scholarly journals Epigenome-Wide Association Study of Infant Feeding and DNA Methylation in Infancy and Childhood in a Population at Increased Risk for Type 1 Diabetes

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4057
Author(s):  
Elizabeth Walker-Short ◽  
Teresa Buckner ◽  
Timothy Vigers ◽  
Patrick Carry ◽  
Lauren A. Vanderlinden ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Type 1 Diabetes ◽  
Breastfeeding Duration ◽  
Solid Foods ◽  
Infant Diet ◽  
Cpg Sites ◽  
Increased Risk ◽  
Infancy And Childhood

We assessed associations between infant diet (e.g., breastfeeding and introduction to solid foods) and DNA methylation in infancy and childhood. We measured DNA methylation in peripheral blood collected in infancy (9–15 months of age) in 243 children; and in a subset of 50 children, we also measured methylation in childhood (6–9 years of age) to examine persistence, and at birth (in cord blood) to examine temporality. We performed multivariable linear regression of infant diet on the outcome of methylation using epigenome-wide and candidate site approaches. We identified six novel CpG sites associated with breastfeeding duration using an EWAS approach. One differentially methylated site presented directionally consistent associations with breastfeeding (cg00574958, CPT1A) in infancy and childhood but not at birth. Two differentially methylated sites in infancy (cg19693031, TXNIP; cg23307264, KHSRP) were associated with breastfeeding and were not present at birth; however, these associations did not persist into childhood. Associations between infant diet and methylation in infancy at three sites (cg22369607, AP001525.1; cg2409200, TBCD; cg27173510, PGBD5) were also present at birth, suggesting the influence of exposures other than infant diet. Infant diet exposures are associated with persistent methylation differences in CPT1A, which may be one mechanism behind infant diet’s long-term health effects.

scholarly journals ACE I/D Polymorphism, Plasma ACE Levels, and Long-term Kidney Outcomes or All-Cause Death in Patients With Type 1 Diabetes

2021 ◽  
Author(s):  
Yawa Abouleka ◽  
Kamel Mohammedi ◽  
Charlyne Carpentier ◽  
Severine Dubois ◽  
Pierre Gourdy ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Primary Outcome ◽  
Rapid Decline ◽  
Genotype Distribution ◽  
Net Reclassification Improvement ◽  
Increased Risk ◽  
Cox Analysis

<b>Objective:</b> The D-allele of <i>ACE</i> I/D polymorphism is a risk factor for diabetic kidney disease. We assessed its contribution to long-term kidney outcomes and all-cause death in patients with long-standing type 1 diabetes. <p><b>Research Design and Methods:</b> 1155 participants from 3 French and Belgian cohorts were followed for a median (interquartile range) duration of 14 (13) years. The primary outcome was the occurrence of end-stage kidney disease (ESKD) or a 40% drop in estimated glomerular filtration rate (eGFR). Secondary outcomes were the individual components of the primary outcome, rapid decline in eGFR (steeper than -3 ml/min/1.73m<sup>2</sup>/year), incident albuminuria, all-cause death, and a composite ESKD or all-cause death. Hazard ratios (HR) for XD versus II genotype and for baseline plasma ACE levels were computed by Cox analysis. Genotype performance in stratifying the primary outcome was tested.</p> <p><b>Results:</b> Genotype distribution was 954 XD and 201 II. The primary outcome occurred in 20% of XD and 13% of II carriers: adjusted HR 2.07 (95%CI, 1.32-3.40), p=0.001. Significant associations were also observed for rapid decline in eGFR, incident albuminuria, ESKD, all-cause death, and ESKD or all-cause death. Baseline plasma ACE levels were higher in XD carriers and significantly associated with increased risk of the primary outcome. ACE genotype enhanced net reclassification improvement (0.154, 95%CI 0.007-0.279, p=0.04) and integrated discrimination improvement (0.012, 95%CI 0.001-0.021, p=0.02) for primary outcome stratification.</p> <b>Conclusions:</b> The D-allele of <i>ACE</i> I/D polymorphism was associated with increased risk of major kidney events and all-cause death in patients with long-standing type 1 diabetes.

scholarly journals Mortality in childhood-onset type 1 diabetes: Nationwide population based data from Norway

