Cerebral blood flow and glucose metabolism in healthy volunteers measured using a high-resolution PET scanner

BACKGROUND: Positron emission tomography (PET) allows for the measurement of cerebral blood flow (CBF; based on [(15)O]H(2)O) and cerebral metabolic rate of glucose utilization (CMR(glu); based on [(18) F]-2-fluoro-2-deoxy-d-glucose ([(18) F]FDG)). By using kinetic modeling, quantitative CBF and CMR(glu) values can be obtained. However, hardware limitations led to the development of semiquantitive calculation schemes which are still widely used. In this paper, the analysis of CMR(glu) and CBF scans, acquired on a current state-of-the-art PET brain scanner, is presented. In particular, the correspondence between nonlinear as well as linearized methods for the determination of CBF and CMR(glu) is investigated. As a further step towards widespread clinical applicability, the use of an image-derived input function (IDIF) is investigated. METHODS: Thirteen healthy male volunteers were included in this study. Each subject had one scanning session in the fasting state, consisting of a dynamic [(15)O]H(2)O scan and a dynamic [(18) F]FDG PET scan, acquired at a high-resolution research tomograph. Time-activity curves (TACs) were generated for automatically delineated and for manually drawn gray matter (GM) and white matter regions. Input functions were derived using on-line arterial blood sampling (blood sampler derived input function (BSIF)). Additionally, the possibility of using carotid artery IDIFs was investigated. Data were analyzed using nonlinear regression (NLR) of regional TACs and parametric methods. RESULTS: After quality control, 9 CMR(glu) and 11 CBF scans were available for analysis. Average GM CMR(glu) values were 0.33 ± 0.04 μmol/cm(3) per minute, and average CBF values were 0.43 ± 0.09 mL/cm(3) per minute. Good correlation between NLR and parametric CMR(glu) measurements was obtained as well as between NLR and parametric CBF values. For CMR(glu) Patlak linearization, BSIF and IDIF derived results were similar. The use of an IDIF, however, did not provide reliable CBF estimates. CONCLUSION: Nonlinear regression analysis, allowing for the derivation of regional CBF and CMR(glu) values, can be applied to data acquired with high-spatial resolution current state-of-the-art PET brain scanners. Linearized models, applied to the voxel level, resulted in comparable values. CMR(glu) measurements do not require invasive arterial sampling to define the input function. TRIAL REGISTRATION: ClinicalTrials.gov NCT0062608

Cell specific microvesicles vary with season and disease predisposition in healthy and previously laminitic ponies

Microvesicles are small (up to 1 μm) vesicles found in plasma and other bodily fluids. They are recognised as part of the normal system of inter-cellular communication but altered numbers are also used as biomarkers of disease. Microvesicles have not been studied in detail in the horse but may be relevant to diseases such as laminitis. Identification of equine cell specific microvesicles was performed by developing a panel of cross reactive antibodies to use in flow cytometry to detect microvesicles of platelet, leucocyte and endothelial origin in plasma from healthy ponies and those predisposed to laminitis. The total number and proportion of microvesicles from the different cell types varied with season and there were more annexin V positive endothelial MV in non laminitic ponies compared to previously laminitic ponies. Development of this antibody panel and the technique for measuring microvesicles in the horse opens a new field for further investigation of these important structures in equine health and disease

Does interference with the renin-angiotensin system protect against diabetes? Evidence and mechanisms

Agents interfering with the renin-angiotensin system (RAS) system were consistently shown to lower the incidence of type 2 diabetes (T2DM), as compared to other antihypertensive drugs, in hypertensive high-risk populations. The mechanisms underlying this protective effect of RAS blockade using angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) on glucose metabolism are not fully understood. In this paper, we will review the evidence from randomized-controlled trials and discuss the proposed mechanisms as to how RAS interference may delay the onset of T2DM. In particular, since T2DM is characterized by beta-cell dysfunction and obesity-related insulin resistance, we address the mechanisms that underlie RAS blockade-induced improvement in beta-cell function and insulin sensitivity

Ectopic Fat Storage in the Pancreas, Liver, and Abdominal Fat Depots: Impact on {beta}-Cell Function in Individuals with Impaired Glucose Metabolism.

Context: Pancreatic fat content (PFC) may have deleterious effects on beta-cell function. Objective: We hypothesized that ectopic fat deposition, in particular pancreatic fat accumulation, is related to beta-cell dysfunction in individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Design, Setting and Participants: This was a cross-sectional study in 64 age- and body mass index-matched individuals, with normal glucose tolerance (NGT; n = 16, 60% males), IFG (n = 29, 52% males), or IFG/IGT (n = 19, 63% males) was conducted. Intervention and Main Outcome Measures: Participants underwent the following: 1) a combined hyperinsulinemic-euglycemic and hyperglycemic clamp, with subsequent arginine stimulation to quantify insulin sensitivity and beta-cell function; 2) proton-magnetic resonance spectroscopy to assess PFC and liver fat content (LFC); and 3) magnetic resonance imaging to quantify visceral (VAT) and sc (SAT) adipose tissue. The disposition index (DI; insulin sensitivity adjusted beta-cell function) was assessed. Results: IFG and IFG/IGT were more insulin resistant (P < 0.001) compared with NGT. Individuals with IFG/IGT had the lowest values of glucose- and arginine-stimulated C-peptide secretion (both P < 0.03) and DI (P < 0.001), relative to IFG and NGT. PFC and LFC gradually increased between NGT, IFG, and IFG/IGT (P = 0.02 and P = 0.01, respectively), whereas VAT and SAT were similar between groups. No direct associations were found between PFC, LFC, VAT, and SAT and C-peptide secretion. The DI was inversely correlated with PFC, LFC, and VAT (all P < 0.05). Conclusions: PFC was increased in individuals with IFG and/or IGT, without a direct relation with beta-cell function