Changes In Glucose Metabolism Research Articles

Exosomes secreted by ST3GAL5high cancer cells promote peritoneal dissemination by establishing a premetastatic microenvironment.

Peritoneal dissemination of cancer affects patient survival. The behavior of peritoneal mesothelial cells (PMCs) and immune cells influences the establishment of a microenvironment that promotes cancer cell metastasis in the peritoneum. Here, we investigated the roles of lactosylceramide alpha-2,3-sialyltransferase (ST3G5; also known as ST3GAL5 and GM3 synthase) in the exosome-mediated premetastatic niche in peritoneal milky spots (MSs). Exosomes secreted from ST3G5high cancer cells (ST3G5high -cExos) were found to contain high levels of hypoxia-inducible factor 1-alpha (HIF1α) and accumulated in MSs via uptake in macrophages (MΦs) owing to increased expression of sialic acid-binding Ig-like lectin 1 (CD169; also known as SIGLEC1). ST3G5high -cExos induced pro-inflammatory cytokines and glucose metabolic changes in MΦs, and the interaction of these MΦs with PMCs promoted mesothelial-mesenchymal transition (MMT) in PMCs, thereby generating αSMA+ myofibroblasts. ST3G5high -cExos also increased the expression of immune checkpoint molecules and T-cell exhaustion in MSs, which accelerated metastasis to the omentum. These events were prevented following ST3G5 depletion in cancer cells. Mechanistically, ST3G5high -cExos upregulated chemokines, including CC-chemokine ligand 5 (CCL5), in recipient MΦs and dendritic cells (DCs), which induced MMT and immunosuppression via activation of signal transducer and activator of transcription 3 (STAT3). Maraviroc, a C-C chemokine receptor type 5 (CCR5) antagonist, prevented ST3G5high -cExo-mediated MMT, T-cell suppression, and metastasis in MSs. Our results suggest ST3G5 as a suitable therapeutic target for preventing cExo-mediated peritoneal dissemination.

GPi-DBS-induced brain metabolic activation in cervical dystonia

BackgroundDeep brain stimulation (DBS) of the globus pallidus interna (GPi) is a highly efficacious treatment for cervical dystonia, but its mechanism of action is not fully understood. Here, we investigate...

A metabolism-functional connectome sparse coupling method to reveal imaging markers for Alzheimer's disease based on simultaneous PET/MRI scans.

Abnormal glucose metabolism and hemodynamic changes in the brain are closely related to cognitive function, providing complementary information from distinct biochemical and physiological processes. However, it remains unclear how to effectively integrate these two modalities across distinct brain regions. In this study, we developed a connectome-based sparse coupling method for hybrid PET/MRI imaging, which could effectively extract imaging markers of Alzheimer's disease (AD) in the early stage. The FDG-PET and resting-state fMRI data of 56 healthy controls (HC), 54 subjective cognitive decline (SCD), and 27 cognitive impairment (CI) participants due to AD were obtained from SILCODE project (NCT03370744). For each participant, the metabolic connectome (MC) was constructed by Kullback-Leibler divergence similarity estimation, and the functional connectome (FC) was constructed by Pearson correlation. Subsequently, we measured the coupling strength between MC and FC at various sparse levels, assessed its stability, and explored the abnormal coupling strength along the AD continuum. Results showed that the sparse MC-FC coupling index was stable in each brain network and consistent across subjects. It was more normally distributed than other traditional indexes and captured more SCD-related brain areas, especially in the limbic and default mode networks. Compared to other traditional indices, this index demonstrated best classification performance. The AUC values reached 0.748 (SCD/HC) and 0.992 (CI/HC). Notably, we found a significant correlation between abnormal coupling strength and neuropsychological scales (p < .05). This study provides a clinically relevant tool for hybrid PET/MRI imaging, allowing for exploring imaging markers in early stage of AD and better understanding the pathophysiology along the AD continuum.

5-Aminovaleric acid betaine predicts impaired glucose metabolism and diabetes

Background5-Aminovaleric acid betaine (5-AVAB) has recently been identified as a diet and microbial-dependent factor inducing obesity and hepatic steatosis in mice fed a Western diet. Accumulating evidence suggests a role in metabolic dysfunction associated with obesity, diabetes, and fatty liver disease. However, whether 5-AVAB plays a role in human disease is unclear, and human data are sparse.MethodsWe measured circulating 5-AVAB serum levels in 143 individuals with overweight or obesity participating in a randomized intervention study (NCT00850629) investigating the long-term effect of a weight maintenance strategy after diet-induced weight reduction.ResultsHigher 5-AVAB serum levels correlate with worse estimates of obesity, glucose metabolism, and hepatic steatosis after weight loss. Furthermore, higher 5-AVAB levels after weight loss independently predict detrimental changes in glucose metabolism 18 months after the successful weight reduction.ConclusionOur human data supports previous findings in rodents indicating a relevant, potentially disadvantageous function of 5-AVAB in the context of metabolic dysbalance.

Unmasking the Warburg Effect: Unleashing the Power of Enzyme Inhibitors for Cancer Therapy

The Warburg effect (or aerobic glycolysis), which was first described in 1926 by Otto Heinrich Warburg, consists of the change in glucose metabolism in cancer cells. In normal cells, glucose metabolism finalizes in the mitochondria through oxidative phosphorylation (OXPHOS) in the presence of oxygen. However, the Warburg effect describes a change in the glucose metabolism in cancer cells, consuming excess glucose and converting it into lactate independently of the presence of oxygen. During this process, a wide variety of enzymes can modify their expression and activity to contribute to the mechanism of deregulated cancer metabolism. Therefore, the modulation of enzymes regulating aerobic glycolysis is a strategy for cancer treatment. Although numerous enzymes play a role in regulating aerobic glycolysis, hexokinase 2 (HK2), pyruvate dehydrogenase kinase (PDK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) are worth mentioning. Numerous modulators of these enzymes have been described in recent years. This review aims to present and group, according to their chemical structure, the most recent emerging molecules targeting the above-mentioned enzymes involved in the Warburg effect in view of the future development of cancer treatments.

Phage-microbe dynamics after sterile faecal filtrate transplantation in individuals with metabolic syndrome: a double-blind, randomised, placebo-controlled clinical trial assessing efficacy and safety

Bacteriophages (phages) are bacterial viruses that have been shown to shape microbial communities. Previous studies have shown that faecal virome transplantation can decrease weight gain and normalize blood glucose tolerance in diet-induced obese mice. Therefore, we performed a double-blind, randomised, placebo-controlled pilot study in which 24 individuals with metabolic syndrome were randomised to a faecal filtrate transplantation (FFT) from a lean healthy donor (n = 12) or placebo (n = 12). The primary outcome, change in glucose metabolism, and secondary outcomes, safety and longitudinal changes within the intestinal bacteriome and phageome, were assessed from baseline up to 28 days. All 24 included subjects completed the study and are included in the analyses. While the overall changes in glucose metabolism are not significantly different between both groups, the FFT is well-tolerated and without any serious adverse events. The phage virion composition is significantly altered two days after FFT as compared to placebo, which coincides with more virulent phage-microbe interactions. In conclusion, we provide evidence that gut phages can be safely administered to transiently alter the gut microbiota of recipients.

Raman microscopy reveals how cell inflammation activates glucose and lipid metabolism

Metabolism of endothelial cells (ECs) depends on the availability of the energy substrates. Since the endothelium is the first line of defence against inflammation in the cardiovascular system and its dysfunction can lead to the development of cardiovascular diseases, it is important to understand how glucose metabolism changes during inflammation. In this work, glucose uptake was studied in human microvascular endothelial cells (HMEC-1) in high glucose (HG), and additionally in an inflammatory state, using Raman imaging. HG state was induced by incubation of ECs with a deuterated glucose analogue, while the EC inflammation was caused by TNF-α pre-treatment. Spontaneous and stimulated Raman scattering spectroscopy provided comprehensive information on biochemical changes, including lipids and the extent of unsaturation induced by excess glucose in ECs., induced by excess glucose in ECs. In this work, we indicated spectroscopic markers of metabolic changes in ECs as a strong increase in the ratio of the intensity of lipids / (proteins + lipids) bands and an increase in the level of lipid unsaturation and mitochondrial changes. Inflamed ECs treated with HG, revealed enhanced glucose uptake, and intensified lipid production i.a. of unsaturated lipids. Additionally, increased cytochrome c signal in the mitochondrial region indicated higher mitochondrial activity and biogenesis. Raman spectroscopy is a powerful method for determining the metabolic markers of ED which will better inform understanding of disease onset, development, and treatment.

