Effect of Liraglutide Treatment on Whole-body Glucose Fluxes in C-peptide-Positive Type 1 Diabetes During Hypoglycemia.

Context: The effect of liraglutide in C-peptide-positive (C-pos) type 1 diabetes (T1D) patients during hypoglycemia remains unclear.

Objective: To investigate the effect of a 12-week liraglutide treatment on the body glucose fluxes during a hypoglycemic clamp in C-pos T1D patients and its impact on the alpha- and beta-cell responses during hypoglycemia.

Design: This was a randomized, double-blind, crossover study.

Evaluation of a novel, rapid antigen detection test for the diagnosis of SARS-CoV-2.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is currently finally determined in laboratory settings by real-time reverse-transcription polymerase-chain-reaction (rt-PCR). However, simple testing with immediately available results are crucial to gain control over COVID-19. The aim was to evaluate such a point-of-care antigen rapid test (AG-rt) device in its performance compared to laboratory-based rt-PCR testing in COVID-19 suspected, symptomatic patients.

Effect of once-weekly semaglutide on the counterregulatory response to hypoglycaemia in people with type 2 diabetes: A randomized, placebo-controlled, double-blind, crossover trial.

Aims: To investigate the effects of semaglutide vs placebo on glucagon and other counterregulatory hormones during hypoglycaemia in type 2 diabetes (T2D).

Methods: In this double-blind, placebo-controlled, single-centre trial, we randomized 38 men and women (treated only with metformin) 1:1 to 2 12-week crossover periods of once-weekly subcutaneous semaglutide or placebo, each followed by a hypoglycaemic clamp procedure. The primary endpoint was change in glucagon concentration from target plasma glucose (PG) level 5.

Impact of C-Peptide Status on the Response of Glucagon and Endogenous Glucose Production to Induced Hypoglycemia in T1DM.

Context: Complete loss of β-cell function in patients with type 1 diabetes mellitus (T1DM) may lead to an increased risk of severe hypoglycemia.

Objective: We aimed to determine the impact of C-peptide status on glucagon response and endogenous glucose production (EGP) during hypoglycemia in patients with T1DM.

Design And Setting: We conducted an open, comparative trial.

A prolonged run-in period of standard subcutaneous microdialysis ameliorates quality of interstitial glucose signal in patients after major cardiac surgery.

We evaluated a standard subcutaneous microdialysis technique for glucose monitoring in two critically ill patient populations and tested whether a prolonged run-in period improves the quality of the interstitial glucose signal. 20 surgical patients after major cardiac surgery (APACHE II score: 10.1 ± 3.

The Distinct Prandial and Basal Pharmacodynamics of IDegAsp Observed in Younger Adults Are Preserved in Elderly Subjects with Type 1 Diabetes.

Background: Management of diabetes in elderly patients is complicated by the elevated risk of insulin-induced hypoglycaemia. This is the first study to report the pharmacodynamic and pharmacokinetic characteristics of IDegAsp (insulin degludec [IDeg]/insulin aspart [IAsp]), a soluble co-formulation of a long-acting basal insulin analogue (IDeg) and a rapid-acting insulin analogue (IAsp) in a single injection, in elderly and younger adult subjects with type 1 diabetes using a glucose clamp.

Methods: In this randomised, single-centre, double-blind, single-dose (SD), two-period, crossover trial, 15 elderly subjects (aged ≥ 65 years) and 13 younger adults (aged 18-35 years) with type 1 diabetes were randomly assigned to two SD administrations of 0.

Steady state is reached within 2-3 days of once-daily administration of degludec, a basal insulin with an ultralong duration of action.

Background: Various factors influence the pharmacokinetic and pharmacodynamic properties of insulin analogs. The aim of the present study was to determine time to steady state of insulin degludec (IDeg), a basal insulin analog with an ultralong duration of action, after once-daily subcutaneous administration in subjects of varying age, diabetes type, and ethnicity.

Methods: Time to steady state was analyzed in 195 subjects across five Phase I randomized single-center double-blind studies: three in subjects with type 1 diabetes (T1DM), including one in elderly subjects, and two in subjects with type 2 diabetes (T2DM), including one with African American and Hispanic/Latino subpopulations.

A feasibility study of a 3-day basal-bolus insulin delivery device in individuals with type 2 diabetes.

Objective: This study tested the feasibility of transition from multiple daily injections (MDI) to a 3-day, basal-bolus insulin delivery device (PaQ) for type 2 diabetes (T2D).

