Brain Clock and Insulin Resistance

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.

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