Alcohol blunts pregnancy-mediated insulin resistance and reduces fetal brain glucose despite elevated fetal gluconeogenesis, and these changes associate with fetal weight outcomes.

Prenatal alcohol exposure (PAE) impairs fetal growth and neurodevelopment. Although alcohol is well known to alter metabolism, its impact on these processes during pregnancy is largely unexplored. Here, we investigate how alcohol affects maternal-fetal glucose metabolism using our established mouse binge model of PAE. In the dam, alcohol reduces the hepatic abundance of glucose and glycolytic intermediates, and the gluconeogenic enzymes glucose-6-phosphtase and phosphoenolpyruvate carboxykinase. Fasting blood glucose is also reduced. In a healthy pregnancy, elevated maternal gluconeogenesis and insulin resistance ensures glucose availability for the fetus. Glucose and insulin tolerance tests reveal that alcohol impairs the dam's ability to acquire insulin resistance. Alcohol-exposed dams have enhanced glucose clearance (p < .05) in early gestation, after just two days of alcohol, and this persists through late term when fetal glucose needs are maximal. However, maternal plasma insulin levels, hepatic insulin signaling, and the abundance of glucose transporter proteins remain unchanged. In the PAE fetus, the expression of hepatic gluconeogenic genes is elevated, and there is a trend for elevated blood and liver glucose levels. In contrast, fetal brain and placental glucose levels remain low. This reduced maternal fasting glucose, reduced hepatic glucose, and elevated glucose clearance inversely correlated with fetal body and brain weight. Taken together, these data suggest that alcohol blunts the adaptive changes in maternal glucose metabolism that otherwise enhance fetal glucose availability. Compensatory attempts by the fetus to increase glucose pools via gluconeogenesis do not normalize brain glucose. These metabolic changes may contribute to the impaired fetal growth and brain development that typifies PAE.

Coordinated Metabolic Responses Facilitate Cardiac Growth in Pregnancy and Exercise.

Pregnancy and exercise are systemic stressors that promote physiological growth of the heart in response to repetitive volume overload and maintenance of cardiac output. This type of remodeling is distinct from pathological hypertrophy and involves different metabolic mechanisms that facilitate growth; however, it remains unclear how metabolic changes in the heart facilitate growth and if these processes are similar in both pregnancy- and exercise-induced cardiac growth. The ability of the heart to metabolize a myriad of substrates balances cardiac demands for energy provision and anabolism. During pregnancy, coordination of hormonal status with cardiac reductions in glucose oxidation appears important for physiological growth. During exercise, a reduction in cardiac glucose oxidation also appears important for physiological growth, which could facilitate shuttling of glucose-derived carbons into biosynthetic pathways for growth. Understanding the metabolic underpinnings of physiological cardiac growth could provide insight to optimize cardiovascular health and prevent deleterious remodeling, such as that which occurs from postpartum cardiomyopathy and heart failure. This short review highlights the metabolic mechanisms known to facilitate pregnancy-induced and exercise-induced cardiac growth, both of which require changes in cardiac glucose metabolism for the promotion of growth. In addition, we mention important similarities and differences of physiological cardiac growth in these models as well as discuss current limitations in our understanding of metabolic changes that facilitate growth.

Fibrosis Development Linked to Alterations in Glucose and Energy Metabolism and Prooxidant-Antioxidant Balance in Experimental Models of Liver Injury.

