Impact of diabetic nephropathy on pharmacodynamic and pharmacokinetic properties of insulin in type 1 diabetic patients

WSTĘP. Celem pracy jest ilościowa ocena parametrów farmakodynamicznych i farmakokinetycznych krótkodziałającej insuliny ludzkiej i insuliny lispro u chorych na cukrzycę typu 1 z i/lub bez jawnej nefropatii cukrzycowej. MATERIAŁ I METODY. Badanie przeprowadzone metodą podwójnie ślepej próby miało charakter krzyżowy. Stosując technikę klamry euglikemicznej (5 mmol/l), oceniano odpowiedź metaboliczną na podskórne wstrzyknięcia insuliny krótkodziałającej i lispro (0,2 j./kg) u 12 chorych z cukrzycą typu 1 i jawną nefropatią cukrzycową (białkomocz > 500 mg/24 h i/lub stężenie kreatyniny w surowicy > 1,5 mg/dl, grupa NP) oraz u 12 chorych na cukrzycę typu 1 z prawidłową funkcją nerek, stanowiących grupę kontrolną (grupa DC). WYNIKI. Szczytowe stężenie wolnej insuliny w osoczu w przypadku lispro (359 [NP] vs. 254 pmol/l [DC]) było wyższe, a czas do osiągnięcia maksymalnego stężenia insuliny (85 [NP] vs. 99 min [DC]) był krótszy niż w przypadku ludzkiej insuliny krótkodziałającej (213 [NP] vs. 144 pmol/l [DC]; 118 [NP] vs. 153 min [DC]) w obu grupach chorych. Podsumowując, stężenia ludzkiej insuliny krótkodziałającej i lispro były wyższe u chorych z jawną nefropatią niż w grupie kontrolnej. Czas do uzyskania maksymalnego efektu metabolicznego był krótszy w przypadku insuliny lispro niż w przypadku insuliny ludzkiej w obu grupach chorych (102 vs. 191 min [NP]; 105 vs. 172 min [DC]). Całkowity efekt metaboliczny insuliny krótkodziałającej w przeciwieństwie do insuliny lispro był mniejszy u chorych z nefropatią cukrzycową niż z grupie kontrolnej (odpowiednio 967 vs. 1510 mg/kg). WNIOSKI. Chociaż stwierdzono wyższe stężenia insuliny u chorych z nefropatią cukrzycową, odpowiedź metaboliczna na ludzką insulinę krótkodziałającą pozostaje zmniejszona. Insulina lispro zachowuje swoją charakterystyczną farkmakokinetykę i farmakodynamikę u chorych z jawną nefropatią cukrzycową.INTRODUCTION. To quantify pharmacokinetic and pharmacodynamic properties of regular insulin and insulin lispro in type 1 diabetic patients with and without overt diabetic nephropathy. MATERIAL AND METHODS. In this double-blind, two- -way cross-over, euglycemic (5 mmol/l) glucose clamp study, we investigated the metabolic response to subcutaneous injections of regular insulin and insulin lispro (0.2 U/kg) in 12 type 1 diabetic patients with overt diabetic nephropathy (proteinuria > 500 mg/24 h and/or serum creatinine > 1.5 mg/dl; NP group) and in a control group of 12 type 1 diabetic patients with normal renal function (DC group). RESULTS. Peak plasma free insulin levels with insulin lispro (359 [NP] vs. 254 pmol/l [DC]) were higher and time to maximal insulin concentrations (85 [NP] vs. 99 min [DC]) shorter than with regular insulin (213 [NP] vs. 144 pmol/l [DC]; 118 [NP] vs. 153 min [DC]) in both patient groups. Overall insulin levels for regular insulin and for insulin lispro were higher in patients with overt diabetic nephropathy compared with control patients. Time to maximal metabolic effect was shorter with insulin lispro than with regular insulin in both patient groups (102 vs. 191 min [NP]; 105 vs. 172 min [DC]). The overall metabolic effect of regular insulin but not of insulin lispro was lower in patients with diabetic nephropathy than in diabetic control patients (967 vs. 1,510 mg/kg, respectively). CONCLUSIONS. Although insulin levels are higher in patients with overt diabetic nephropathy, the metabolic response to regular insulin is reduced. Insulin lispro maintains its characteristic pharmacokinetic and pharmacodynamic properties in patients with overt diabetic nephropathy

Improved Preservation of Residual Beta Cell Function by Atorvastatin in Patients with Recent Onset Type 1 Diabetes and High CRP Levels (DIATOR Trial)

A recent randomized placebo-controlled trial of the effect of atorvastatin treatment on the progression of newly diagnosed type 1 diabetes suggested a slower decline of residual beta cell function with statin treatment. Aim of this secondary analysis was to identify patient subgroups which differ in the decline of beta cell function during treatment with atorvastatin.The randomized placebo-controlled Diabetes and Atorvastatin (DIATOR) Trial included 89 patients with newly diagnosed type 1 diabetes and detectable islet autoantibodies (mean age 30 years, 40% females), in 12 centers in Germany. Patients received placebo or 80 mg/d atorvastatin for 18 months. As primary outcome stimulated serum C-peptide levels were determined 90 min after a standardized liquid mixed meal. For this secondary analysis patients were stratified by single baseline characteristics which were considered to possibly be modified by atorvastatin treatment. Subgroups defined by age, sex or by baseline metabolic parameters like body mass index (BMI), total serum cholesterol or fasting C-peptide did not differ in C-peptide outcome after atorvastatin treatment. However, the subgroup defined by high (above median) baseline C-reactive protein (CRP) concentrations exhibited higher stimulated C-peptide secretion after statin treatment (p = 0.044). Individual baseline CRP levels correlated with C-peptide outcome in the statin group (r(2) = 0.3079, p<0.004). The subgroup with baseline CRP concentrations above median differed from the corresponding subgroup with lower CRP levels by higher median values of BMI, IL-6, IL-1RA, sICAM-1 and E-selectin.Atorvastatin treatment may be effective in slowing the decline of beta cell function in a patient subgroup defined by above median levels of CRP and other inflammation associated immune mediators.ClinicalTrials.gov NCT00974740

Center for Interdisciplinary Remotely-Piloted Aircraft Studies (CIRPAS)

A remotely piloted aircraft research facility is described that will provide new capabilities for atmospheric and oceanographic measurements. The aircraft can fly up to 24 h over remote ocean regions, at low or high altitude, and in various other challenging mission scenarios. The aircraft will fly research missions at speeds of 40 m s^(−1) and provide high spatial resolution measurements. Data will be transmitted in real time to a ground station for analysis and decision-making purposes. The facility will expand the opportunities for universities to participate in field measurement programs

Assessing the effectiveness of 3 months day and night home closed-loop insulin delivery in adults with suboptimally controlled type 1 diabetes: a randomised crossover study protocol.

INTRODUCTION: Despite therapeutic advances, many people with type 1 diabetes are still unable to achieve optimal glycaemic control, limited by the occurrence of hypoglycaemia. The objective of the present study is to determine the effectiveness of day and night home closed-loop over the medium term compared with sensor-augmented pump therapy in adults with type 1 diabetes and suboptimal glycaemic control. METHODS AND ANALYSIS: The study will adopt an open label, three-centre, multinational, randomised, two-period crossover study design comparing automated closed-loop glucose control with sensor augmented insulin pump therapy. The study will aim for 30 completed participants. Eligible participants will be adults (≥18 years) with type 1 diabetes treated with insulin pump therapy and suboptimal glycaemic control (glycated haemoglobin (HbA1c)≥7.5% (58 mmol/mmol) and ≤10% (86 mmol/mmol)). Following a 4-week optimisation period, participants will undergo a 3-month use of automated closed-loop insulin delivery and sensor-augmented pump therapy, with a 4-6 week washout period in between. The order of the interventions will be random. All analysis will be conducted on an intention to treat basis. The primary outcome is the time spent in the target glucose range from 3.9 to 10.0 mmol/L based on continuous glucose monitoring levels during the 3 months free living phase. Secondary outcomes include HbA1c changes; mean glucose and time spent above and below target glucose levels. Further, participants will be invited at baseline, midpoint and study end to participate in semistructured interviews and complete questionnaires to explore usability and acceptance of the technology, impact on quality of life and fear of hypoglycaemia. ETHICS AND DISSEMINATION: Ethical approval has been obtained at all sites. Before screening, all participants will be provided with oral and written information about the trial. The study will be disseminated by peer-review publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT01961622 (ClinicalTrials.gov)

Geometric properties of nucleic acids with potential for autobuilding

Algorithms and geometrical properties are described for the automated building of nucleic acids in experimental electron density

Standard for Synthesis of Customized Peptides by Non-Ribosomal Peptide Synthetases

The purpose of this RFC is to introduce a standardized framework for the engineering of customizable non-ribosomal peptide synthetases (NRPS) and their application for in vivo and in vitro synthesis of short non-ribosomal peptides (NRPs) of user-defined sequence and structure

HiCT: High Throughput Protocols For CPE Cloning And Transformation

The purpose of this RFC is to provide instructions for a rapid and cost efficient cloning and transformation method which allows for the manufacturing of multi-fragment plasmid constructs in a parallelized manner: High Throughput Circular Extension Cloning and Transformation (HiCT). Description of construct libraries generated by the HiCT method can be found at http://2013.igem.org/Team:Heidelberg/Indigoidine. This RFC also points out further optimization strategies with regard to construct stability, reduction of transformation background and the generation of competent cells