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| Name | Class |
|---|---|
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
| BC Children's Hospital Research Institute | OTHER |
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Cardiovascular disease is a complication of type 1 diabetes (T1D), a life-long disease, usually diagnosed in childhood. The goal of this project is to determine the timing and factors leading to vascular damage in children from T1D diagnosis.
This is a prospective longitudinal cohort study investigating vascular health in children over the first 2 years of type1 diabetes (T1D) diagnosis living in Metro Vancouver, Canada.
Cardiovascular disease is a major complication of T1D traditionally considered a longterm complication that manifests in adulthood. However, several studies have reported evidence of cardiovascular disease in children who have had T1D for more than 1 year but it is unclear how and when the cardiovascular damage begins. There is also minimal data on cardiovascular complications in children with type 1 diabetes living in Canada.
The goal of this project is to determine the timing and factors leading to vascular damage in children from T1D diagnosis.
We will follow children (aged 8-18 years) from T1D diagnosis over the first 2 years. The primary objective of the study is to assess changes in arterial stiffness (pulse wave velocity; augmentation index), 24-h ambulatory blood pressure (24h-ABPM), and blood biomarkers of vascular damage during the first 2 years of T1D diagnosis.
The secondary objectives of the study are to assess changes in body composition, surrogate markers of adiposity (BMI, waist circumference), and dietary intakes during the first 2 years of T1D diagnosis; and to determine the relationships to measures of arterial stiffness, blood pressure, and blood biomarkers of vascular damage. We will also collect sociodemographic data, estimates of physical activity, and glycated hemoglobin (A1C) as an indicator of glycemic control.
Children with a T1D diagnosis aged 8-18 years will be recruited through the Endocrine and Diabetes Unit at BC Children's Hospital (BCCH). Vascular assessments, blood samples, and data will be collected at diagnosis (within 14 weeks of T1D diagnosis; baseline) and at 6, 12, 18, and 24 months post-diagnosis; there will be a total of 5 visits. Each subject will undergo a clinical assessment, interview/questionnaires, blood collection, and cardiovascular assessment.
Statistical Analysis: . Linear regression models will be used to assess changes in 24-h ABPM mean, daytime and nighttime blood pressure, pulse wave velocity, augmentation index, and biomarkers of vascular damage at diagnosis with values collected during the first 24 months post diagnoses. Models will be adjusted for appropriate covariates. To fully understand the biological differences between males and females, data from boys and girls will be analyzed separately.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Children with Type 1 diabetes | children recruited within 14 weeks of type 1 diabetes diagnosis and followed for 24 months. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in pulse wave velocity during the first 24 months of type 1 diabetes diagnosis | Carotid-femoral pulse wave velocity (PWV) will be measured with a SphygmoCor® XCEL System (AtCor Medical Pty Ltd). | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 6,12, 18 and 24 months post-diagnosis. |
| Change in clinic blood pressure during the first 24 months of type 1 diabetes diagnosis | Systolic and diastolic blood pressure measures (average of 3 readings) will be collected using a Dinamap automated monitor (PRO 100-400, GE Medical Systems) and an appropriately sized cuff. Values will be standardized for age, sex, and height using the 2017 American Academy of Pediatrics guidelines. | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 6,12, 18 and 24 months post-diagnosis. |
| Change in augmentation index during the first 24 months of type 1 diabetes diagnosis | Augmentation index will be measured with a SphygmoCor® XCEL System (AtCor Medical Pty Ltd). | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 6,12,18 and 24 months post-diagnosis. |
| Change in 24-h automated blood pressure monitoring (ABPM) during the first 24 months of type 1 diabetes diagnosis | Children will wear a 24h-ABMP (SpaceLabs) that measures blood pressure every 20 minutes for 24 hours. This will allow for any abnormalities not detected in the clinic to be identified (e.g. masked hypertension). Data will be standardized and categorized according to the 2022 American Academy of Pediatrics guidelines. | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 12 and 24 months post-diagnosis. |
| Change in biomarkers of vascular health during the first 24 months of type 1 diabetes diagnosis | Blood biomarkers of vascular health will be assessed in plasma, serum and PBMCs. This includes: a) E-selectin, intracellular adhesion molecule 1 (ICAM), vascular cellular adhesion molecule 1 (VCAM), and von Willebrand factor (vWF) will be quantified as circulating indicators of endothelial damage. b) C-reactive protein (CRP), interleukin (IL)-6, IL-8, monocyte chemotactic protein-1 (MCP-1), isoprostane and tumor necrosis factor alpha (TNFα) will be quantified as indicators of inflammation. c) Creatinine and total homocysteine will be quantified as indicators of kidney function; d) genome wide DNA methylation patters in PBMCs. |
| Measure | Description | Time Frame |
|---|---|---|
| Sociodemographic information | Sociodemographic information will be collected including: age, sex, gender, self-reported ethnicity, and family medical history of cardiovascular disease. and diabetes. | Baseline (within 14 weeks of type 1 diabetes diagnosis). Family history of cardiovascular disease and diabetes and gender will also be assessed at 6, 12, 18, and 24 months. |
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Inclusion Criteria
Exclusion Criteria
Children will be ineligible to participate in the study if they meet any of the following:
Transgender children taking hormone blockers or exogenous sex steroids will be excluded because of the potential effect on metabolic health.
