MiR-126 Is an Independent Predictor of Long-Term All-Cause Mortality in Patients with Type 2 Diabetes Mellitus.
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ABSTRACT:
SUBMITTER: Pordzik J
PROVIDER: S-EPMC8198825 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundTo investigate whether diabetes contributes to mortality for major types of diseases.MethodsSix National Health and Nutrition Examination Survey data cycles (1999 to 2000, 2001 to 2002, 2003 to 2004, 2005 to 2006, 2007 to 2008, and 2009 to 2010) and their linked mortality files were used. A population of 15,513 participants was included according to the availability of diabetes and mortality status.ResultsParticipants with diabetes tended to have higher all-cause mortality and mortality due to cardiovascular disease, cancer, chronic lower respiratory diseases, cerebrovascular disease, influenza and pneumonia, and kidney disease. Confounder-adjusted Cox proportional hazard models showed that both diagnosed diabetes category (yes or no) and diabetes status (diabetes, prediabetes, or no diabetes) were associated with all-cause mortality and with mortality due to cardiovascular disease, chronic lower respiratory diseases, influenza and pneumonia, and kidney disease. No associations were found for cancer-, accidents-, or Alzheimer's disease-related mortality.ConclusionThe current study's findings provide epidemiological evidence that diagnosed diabetes at the baseline is associated with increased mortality risk due to cardiovascular disease, chronic lower respiratory diseases, influenza and pneumonia, and kidney disease, but not with cancer or Alzheimer's disease.
| S-EPMC6581547 | biostudies-literature
Project description:BACKGROUND:Resistant hypertension is independently associated with an increased risk of death in the general hypertensive population. We assessed whether resistant hypertension is an independent predictor of all-cause mortality in individuals with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study. METHODS:On 31 October 2015, vital status information was retrieved for 15,656 of the 15,773 participants enrolled in 2006-2008. Based on baseline blood pressure (BP) values and treatment, participants were categorized as normotensive, untreated hypertensive, controlled hypertensive (i.e., on-target with <?3 drugs), uncontrolled hypertensive (i.e., not on-target with 1-2 drugs), or resistant hypertensive (i.e., uncontrolled with >?3 drugs or controlled with >?4 drugs). Kaplan-Meier and Cox proportional hazards regression analyses were used to assess the association with all-cause mortality. RESULTS:Using the 130/80?mmHg targets for categorization, crude mortality rates and Kaplan-Meier estimates were highest among resistant hypertension participants, especially those with controlled resistant hypertension. As compared with resistant hypertension, risk for all-cause mortality was significantly lower for all the other groups, including individuals with controlled hypertension (hazard ratio 0.81 [95% confidence interval 0.74-0.89], P?<?0.0001), but became progressively similar between resistant and controlled hypertension after adjustment for cardiovascular risk factors and complications/comorbidities. Also when compared with controlled resistant hypertension, mortality risk was significantly lower for all the other groups, including controlled hypertension, even after adjusting for cardiovascular risk factors (0.77 [0.63-0.95], P?=?0.012), but not for complications/comorbidities (0.88 [0.72-1.08], P?=?0.216). BP was well below target in the controlled hypertensive groups (resistant and non-resistant) and values <?120/70?mmHg were associated with an increased mortality risk. Results changed only partly when using the 140/90?mmHg targets for categorization. CONCLUSIONS:In the RIACE cohort, at variance with the general hypertensive population, resistant hypertension did not predict death beyond target organ damage. Our findings may be explained by the high mortality risk conferred by type 2 diabetes and the low BP values observed in controlled hypertensive patients, which may mask risk associated with resistant hypertension. Less stringent BP goals may be preferable in high-risk patients with type 2 diabetes. TRIAL REGISTRATION:ClinicalTrials.gov, NCT00715481 , retrospectively registered 15 July, 2008.
