Measurement of glycated hemoglobin (HbA1c) has been the traditional method for assessing glycemic control. However, it does not reflect intra- and interday glycemic excursions that may lead to acute events (such as hypoglycemia) or postprandial hyperglycemia, which have been linked to both microvascular and macrovascular complications. Continuous glucose monitoring (CGM), either from real-time use (rtCGM) or intermittently viewed (iCGM), addresses many of the limitations inherent in HbA1c testing and self-monitoring of blood glucose. Although both provide the means to move beyond the HbA1c measurement as the sole marker of glycemic control, standardized metrics for analyzing CGM data are lacking. Moreover, clear criteria for matching people with diabetes to the most appropriate glucose monitoring methodologies, as well as standardized advice about how best to use the new information they provide, have yet to be established. In February 2017, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address these issues. This article summarizes the ATTD consensus recommendations and represents the current understanding of how CGM results can affect outcomes.

/pdf/international-consensus-on-use-of-continuous-glucose-cnnnkmnod1.pdf

International Consensus on Use of Continuous Glucose Monitoring

The brain is a heterogeneous organ with regionally varied and constantly changing energetic needs. Blood vessels in the brain are equipped with control mechanisms that match oxygen and glucose delivery through blood flow with the local metabolic demands that are imposed by neural activity. However, the cellular bases of this mechanism have remained elusive. A major advance has been the demonstration that astrocytes, cells with extensive contacts with both synapses and cerebral blood vessels, participate in the increases in flow evoked by synaptic activity. Their organization in nonoverlapping spatial domains indicates that they are uniquely positioned to shape the spatial distribution of the vascular responses that are evoked by neural activity. Astrocytic calcium is an important determinant of microvascular function and may regulate flow independently of synaptic activity. The involvement of astrocytes in neurovascular coupling has broad implications for the interpretation of functional imaging signals and for the understanding of brain diseases that are associated with neurovascular dysfunction.

Glial regulation of the cerebral microvasculature

Metabolomics is an emerging 'omics' science involving the comprehensive characterization of metabolites and metabolism in biological systems. Recent advances in metabolomics technologies are leading to a growing number of mainstream biomedical applications. In particular, metabolomics is increasingly being used to diagnose disease, understand disease mechanisms, identify novel drug targets, customize drug treatments and monitor therapeutic outcomes. This Review discusses some of the latest technological advances in metabolomics, focusing on the application of metabolomics towards uncovering the underlying causes of complex diseases (such as atherosclerosis, cancer and diabetes), the growing role of metabolomics in drug discovery and its potential effect on precision medicine.

Emerging applications of metabolomics in drug discovery and precision medicine

Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and γ-aminobutyric acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA-glutamine cycle describes the release of neurotransmitter glutamate or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA-glutamine cycle will be discussed, including aspects of transport and metabolism. Discussions of stoichiometry, the relative role of glutamate vs. GABA and pathological conditions affecting the glutamate/GABA-glutamine cycling are presented. Furthermore, a section is devoted to the accompanying ammonia homeostasis of the glutamate/GABA-glutamine cycle, examining the possible means of intercellular transfer of ammonia produced in neurons (when glutamine is deamidated to glutamate) and utilized in astrocytes (for amidation of glutamate) when the glutamate/GABA-glutamine cycle is operating. A main objective of this review is to endorse the view that the glutamate/GABA-glutamine cycle must be seen as a bi-directional transfer of not only carbon units but also nitrogen units.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1471-4159.2006.03913.x

The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer.

The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.

/pdf/biomarkers-of-nutrition-for-development-bond-iron-review-4ibc6okj7y.pdf

Biomarkers of Nutrition for Development (BOND)-Iron Review.

Introduction Hereditary spinocerebellar ataxias (SCAs) are movement disorders characterized by loss of cerebellar Purkinje cells in combination with neuronal loss in other regions, such as the pons (1). SCA type 1 (SCA1), a polyglutamine disorder, was the first SCA for which the genetic defect was uncovered (2). As potential treatments for SCA1 enter the pipeline, robust, noninvasive biomarkers of cerebral pathology are urgently needed. A prior MRS study demonstrated neurochemical alterations in SCA1 using a 4T research scanner (3). The goal of the current study was to investigate the current and future potential of this technology on clinical platforms. Therefore, we investigated 1) if similar neurochemical alterations are detectable at 3T using widely available hardware and 2) if increased sensitivity and resolution at 7T enables detection of additional neurochemical alterations.

MRS Biomarkers of Neurodegeneration in Spinocerebellar Ataxia type 1 (SCA1): Current and Future Potential

The S-Factor, a New Measure of Disease Severity in Spinocerebellar Ataxia: Findings and Implications.

Metallothioneins (MTs) are low molecular weight (2–7 kDa), cysteine-rich proteins which bind with high affinity to metal ions, such as Zn(II), Cd(II), Cu(I) and Ag(I), in unusual metal-thiolate clusters [1-3] MT biosynthesis is induced by a wide range of factors, including metal ions, oxidative stress, glucocorticoid hormones and cytokines, leading to their implication in many diverse cellular processes However, the primary function of MTs under normal physiological conditions is in the transport and storage of the essential metals: zinc and copper

Metallothionein structure update

In Table 3 of this article as originally published, a sentence within the column “Comments” in the row “SCA6” contains an error. The text incorrectly reads “Needs rigorous preclinical studies in SCA3 animal models”. This sentence has been corrected to “Needs rigorous preclinical studies in SCA6 animal models” in the PDF and HTML versions of the article.

/pdf/author-correction-spinocerebellar-ataxias-prospects-and-57c66xbixt.pdf

Author Correction: Spinocerebellar ataxias: prospects and challenges for therapy development.

Ataxia refers to deficits in coordination of movement and balance. This chapter focuses on recessively and dominantly inherited as well as sporadic degenerative ataxias. These diseases are characterized by neurodegeneration in the cerebellar system, including the cerebellum and its afferent and efferent connections, and frequently also in other brain regions such as the pontine nuclei. They display great pathological diversity, as well as phenotypic variability; thus there is a great need for imaging biomarkers that reflect the underlying pathology and that can be used for diagnostic, prognostic, and treatment monitoring purposes. Despite technical challenges of magnetic resonance spectroscopy (MRS) in the cerebellum and brainstem, MRS has been shown to be sensitive to neurochemical alterations in various degenerative ataxias. Namely, early neurochemical abnormalities have been detected by MRS in ataxias prior to the structural atrophy detectable by conventional MRI and prior to symptoms. Correlations with clinical status and pathological severity were demonstrated in clinical and animal model studies, respectively. MRS was also shown to distinguish different ataxia subtypes, with potential utility in differential diagnosis, especially valuable for sporadic ataxias in the absence of genetic testing. Finally, a few studies have utilized MRS for treatment monitoring in clinical trials of recessive ataxias, and a great need exists in this area for all degenerative ataxias. More longitudinal investigations and standardization of advanced MRS methodology for multi-site trials will be critical in this respect.

Gülin Öz

Papers

MRS Biomarkers of Neurodegeneration in Spinocerebellar Ataxia type 1 (SCA1): Current and Future Potential

The S-Factor, a New Measure of Disease Severity in Spinocerebellar Ataxia: Findings and Implications.

Metallothionein structure update

Author Correction: Spinocerebellar ataxias: prospects and challenges for therapy development.

Magnetic Resonance Spectroscopy in Ataxias