Regional cerebral effects of ketone body infusion with 3-hydroxybutyrate in humans: Reduced glucose uptake, unchanged oxygen consumption and increased blood flow by positron emission tomography. A randomized, controlled trial.

Ketone bodies are neuroprotective in neurological disorders such as epilepsy. We randomly studied nine healthy human subjects twice-with and without continuous infusion of 3-hydroxybutyrate-to define potential underlying mechanisms, assessed regionally (parietal, occipital, temporal, cortical grey, and frontal) by PET scan. During 3-hydroxybutyrate infusions concentrations increased to 5.5±0.4 mmol/l and cerebral glucose utilisation decreased 14%, oxygen consumption remained unchanged, and cerebral blood flow increased 30%. We conclude that acute 3-hydroxybutyrate infusion reduces cerebral glucose uptake and increases cerebral blood flow in all measured brain regions, without detectable effects on cerebral oxygen uptake though oxygen extraction decreased. Increased oxygen supply concomitant with unchanged oxygen utilisation may contribute to the neuroprotective effects of ketone bodies.

Gestational diabetes: A clinical update.

Gestational diabetes mellitus (GDM) is increasing in prevalence in tandem with the dramatic increase in the prevalence of overweight and obesity in women of childbearing age. Much controversy surrounds the diagnosis and management of gestational diabetes, emphasizing the importance and relevance of clarity and consensus. If newly proposed criteria are adopted universally a significantly growing number of women will be diagnosed as having GDM, implying new therapeutic challenges to avoid foetal and maternal complications related to the hyperglycemia of gestational diabetes. This review provides an overview of clinical issues related to GDM, including the challenges of screening and diagnosis, the pathophysiology behind GDM, the treatment and prevention of GDM and the long and short term consequences of gestational diabetes for both mother and offspring.

The association between aerobic fitness and physical activity in children and adolescents: the European youth heart study.

The link between aerobic fitness and physical activity in children has been studied in a number of earlier studies and the results have generally shown weak to moderate correlations. This overall finding has been widely questioned partly because of the difficulty in obtaining valid estimates of physical activity. This study investigated the cross-sectional and longitudinal relationship between aerobic fitness and physical activity in a representative sample of 9 and 15-year-old children (n = 1260 cross-sectional, n = 153 longitudinal). The specific goal was to improve past studies using an objective method of activity assessment and taking into account a number of major sources of error. Data came from the Danish part of the European youth heart study, 1997-2003. The cross-sectional results generally showed a weak to moderate association between aerobic fitness and physical activity with standardized regression coefficients ranging from 0.14 to 0.33. The longitudinal results revealed a tendency towards an interaction effect of baseline physical activity on the relationship between changes in physical activity and aerobic fitness. Moderate to moderately strong regression effect sizes were observed in the lower quadrant of baseline physical activity compared to weak effect sizes in the remaining quadrants. In conclusion, the present study confirms earlier findings of a weak to moderate association between aerobic fitness and physical activity in total population of children. However, the study also indicates that inactive children can achieve notable increase in aerobic fitness by increasing their habitual physical activity level. A potential physiological explanation for these results is highlighted.

No increased risk of hypoglycaemic episodes during 48 h of subcutaneous glucagon-like-peptide-1 administration in fasting healthy subjects.

OBJECTIVE: It is uncertain whether the ability to avoid hypoglycaemia during fasting is preserved, and the risk of reactive hypoglycaemia after an oral glucose stimulus following a prolonged fasting period is increased at augmented glucagon-like peptide-1 (GLP-1) levels. DESIGN: A randomized, double-blind placebo-controlled cross-over study in eight healthy men to assess the safety, in terms of hypoglycaemia, of a continuously infused pharmacological dose of native GLP-1 during long-term fasting. After an overnight fast the fasting period continued for 48 h and was followed by a 3-h oral glucose tolerance test (OGTT). GLP-1(7-36 amide) or placebo was continuously infused subcutaneously and titrated to a dose of 4.8 pmol/kg per min. RESULTS: Two subjects in the GLP-1 group and one subject in the placebo group were withdrawn due to protocol specified plasma glucose (PG) < or = 2.8 mm and neuroglycopaenic symptoms. The infusion of GLP-1 resulted in pharmacological levels of intact GLP-1. During the fasting period PG, insulin and C-peptide levels declined and glucagon, GH and free fatty acid (FFA) levels increased with no differences between GLP-1 and placebo. During OGTT circulating levels of insulin and C-peptide were higher with GLP-1 infusion. However, PG was similar during GLP-1 vs. placebo infusions. GLP-1 infusion increased norepinephrine and cortisol levels during OGTT. CONCLUSION: The counter-regulatory response during 48 h of subcutaneous GLP-1 infusion was preserved despite long-term fasting with no apparent increased risk of hypoglycaemic episodes. No reactive hypoglycaemia was observed when the fast was followed by an OGTT. Thus use of long-acting GLP-1 analogues may not increase the risk of hypoglycaemia.

Unit-specific calibration of Actigraph accelerometers in a mechanical setup - is it worth the effort? The effect on random output variation caused by technical inter-instrument variability in the laboratory and in the field.

BACKGROUND: Potentially, unit-specific in-vitro calibration of accelerometers could increase field data quality and study power. However, reduced inter-unit variability would only be important if random instrument variability contributes considerably to the total variation in field data. Therefore, the primary aim of this study was to calculate and apply unit-specific calibration factors in multiple accelerometers in order to examine the impact on random output variation caused by inter-instrument variability. METHODS: Instrument-specific calibration factors were estimated in 25 MTI- and 53 CSA accelerometers in a mechanical setup using four different settings varying in frequencies and/or amplitudes. Calibration effect was analysed by comparing raw and calibrated data after applying unit-specific calibration factors to data obtained during quality checks in a mechanical setup and to data collected during free living conditions. RESULTS: Calibration reduced inter-instrument variability considerably in the mechanical setup, both in the MTI instruments (raw SDbetween units = 195 counts*min-1 vs. calibrated SDbetween units = 65 counts*min-1) and in the CSA instruments (raw SDbetween units = 343 counts*min-1 vs. calibrated SDbetween units = 67 counts*min-1). However, the effect of applying the derived calibration to children's and adolescents' free living physical activity data did not alter the coefficient of variation (CV) (children: CVraw = 30.2% vs. CVcalibrated = 30.4%, adolescents: CVraw = 36.3% vs. CVcalibrated = 35.7%). High correlations (r = 0.99 & r = 0.98, respectively) were observed between raw and calibrated field data, and the proportion of the total variation caused by the MTI- and CSA monitor was estimated to be only 1.1% and 4.2%, respectively. Compared to the CSA instruments, a significantly increased (9.95%) mean acceleration response was observed post hoc in the batch of MTI instruments, in which a significantly reduced inter-instrumental reliability was observed over time. CONCLUSION: The application of unit-specific calibration factors to data collected during free living conditions had no apparent effect on inter-instrument variability. In all probability, the effect of technical calibration was primarily attenuated in the field by other more dominant sources of variation. However, routine technical assessments are still very important for determining the acceleration responses in the batch of instruments being used and, if performed after every field use, for preventing decidedly broken instruments from being returned into the field repeatedly.