Research Design And Methods: Twenty MDI-treated individuals with T2D with HbA(1c) ≤9% (75 mmol/mol) were enrolled in a single-center, single-arm pilot study, lasting three 2-week periods: baseline (MDI), transition to PaQ, and PaQ therapy. Feasibility of use, glycemic control, safety, and patient satisfaction were assessed.

Insulin degludec is not associated with a delayed or diminished response to hypoglycaemia compared with insulin glargine in type 1 diabetes: a double-blind randomised crossover study.

Aims/hypothesis: Insulin degludec (Des(B30)LysB29(γ-Glu Nε-hexadecandioyl) human insulin; IDeg) is a new basal insulin with an ultra-long flat action profile. The acute physiological responses to hypoglycaemia with IDeg and insulin glargine (A21Gly,B31Arg,B32Arg human insulin; IGlar) were compared.

Methods: Twenty-eight adult type 1 diabetic patients with normal hypoglycaemia awareness (age = 41 ± 12 years, HbA1c = 7.

A comparison of the steady-state pharmacokinetic and pharmacodynamic profiles of 100 and 200 U/mL formulations of ultra-long-acting insulin degludec.

Background And Objective: Insulin degludec (IDeg) is a new-generation basal insulin that forms soluble multi-hexamers upon subcutaneous injection, resulting in a depot from which IDeg monomers are slowly and continuously absorbed to provide an ultra-long action profile. This double-blind, crossover, randomized study compared the pharmacokinetic and pharmacodynamic properties between IDeg 100 U/mL (U100) and IDeg 200 U/mL (U200) under steady-state (SS) conditions in subjects with type 1 diabetes mellitus.

Methods: Participants (n = 33 adults) underwent 8-day treatment periods with 0.

Enhanced absorption of insulin aspart as the result of a dispersed injection strategy tested in a randomized trial in type 1 diabetic patients.

Objective: We investigated the impact of two different injection strategies on the pharmacokinetics and pharmacodynamics of insulin aspart in vivo in an open-label, two-period crossover study and verified changes in the surface-to-volume ratio ex vivo.

Research Design And Methods: Before the clinical trial, insulin aspart was injected ex vivo into explanted human abdominal skin flaps. The surface-to-volume ratio of the subcutaneous insulin depot was assessed by microfocus computed tomography that compared 1 bolus of 18 IU with 9 dispersed boluses of 2 IU.

Periodic extraction of interstitial fluid from the site of subcutaneous insulin infusion for the measurement of glucose: a novel single-port technique for the treatment of type 1 diabetes patients.

Background: Treatment of type 1 diabetes patients could be simplified if the site of subcutaneous insulin infusion could also be used for the measurement of glucose. This study aimed to assess the agreement between blood glucose concentrations and glucose levels in the interstitial fluid (ISF) that is extracted from the insulin infusion site during periodic short-term interruptions of continuous subcutaneous insulin infusion (CSII).

Subjects And Methods: A perforated cannula (24 gauge) was inserted into subcutaneous adipose tissue of C-peptide-negative type 1 diabetes subjects (n=13) and used alternately to infuse rapid-acting insulin (100 U/mL) and to extract ISF glucose during a fasting period and after ingestion of a standard oral glucose load (75 g).

Development and validation of a low cost blood filtration element separating plasma from undiluted whole blood.

Clinical point of care testing often needs plasma instead of whole blood. As centrifugation is labor intensive and not always accessible, filtration is a more appropriate separation technique. The complexity of whole blood is such that there is still no commercially available filtration system capable of separating small sample volumes (10-100 μl) at the point of care.

Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling.

Background: Methodologies for continuous sampling of lipophilic drugs and high-molecular solutes in the dermis are currently lacking. We investigated the feasibility of sampling a lipophilic topical drug and the locally released biomarker in the dermis of non-lesional and lesional skin of psoriatic patients over 25h by means of membrane-free dermal open-flow microperfusion probes (dOFM) and novel wearable multi-channel pumps.

Methods: Nine psoriatic patients received a topical p-38 inhibitor (BCT194, 0.

A stepwise approach toward closed-loop blood glucose control for intensive care unit patients: results from a feasibility study in type 1 diabetic subjects using vascular microdialysis with infrared spectrometry and a model predictive control algorithm.

