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Alssema M.,Unilever | Alssema M.,EMGO Institute for Health and Care Research | Boers H.M.,Unilever | Ceriello A.,Insititut dInvestigacions Biomediques August Pi i Sunyer IDIBAPS | And 7 more authors.
British Journal of Nutrition | Year: 2015

Consumption of carbohydrate-containing foods leads to transient postprandial rises in blood glucose concentrations that vary between food types. Higher postprandial glycaemic exposures have particularly been implicated in the development of chronic cardiometabolic diseases. Reducing such diet-related exposures may be beneficial not only for diabetic patients but also for the general population. A variety of markers have been used to track different aspects of glycaemic exposures, with most of the relevant knowledge derived from diabetic patients. The assessment of glycaemic exposures among the non-diabetic population may require other, more sensitive markers. The present report summarises key messages of presentations and related discussions from a workshop organised by Unilever intended to consider currently applied markers of glycaemic exposure. The particular focus of the meeting was to identify the potential applicability of glycaemic exposure markers for studying dietary effects in the non-diabetic population. Workshop participants concluded that markers of glycaemic exposures are sparsely used in intervention studies among non-diabetic populations. Continuous glucose monitoring remains the optimal approach to directly assess glycaemic exposure. Markers of glycaemic exposure such as glycated Hb, fructosamine, glycated albumin, 1,5-anhydroglucitol and advanced glycation end products can be preferred dependent on the aspect of interest (period of exposure and glucose variability). For all the markers of glycaemia, the responsiveness to interventions will probably be smaller among the non-diabetic than among the diabetic population. Further validation and acceptance of existing glycaemic exposure markers applied among the non-diabetic population would aid food innovation and better design of dietary interventions targeting glycaemic exposure. Copyright © 2014 The Authors .


Diederich S.,Diabetes and Nutrition | Diederich S.,Center for Endocrine and Metabolism Diseases | Quinkler M.,Center for Internal Medicine | Mai K.,Diabetes and Nutrition | And 5 more authors.
Hormone and Metabolic Research | Year: 2011

The 11β-Hydroxysteroid dehydrogenases (11β-HSDs) play a pivotal role in glucocorticoid (GC) action. 11β-HSD1 is a predominant reductase, activating GCs from inert metabolites, whereas 11β-HSD2 is a potent dehydrogenase inactivating GCs. Knowing the metabolic effects of GCs, a selective inhibition of 11β-HSD1 represents a potential target for therapy of impaired glucose tolerance, insulin insensitivity and central obesity. In vitro, 11β-HSD1 is selectively inhibited by chenodesoxycholic acid (CDCA) and upregulated under GC exposure. Therefore, we aimed to investigate the effects of CDCA and prednisolone on hepatic 11β-HSD1 activity in vivo by measuring 11-reduction of orally given cortisone (E) acetate to cortisol (F). CDCA or placebo was given to 5 male healthy volunteers within a randomised cross-over trial before and after oral administration of 12.5 mg E acetate at 8:00 h. For measurement of in vivo effects of GCs on 11β-HSD1 activity, hepatic reduction of 25 mg E acetate before and after treatment with prednisolone (30 mg for 6 days) was determined in 7 healthy males. Serum GC levels were determined using a fully automated liquid chromatographic system. CDCA had no effect on the activity of 11β-HSD1 in vivo. Prednisolone therapy leads to a marked rise in serum F concentrations and an elevated F/E serum ratio. This proves GC-induced activation of hepatic 11β-HSD1, which could not be extinguished by a parallel increase of IGF-1 under prednisolone. CDCA does not affect in vivo activity of 11β-HSD1 when given in therapeutic dosages. During GC treatment, increased hepatic activation of E to F may aggravate metabolic side effects of GCs such as seen in the metabolic syndrome. © Georg Thieme Verlag KG, Stuttgart - New York.


PubMed | Childrens Hospital AUF DER BULT Janusz Korczak Allee 12 30173 Hanover Germany, Robert d Patricia rn Center For The Science Of Health Care Delivery, Mayo Medical School, University Hospital Sainte Marguerite and 3 more.
Type: | Journal: Clinical endocrinology | Year: 2016

