In or out of reach? Long-term trends in the reach of health assessments in the Swedish occupational setting.

Objectives: This study aimed to investigate the reach of a large-scale health assessment delivered by the occupational health service in Sweden for almost 30 years.

Methods: A total of 418 286 individuals who participated in a health assessment (Health Profile Assessment, HPA) between 1995-2021 were included. A comparative sample was obtained from Statistics Sweden, comprising the entire working population for each year (4 962 127-6 011 829 unique individuals per time period).

Phase III, randomised, double-blind, placebo-controlled, multicentre trial to evaluate the efficacy and safety of rhGAD65 to preserve endogenous beta cell function in adolescents and adults with recently diagnosed type 1 diabetes, carrying the genetic HLA DR3-DQ2 haplotype: the DIAGNODE-3 study protocol.

Introduction: Type 1 diabetes (T1D) is an autoimmune disease leading to the destruction of the insulin-producing beta cells resulting in insulin deficiency and hyperglycaemic. Today, no approved therapy exists to halt this detrimental immunologic process. In a recent phase 2b study, intralymphatic administration of recombinant human glutamic acid decarboxylase 65 kDa (rhGAD65) adsorbed to Alhydrogel adjuvant to individuals recently diagnosed with T1D and carrying the HLA DR3-DQ2 haplotype showed promising results in preserving endogenous insulin secretion, confirming the results of a large meta-analysis of three randomised placebo-controlled trials of subcutaneous rhGAD65.

Dipeptidyl peptidase-4 is increased in the abdominal aortic aneurysm vessel wall and is associated with aneurysm disease processes.

Background: Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease, and until today there is no other treatment available than surgical intervention. Dipeptidyl peptidase-4 (DPP4)-inhibitors, used clinically to treat type 2 diabetes, have in murine models been shown to attenuate aneurysm formation and decrease aortic wall matrix degradation, inflammation and apoptosis. Our aim was to investigate if DPP4 is present, active and differentially expressed in human AAA.

Dual roles of heparanase in human carotid plaque calcification.

Background And Aims: Calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-β-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of HPSE is controversial in osteogenesis and bone remodeling while it is unexplored in vascular calcification.

Noninvasive in vivo Assessment of the Re-endothelialization Process Using Ultrasound Biomicroscopy in the Rat Carotid Artery Balloon Injury Model.

Objectives: Ultrasound biomicroscopy (UBM), or ultra high-frequency ultrasound, is a technique used to assess the anatomy of small research animals. In this study, UBM was used to assess differences in intimal hyperplasia thickness as a surrogate measurement of the re-endothelialization process after carotid artery balloon injury in rats.

Methods: Ultrasound biomicroscopic data from 3 different experiments and rat strains (Sprague Dawley, Wistar, and diabetic Goto-Kakizaki) were analyzed.

Effects of Linagliptin on Vessel Wall Healing in the Rat Model of Arterial Injury Under Normal and Diabetic Conditions.

Diabetic patients suffer an increased risk of restenosis and late stent thrombosis after angioplasty, complications which are related to a defective reendothelialization. Dipeptidyl peptidase-4 inhibitors have been suggested to exert a direct effect on endothelial and smooth muscle cells (SMCs). Therefore, the objective was to study if the dipeptidyl peptidase-4 inhibitor linagliptin could influence vascular repair and accelerate reendothelialization after arterial injury in healthy and diabetic animals.

Glucagon-Like Peptide-1 Receptor Activation Does not Affect Re-Endothelialization but Reduces Intimal Hyperplasia via Direct Effects on Smooth Muscle Cells in a Nondiabetic Model of Arterial Injury.

Unlabelled: Diabetic patients have an increased risk of restenosis and late stent thrombosis after angioplasty, i.e. complications that are related to a defective re-endothelialization.

Perlecan heparan sulfate deficiency impairs pulmonary vascular development and attenuates hypoxic pulmonary hypertension.

Aims: Excessive vascular cell proliferation is an important component of pulmonary hypertension (PH). Perlecan is the major heparan sulfate (HS) proteoglycan in the vascular extracellular matrix. It binds growth factors, including FGF2, and either restricts or promotes cell proliferation.

Antidiabetic agents and endothelial dysfunction - beyond glucose control.

Diabetes is rapidly increasing worldwide, and the number of patients suffering from diabetes is projected to rise by 50% over the next 25 years, then affecting almost 600 million adults. Type 2 diabetes comprises 90-95% of all people with diabetes, and they constitute a patient group that carries a high burden of cardiovascular disease. The relationship between hyperglycaemia and macrovascular complications is still uncertain, at least in terms of the possibility of reducing cardiovascular events solely by improving glycaemic control.

Activation of AMP-activated protein kinase by metformin protects human coronary artery endothelial cells against diabetic lipoapoptosis.

Background: The prevalence of type 2 diabetes (T2D) among adults worldwide is rapidly increasing, and in patients with diabetes the major cause of death is macrovascular disease. Endothelial cells play an important role in maintaining vascular homeostasis. Free fatty acids, which are elevated in T2D, have previously been shown to induce endothelial dysfunction and apoptosis of endothelial cells, which is considered as an important and early factor in the onset of atherosclerosis and cardiovascular disease.

Exendin-4 protects endothelial cells from lipoapoptosis by PKA, PI3K, eNOS, p38 MAPK, and JNK pathways.

Experimental studies have indicated that endothelial cells play an important role in maintaining vascular homeostasis. We previously reported that human coronary artery endothelial cells (HCAECs) express the glucagon-like peptide 1 (GLP1) receptor and that the stable GLP1 mimetic exendin-4 is able to activate the receptor, leading to increased cell proliferation. Here, we have studied the effect of exendin-4 and native GLP1 (7-36) on lipoapoptosis and its underlying mechanisms in HCAECs.

Effects of some anti-diabetic and cardioprotective agents on proliferation and apoptosis of human coronary artery endothelial cells.

Background: The leading cause of death for patients suffering from diabetes is macrovascular disease. Endothelial dysfunction is often observed in type 2 diabetic patients and it is considered to be an important early event in the pathogenesis of atherogenesis and cardiovascular disease. Many drugs are clinically applied to treat diabetic patients.

Exendin-4 restores glucolipotoxicity-induced gene expression in human coronary artery endothelial cells.

Exendin-4, a stable GLP-1 receptor agonist, has been shown to stimulate insulin secretion. It has also been shown to exert beneficial effects on endothelial function that are independent of its glycemic effects. The molecular mechanisms underlying the protective actions of exendin-4 against diabetic glucolipotoxicity in endothelial cells largely remain elusive.