| S-EPMC6482506 | biostudies-literature
Project description:Heart rate-corrected QT (QTc) interval is associated with mortality in the general population, but this association is less clear in individuals with type 2 diabetes. We assessed the association of QTc interval with all-cause and cardiovascular disease (CVD) mortality in the Diabetes Heart Study.We studied 1,020 participants with type 2 diabetes (83% European Americans; 55% women; mean age 61.4 years) who were free of atrial fibrillation, major ventricular conduction defects, and antiarrhythmic therapy at baseline. QT duration was automatically calculated from a standard 12-lead electrocardiogram (ECG). Following American Heart Association/American College of Cardiology Foundation recommendations, a linear scale was used to correct the QT for heart rate. Using Cox regression, risk was estimated per 1-SD increase in QTc interval as well as prolonged QTc interval (>450 ms) vs. normal QTc interval for mortality.At baseline, the mean (SD) QTc duration was 414.9 ms (18.1), and 3.0% of participants had prolonged QTc. After a median follow-up time of 8.5 years (maximum follow-up time 13.9 years), 204 participants were deceased. In adjusted multivariate models, a 1-SD increase in QTc interval was associated with an 18% higher risk for all-cause mortality (hazard ratio 1.18 [95% CI 1.03-1.36]) and 29% increased risk for CVD mortality (1.29 [1.05-1.59]). Similar results were obtained when QTc interval was used as a categorical variable (prolonged vs. normal) (all-cause mortality 1.73 [0.95-3.15]; CVD mortality 2.86 [1.35-6.08]).Heart rate QTc interval is an independent predictor of all-cause and CVD mortality in this population with type 2 diabetes, suggesting that additional prognostic information may be available from this simple ECG measure.
| S-EPMC4182905 | biostudies-other
Project description:BackgroundFew studies have examined the impact of treatment-related morbidity on long-term, cause-specific mortality in Hodgkin lymphoma (HL) patients.MethodsThis multicenter cohort included 4919 HL patients, treated before age 51 years between 1965 and 2000, with a median follow-up of 20.2 years. Standardized mortality ratios, absolute excess mortality (AEM) per 10 000 person-years, and cause-specific cumulative mortality by stage and primary treatment, accounting for competing risks, were calculated.ResultsHL patients experienced a 5.1-fold (AEM = 123 excess deaths per 10 000 person-years) higher risk of death due to causes other than HL. This risk remained increased in 40-year survivors (standardized mortality ratio = 5.2, 95% confidence interval [CI] = 4.2 to 6.5, AEM = 619). At age 54 years, HL survivors experienced similar cumulative mortality (20.0%) from causes other than HL to 71-year-old individuals from the general population. Whereas HL mortality statistically significantly decreased over the calendar period (P < .001), solid tumor mortality did not change in the most recent treatment era. Patients treated in 1989-2000 had lower 25-year cardiovascular disease mortality than patients treated in 1965-1976 (4.3% vs 5.7%; subdistribution hazard ratio = 0.65, 95% CI = 0.46 to 0.93). Infectious disease mortality was not only increased after splenectomy but also after spleen irradiation (hazard ratio = 2.81, 95% CI = 1.55 to 5.07). For stage I-II, primary treatment with chemotherapy (CT) alone was associated with statistically significantly higher HL mortality (P < .001 for CT vs radiotherapy [RT]; P = .04 for CT vs RT+CT) but lower 30-year mortality from causes other than HL (15.8%, 95% CI = 9.7% to 23.3%) compared with RT alone (36.9%, 95% CI = 34.0% to 39.8%, P = .001) and RT and CT combined (29.8%, 95% CI = 26.8% to 32.9%, P = .02).ConclusionsCompared with the general population, HL survivors have a substantially reduced life expectancy. Optimal selection of patients for primary CT is crucial, weighing risks of HL relapse and long-term toxicity.
| S-EPMC8168246 | biostudies-literature
Project description:Atherosclerotic lesions in the great arteries are frequent findings in the elderly. Numerous studies have shown their strong predictive value for cardiovascular disease, embolic events, and mortality. We sought to determine the risk of all-cause mortality depending on the localization of plaques in the thoracic aorta evaluated by transesophageal echocardiography (TEE). A total of 2,054 patients (median age 65 years, interquartile range 52-73; 58% men) who underwent a TEE examination between 01/2007 and 03/2015 were retrospectively analyzed. For each patient, the presence of atherosclerotic lesions in the ascending aorta, the aortic arch, and in the descending aorta, as well as cardiovascular risk factors and survival were documented. Median follow-up period was 48 months (interquartile range 38-58). Multivariate Cox regression analysis indicated plaque in the ascending aorta (HR of 1.36, 95% CI 1.01-1.83, P = 0.046), the aortic arch (HR of 1.78, 95% CI 1.29-2.45, P < 0.001), the descending aorta (HR of 2.01, 95% CI 1.54-2.77, P < 0.001), and plaque in any part of the thoracic aorta (HR of 1.84, 95% CI 1.42-2.4, P < 0.001), as independent predictors for all-cause mortality after adjusting for age, sex, arterial hypertension, hyperlipidemia, smoking, and diabetes. In this study, we could demonstrate that more than mild plaque at any site of the thoracic aorta predicts all-cause mortality. Assessment of atherosclerotic lesions in all segments of the thoracic aorta should be part of every routine TEE examination.
