lifestyle were assessed. Family 132 & 134 miRNA expressions were assessed by real-time PCR. RESULTS:MCI was detected among 14 / 186 (7.5%). miRNA 132 expression was the only significant miRNAs to detect MCI with low sensitivity and specificity (70%). The logistic analysis revealed that higher miRNA132 expressions, low monthly intake of; vegetables, unroasted nuts, low education and higher ALT levels were predicting factors for MCI with AOR 1.1 (1.01-3.3), 1.2 (1.04-1.43), 0.8 (0.8-0.98), 2.7 (1.9-7.4) and 1.6 (1.1-2.3) respectively. CONCLUSION:MiRNAs expression showed low sensitivity and specificity in detecting MCI; only miRNA 132 might be used. Several modifiable factors seem to reduce the risk of MCI.
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Project description:Presence of a systolic murmur is not always indicative of organic heart disease or abnormality, especially so in asymptomatic individuals. We studied 210 young adults (192 males, 18 females) of the age group 16 to 23 years with systolic murmurs to evaluate the utility of noninvasive tests in ascertaining the presence or absence of heart disease. Each case was categorized after clinical evaluation and again after noninvasive investigations (chest radiogram, 12 lead ECG, and echocardiography) into 3 groups. Based on clinical evaluation alone, 190 (90.5%) cases had no evidence of heart disease (group A), 16 (7.6%) cases had definite heart disease (group C) and in 4 (1.9%) cases the presence of heart disease could not be ruled out definitely (group B). The recategorization after investigations did not alter the initial diagnosis in any of the subjects from groups A and C (98.1%). Two cases from group B (0.95%) changed groups whereas in the remaining 2 cases (0.95%) from group B no definite conclusions could be reached even after echocardiography.
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Project description:BACKGROUND: Hypercholesterolemia (HC) is a major risk factor in the development of coronary heart disease (CHD). Serum cholesterol is directly related to complications and mortalities associated with heart diseases. There are a few studies that describe HC among youths in the Arab Gulf countries. We sought to evaluate HC among young healthy university students to assess their risk of developing CHD. METHODS: Lipid profile of 166 students between the ages of 16-30 years (Mean: 20.49±2.96) were examined and blood glucose, total protein, albumin, thyroid stimulating hormone (TSH) and the inflammation marker high sensitivity CRP (hsCRP) were determined. Each volunteer filled a questionnaire about her/his lifestyle and personal and family medical histories and height and weight were measured to determine body mass index (BMI). The data were analyzed using SPSS version 17. Chi-Square was used to determine the relation between categorical variables. A p-value <0.05 was considered statistically significant. RESULTS: According to the American Heart Association criteria, 44 (26.5%) students were identified with primary hypercholesterolemia (PHC) in the first testing round. After proper health counseling, the same tests were repeated after 2-3 weeks in all 44 hypercholesterolemic students. We found only 26 (15.6%) of them to be hypercholesterolemic. There was a significant relation between high total cholesterol (TC) and high TC/HDLC, as well as high or very high hsCRP and high TC/HDLC (both, p<0.001). Males tend to have higher TC/HDLC and hsCRP than females (both p0.002 and 0.005, respectively). Family history of CHD was found in 8 students and obesity was recorded in 5 volunteers. CONCLUSION: The results necessitate further studies in determining the cause of PHC. We predict a genetic element contributing to the high percentage of PHC in the current study.
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Project description:Equine coronavirus (ECoV) infection is the cause of an emerging enteric disease of adult horses. Outbreaks have been reported in the USA, EU and Japan, as well as sporadic cases in the UK and Saudi Arabia. Infection of ECoV in horses in Israel has never been reported, and the risk of exposure is unknown. Importation and exportation of horses from and into Israel may have increased the exposure of horses in Israel to ECoV. While the disease is mostly self-limiting, with or without supportive treatment, severe complications may occur in some animals, and healthy carriers may pose a risk of infection to other horses. This study was set to evaluate the risk of exposure to ECoV of horses in Israel by using a previously validated, S1-based enzyme-linked immunosorbent assay (ELISA). A total of 41 out of 333 horses (12.3%) were seropositive. Exposure to ECoV was detected in 17 of 29 farms (58.6%) and the seroprevalence varied between 0 and 37.5% amongst farms. The only factor found to be significantly associated with ECoV exposure in the multivariable model was the geographical area (p < 0.001). ECoV should be included in the differential diagnosis list of pathogens in cases of adult horses with anorexia, lethargy, fever and gastrointestinal signs in Israel.
