The Danish Diabetes Academy

Odense, Denmark

The Danish Diabetes Academy

Odense, Denmark
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Sondergaard E.,Aarhus University Hospital | Sondergaard E.,The Danish Diabetes Academy | Andersen I.R.,Aarhus University Hospital | Sorensen L.P.,Aarhus University Hospital | And 2 more authors.
Scandinavian Journal of Medicine and Science in Sports | Year: 2017

Exercise lowers plasma triglyceride levels, but the physiological mechanisms remain not fully elucidated. Lipoprotein lipase (LPL) is a key enzyme in facilitating fatty acid uptake from lipoproteins. As exercise increases the efficiency of very low-density lipoprotein-triglyceride (VLDL-TG) oxidation, we hypothesized that muscle LPL activity would be a rate-limiting step and predict VLDL-TG Fatty acids oxidation during exercise. Sixteen healthy, lean subjects (eight men and eight women) were examined before and during an acute exercise bout (90 minutes at 50% of VO2-max). Heparin-releasable LPL activity was measured in muscle and adipose tissue biopsies. Breath 14CO2 was measured after a primed-constant infusion of ex vivo labeled [14C]-triolein VLDL-TG. Fractional VLDL-TG storage was measured in adipose tissue biopsies. Exercise did not affect muscle LPL activity (P=.30). No association was observed between muscle LPL activity and VLDL-TG oxidation, neither in the basal state (P=.17) nor during exercise (P=.83). Exercise did not affect upper body or lower body adipose tissue LPL activity (both P=.92). The basal adipose tissue fractional VLDL-TG storage (abdominal.13%±9%; femoral 17%±10% (P=.18)) was not associated with upper body (P=.56) or lower body (P=.44) subcutaneous adipose tissue LPL activity. Muscle LPL activity does not predict VLDL-TG oxidation during rest or exercise. In addition, adipose tissue LPL activity was not associated with VLDL-TG storage during rest. This suggests that LPL activity is present in excess of what is required to facilitate lipid uptake for oxidation during both rest and exercise. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Lebeck J.,The Danish Diabetes Academy | Lebeck J.,University of Aarhus
Journal of Molecular Endocrinology | Year: 2014

Obesity and secondary development of type 2 diabetes (T2D) are major health care problems throughout the developed world. Accumulating evidence suggest that glycerol metabolism contributes to the pathophysiology of obesity and T2D. Glycerol is a small molecule that serves as an important intermediate between carbohydrate and lipid metabolism. It is stored primarily in adipose tissue as the backbone of triglyceride (TG) and during states of metabolic stress, such as fasting and diabetes, it is released for metabolism in other tissues. In the liver, glycerol serves as a gluconeogenic precursor and it is used for the esterification of free fatty acid into TGs. Aquaporin 7 (AQP7) in adipose tissue and AQP9 in the liver are transmembrane proteins that belong to the subset of AQPs called aquaglyceroporins. AQP7 facilitates the efflux of glycerol from adipose tissue and AQP7 deficiency has been linked to TG accumulation in adipose tissue and adult onset obesity. On the other hand, AQP9 expressed in liver facilitates the hepatic uptake of glycerol and thereby the availability of glycerol for de novo synthesis of glucose and TG that both are involved in the pathophysiology of diabetes. The aim of this review was to summarize the current knowledge on the role of the two glycerol channels in controlling glycerol metabolism in adipose tissue and liver. © 2014 Society for Endocrinology.

Laugesen E.,University of Aarhus | Laugesen E.,Aarhus University Hospital | Laugesen E.,The Danish Diabetes Academy | Ostergaard J.A.,University of Aarhus | And 3 more authors.
Diabetic Medicine | Year: 2015