2013 ◽  
Vol 23 (1) ◽  
Author(s):  
Torild Skrivarhaug
Keyword(s):  
Type 1 Diabetes ◽  
Premature Mortality ◽  
Diabetic Coma ◽  
Diabetic Patients ◽  
Childhood Onset ◽  
Onset Type ◽  
Treatment Type ◽  
Increased Risk

Type 1 diabetes with onset in childhood (0-14.9 years) represents one of the most frequent chronic diseases in children and young adults. Norway has one of the highest incidences of childhood onset type 1 diabetes in the world. Before introduction of insulin therapy in 1922, few children survived more than one to two years after clinical onset. When insulin came available, a major shift occurred in the distribution of causes of death in type 1 diabetic patients away from diabetic coma, which dominated the pre-insulin era, to renal and cardiac diseases. The disease is related to a significant burden to society and patients because most cases require lifelong treatment with insulin as well as day-to-day monitoring. Type 1 diabetes also confers increased risk of severe late complications such as renal failure, blindness, amputations, heart disease and stroke. Despite advances in diabetes treatment, type 1 diabetes is still associated with considerable premature mortality resulting from acute and chronic complications of diabetes and an increase in mortality at every age. Although the main cause of death in type 1 diabetes is long-term complications, an excess death rate has also been reported in subjects with short duration without signs of long-term complications.

scholarly journals Reduced expression of OXPHOS and DNA damage genes is linked to protection from microvascular complications in long-term type 1 diabetes: the PROLONG study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Türküler Özgümüş ◽  
Oksana Sulaieva ◽  
Leon Eyrich Jessen ◽  
Ruchi Jain ◽  
Henrik Falhammar ◽  
...  
Keyword(s):  
Dna Repair ◽  
Type 1 Diabetes ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Diabetes Duration ◽  
Chronic Hyperglycemia ◽  
Increased Risk ◽  
Term Type

AbstractType 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1 diabetes who have remained largely free from vascular complications constitute an ideal group for investigation of natural defense mechanisms against prolonged exposure of diabetes. Transcriptomic signatures obtained from RNA sequencing of the peripheral blood cells were analyzed in non-progressors with more than 30 years of diabetes duration and compared to the patients who progressed to microvascular complications within a shorter duration of diabetes. Analyses revealed that non-progressors demonstrated a reduction in expression of the oxidative phosphorylation (OXPHOS) genes, which were positively correlated with the expression of DNA repair enzymes, namely genes involved in base excision repair (BER) machinery. Reduced expression of OXPHOS and BER genes was linked to decrease in expression of inflammation-related genes, higher glucose disposal rate and reduced measures of hepatic fatty liver. Results from the present study indicate that at transcriptomic level reduction in OXPHOS, DNA repair and inflammation-related genes is linked to better insulin sensitivity and protection against microvascular complications in persons with long-term type 1 diabetes.

scholarly journals Time in Range Does Not Associate With Carotid Artery Wall Thickness and Endothelial Function in Type 1 Diabetes

2021 ◽  
pp. 193229682199317
Author(s):  
Antonio Cutruzzolà ◽  
Martina Parise ◽  
Faustina B Scavelli ◽  
Milena Barone ◽  
Agostino Gnasso ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Carotid Artery ◽  
Endothelial Function ◽  
Brachial Artery ◽  
Target Range ◽  
Increased Risk ◽  
Short And Long Term

Background: Patients with Type 1 diabetes (T1D) have an increased risk of developing atherosclerosis and complications as myocardial infarction and peripheral artery disease. The thickening of the carotid wall and the brachial artery dysfunction are early and preclinical manifestations of atherosclerosis. The standard marker of care for assessment of glycemic control, glycated hemoglobin, does not associate with early atherosclerosis. We have hypothesized that the emerging metric of glycemic control, as the time spent in the target range (TIR), might be associated with carotid thickening and endothelial dysfunction. According to the hypothesis, we have designed the present research with the aim to evaluate the association between TIR collected in the short and long term and the measures of arterial morphology and function in patients with T1D. Methods: In our study, 70 patients and 35 healthy controls underwent ultrasound vascular study to measure carotid artery intima-media thickness (IMT) and brachial artery endothelial function by the flow-mediated dilation (FMD) technique. TIR was collected by a continuous glucose monitoring system for 2 weeks, 3 months, and 6 months before the vascular study. Results: Patients with T1D showed a significantly higher carotid IMT (mean±SE, 644±19 vs. 568±29 µ; p= 0.04) and a significantly lower FMD (mean±SE, 7.6±0.4 vs. 9.8±0.6%; p=0.01) compared with control subjects. No significant relationship between IMT, FMD, and TIR collected in the short and long term emerged. Conclusions: Young patients with T1D have early vascular abnormalities. The percent of TIR does not correlate with preclinical atherosclerosis. This finding underlines the complexity of the interplay between diabetes and atherosclerosis.