| S-EPMC8004030 | biostudies-literature
Project description:Mitochondrial function has been implicated and studied in numerous complex age-related diseases. Understanding the potential role of mitochondria in disease pathophysiology is of importance due to the rise in prevalence of complex age-related diseases, such as type 2 diabetes (T2D) and Alzheimer's disease (AD). These two diseases specifically share common pathophysiological characteristics which potentially point to a common root cause or factors for disease exacerbation. Studying the shared phenomena in Mexican Americans is of particular importance due to the disproportionate prevalence of both T2D and AD in this population. Here, we assessed the potential role of mitochondria in T2D and cognitive impairment (CI) in a Mexican American cohort by analyzing blood-based indices of mitochondrial DNA copy number (mtDNACN) and cell-free mitochondrial DNA (CFmtDNA). These mitochondrial metrics were also analyzed for correlation with relevant neuropsychological variables and physiological data collected as indicators of disease and/or disease progression. We found mtDNACN to be significantly decreased in individuals with CI, while CFmtDNA was significantly elevated in T2D; further, CFmtDNA elevation was significantly exacerbated in individuals with both diseases. MtDNACN was found to negatively correlate with age and fatty acid binding protein concentration, while positively correlating with CFmtDNA as well as CERAD total recall score. Candidate gene SNP-set analysis was performed on genes previously implicated in maintenance and control of mitochondrial dynamics to determine if nuclear variants may account for variability in mtDNACN. The results point to a single significant locus, in the LRRK2/MUC19 region, encoding leucine rich repeat kinase 2 and mucin 19. This locus has been previously implicated in Parkinson's disease, among others; rs7302859 was the driver SNP. These combined findings further indicate that mitochondrial dysfunction (as assessed by proxy via mtDNACN) is intimately linked to both T2D and CI phenotypes as well as aging.
| S-EPMC6414026 | biostudies-literature
Project description:IntroductionThe global prevalence of metabolic syndrome and its association with increased morbidity and mortality has been rigorously studied. However, the true prevalence of "metabolic health", i.e. individuals without any metabolic abnormalities is not clear. Here, we sought to determine the prevalence of "metabolically healthy" individuals and characterize the "transition phase" from metabolic health to development of dysfunction over a follow-up period of 5 years.MethodsWe included 20,507 individuals from the Tel Aviv Sourasky Medical Center Inflammation Survey (TAMCIS) which comprises apparently healthy individuals attending their annual health survey. A second follow-up visit was documented after 4.8 (± 0.6) years. We defined a group of metabolically healthy participants without metabolic abnormalities nor obesity and compared their characteristics and change in biomarkers over time to participants who developed metabolic impairment on their follow-up visit. The intersections of all metabolic syndrome components and elevated high sensitivity C-reactive protein (hs-CRP) were also analyzed.ResultsA quarter of the cohort (5379 individuals, (26.2%) did not fulfill any metabolic syndrome criteria during their baseline visit. A total of 985 individuals (12.7% of returning participants) developed metabolic criteria over time with hypertension being the most prevalent component to develop among these participants. Individuals that became metabolically impaired over time demonstrated increased overlap between metabolic syndrome criteria and elevated hs-CRP levels. The group that became metabolically impaired over time also presented higher delta values of WBC, RBC, liver biomarkers, and uric acid compared with participants who were consistently metabolically impaired. LDL-C (low-density lipoprotein cholesterol) delta levels were similar.ConclusionsRoughly one-quarter of apparently healthy adults are defined as "metabolically healthy" according to current definitions. The transition from health to metabolic dysfunction is accompanied with active inflammation and several non-metabolic syndrome biomarkers. Aggressive screening for these biomarkers, blood pressure and hs-CRP might help identify apparently healthy individuals at increased risk of developing metabolic syndrome over time.