Background: Glycemic control can reduce the mortality and morbidity of intensive care patients. The CLINICIP (closed-loop insulin infusion for critically ill patients) project aimed to develop a closed-loop control system for this patient group. Following a stepwise approach, we combined three independently tested subparts to form a semiautomatic closed-loop system and evaluated it with respect to safety and performance aspects by testing it in subjects with type 1 diabetes mellitus (T1DM) in a first feasibility trial.

Hospital glucose control: safe and reliable glycemic control using enhanced model predictive control algorithm in medical intensive care unit patients.

Background: The aim of this study was to investigate the performance of the enhanced Model Predictive Control (eMPC) algorithm for glycemic control in medical critically ill patients for the whole length of intensive care unit (ICU) stay.

Methods: The trial was designed as a single-center, open, noncontrolled clinical investigation in a nine-bed medical ICU in a tertiary teaching hospital. In 20 patients, blood glucose (BG) was controlled with a laptop-based bedside version of the eMPC.

Interleukin-6 produced in subcutaneous adipose tissue is linked to blood pressure control in septic patients.

Cytokines are inflammatory mediators of major relevance during sepsis. Recent evidence shows that adipose tissue can produce many distinct cytokines under physiological and pathological conditions, but the role of cytokines produced in adipose tissue was not addressed in sepsis. In the present study the open-flow microperfusion (OFM) technique was used to investigate whether the cytokines produced in subcutaneous adipose tissue (SAT) of patients with severe sepsis correlate with clinical variables.

The effect of terbutaline on the absorption of pulmonary administered insulin in subjects with asthma.

Aim: To investigate the effect of prior administration of a bronchodilator on the absorption of inhaled insulin in people with asthma treated with inhaled corticosteroids.

Methods: A single-centre, randomized, open-label, two-period cross-over trial was carried out in 41 nondiabetic subjects with asthma treated with inhaled steroids, with reversible bronchoconstriction (Rev+; n= 25) or without reversible bronchoconstriction (Rev-; n= 16). A dose of 0.

Glucose levels at the site of subcutaneous insulin administration and their relationship to plasma levels.

Objective: To examine insulin's effect on the tissue glucose concentration at the site of subcutaneous insulin administration.

Research Design And Methods: A CMA-60 microdialysis (MD) catheter and a 24-gauge microperfusion (MP) catheter were inserted into the subcutaneous adipose tissue of fasting, healthy subjects (n = 5). Both catheters were perfused with regular human insulin (100 units/ml) over a 6-h period and used for glucose sampling and simultaneous administration of insulin at sequential rates of 0.

Use of the site of subcutaneous insulin administration for the measurement of glucose in patients with type 1 diabetes.

OBJECTIVE To simplify and improve the treatment of patients with type 1 diabetes, we ascertained whether the site of subcutaneous insulin infusion can be used for the measurement of glucose. RESEARCH DESIGN AND METHODS Three special indwelling catheters (24-gauge microperfusion [MP] catheters) were inserted into the subcutaneous adipose tissue of subjects with type 1 diabetes (n = 10; all C-peptide negative). One MP catheter was perfused with short-acting insulin (100 units/ml, Aspart) and used for insulin delivery and simultaneous glucose sampling during an overnight fast and after ingestion of a standard glucose load (75 g).

The effect of exercise on the absorption of inhaled human insulin in healthy volunteers.

What Is Already Known About This Subject: Exercise is known to affect absorption of other inhaled substances, but so far there are no reports on the effect of exercise on the absorption of inhaled insulin in humans.

What This Paper Adds: This report is the first to investigate the effect of exercise on the absorption of inhaled insulin. In this study in healthy volunteers we found that exercise early after dosing increased absorption (15-20%) of inhaled insulin over the first 2 h after start of exercise, with an approximately 30% increase in maximal insulin concentration, and unchanged overall absorption.

The effect of exercise on the absorption of inhaled human insulin via the AERx insulin diabetes management system in people with type 1 diabetes.

Objective: This study investigated the effect of moderate exercise on the absorption of inhaled insulin via the AERx insulin diabetes management system (iDMS).

Research Design And Methods: In this randomized, open-label, four-period, crossover, glucose clamp study 23 nonsmoking subjects with type 1 diabetes received a dose of 0.19 units/kg inhaled human insulin followed in random order by either 1) no exercise (NOEX group) or 30 min exercise starting, 2) 30 min after dosing (EX30), 3) 120 min after dosing (EX120), or 4) 240 min after dosing (EX240).