scholarly journals Experiences From a Coaching Program for Parents of Children and Adolescents With Type 1 Diabetes Developed Through Experienced-Based Co-Design (EBCD)

2020 ◽  
Vol 7 (6) ◽  
pp. 1181-1188
Author(s):  
Kerstin Ramfelt ◽  
Christina Petersson ◽  
Karin Åkesson
Keyword(s):  
Type 1 Diabetes ◽  
Children And Adolescents ◽  
Qualitative Content Analysis ◽  
Pediatric Diabetes ◽  
Increased Risk ◽  
The Family ◽  
Parental Coaching ◽  
Coach Program

Many children and adolescents with type 1 diabetes (T1D) have difficulties reaching the national treatment goal for HbA1c (long-term blood sugar) which is associated with increased risk for complications. This makes it important to explore what patients and their caregivers describe important in coping with everyday life. The study has been conducted within a pediatric diabetes team in the south of Sweden. The aim was to explore how Experienced-Based Co-Design (EBCD) can be used to identify, test, and evaluate improvement efforts in order to support the family with a child with T1D. A modified variant of EBCD based on focus groups, workshops, and interviews with stakeholders was used. The improvement proposal parental coaching was tested and was appreciated by the participants. The qualitative content analysis of the interviews showed that the coaching program contributed to better confidence and self-efficacy. Both coaches and coachees described that the coaching contributed to better competence and a feeling of hope after attending the coach program. Experienced-Based Co-Design gave an opportunity to explore what´s important to improve, based on experiences and needs of several stakeholders.

scholarly journals Dyslipidaemia in Type 1 Diabetes: Molecular Mechanisms and Therapeutic Opportunities

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 826
Author(s):  
Stephen T. O’Brien ◽  
Orla M. Neylon ◽  
Timothy O’Brien
Keyword(s):  
Type 1 Diabetes ◽  
Best Practice ◽  
Molecular Mechanisms ◽  
Clinical Situation ◽  
Lipid Lowering ◽  
Cvd Risk ◽  
Ongoing Research ◽  
Increased Risk

Cardiovascular disease (CVD) is the leading cause of death in Type 1 Diabetes (T1D). The molecular basis for atherosclerosis in T1D is heavily influenced by hyperglycaemia and its atherogenic effects on LDL. Ongoing research into the distinct pathophysiology of atherosclerosis in T1D offers exciting opportunities for novel approaches to calculate CVD risk in patients with T1D and to manage this risk appropriately. Currently, despite the increased risk of CVD in the T1D population, there are few tools available for estimating the risk of CVD in younger patients. This poses significant challenges for clinicians in selecting which patients might benefit from lipid-lowering therapies over the long term. The current best practice guidance for the management of dyslipidaemia in T1D is generally based on evidence from patients with T2D and the opinion of experts in the field. In this review article, we explore the unique pathophysiology of atherosclerosis in T1D, with a specific focus on hyperglycaemia-induced damage and atherogenic LDL modifications. We also discuss the current clinical situation of managing these patients across paediatric and adult populations, focusing on the difficulties posed by a lack of strong evidence and various barriers to treatment.

scholarly journals ACE I/D Polymorphism, Plasma ACE Levels, and Long-term Kidney Outcomes or All-Cause Death in Patients With Type 1 Diabetes

2021 ◽  
Author(s):  
Yawa Abouleka ◽  
Kamel Mohammedi ◽  
Charlyne Carpentier ◽  
Severine Dubois ◽  
Pierre Gourdy ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Primary Outcome ◽  
Rapid Decline ◽  
Genotype Distribution ◽  
Net Reclassification Improvement ◽  
Increased Risk ◽  
Cox Analysis

