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Effect of Acute Hyperglycemia on Renal Tissue Oxygenation

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Centre Hospitalier Universitaire Vaudois

关键词

抽象

Diabetes Mellitus (DM) includes several metabolic diseases all characterized by high sugar levels in the blood. Although diabetic nephropathy is widespread, its underlying pathophysiological mechanisms remain poorly understood and, so far, little progress has been made to prevent the development of diabetic nephropathy and to delay kidney functions decline.
Increasing amount of data based on animal studies support the pathogenic role of tissue hypoxia in the development and progression of diabetic nephropathy. Blood Oxygenation-Level Dependent Magnetic Resonance Imaging (BOLD-MRI) is increasingly used in research to measure cortical and medullary oxygenation in a non-invasive manner. Interestingly, in two cross-sectional clinical studies, we have recently found a positive correlation between high circulating blood glucose levels and cortical R2* levels in type 2 DM patients. This discovery suggests that an increase in glycemia might acutely decrease renal tissue oxygenation.
The goal of this study is to investigate the impact of serum glucose on renal tissue oxygenation in healthy subjects and subjects with glucose intolerance.

描述

Therefore, we plan to recruit 10 healthy subjects and 10 glucose intolerant patients with preserved kidney functions and to perform repetitive BOLD-MRI, before and after the administration of IV glucose. This will allow us to study the influence of hyperglycemia as a single factor, regardless of inflammation, oxidative stress and medical treatments, such as oral hypoglycemic agents and/or insulin, which are confounding factors present in all DM patients.

The main hypothesis of the project is that acute hyperglycemia could be partially responsible for renal tissue hypoxia detected in diabetic nephropathy cases.

In this study we will include 60 participants with a family history of diabetes, with a Body Mass Index (BMI) over 25 kg / m2 and/or having glucose intolerance. Each participant will undergo an initial glucose tolerance test. In total, we will select 10 participants with impaired glucose tolerance and 10 healthy subjects (matched for sex and age), to be included as control group.

Selected subjects will return for a third visit at CHUV (V3): they will start at home with an oral hydration protocol (load dose of 3 ml / kg at 8:00 am, followed by 1 ml / kg every hour between 9:00 am and 3:00 pm to avoid as much as possible changes in kidney perfusion). Patients will arrive at the Department of Nephrology and Hypertension (CHUV) at 11.00 am. In this occasion, two catheters will be placed into each patient's arm. Later, participants will be escorted to the Radiology Department to undergo four renal oxygenation imaging (between 1:00 pm and 2:00 pm) by the mean of BOLD-MRI technique. During this period, patients and control subjects will lie down and are not allowed to stand up. At T0, they will receive a bolus (0.75 ml / kg) of glucose 20%. Subsequently, four BOLD-MRI scans, together with blood tests, will be performed at T0, T1 (+10 min), T2 (+20 min), T3 (+30 min). Sodium intake will be measured by 24 hours urinary collection the day before V3 (sodium is known to influence R2*).

日期

最后验证: 06/30/2019
首次提交: 01/19/2015
提交的预估入学人数: 01/22/2015
首次发布: 01/25/2015
上次提交的更新: 07/28/2019
最近更新发布: 07/30/2019
实际学习开始日期: 05/31/2015
预计主要完成日期: 11/30/2018
预计完成日期: 01/30/2019

状况或疾病

Hyperglycemia
Glucose Intolerance

干预/治疗

Other: Patient with impaired glucose tolerance

-

手臂组

干预/治疗
Other: Patient with impaired glucose tolerance
Bold-MRI before and after glucose injection
Other: Patient with impaired glucose tolerance
Intravenous infusion (0.75 ml / kg) over 1 min

资格标准

有资格学习的年龄 18 Years 至 18 Years
有资格学习的性别All
接受健康志愿者
标准

Inclusion Criteria:

- Positive family history of diabetes

- BMI > 25 kg / m2

- eGFR > 60 ml / min / 1.73 m2

- Understanding and signing the informed consent

Exclusion Criteria:

- Documented cardiac disease

- Documented liver failure

- Renal malformations, kidney diseases or documented renal artery stenosis

- History of organ transplantation

- Significant comorbidities compromising life expectancy

- Anemia

- Type 1 or 2 diabetes

- Psychiatric illness

- Contraindication to MRI

- Pregnancy or breastfeeding

- Chronic drug intake such as antihypertensive (except for beta blockers and calcium antagonists), non steroidal anti-inflammatory drugs, diuretics or oral antidiabetics

- Blood donation 2 months before the MRI investigation day

结果

主要结果指标

1. Cortical and medullary renal R2* MRI signal variation, before, during and after an induced hyperglycemic state [Four R2* imaging will be performed during an investigation day between 1:00 pm and 2:00 pm]

2. Intergroup variability of MRI R2* signal, before, during and after an induced hyperglycemic state [Four R2* imaging will be performed during an investigation day between 1:00 pm and 2:00 pm]

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