Publications by authors named "John Kirwan"

Objective: To determine the influence of dietary glycemic index on exercise training-induced adaptations in substrate oxidation in obesity.

Design And Methods: Twenty older, obese individuals undertook 3 months of fully supervised aerobic exercise and were randomized to low- (LoGIX) or high-glycemic (HiGIX) diets. Changes in indirect calorimetry (VO2 ; VCO2 ) were assessed at rest, during a hyperinsulinemic-euglycemic clamp, and during submaximal exercise (walking: 65% VO2 max, 200 kcal energy expenditure).

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Background: Potential mechanisms underlying the antidiabetic effects of Roux-en-Y gastric bypass (RYGB) include altered nutrient exposure in the gut. The aim of this study was to evaluate the effects of selective gut stimulation on glucose metabolism in an obese diabetic rat model.

Methods: Sixteen male Zucker diabetic fatty rats were randomly assigned to 1 of 2 groups: RYGB with gastrostomy tube (GT) insertion into the excluded stomach or a control group with GT insertion into the stomach.

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In rheumatoid arthritis (RA), nocturnal release of proinflammatory cytokines is not adequately counteracted by endogenous glucocorticoid and is associated with symptoms of morning stiffness and pain. Taking exogenous glucocorticoid during the night reduces morning stiffness significantly more than treatment at the conventional time in the morning, although waking to take tablets is unacceptable for patients. Modified-release prednisone tablets were developed to allow administration at bedtime for programmed delivery of glucocorticoid during the night.

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Objective: To evaluate the effects of two bariatric procedures versus intensive medical therapy (IMT) on β-cell function and body composition.

Research Design And Methods: This was a prospective, randomized, controlled trial of 60 subjects with uncontrolled type 2 diabetes (HbA1c 9.7 ± 1%) and moderate obesity (BMI 36 ± 2 kg/m(2)) randomized to IMT alone, IMT plus Roux-en-Y gastric bypass, or IMT plus sleeve gastrectomy.

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Background And Objectives: Previous studies reported an association between metabolic syndrome , incident CKD, and proteinuria. This study examined the associations between metabolic syndrome and its components with ESRD and death among those patients with stages 3 and 4 CKD (estimated GFR=15-59 ml/min per 1.73 m(2)).

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Objective: The Disease Activity Score in 28 joints (DAS28) is a key measure in clinical practice and clinical trials. There are at least five different versions of the 'Patient Global' Visual Analogue Scale (PG-VAS) being used in the DAS28. The developers suggested that the PG-VAS can be an assessment of global health or disease activity, but did not specify the wording of the question.

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Patients with cirrhosis have increased gluconeogenesis and fatty acid oxidation that may contribute to a low respiratory quotient (RQ), and this may be linked to sarcopenia and metabolic decompensation when these patients are hospitalized. Therefore, we conducted a prospective study to measure RQ and its impact on skeletal muscle mass, survival, and related complications in hospitalized cirrhotic patients. Fasting RQ and resting energy expenditure (REE) were determined by indirect calorimetry in cirrhotic patients (n = 25), and age, sex, and weight-matched healthy controls (n = 25).

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Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation that can increase the risk of atherothrombosis. We performed a cross-sectional study to examine the effect of glucose ingestion on markers of atherothrombotic inflammation in mononuclear cells (MNC) of 16 women with PCOS (8 lean, 8 obese) and 16 weight-matched controls. Activator protein-1 (AP-1) activation and the protein content of early growth response-1 (EGR-1), matrix matalloproteinases-2 (MMP2), and tissue factor (TF) were quantified from MNC obtained from blood drawn fasting and 2 h after glucose ingestion.

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Background: The efficacy of combining carbohydrate quality with exercise on metabolic syndrome risk is unclear. Thus, we determined the effects of exercise training with a low (LoGIx)- or high (HiGIx)-glycemic index diet on the severity of the metabolic syndrome (Z-score).

Methods: Twenty-one adults (66.

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Background/aims: Anthropometric measures such as body mass index (BMI) and waist circumference (WC) have differential associations with incident chronic kidney disease (CKD) and mortality. We examined the associations of BMI and WC with various CKD complications.

Methods: We conducted a cross-sectional analysis of 2,853 adult participants with CKD in the National Health and Nutrition Examination Surveys 1999-2006.

