100 Jahre Insulin - Segen, aber nicht immer
Ontology highlight
ABSTRACT:
SUBMITTER: Martin S
PROVIDER: S-EPMC8210963 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Insulin glargine is processed in vivo into soluble 21(A) -Gly-human insulin (M1), the principal moiety responsible for metabolic effects, and subsequently into M2. This sub-study compared metabolism and metabolite pharmacokinetic (PK) profiles of investigational new insulin glargine U300 (Gla-300) with insulin glargine 100 U/ml (Gla-100, Lantus®, Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany) in people with type 1 diabetes. Participants received 0.4 (n = 18) or 0.6 U/kg Gla-300 (n = 12), and 0.4 U/kg Gla-100 (n = 30) once daily in randomized order for 8 days prior to a 36-h euglycaemic clamp. Metabolites were quantified using immunoaffinity enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS). Glargine metabolism was the same regardless of Gla-100 or Gla-300 administration; M1 was confirmed as the principal active moiety circulating in blood. Steady state concentrations of M1 were achieved after 2 days for Gla-100, and 4 days for Gla-300. Steady state M1 values defined prolonged and even flatter PK profiles after Gla-300 administration compared with M1 profiles after Gla-100.
| S-EPMC4237557 | biostudies-literature
Project description:The discovery of insulin has inspired several pivotal medical and scientific developments during the past 100 years. Here, we describe how insulin as a model protein will drive future advances in peptide- and protein-based therapies for chronic diseases.
| S-EPMC9053185 | biostudies-literature
Project description:In this review, we bring our personal experiences to showcase insulin from its breakthrough discovery as a life-saving drug 100 years ago to its uncovering as the autoantigen and potential cause of type 1 diabetes and eventually as an opportunity to prevent autoimmune diabetes. The work covers the birth of insulin to treat patients, which is now 100 years ago, the development of human insulin, insulin analogues, devices, and the way into automated insulin delivery, the realization that insulin is the primary autoimmune target of type 1 diabetes in children, novel approaches of immunotherapy using insulin for immune tolerance induction, the possible limitations of insulin immunotherapy, and an outlook how modern vaccines could remove the need for another 100 years of insulin therapy.
| S-EPMC8730368 | biostudies-literature
Project description:AimsA post-hoc analysis to assess the impact in people with type 2 diabetes, of increasing doses of basal insulin on glycaemic measures, body weight and hypoglycaemia.Research design and methodsWe included data from prospective, randomized controlled treat-to-target trials of ≥24 weeks' duration in people with type 2 diabetes, uncontrolled on metformin and sulphonylureas, and treated with insulin glargine 100 units/mL (U100), who had at least six fasting plasma glucose (FPG) measurements. The impact of insulin dose on glycated haemoglobin (HbA1c) values, FPG, hypoglycaemia incidence (<3.9 mmol/L [70 mg/dL]), and body weight was analysed. A total of 458 participants from three eligible trials were included.ResultsThe observed relationship between higher basal insulin doses and glycaemic control was non-linear, with increasing insulin dose leading to smaller reductions in FPG and HbA1c for doses >0.3 IU/kg/d, with a plateauing effect at 0.5 IU/kg/d. Total daily dose of insulin >0.5 IU/kg/d resulted in greater weight gain, but without higher rates of hypoglycaemia, compared with insulin doses ≤0.5 IU/kg/d.ConclusionsThis analysis indicates that basal insulin doses >0.5 IU/kg/d have diminishing additional impact on improving glycaemic measures, with the disadvantage of additional weight gain. Clinicians should consider anti-hyperglycaemic treatment intensification at doses approaching 0.5 IU/kg/d.
| S-EPMC6594069 | biostudies-literature
Project description:Insulin lispro 200 U/mL (IL200) is a new strength formulation of insulin lispro (Humalog®, IL100), developed as an option for diabetic patients on higher daily mealtime insulin doses. This phase 1, open-label, 2-sequence, 4-period crossover, randomized, 8-hour euglycemic clamp study aimed to demonstrate the bioequivalence of IL200 and IL100 after subcutaneous administration of 20 U (U) to healthy subjects (n = 38). Pharmacokinetic (PK) and pharmacodynamic (PD) responses were similar in both formulations. All 90%CIs for the ratios of area under the concentration-versus-time curve from time zero to the time of the last measurable concentration (AUC0-tlast) and maximum observed drug concentration (Cmax), as well as the total glucose infused throughout the clamp (Gtot) and the maximum glucose infusion rate (Rmax), were contained within 0.80 and 1.25. Time of maximum observed drug concentration (tmax) was similar between formulations, with a median difference of 15 minutes and a 95%CI of the difference that included zero. Inter- and intrasubject variability estimates were similar for both formulations. Both formulations were well tolerated. IL200 was bioequivalent to IL100 after subcutaneous administration of 20-U single doses, and PD responses were comparable between formulation strengths.
| S-EPMC5054907 | biostudies-literature
Project description:Type 1 diabetes (T1D) is an autoimmune disease characterised by T cell-mediated destruction of the insulin-producing β cells in the pancreas. Similar to other autoimmune diseases, the incidence of T1D is increasing globally. The discovery of insulin 100 years ago dramatically changed the outlook for people with T1D, preventing this from being a fatal condition. As we celebrate the centenary of this milestone, therapeutic options for T1D are once more at a turning point. Years of effort directed at developing immunotherapies are finally starting to pay off, with signs of progress in new onset and even preventative settings. Here, we review a selection of immunotherapies that have shown promise in preserving β cell function and highlight future considerations for immunotherapy in the T1D setting.
| S-EPMC8826223 | biostudies-literature
Project description:Metagenomic diversity of soil co-contaminated with lead and amended with microbes and root exudates
| PRJNA769188 | ENA
Project description:Metagenomic diversity of soil co-contaminated with lead and amended with microbes and root exudates
| PRJNA769555 | ENA
Project description:AimTreat-to-target, randomized controlled trials have confirmed lower rates of hypoglycaemia at equivalent glycaemic control with insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in patients with type 1 (T1D) or type 2 diabetes (T2D). Treat-to-target trials are designed to enable comparisons of safety and tolerability at a similar HbA1c level. In this post hoc analysis of the SWITCH 1 and 2 trials, we utilised a patient-level modelling approach to compare how glycaemic control might differ between basal insulins at a similar rate of hypoglycaemia.Materials and methodsData for HbA1c and symptomatic hypoglycaemia from the SWITCH 1 and SWITCH 2 trials were analyzed separately for patients with type 1 diabetes and type 2 diabetes, respectively. The association between the individual patient-level risk of hypoglycaemia and HbA1c was investigated using a Poisson regression model and used to estimate potential differences in glycaemic control with degludec versus glargine U100, at the same rate of hypoglycaemia.ResultsImprovements in glycaemic control increased the incidence of hypoglycaemia with both basal insulins across diabetes types. Our analysis suggests that patients could achieve a mean HbA1c reduction of 0.70 [0.05; 2.20]95% CI (for type 1 diabetes) or 0.96 [0.39; 1.99]95% CI (for type 2 diabetes) percentage points (8 [1; 24]95% CI or 10 [4; 22]95% CI mmol/mol, respectively) further with degludec than with glargine U100 before incurring an equivalent risk of hypoglycaemia.ConclusionOur findings suggest that patients in clinical practice may be able to achieve lower glycaemia targets with degludec versus glargine U100, before incurring an equivalent risk of hypoglycaemia.
| S-EPMC7186831 | biostudies-literature
Project description:ObjectiveHuman regular U-500 (U-500R) insulin (500 units/mL) is increasingly being used clinically, yet its pharmacokinetics (PK) and pharmacodynamics (PD) have not been well studied. Therefore, we compared PK and PD of clinically relevant doses of U-500R with the same doses of human regular U-100 (U-100R) insulin (100 units/mL).Research design and methodsThis was a single-site, randomized, double-blind, crossover euglycemic clamp study. Single subcutaneous injections of 50- and 100-unit doses of U-500R and U-100R were administered to 24 healthy obese subjects.ResultsBoth overall insulin exposure (area under the serum insulin concentration versus time curve from zero to return to baseline [AUC(0-)(t)(')]) and overall effect (total glucose infused during a clamp) were similar between formulations at both 50- and 100-unit doses (90% [CI] of ratios contained within [0.80, 1.25]). However, peak concentration and effect were significantly lower for U-500R at both doses (P < 0.05). Both formulations produced relatively long durations of action (18.3 to 21.5 h). Time-to-peak concentration and time to maximum effect were significantly longer for U-500R than U-100R at the 100-unit dose (P < 0.05). Time variables reflective of duration of action (late tR(max50), tR(last)) were prolonged for U-500R versus U-100R at both doses (P < 0.05).ConclusionsOverall exposure to and action of U-500R insulin after subcutaneous injection were no different from those of U-100R insulin. For U-500R, peaks of concentration and action profiles were blunted and the effect after the peak was prolonged. These findings may help guide therapy with U-500R insulin for highly insulin-resistant patients with diabetes.
| S-EPMC3220843 | biostudies-literature