The development of liver fibrosis is one of the most severe and life-threatening outcomes of chronic liver disease (CLD). For targeted therapy of CLD, it is highly needed to reveal molecular targets for normalizing metabolic processes impaired in damaged liver and associated with fibrosis. In this study, we investigated the morphological and biochemical changes in rat liver models of fibrosis induced by chronic administration of thioacetamide, carbon tetrachloride, bile duct ligation (BDL), and ischemia/reperfusion (I/R), with a specific focus on carbohydrate and energy metabolism. Changes in the levels of substrates and products, as well as enzyme activities of the major glucose metabolic pathways (glycolysis, glucuronidation, and pentose phosphate pathway) were examined in rat liver tissue after injury. We examined key markers of oxidative energy metabolism, such as the activity of the Krebs cycle enzymes, and assessed mitochondrial respiratory activity. In addition, pro- and anti-oxidative status was assessed in fibrotic liver tissue. We found that 6 weeks of exposure to thioacetamide, carbon tetrachloride, BDL or I/R resulted in a decrease in the activity of glycolytic enzymes, retardation of mitochondrial respiration, elevation of glucuronidation, and activation of pentose phosphate pathways, accompanied by a decrease in antioxidant activity and the onset of oxidative stress in rat liver. Resemblance and differences in the changes in the fibrosis models used are described, including energy metabolism alterations and antioxidant status in the used fibrosis models. The least pronounced changes in glucose metabolism and mitochondrial functions in the I/R and thioacetamide models were associated with the least advanced fibrosis. Ultimately, liver fibrosis significantly altered the metabolic profile in liver tissue and the flux of glucose metabolic pathways, which could be the basis for targeted therapy of liver fibrosis in CLD caused by toxic, cholestatic, or I/R liver injury.

Whole Blood-based Transcriptional Risk Score for Nonobese Type 2 Diabetes Predicts Dynamic Changes in Glucose Metabolism.

The performance of peripheral blood transcriptional markers in evaluating risk of type 2 diabetes (T2D) with normal body mass index (BMI) is unknown. We developed a whole blood-based transcriptional risk score (wb-TRS) for nonobese T2D and assessed its contributions on disease risk and dynamic changes in glucose metabolism. Using a community-based cohort with blood transcriptome data, we developed the wb-TRS in 1105 participants aged ≥40 years who maintained a normal BMI for up to 10 years, and we validated the wb-TRS in an external dataset. Potential biological significance was explored. The wb-TRS included 144 gene transcripts. Compared to the lowest tertile, wb-TRS in tertile 3 was associated with 8.91-fold (95% CI, 3.53-22.5) higher risk and each 1-unit increment was associated with 2.63-fold (95% CI, 1.87-3.68) higher risk of nonobese T2D. Furthermore, baseline wb-TRS significantly associated with dynamic changes in average, daytime, nighttime, and 24-hour glucose, HbA1c values, and area under the curve of glucose measured by continuous glucose monitoring over 6 months of intervention. The wb-TRS improved the prediction performance for nonobese T2D, combined with fasting glucose, triglycerides, and demographic and anthropometric parameters. Multi-contrast gene set enrichment (Mitch) analysis implicated oxidative phosphorylation, mTORC1 signaling, and cholesterol metabolism involved in nonobese T2D pathogenesis. A whole blood-based nonobese T2D-associated transcriptional risk score was validated to predict dynamic changes in glucose metabolism. These findings suggested several biological pathways involved in the pathogenesis of nonobese T2D.

Plant-based medicines in the treatment of cardiometabolic disorders: A special view on sarcopenic obesity

The incidence and prevalence of obesity-mediated cardiometabolic complications are increasing gradually worldwide. In the elderly population, sarcopenic obesity causes significant changes in glucose and lipid metabolism, increasing morbidity and mortality rates. Early assessment and strategic treatment patterns for sarcopenic obesity is crucial in preventing the development and worsening of metabolic conditions like diabetes, renal, hepatic complications, cardiovascular dysfunction, etc. Plant-derived medicines have a long history of use in various chronic complications. Since the majority of the patient believe alternative therapies are inherently safe. Existing preclinical and clinical studies ensure that most bioactive compounds play a significant role in glucose and lipid homeostasis.

Attention-based 3D CNN with Multi-layer Features for Alzheimer's Disease Diagnosis using Brain Images.

Structural MRI and PET imaging play an important role in the diagnosis of Alzheimer's disease (AD), showing the morphological changes and glucose metabolism changes in the brain respectively. The manifestations in the brain image of some cognitive impairment patients are relatively inconspicuous, for example, it still has difficulties in achieving accurate diagnosis through sMRI in clinical practice. With the emergence of deep learning, convolutional neural network (CNN) has become a valuable method in AD-aided diagnosis, but some CNN methods cannot effectively learn the features of brain image, making the diagnosis of AD still presents some challenges. In this work, we propose an end-to-end 3D CNN framework for AD diagnosis based on ResNet, which integrates multi-layer features obtained under the effect of the attention mechanism to better capture subtle differences in brain images. The attention maps showed our model can focus on key brain regions related to the disease diagnosis. Our method was verified in ablation experiments with two modality images on 792 subjects from the ADNI database, where AD diagnostic accuracies of 89.71% and 91.18% were achieved based on sMRI and PET respectively, and also outperformed some state-of-the-art methods.

Changes in glucose metabolism during detachment of metastatic cells

The purpose of the work is to investigate changes in survival rates, proliferative potential, glucose metabolism and redox metabolism in metastatically active cells of Lewis lung carcinoma during the transition from anchorage-dependent to anchorage-independent growth. It was shown that the transition from anchorage-dependent growth to anchorage-independent growth is accompanied by a considerable intensification of glucose consumption rate. An increase in glucose consumption during anchorage-independent growth does not cause stimulation of proliferative activity. An increase in glucose consumption and a decrease in proliferative activity indicates a redirection of glucose to the synthesis of enzymes of the antioxidant system in order to prevent apoptotic death during anchorage-independent growth.

Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential.

Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cancer cells, metabolic pathway activity varies during tumorigenesis and cancer progression, indicating regulated metabolic plasticity. Metabolic changes are often closely related to epigenetic changes, such as alterations in the expression or activity of epigenetically modified enzymes, which may exert a direct or an indirect influence on cellular metabolism. Therefore, exploring the mechanisms underlying epigenetic modifications regulating the reprogramming of tumor cell metabolism is important for further understanding tumor pathogenesis. Here, we mainly focus on the latest studies on epigenetic modifications related to cancer cell metabolism regulations, including changes in glucose, lipid and amino acid metabolism in the cancer context, and then emphasize the mechanisms related to tumor cell epigenetic modifications. Specifically, we discuss the role played by DNA methylation, chromatin remodeling, noncoding RNAs and histone lactylation in tumor growth and progression. Finally, we summarize the prospects of potential cancer therapeutic strategies based on metabolic reprogramming and epigenetic changes in tumor cells.

Hybrid PET/MRI with Flutemetamol and FDG in Alzheimer's Disease Clinical Continuum.

We aimed to investigate the interaction between β -amyloid (Aβ) accumulation and cerebral glucose metabolism, cerebral perfusion, and cerebral structural changes in the Alzheimer's disease (AD) clinical continuum. Utility of positron emission tomography (PET) / magnetic resonance imaging (MRI) hybrid imaging for diagnostic categorization of the AD clinical continuum including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD) has not been fully crystallized. To evaluate the interaction between Aβ accumulation and cerebral glucose metabolism, cerebral perfusion, and cerebral structural changes such as cortex thickness or cerebral white matter disease burden and to detect the discriminative yields of these imaging modalities in the AD clinical continuum. Fifty patients (20 women and 30 men; median age: 64 years) with clinical SCD (n=11), aMCI (n=17) and ADD (n=22) underwent PET/MRI with [18F]-fluoro-D-glucose (FDG) and [18F]- Flutemetamol in addition to cerebral blood flow (CBF) and quantitative structural imaging along with detailed cognitive assessment. High Aβ deposition (increased temporal [18F]-Flutemetamol standardized uptake value ratio (SUVr) and centiloid score), low glucose metabolism (decreased temporal lobe and posterior cingulate [18F]-FDG SUVr), low parietal CBF and right hemispheric cortical thickness were independent predictors of low cognitive test performance. Integrated use of structural, metabolic, molecular (Aβ) and perfusion (CBF) parameters contribute to the discrimination of SCD, aMCI, and ADD.

Ultra-high performance liquid chromatography coupled to tandem mass spectrometry-based metabolomics study of diabetic distal symmetric polyneuropathy.

