11,160 research outputs found

    Increased glycation and oxidative damage to apolipoprotein B100 of LDL cholesterol in patients with type 2 diabetes and effect of metformin

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    OBJECTIVE The aim of this study was to investigate whether apolipoprotein B100 of LDL suffers increased damage by glycation, oxidation, and nitration in patients with type 2 diabetes, including patients receiving metformin therapy. RESEARCH DESIGN AND METHODS For this study, 32 type 2 diabetic patients and 21 healthy control subjects were recruited; 13 diabetic patients were receiving metformin therapy (median dose: 1.50 g/day). LDL was isolated from venous plasma by ultracentrifugation, delipidated, digested, and analyzed for protein glycation, oxidation, and nitration adducts by stable isotopic dilution analysis tandem mass spectrometry. RESULTS Advanced glycation end product (AGE) content of apolipoprotein B100 of LDL from type 2 diabetic patients was higher than from healthy subjects: arginine-derived AGE, 15.8 vs. 5.3 mol% (P < 0.001); and lysine-derived AGE, 2.5 vs. 1.5 mol% (P < 0.05). Oxidative damage, mainly methionine sulfoxide residues, was also increased: 2.5 vs. 1.1 molar equivalents (P < 0.001). 3-Nitrotyrosine content was decreased: 0.04 vs. 0.12 mol% (P < 0.05). In diabetic patients receiving metformin therapy, arginine-derived AGE and methionine sulfoxide were lower than in patients not receiving metformin: 19.3 vs. 8.9 mol% (P < 0.01) and 2.9 vs. 1.9 mol% (P < 0.05), respectively; 3-nitrotyrosine content was higher: 0.10 vs. 0.03 mol% (P < 0.05). Fructosyl-lysine residue content correlated positively with fasting plasma glucose. Arginine-derived AGE residue contents were intercorrelated and also correlated positively with methionine sulfoxide. CONCLUSIONS Patients with type 2 diabetes had increased arginine-derived AGEs and oxidative damage in apolipoprotein B100 of LDL. This was lower in patients receiving metformin therapy, which may contribute to decreased oxidative damage, atherogenicity, and cardiovascular disease

    The combinational effect of cardiac and biochemical markers in diabetic patients with cardiovascular disease

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    Background: Clinicopathological correlations, as well as several angiographic studies, suggest that diabetic patients have more extensive atherosclerotic disease, affecting the coronary arteries in particular. We sought to examine the combinational effect of cardiac and biochemical markers in diabetic patients with cardiovascular disease.\ud Method: The study population constituted 50 healthy subjects, 50 cardiovascular subjects with diabetes and 50 cardiovascular subjects without diabetes. The population was subjected to biochemical and cardiac marker analysis and the results were verified.\ud Results and discussion: Studies suggest that glycated hemoglobin values in the abnormal range can identify persons at increased risk for coronary heart disease, stroke, and death before the diagnosis of diabetes, indicating that glycated hemoglobin is a useful marker of cardiovascular risk and death from any cause.\u

    Endocrine and metabolic evaluation of classic Klinefelter syndrome and high-grade aneuploidies of sexual chromosomes with male phenotype: are they different clinical conditions?

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    Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy in males. As well as classic KS, less frequent higher-grade aneuploidies (HGAs) are also possible. While KS and HGAs both involve testicular dysgenesis with hypergonadotropic hypogonadism, they differ in many clinical features. The aim of this study was to investigate the endocrinal and metabolic differences between KS and HGAs.Objective: Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy in males. As well as classic KS, less frequent higher-grade aneuploidies (HGAs) are also possible. While KS and HGAs both involve testicular dysgenesis with hypergonadotropic hypogonadism, they differ in many clinical features. The aim of this study was to investigate the endocrinal and metabolic differences between KS and HGAs. Design: Cross-sectional, case-control study. Methods: 88 patients with KS, 24 with an HGA and 60 healthy controls. Given the known age-related differences all subjects were divided by age into subgroups 1, 2 and 3. Pituitary, thyroid, gonadal and adrenal functions were investigated in all subjects. Metabolic aspects were only evaluated in subjects in subgroups 2 and 3. Results: FT4 and FT3 levels were significantly higher in HGA than in KS patients in subgroups 1 and 2; in subgroup 3, FT4 was significantly higher in controls than in patients. Thyroglobulin was significantly higher in HGA patients in subgroup 1 than in KS patients and controls. Hypergonadotropic hypogonadism was confirmed in both KS and HGA patients, but was more precocious in the latter, as demonstrated by the earlier increase in gonadotropins and the decrease in testosterone, DHEA-S and inhibin B. Prolactin was significantly higher in HGA patients, starting from subgroup 2. Total and LDL cholesterol were significantly higher in HGA patients than in KS patients and controls, while HDL cholesterol was higher in controls than in patients. Conclusions: KS and HGAs should be considered as two distinct conditions

    High serum osteopontin levels are associated with prevalent fractures and worse lipid profile in post-menopausal women with type 2 diabetes

