Brain Clock and Insulin Resistance

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)28 enrolled

Overview

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).

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Insulin Resistance Type 2 Diabetes

Interventions

functional MRIDEVICE

Subjects will undergo functional MRI at 4 time points in 24 hours.

Eligibility

Sex: ALLMin age: 25 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Amsterdam University Medical Centers, location AMC

Amsterdam, North Holland, Netherlands

Outcomes

Primary Outcomes

SCN blood oxygen level dependent (BOLD) response to light: mean SCN activity

SCN BOLD response to light stimulus (percent BOLD signal change)

Time frame: mean activity over 24 hours

SCN BOLD response to light: time point of peak SCN activity

time point (zeitgeber time in hh:mm)

Time frame: 24 hours

SCN BOLD) response to light: time point of trough SCN activity

time point (zeitgeber time in hh:mm)

Time frame: 24 hours

Amplitude of SCN activity rhythm (peak-trough change in SCN activity)

Peak-trough difference in SCN activity (percent BOLD signal change)

Time frame: 24 hours

Data from ClinicalTrials.gov

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