A cross-sectional, prospective study illustrated the role hypothalamic gliosis may play in the progression of insulin resistance in obesity, progression to type 2 diabetes (T2D), and impairment of central nervous system glucose regulation. These findings were published in Diabetes Care.
Individuals (N=69) living in Seattle were recruited to enroll in the study. Participants were aged 25 to 60 years, had obesity, did not have type 1 or uncontrolled type 2 diabetes (TD1, T2D, respectively), and did not use insulin. After an overnight fast and cessation of any diabetes medication for 72 hours, study members had their weight, height, and body composition measured. Blood was drawn to measure glucose, insulin and C-peptide values, and participants with a fasting blood glucose of <200 mg/dL were given an oral glucose tolerance test. . Magnetic resonance imaging (MRI) was used to measure the mediobasal hypothalamus (MBH). Patients with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) were reassessed again for all parameters except MRI after 12 months.
Participants were aged mean 48±11 years, 72% were women, and had a body mass index (BMI) of 36±4 kg/m2. Participants either had NGT (n=29), IGT (n=21), or T2D (n=17). These 3 groups were balanced for baseline measures, but the T2D group was older, had higher triglycerides, and tended to have higher blood pressure.
The T2D group had higher mean fasting glucose, poorer glucose tolerance, reduced b-cell function, glucose sensitivity, and lower insulin sensitivity than the NGT and IGT groups. The MBH T2 relaxation times were significantly longer among the T2D cohort (c2 (6) = 65.4; P <.0001) with no evidence of lateralization (c2, (1) = 0.06; P =.81).
Among all study participants, fasting plasma glucose, glucose concentrations, glycated hemoglobin (HBA1c), and 2-hour post-glucose load (b, = 2.78 ms; P <.0001) were positively associated with longer T2 relaxation times in the MBH.
At the 12-month follow-up, changes to body composition and glucose were minimal. There was a significant relationship between MBH relaxation time and change to oral glucose insulin sensitivity (b, -0.25; P =.03). However, after accounting for the changes to total body adiposity, the relationship was attenuated (b, -0.16; P =.13).
Researchers noted the study was limited by focusing only on measuring the MBH region. Additionally, MBH T2 relaxation times at baseline were related to worsening insulin sensitivity over 1 year of follow-up among the participants with NGT or IGT.
“These translational findings support a role for the central nervous system in T2D pathogenesis,” the researchers concluded. “Specifically, MBH gliosis may represent a shared pathogenic process that contributes to both obesity and impaired glucose homeostasis through its effects on their integrated neurocircuitry.”
Rosenbaum JL, Melhorn SJ, Schoen S, et al. Evidence that hypothalamic gliosis is related to impaired glucose homeostasis in adults with obesity. Diabetes Care. Published online November 30, 2021. doi:10.2337/dc21-1535. Supplementary material at doi:10.2337/figshare.16941028.