140 research outputs found
A System of ODEs for Representing Trends of CGM Signals
Diabetes Mellitus is a metabolic disorder which may result in severe and
potentially fatal complications if not well-treated and monitored. In this
study, a quantitative analysis of the data collected using CGM (Continuous
Glucose Monitoring) devices from eight subjects with type 2 diabetes in good
metabolic control at the University Polyclinic Agostino Gemelli, Catholic
University of the Sacred Heart, was carried out. In particular, a system of
ordinary differential equations whose state variables are affected by a
sequence of stochastic perturbations was proposed and used to extract more
informative inferences from the patients' data. For this work, Matlab and R
programs were used to find the most appropriate values of the parameters
(according to the Akaike Information Criterion (AIC) and the Bayesian
Information Criterion (BIC)) for each patient. Fitting was carried out by
Particle Swarm Optimization to minimize the ordinary least squares error
between the observed CGM data and the data from the ODE model. Goodness of fit
tests were made in order to assess which probability distribution was best
suitable for representing the waiting times computed from the model parameters.
Finally, both parametric and non-parametric density estimation of the frequency
histograms associated with the variability of the glucose elimination rate from
blood were conducted and their representative parameters assessed from the
data. The results show that the chosen models succeed in capturing most of the
glucose fluctuations for almost every patient
Early Increase of Oxidative Stress and Reduced Antioxidant Defenses in Patients With Uncomplicated Type 1 Diabetes
OBJECTIVE—Diabetes increases the risk of coronary heart disease (CHD) to a greater extent in women than in men. We investigated whether type 1 diabetic patients with short duration of disease and without complications have an altered oxidative status and whether there are differences between men and women.
RESEARCH DESIGN AND METHODS—We investigated oxidative status in 29 control subjects and 37 patients with uncomplicated type 1 diabetes with duration of 6 ± 3 years.
RESULTS—Compared with control subjects, type 1 diabetic patients had lower total plasma antioxidant capacity (TRAP) (720.3 ± 111.2 vs. 972.5 ± 97.7 μmol/l in men, P < 0.001; 579.8 ± 95.4 vs. 930.1 ± 84.2 in women, P < 0.001), higher lipid hydroperoxide (ROOH) levels (6.4 ± 2.2 vs. 2.0 ± 0.7 μmol/l in men, P < 0.001; 8.1 ± 1.9 vs. 2.2 ± 0.6 in women, P < 0.001), higher total conjugated diene (CD) levels (0.037 ± 0.003 vs. 0.033 ± 0.002 A.U. in men, P < 0.001), lower 246-nm CD levels (0.0032.± 0.0010 vs. 0.0070 ± 0.0012 A.U. in men, P < 0.001; 0.0022 ± 0.0011 vs. 0.0072 ± 0.0014 A.U. in women, P < 0.001), and higher 232-nm CD levels (0.0348 ± 0.0041 vs. 0.0257 ± 0.0022 A.U. in men, P < 0.001; 0.0346 ± 0.0031 vs. 0.0246 ± 0.0074 A.U. in women, P < 0.001). Compared with diabetic men, diabetic women had lower TRAP (P < 0.01), higher ROOH levels (P < 0.01), and lower 246-nm CD levels (P < 0.05). Plasma concentration of uric acid was significantly lower in patients with type 1 diabetes than in control subjects (3.3 ± 0.3 vs. 4.3 ± 0.2 mg/dl; P = 0.009) with a significant difference between women and men with type 1 diabetes (2.6 ± 0.3 vs. 3.9 ± 0.3, respectively; P = 0.009).
CONCLUSIONS—Our findings suggest that reduced antioxidant activity and increased oxidative stress occur early after the diagnosis of type 1 diabetes, especially in women, and this might explain, at least in part, the increased susceptibility of diabetic women to cardiovascular complications
Inflammatory Cytokines Associated With Failure of Lower-Extremity Endovascular Revascularization (LER): A Prospective Study of a Population With Diabetes
OBJECTIVE
Peripheral artery disease (PAD) is one of the most relevant complications of diabetes. Although several pharmacological and revascularization approaches are available for treating patients with diabetes and PAD, an endovascular approach is often associated with postprocedural complications that can increase the risk for acute limb ischemia or amputation. However, no definitive molecular associations have been described that could explain the difference in outcomes after endovascular treatment in patients with diabetes, PAD, and chronic limb-threatening ischemia (CLTI).
