Brain Clock and Insulin Resistance

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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Role of the Central Brain Clock in the Pathophysiology of Insulin Resistance

Conditions
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Insulin Resistance, Type 2 Diabetes

Intervention / Treatment
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* Device: functional MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group 1: obese people with normal insulin sensitivity age 25-65 years BMI>30 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 BMI>30 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 age 25-65 years BMI>30 diagnosis type 2 DM according to ADA criteria Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Obese individuals with normal insulin sensitivity<br> | Device: functional MRI<br>* Subjects will undergo functional MRI at 4 time points in 24 hours.<br>|
| Obese individuals with impaired insulin sensitivity<br> | Device: functional MRI<br>* Subjects will undergo functional MRI at 4 time points in 24 hours.<br>|
| Obese patients with type 2 diabetes<br> | Device: functional MRI<br>* Subjects will undergo functional MRI at 4 time points in 24 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SCN blood oxygen level dependent (BOLD) response to light: mean SCN activity | SCN BOLD response to light stimulus (percent BOLD signal change) | mean activity over 24 hours | 
| SCN BOLD response to light: time point of peak SCN activity | time point (zeitgeber time in hh:mm) | 24 hours | 
| SCN BOLD) response to light: time point of trough SCN activity | time point (zeitgeber time in hh:mm) | 24 hours | 
| Amplitude of SCN activity rhythm (peak-trough change in SCN activity) | Peak-trough difference in SCN activity (percent BOLD signal change) | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes Mellitus, Insulin resistance, Suprachiasmatic nucleus, functional MRI