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Grant
Agency: Cordis | Branch: FP7 | Program: BSG-SME | Phase: SME-1 | Award Amount: 713.80K | Year: 2008

Blood glucose monitoring is important in the care of diabetes mellitus and is presently accomplished via a finger-stick in which a lancet is used to prick the finger and withdraw a small amount of blood for testing. The problem with the existing finger-stick-devices is that blood sampling is painful, it increases the risk for infections and the test is discontinuous. A method for measuring the status of a diabetes patient continuously is preferred, especially at night when the risk of undetected hypoglycaemia is present. Systems for continuous (non-invasive) blood glucose monitoring show promising results for measuring high blood glucose values (hyperglycaemia). However, these systems are not reliable when it comes to measuring low blood glucose values (hypoglycaemia). This is due to the fact that a small variation in the blood glucose concentration in the hypo-region has a great impact on the status of the patient. In this project volatile components emanated from the skin are used to determine the state of diabetes patient; one of these components is acetone. An apparatus to clinically test the relation between the amount of acetone and the state of hypoglycaemia (and the concentration of blood glucose) has to be developed. Clinical tests (clamp tests) will be performed in an (academic)hospital. Furthermore, research has to be performed into the combination of several techniques (e.g. impedance spectroscopy) with skin gas measurements to obtain an overall picture of the status of a diabetes patient. Measurements of acetone permeation through the skin and the use of membranes to protect the sensor and/or to enhance the signal are needed. Sensors need to be developed to miniaturise the system. The ultimate goal is to develop a sensing system capable of measuring the condition of a diabetes patient satisfactory and in addition is able to steer the function of, among others an insulin pump.


Stirban A.,Profil Institute fur Stoffwechselforschung GmbH | Gawlowski T.,University of Paderborn | Roden M.,Heinrich Heine University Düsseldorf | Roden M.,University Clinics Dusseldorf
Molecular Metabolism | Year: 2014

The enhanced generation and accumulation of advanced glycation endproducts (AGEs) have been linked to increased risk for macrovascular and microvascular complications associated with diabetes mellitus. AGEs result from the nonenzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids, potentially altering their function by disrupting molecular conformation, promoting cross-linking, altering enzyme activity, reducing their clearance, and impairing receptor recognition. AGEs may also activate specific receptors, like the receptor for AGEs (RAGE), which is present on the surface of all cells relevant to atherosclerotic processes, triggering oxidative stress, inflammation and apoptosis. Understanding the pathogenic mechanisms of AGEs is paramount to develop strategies against diabetic and cardiovascular complications. © 2013 The Authors.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.3-1 | Award Amount: 5.49M | Year: 2012

The aim of PCDIAB is to build and evaluate a bihormonal (insulin and glucagon) artificial pancreas (AP) with automated closed loop glycaemic control for insulin treated patients with diabetes. This will be a breakthrough in diabetes management. We will miniaturize our current prototype consisting of well-established continuous glucose monitors, an insulin pump and a glucagonpump. The housing will be redesigned with dedicated miniature motors and the software will be embedded. The algorithm will be improved and a continuous glucose sensor (CGM) per-formance alert will be developed. In parallel, glucagon pharmacology will be investigated and a stable liquid glu-cagon analogue will be developed. Furthermore, administration of insulin and glucagon together with continuous glucose monitoring at the same subcutaneous site will be investigated, to enable even further miniaturization in the future. Deliverables include description of system integration of the bihormonal AP system and of an online detection of continuous glucose monitor performance. In a multinational controlled trial the bihormonal AP will be compared with standard intensive insulin therapy in daily life. Impact of the project includes simplified diabetes care, improved quality of life for patients with diabetes, dimin-ished occurrence of diabetes related complications and diminished health costs in the long run. Also, the project will strengthen competitiveness of European industry across a complete value chain involving large, mid-sized and small companies, enabling Europe to lead progress in AP systems. Finally, the project will put European research and clinical organizations in leading positions with an increased number of high-skilled jobs in the medical device industry. Dissemination and exploitation comprises a website, a conference, patents and scientific publications. The bihormonal closed loop system and the glucagon analogue can be developed into a product and brought to the market.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2009.5.1 | Award Amount: 13.64M | Year: 2010

