Brain Clock and Insulin Resistance

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05314855
• Other study ID #: NL79698.018.21
• Status: Recruiting
• Start date: January 4, 2023
• Est. completion date: July 1, 2025

Study information

• Verified date: February 2024
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: E.M. Speksnijder
• Phone: +31 20 5666071
• Email: e.m.speksnijder[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: July 1, 2025
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Insulin Resistance
• Type 2 Diabetes

Intervention

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

Locations

Country	Name	City	State
Netherlands	Amsterdam University Medical Centers, location AMC	Amsterdam	Noord-Holland

Sponsors (1)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Country where clinical trial is conducted

Netherlands, 

References & Publications (8)

American Diabetes Association. (2) Classification and diagnosis of diabetes. Diabetes Care. 2015 Jan;38 Suppl:S8-S16. doi: 10.2337/dc15-S005. No abstract available. — View Citation

Cleland SJ, Fisher BM, Colhoun HM, Sattar N, Petrie JR. Insulin resistance in type 1 diabetes: what is 'double diabetes' and what are the risks? Diabetologia. 2013 Jul;56(7):1462-70. doi: 10.1007/s00125-013-2904-2. Epub 2013 Apr 24. — View Citation

Hogenboom R, Kalsbeek MJ, Korpel NL, de Goede P, Koenen M, Buijs RM, Romijn JA, Swaab DF, Kalsbeek A, Yi CX. Loss of arginine vasopressin- and vasoactive intestinal polypeptide-containing neurons and glial cells in the suprachiasmatic nucleus of individuals with type 2 diabetes. Diabetologia. 2019 Nov;62(11):2088-2093. doi: 10.1007/s00125-019-4953-7. Epub 2019 Jul 20. — View Citation

Roenneberg T, Kuehnle T, Pramstaller PP, Ricken J, Havel M, Guth A, Merrow M. A marker for the end of adolescence. Curr Biol. 2004 Dec 29;14(24):R1038-9. doi: 10.1016/j.cub.2004.11.039. No abstract available. — View Citation

Stenvers DJ, Scheer FAJL, Schrauwen P, la Fleur SE, Kalsbeek A. Circadian clocks and insulin resistance. Nat Rev Endocrinol. 2019 Feb;15(2):75-89. doi: 10.1038/s41574-018-0122-1. — View Citation

ter Horst KW, Gilijamse PW, Koopman KE, de Weijer BA, Brands M, Kootte RS, Romijn JA, Ackermans MT, Nieuwdorp M, Soeters MR, Serlie MJ. Insulin resistance in obesity can be reliably identified from fasting plasma insulin. Int J Obes (Lond). 2015 Dec;39(12):1703-9. doi: 10.1038/ijo.2015.125. Epub 2015 Jul 9. — View Citation

World Health Organization, Global report on diabetes., in WHO Library. 2016

World report on vision. Geneva: World Health Organization. 2019

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	SCN BOLD response to light: time point of peak SCN activity	time point (zeitgeber time in hh:mm)	24 hours
Primary	SCN BOLD) response to light: time point of trough SCN activity	time point (zeitgeber time in hh:mm)	24 hours
Primary	Amplitude of SCN activity rhythm (peak-trough change in SCN activity)	Peak-trough difference in SCN activity (percent BOLD signal change)	24 hours