Children will be recruited within 14 weeks of type 1 diabetes diagnosis through the Endocrine and Diabetes Unit at BC Children's Hospital.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Angela Devlin, PhD | Contact | 6048752000 | 5378 | adevlin@bcchr.ubc.ca |
| Constadina Panagiotopoulos, MD | Contact | dpanagiotopoulos@cw.bc.ca |
| Name | Affiliation | Role |
|---|---|---|
| Angela Devlin, PhD | UBC Pediatrics/BC Children's Hospital Research Institute | Principal Investigator |
| Constadina Panagiotopoulos, MD | UBC Pediatrics/BC Children's Hospital Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Endocrine and Diabetes Unit, BC Children's Hospital | Recruiting | Vancouver | British Columbia | V5Z4H4 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16567818 | Background | Soedamah-Muthu SS, Fuller JH, Mulnier HE, Raleigh VS, Lawrenson RA, Colhoun HM. High risk of cardiovascular disease in patients with type 1 diabetes in the U.K.: a cohort study using the general practice research database. Diabetes Care. 2006 Apr;29(4):798-804. doi: 10.2337/diacare.29.04.06.dc05-1433. | |
| 669100 | Background |
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The data will be available after the study is completed (Dec 2026).
Written requests specifying need to access the data should be made to the co-PIs: Dr Angela Devlin and Dr Dina Panagiotopoulos
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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Venous blood samples (20ml) will be collected to evaluate biomarkers of vascular damage. Serum, plasma, and PBMCs will be obtained from the blood samples.
| Baseline (within 14 weeks of type 1 diabetes diagnosis), and at 12 and 24 months post diagnosis. |
| Puberty Status | Pubertal development (Tanner stage) will be evaluated by self-reported Tanner staging. The form used for the self-report development stage will be provided to participants according to their sex at birth. | Baseline (within 14 weeks of type 1 diabetes diagnosis), and 12 and 24 months post diagnosis. |
| Body weight | Body weight will be measured measured in children wearing light clothing, pockets emptied, and without shoes using a balance scale. Weight will be recorded to the nearest 0.1 kg. | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 6,12,18 and 24 months post-diagnosis. |
| BMI | Body mass index (BMI) will be calculated using weight and height measures [weight (kg)/height (m2)] and standardized for sex and age (z-score and percentile) according to WHO growth reference charts. | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 6,12,18 and 24 months post-diagnosis. |
| Physical activity | Physical activity questionnaire (PAQ) will be administered to quantify relative levels of daily physical activity. There are two versions of the questionnaires: one for elementary school aged children and the second for high school aged children. Participants will be given the questionnaire that corresponds with whether they are in elementary school or high school . | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 6,12,18 and 24 months post-diagnosis. |
| Nutritional assessment | 3x 24-hr dietary recalls will be used to assess dietary intakes. We will conduct 3 dietary recalls for 3 non-consecutive days. The first dietary recall will be will be conducted in person by a member of the research staff during the study visit. The other two diary recalls will be completed over the phone. During the in-person dietary recall, the participants and their parents/caregivers will be shown food models, plates, bowls, cups, and spoons to help them better gauge the amounts of foods and beverages consumed. | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 12 and 24 months post-diagnosis. |
| Glycated hemoglobin (A1C) | Blood A1C levels will be measured to assess glycemic control over the past few months. The values for each time point will be obtained from the clinical charts. This is routinely done at clinic visits, thus we will obtain this information from medical chart | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 6,12,18 and 24 months post-diagnosis. |
| Body composition | Body composition will be assessed by Dual-energy X-ray absorptiometry (DEXA) scan (Horizon® Hologic Inc). The percent lean and fat mass and bone density will be calculated from the scans. | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 6,12,18 and 24 months post-diagnosis. |
| Height | Height will be measured in the children wearing no shoes. Height will be recorded to the nearest 0.1 cm with a stadiometer. | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 6,12,18 and 24 months post-diagnosis. |
| Waist circumference | Waist circumference will be assessed using a non-elastic flexible tape measure at the level of the umbilicus. The values will be standardized for sex and age (z-score) according to Sharma et al. | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 6,12,18 and 24 months post-diagnosis. |
| Smoking and substance use | Smoking and substance use will be collected as self-reported through direct interview with the subject/family. Collecting this information will allow us to assess the potential impact of smoking habits on vascular health. In addition, tobacco, vaping, e-cigarette, and cannabis use has been described to influence appetite and may affect dietary habits. | Baseline (within 14 weeks of type 1 diabetes diagnosis) and at 6,12,18 and 24 months post-diagnosis. |
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| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |