EFFECT OF TYPE 2 DIABETES MELLITUS ON BRAIN METABOLITES BY USING PROTON MAGNETIC RESONANCE SPECTROSCOPY-A SYSTEMATIC REVIEW (original) (raw)
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Neuropsychopharmacology, 2007
Type 2 diabetes and major depression are disorders that are mutual risk factors and may share similar pathophysiological mechanisms. To further understand these shared mechanisms, the purpose of our study was to examine the biochemical basis of depression in patients with type 2 diabetes using proton MRS. Patients with type 2 diabetes and major depression (n ¼ 20) were scanned along with patients with diabetes alone (n ¼ 24) and healthy controls (n ¼ 21) on a 1.5 T MRI/MRS scanner. Voxels were placed bilaterally in dorsolateral white matter and the subcortical nuclei region, both areas important in the circuitry of late-life depression. Absolute values of myoinositol, creatine, N-acetyl aspartate, glutamate, glutamine, and choline corrected for CSF were measured using the LC-Model algorithm. Glutamine and glutamate concentrations in depressed diabetic patients were significantly lower (po0.001) in the subcortical regions as compared to healthy and diabetic control subjects. Myo-inositol concentrations were significantly increased (po0.05) in diabetic control subjects and depressed diabetic patients in frontal white matter as compared to healthy controls. These findings have broad implications and suggest that alterations in glutamate and glutamine levels in subcortical regions along with white matter changes in myo-inositol provide important neurobiological substrates of mood disorders.
Diabetes Care, 2013
OBJECTIVE Insulin may play important roles in brain metabolism. Proton magnetic resonance spectroscopy (1H-MRS) of the central nervous system gives information on neuronal viability, cellular energy, and membrane status. To elucidate the specific role of insulin action in the brain, we estimated neurometabolites with 1H-MRS and assessed their regulation by insulin infusion and their relationship with insulin sensitivity. RESEARCH DESIGN AND METHODS We studied 16 healthy young men. 1H-MRS was performed at baseline and after 240 min of euglycemic-hyperinsulinemic clamp. Voxels were positioned in the left frontal lobe, left temporal lobe, and left thalamus. The ratios of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol, and glutamate/glutamine/γ-aminobutyric acid complex (Glx) to creatine (Cr) and nonsuppressed water signal were determined. The participants were divided into subgroups of high (high IS) and low (low IS) insulin sensitivity. RESULTS Baseline neur...
PLOS ONE, 2020
Glucose metabolism is pivotal for energy and neurotransmitter synthesis and homeostasis, particularly in Glutamate and GABA systems. In turn, the stringent control of inhibitory/excitatory tonus is known to be relevant in neuropsychiatric conditions. Glutamatergic neurotransmission dominates excitatory synaptic functions and is involved in plasticity and excitotoxicity. GABAergic neurochemistry underlies inhibition and predicts impaired psychophysical function in diabetes. It has also been associated with cognitive decline in people with diabetes. Still, the relation between metabolic homeostasis and neurotransmission remains elusive. Two 3T proton MR spectroscopy studies were independently conducted in the occipital cortex to provide insight into inhibitory/excitatory homeostasis (GABA/Glutamate) and to evaluate the impact of chronic metabolic control on the levels and regulation (as assessed by regression slopes) of the two main neurotransmitters of the CNS in type 2 diabetes (T2DM) and type 1 diabetes (T1DM). Compared to controls, participants with T2DM showed significantly lower Glutamate, and also GABA. Nevertheless, higher levels of GABA/Glx (Glutamate+Glutamine), and lower levels of Glutamate were associated with poor metabolic control in participants with T2DM. Importantly, the relationship between GABA/Glx and HbA 1c found in T2DM supports a relationship between inhibitory/excitatory balance and metabolic control. Interestingly, this neurometabolic profile was undetected in T1DM. In this condition we found strong evidence for alterations in MRS surrogate measures of neuroinflammation (myo-Inositol), positively related to chronic metabolic control. Our results suggest a role for Glutamate as a global marker of T2DM and a sensitive marker of glycemic status. GABA/Glx may provide a signature of cortical metabolic state in poorly controlled patients as assessed by HbA 1c levels, which indicate long-term blood Glucose control. These findings are consistent with an interplay between abnormal
