Hypothalamic gliosis tied to impaired glucose homeostasis in obesity and type 2 diabetes: Study
Seattle, WA: A recent study in the journal Diabetes Care has suggested a role of hypothalamic gliosis in insulin resistance progression in obesity and hence in the pathogenesis of type 2 diabetes (T2D) in humans.
Preclinical research had indicated hypothalamic glial cell responses to be involved in the pathogenesis of obesity and type 2 diabetes. In the study, Ellen A. Schur, UW Medicine Diabetes Institute, University of Washington, Seattle, WA, and colleagues aimed to translate such findings to humans by testing of radiologic markers of gliosis in the mediobasal hypothalamus (MBH) were higher in patients with obesity and impaired glucose homeostasis or T2D in a cross-sectional and prospective cohort study.
For this purpose, the researchers applied a validated quantitative MRI approach for assessing gliosis in 67 adults with obesity and normal glucose tolerance, impaired glucose tolerance (IGT), or T2D. Glucose homeostasis assessments were conducted via oral glucose tolerance tests (OGTT) and β-cell modeling.
The study revealed the following findings:
- There was a significantly greater T2 relaxation times (a marker of gliosis by MRI), that were independent of adiposity, in the groups with IGT and T2D as compared with the group with normal glucose tolerance.
- Findings were present in the MBH, but not control regions. Moreover, positive linear associations were present in the MBH but not control regions between T2 relaxation time and glucose area under the curve during an OGTT, fasting glucose concentrations, hemoglobin A1c, and visceral adipose tissue mass, whereas negative linear relationships were present in the MBH for markers of insulin sensitivity and β-cell function.
- In a prospective cohort study, greater MBH T2 relaxation times predicted declining insulin sensitivity over 1 year.
The authors conclude, our findings support a role for hypothalamic gliosis in the progression of insulin resistance in obesity and thus T2D pathogenesis in humans.
Reference:
Jennifer L. Rosenbaum, Susan J. Melhorn, Stefan Schoen, Mary F. Webb, Mary Rosalynn B. De Leon, Madelaine Humphreys, Kristina M. Utzschneider, Ellen A. Schur; Evidence That Hypothalamic Gliosis Is Related to Impaired Glucose Homeostasis in Adults With Obesity. Diabetes Care 2021; dc211535. https://doi.org/10.2337/dc21-1535
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