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Latus J.,Robert Bosch GmbH | Kitterer D.,Robert Bosch GmbH | Segerer S.,University of Zürich | Artunc F.,Diabetology | And 2 more authors.
Kidney and Blood Pressure Research | Year: 2014

Background/Aims: Puumala virus causes nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome that occurs in Central and Northern Europe. Several studies have sought to identify risk factors for severe NE. However, elevated procalcitonin (PCT) levels have not previously been investigated as a predictive marker for a severe course of NE. Methods: A cross-sectional prospective survey of 456 adults with serologically confirmed NE was performed. Results: PCT levels at the time of diagnosis were available for 43 out of 456 patients, and in 24 of these patients (56%) PCT levels were elevated ('PCT positive'). C-reactive protein (CRP) levels at admission to hospital and peak CRP levels during the acute course of the disease were higher in the PCT-positive compared with the PCT-negative group (p<0.05). Severe acute kidney injury (AKI) (RIFLE I and F) was present in similar numbers of PCT-positive and-negative patients (p=0.7), but antibiotics were more frequently used in the PCT-positive than the PCT-negative group (p<0.05). Within the PCT-positive group, PCT levels were similar among those receiving and not receiving antibiotics (p=0.13), and neither the duration of hospital stay nor CRP peak levels were lower in those treated with antibiotics (p=0.12 and p=0.13, respectively). Conclusions: Elevated PCT levels are common in patients with acute NE. There was no association between PCT levels and severity of disease, including AKI or thrombocytopenia. It is important to distinguish Puumala virus infection from other causes of AKI with thrombocytopenia. However, PCT might not be useful in differentiating hantavirus infection from bacterial infection. © 2015 S. Karger AG, Basel.

Faganello G.,Cardiovascular Center | Faggiano P.,Cardiology Unit | Candido R.,Diabetology | Tarantini L.,Ospedale civile S. Martino | And 3 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2013

Background and Aim: Mitral annulus calcification (MAC) is a marker for coronary artery disease (CAD) and predicts poor outcome in the general population. No data are available on MAC in patients with type 2 diabetes. In these patients we assessed prevalence of MAC and the relation between MAC and left ventricular (LV) systolic function. Methods and Results: As many as 386 patients with type 2 diabetes without CAD were studied with Doppler echocardiography. LV systolic dysfunction was defined by analyzing 120 healthy subjects. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (peak S') were considered as indexes of LV circumferential and longitudinal shortening and classified low if <89% and <8.5cm/s, respectively (10th percentiles of controls). Patients who had MAC (107=28%) were older with longer duration of DM and were receiving more anti-hypertension medications than those who had not. At echocardiographic evaluation patients with MAC showed higher LV mass, larger left atrial volume (LAV), reduced sc-MS (88.4±14.9 vs 92.6±14.3%; p=0.01) and peak S' (8.9±2.2 vs 10.0±2.0cm/s; p<0.001) than patients without MAC. Multiple logistic regression demonstrated older age (OR 1.03 [IC 1.01-1.06], p=0.009), larger LAV (OR 1.19 [IC 1.11-1.28], p<0.001) and combined reduction in sc-MS and peak S' (OR 3.00 [IC 1.57-5.72], p=0.001) as independent factors associated with MAC. Conclusions: MAC is detectable in one fourth of patients with type 2 diabetes without CAD and is mostly related to LV systolic dysfunction expressed as combined impairment of LV circumferential and longitudinal fibers, independent of age and LAV. © 2013 Elsevier B.V.

Khalil C.A.,Diabetology | Khalil C.A.,French Institute of Health and Medical Research | Khalil C.A.,University Paris Diderot | Roussel R.,Diabetology | And 9 more authors.
European Journal of Preventive Cardiology | Year: 2012

Diabetes is one of the most chronic diseases in Western populations. Mortality rates in diabetic patients are higher than in the general population and their prognosis following any cardiovascular event is generally worse. Type 1 diabetic patients' acute complications-related mortality decreases with time and the interval free from the diagnosis of diabetes until the development of chronic complications is larger although global mortality is still higher than that of sex- and age-matched healthy individuals. As a consequence of better primary and secondary preventions, recent data in the general population show that there is a trend towards decreased cardiovascular events and increased life expectancy. The same thing applies for type 2 diabetic patients. However, increased survival in the general population associated to epidemic bursts of obesity and sedentarily all over the globe, leads to a higher incidence of type 2 diabetes worldwide. This counteracts the diminution of diabetes-related mortality that would move forward on an ascending slope in the next decades. © The European Society of Cardiology 2011 Reprints and permissions:

Faganello G.,Cardiovascular Center | Cioffi G.,Villa Bianca Hospital | Faggiano P.,Cardiology Unit | Candido R.,Diabetology | And 4 more authors.
Acta Diabetologica | Year: 2015

Patients with metabolic syndrome (MetS) have high cardiovascular event rates. The additional effect of MetS on left ventricular (LV) systolic function in patients with type 2 diabetes mellitus (T2DM) is unknown. We studied the relation between MetS and LV systolic function in T2DM patients without coronary artery disease (CAD). Clinical and echocardiographic data from 331 T2DM patients were analyzed. Prevalence of MetS was assessed based on NCEP ATPIII definition. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (S’) were analyzed as indexes of circumferential and longitudinal shortening, respectively. Sc-MS was impaired if <89 %, S’ if <8.5 cm/s (10th percentile of healthy controls). MetS was diagnosed in 172 patients. Sc-MS and S’ were similar in T2DM patients with and without MetS (91 ± 14 vs 92 ± 15 %; 9.8 ± 2.0 vs 9.5 ± 2.1 cm/s, respectively; p = ns) but significantly reduced comparing to controls (102 ± 11 % and 10.8 cm/s; p < 0.0001). Impairment of sc-MS and S’ were detected in 37 vs 40 % and in 29 vs 32 % of T2DM patients with and without MetS (p = ns), respectively. LV systolic function measured as sc-MS and S’ is frequently impaired in T2DM patients without CAD; however, the coexistence of MetS is not associated with more severe LV systolic dysfunction. Further pathological mechanisms have to be considered to explain the negative prognostic impact of MetS in T2DM patients. © 2014, Springer-Verlag Italia.

Peter A.,Diabetology | Stefan N.,Diabetology | Cegan A.,University of Pardubice | Walenta M.,Diabetology | And 7 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Background/Aims: Glucokinase (GCK) phosphorylates glucose to form glucose 6-phosphate and thereby regulates hepatic glucose disposal and activates hepatic lipogenesis. Hepatic GCK activity is regulatedonthe level of GCK mRNA expression and by the inhibitory glucokinase regulatory protein. In this study, we aimed to investigate the relation between GCK mRNA expression and markers of lipogenesis as well as liver fat content in human liver biopsies. Additionally, we investigated whether genetic variation in the liver specific GCK promoter determines liver fat content in humans. Methods: Hepatic mRNA expression and liver triglyceride content was analyzed in 50 human liver biopsies. In a second cohort of 330 individuals, liver fat was precisely measured by 1H magnetic resonance spectroscopy. Results: Hepatic GCK mRNA expression is associated with triglyceride content in human liver biopsies (r = 0.50, P = 0.0002). Furthermore, hepatic GCK mRNA expression is associated with lipogenic gene expression (fatty acid synthase, r = 0.49, P = 0.0003; acetyl-coenzyme A carboxylase-α, r = 0.44, P = 0.0015, and acetyl-coenzyme A carboxylase-β, r = 0.48, P = 0.0004) and the de novo lipogenesis index (r = 0.36, P = 0.01). In support of these findings, the single-nucleotide polymorphism rs2041547 in the liver-specific GCK promoter is associated with liver fat content in prediabetic individuals (P = 0.047). Conclusions: In this study, we demonstrate for the first time that GCK mRNA expression is associated with markers of de novo lipogenesis and liver triglyceride content in humans. This suggests that increased GCK activity may induce fatty liver and its metabolic and hepatic consequences in humans. Thus, the widely used approach to nonspecifically activate β-cell and hepatic GCK to treat diabetes mellitus is therefore questionable and may cause serious side effects. Copyright © 2011 by The Endocrine Society.

Penfornis A.,University of Franche Comte | San-Galli F.,Endocrinology and Fenarediam | Cimino L.,Diabetology | Huet D.,Saint Joseph Hospital
Diabetes and Metabolism | Year: 2011

