22 research outputs found
Celiac Disease and Pediatric Type 1 Diabetes: Diagnostic and Treatment Dilemmas
Despite the advent
of sensitive and specific serologic testing,
routine screening for celiac disease (CD) in
diabetic populations may not be universal
practice, and many clinicians struggle to find
the optimal approach to managing CD in pediatric
Type 1 diabetes (T1D) patients. While some
clinicians advocate screening for CD in all
patients with T1D, others are unsure whether
this is warranted. The diagnosis of patients who
present with symptomatic CD, including
malabsorption and obvious pathology upon biopsy,
remains straightforward, with improvements noted
on a gluten-free diet. Many patients identified
by screening, however, tend to be asymptomatic.
Evidence is inconclusive as to whether the
benefits of screening and potentially treating
asymptomatic individuals outweigh the harms of
managing a population already burdened with a
serious illness. This review focuses on current
knowledge of CD in children and youth with T1D,
highlighting important elements of the
disease's pathophysiology, epidemiology,
clinical presentation, and diagnostic
challenges
Design of a dietary intervention to assess the impact of a gluten-free diet in a population with type 1 Diabetes and Celiac Disease
The Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD-DIET) protocol: A randomised controlled study to evaluate treatment of asymptomatic coeliac disease in type 1 diabetes
Introduction: Coeliac disease (CD) is an autoimmune condition characterised by gluten-induced intestinal inflammation, and observed at a 5-10 fold greater prevalence in type 1 diabetes. While universal screening for CD in patients with diabetes is frequently advocated, objective data is limited as to benefits on diabetes control, bone health or quality of life related to the adoption of a gluten-free diet (GFD) in the large proportion of patients with diabetes with asymptomatic CD. The Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD-DIET) study is a multicenter, randomised controlled trial to evaluate the efficacy and safety of a GFD in patients with type 1 diabetes with asymptomatic CD. Methods and analysis: Children and adults (8-45 years) with type 1 diabetes will be screened for asymptomatic CD. Eligible patients with biopsy-proven CD will be randomly assigned in a 1:1 ratio to treatment with a GFD for 1 year, or continue with a gluten-containing diet. The primary outcome will evaluate the impact of the GFD on change in glycated haemoglobin. Secondary outcomes will evaluate changes in bone mineral density, blood glucose variability and health-related quality of life between GFD-treated and the regular diet group over a 1-year period. The study was initiated in 2012 and has subsequently expanded to multiple paediatric and adult centres in Ontario, Canada. Ethics and dissemination: The findings from this study will provide high-quality evidence as to the impact of GFD treatment on glycaemic control and complications in asymptomatic children and adults with CD and type 1 diabetes. Trial registration number: NCT01566110
Screening and Treatment Outcomes in Adults and Children With Type 1 Diabetes and Asymptomatic Celiac Disease: The CD-DIET Study.
OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD.
RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA
RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%,
CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD
Rapid method for determination of DNA repair capacity in human peripheral blood lymphocytes amongst smokers
<p>Abstract</p> <p>Background</p> <p>DNA repair capacity is an important determinant of susceptibility to cancer. The hOGG1 enzyme is crucial for repairing the 8-oxoguanine lesion that occurs either as a byproduct of oxidative metabolism or as a result of exogenous sources such as exposure to cigarette smoke. It has been previously reported that smokers with low hOGG1 activity had significantly higher risk of developing lung cancer as compared to smokers with high hOGG1 activity.</p> <p>Methods</p> <p>In the current study we elucidate the association between plasma levels of 8-OHdG and the OGG1 repair capacity. We used the commercially available 8-OHdG ELISA (enzyme-linked immunosorbent assay), the Comet assay/FLARE hOGG1 (Fragment Length Analysis by Repair Enzymes) assay for quantification of the levels of 8-OHdG and measured the constitutive, induced and unrepaired residual damage, respectively. We compared the DNA repair capacity in peripheral blood lymphocytes following H<sub>2</sub>O<sub>2 </sub>exposure in 30 lung cancer patients, 30 non-, 30 former and 30 current smoker controls matched by age and gender.</p> <p>Results</p> <p>Our results show that lung cancer cases and current smoker controls have similar levels of 8-OHdG lesions that are significantly higher compared to the non-smokers controls. However, lung cancer cases showed significantly poorer repair capacity compared to all controls tested, including the current smokers controls. After adjustment for age, gender and family history of smoking-related cancer using linear regression, we observed a 5-fold increase in risk of lung cancer associated with high levels of residual damage/reduced repair capacity. Reduced OGG1 activity could be expected to be a risk factor in other smoking-related cancers.</p> <p>Conclusion</p> <p>Our study shows that the Comet/FLARE assay is a relatively rapid and useful method for determination of DNA repair capacity. Using this assay we could identify individuals with high levels of residual damage and hence poor repair capacity who would be good candidates for intensive follow-up and screening.</p
Rare Variants in APP, PSEN1 and PSEN2 Increase Risk for AD in Late-Onset Alzheimer's Disease Families
Pathogenic mutations in APP, PSEN1, PSEN2, MAPT and GRN have previously been linked to familial early onset forms of dementia. Mutation screening in these genes has been performed in either very small series or in single families with late onset AD (LOAD). Similarly, studies in single families have reported mutations in MAPT and GRN associated with clinical AD but no systematic screen of a large dataset has been performed to determine how frequently this occurs. We report sequence data for 439 probands from late-onset AD families with a history of four or more affected individuals. Sixty sequenced individuals (13.7%) carried a novel or pathogenic mutation. Eight pathogenic variants, (one each in APP and MAPT, two in PSEN1 and four in GRN) three of which are novel, were found in 14 samples. Thirteen additional variants, present in 23 families, did not segregate with disease, but the frequency of these variants is higher in AD cases than controls, indicating that these variants may also modify risk for disease. The frequency of rare variants in these genes in this series is significantly higher than in the 1,000 genome project (p = 5.09×10−5; OR = 2.21; 95%CI = 1.49–3.28) or an unselected population of 12,481 samples (p = 6.82×10−5; OR = 2.19; 95%CI = 1.347–3.26). Rare coding variants in APP, PSEN1 and PSEN2, increase risk for or cause late onset AD. The presence of variants in these genes in LOAD and early-onset AD demonstrates that factors other than the mutation can impact the age at onset and penetrance of at least some variants associated with AD. MAPT and GRN mutations can be found in clinical series of AD most likely due to misdiagnosis. This study clearly demonstrates that rare variants in these genes could explain an important proportion of genetic heritability of AD, which is not detected by GWAS
Design of a dietary intervention to assess the impact of a gluten-free diet in a population with type 1 Diabetes and Celiac Disease
Abstract
Background
Celiac Disease occurs at a 5–10 fold greater prevalence in patients with type-1 diabetes (T1D), despite this increased risk, there is limited objective evidence regarding the impact of a Gluten-Free Diet (GFD) in the large proportion of asymptomatic (30–70 %) patients with both autoimmune diseases. Given the requirements and intricacies inherent to each condition, we describe the rationale and design a dietary curriculum specifically addressing the educational requirements for children and adults with CD and diabetes as part of the CD-DIET Study.