<b>Objective:</b> The D-allele of <i>ACE</i> I/D polymorphism is a risk factor for diabetic kidney disease. We assessed its contribution to long-term kidney outcomes and all-cause death in patients with long-standing type 1 diabetes. <p><b>Research Design and Methods:</b> 1155 participants from 3 French and Belgian cohorts were followed for a median (interquartile range) duration of 14 (13) years. The primary outcome was the occurrence of end-stage kidney disease (ESKD) or a 40% drop in estimated glomerular filtration rate (eGFR). Secondary outcomes were the individual components of the primary outcome, rapid decline in eGFR (steeper than -3 ml/min/1.73m<sup>2</sup>/year), incident albuminuria, all-cause death, and a composite ESKD or all-cause death. Hazard ratios (HR) for XD versus II genotype and for baseline plasma ACE levels were computed by Cox analysis. Genotype performance in stratifying the primary outcome was tested.</p> <p><b>Results:</b> Genotype distribution was 954 XD and 201 II. The primary outcome occurred in 20% of XD and 13% of II carriers: adjusted HR 2.07 (95%CI, 1.32-3.40), p=0.001. Significant associations were also observed for rapid decline in eGFR, incident albuminuria, ESKD, all-cause death, and ESKD or all-cause death. Baseline plasma ACE levels were higher in XD carriers and significantly associated with increased risk of the primary outcome. ACE genotype enhanced net reclassification improvement (0.154, 95%CI 0.007-0.279, p=0.04) and integrated discrimination improvement (0.012, 95%CI 0.001-0.021, p=0.02) for primary outcome stratification.</p> <b>Conclusions:</b> The D-allele of <i>ACE</i> I/D polymorphism was associated with increased risk of major kidney events and all-cause death in patients with long-standing type 1 diabetes.

scholarly journals Epigenetic And Transcriptomic Alterations in Offspring Born To Women With Type 1 Diabetes (The EPICOM Study)

2021 ◽  
Author(s):  
Sine Knorr ◽  
Anne Skakkebæk ◽  
Jesper Just ◽  
Christian Trolle ◽  
Søren Vang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Disease ◽  
Dna Methylation ◽  
Type 1 Diabetes ◽  
Functional Enrichment ◽  
Postal Code ◽  
Rna Expression ◽  
Increased Risk ◽  
Using Data

Abstract Background: Offspring born to women with pregestational type 1 diabetes (T1DM) are exposed to an intrauterine hyperglycemic milieu and has an increased risk of metabolic disease in later in life. In this present study we hypothesize that in utero exposure to T1DM alters offspring DNA methylation and gene expression, thereby altering their risk of future disease. Design: Follow-up study using data from the Epigenetic, Genetic and Environmental Effects on Growth, Metabolism and Cognitive Functions in Offspring of Women with Type 1 Diabetes (EPICOM) collected between 2012-2013.Setting: Exploratory sub study using data from the nationwide EPICOM study.Participants: Adolescent offspring born to women with T1DM (n=20) and controls (n=20) matched on age, sex and postal code. Main outcome measures: This study investigates DNA methylation using the 450K-Illumina Infinium assay® and RNA expression (RNA sequencing) of leucocytes from peripheral blood samples. Results: We identified 9 hypermethylated and 5 hypomethylated positions (p < 0.005, |DM-value| > 1). RNA expression profiling identified 38 up- and 1 down-regulated genes (p < 0.005, log2FC ≥ 0.3.). Functional enrichment analysis revealed enrichment in ontologies related to diabetes, carbohydrate and glucose metabolism, pathways including MAPK1/MAPK3 and MAPK family signaling and genes related to T1DM, obesity and atherosclerosis. Lastly, by integrating the DNA methylation and RNA expression data, we identified six genes where relevant methylation changes corresponded with RNA expression (CIITA, TPM1, PXN, ST8SIA1, LIPA, DAXX). Conclusions: Findings suggest the possibility for intrauterine hyperglycemia to impact later life methylation and gene expression, a profile that may be linked to the increased risk of metabolic disease.

Immune status is associated with the mode of delivery in infants at increased risk for Type 1 Diabetes

2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
O D'Orlando ◽  
R Puff ◽  
A Henniger ◽  
S Krause ◽  
F Haupt ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Status ◽  
Mode Of Delivery ◽  
Increased Risk
Sign in / Sign up

Export Citation Format

Share Document