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1.
J Diabetes Complications ; 35(6): 107913, 2021 06.
Article in English | MEDLINE | ID: mdl-33867245

ABSTRACT

AIMS: Prevalence and risk factors of pre-symptomatic left ventricular systolic dysfunction (LVSD) in individuals with type 1 diabetes (T1D) have not been adequately studied. The present cross-sectional study assessed the prevalence of early LVSD in asymptomatic patients with type 1 diabetes and investigated potential risk factors. METHODS: Consecutive patients with T1D, free of cardiovascular disease and significant evident microvascular complications were examined. LVSD was assessed by speckle-tracking echocardiography and calculation of global longitudinal strain (GLS). Abnormal GLS was defined as a value>-18.7%. We looked for possible associations between the presence of LVSD and patient demographic, clinical and laboratory characteristics, as well as with autonomic nervous system (ANS) function and arterial stiffness. RESULTS: We enrolled 155 T1D patients (29.7% men, age 36.7 ±â€¯13.1 years, diabetes duration 19.1 ±â€¯10.0 years, HbA1c 7.5 ±â€¯1.4% [58 ±â€¯15 mmol/mol]). Early LVSD was prevalent in 53 (34.2%) patients. Multivariable analysis identified male gender (OR:4.14; 95% CI:1.39-12.31, p = 0.011), HbA1c (OR:1.59 per 1% increase; 95% CI:1.11-2.28, p = 0.011), glomerular filtration rate (GFR, OR:0.97; 95% CI:0.95-0.99, p = 0.010) and BMI (OR:1.19; 95% CI:1.06-1.34, p = 0.003) as independent predictors of LVSD presence. CONCLUSIONS: Early subclinical LVSD is a common finding in asymptomatic patients with T1D, free of macrovascular and significant microvascular complications. Apart from chronic hyperglycemia, increased adiposity may be implicated in its etiology. Further investigation is warranted to identify patients at high risk for whom early screening is required and to determine possible associations between risk markers identified in the present analysis and long-term outcomes.


Subject(s)
Diabetes Mellitus, Type 1 , Ventricular Dysfunction, Left , Adult , Cross-Sectional Studies , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Female , Glycated Hemoglobin , Humans , Male , Middle Aged , Pilot Projects , Risk Factors , Ventricular Dysfunction, Left/epidemiology , Ventricular Function, Left , Young Adult
2.
J Biol Chem ; 279(23): 24540-51, 2004 Jun 04.
Article in English | MEDLINE | ID: mdl-15037622

ABSTRACT

The plant glutathione S-transferase BI-GST has been identified as a potent inhibitor of Bax lethality in yeast, a phenotype associated with oxidative stress and disruption of mitochondrial functions. Screening of a tomato two-hybrid library for BI-GST interacting proteins identified five homologous Tau class GSTs, which readily form heterodimers between them and BI-GST. All six LeGSTUs were found to be able to protect yeast cells from prooxidant-induced cell death. The efficiency of each LeGSTU was prooxidant-specific, indicating a different role for each LeGSTU in the oxidative stress-response mechanism. The prooxidant protective effect of all six proteins was suppressed in the absence of YAP1, a transcription factor that regulates hydroperoxide homeostasis in Saccharomyces cerevisiae, suggesting a role for the LeGSTUs in the context of the YAP1-dependent stress-responsive machinery. The different LeGSTUs exhibited varied substrate specificity and showed activity against oxidative stress by-products, indicating that their prooxidant protective function is likely related to the minimization of oxidative damage. Taken together, these results indicate that Tau class GSTs participate in a broad network of catalytic and regulatory functions involved in the oxidative stress response.


Subject(s)
Glutathione Transferase/physiology , Oxidative Stress , Proto-Oncogene Proteins c-bcl-2 , Amino Acid Sequence , Catalysis , Dimerization , Dose-Response Relationship, Drug , Glutathione/chemistry , Glutathione/metabolism , Glutathione Disulfide/chemistry , Glutathione Transferase/metabolism , Hydrogen-Ion Concentration , Kinetics , Solanum lycopersicum/metabolism , Models, Molecular , Molecular Sequence Data , Oxidants/chemistry , Oxidants/metabolism , Phenotype , Precipitin Tests , Protein Binding , Protein Structure, Secondary , Proto-Oncogene Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Sequence Homology, Amino Acid , Substrate Specificity , Two-Hybrid System Techniques , bcl-2-Associated X Protein
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