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Human skeletal muscles have different fiber types with distinct metabolic functions and physiological properties. The quantitative metabolic responses of muscle fibers to exercise provide essential information for understanding and modifying the regulatory mechanisms of skeletal muscle. Since in vivo data from skeletal muscle during exercise is limited, a computational, physiologically based model has been developed to quantify the dynamic metabolic responses of many key chemical species.

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Glucocorticoids (GCs) provide a powerful and widely used anti-inflammatory and disease-modifying therapy for rheumatoid arthritis (RA). However, concerns about adverse effects are driving efforts to find 'safer' GC or GC analogues. One novel approach has been to change the timing of GC delivery, targeting the early hours of the morning to suppress the observed circadian peak in interleukin-6 (IL-6).

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Even in patients with apparently well-controlled RA, debilitating symptoms such as morning stiffness, fatigue and pain may occur. The key to controlling these symptoms may be in understanding their pathophysiology, which is probably most advanced for morning stiffness. Nocturnal plasma levels of the pro-inflammatory cytokine IL-6 are elevated in patients with RA and correlate with levels of morning stiffness.

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Nonalcoholic fatty liver disease (NAFLD) is a chronic disease with a histological spectrum ranging from steatosis alone, to nonalcoholic steatohepatitis (NASH). The latter is associated with an increased risk for progression to cirrhosis. Ceramides are a lipid species that exert biological effects through cellular proliferation, differentiation, and cell death, and interact with several pathways involved in insulin resistance, oxidative stress, inflammation, and apoptosis, all of which are linked to NAFLD.

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Increased hepatocyte apoptosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and contributes to the profibrogenic state responsible for the progression to nonalcoholic steatohepatitis (NASH). Strategies aimed at reducing apoptosis may result in better outcomes for individuals with NAFLD. We therefore examined the effect of a short-term exercise program on markers of apoptosis-plasma cytokeratin 18 (CK18) fragments, alanine aminotransferase (ALT), aspartate aminotransferase (AST), soluble Fas (sFas), and sFas ligand (sFasL)-in 13 obese individuals with NAFLD [body mass index 35.

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Objective: To assess the efficacy and safety of low-dose prednisone chronotherapy using a new modified-release (MR) formulation for the treatment of rheumatoid arthritis (RA).

Methods: In this 12-week, double-blind, placebo-controlled study, patients with active RA (n=350) were randomised 2:1 to receive MR prednisone 5 mg or placebo once daily in the evening in addition to their existing RA disease-modifying antirheumatic drug (DMARD) treatment. The primary end point was the percentage of patients achieving a 20% improvement in RA signs and symptoms according to American College of Rheumatology criteria (ie, an ACR20 response) at week 12.

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Unlabelled: Pentoxifylline (PTX) improved the histological features of nonalcoholic steatohepatitis (NASH) in a recent randomized placebo-controlled trial. However, the underlying mechanism responsible for the beneficial effects of PTX in NASH remains unidentified. A key role of lipid oxidation in the pathogenesis and progression of NASH has been established.

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Background: Observational studies have shown improvement in patients with type 2 diabetes mellitus after bariatric surgery.

Methods: In this randomized, nonblinded, single-center trial, we evaluated the efficacy of intensive medical therapy alone versus medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy in 150 obese patients with uncontrolled type 2 diabetes. The mean (±SD) age of the patients was 49±8 years, and 66% were women.

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Understanding the pathologies related to the regulation of protein metabolism requires methods for studying the kinetics of individual proteins. We developed a (2)H(2)O metabolic labeling technique and software for protein kinetic studies in free living organisms. This approach for proteome dynamic studies requires the measurement of total body water enrichments by GC-MS, isotopic distribution of the tryptic peptide by LC-MS/MS, and estimation of the asymptotical number of deuterium incorporated into a peptide by software.

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Women with polycystic ovary syndrome (PCOS) have coagulation disturbances and inflammation, which increases the risk of atherothrombosis. We evaluated the status of circulating tissue factor (TF), the receptor for coagulation factor VII involved in atherothrombosis, in women with PCOS and weight-matched controls. Two-way analysis of variance models were fit to evaluate the effect of PCOS status and weight class on TF and other parameters.

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Background: Roux-en-Y gastric bypass (RYGB) surgery achieves high remission rates of type 2 diabetes mellitus in obese diabetic patients. It has been hypothesized that the changes in bowel nutrient exposure after RYGB results in altered release of gut hormones and improved glucose homeostasis. Our objective was to assess the feasibility of, and report on, our technique and initial experience with selective gut stimulation in a gastric bypass rat model at an academic medical center in the United States.

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