Alterations of Cerebral Metabolism in Patients with Diabetes Mellitus Studied by Proton Magnetic Resonance Spectroscopy

Abstract

To evaluate possible pathophysiologic links between cerebral changes in diabetic patients detected by proton magnetic resonance spectroscopy and clinical as well as laboratory parameters. The brains of 30 patients with diabetes mellitus and 30 healthy volunteers were examined using a STEAM sequence (TR 1500 ms, TE 20 ms). We measured in occipital gray matter and parietal white matter in a 1.5-Tesla magnet. Laboratory parameters were acquired before and after the examination. In diabetic patients a significant elevation of the myo-inositol/creatine ratio in gray and white matter was present (p = 0.006). Choline/creatine ratio in gray matter was elevated compared to normal controls (p = 0.002). No correlation with laboratory parameters was detected. Myo-inositol was even more elevated in patients with polyneuropathy (p = 0.024). No correlation with age or sex was detected. The changes found in diabetes are similar to those found in patients with Alzheimer's disease, dialysis, and after renal transplant, suggesting a similar etiology. Elevated myo-inositol may not only indicate osmolar changes in glial cells but also glial cell alteration due to amyloid or amylin deposition with formation of neurofibrillary tangles, especially as these changes are found in all of these diseases and no correlation to osmolar deterioration exists.

Measurement of Brain Metabolites in Patients with type 2 Diabetes and Major Depression Using Proton Magnetic Resonance Spectroscopy

“…Most recently, myo-inositol increases in white matter were seen in diabetic patients with retinopathy and autonomic neuropathy (Makimattila et al, 2004). It has been suggested that the increases seen in myoinositol found in diabetic patients are associated with gliosis (Geissler et al, 2003). This hypothesis is consistent with our findings showing significant myo-inositol changes only in frontal white matter.…”

“…For Brain MRS in type 2 diabetes and major depression O Ajilore et al example, increases in myo-inositol, glucose, and choline were seen in both gray and white matter in an early study of diabetic patients (Kreis and Ross, 1992). Also, myoinositol : creatine ratios have been shown to be increased in diabetic patients in both gray and white matter (Geissler et al, 2003). Myo-inositol increases have also been demonstrated in animal models of diabetes, albeit in hippocampus (van der Graaf et al, 2004).…”

“…Previous papers that have used MRS to probe the biochemical changes in the brain induced by major depression and diabetes have shown relatively consistent patterns particular to each disease. Studies that have used MRS to examine changes in brain metabolites related to diabetes have consistently shown increases in myo-inositol (Kreis and Ross, 1992;Geissler et al, 2003;van der Graaf et al, 2004;Makimattila et al, 2004). Use of MRS to study the biochemical changes associated with major depression has shown a number of findings over the past few years.…”

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

“…Therefore, under chronic hyperglycemia, the accumulation of organic osmolytes in the hippocampus is suitable to avoid ioninduced perturbation of protein function. Consistent with this, a high concentration of myo-inositol has also been reported in the hippocampus of Zucker diabetic fatty rats compared to controls (van der Graaf et al, 2004) and in the brain of diabetes patients (Geissler et al, 2003;Kreis and Ross, 1992). Thus, the study of the neurochemical profile supports the hypothesis that hyperglycemia-induced hippocampal dysfunction mainly involves deregulation of osmotic balance rather than modification of primary metabolism.…”

“…Metabolic disorders such as diabetes result in alterations of the neurochemical profile (Duarte et al, 2009a;Geissler et al, 2003;Kreis and Ross, 1992;van der Graaf et al, 2004), regarding metabolites involved in energy metabolism. Hyperglycemia increases brain levels of glucose and β-hydroxybutyrate, is an indicator of ketoacidosis, and is quantifiable at a high magnetic field (Duarte et al, 2009a;Lei et al, 2010a).…”