| S-EPMC7381477 | biostudies-literature
Project description:BackgroundType 2 diabetes mellitus (DM) is a frequent co-morbidity among patients undergoing coronary artery bypass grafting (CABG) surgery. The aim of this study was to evaluate the impact of DM on the early- and long-term outcomes of patients who underwent isolated CABG.MethodsWe performed an observational cohort study in a large tertiary medical center over a period of 11 years. All data from patients who had undergone isolated CABG surgery between 2004 and 2014 were obtained from our departmental database. The study population included 2766 patients who were divided into two groups: Group I (1553 non-diabetic patients), and Group II (1213 patients suffering from type 2 DM). Group II patients were then divided into two subgroups: subgroup IIA (981 patients treated with oral antihyperglycemic medications) and subgroup IIB (232 insulin-treated patients with or without additional oral antihyperglycemic drugs). In-hospital, 1-, 3-, 5- and 10-year mortality outcome variables were evaluated. Mean follow-up was 97 ± 41 months.ResultsIn-hospital mortality was similar between Group I and Group II patients (1.87% vs. 2.31%, p = 0.422) and between the subgroups IIA and IIB (2.14% vs. 3.02%, p = 0.464). Long-term mortality (1, 3, 5 and 10 years) was higher in Group II (DM type 2) compared with Group I (non-diabetic patients) (5.3% vs. 3.6%, p = 0.038; 9.3% vs. 5.6%, p < 0.001; 15.3% vs. 9.3%, p < 0.001 and 47.3% vs. 29.6% p < 0.001). Kaplan-Meier analysis demonstrated that all-cause mortality was higher in Group II compared with Group I (p < 0.001) and in subgroup IIB compared with subgroup IIA (p = 0.001). Multivariable analysis showed that DM increased the mortality hazard by twofold, and among diabetic patients, insulin treatment increased the mortality hazard by twofold.ConclusionsDiabetic and non-diabetic patients have similar in-hospital mortality rates. Survival rates of diabetic patients start to deteriorate 3 year after surgery. Type 2 DM is an independent predictor for long-term mortality after isolated CABG surgery. Mortality is even higher when the diabetes treatment strategy included insulin.
| S-EPMC6264047 | biostudies-literature
Project description:ObjectiveThis retrospective study incorporated long-term mortality results after different bariatric surgery procedures and for multiple age at surgery groups.MethodsParticipants with bariatric surgery (surgery) and without (non-surgery) were matched (1:1) for age, sex, BMI, and surgery date with a driver license application/renewal date. Mortality rates were compared by Cox regression, stratified by sex, surgery type, and age at surgery.ResultsParticipants included 21,837 matched surgery and non-surgery pairs. Follow-up was up to 40 years (mean [SD], 13.2 [9.5] years). All-cause mortality was 16% lower in surgery compared with non-surgery groups (hazard ratio, 0.84; 95% CI: 0.79-0.90; p < 0.001). Significantly lower mortality after bariatric surgery was observed for both females and males. Mortality after surgery versus non-surgery decreased significantly by 29%, 43%, and 72% for cardiovascular disease, cancer, and diabetes, respectively. The hazard ratio for suicide was 2.4 times higher in surgery compared with non-surgery participants (95% CI: 1.57-3.68; p < 0.001), primarily in participants with ages at surgery between 18 and 34 years.ConclusionsReduced all-cause mortality was durable for multiple decades, for multiple bariatric surgical procedures, for females and males, and for greater than age 34 years at surgery. Rate of death from suicide was significantly higher in surgery versus non-surgery participants only in the youngest age at surgery participants.
| S-EPMC9881843 | biostudies-literature
Project description:BackgroundAtrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Diabetes mellitus (DM) is one of the risk factors for the development of stroke and thromboembolism in patients with AF. Early identification may reduce the incidence of complications and mortality in AF patients.HypothesisAF patients with DM have different pattern of small extracellular vesicle (sEV) levels and sEV-derived microRNA (miRNA) expression compared with those without DM.MethodsWe compared sEV levels and sEV-miRNA expression in plasma from AF patients with and without DM using nanoparticle tracking analysis and droplet digital polymerase chain reaction, respectively.ResultsWe observed a significant increase in total sEV levels (p = .004) and a significant decrease in sEV-miR-126 level (p = .004) in AF patients with DM. Multivariate logistic regression analysis revealed a positive association between total sEV levels and AF with DM (p = .019), and a negative association between sEV-miR-126 level and AF with DM (p = .031). The combination of clinical data, total sEVs, and sEV-miR-126 level had an area under the curve of 0.968 (p < .0001) for discriminating AF with DM, which was shown to be significantly better than clinical data analysis alone (p = .0368).ConclusionsThese results suggest that an increased level of total sEV and a decreased sEV-miR-126 level may play a potential role in the pathophysiology and complications of AF with DM, especially endothelial dysfunction, and can be considered as an applied biomarker for distinguishing between AF with and without DM.