Real time continuous glucose monitoring (RTCGM) may help in the management of individuals with type 1 diabetes mellitus (T1DM); however, the evidence supporting its use is unclear. The available meta-analyses on this topic use aggregate data which weaken inference.Individual patient data were obtained from randomized trials (RCTs) to conduct a meta-analysis and synthesize evidence about the effect of RTCGM on glycosylated haemoglobin (HbA1c), hypoglycaemic events and time spent in hypoglycaemia in T1DM.We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus through January 2015. We included RCTs that enrolled individuals with T1DM and compared RTCGM vs control group. A two-step regression model was used to pool individual patient data.We included 11 RCTs at moderate risk of bias. Meta-analysis suggests that the use of RTCGM is associated with a statistically significant but modest reduction in HbA1c (-0.276; 95% confidence interval -0.465 to -0.087). The improvements in HbA1c were primarily seen in individuals over age 15 years. We were unable to identify a statistically significant difference in time spent in hypoglycaemia or the number of hypoglycaemic episodes although these analyses were imprecise and warrant lower confidence. There was no difference between males and females.RTCGM in T1DM is associated with a reduction in HbA1c primarily in individuals over 15 years of age. We were unable to identify a statistically significant difference in the time spent in hypoglycaemia or the incidence of hypoglycaemic episodes. This article is protected by copyright. All rights reserved.


Hocher B.,University of Potsdam | Hocher B.,Institute of Pharmacology | Heiden S.,Institute of Pharmacology | von Websky K.,University of Potsdam | And 10 more authors.
PLoS ONE | Year: 2011

Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A1 receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A1 receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold) and natriuretic (up to 13.5-fold) effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (-36.5%, p<0.05), especially in those receiving furosemide (-41.9%, p<0.01). SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05). SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A1 receptor antagonists are clinically beneficial at different stages of liver cirrhosis. © 2011 Hocher et al.


Byrne E.M.,University of Queensland | Byrne E.M.,Queensland Institute of Medical Research | Raheja U.K.,Mood and Anxiety Program | Raheja U.K.,Saint Elizabeths Hospital | And 21 more authors.
Journal of Clinical Psychiatry | Year: 2015

Objective: To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality. Method: Genome-wide association studies (GWASs) were conducted in Australian (between 1988 and 1990 and between 2010 and 2013) and Amish (between May 2010 and December 2011) samples in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered, and the results were meta-analyzed in a total sample of 4,156 individuals. Genetic risk scores based on results from prior large GWAS studies of bipolar disorder, major depressive disorder (MDD), and schizophrenia were calculated to test for overlap in risk between psychiatric disorders and seasonality. Results: The most significant association was with rs11825064 (P = 1.7 × 10-6, β = 0.64, standard error = 0.13), an intergenic single nucleotide polymorphism (SNP) found on chromosome 11. The evidence for overlap in risk factors was strongest for schizophrenia and seasonality, with the schizophrenia genetic profile scores explaining 3% of the variance in logtransformed global seasonality scores. Bipolar disorder genetic profile scores were also associated with seasonality, although at much weaker levels (minimum P value = 3.4 × 10-3), and no evidence for overlap in risk was detected between MDD and seasonality. Conclusions: Common SNPs of large effect most likely do not exist for seasonality in the populations examined. As expected, there were overlapping genetic risk factors for bipolar disorder (but not MDD) with seasonality. Unexpectedly, the risk for schizophrenia and seasonality had the largest overlap, an unprecedented finding that requires replication in other populations and has potential clinical implications considering overlapping cognitive deficits in seasonal affective disorders and schizophrenia. © Copyright 2014 Physicians Postgraduate Press, Inc.


McDonough C.W.,University of Florida | Burbage S.E.,University of Florida | Duarte J.D.,University of Illinois at Chicago | Gong Y.,University of Florida | And 10 more authors.
Journal of Hypertension | Year: 2013

OBJECTIVE:: Single-nucleotide polymorphisms (SNPs) in NEDD4L may influence the ability of the NEDD4L protein to reduce epithelial sodium channel expression. A variant in NEDD4L, rs4149601, was associated with antihypertensive response and cardiovascular outcomes during treatment with thiazide diuretics and β-blockers in a Swedish population. We sought to further evaluate associations between NEDD4L polymorphisms, blood pressure response and cardiovascular outcomes with thiazide diuretics and β-blockers. METHODS:: Four SNPs, rs4149601, rs292449, rs1008899 and rs75982813, were genotyped in 767 patients from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) clinical trial and association was assessed with blood pressure response to hydrochlorothiazide and atenolol. One SNP, rs4149601, was also genotyped in 1345 patients from the International Verapmil SR Trandolapril Study (INVEST), and association was examined with adverse cardiovascular outcomes relative to hydrochlorothiazide treatment. RESULTS:: Significant associations or trends were found between rs4149601, rs292449, rs75982813 and rs1008899 and decreases in blood pressure in whites on hydrochlorothiazide, and a significant association was observed with increasing copies of the GC rs4149601-rs292449 haplotype and greater blood pressure response to hydrochlorothiazide in whites (P = 0.0006 and 0.006, SBP and DBP, respectively). Significant associations were also seen with rs4149601 and an increased risk for adverse cardiovascular outcomes in whites not treated with hydrochlorothiazide [P = 0.022, odds ratio (95% confidence interval) = 10.65 (1.18-96.25)]. CONCLUSION:: NEDD4L rs4149601, rs292449 and rs75982813 may be predictors for blood pressure response to hydrochlorothiazide in whites, and NEDD4L rs4149601 may be a predictor for adverse cardiovascular outcomes in whites not treated with hydrochlorothiazide. © 2013 Lippincott Williams & Wilkins, Inc.


Kirchsteiger H.,Johannes Kepler University | Zaccarian L.,Roche Holding AG | Renard E.,Diabetes and Nutrition | Del Re L.,Johannes Kepler University
Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS | Year: 2013

This paper considers the problem of online calibration and recalibration of continuous glucose monitoring devices. A parametric relation between interstitial and blood glucose is investigated and a constructive algorithm to adaptively estimate the parameters within this relation is proposed. The algorithm explicitly considers measurement uncertainty of the device used to collect the calibration measurements and enables automatic detection of measurements which are not suitable to be used for calibration. The method was assessed on clinical data from 17 diabetic patients and the improvements with respect to the current state of the art is shown. © 2013 IEEE.


Vouillarmet J.,Diabetes and Nutrition | Morelec I.,Center Hospitalier Lyon Sud | Thivolet C.,Diabetes and Nutrition | Thivolet C.,French Institute of Health and Medical Research
Diabetic Medicine | Year: 2014

Aims: Diabetic foot osteomyelitis is an important risk factor of lower limb amputation. Antibiotic therapy is often effective in preventing surgery. However, the duration of antibiotic therapy is difficult to define in the absence of a marker to diagnose osteomyelitis remission at the end of the treatment. In this study, we assessed the diagnostic performance of white blood cell SPECT/CT imaging for evaluating osteomyelitis remission. Patients and methods: Twenty-nine out of 42 episodes of diabetic foot osteomyelitis seen between December 2009 and April 2012 had radiographs, a three-phase bone scintigraphy and a white blood cell SPECT/CT at the end of antibiotic therapy. They were treated with antibiotics alone and considered in clinical remission. White blood cell SPECT/CT results were considered positive when abnormal uptake in the osteomyelitis location was identified. Osteomyelitis remission was defined by the absence of an osteomyelitis relapse after 12 months' follow-up. Results: A negative white blood cell SPECT/CT was seen for 22 episodes of osteomyelitis. All of them were in remission. A positive white blood cell SPECT/CT was observed for seven episodes. A relapse occurred in five episodes (71.5%) after a median duration of 4 months (2-7 months). Sensitivity, specificity, positive predictive value and predictive negative value in predicting osteomyelitis relapse after the discontinuation of antibiotic treatment were, respectively, for radiographs 80%, 33%, 20% and 89%; for three-phase bone scintigraphy 100%, 12.5%, 15.5% and 100%; and for the white blood cell SPECT/CT 100%, 91.5%, 71.5% and 100%. Conclusion: Negative uptake on white blood cell SPECT/CT is a good marker for diagnosis of diabetic foot osteomyelitis remission and might be very useful in guiding antibiotic therapy. © 2014 Diabetes UK.


PubMed | Diabetes and Nutrition. and University of Maryland Baltimore County
Type: | Journal: Diabetes, metabolic syndrome and obesity : targets and therapy | Year: 2017

To compare length of stay (LOS) and incidence of hypoglycemic events and infections in hospitalized patients with diabetes mellitus (DM) undergoing renal transplantation, among groups of patients defined by admission glucose and mean inpatient daily glucose.A retrospective analysis of 190 charts of patients with DM who underwent renal transplantation over a 2-year period was conducted. Patients were grouped according to admission glucose and mean inpatient daily glucose (140 mg/dL, 141-180 mg/dL, and >180 mg/dL).Admission glucose was not associated with LOS. A mean inpatient daily glucose of 140 mg/dL was associated with a longer LOS compared to a mean inpatient daily glucose of >180 mg/dL (Lower mean daily inpatient glucose levels (140 mg/dL) are associated with longer LOS and greater incidence of hypoglycemic episodes in diabetes patients undergoing renal transplantation. Our findings suggest that target blood glucose levels of 140-180 mg/dL may be appropriate in this specific population. Additional prospective research is needed to confirm these findings.

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