Patients with adult-onset autoimmune diabetes have less Human Leucocyte Antigen (HLA)-associated genetic risk and fewer diabetes-associated autoantibodies compared with patients with childhood-onset Type 1 diabetes. Metabolic changes at diagnosis reflect a broad clinical phenotype ranging from diabetic ketoacidosis to mild non-insulin-requiring diabetes, also known as latent autoimmune diabetes of the adult (LADA). This latter phenotype is the most prevalent form of adult-onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. Although LADA is associated with the same genetic and immunological features as childhood-onset Type 1 diabetes, it also shares some genetic features with Type 2 diabetes, which raises the question of genetic heterogeneity predisposing to this form of the disease. The potential value of screening patients with adult-onset diabetes for diabetes-associated autoantibodies to identify those with LADA is emphasized by their lack of clinically distinct features, their different natural history compared with Type 2 diabetes and their potential need for a dedicated management strategy. The fact that, in some studies, patients with LADA show worse glucose control than patients with Type 2 diabetes, highlights the need for further therapeutic studies. Challenges regarding classification, epidemiology, genetics, metabolism, immunology, clinical presentation and treatment of LADA were discussed at a 2014 workshop arranged by the Danish Diabetes Academy. The presentations and discussions are summarized in this review, which sets out the current ideas and controversies surrounding this form of diabetes. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

PubMed | Holbaek Hospital, Steno Diabetes Center, The Danish Diabetes Academy, Nordsjaellands University Hospital and University of Aarhus
Type: Journal Article | Journal: Diabetologia | Year: 2016

Screening programmes for type 2 diabetes inevitably find more people at high risk of developing diabetes than people with undiagnosed prevalent diabetes. We describe the incidence of diabetes for risk groups according to advancement in a screening process.In 2001-2006, a diabetes screening programme based on the Danish diabetes risk score and measures of HbA1c and glucose was carried out in Danish general practices. The present study includes 13,249 individuals with low diabetes risk scores and 22,726 with high diabetes risk scores but no diabetes according to WHO 1999 criteria. Seven incremental levels of diabetes risk were defined and followed for incident diabetes recorded in the Danish National Diabetes Register until December 2012. For each group, cumulative diabetes incidence was calculated. Incidence rates and rate ratios were estimated by Poisson regression analyses.After 10 years of follow-up 1,164 new diabetes cases were registered. Incidence rates were 1.0, 4.2, 14.5, 28.8 and 52.6 per 1,000 person-years in individuals at low risk and in those with normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance and one diabetic glucose value, respectively. For each step in the screening algorithm, the risk of developing diabetes was higher than in the previous step.The risk of developing clinical diabetes in people who screen negative for diabetes depends on the level of risk stratification at screening, even at lower risk levels. This risk increases markedly in the presence of impaired glucose regulation. These results can inform policy recommendations concerning prevention strategies following screening.

Huang H.,Copenhagen University | Huang H.,University of Southern Denmark | Huang H.,The Danish Diabetes Academy | Larsen M.R.,University of Southern Denmark | And 4 more authors.
Journal of Proteomics | Year: 2014

Protein phosphorylation can regulate most of the important processes in muscle, such as metabolism and contraction. The postmortem (PM) metabolism and rigor mortis have essential effects on meat quality. In order to identify and characterize the protein phosphorylation events involved in meat quality development, a quantitative mass spectrometry-based phosphoproteomic study was performed to analyze the porcine muscle within 24. h PM using dimethyl labeling combined with the TiSH phosphopeptide enrichment strategy. In total 305 unique proteins were identified, including 160 phosphoproteins with 784 phosphorylation sites. Among these, 184 phosphorylation sites on 93 proteins had their phosphorylation levels significantly changed. The proteins involved in glucose metabolism and muscle contraction were the two largest clusters of phosphoproteins with significantly changed phosphorylation levels in muscle within 24. h PM. The high phosphorylation level of heat shock proteins (HSPs) in early PM may be an adaptive response to slaughter stress and protect muscle cell from apoptosis, as observed in the serine 84 of HSP27. This work indicated that PM muscle proteins underwent significant changes at the phosphorylation level but were relatively stable at the total protein level, suggesting that protein phosphorylation may have important roles in meat quality development through the regulation of proteins involved in glucose metabolism and muscle contraction, thereby affecting glycolysis and rigor mortis development in PM muscle. Biological significance: The manuscript describes the characterization of postmortem (PM) porcine muscle within 24. h postmortem from the perspective of protein phosphorylation using advanced phosphoproteomic techniques. In the study, the authors employed the dimethyl labeling combined with the TiSH phosphopeptide enrichment and LC-MS/MS strategy.This was the first high-throughput quantitative phosphoproteomic study in PM muscle of farm animals. In the work, both the proteome and phosphoproteome were analyzed, and the large number of identified peptides, phosphopeptides and phosphorylation sites can greatly enrich the current farm animal protein database.The proteins involved in glycometabolism, muscle contraction and heat shock proteins (HSPs) showed significantly changed phosphorylation levels during PM meat development. This work indicated that PM muscle proteins underwent significant changes at phosphorylation level but were relatively stable at the total protein level, suggesting that protein phosphorylation may have important roles in meat development through the regulation of proteins involved in metabolism and muscle contraction, thereby affecting glycolysis and rigor mortis development in PM muscle.The work can promote the understanding of PM muscle metabolism and meat quality development, and be helpful for future meat quality control. © 2014 Elsevier B.V.

