Inter-relationships Among Iron Stores, the Gut Metagenome, Glucose Levels, and Different Cognitive Domains: the Role of Circulating MicroRNAs (IRONmiRNA Study).
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 133
- 试验地点
- 1
- 主要终点
- Glycemic variability.
研究概览
简要总结
The brain is a recognized target of iron deposition. This process is enhanced by the presence of obesity and hyperglycemia and impacts cognitive functions. There is evidence suggesting that the gut microbiota composition modulates this process. It has been proposed that microRNAs are mediators in the dialogue between the composition and functionality of the intestinal microbiota and increased iron deposition in the brain.
The hypothesis is that circulating microRNAs are associated with parameters of cognitive dysfunction, gut microbiota, brain iron content, glucose levels, and physical activity in subjects with and without 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 patients with obesity) to evaluate the associations between circulating microRNAs, 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 glycemia sensor will be inserted for ten days, as well as an activity and sleep tracker device (Fitbit) 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 Food and Drug Administration (Dexcom G6 ®). The sensor will be inserted on day 0 and it will retire on day 10 mid-morning.
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.
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
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.
Concentration of advanced glycation end products (AGE) receptor agonists.
时间窗: 30 months
Enzyme-linked immunosorbent assay (ELISA).
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
The percentage of time in glucose target range (glucose level 100mg/dl-125mg/dl)
时间窗: 30 months
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
Minutes light sleep
时间窗: 30 months
Mean and standard deviation of minutes light sleep measures by activity and sleep tracker device.
Minutes deep sleep
时间窗: 30 months
Mean and standard deviation of minutes deep 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.
The glycaemic variability measured with mean amplitude of glycaemic excursions (MAGE)
时间窗: 30 months
measured in mg/dl
次要结局
- Effect on brain structure.(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)
- Anxiety state(30 months)
- Audioverbal memory(30 months)
- Depressive symptomatology(30 months)
- Behavioral inhibition(30 months)
- Facial recognition(30 months)
- Visual memory(30 months)
- Behavioral activation(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)
- Number time awake(30 months)
- Effect on gut microbiota.(30 months)
- Impulsivity(30 months)
- Selective and alternating attention(30 months)
- Diffusion Tensor Imaging brain sequences(30 months)
- Inhibition(30 months)
- Food Addiction(30 months)
- Visoconstructive function(30 months)
- Attention and working memory(30 months)
- Phonemic verbal fluency(30 months)
- Brain iron accumulation(30 months)
- Resting-state functional brain sequences(30 months)
- Semantic verbal fluency(30 months)
- Emotion recognition(30 months)
- Markers of chronic inflammation: C-reactive protein, IL-6, adiponectin and soluble, tumor necrosis factor-α receptor fractions.(30 months)
- Glycosylated hemoglobin (HbA1c) value(30 months)
- Distance(30 months)
- Minutes mean activity(30 months)
- Calories(30 months)
- Minutes asleep(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)
- Steps(30 months)
- Minutes slight activity(30 months)
- Insulin resistance(30 months)
- The percentage of time in glucose range (glucose level between 126-139 mg/dl)(30 months)
- Minutes null activity(30 months)
- Minutes awake(30 months)
- The percentage of time in glucose range (glucose level above 200 mg/dl)(30 months)
- Burned calories(30 months)
- Minutes high activity(30 months)
- Bed time(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