RESEARCH DESIGN AND METHODS
We evaluated the relationship between the levels of the main cytokines associated with diabetic atherosclerosis and the outcomes after endovascular procedures in patients with diabetes, PAD, and CLTI.
RESULTS
A total of 299 patients with below-the-knee occlusive disease who were undergoing an angioplasty procedure were enrolled. The levels of key cytokines—osteoprotegerin (OPG), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP)—were measured, and major adverse limb events (MALE) and major adverse cardiovascular events (MACE) were assessed 1, 3, 6, and 12 months after the procedure. There was a linear trend from the lowest to the highest quartile for each cytokine at baseline and incident MALE. A linear association was also observed between increasing levels of each cytokine and incident MACE. Receiver operating characteristics models were constructed using clinical and laboratory risk factors, and the inclusion of cytokines significantly improved the prediction of incident events.
CONCLUSIONS
We demonstrated that elevated OPG, TNF-α, IL-6, and CRP levels at baseline correlate with worse vascular outcomes in patients with diabetes, PAD, and CLTI undergoing an endovascular procedure
Effect of very long-term storage and multiple freeze and thaw cycles on 11-dehydro-thromboxane-B2 and 8-iso-prostaglandin F2α, levels in human urine samples by validated enzyme immunoassays
: Biological samples are often frozen and stored for years and/or thawed multiple times, thus assessing their stability on long-term storage and repeated freeze-thaw cycles is crucial. The study aims were to assess:-the long-term stability of two major enzymatic and non-enzymatic metabolites of arachidonic acid, i.e. urinary 11-dehydro-thromboxane-(Tx) B2, 8-iso-prostaglandin (PG)F2α, and creatinine in frozen urine samples;-the effect of multiple freeze-thaw cycles. Seven-hundred and three urine samples measured in previously-published studies, stored at -40 °C, and measured for a second time for 11-dehydro-TxB2 (n = 677) and/or 8-iso-PGF2α (n = 114) and/or creatinine (n = 610) were stable over 10 years and the 2 measurements were highly correlated (all rho = 0.99, P < 0.0001). Urine samples underwent 10 sequential freeze-thaw cycles, with and without the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (10 mM); urinary 11-dehydro-TxB2 and creatinine were stable across all cycles (11-dehydro-TxB2: 100.4 ± 21%; creatinine: 101 ± 7% of baseline at cycle ten; n = 17), while 8-iso-PGF2α significantly increased by cycle 6 (151 ± 22% of baseline at cycle ten, n = 17, P < 0.05) together with hydrogen peroxide only in the absence of antioxidant. Arachidonic acid metabolites and creatinine appear stable in human urines stored at -40 °C over 10 years. Multiple freeze-thaw cycles increase urinary 8-iso-PGF2α in urine samples without antioxidants. These data are relevant for studies using urine samples stored over long-term and/or undergoing multiple freezing-thawing
Red blood cells membrane micropolarity as a novel diagnostic indicator of type 1 and type 2 diabetes
Classification of the category of diabetes is extremely important for clinicians to diagnose and select the correct treatment plan. Glycosylation, oxidation and other post-translational modifications of membrane and transmembrane proteins, as well as impairment in cholesterol homeostasis, can alter lipid density, packing, and interactions of Red blood cells (RBC) plasma membranes in type 1 and type 2 diabetes, thus varying their membrane micropolarity. This can be estimated, at a submicrometric scale, by determining the membrane relative permittivity, which is the factor by which the electric field between the charges is decreased relative to vacuum. Here, we employed a membrane micropolarity sensitive probe to monitor variations in red blood cells of healthy subjects (n=16) and patients affected by type 1 (T1DM, n=10) and type 2 diabetes mellitus (T2DM, n=24) to provide a cost-effective and supplementary indicator for diabetes classification. We find a less polar membrane microenvironment in T2DM patients, and a more polar membrane microenvironment in T1DM patients compared to control healthy patients. The differences in micropolarity are statistically significant among the three groups (p<0.01). The role of serum cholesterol pool in determining these differences was investigated, and other factors potentially altering the response of the probe were considered in view of developing a clinical assay based on RBC membrane micropolarity. These preliminary data pave the way for the development of an innovative assay which could become a tool for diagnosis and progression monitoring of type 1 and type 2 diabetes. Keywords: Diabetes mellitus, Membrane micropolarity, Red blood cells, Fluorescence lifetime microscopy, Metabolic imaging, Personalized medicin
SARS-CoV-2 and DPP4 inhibition: Is it time to pray for Janus Bifrons?
