A systematic review and meta-analysis of the child-level effects of family-based interventions for the prevention of type 2 diabetes mellitus.

Aims: The purpose of this systematic review and meta-analysis was to investigate the effects of family-based health promotion interventions on child-level risk factors for type 2 diabetes in vulnerable families.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist for systematic reviews formed the methodological framework. CINAHL, Embase, MEDLINE, PsycINFO, and Web of Science were searched on January 12, 2024.

Molecular engineering of insulin for recombinant expression in yeast.

Since the first administration of insulin to a person with diabetes in 1922, scientific contributions from academia and industry have improved insulin therapy and access. The pharmaceutical need for insulin is now more than 40 tons annually, half of which is produced by recombinant secretory expression in Saccharomyces cerevisiae. We discuss how, in this yeast species, adaptation of insulin precursors by removable structural elements is pivotal for efficient secretory expression.

The role of weight control in the management of type 2 diabetes mellitus: Perspectives on semaglutide.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used to address multiple aspects of type 2 diabetes mellitus (T2DM) management, including glycaemic control, weight loss, and cardiovascular risk reduction. Semaglutide, a well-established GLP-1 RA approved for T2DM treatment and weight management, demonstrates marked efficacy in achieving these clinically important goals. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) consensus report emphasizes the importance of a holistic approach to T2DM treatment, with weight control as a key component for improving patient outcomes.

Glucagon-like peptide-1 receptor agonists to expand the healthy lifespan: Current and future potentials.

To help ensure an expanded healthy lifespan for as many people as possible worldwide, there is a need to prevent or manage a number of prevalent chronic diseases directly and indirectly closely related to aging, including diabetes and obesity. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have proven beneficial in type 2 diabetes, are amongst the few medicines approved for weight management, and are also licensed for focused cardiovascular risk reduction. In addition, strong evidence suggests several other beneficial effects of the pleiotropic peptide hormone, including anti-inflammation.

Derivatization with fatty acids in peptide and protein drug discovery.

Peptides and proteins are widely used to treat a range of medical conditions; however, they often have to be injected and their effects are short-lived. These shortcomings of the native structure can be addressed by molecular engineering, but this is a complex undertaking. A molecular engineering technology initially applied to insulin - and which has now been successfully applied to several biopharmaceuticals - entails the derivatization of peptides and proteins with fatty acids.

Insulin at 100: still central in protein-based therapy for chronic disease.

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.

Commemorating insulin's centennial: engineering insulin pharmacology towards physiology.

The life-saving discovery of insulin in Toronto in 1921 is one of the most impactful achievements in medical history, at the time being hailed as a miracle treatment for diabetes. The insulin molecule itself, however, is poorly amenable as a pharmacological intervention, and the formidable challenge of optimizing insulin therapy has been ongoing for a century. We review early academic insights into insulin structure and its relation to self-association and receptor binding, as well as recombinant biotechnology, which have all been seminal for drug design.

Pharmacology of insulin detemir.

Insulin detemir (Levemir [Novo Nordisk A/S, Bagsvaerd, Denmark]) is a soluble, long-acting basal insulin analog. It differs from human insulin in that the amino acid threonine in position B30 has been removed and a 14-carbon fatty acid (myristic acid) has been acylated to lysine at B29. This modification increases self-association and enables albumin binding of insulin detemir.

Insulin's 85th anniversary--An enduring medical miracle.

In 1922, the discovery of insulin led to a revolution in diabetes management. Since then, many improvements have been made to insulin preparations: early preparations of bovine and porcine insulins were purified and their duration of action prolonged, giving rise to the introduction of Neutral Protamine Hagedorn (NPH) insulin and monocomponent insulins. Then, with the advances in genetic engineering in the 1980s, it became possible to produce recombinant human insulin.

Insulin detemir: from concept to clinical experience.

Insulin detemir (Levemir, Novo Nordisk) is a novel, biologically engineered analogue of human insulin that has been successfully developed for clinical use in diabetes as a basal insulin. Its unique mechanism of prolongation of action, achieved through acylation to give reversible albumin binding and additional self-association, goes some way to addressing one of the fundamental limitations of previously available, subcutaneously administered basal insulins, a high level of within-person variability in time-action profile from one injection to another. The pharmacological profile of insulin detemir, characterised in a series of studies, suggested it had the potential to offer efficacy and tolerability advantages in the clinical setting.

The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin.

Purpose: Insulin detemir has been found in clinical trials to be absorbed with very low variability. A series of experiments were performed to elucidate the underlying mechanisms.

Methods: The disappearance from an injected subcutaneous depot and elimination studies in plasma were carried out in pigs.

Synthesis and in vitro characterization of 1-(4-aminofurazan-3-yl)-5-dialkylaminomethyl-1H-[1,2,3]triazole-4-carboxylic acid derivatives. A new class of selective GSK-3 inhibitors.

A novel class of GSK-3 inhibitors with favorable water solubility was identified in a HTS screen. SAR studies identified bioisosteric structural moieties in this class of compounds. The compounds were tested in a GSK-3 inhibition assay at 100 microM ATP giving IC(50)'s in the range from 0.

Insulin aspart: promising early results borne out in clinical practice.

The novel, rapid-acting insulin analogue insulin aspart (IAsp; Novo Nordisk) has been shown in preclinical studies to be more rapidly absorbed than human insulin (HI) when administered subcutaneously. IAsp reaches higher peak serum concentrations in a shorter time than HI, whilst maintaining a similar receptor binding and safety profile. The physiological pharmacokinetic profile of IAsp compared to that of HI has been demonstrated in both adult and paediatric populations and was accompanied by small but statistically significant reductions in HbA(1c), lower postprandial glucose excursions and a reduced risk of late postprandial and major nocturnal hypoglycaemia.