Diabetic brain or retina? Visual psychophysical performance in diabetic patients in relation to GABA levels in occipital cortex

Abstract

Visual impairment is one of the most feared complications of Type 2 Diabetes Mellitus. Here, we aimed to investigate the role of occipital cortex γ-aminobutyric acid (GABA) as a predictor of visual performance in type 2 diabetes. 18 type 2 diabetes patients were included in a longitudinal prospective one-year study, as well as 22 healthy age-matched controls. We collected demographic data, HbA1C and used a novel set of visual psychophysical tests addressing color, achromatic luminance and speed discrimination in both groups. Psychophysical tests underwent dimension reduction with principle component analysis into three synthetic variables: speed, achromatic luminance and color discrimination. A MEGA-PRESS magnetic resonance brain spectroscopy sequence was used to measure occipital GABA levels in the type 2 diabetes group. Retinopathy grading and retinal microaneurysms counting were performed in the type 2 diabetes group for single-armed correlations. Speed discrimination thresholds were significantly higher in the type 2 diabetes group in both visits; mean difference (95% confidence interval), [0.86 (0.32-1.40) in the first visit, 0.74 (0.04-1.44) in the second visit]. GABA from the occipital cortex predicted speed and achromatic luminance discrimination thresholds within the same visit (r = 0.54 and 0.52; p = 0.02 and 0.03, respectively) in type 2 diabetes group. GABA from the occipital cortex also predicted speed discrimination thresholds one year later (r = 0.52; p = 0.03) in the type 2 diabetes group. Our results suggest that speed discrimination is impaired in type 2 diabetes and that occipital cortical GABA is a novel predictor of visual psychophysical performance independently from retinopathy grade, metabolic control or disease duration in the early stages of the disease.

The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes

“…This is consistent with the study of Van Bussel et al . [ 47 ] showing that cognitive impairment in diabetes is related to higher GABA levels [ 47 ] and previous data showing that higher GABA/tCr levels were related to higher (worse) psychophysical thresholds [ 19 ] and lower brain activity as measured by the BOLD signal [ 48 ]. In fact, steady-state neurotransmitter levels may have distinct forms of biological impact (positive or negative), depending on the physiological system [ 49 ].…”

“…The pathophysiological effects of long-term glycemic disturbances in the central nervous system are still controversial. We had previously found that higher GABA levels were predictive of impaired psychophysical performance (speed and achromatic contrast discrimination) in T2DM, both at the time of evaluation and after one year [ 19 ]. However, the relation between changes in neurotransmission and chronic metabolic control remains elusive.…”

“…Regarding inhibitory neurotransmission, we previously found that impaired visual function in T2DM could be related to altered cortical neurochemistry within the GABAergic system (i.e. higher GABA levels have a deleterious effect on visual brain function) [ 19 ]. Also, van Bussel et al .…”

High level of pattern glare in major depressive disorder

“…Visual deficit-poor vision-was found to be rendered by loss of dendritic cell factor 1 through the GABA system in mouse primary visual cortex [56]. In the early stage of type 2 diabetes, occipital cortical GABA has been reported to be a novel predictor of visual psychophysical performance, that is, speed and achromatic discrimination thresholds [57]. The application of GABA and its agonist to senescent macaques lead to improved orientation and direction, an enhanced ability to signal visual stimuli, combined with decreased visual responsiveness and spontaneous activity [58].…”

High‐fat diet induces a neurometabolic state characterized by changes in glutamate and N‐acetylaspartate pools associated with early glucose intolerance: An in vivo multimodal MRI study

“…Additionally, it could be important to explore how distinct high‐caloric diet compositions, comprising different amounts of triglycerides and carbohydrates, may influence the rodent brain given that studies designed to investigate such impact are lacking. Also caution should be taken when attempting to generalize these findings to humans, although our previous work in humans highlights the functional relevance of measuring neurotransmitter levels in humans with metabolic disorders such as obesity and diabetes . Finally, we restricted the assessment of neurometabolic changes to the posterior hippocampus, because of the larger signal to noise ratios in this region.…”