Diabetes could be a risk factor for severity and mortality in patients with coronavirus disease 2019 COVID-19. It has been hypothesized that DPP4 inhibition, a therapy currently available for type 2 diabetes, might represent a target for decreasing the risk of the acute respiratory complications of the COVID-19 infection but (1) lack of demonstration of SARS-CoV2 binding to DPP4 (2) possible protective role of sDPP4 in Middle East respiratory Syndrome (MERS-CoV) (3) demonstrated inhibition and downregulation of DPP4 by HIV1 and MERS-CoV and (4) not exclusive role of the receptor binding in tropism of the Coronavirus family, support that DPP4 inhibition at present doesn't represent a plausible approach to mitigate COVID-19
Targeting prolyl-isomerase Pin1 prevents mitochondrial oxidative stress and vascular dysfunction: insights in patients with diabetes
The present study demonstrates that Pin1 is a common activator of key pathways involved in diabetic vascular disease in different experimental settings including primary human endothelial cells, knockout mice, and diabetic patients. Gene silencing and genetic disruption of Pin1 prevent hyperglycaemia-induced mitochondrial oxidative stress, endothelial dysfunction, and vascular inflammation. Moreover, we have translated our findings to diabetic patients. In line with our experimental observations, Pin1 up-regulation is associated with impaired flow-mediated dilation, increased oxidative stress, and plasma levels of adhesion molecules. In perspective, these findings may provide the rationale for mechanism-based therapeutic strategies in patients with diabete
Lights and shadows on the use of metformin in pregnancy: from the preconception phase to breastfeeding and beyond
During pregnancy, the complex hormonal changes lead to a progressive decrease of insulin sensitivity that can drive the onset of gestational diabetes (GDM) or worsen an already-known condition of insulin resistance like type 2 diabetes, polycystic ovarian syndrome (PCOS), and obesity, with complications for the mother and the fetus. Metformin during pregnancy is proving to be safe in a growing number of studies, although it freely crosses the placenta, leading to a fetal level similar to maternal concentration. The aim of this literature review is to analyze the main available evidence on the use of metformin during, throughout, and beyond pregnancy, including fertilization, lactation, and medium-term effects on offspring. Analyzed studies support the safety and efficacy of metformin during pregnancy. In pregnant women with GDM and type 2 diabetes, metformin improves obstetric and perinatal outcomes. There is no evidence that it prevents GDM in women with pregestational insulin resistance or improves lipid profile and risk of GDM in pregnant women with PCOS or obesity. Metformin could have a role in reducing the risk of preeclampsia in pregnant women with severe obesity, the risk of late miscarriages and preterm delivery in women with PCOS, and the risk of ovarian hyperstimulation syndrome, increasing the clinical pregnancy rate in women with PCOS undergoing in vitro fertilization (IVF/FIVET). Offspring of mothers with GDM exposed to metformin have no significant differences in body composition compared with insulin treatment, while it appears to be protective for metabolic and cardiovascular risk
The Role of Klotho and FGF23 in Cardiovascular Outcomes of Diabetic Patients With Chronic Limb Threatening Ischemia: A Prospective Study
Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-fibroblast growth factor 23 (FGF23) axis is associated with endothelial injury and cardiovascular risk. We aimed to analyze the relationship between Klotho and FGF23 serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI. Baseline levels of Klotho and FGF23, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population of diabetic patients with PAD and CLTI requiring LER. A total of 220 patients were followed for 12 months after LER. Sixty-three MACE and 122 MALE were recorded during follow-up period. Baseline lower Klotho serum levels (295.3 ± 151.3 pg/mL vs. 446.4 ± 171.7 pg/mL, p \u3c 0.01), whereas increased serum levels FGF23 (75.0 ± 11.8 pg/mL vs. 53.2 ± 15.4 pg/mL, p \u3c 0.01) were significantly associated with the development of MACE. Receiver operating characteristic (ROC) analysis confirmed the predictive power of Klotho and FGF23 baseline levels. Furthermore, decreased Klotho levels were associated with the occurrence of MALE after LER (329.1 ± 136.8 pg/mL vs 495.4 ± 183.9 pg/mL, p \u3c 0.01). We found that Klotho and FGF23 baseline levels are a potential biomarker for increased cardiovascular risk after LER in diabetic patients with PAD and CLTI
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