Neurochemical profile of patients with type 1 diabetes measured by ¹H-MRS at 4 T
Journal of Cerebral Blood Flow and Metabolism, 2013
The impact of type 1 diabetes mellitus (T1DM) on a comprehensive neurochemical profile of the human brain has not been reported yet. Our previous proton magnetic resonance spectroscopy (1 H-MRS) studies on T1DM were focused exclusively on the assessment of brain glucose levels. In this study, we reexamined our previously acquired data to investigate concentration differences of a broad range of neurochemicals in T1DM subjects relative to nondiabetic controls. We selected MRS data from 13 subjects (4 F/9 M, age ¼ 41 ± 11 years, body mass index ¼ 26 ± 3 kg/m 2) with well-controlled T1DM (disease duration ¼ 22 ± 12 years, A1C ¼ 7.5% ± 2.0%) and 32 nondiabetic controls (14 F/18 M, age ¼ 36 ± 10 years, body mass index ¼ 27 ± 6 kg/m 2) acquired during a hyperglycemic clamp (target [Glc] plasma ¼ 300±15 mg/dL). The 1 H-MR spectra were collected from two 15.6-mL voxels localized in gray-matter-rich occipital lobe and in white-matter-rich parieto-occipital region using ultra-short echo-time STEAM at 4 T. LCModel analysis allowed reliable quantification of 17 brain metabolites. Lower levels of N-acetylaspartate (by 6%, P ¼ 0.007) and glutamate (by 6%, P ¼ 0.045) were observed in the gray matter of T1DM patients as compared with controls, which might indicate a partial neuronal loss or dysfunction as a consequence of long-term T1DM. No other differences in metabolites were observed between subjects with T1DM and controls.
Metabolism, 2005
Hyperglycemia and diabetes alter the function and metabolism of many tissues. The effect on the brain remains poorly defined, but some animal data suggest that chronic hyperglycemia reduces rates of brain glucose transport and/or metabolism. To address this question in human beings, we measured glucose in the occipital cortex of patients with poorly controlled diabetes and healthy volunteers at the same levels of plasma glucose using proton magnetic resonance spectroscopy. Fourteen patients with poorly controlled diabetes (hemoglobin A 1c = 9.8% F 1.7%, mean F SD) and 14 healthy volunteers similar with respect to age, sex, and body mass index were studied at a plasma glucose of 300 mg/dL. Brain glucose concentrations of patients with poorly controlled diabetes were lower but not statistically different from those of control subjects (4.7 F 0.9 vs 5.3 F 1.1 lmol/g wet wt; P = .1). Our sample size gave 80% power to detect a difference as small as 1.1 lmol/g wet wt.
Magnetic Resonance Imaging, 2008
The metabolic changes in the brain of patients affected with Type 2 diabetes mellitus (DM) alone, both Type 2 DM and hypothyroidism and hypothyroidism only were investigated using proton magnetic resonance spectroscopy ( 1 H MRS). Single-voxel spectroscopy was carried out in right and left frontal lobe white matter, left parietal white matter and left occipital gray matter. Choline (Cho)/creatine (Cr) value was found to be increased in the left occipital gray matter of the subjects affected with Type 2 DM and both Type 2 DM and hypothyroidism as compared to controls. No significant change in the Cho/Cr value in the occipital gray matter was observed in hypothyroid subjects as compared to controls. However, they showed an increased level of Cho/Cr in the frontal white matter. High Cho is associated with altered membrane phospholipid metabolism. The high Cho in frontal white matter in hypothyroids and occipital gray matter in diabetic patients suggests that, though both the diseases are endocrine disorders, they differ from each other in terms of regional brain metabolite changes.