Bronden A.,Copenhagen University | Bronden A.,The Danish Diabetes Academy | Hansen M.,Copenhagen University | Sonne D.P.,Copenhagen University | And 3 more authors.
Diabetes, Obesity and Metabolism | Year: 2015

Sevelamer is a calcium-free and metal-free phosphate-binding oral drug used in the management of hyperphosphataemia in chronic kidney disease. Preclinical and clinical trials have shown glucose and lipid-lowering effects of sevelamer, thereby giving rise to a potential role of the drug in the treatment of patients with type 2 diabetes. These 'novel' effects are most probably derived from the bile acid-binding properties of sevelamer. The proposed potential is supported by the approval of the bile acid sequestrant colesevelam in the United States for the treatment of type 2 diabetes and hypercholesterolaemia. This article offers a brief review on the effects of sevelamer and a perspective on the potential mechanisms behind the glucose-lowering effect of the drug. © 2014 John Wiley & Sons Ltd.

Johansen R.F.,Aarhus University Hospital | Sondergaard E.,Aarhus University Hospital | Sondergaard E.,The Danish Diabetes Academy | Sorensen L.P.,Aarhus University Hospital | And 3 more authors.
Diabetologia | Year: 2016

Aims/hypothesis: Hypertriacylglycerolaemia is a hallmark of diabetic dyslipidaemia with increased concentrations of triacylglycerol (TG)-rich VLDL1 particles. However, whether VLDL1 secretion or removal is abnormal in type 2 diabetes remains unclear. The aim of this study was to compare basal and insulin-mediated VLDL1- and VLDL2-TG kinetics in men with type 2 diabetes and healthy men using a novel direct VLDL1- and VLDL2-TG labelling method. Methods: Twelve men with type 2 diabetes and 12 healthy men matched for age and BMI were recruited. VLDL1- and VLDL2-TG turnover were measured during a 4 h basal period and a 3.5 h hyperinsulinaemic clamp period using a primed-constant infusion of ex vivo labelled VLDL1-TG and VLDL2-TG. Results: Basal VLDL1-TG and VLDL2-TG secretion rates were similar in men with diabetes and healthy men. During hyperinsulinaemia, VLDL1-TG secretion rates were suppressed significantly in both groups, whereas no suppression of VLDL2-TG secretion rate was observed. VLDL1-TG to VLDL2-TG transfer rate was not significantly different from zero in both groups, while VLDL1-TG fatty acid oxidation rate was substantial, with a contribution to total energy expenditure of approximately 15% during postabsorptive conditions. VLDL1 and VLDL2 particle size (TG/apolipoprotein B [apoB] ratio) and apoB-100 concentration were unaltered by hyperinsulinaemia in men with type 2 diabetes, but significantly reduced in healthy men. Conclusions/interpretation: Insulin inhibits VLDL1-TG secretion rate similarly in age- and BMI-matched men with type 2 diabetes and healthy men, while VLDL2-TG secretion is unaltered by hyperinsulinaemia. However, VLDL1- and VLDL2-apoB levels are not lowered by hyperinsulinaemia in men with type 2 diabetes, which is indicative of a diminished hepatic response to insulin. Trial registration: NCT01564550 © 2016, Springer-Verlag Berlin Heidelberg.

