Dopamine Receptor Availability and Insulin Resistance
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Leptin
研究概览
简要总结
Obese individuals have fewer striatal dopamine type 2 receptors (DRD2) than normal weight individuals. Lower DRD2 levels are associated with addiction and a decreased sense of pleasure.Obesity is also associated with insulin resistance (poor insulin action).We propose that insulin resistance and low DRD2 are associated. Using PET imaging,we aim to determine DRD2 binding potential (BP) in the brain is associated with insulin resistance and neuroendocrine hormone levels. Obese participants will be compared to lean, gender and age similar participants. We also aim to determine the effect of caloric restriction on DRD2 BP in obese subjects
详细描述
In has been reported obese individuals have fewer striatal dopamine type 2 receptors (DRD2) compared to normal weight individuals congruent with diet induced obese rodent models and similar to models of addiction. Lower DRD2 levels are associated with addiction and a decreased sense of pleasure. Excessive weight gain also contributes to the onset of impaired insulin signaling (insulin resistance). In the brain insulin regulates monoamines and has trophic effects. We propose that the previous reports of low DRD2 in individuals with obesity will be associated with the degree of insulin resistance. Using PET imaging, we aim to determine DRD2 binding potential (BP) in the striatum and hypothesize these measurements will be associated with insulin resistance and potentially other neuroendocrine hormone levels. Obese participants will be compared to lean, sex and age similar participants. We also aim to determine the effect of caloric restriction on DRD2 BP in obese subjects. We hypothesize the caloric restriction will improve insulin resistance and that changes in DRD2 binding will be associated with changes in insulin signaling.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ages 18-60 yrs
- •obese BMI > 30kg/m2 and Weight less than 350 lbs
- •lean control BMI 18-25kg/m2
排除标准
- •Structured exercise > equivalent to 30mins 5x week of walking times a week
- •History of Substance Abuse, including but exclusive to alcohol, cocaine, marijuana, heroin, nicotine
- •Current psychiatric disorder or significant h/o disorder
- •Use or any antidepressants or antipsychotics for last 3-6months or depot antipsychotics in the last 12 months
- •Any condition felt by PI or co-investigators to interfere with ability to complete the study
- •Inability to abstain from alcohol, physical exercise or > 1 cup of coffee or equivalent daily for 3 days prior to imaging studies
- •Significant co-morbidities including atherosclerotic disease, metabolic disease, liver or renal insufficiency or abnormality found on MRI
- •Any condition which would interfere with MRI or PET studies, e.g. claustrophobia, cochlear implant, metal fragments in eyes, cardiac pacemaker, neural stimulator, tattoos with iron pigment and metallic body inclusions or other metal implanted in the body which may interfere with MRI scanning
- •Subjects on medications determined by PI, ex. sibutramine, frequent benzodiazepines or related drugs, which could affect quality of study for last 3 months.
结局指标
主要结局
Leptin
时间窗: Baseline to post 8-10days after VLCD
Striatal DRD2 Receptor Binding
时间窗: Baseline and after 8-10days VLCD
Region of interest compared to reference region to calculate binding potential
Insulin
时间窗: Baseline to post 8-10days after VLCD
microU/ml
Acyl Ghrelin
时间窗: Baseline to post 8-10days after VLCD
Glucose
时间窗: Baseline to post 8-10days after VLCD
Insulin Sensitivity From Oral Glucose Tolerance Test (OGTT_SI)
时间窗: Baseline to post 8-10days after VLCD
Insulin Sensitivity from Oral Glucose Tolerance Test was estimated using the minimal model method
次要结局
- Binge Eating Score Questionnaire(Baseline)
研究者
Julia P.Dunn,MD
Physician
Vanderbilt University