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Project description:MicroRNAs (miRNAs) regulate gene expression and have many roles in the brain, but a role in oligodendrocyte (OL) function has not been demonstrated.A Dicer floxed conditional allele was crossed with the proteolipid protein promoter-driven inducible Cre allele to generate inducible, OL-specific Dicer-floxed mice.OL-specific Dicer mutants show demyelination, oxidative damage, inflammatory astrocytosis and microgliosis in the brain, and eventually neuronal degeneration and shorter lifespan. miR-219 and its target ELOVL7 (elongation of very long chain fatty acids protein 7) were identified as the main molecular components that are involved in the development of the phenotype in these mice. Overexpressing ELOVL7 results in lipid accumulation, which is suppressed by miR-219 co-overexpression. In Dicer mutant brain, excess lipids accumulate in myelin-rich brain regions, and the peroxisomal beta-oxidation activity is dramatically reduced.Postnatal Dicer ablation in mature OLs results in inflammatory neuronal degeneration through increased demyelination, lipid accumulation, and peroxisomal and oxidative damage, and therefore indicates that miRNAs play an essential role in the maintenance of lipids and redox homeostasis in mature OLs that are necessary for supporting axonal integrity as well as the formation of compact myelin.
| S-EPMC2885004 | biostudies-literature
Project description:BackgroundThe purpose of this study was to examine the impact of combined cardiorespiratory fitness and waist-to-height ratio in the form of a fit-fat index on incident diabetes risk. Additionally, the independent predictive performance of cardiorespiratory fitness, waist-to-height ratio, and body mass index also were estimated and compared.MethodsThis was a prospective cohort study of 10,381 men who had a normal electrocardiogram and no history of major chronic disease at baseline from 1979 to 2005. Random survival forest models and traditional Cox proportional hazards models were used to predict diabetes at 5-, 10-, and 15-year incidence horizons.ResultsOverall, 4.8% of the participants developed diabetes. Receiver operating characteristic curve analyses for incidence risk demonstrated good discrimination using random survival forest models across fitness and fatness measures; Cox models were poor to fair. The differences between fitness and fatness measures across horizons were clinically negligible. Smoothed random survival forest estimates demonstrated the impact of each fitness and fatness measure on incident diabetes was intuitive and graded.ConclusionsAlthough fitness and fatness measures showed a similar discriminative ability in predicting incident diabetes, unique to the study was the ability of the fit-fat index to demonstrate a better indication of incident risk when compared to fitness or fatness alone. A single index combining cardiorespiratory fitness and waist-to-height ratio may be more useful because it can indicate improvements in either or both of the measures.
| S-EPMC4920380 | biostudies-literature
Project description:Mitochondrial dysfunction plays a pivotal role in the development of heart failure. Animal studies suggest that impaired mitochondrial biogenesis attributable to downregulation of the peroxisome proliferator-activated receptor gamma coactivator (PGC)-1 transcriptional pathway is integral of mitochondrial dysfunction in heart failure.The study sought to define mechanisms underlying the impaired mitochondrial biogenesis and function in human heart failure.We collected left ventricular tissue from end-stage heart failure patients and from nonfailing hearts (n=23, and 19, respectively). The mitochondrial DNA (mtDNA) content was decreased by >40% in the failing hearts, after normalization for a moderate decrease in citrate synthase activity (P<0.05). This was accompanied by reductions in mtDNA-encoded proteins (by 25% to 80%) at both mRNA and protein level (P<0.05). The mRNA levels of PGC-1alpha/beta and PRC (PGC-1-related coactivator) were unchanged, whereas PGC-1alpha protein increased by 58% in the failing hearts. Among the PGC-1 coactivating targets, the expression of estrogen-related receptor alpha and its downstream genes decreased by up to 50% (P<0.05), whereas peroxisome proliferator-activated receptor alpha and its downstream gene expression were unchanged in the failing hearts. The formation of D-loop in the mtDNA was normal but D-loop extension, which dictates the replication process of mtDNA, was decreased by 75% in the failing hearts. Furthermore, DNA oxidative damage was increased by 50% in the failing hearts.Mitochondrial biogenesis is severely impaired as evidenced by reduced mtDNA replication and depletion of mtDNA in the human failing heart. These defects are independent of the downregulation of the PGC-1 expression suggesting novel mechanisms for mitochondrial dysfunction in heart failure.
| S-EPMC2880225 | biostudies-literature