Elevated brain glutamate levels in type 1 diabetes: correlations with glycaemic control and age of disease onset but not with hypoglycaemia awareness status

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PET imaging during hypoglycaemia to study adipose tissue metabolism

Contains fulltext : 205513.pdf (publisher's version ) (Open Access)BACKGROUND: Disturbances in adipose tissue glucose uptake may play a role in the pathogenesis of type 2 diabetes, yet its examination by 2-deoxy-2-[(18) F]fluorodeoxyglucose ([(18) F]FDG) PET/CT is challenged by relatively low uptake kinetics. We tested the hypothesis that performing [(18) F]FDG PET/CT during a hypoglycaemic clamp would improve adipose tissue tracer uptake to allow specific comparison of adipose tissue glucose handling between people with or without type 2 diabetes. DESIGN: We enrolled participants with or without diabetes who were at least overweight, to undergo a hyperinsulinaemic hypoglycaemic clamp or a hyperinsulinaemic euglycaemic clamp (n = 5 per group). Tracer uptake was quantified using [(18) F]FDG PET/CT. RESULTS: Hypoglycaemic clamping increased [(18) F]FDG uptake in visceral adipose tissue of healthy participants (P = 0.002). During hypoglycaemia, glucose uptake in visceral adipose tissue of type 2 diabetic participants was lower as compared to healthy participants (P < 0.0005). No significant differences were observed in skeletal muscle, liver or pancreas. CONCLUSIONS: The present findings indicate that [(18) F]FDG PET/CT during a hypoglycaemic clamp provides a promising new research tool to evaluate adipose tissue glucose metabolism. Using this method, we observed a specific impairment in visceral adipose tissue [(18) F]FDG uptake in type 2 diabetes, suggesting a previously underestimated role for adipose tissue glucose handling in type 2 diabetes

Functional implications of the microbial community structure of undefined mesophilic starter cultures

This review describes the recent advances made in the studies of the microbial community of complex and undefined cheese starter cultures. We report on work related to the composition of the cultures at the level of genetic lineages, on the presence and activity of bacteriophages and on the population dynamics during cheese making and during starter culture propagation. Furthermore, the link between starter composition and starter functionality will be discussed. Finally, recent advances in predictive metabolic modelling of the multi-strain cultures will be discussed in the context of microbe-microbe interactions

Development of the Gastrointestinal Dysfunction Score (GIDS) for critically ill patients – A prospective multicenter observational study (iSOFA study)

Background & aims: To develop a five grade score (0–4 points) for the assessment of gastrointestinal (GI) dysfunction in adult critically ill patients. Methods: This prospective multicenter observational study enrolled consecutive adult patients admitted to 11 intensive care units in nine countries. At all sites, daily clinical data with emphasis on GI clinical symptoms were collected and intra-abdominal pressure measured. In five out of 11 sites, the biomarkers citrulline and intestinal fatty acid-binding protein (I-FABP) were measured additionally. Cox models with time-dependent scores were used to analyze associations with 28- and 90-day mortality. The models were estimated with stratification for study center. Results: We included 540 patients (224 with biomarker measurements) with median age of 65 years (range 18–94), the Simplified Acute Physiology Score II score of 38 (interquartile range 26–53) points, and Sequential Organ Failure Assessment (SOFA) score of 6 (interquartile range 3–9) points at admission. Median ICU length of stay was 3 (interquartile range 1–6) days and 90-day mortality 18.9%. A new five grade Gastrointestinal Dysfunction Score (GIDS) was developed based on the rationale of the previously developed Acute GI Injury (AGI) grading. Citrulline and I-FABP did not prove their potential for scoring of GI dysfunction in critically ill. GIDS was independently associated with 28- and 90-day mortality when added to SOFA total score (HR 1.40; 95%CI 1.07–1.84 and HR 1.40; 95%CI 1.02–1.79, respectively) or to a model containing all SOFA subscores (HR 1.48; 95%CI 1.13–1.92 and HR 1.47; 95%CI 1.15–1.87, respectively), improving predictive power of SOFA score in all analyses. Conclusions: The newly developed GIDS is additive to SOFA score in prediction of 28- and 90-day mortality. The clinical usefulness of this score should be validated prospectively. Trial registration: NCT02613000, retrospectively registered 24 November 2015.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A Single Bout of High-Intensity Interval Training Reduces Awareness of Subsequent Hypoglycemia in Patients with Type 1 Diabetes.

High-intensity interval training (HIIT) gains increasing popularity in patients with diabetes. HIIT acutely increases plasma lactate levels. This may be important, since administration of lactate during hypoglycemia suppresses symptoms and counterregulation, whilst preserving cognitive function. We tested the hypothesis that HIIT acutely reduces awareness of hypoglycemia and attenuates hypoglycemia-induced cognitive dysfunction. In a randomized crossover trial, patients with type 1 diabetes and normal awareness of hypoglycemia (NAH), patients with impaired awareness of hypoglycemia (IAH), and healthy participants (n=10 per group) underwent a hyperinsulinemic-hypoglycemic (2.6 mmol/L) clamp, either after a HIIT session or after seated rest. Compared to rest, HIIT reduced symptoms of hypoglycemia in patients with NAH, but not in healthy participants or patients with IAH. HIIT attenuated hypoglycemia-induced cognitive dysfunction, which was mainly driven by changes in the NAH subgroup. HIIT suppressed cortisol and growth hormone responses, but not catecholamine responses to hypoglycemia. The present findings demonstrate that a single HIIT session rapidly reduces awareness of subsequent hypoglycemia in patients with type 1 diabetes and NAH, but not in patients with IAH, and attenuates hypoglycemia-induced cognitive dysfunction. The role of exercise-induced lactate in mediating these effects, potentially serving as an alternative fuel for the brain, should be further explored

Contribution of Eat1 and Other Alcohol Acyltransferases to Ester Production in Saccharomyces cerevisiae

Esters are essential for the flavor and aroma of fermented products, and are mainly produced by alcohol acyl transferases (AATs). A recently discovered AAT family named Eat (Ethanol acetyltransferase) contributes to ethyl acetate synthesis in yeast. However, its effect on the synthesis of other esters is unknown. In this study, the role of the Eat family in ester synthesis was compared to that of other Saccharomyces cerevisiae AATs (Atf1p, Atf2p, Eht1p, and Eeb1p) in silico and in vivo. A genomic study in a collection of industrial S. cerevisiae strains showed that variation of the primary sequence of the AATs did not correlate with ester production. Fifteen members of the EAT family from nine yeast species were overexpressed in S. cerevisiae CEN.PK2-1D and were able to increase the production of acetate and propanoate esters. The role of Eat1p was then studied in more detail in S. cerevisiae CEN.PK2-1D by deleting EAT1 in various combinations with other known S. cerevisiae AATs. Between 6 and 11 esters were produced under three cultivation conditions. Contrary to our expectations, a strain where all known AATs were disrupted could still produce, e.g., ethyl acetate and isoamyl acetate. This study has expanded our understanding of ester synthesis in yeast but also showed that some unknown ester-producing mechanisms still exist