Brain Clock and Insulin Resistance

Recruiting

• Conditions: Insulin Resistance; Type 2 Diabetes
• Interventions: Device: functional MRI

• Registration Number: NCT05314855
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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.

Study Timeline

• Study First Submitted: 2022-03-07
• Study First Submitted QC: 2022-04-04
• Study First Posted: 2022-04-06
• Study Start: 2023-01-04
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-05
• Last Update Posted: 2024-02-06
• Primary Completion: 2024-07-01
• Study Completion: 2025-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Obese patients with type 2 diabetes	functional MRI	-
Obese individuals with normal insulin sensitivity	functional MRI	-
Obese individuals with impaired insulin sensitivity	functional MRI	-

Primary Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (1)

Amsterdam University Medical Centers, location AMC; 🇳🇱 Amsterdam, Noord-Holland, Netherlands