Aim: In France, the Afssaps/HAS 2006 guidelines for insulin-treated type 2 diabetic patients recommend a target glycated haemoglobin level (HbA 1c) of less than 7%, achieved by optimalizing the insulin dose or increasing the number of daily injections. The present study investigated to what extent these recommendations are followed in clinical practice by general practitioners (GPs) and diabetologists (DTs). Methods: The ADHOC study (observational, transversal) was a survey of 267 GPs and 180 DTs prescribing insulin in France (participation rate: 4.45% and 11.6% of GPs and DTs, respectively). Physicians answered a questionnaire focused on aspects of insulin therapy in type 2 diabetic patients receiving oral antidiabetic drugs (OADs) and insulin for at least six months. Results: A total of 1874 patients were included in the study (959 from GPs and 915 from DTs). Insulin was initiated about 10 years after the diagnosis of diabetes, when patients had high HbA 1c levels (mean value: 9.2%). At the time of the survey, patients had been treated with insulin for 3.4 ± 3.5 years (mean ± SD), and the mean HbA 1c was significantly reduced (P<0.05) to 7.8% and 7.9% in patients treated by GPs and DTs, respectively. However, almost 80% of patients had HbA 1c levels greater than 7%, and 35% had levels greater than 8%. The last fasting blood glucose level was 144 ± 45mg/dL. More than 60% of patients with HbA 1c greater than 8% were using single daily injection therapy. On consultation day, insulin treatment (dose, number of injections and type of insulin) was not optimalized in more than 40% of the latter patients. Differences in data between patients treated by GPs and DTs were small and often not statistically significant. Conclusion: In this study, the main therapeutic goals of insulin therapy, as defined by the Afssaps/HAS 2006 guidelines, were only attained in around 20% of type 2 diabetic patients, irrespective of follow-up by a GP or DT. During consultation, insulin therapy was not optimalized in a large proportion of inadequately controlled patients. © 2011 Elsevier Masson SAS.

Weigert C.,Diabetology | Weigert C.,Helmholtz Center Munich | Weigert C.,German Center for Diabetes Research | Lehmann R.,Diabetology | And 6 more authors.
Proteomics - Clinical Applications | Year: 2014

Recent years have provided clear evidence for the skeletal muscle as an endocrine organ. Muscle contraction during physical activity has emerged as an important activator of the release of the proteins and peptides called "myokines." Diverse proteomic profiling approaches were applied to rodent and human skeletal muscle cells to characterize the complete secretome, to study the regulation of the secretome during cell differentiation or the release of myokines upon contractile activity of myotubes. Several of the exercise-regulated factors have the potency to mediate an interorgan crosstalk. The paracrine function of the secreted peptides and proteins to regulate muscle regeneration, tissue remodeling, and trainability can have direct effects on whole-body glucose disposal and oxygen consumption. The overall composition and dynamic of the myokinome are still incompletely characterized. Recent advantages in metabolomics and lipidomics will add metabolites and lipids with autocrine, paracrine, or endocrine function to the contraction-induced secretome of the skeletal muscle. The identification of these metabolites will lead to a more comprehensive view described by a new myo(metabo)kinome consisting of peptides, proteins, and metabolites. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PubMed | Diabetology
Type: Journal Article | Journal: Journal of diabetes science and technology | Year: 2016

Glucose variability has been suspected to be a major factor of diabetic complications. Several indices have been proposed for measuring glucose variability, but their interest remains discussed. Our aim was to compare different indices.Glucose variability was studied in 150 insulin-treated diabetic patients (46% men, 42% type 1 diabetes, age 52 11 years) using a continuous glucose monitoring system (668 564 glucose values; mean glucose value 173 38 mg/dL). Results from the mean, the median, different indices (SD, MAGE, MAG, glucose fluctuation index (GFI), and percentages of low [<60 mg/dL] and high [>180 mg/dL] glucose values), and ratios (CV = SD/m, MAGE/m, MAG/m, and GCF = GFI/m) were compared using Pearson linear correlations and a multivariate principal component analysis (PCA).CV, MAGE/m (ns), GCF and GFI (P < .05), MAG and MAG/m (P < .01) were not strongly correlated with the mean. The percentage of high glucose values was mainly correlated with indices. The percentage of low glucose values was mainly correlated with ratios. PCA showed 3 main axes; the first was associated with descriptive data (mean, SD, CV, MAGE, MAGE/m, and percentage of high glucose values); the second with ratios MAG/m and GCF and with the percentage of low glucose values; and the third with MAG, GFI, and the percentage of high glucose values.Indices and ratios provide complementary pieces of information associated with high and low glucose values, respectively. The pairs MAG+MAG/m and GFI+GCF appear to be the most reliable markers of glucose variability in diabetic patients.