The objective of AP@home is to build and evaluate an artificial pancreas (AP) with automated closed loop glycaemic control for insulin treated patients with diabetes. AP systems require algorithms using blood glucose levels obtained via glucose monitoring for controlling subcutaneous insulin administration. First, well established subcutaneous continuous glucose sensors and insulin pumps will be combined to improve and verify the functionality of enhanced closed-loop algorithms. We will advance algorithm quality, improve sensors by bringing their accuracy below the desired 5% error level and add a remote hypoglycaemia alarm. Second, in parallel, two AP systems will be developed by combining an insulin pump and a sensor into a single device, using only one access point through the skin (single-port). Thereby the need to puncture the skin twice, once for the glucose sensor and once for the insulin infusion, can be avoided (two-port). If proven successful in computer simulations we will evaluate the best selected single-port system under clinical conditions.\nDeliverables include: description of more precise glucose sensing methods; description of system integration of the two-port and both single-port AP systems; validation of prototypes in the clinic and at home. In a multinational controlled trial AP performance will be compared with standard intensive insulin therapy in daily life.\nImpact of the project includes strengthened competitiveness of European industry across a complete value chain involving large, mid-sized and small companies, enabling Europe to lead progress in AP systems. Also, the project will put European research and clinical organizations in leading positions with an increased number of high-skilled jobs in the medical device industry. Finally, diabetes care will be simplified, quality of life of patients with diabetes will be improved and diabetes related complications and health costs will diminish in the long run.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.3-1 | Award Amount: 6.38M | Year: 2012

Existing therapeutic devices for diabetic patients suffer from bulky size, inaccurate measurements and the difficulties of handling two body interfaces. Suboptimal control of blood glucose levels in type 1 or type 2 diabetes mellitus patients results in periods of hypo- and hyperglycaemia leading to severe and life-threatening complications. Exploiting a novel glucose sensor technology, SPIDIMAN aims to improve glycaemic management for better quality of life and healthier aging. The consortium will develop a new coating technology to apply a glucose-sensitive fluorescent dye onto a standard insulin catheter and incorporate this integrated glucose sensor into a single-port artificial pancreas system. Advanced optical continuous glucose monitoring technology (smart tattoos) with improved sensor accuracy, faster response times, wider dynamic range and higher signal stability will advance diabetes management by reducing hypo- and hyperglycaemic episodes. Within SPIDIMAN, research-intensive European SMEs will develop an innovative artificial pancreas approach, and experienced participants will perform clinical validation in a European network of specialised diabetes centres. SPIDIMAN will thus pave the way for a single-port device that integrates improved glucose measurement and more accurate insulin delivery to provide better glycaemic management in patients with insulin-dependent diabetes. The new device is expected to be particularly suitable for patients in childhood and adolescence, who will form a special focus of the project.


Grant
Agency: Cordis | Branch: FP7 | Program: BSG-SME | Phase: SME-1 | Award Amount: 1.19M | Year: 2010

Europe faces a diabetes epidemic. More than 55 million people in Europe are currently diagnosed with diabetes and with an estimated 20% increase by 2030, the disease is certain to stay one of the most challenging health problems this century. Especially as diabetes no longer is a disease exclusively for adults, but affects children, young people and adults of all ages. Despite the high prevalence of diabetes, the choice of anti-diabetic drugs is still limited and two thirds of patients with diabetes do not achieve the recommended glycaemic target levels. For each new anti-diabetic drug, it is essential to investigate the metabolic effect over time. The glucose clamp technique is regarded as the gold standard to evaluate the effectiveness of new anti-diabetic drugs. There are however only a few centers with limited research capacities that have experience in using the clamp technique, because automated clamp devices are no longer commercially available and the existing techniques are confounded by a number of limitations. Increased clamp capacities are urgently needed for the development of new, more efficacious anti-diabetic drugs. Through the integration of newly emerging technologies proposed in part by the 4 participating SME organisations and with the outsourced research capacity of 3 of Europes leading RTD performers, the EU-CLAMP project aims to develop a new generation automated clamp device that will overcome the limitations of the existing devices by incorporating microdialysis technique for reliable continuous glucose monitoring without blood loss. The EU-CLAMP project will facilitate clamp testing in a more efficient and cost effective manner. In addition to the significant contribution that will be made to development of improved treatment options for diabetes, the project will provide a platform from which the competitiveness of the participating SMEs can be improved offering alignment to the needs of their long term business strategies.


Heise T.,Profil Institute fur Stoffwechselforschung GmbH | Hermanski L.,Profil Institute fur Stoffwechselforschung GmbH | Nosek L.,Profil Institute fur Stoffwechselforschung GmbH | Feldman A.,Profil Institute fur Stoffwechselforschung GmbH | And 2 more authors.
Diabetes, Obesity and Metabolism | Year: 2012

Aims: Insulin degludec (IDeg) is a new-generation basal insulin with an ultra-long duration of action. We compared the pharmacodynamic (PD) variability of IDeg and insulin glargine (IGlar) under steady-state conditions. Methods: Day-to-day variability in glucose-lowering effect was investigated in 54 subjects with type 1 diabetes who underwent a 24-h euglycaemic glucose clamp on the 6th, 9th and 12th day of treatment with 0.4 U/kg of IDeg or IGlar once daily. Within-subject variability was estimated using a linear mixed model on log-transformed PD endpoints derived from the glucose infusion rate (GIR) profiles during the clamps. Results: For IDeg the day-to-day variability in glucose-lowering effect was four-times lower than for IGlar for total metabolic effect (AUCGIR,0-24h,SS, CV 20% vs. 82%) and for the last 22 h [AUCGIR,2-24h,SS (not influenced by intravenous insulin during the clamp), CV 22% vs. 92%]. Furthermore, lower variability in the maximum effect was observed for IDeg vs. IGlar (GIRmax,SS, CV 18% vs. 60%). The lower within-subject variability of IDeg was consistent over time (CVs of 33% for AUCGIR,0-2h,SS, 32% for AUCGIR,10-12h,SS and 33% for AUCGIR,22-24h,SS), whereas the variability of IGlar was higher and increased substantially 8 h post-dosing (CVs of 60% for AUCGIR,0-2h,SS, 135% for AUCGIR,10-12h,SS and 115% for AUCGIR,22-24h,SS). Conclusions: These results show that IDeg has a significantly more predictable glucose-lowering effect from day to day than IGlar. © 2012 Blackwell Publishing Ltd.


Flint A.,Novo Nordisk AS | Kapitza C.,PROFIL Institute fur Stoffwechselforschung GmbH | Hindsberger C.,Novo Nordisk AS | Zdravkovic M.,Novo Nordisk AS
Advances in Therapy | Year: 2011

Introduction: Fasting and postprandial plasma glucose (FPG, PPG) control are both necessary to achieve glycosylated hemoglobin (HbA 1c) regulation goals. Liraglutide, based on its glucagon-like peptide 1 (GLP-1)-mediated pharmacology and pharmacokinetics may reduce HbA 1c through both FPG and PPG levels. The objective of the present study was to investigate the effect of once-daily liraglutide (0.6, 1.2, and 1.8 mg) at steady state on FPG, PPG, postprandial insulin, and gastric emptying. Methods: Eighteen subjects with type 2 diabetes, aged 18-70 years, with a body mass index of 18.5-40 kg/m 2 and HbA 1c of 7.0%-9.5% were included in this single-centre, randomized, placebo-controlled, double-blind, two-period, cross over trial. Patients were randomized into two groups (A or B). Group A received oncedaily liraglutide for 3 weeks, followed by a 3-4-week washout period and 3 weeks of oncedaily placebo. Group B was treated as for Group A, but treatment periods were reversed (ie, placebo followed by liraglutide). A meal test was performed at steady-state liraglutide/placebo doses of 0.6, 1.2, and 1.8 mg/day. Plasma glucose, insulin, and paracetamol (acetaminophen) concentrations (to assess gastric emptying) were measured pre- and postmeal. Results: PPG levels significantly decreased (P<0.001) after all three liraglutide doses when compared with placebo. This decrease was also apparent when corrected for baseline (incremental excursions), with the exception of average incremental increase calculated as area under the concentration curve (AUC) over the fasting value from time zero to 5 hours (iAUC 0-5 h/5 hours) after liraglutide 0.6 mg, where there was a trend to decrease (P=0.082). In addition, FPG levels significantly decreased at all three liraglutide dose levels when compared to placebo (P<0.001). Fasting and postprandial insulin levels significantly increased with liraglutide versus placebo at all doses studied (P<0.001). A significant delay in gastric emptying during the first hour postmeal was observed at the two highest liraglutide doses versus placebo. Conclusion: In addition to lowering FPG levels, liraglutide improves PPG levels (absolute and incremental) possibly by both stimulating postprandial insulin secretion and delaying gastric emptying. © The Author(s) 2011.


Kapitza C.,Profil Institute fur Stoffwechselforschung GmbH | Forst T.,Institute for Clinical Research and Development | Coester H.-V.,Profil Institute fur Stoffwechselforschung GmbH | Poitiers F.,Sanofi S.A. | And 2 more authors.
Diabetes, Obesity and Metabolism | Year: 2013

Aim: Assess the pharmacodynamics of lixisenatide once daily (QD) versus liraglutide QD in type 2 diabetes insufficiently controlled on metformin. Methods: In this 28-day, randomized, open-label, parallel-group, multicentre study (NCT01175473), patients (mean HbA1c 7.3%) received subcutaneous lixisenatide QD (10μg weeks 1-2, then 20μg; n=77) or liraglutide QD (0.6mg week 1, 1.2mg week 2, then 1.8mg; n=71) 30min before breakfast. Primary endpoint was change in postprandial plasma glucose (PPG) exposure from baseline to day 28 during a breakfast test meal. Results: Lixisenatide reduced PPG significantly more than liraglutide [mean change in AUC0:30-4:30h: -12.6 vs. -4.0h·mmol/L, respectively; p<0.0001 (0:30h=start of meal)]. Change in maximum PPG excursion was -3.9mmol/l vs. -1.4mmol/l, respectively (p<0.0001). More lixisenatide-treated patients achieved 2-h PPG <7.8mmol/l (69% vs. 29%). Changes in fasting plasma glucose were greater with liraglutide (-0.3 vs. -1.3mmol/l, p<0.0001). Lixisenatide provided greater decreases in postprandial glucagon (p<0.05), insulin (p<0.0001) and C-peptide (p<0.0001). Mean HbA1c decreased in both treatment groups (from 7.2% to 6.9% with lixisenatide vs. 7.4% to 6.9% with liraglutide) as did body weight (-1.6kg vs. -2.4kg, respectively). Overall incidence of adverse events was lower with lixisenatide (55%) versus liraglutide (65%), with no serious events or hypoglycaemia reported. Conclusions: Once daily prebreakfast lixisenatide provided a significantly greater reduction in PPG (AUC) during a morning test meal versus prebreakfast liraglutide. Lixisenatide provided significant decreases in postprandial insulin, C-peptide (vs. an increase with liraglutide) and glucagon, and better gastrointestinal tolerability than liraglutide. © 2013 Blackwell Publishing Ltd.


Heinemann L.,Profil Institute fur Stoffwechselforschung GmbH | Heinemann L.,Profil Institute for Clinical Research Inc.
Diabetes Technology and Therapeutics | Year: 2010

Aim: A good understanding of the relevance of interfering factors having an impact on blood glucose (BG) measurement is needed to obtain the required quality. This depends on the application in which meters designed for self-monitoring of BG (SMBG) are used. Methods: By means of a literature search all publications (from January 1, 1980 to August 10, 2009) were identified that report about the influence of potentially interfering substances/factors on the measurement quality of BG meters. Results: Certain substances (e.g., maltose) can have a profound and misleading impact on the BG measurement result when the enzymatic reaction embedded on the given test strips cross-reacts. Also, a number of other drugs (e.g., acetaminophen) and factors (like temperature and altitude) affect the reliability of BG measurement massively. However, the susceptibility of the BG meter (depending on the enzyme technology of the test strips) differs significantly. Conclusions: In daily practice the factors that have a relevant impact on the reliability of BG measurements with modern BG meters are rarely met. Clearly this also depends on the intended use (SMBG in patient hands vs. point-of-care testing in hospitals). To avoid misleading measurement results requires adequate training of all people involved. © Copyright 2010, Mary Ann Liebert, Inc.

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