Distal symmetric polyneuropathy (DSPN) is a common complication of type 2 diabetes mellitus, but the underlining mechanisms have not yet been elucidated. The current study was designed to screen the feature metabolites classified as potential biomarkers, and to provide deeper insights into the underlying distinctive metabolic changes during disease progression. Plasma metabolite profiles were obtained by the ultra-high liquid chromatography coupled to tandem mass spectrometry method from healthy control participants, patients with type 2 diabetes mellitus and patients with DSPN. Potential biomarkers were selected through comprehensive analysis of statistically significant differences between groups. Overall, 938 metabolites were identified. Among them, 12 metabolites (dimethylarginine, N6-acetyllysine, N-acetylhistidine, N,N,N-trimethyl-alanylproline betaine, cysteine, 7-methylguanine, N6-carbamoylthreonyladenosine, pseudouridine, 5-methylthioadenosine, N2,N2-dimethylguanosine, aconitate and C-glycosyl tryptophan) were identified as the specific biomarkers. The content of 12 metabolites were significantly higher in the DSPN group compared with the other two groups. Additionally, they showed good performance to discriminate the DSPN state. Correlation analyses showed that the levels of 12 metabolites might be more closely related to the glucose metabolic changes, followed by the levels of lipid metabolism. The finding of the 12 signature metabolites might provide a novel perspective for the pathogenesis of DSPN. Future studies are required to test this observation further.

134-OR: Associations of Growth Hormone (GH) Mediators with Loss of Glycemic Control in Youth with Type 2 Diabetes (T2D)

T2D in youth has a more severe phenotype than in adults, with puberty as a potential contributor to this difference. Pubertal changes in GH mediators (e.g., insulin-like growth factor 1 (IGF-1), growth hormone receptor (GHR), insulin-like growth factor binding protein 1 (IGFBP-1)) may impact insulin sensitivity and beta cell function. We examined associations of GH mediators with loss of glycemic control in youth with T2D using the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort (N= 310). We performed paired comparison of plasma concentrations of IGF-1, GHR, and IGFBP-1 (ELISA), between 0mo and 36mo based on TODAY primary outcome of loss of glycemic control vs. maintained glycemic control (LGC vs MGC), with LGC defined as HbA1c ≥ 8% for 6 months and/or insulin dependence. We studied associations of GH mediators with HbA1c, insulinogenic index, oral disposition index, and 1/fasting insulin. Models were adjusted for age, sex, race, treatment arm, and baseline HbA1c (linear regression). Mean plasma IGF-1 (ng/mL) was lower in LGC group at 0mo (LGC: 451 ± 141, MGC: 485 ± 155, p = 0.04), and at 36mo (LGC: 340 ± 117, MGC: 400 ± 136, p&amp;lt; 0.0001). Increase in IGF-1 between 0-36mo predicted lower HbA1c at 36mo (B = -3.2E-3, SE = 9.0E-4, p &amp;lt; 0.001). Higher GHR was associated with higher HbA1c (B = 1.2E-2, SE = 3.0E-3, p &amp;lt; 0.001) and lower 1/fasting insulin (B = -6.6E-4, SE = 2.1E-4, P &amp;lt; 0.01) at 0mo. Increase in GHR between 0-36mo predicted higher 36mo HbA1c (B = 3.0E-2, SE = 9.4E-3, p &amp;lt; 0.01). IGFBP-1 was positively associated with 1/fasting insulin at 0m (B = 1.1E-3, SE = 4.9E-4, p = 0.03). In exploratory analyses stratified by Tanner stage (TS) at study entry, GH mediators changed differentially between TS 1-3 (n = 31) vs TS 4-5 (n = 274). In conclusion, GH mediators differed based on primary outcome in TODAY, and were associated with HbA1c and insulin sensitivity. Whether changes in GH mediators contribute to, or are the result of, changes in glucose metabolism is a key area for future studies. Disclosure C.Lu: None. D.Wolfs: None. L.El ghormli: None. L.M.Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. M.Patti: Consultant; MBX Biosciences, AstraZeneca, Hanmi Pharm. Co., Ltd., Other Relationship; Fractyl Health, Inc. E.M.Isganaitis: None. Funding National Institutes of Health (2T32DK007260-46); National Institute of Diabetes and Digestive and Kidney Diseases (5U01DK061230-16)

Correlation analysis between 18F-fluorodeoxyglucose positron emission tomography and cognitive function in first diagnosed Parkinson's disease patients.

