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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Obese individuals with normal insulin sensitivity |
| ||
| Obese individuals with impaired insulin sensitivity |
| ||
| Obese patients with type 2 diabetes |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| functional MRI | Device | Subjects will undergo functional MRI at 4 time points in 24 hours. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| SCN BOLD response to light: time point of peak SCN activity | time point (zeitgeber time in hh:mm) | 24 hours |
| SCN BOLD) response to light: time point of trough SCN activity | time point (zeitgeber time in hh:mm) | 24 hours |
| Amplitude of SCN activity rhythm (peak-trough change in SCN activity) | Peak-trough difference in SCN activity (percent BOLD signal change) | 24 hours |
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Inclusion Criteria:
Group 1: obese people with normal insulin sensitivity
Group 2: obese people with insulin resistance
Group 3: obese subjects with overt type 2 DM
Exclusion Criteria:
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Primary care clinics, community sample
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| Name | Affiliation | Role |
|---|---|---|
| Dr. D.J. Stenvers | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amsterdam University Medical Centers, location AMC | Amsterdam | North Holland | 1105AZ | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | World Health Organization, Global report on diabetes., in WHO Library. 2016 | ||
| 23613085 | Background | 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. | |
| 30531917 |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D008279 | Magnetic Resonance Imaging |
| ID | Term |
|---|---|
| D014054 | Tomography |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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Whole blood samples
| Background |
| 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. |
| 31327049 | Background | 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. |
| 26155920 | Background | 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. |
| 25537714 | Background | 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. |
| 15620633 | Background | 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. |
| Background | World report on vision. Geneva: World Health Organization. 2019 |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |