Role of the Central Brain Clock in the Pathophysiology of Insulin Resistance
概览
- 阶段
- 不适用
- 干预措施
- functional MRI
- 疾病 / 适应症
- Insulin Resistance
- 发起方
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- SCN blood oxygen level dependent (BOLD) response to light: mean SCN activity
- 状态
- 已完成
- 最后更新
- 3个月前
概览
简要总结
In this observational cohort study the investigators will determine the activity rhythm of the suprachiasmatic nucleus in humans with progressive stages of insulin resistance, using advanced functional brain imaging (7 Tesla functional MRI).
详细描述
Type 2 diabetes mellitus (T2DM) has an increasing worldwide incidence. Insulin resistance is a key pathophysiological process in the development of hyperglycemia in patients with T2DM. Disruption of circadian synchrony leads to insulin resistance. Animal studies and post-mortem human brain studies suggest that the master brain clock in the hypothalamic suprachiasmatic nucleus (SCN) plays a role in the development of insulin resistance. Up to now, no-one has investigated whether the in vivo activity rhythm of the SCN is affected in patients with insulin resistance. The investigators hypothesize that the master brain clock has an important role in the development of human insulin resistance.
研究者
Dirk Jan Stenvers
Principal Investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
入排标准
入选标准
- •Group 1: obese people with normal insulin sensitivity
- •age 25-65 years
- •fasting plasma insulin ≤62 pmol/L
- •fasting plasma glucose \<5.6 mmol/L
- •Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≤ 4.5
- •Group 2: obese people with insulin resistance
- •age 25-65 years
- •fasting plasma insulin \>62 pmol/L
- •not fulfilling the American Diabetes Association (ADA) criteria for type 2 DM
- •Group 3: obese subjects with overt type 2 DM
排除标准
- •An extreme chronotype (midpoint of sleep on free days (MSFsc) before 2:00 or after 6:00).
- •Active psychiatric disorder (including circadian rhythm sleep disorder) as defined in Diagnostic and Statistical Manual of Mental Disorders (DSM) 5
- •Disorders of the central nervous system (Early-onset dementia, stroke, epilepsy, Parkinson's disease, brain tumor)
- •Severe visual impairment (WHO classification)
- •Shift workers
- •Crossing \> 2 time zones in the 3 months before the study
- •Patients with type 2 DM receiving insulin treatment or glucagon-like peptide (GLP) 1 agonists
- •MRI contraindications
研究组 & 干预措施
Obese individuals with normal insulin sensitivity
干预措施: functional MRI
Obese individuals with impaired insulin sensitivity
干预措施: functional MRI
Obese patients with type 2 diabetes
干预措施: functional MRI
结局指标
主要结局
SCN blood oxygen level dependent (BOLD) response to light: mean SCN activity
时间窗: mean activity over 24 hours
SCN BOLD response to light stimulus (percent BOLD signal change)
SCN BOLD response to light: time point of peak SCN activity
时间窗: 24 hours
time point (zeitgeber time in hh:mm)
SCN BOLD) response to light: time point of trough SCN activity
时间窗: 24 hours
time point (zeitgeber time in hh:mm)
Amplitude of SCN activity rhythm (peak-trough change in SCN activity)
时间窗: 24 hours
Peak-trough difference in SCN activity (percent BOLD signal change)