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Hyperglycemia disturbs brain’s functional connectivity, may prompt depression in type 1 diabetes
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CHICAGO — High levels of the neurotransmitter glutamate observed in patients with type 1 diabetes led one researcher, Nicolas R. Bolo, PhD, director of neuroimaging in psychiatry at the Beth Israel Deaconess Medical Center, and colleagues to explore further neurological associations shared by type 1 diabetes and depression.
A disturbance in resting-state functional connectivity in the brain caused by hyperglycemia may also explain the higher prevalence of depression found in patients with type 1 diabetes.
“The findings suggest that dysregulation in the effect of hyperglycemia on glutamate levels in brain regions related to mood and emotion may predispose patients with type 1 diabetes to affective disorders such as depression,” Bolo, the lead investigator of the study, told Endocrine Today.
In a presentation by Donald C. Simonson, MD, MPH, ScD, a co-investigator on the study, at the joint meeting of the International Congress of Endocrinology and the Endocrine Society, Bolo and Simonson shared data from a study of eight non-depressed individuals with type 1 diabetes and 11 control individuals without depression and without diabetes.
Donald C. Simonson
Both study groups were observed during a 1-hour euglycemic (EU) basal period (mean glucose in patients with type 1 diabetes, 111±8 mg/dl; control patients, 93±2 mg/dl) followed by a 1-hour +90 mg/dl hyperglycemic (HY) clamp (patients with type 1 diabetes, 202±7 mg/dl; control patients, 182±3 mg/dl). The patients with type 1 diabetes received basal insulin replacement at .25 mU/kg/min during the test period.
During steady-state EU and HY, functional connectivity in the brain was measured by MRI, and glutamate was measured in the anterior cingulate cortex and in a control region (the occipital cortex), by proton magnetic resonance spectroscopy. Depression symptoms were assessed with the Symptom Checklist-90R depression subscale.
Analysis revealed that the functional connectivity of the right posterior insula and posterior cingulate cortex with the salience network was significantly lower in patients with type 1 diabetes than the control group during HY (P<.05). HbA1c was negatively associated with insula functional connectivity (r2=0.43, P=.08) in the patients with type 1 diabetes.
Glutamate levels in the anterior cingulate cortex showed a greater increase in patients with type 1 diabetes during the HY clamp (4.8±1.3 vs -0.7±2.2 mmol/l brain weight; P=.07) compared with the control group; however, glutamate levels did not change in the occipital lobe during HY in either group. Depression ratings from the assessment checklist were higher overall in the type 1 diabetes cohort (5.5±1.7 vs. 1.5±0.5, P<0.05) than in the control group, but both groups exhibited depression symptoms that were substantially below the clinical range.
“I think the interesting implication of these studies is that if there are some drugs that antagonize the effects of glutamate that are used in the treatment of depression — they’re just not used very much. This might provide a platform for potentially developing drugs that might be more specific to the etiology of depression in patients with diabetes,” Simonson said during the presentation.
In general, type 1 diabetes is associated with higher prevalence of clinical depression and depression symptoms when patients are compared with age- and sex-matched controls, Bolo’s study said. — by Reagan Copeland
For More Information: Bolo N. Abstract OR23-5. Presented at: The joint meeting of the International Congress of Endocrinology and the Endocrine Society; June 21-24, 2014; Chicago.
Disclosures: This study received grant funding from the NIH.