Methods and design
The CD-DIET Study (Celiac Disease and Diabetes - Dietary Intervention and Evaluation Trial) is a multicenter randomized controlled trial aimed at evaluating the safety and efficacy of a GFD in patients with asymptomatic celiac disease and T1D on key diabetes and patient-centered outcomes.
Discussion
Key dietary components of the trial include a description and evaluation of food consumption patterns including glycemic index and glycemic load, novel assessments of gluten quantification, and objective and subjective measures of GFD adherence. This dietary curriculum will establish rigorous guidelines to assess adherence and facilitate evaluation of a GFD on metabolic control, bone health and patient quality of life in patients with CD and diabetes.
Trial registration Number
NCT01566110
. Date of Registration: March, 2012
Design of a dietary intervention to assess the impact of a gluten-free diet in a population with type 1 Diabetes and Celiac Disease
Abstract
Background
Celiac Disease occurs at a 5–10 fold greater prevalence in patients with type-1 diabetes (T1D), despite this increased risk, there is limited objective evidence regarding the impact of a Gluten-Free Diet (GFD) in the large proportion of asymptomatic (30–70 %) patients with both autoimmune diseases. Given the requirements and intricacies inherent to each condition, we describe the rationale and design a dietary curriculum specifically addressing the educational requirements for children and adults with CD and diabetes as part of the CD-DIET Study.
Methods and design
The CD-DIET Study (Celiac Disease and Diabetes - Dietary Intervention and Evaluation Trial) is a multicenter randomized controlled trial aimed at evaluating the safety and efficacy of a GFD in patients with asymptomatic celiac disease and T1D on key diabetes and patient-centered outcomes.
Discussion
Key dietary components of the trial include a description and evaluation of food consumption patterns including glycemic index and glycemic load, novel assessments of gluten quantification, and objective and subjective measures of GFD adherence. This dietary curriculum will establish rigorous guidelines to assess adherence and facilitate evaluation of a GFD on metabolic control, bone health and patient quality of life in patients with CD and diabetes.
Trial registration Number
NCT01566110
. Date of Registration: March, 2012
Commonly used preparations for colonoscopy: Efficacy, tolerability and safety – A Canadian Association of Gastroenterology position paper
INTRODUCTION: The increased demand for colonoscopy, coupled with the introduction of new bowel cleansing preparations and recent caution advisories in Canada, has prompted a review of bowel preparations by the Canadian Association of Gastroenterology
Clinical Characteristics and Long-term Outcomes of Children With Fibrosing Pancreatitis :
OBJECTIVES: Fibrosing pancreatitis (FP) shares clinical features with autoimmune pancreatitis (AIP), although both entities have not been definitely linked. This study aimed to assess the presence of AIP criteria in an historic FP patient cohort and investigate the clinical features, management, and long-term outcomes of pediatric FP (P-FP). METHODS: Clinical data of 14 P-FP patients from Toronto and 42 P-FP cases from a literature review were collected and compared to pediatric AIP (P-AIP). Toronto P-FP patients were recontacted to assess their current health status using a brief questionnaire. RESULTS: Jaundice and abdominal pain were the symptoms at presentation in 44 of 56 (79%) and 50 of 56 (89%) P-FP patients, respectively. Common findings on cross sectional imaging were an enlarged pancreas head with narrowing of the distal common bile duct (51/54, 94%). Histopathology mainly showed gland fibrosis (39/39, 100%). Three of twelve (25%) P-FP patients had elevated IgG4 in serum. None of the patients were treated with corticosteroids, but some underwent surgical or endoscopic intervention. Toronto patients were followed for a median of 13.6 years (interquartile range: 2.9-22.8). Complications during follow-up included exocrine pancreatic insufficiency (3/14, 21%) and pancreatic gland atrophy (5/13, 38%); but none of the patients had disease relapse or developed diabetes type 3c. Five (5/14 36%) patients developed other immune-mediated diseases over time. CONCLUSIONS: Clinical features of patients with P-FP resembled those recently described in a subgroup of P-AIP presenting with jaundice. Long-term outcome of these patients is generally good, with or without invasive interventions. As some patients may develop exocrine pancreatic insufficiency and/or other immune-mediated diseases, ongoing clinical monitoring is recommended