Evaluation of the correlation between 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET) and cognitive function in first-diagnosed and untreated Parkinson's disease (PD) patients. This cross-sectional study included 84 first diagnosed and untreated PD patients. The individuals were diagnosed by movement disorder experts based on the 2015 MDS Parkinson's disease diagnostic criteria. The patients also underwent 18F-FDG PET scans and clinical feature assessments including the Montreal Cognitive Assessment (MoCA) scale. Glucose metabolism rates were measured in 26 brain regions using region of interest (ROI) and pixel-wise analyses with displayed Z scores. The cognitive function was assessed by professionals using the MoCA scale, which covers five cognitive domains. Spearman's linear correlation and linear regression models were used to compare the correlations between 18F-FDG metabolism in each brain region and cognitive domain, using SPSS 25.0 software. The results indicated a positive correlation between executive function and glucose metabolism in the lateral prefrontal cortex of the left hemisphere (p = 0.041). Additionally, a positive correlation between memory function and glucose metabolism in the right precuneus (p = 0.014), right lateral occipital cortex (p = 0.017), left lateral occipital cortex (p = 0.031), left primary visual cortex (p = 0.008), and right medial temporal cortex (p = 0.046). Further regression analysis showed that for every one-point decrease in the memory score, the glucose metabolism in the right precuneus would decrease by 0.3 (B = 0.30, p = 0.005), the glucose metabolism in the left primary visual cortex would decrease by 0.25 (B = 0.25, p = 0.040), the glucose metabolism in the right lateral occipital cortex would decrease by 0.38 (B = 0.38, p = 0.012), and the glucose metabolism in the left lateral occipital cortex would decrease by 0.32 (B = 0.32, p = 0.045). This study indicated that cognitive impairment in PD patients mainly manifests as changes in executive function, visual-spatial function and memory functions, while glucose metabolism mainly decreases in the frontal and posterior cortex. Further analysis shows that executive function is related to glucose metabolism in the left lateral prefrontal cortex. On the other hand, memory ability involves changes in glucose metabolism in a more extensive brain region. This suggests that cognitive function assessment can indirectly reflect the level of glucose metabolism in the relevant brain regions.

Functional PET Neuroimaging in Consciousness Evaluation: Study Protocol.

Ensuring a robust and reliable evaluation of coma deepness and prognostication of neurological outcome is challenging. We propose to develop PET neuroimaging as a new diagnostic and prognosis tool for comatose patients using a recently published methodology to perform functional PET (fPET). This exam permits the quantification of task-specific changes in neuronal metabolism in a single session. The aim of this protocol is to determine whether task-specific changes in glucose metabolism during the acute phase of coma are able to predict recovery at 18 months. Participation will be proposed for all patients coming for a standard PET-CT in our center in order to evaluate global cerebral metabolism during the comatose state. Legally appointed representative consent will be obtained to slightly modify the exam protocol: (1) 18F-fluorodeoxyglucose (18F-FDG) bolus plus continuous infusion instead of a simple bolus and (2) more time under camera to perform dynamic acquisition. Participants will undergo a 55-min fPET session with a 20% bolus + 80% infusion protocol. Two occurrences of three block (5-min rest, 10-min auditory stimulation and 10-min emotional auditory stimulation) will be performed after reaching equilibrium of FDG arterial concentration. We will compare the regional brain metabolism at rest and during the sessions of auditory and emotional auditory stimulation to search for a determinant of coma recovery (18 months of follow-up after the exam). Emotional auditory stimulation should induce an activation of: the auditory cortex, the consciousness areas and the neural circuitry for emotion (function to coma deepness). An activation analysis will be carried out to highlight regional brain activation using dedicated custom-made software based on Python statistical and image processing toolboxes. The association between activation levels and the Coma Recovery Scale-Revisited (CRS-R) will be assessed using multivariate analysis. If successful, the results from this study will help improve coma prognosis evaluation based on the pattern of neuronal metabolism at the onset of the pathology. The study protocol, rationale and methods are described in this paper.