| S-EPMC10642338 | biostudies-literature
Project description:Background Diabetes mellitus is a risk factor for cardiovascular disease ( CVD ) and has been associated with 2- to 4-fold higher mortality. Diabetes mellitus-related mortality has not been reassessed in individuals receiving routine care in the United States in the contemporary era of CVD risk reduction. Methods and Results We retrospectively studied 963 648 adults receiving care in the US Veterans Affairs Healthcare System from 2002 to 2014; mean follow-up was 8 years. We estimated associations of diabetes mellitus status and hemoglobin A1c (HbA1c) with all-cause and CVD mortality using covariate-adjusted incidence rates and multivariable Cox proportional hazards regression. Of participants, 34% had diabetes mellitus. Compared with nondiabetic individuals, patients with diabetes mellitus had 7.0 (95% CI , 6.7-7.4) and 3.5 (95% CI, 3.3-3.7) deaths/1000-person-years higher all-cause and CVD mortality, respectively. The age-, sex-, race-, and ethnicity-adjusted hazard ratio for diabetes mellitus-related mortality was 1.29 (95% CI, 1.28-1.31), and declined with adjustment for CVD risk factors (hazard ratio, 1.18 [95% CI, 1.16-1.19]) and glycemia (hazard ratio, 1.03 [95% CI, 1.02-1.05]). Among individuals with diabetes mellitus, CVD mortality increased as HbA1c exceeded 7% (hazard ratios, 1.11 [95% CI, 1.08-1.14], 1.25 [95% CI, 1.22-1.29], and 1.52 [95% CI, 1.48-1.56] for HbA1c 7%-7.9%, 8%-8.9%, and ≥9%, respectively, relative to HbA1c 6%-6.9%). HbA1c 6% to 6.9% was associated with the lowest mortality risk irrespective of CVD history or age. Conclusions Diabetes mellitus remains significantly associated with all-cause and CVD mortality, although diabetes mellitus-related excess mortality is lower in the contemporary era than previously. We observed a gradient of mortality risk with increasing HbA1c >6% to 6.9%, suggesting HbA1c remains an informative predictor of outcomes even if causality cannot be inferred.
| S-EPMC6405678 | biostudies-other
Project description:Background and Purpose- Stroke patients with type 2 diabetes mellitus (T2DM) exhibit increased vascular and white matter damage and have worse prognosis compared with nondiabetic stroke patients. We investigated the neurorestorative effects of exosomes derived from mouse brain endothelial cells (EC-Exo) as treatment for stroke in T2DM mice and investigated the role of miR-126 in mediating EC-Exo-derived therapeutic benefits in T2DM-stroke mice. Methods- Adult, male BKS.Cg-m+/+Leprdb/J (T2DM) mice were subjected to photothrombotic stroke model. T2DM mice were intravenously injected at 3 days after stroke with (1) PBS; (2) liposome mimic (vehicle control, 3×1010); (3) EC-Exo (3×1010); (4) knockdown of miR-126 in EC-Exo (miR-126-/- EC-Exo, 3×1010). Behavioral and cognitive tests were performed, and mice were sacrificed at 28 days after stroke. Results- Compared with non-DM stroke mice, T2DM-stroke mice exhibit significantly decreased serum and brain tissue miR-126 expression. Endothelial cells and EC-Exo contain high levels of miR-126 compared with other cell types or exosomes derived from other types of cells, respectively (smooth muscle cells, astrocytes, and marrow stromal cells). Compared with PBS or liposome mimic treatment, EC-Exo treatment of T2DM-stroke mice significantly improves neurological and cognitive function, increases axon density, myelin density, vascular density, arterial diameter, as well as induces M2 macrophage polarization in the ischemic boundary zone. MiR-126-/- EC-Exo treatment significantly decreases miR-126 expression in serum and brain, as well as attentuates EC-Exo treatment-induced functional improvement and does not significantly increase axon and myelin density, vascular density, arterial diameter or induce M2 macrophage polarization in T2DM-stroke mice. In vitro, EC-Exo treatment significantly increases primary cortical neuron axonal outgrowth and increases endothelial capillary tube formation whereas miR-126-/- EC-Exo attentuates EC-Exo induced capillary tube formation and axonal outgrowth. Conclusions- EC-Exo treatment of stroke promotes neurorestorative effects in T2DM mice. MiR-126 may mediate EC-Exo-induced neurorestorative effects in T2DM mice. Visual Overview- An online visual overview is available for this article.
| S-EPMC6756941 | biostudies-literature