Integrated Analysis of the Interactions Between Glycemia and Microbiota Composition, and Their Impact on Brain Iron Deposition and Cognition in Subjects With Obesity
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 128
- 试验地点
- 1
- 主要终点
- The percentage of time in glucose target range (glucose level 100mg/dl-125mg/dl)
研究概览
简要总结
The accumulation of iron is known to affect the functions of the liver, adipose tissue and muscle. The brain is a well-known place of iron deposition, which is associated with cognitive parameters of subjects with obesity.
The hypothesis is that certain parameters related to glucose metabolism (glycemic variability, the circulating concentration of AGE receptor agonists, pentosidine and HbA1c) are associated with cognitive function, brain iron content and gut microbiota composition in subjects with obesity.
The study includes both a cross-sectional (comparison of subjects with and without obesity) and a longitudinal design (evaluation one year after weight loss induced by bariatric surgery or by diet in patient with obesity) to evaluate the associations between continuous glucose monitoring, brain iron content (by magnetic resonance), cognitive function (by means of cognitive tests), physical activity (measured by activity and sleep tracker device) and the composition of the microbiota, evaluated by metagenomics.
详细描述
Subjects and methods:
A. Cross-sectional study:
Patients with obesity previously scheduled at the Service of Endocrinology, Diabetes and Nutrition (UDEN) of the Hospital "Dr. Josep Trueta" of Girona (Spain) will be recruited and studied. Subjects without obesity will also be recruited through a public announcement.
A blood glucose sensor will be implanted for ten days, as well as an activity and sleep tracker device to record physical activity during this period of time. Interstitial subcutaneous glucose concentrations will be monitored on an outpatient basis for a period of time of 10 consecutive days using a glucose sensor validated by the FDA (Dexcom G6 ®). The sensor will be implanted in on day 0 and will retire on day 10 midmorning. Glucose records will preferably be evaluated on days 2 to 9 to avoid the bias caused by the insertion and removal of the sensor, which prevents a sufficient stabilization of the monitoring system. The characteristic glycemic pattern of each patient will be calculated on average from the profiles obtained on days 2 to 9.
At the end of the week an magnetic resonance imaging will be done to evaluate the iron content in the brain and parameters of "Diffusion Tensor Imaging" in different brain territories.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women aged 30-65 years.
- •Informed consent for participation in the study.
排除标准
- •Serious systemic disease unrelated to obesity such as cancer, severe kidney, or liver disease, known type 1 or type 2 diabetes.
- •Systemic diseases with intrinsic inflammatory activity such as rheumatoid arthritis, Crohn's disease, asthma, chronic infection (e.g., HIV, active tuberculosis) or any type of infectious disease.
- •Pregnancy and lactation.
- •Patients with severe disorders of eating behaviour.
- •Persons whose liberty is under legal or administrative requirement.
- •Clinical symptoms and signs of infection in the previous month.
- •Antibiotic, antifungal or antiviral treatment in the previous 3 months.
- •Anti-inflammatory chronic treatment with steroidal and/or non-steroidal anti-inflammatory drugs.
- •Major psychiatric antecedents.
- •Excessive alcohol intake, either acute or chronic (alcohol intake greater than 40 g a day (women) or 80 g/day (men)) or drugs abuse.
- •Serum liver enzymes (AST, ALT) activity over twice the upper limit of normal.
- •History of disturbances in iron balance (e.g., genetic hemochromatosis, hemosiderosis from any cause, atransferrinemia, paroxysmal nocturnal hemoglobinuria).
结局指标
主要结局
The percentage of time in glucose target range (glucose level 100mg/dl-125mg/dl)
时间窗: 30 months
Minutes light sleep
时间窗: 30 months
Mean and standard deviation of minutes light sleep measures by activity and sleep tracker device.
Minutes rapid eye movement (REM)
时间窗: 30 months
Mean and standard deviation of minutes REM measures by activity and sleep tracker device.
Glycemic variability.
时间窗: 30 months
Mean and standard deviation of glucose measures in mg/dL using a continuous glucose monitoring during 10 days.
The glycaemic risk measured with low blood glucose index (LBGI)
时间窗: 30 months
Low blood glucose index (LBGI) is a parameter that quantifies the risk of glycaemic excursions in non-negative numbers.
The glycaemic risk measured with high blood glucose index (HBGI)
时间窗: 30 months
High blood glucose index (HBGI) is a parameter that quantifies the risk of glycaemic excursions in non-negative numbers.
The glycaemic variability measured with mean amplitude of glycaemic excursions (MAGE)
时间窗: 30 months
measured in mg/dl
Minutes deep sleep
时间窗: 30 months
Mean and standard deviation of minutes deep sleep measures by activity and sleep tracker device.
Concentration of advanced glycation end products (AGE) receptor agonists.
时间窗: 30 months
Enzyme-linked immunosorbent assay (ELISA).
次要结局
- Naming(30 months)
- Depressive symptomatology(30 months)
- Impulsivity(30 months)
- Effect on gut microbiota.(30 months)
- Cognitive impairment(30 months)
- Minutes high activity(30 months)
- Visuospatial perception(30 months)
- The percentage of time in glucose range (glucose level below 100 mg/dl)(30 months)
- The percentage of time in glucose range (glucose level between 140-199 mg/dl)(30 months)
- Burned calories(30 months)
- Changes from baseline in circulating concentration of AGE receptor agonists and glycemic variability one year of follow-up after weight loss in association with changes in brain structure and gut microbiota.(30 months)
- Behavioral activation(30 months)
- Phonemic verbal fluency(30 months)
- Semantic verbal fluency(30 months)
- Markers of chronic inflammation: C-reactive protein, IL-6, adiponectin and soluble, tumor necrosis factor-α receptor fractions.(30 months)
- Distance(30 months)
- Calories(30 months)
- Minutes asleep(30 months)
- Bed time(30 months)
- Effect on brain structure.(30 months)
- Visoconstructive function(30 months)
- Glycosylated hemoglobin (HbA1c) value(30 months)
- Minutes slight activity(30 months)
- Minutes mean activity(30 months)
- Number time awake(30 months)
- Audioverbal memory(30 months)
- Visual memory(30 months)
- Selective and alternating attention(30 months)
- Diffusion Tensor Imaging brain sequences(30 months)
- Insulin resistance(30 months)
- The percentage of time in glucose range (glucose level between 126-139 mg/dl)(30 months)
- The percentage of time in glucose range (glucose level above 200 mg/dl)(30 months)
- Steps(30 months)
- Minutes awake(30 months)
- Food Addiction(30 months)
- Behavioral inhibition(30 months)
- Attention and working memory(30 months)
- Inhibition(30 months)
- Brain iron accumulation(30 months)
- Resting-state functional brain sequences(30 months)
- The percentage of time in hyperglycaemia (glucose level above 250 mg/dl)(30 months)
- The percentage of time in hypoglycaemia (glucose level below 70mg/dl)(30 months)
- Minutes null activity(30 months)
研究者
José Manuel Fernández-Real
Principal investigator, clinical professor, section chief of Endocrinology and Nutrition Department of Josep Trueta University Hospital
Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta