Early Detection of Long-term Diabetic Complications in Children and Adolescents With Type 1 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- Autonom neuropathy assed by Sudoscan in children and adolescent with type 1 diabetes (T1D) > 12 months
研究概览
简要总结
Aims: To investigate early markers of long-term diabetic complications and the association to an extended glucose metabolic profile comprising glucose control (current and past), glucose variability and insulin sensitivity in children and adolescents with type 1 diabetes (T1D).
Background: Most Danish children and adolescents with T1D do not achieve their metabolic target and are at increased risk of developing long-term diabetic complications, reducing their life expectancy and increase their morbidity rate. Hence, improved metabolic control, a better understanding of what optimal metabolic control means, combined with detailed monitoring of the first markers of long-term complications and their reversibility or lack thereof are needed.
Methods: A prospectivel study of 400 children, aged 6-18 years old, with T1D>12 months. Early markers of long-term diabetic complications will be investigated as arterial stiffness, nerve dysfunction and nephropathy. Data on T1D onset, duration, treatment modality, self-monitoring-blood-glucose profiles, growth, weight, and pubertal status will be collected.
Blood sampling will include routine tests and markers of glucose, lipid, bone, and gastrointestinal metabolism. DXA-scan, Fibroscan, bone-age, eye-examination and physical activity will be measured. Data on retrospective glucose- and lipid-profiles will be collected. The children will be offered a followup every 5 years for the next two decades.
Perspectives: This study provides novel insight into the frequency of early markers of long-term diabetic complications and its association to the interplay of the pancreas, adipose, gastrointestinal and bone metabolic axis. Which can assist in identifying subgroups of children and adolescents requiring earlier in-depth screening for early markers of long-term diabetic complications, for putative interventions for prevention, hence reducing morbidity and mortality in T1D.
详细描述
The project is designed as a cross-sectional cohort study. The study consists of a one-day visit where 400 children and adolescents with T1D will be thoroughly examined after an overnight fast.
The following examinations are parof this study:
- Standard physical examination: Including cor/pulm/abdomen, heart rate and blood pressure measurement. Data regarding age, sex, diabetes duration, growth, weight, and pubertal status.
Blood sampling
- Bloodsampling: Include routine tests (hemoglobin and iron metabolites, BS, HbA1c, electrolytes, creatinine, urea, LDL, HDL, triglyceride, total cholesterol), and markers of glucose (insulin, c-peptide), lipid (leptin, adiponectin), bone (VitD, calcium, PTH, phosphate, magnesium, BASP, OCN, P1NP, CTX, uOCN, sclerostine, RANKL, osteoprotegrin and osteoglycin), gastrointestinal (GLP-1, GIP and glucagon) metabolism. IGF-1, IGF-BP3, thyroid metabolism (TSH, T3, free T4), sex hormones, adrenal androgens, aldosterone. Thyroid and celiac disease autoantibodies. Markers for inflammation and endothelial dysfunction will be examined. Plasma, serum and urine will also be collected for a Biobank for future research e.g. for studying metabolomics.
- Carotid-femoral pulse wave velocity: Assessed with the Sphygmocor (AtCor Medical) device to measure arterial stiffness in the large arteries.
- Evaluation of the nervous system function:
- Cardiac autonomic neuropathy function will be assessed by the Vagus device.
- Large sensory nerve function test assessed by sural nerve conduction velocity and sural nerve amplitude, measured with the non-invasive handheld device DPNCheckTM (NeuroMetrix, Inc., Waltham, USA).
- Small sympathetic nerve fiber function assessed by electrochemical skin conductance assessed using the non- invasive device Sudoscan™ (Impeto Medical, Paris, France).
- Kidney: Three morning urine samples will be collected at home for analyses of albumin/creatinine ratio.
- Bone age Measured on an x-ray of the left hand using BoneXpert software to adjust for potentially biological age.
- Dual energy X-ray absorptiometry scan: Performed to evaluate body composition and bone mineral density.
- Fibroscan: To determine the stiffness of the liver (liver elastography).
- Eye-examination: Visus, OPTOS, OCT og OCTA.
- Continuous blood glucose monitoring (CGM) Evaluation of glucose variability for at least 14 days. Most children and adolescent at our outpatient clinics use these as part of their regular regulation and treatment. If the participant normally uses a CGM-device, data on blood glucose variation from the past 90 days will be collected. If not a CGM-monitor will be placed on the upper arm and the participants will be instructed to wear it for the next 14 days.
- AX3: Physical activity for 7 days will be measured. Questionnaire Physical activity, Life quality
- Extended lungfunction
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •T1D>12 months
- •6-18 years old prior to inclusion
- •Followed at the Pediatric Diabetes outpatient clinic at Steno Diabetes Center Copenhagen
- •Speaks and reads Danish well enough to understanding the given oral and written information.
- •There is a written consent from the guardianship holder/holders for the child.
排除标准
- •T1D < 12 months
- •Known cardiovascular disease
- •Antihypertensive treatment
结局指标
主要结局
Autonom neuropathy assed by Sudoscan in children and adolescent with type 1 diabetes (T1D) > 12 months
时间窗: 15.01.2022-15.02.2024
Neuropathy assesed by Sudoscan: Peripheral small-fiber sympathetic function (Sudoscan), measuring sudomotor function by electrochemical skin conductance (µS) in feet
Peripheral neuropathy assed by DPN-check in children and adolescent with type 1 diabetes (T1D) > 12 months
时间窗: 15.01.2022-15.02.2024
Neuropathy assesed by DPN-check: Sural Nerve conduction velocity(m/s) of the Sural nerves by DPN-check.
Arterial stiffness in children and adolescent with type 1 diabetes (T1D) > 12 months and its association to glycemic control (current and past).
时间窗: 15.01.2022-15.02.2024
PWV is a measure of arterial stiffness (m/s) which can be done non invasively at bedside using a device called SphygmoCor CVMS machine (Atcor Medical, Sydney, Australia).
Prevalence of cardivascular autonomic neuropathy assed by VagusDevice in children and adolescent with type 1 diabetes (T1D) > 12 months
时间窗: 15.01.2022-15.02.2024
The examination consists of 4 measures, all aimed at measuring heart rate. Measurements are taken for 5 minutes rest, change of position from lying to standing position, during deep breathing and by Valsalva (by breathing in a mouthpiece with a 40 mmHg resistance).
次要结局
- The association between early markers of diabetic complications and glycemic control(15.01.2022-15.02.2024)