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    Purpose: Patients with type 2 diabetes (T2DM) have increased fracture risk. Osteopontin (OPN) is a protein involved in bone remodeling and inflammation. The aim of this study was to evaluate the association of OPN with fracture prevalence and with metabolic parameters in post-menopausal women with T2DM. Methods: Sixty-four post-menopausal women with T2DM (age 67.0 ± 7.8 years, diabetes duration 8.9 ± 6.7 years), enrolled in a previous study, were followed up (3.6 ± 0.9 years). Previous fragility fractures were recorded. The FRAX score (without BMD) was calculated and biochemical parameters (plasma glucose, HbA1c, lipid profile and renal function) were assessed. Serum 25OH-vitamin D, calcium, PTH and OPN were evaluated at baseline. The association between OPN and fracture prevalence at baseline was evaluated by a logistic model. Results: OPN levels were higher in patients with previous fractures (n.25) than in patients without previous fractures at baseline (n.39) (p = 0.006). The odds of having fractures at baseline increased by 6.7 (1.9–31.4, 95% CI, p = 0.007) for each increase of 1 ng/ml in OPN levels, after adjustment for vitamin D and HbA1c levels. Fracture incidence was 4.7%. Higher OPN associated with a decrease in HDL-cholesterol (p = 0.048), after adjustment for age, basal HDL-cholesterol, basal and follow-up HbA1c and follow-up duration. 25OH-vitamin D associated with an increase in FRAX-estimated probability of hip fracture at follow-up (p = 0.029), after adjustment for age, 25OH-vitamin D and time. Conclusions: In post-menopausal women with T2DM, OPN might be a useful marker of fracture and worse lipid profile

    The relationship of individual comorbid chronic conditions to diabetes care quality.

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    ObjectiveMultimorbidity affects 26 million persons with diabetes, and care for comorbid chronic conditions may impact diabetes care quality. The aim of this study was to determine which chronic conditions were related to lack of achievement or achievement of diabetes care quality goals to determine potential targets for future interventions.Research design and methodsThis is an exploratory retrospective analysis of electronic health record data for 23 430 adults, aged 18-75, with diabetes who were seen at seven Midwestern US health systems. The main outcome measures were achievement of six diabetes quality metrics in the reporting year, 2011 (glycated haemoglobin (HbA1c) control and testing, low-density lipoprotein control and testing, blood pressure control, kidney testing). Explanatory variables were 62 chronic condition indicators. Analyses were adjusted for baseline patient sociodemographic and healthcare utilization factors.ResultsThe 62 chronic conditions varied in their relationships to diabetes care goal achievement for specific care goals. Congestive heart failure was related to lack of achievement of cholesterol management goals. Obesity was related to lack of HbA1c and BP control. Mental health conditions were related to both lack of achievement and achievement of different care goals. Three conditions were related to lack of cholesterol testing, including congestive heart failure and substance-use disorders. Of 17 conditions related to achieving control goals, 16 were related to achieving HbA1c control. One-half of the comorbid conditions did not predict diabetes care quality.ConclusionsFuture interventions could target patients at risk for not achieving diabetes care for specific care goals based on their individual comorbidities

    Prevalence of pre-diabetes and undiagnosed diabetes in the Mollerussa prospective observational cohort study in a semi-rural area of Catalonia

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    Objectives: To assess the prevalence of undiagnosed diabetes and pre-diabetes in the healthy population in the Mollerussa cohort. As a secondary objective, to identify the variables associated with these conditions and to describe the changes in glycaemic status after 1 year of follow-up in subjects with pre-diabetes. Design: Prospective observational cohort study. Setting: General population from a semi-rural area. Participants: The study included 583 participants without a diagnosis of diabetes recruited between March 2011 and July 2014. Results: The prevalence of undiagnosed diabetes was 20, 3.4% (95% CI 2.6 to 4.2) and that of pre-diabetes was 229, 39.3% (37.3 to 41.3). Among those with pre-diabetes, 18.3% had isolated impaired fasting plasma glucose (FPG) (FPG: 100 to <126 mg/dL), 58.1% had isolated impaired glycated haemoglobin (HbA1c) (HbA1c 5.7 to <6.5) and 23.6% fulfilled both criteria. Follow-up data were available for 166 subjects; 41.6%(37.8 to 45.4) returned to normoglycaemia, 57.6% (57.8 to 61.4) persisted in pre-diabetes and 0.6% (0 to 1.2) progressed to diabetes. Individuals with pre-diabetes had worse cardiometabolic risk profiles and sociodemographic features than normoglycaemic subjects. In the logistic regression model, variables significantly associated with pre-diabetes were older age (OR; 95% CI) (1.033; 1.011 to 1.056), higher physical activity (0.546; 0.360 to 0.827), body mass index (1.121; 1.029 to 1.222) and a family history of diabetes (1.543; 1.025 to 2.323). The variables significantly associated with glycaemic normalisation were older age (0.948; 0.916 to 0.982) and body mass index (0.779; 0.651 to 0.931). Conclusions: Among adults in our region, the estimated prevalence of undiagnosed diabetes was 3.4% and that of pre-diabetes was 39.3%. After a 1-year follow-up, a small proportion of subjects (0.6%) with pre-diabetes progressed to diabetes, while a high proportion (41.6%) returned to normoglycaemia. Individuals with pre-diabetes who returned to normoglycaemia were younger and had a lower body mass inde

    Liver Adiposity and Metabolic Profile in Individuals with Chronic Spinal Cord Injury

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    Purpose. To quantify liver adiposity using magnetic resonance imaging (MRI) and to determine its association with metabolic profile in men with spinal cord injury (SCI). Materials and Methods. MRI analysis of liver adiposity by fat signal fraction (FSF) and visceral adipose tissue (VAT) was completed on twenty participants. Intravenous glucose tolerance test was conducted to measure glucose effectiveness (g) and insulin sensitivity (i ). Lipid panel, fasting glucose, glycated hemoglobin (HbA1c), and inflammatory cytokines were also analyzed. Results. Average hepatic FSF was 3.7% ± 2.1. FSF was positively related to TG, non-HDL-C, fasting glucose, HbA1c, VAT, and tumor necrosis factor alpha (TNF-). FSF was negatively related to i and testosterone. FSF was positively related to VAT ( = 0.48, = 0.032) and TNF- ( = 0.51, = 0.016) independent of age, level of injury (LOI), and time since injury (TSI). The associations between FSF and metabolic profile were independent of VAT. Conclusions. MRI noninvasively estimated hepatic adiposity in men with chronic SCI. FSF was associated with dysfunction in metabolic profile, central adiposity, and inflammation. Importantly, liver adiposity influenced metabolic profile independently of VAT. These findings highlight the significance of quantifying liver adiposity after SCI to attenuate the development of metabolic disorders

    FABP-2 and PPAR-Îł Haplotype as Risk Factors for Dyslipidemia in a Type 2 Diabetes Mellitus Population of Santa Rosa del Conlara, San Luis, Argentina

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    Introduction: Type 2 Diabetes Mellitus (T2DM) is a complex disorder caused by the interaction between genetic predisposition and environmental factors. Genetics plays an important role on lipid homeostasis. Many genes are involved in the lipid metabolism, such as FABP-2 and PPAR-Îł. Aim: To evaluate the association between specific SNPs and haplotypes of the FABP-2 and PPAR-Îł genes with T2DM and lipid profile in an Argentinean population. Methods: The FABP-2 (rs1799883) and PPAR-Îł (rs1801282) polymorphisms were genotyped and analyzed in association with lipid profile and T2DM, separately and also combined in haplotypes. Results: The frequency of the rare Thr54 allele of the FABP-2 polymorphism in control (0.33) was not different from the frequency in T2DM (0.27), whereas the frequency of the rare Ala12 allele of the PPAR-Îł polymorphism in control was different from the frequency in T2DM (0.26 and 0.14, respectively; p = 0.0031). Frequencies of haplotypes for these two single-nucleotide polymorphisms differed significantly in control and T2DM. Haplotype association analysis showed the associations between ThrPro haplotype and TG levels (OR = 2.520; 95% CI = 1.139 - 5.575; p = 0.027) and between ThrPro haplotype and TC and LDL-c levels when compared to AlaPro haplotype (difference = 0.175, 95% CI = 0068 - 0.499, p < 0.0001; difference = 0.052, 95% CI = 0.017 - 0.158, p < 0.0001, respectively). Conclusions: These results from a haplotype analysis show for the first time that genetic combinations of alleles of the FABP-2 and PPAR-Îł gene could play a role in the susceptibility to develop dyslipemia in T2DM.Fil: Siewert, Susana Elfrida. Universidad Nacional de San Luis. Facultad de QuĂ­mica, BioquĂ­mica y Farmacia. Departamento de BioquĂ­mica y Ciencias BiolĂłgicas. Laboratorio de Diabetes; ArgentinaFil: Olmos Nicotra, Maria Florencia. Universidad Nacional de San Luis. Facultad de QuĂ­mica, BioquĂ­mica y Farmacia. Departamento de BioquĂ­mica y Ciencias BiolĂłgicas. Laboratorio de Diabetes; Argentina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; ArgentinaFil: Gonzalez, Irma Ines. Universidad Nacional de San Luis. Facultad de QuĂ­mica, BioquĂ­mica y Farmacia. Departamento de BioquĂ­mica y Ciencias BiolĂłgicas. Laboratorio de Diabetes; ArgentinaFil: Fernandez, Gustavo. Universidad Nacional de San Luis. Facultad de QuĂ­mica, BioquĂ­mica y Farmacia. Departamento de BioquĂ­mica y Ciencias BiolĂłgicas. Laboratorio de Diabetes; ArgentinaFil: Ojeda, Marta Susana. Universidad Nacional de San Luis. Facultad de QuĂ­mica, BioquĂ­mica y Farmacia. Departamento de BioquĂ­mica y Ciencias BiolĂłgicas. Laboratorio de Diabetes; Argentin
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