Metabolism, 2010
The aim of the present study was to use 13 C NMR to measure the cerebral oxidative metabolic rate of glucose (CMRglc(ox)) in patients with diabetes and to compare these measurements with those collected from matched controls. We elected to study a group with type 1 diabetes and hypoglycemia unawareness, since we had previously found such patients to have higher brain glucose concentrations than normal volunteers under steady state conditions. We sought to determine if this difference in steady-state brain concentrations could be explained by a difference in CMRglc(ox). Time courses of 13 C label incorporation in brain amino acids were measured in occipital cortex during infusion of [1-13 C]glucose. These time courses were fitted using a one-compartment metabolic model to determine CMRglc(ox). Our results show that the TCA cycle rate (V TCA , which is twice CMRglc (ox)) in subjects with type 1 diabetes was not significantly different from normal controls (0.84 ± 0.03 vs 0.79 ± 0.03 μmol/gm/min, n=5 in each group, mean ± SEM). We conclude that the changes in steady-state brain glucose concentrations that we observed in patients with type 1 diabetes in a previous study (1) cannot be explained by changes in oxidative glucose consumption Diabetes mellitus is a devastating disease that affects the metabolism, structure, and function of many organs. It has been long recognized that diabetes has effects on the kidneys, eyes, peripheral nerves and vasculature, and there is a growing body of evidence that diabetes affects the brain as well (2) Patients with diabetes have an increased incidence of cognitive dysfunction and dementia (3-5), and have been found to have abnormalities in white matter structure and function (6,7) as well as reductions in gray matter volumes and densities . Such functional and structural abnormalities presumably result from the extremes in glycemia experienced by patients with the disease. However, the extent to which these functional and structural abnormalities are associated with or caused by alterations in glucose metabolism is uncertain.
NMR in Biomedicine, 2004
Localized in vivo 1 H magnetic resonance spectroscopy (MRS) was used to investigate metabolite levels in the brain of adult Zucker Diabetic Fatty (ZDF) rats, an animal model for type 2 diabetes mellitus. This study focussed on the hippocampus, assumed to be one of the main brain areas affected by this disease. Together with an almost 5-fold increase in blood glucose concentration measured by glucose oxidation, significant increases were found in the hippocampal concentrations of glucose (4.93 vs 1.66 mM p < 0.001), myo-inositol (6.52 vs 4.30 mM; p < 0.05), and total creatine (12.71 vs 10.50 mM; p < 0.05) in ZDF rats (n ¼ 5) compared with littermates (n ¼ 5). Although no obvious alterations were detected in the hippocampal levels of other metabolites, including NAA þ NAAG and choline-containing compounds in the ZDF rats, the increase in Glc and Ins levels is in line with elevated brain tissue contents of these metabolites in patients with diabetes mellitus.
Metabolic Alterations Associated to Brain Dysfunction in Diabetes
Aging and Disease, 2015
From epidemiological studies it is known that diabetes patients display increased risk of developing dementia. Moreover, cognitive impairment and Alzheimer's disease (AD) are also accompanied by impaired glucose homeostasis and insulin signalling. Although there is plenty of evidence for a connection between insulin-resistant diabetes and AD, definitive linking mechanisms remain elusive. Cerebrovascular complications of diabetes, alterations in glucose homeostasis and insulin signalling, as well as recurrent hypoglycaemia are the factors that most likely affect brain function and structure. While difficult to study in patients, the mechanisms by which diabetes leads to brain dysfunction have been investigated in experimental models that display phenotypes of the disease. The present article reviews the impact of diabetes and AD on brain structure and function, and discusses recent findings from translational studies in animal models that link insulin resistance to metabolic alterations that underlie brain dysfunction. Such modifications of brain metabolism are likely to occur at early stages of neurodegeneration and impact regional neurochemical profiles and constitute non-invasive biomarkers detectable by magnetic resonance spectroscopy (MRS).