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Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning.

ABSTRACT: Type 2 diabetes mellitus is associated with accelerated cognitive decline. The underlying pathophysiological mechanisms still remain to be elucidated although it is known that insulin signaling modulates neurotransmitter activity, including inhibitory ?-aminobutyric acid (GABA) and excitatory glutamate (Glu) receptors. Therefore, we examined whether levels of GABA and Glu are related to diabetes status and cognitive performance.Forty-one participants with type 2 diabetes and 39 participants without type 2 diabetes underwent detailed cognitive assessments and 3-Tesla proton MR spectroscopy. The associations of neurotransmitters with type 2 diabetes and cognitive performance were examined using multivariate regression analyses controlling for age, sex, education, BMI, and percentage gray/white matter ratio in spectroscopic voxel.Analysis revealed higher GABA+ levels in participants with type 2 diabetes, in participants with higher fasting blood glucose levels and in participants with higher HbA1c levels, and higher GABA+ levels in participants with both high HbA1c levels and less cognitive performance.To conclude, participants with type 2 diabetes have alterations in the GABAergic neurotransmitter system, which are related to lower cognitive functioning, and hint at the involvement of an underlying metabolic mechanism.

SUBMITTER: van Bussel FC

PROVIDER: S-EPMC5023915 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning.

van Bussel Frank C G FCG Backes Walter H WH Hofman Paul A M PAM Puts Nicolaas A J NAJ Edden Richard A E RAE van Boxtel Martin P J MPJ Schram Miranda T MT Stehouwer Coen D A CDA Wildberger Joachim E JE Jansen Jacobus F A JFA

Medicine 20160901 36

Type 2 diabetes mellitus is associated with accelerated cognitive decline. The underlying pathophysiological mechanisms still remain to be elucidated although it is known that insulin signaling modulates neurotransmitter activity, including inhibitory γ-aminobutyric acid (GABA) and excitatory glutamate (Glu) receptors. Therefore, we examined whether levels of GABA and Glu are related to diabetes status and cognitive performance.Forty-one participants with type 2 diabetes and 39 participants with ...[more]

PMID: 27603392

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Project description:OBJECTIVE: Integrity of resting-state functional brain networks (RSNs) is important for proper cognitive functioning. In type 1 diabetes mellitus (T1DM) cognitive decrements are commonly observed, possibly due to alterations in RSNs, which may vary according to microvascular complication status. Thus, we tested the hypothesis that functional connectivity in RSNs differs according to clinical status and correlates with cognition in T1DM patients, using an unbiased approach with high spatio-temporal resolution functional network. METHODS: Resting-state magnetoencephalographic (MEG) data for T1DM patients with (n = 42) and without (n = 41) microvascular complications and 33 healthy participants were recorded. MEG time-series at source level were reconstructed using a recently developed atlas-based beamformer. Functional connectivity within classical frequency bands, estimated by the phase lag index (PLI), was calculated within eight commonly found RSNs. Neuropsychological tests were used to assess cognitive performance, and the relation with RSNs was evaluated. RESULTS: Significant differences in terms of RSN functional connectivity between the three groups were observed in the lower alpha band, in the default-mode (DMN), executive control (ECN) and sensorimotor (SMN) RSNs. T1DM patients with microvascular complications showed the weakest functional connectivity in these networks relative to the other groups. For DMN, functional connectivity was higher in patients without microangiopathy relative to controls (all p < 0.05). General cognitive performance for both patient groups was worse compared with healthy controls. Lower DMN alpha band functional connectivity correlated with poorer general cognitive ability in patients with microvascular complications. DISCUSSION: Altered RSN functional connectivity was found in T1DM patients depending on clinical status. Lower DMN functional connectivity was related to poorer cognitive functioning. These results indicate that functional connectivity may play a key role in T1DM-related cognitive dysfunction.

Project description:COVID-19 infection in patients with type 2 diabetes mellitus (T2DM) -a chronic illness in Lebanon-is not well described. This was a single-centre retrospective observational study of 491 patients, including 152 patients with T2DM, who were hospitalised for COVID-19 between 20 August 2020 and 21 April 2021. Data on clinical characteristics, laboratory and radiological findings and outcomes were collected from the electronic medical records. Clinical characteristics and in-hospital mortality between patients with and without T2DM infected with COVID-19 using multivariate analysis were compared. Patients with T2DM were significantly older than those without T2DM (mean age, 68.7 vs. 60.3 years). Patients with T2DM were more likely to present with a body temperature of <38.3°C (83.9% vs. 69.9%) and less likely to present with chest pain (3.9% vs. 9.1%) and sore throat (2.0% vs. 6.8%). Patients with T2DM were more likely to be hypertensive (76.35% vs. 41%) and dyslipidaemic (58.6% vs. 25.7%) and had more frequent underlying coronary artery disease (33.6% vs. 12.4%). The rates of patients with creatinine levels of ≥1.17 mg/L and troponin T levels of ≥4 ng/dL were higher in the T2DM group than in the non-T2DM group (30.4% vs. 15% and 93.3% vs. 83.1%, respectively). Patients with T2DM were more likely to be admitted to the intensive care unit (ICU) (34.2% vs. 22.1%), require invasive ventilation (18.4% vs. 10.3%) and receive vasopressors (16.4% vs. 10.0%). Increasing age and the use of invasive ventilation and vasopressors were associated with higher odds of mortality (odds ratio (OR), 1.08, 9.95 and 19.83, respectively), whereas longer ICU stay was associated with lower odds of mortality (OR, 0.38). The odds of mortality were lower in the T2DM group than in the non-T2DM group (OR, 0.27). Among patients hospitalised for COVID-19, those with T2DM were older, presented with milder symptoms and had more comorbidities and higher troponin T levels compared with those without T2DM. Despite the worse clinical course, the patients with T2DM had lower odds of mortality than those without T2DM.

Dataset Information

Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning.

Publications

Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning.

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