Insulin Resistance, Type 2 Diabetes
Conditions
Keywords
Type 2 Diabetes Mellitus, Insulin resistance, Suprachiasmatic nucleus, functional MRI
Brief summary
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
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.
Interventions
DEVICEfunctional MRI
Subjects will undergo functional MRI at 4 time points in 24 hours.
Sponsors
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SCN blood oxygen level dependent (BOLD) response to light: mean SCN activity | 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 | 24 hours | time point (zeitgeber time in hh:mm) |
| SCN BOLD) response to light: time point of trough SCN activity | 24 hours | time point (zeitgeber time in hh:mm) |
| Amplitude of SCN activity rhythm (peak-trough change in SCN activity) | 24 hours | Peak-trough difference in SCN activity (percent BOLD signal change) |
Countries
Netherlands
Outcome results
None listed