PubMed | University of Southern Denmark and The Danish Diabetes Academy
Type: Journal Article | Journal: Diabetologia | Year: 2016

Gestational diabetes mellitus (GDM) is associated with an increased risk of pre-eclampsia, macrosomia and the future development of type 2 diabetes mellitus in both mother and child. Although an early and accurate prediction of GDM is needed to allow intervention and improve perinatal outcome, no single protein biomarker has yet proven useful for this purpose. In the present study, we hypothesised that multimarker panels of serum proteins can improve first-trimester prediction of GDM among obese and non-obese women compared with single markers.A nested case-control study was performed on first-trimester serum samples from 199 GDM cases and 208 controls, each divided into an obese group (BMI 27kg/m(2)) and a non-obese group (BMI <27kg/m(2)). Based on their biological relevance to GDM or type 2 diabetes mellitus or on their previously reported potential as biomarkers for these diseases, a number of proteins were selected for targeted nano-flow liquid chromatography (LC) MS analysis. This resulted in the development and validation of a 25-plex multiple reaction monitoring (MRM) MS assay.After false discovery rate correction, six proteins remained significantly different (p<0.05) between obese GDM patients (n=135) and BMI-matched controls (n=139). These included adiponectin, apolipoprotein M and apolipoprotein D. Multimarker models combining protein levels and clinical data were then constructed and evaluated by receiver operating characteristic (ROC) analysis. For the obese, non-obese and all GDM groups, these models achieved marginally higher AUCs compared with adiponectin alone.Multimarker models combining protein markers and clinical data have the potential to predict women at a high risk of developing GDM.

PubMed | University of Southern Denmark, The Danish Diabetes Academy and Hospital Lillebaelt
Type: Journal Article | Journal: PloS one | Year: 2016

The objective of the present study was to evaluate the effectiveness of a one-year multi-component immersive day-camp weight-loss intervention for children with overweight and obesity. The study design was a parallel-group randomized controlled trial. One hundred fifteen 11-13-year-old children with overweight and obesity were randomized into either: A six-week day-camp intervention arm focusing on increased physical activity, and healthy diet followed by a subsequent one-year family-based intervention, or a standard intervention arm consisting of one weekly exercise session for six weeks. Body mass index (BMI) was the primary outcome. BMI z-score, clustered cardiovascular risk z-score, and body composition were secondary outcomes. All outcomes were measured at baseline, six week-, and 52 week follow-up. After six weeks, children from the day-camp intervention arm had improved their BMI (-2.2 kg/m2 (95% CI -2.6 to -1.7, P<0.001)) and all secondary outcomes when compared to the children from the standard intervention arm. After 52 weeks, the day-camp intervention arm had a lower BMI (-1.2 kg/m2 (95% CI -1.8 to -0.5, P = 0.001)), and BMI z-score (-0.20 (95% CI -0.35 to -0.05, P = 0.008)), and clustered cardiovascular risk z-score (-0.23 (95% CI -0.37 to -0.08, P = 0.002)) compared to the standard intervention arm. No group differences were detected in body composition after 52 weeks. This study shows that the day-camp intervention arm is effective in reducing BMI and improving the metabolic health of children with overweight and obesity. However, the effects seem to be diminishing over time.

Sondergaard E.,Aarhus University Hospital | Sondergaard E.,The Danish Diabetes Academy | Gormsen L.C.,Aarhus University Hospital | Christensen M.H.,Aarhus University Hospital | And 5 more authors.
Diabetic Medicine | Year: 2015

Background: Recruitment of brown adipose tissue is a promising strategy to treat obesity and Type 2 diabetes, but the physiological effects of a large amount of metabolically active brown adipose tissue in humans are unknown. Case report: In the present paper, we report a case of massive brown adipose tissue infiltration of the visceral adipose tissue depot in a person with Type 2 diabetes with a catecholamine-secreting paraganglioma. The patient was evaluated with [18F]-fludeoxyglucose positron emission tomography/computed tomography on three occasions: pre-therapy, during α-blockade and postoperatively. During surgery, biopsies of visceral and subcutaneous adipose tissue were obtained and evaluated for brown adipose tissue. At diagnosis, brown adipose tissue glucose uptake, assessed by [18F]-fludeoxyglucose-positron emission tomography, was massively increased. [18F]-fludeoxyglucose uptake was confined to known locations for brown adipose tissue, with additional uptake in the visceral adipose tissue. As a result of increased thermogenesis, resting energy expenditure was doubled. After surgical removal of the tumour, antidiabetic medicine was no longer needed, despite an 8.2-kg weight gain. Conclusion: These results show that human visceral adipose tissue holds an unprecedented potential for brown adipogenic differentiation; however, a detrimental effect on glucose metabolism persisted despite massive brown adipose tissue activity, with a doubling of resting energy expenditure. © 2014 Diabetes UK.

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