Critical limb ischemia (CLI) is a life-threatening complication of peripheral arterial disease (PAD). In patients who are ineligible for revascularization procedures, there are few therapeutic alternatives, leading to amputations and death.To provide a systematic review of the literature and a meta-analysis of studies evaluating safety and efficacy of autologous cell therapy for intractable PAD/CLI.We retrieved 19 randomized controlled trials (RCTs; 837 patients), 7 non-randomized trials (338 patients), and 41 non-controlled studies (1,177 patients). The primary outcome was major amputation. Heterogeneity was high and publication bias could not be excluded. Despite these limitations, the primary analysis (all RCTs) showed that cell therapy reduced the risk of amputation by 37%, improved amputation-free survival by 18% and improved wound healing by 59%, without affecting mortality. Cell therapy significantly increased ABI, TcO2, and reduced rest pain. The secondary analysis (all controlled trials; n=1,175 patients) shows there may be potential to avoid approximately 1 amputation/year for every 2 patients successfully treated. The tertiary analysis (all studies; n=2,332 patients) precisely estimated the changes in ABI, TcO2, rest pain, and walking capacity after cell therapy. Intra-muscular implantation appeared more effective than intra-arterial infusion, and mobilized peripheral blood mononuclear cells (MNCs) may outperform bone marrow-MNCs and mesenchymal stem cells. Amputation rate was improved more in trials wherein the prevalence of diabetes was high. Cell therapy was not associated with severe adverse events. Remarkably, efficacy of cell therapy on all end-points was no longer significant in placebo-controlled RCTs and disappeared in RCTs with a low risk of bias.Although this meta-analysis highlights the need for more high quality placebo-controlled trials, equipoise may no longer be guaranteed, because autologous cell therapy has the potential to modify the natural history of intractable CLI.

This material is intended for global medical media only. For journalistic assessment and preparation before publication. Abstract: 69477 New data from the first health-related quality of life (HRQL) study related to post-meal or postprandial glucose (PPG) control, show that poor PPG control has a significant negative impact on quality of life for people with diabetes[1]. Findings will be presented today at the 19th Annual European Congress of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) in Vienna, Austria. The study sought to evaluate the perceived impact of postprandial hyperglycaemia on people with type 1 and type 2 diabetes. Three health state descriptions characterising postprandial hyperglycaemia symptoms of varying frequency and severity (mild, moderate and severe) were evaluated using a Time Trade-Off (TTO)[*] approach by members of the general public in the UK and people with diabetes in Sweden[1]. Findings showed the following mean health state utility values, where 0 indicates death and 1 indicates full health: TTO 0.89 and 0.76 for the mild state, TTO 0.75 and 0.71 for the moderate state and TTO 0.56 and 0.58 for the severe state, among the UK general public and Swedish people with type 1 and type 2 diabetes respectively[1]. "Good metabolic control cannot solely be indicated by the percentage of patients reaching their glycaemic targets measured as HbA . Also the glucose excursions and the degree of postprandial hyperglycaemia need to be addressed," said Professor Johan Jendle, Örebro University of Sweden and scientific secretary for the Swedish Society of Diabetology. "Postprandial glucose control is important for the quality of life of people with both type 1 and type 2 diabetes." Overall, the study indicates that increasing severity in postprandial hyperglycaemic symptoms is perceived to have significant negative consequences for the short-term HRQL of people with diabetes[1]. The aim of this analysis was to quantify the impact of PPG control on HRQL of people with diabetes, expressed as health utilities using a TTO approach. In the first stage of the study, an initial literature review was conducted, followed by interviews with people with diabetes, clinicians and nurses, to characterise the nature of impact of postprandial hyperglycaemic symptoms of varying severity and frequency. Based on these findings, three health state descriptions were drafted with mild, moderate and severe symptoms of postprandial hyperglycaemia. For the valuation part of the study, a total of 300 people, including 150 members of the UK general public and 150 Swedish people with type 1 and type 2 diabetes, were recruited to take part in a face-to-face TTO interview, a standard technique used to determine a utility value for each of the three health states. Participants were asked to choose between living in the health state for a 10-year time frame or living in full health for a reduced amount of time. The study was funded by Novo Nordisk A/S. Post-meal or postprandial, glucose (PPG) is the level of blood glucose concentration measured 1-2 hours after eating. When PPG levels rise too high after eating, it is known as post-meal, or postprandial, hyperglycaemia. Postprandial hyperglycaemia is associated with increased risk of cardiovascular disease, cancer, damage to eyes, impaired cognitive function (in people with type 2 diabetes) among other diabetes-related complications[2],[3]. The longer time spent in a hyperglycaemic state, the worse overall blood glucose control. Achieving tight PPG control is important to achieve optimal blood glucose control, HbA targets[4], and to reduce risk of short-term and long-term complications associated with hyperglycaemia[5]. Novo Nordisk is a global healthcare company with more than 90 years of innovation and leadership in diabetes care. This heritage has given us experience and capabilities that also enable us to help people defeat other serious chronic conditions: haemophilia, growth disorders and obesity. Headquartered in Denmark, Novo Nordisk employs approximately 42,600 people in 75 countries and markets its products in more than 180 countries. For more information, visit, Facebook, Twitter, LinkedIn, YouTube *A TTO approach was used to provide a utility value for each state. Participants were asked to choose between living in a selected health state for a 10-year time frame or living in full health for a reduced amount of time.

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