Comparative proximity biotinylation implicates the small GTPase RAB18 in sterol mobilization and biosynthesis.

Loss of functional RAB18 causes the autosomal recessive condition Warburg Micro syndrome. To better understand this disease, we used proximity biotinylation to generate an inventory of potential RAB18 effectors. A restricted set of 28 RAB18 interactions were dependent on the binary RAB3GAP1-RAB3GAP2 RAB18-guanine nucleotide exchange factor complex.

Sustained low-grade inflammation in young participants with childhood onset type 1 diabetes: The Norwegian atherosclerosis and childhood diabetes (ACD) study.

Background And Aims: Persons with type 1 diabetes (T1D) have increased mortality from cardiovascular disease. Early inflammation is important in the development of atherosclerosis. We aimed to evaluate the extent of inflammation and difference in mean over a five-year period in young persons with T1D compared to healthy controls.

Germline homozygous missense DEPDC5 variants cause severe refractory early-onset epilepsy, macrocephaly and bilateral polymicrogyria.

DEPDC5 (DEP Domain-Containing Protein 5) encodes an inhibitory component of the mammalian target of rapamycin (mTOR) pathway and is commonly implicated in sporadic and familial focal epilepsies, both non-lesional and in association with focal cortical dysplasia. Germline pathogenic variants are typically heterozygous and inactivating. We describe a novel phenotype caused by germline biallelic missense variants in DEPDC5.

Retinal venular oxygen saturation is associated with non-proliferative diabetic retinopathy in young patients with type 1 diabetes.

Purpose: To determine the contribution of retinal vessel density (VD), central retinal vessel diameter and retinal oxygen (O ) saturation independently of other known risk factors in the development of non-proliferative diabetic retinopathy (NPDR).

Methods: Macular optical coherence tomography angiography (OCTA), central retinal artery/vein equivalent diameter (CRAE/CRVE) measurements and retinal oximetry were performed in a cross-sectional study of 166 eyes from 166 individuals with type 1 diabetes (T1D) aged 14-30 years. Multiple logistic regression analysis was used to investigate whether O saturation, retinal vessel diameters and vessel density in the deep capillary plexus (VD-DCP) were associated with NPDR, when adjusting for known risk factors.

Children with familial hypercholesterolemia display changes in LDL and HDL function: A cross-sectional study.

Background: The functional status of lipoprotein particles contributes to atherogenesis. The tendency of plasma low-density lipoprotein (LDL) particles to aggregate and the ability of igh-density lipoprotein (HDL) particles to induce and mediate reverse cholesterol transport associate with high and low risk for cardiovascular disease in adult patients, respectively. However, it is unknown whether children with familial hypercholesterolemia (FH) display lipoprotein function alterations.

Associations between Macular OCT Angiography and Nonproliferative Diabetic Retinopathy in Young Patients with Type 1 Diabetes Mellitus.

Methods: OCTA of both eyes was performed in a cross-sectional study of 14 to 30-year-old individuals with at least 10-year duration of T1D and controls recruited from the Norwegian Atherosclerosis and Childhood Diabetes (ACD) study. Vessel density (VD) and foveal avascular zone (FAZ) area in the superficial and deep capillary plexus (SCP and DCP), total retinal volume (TRV), and central macular thickness (CMT) were calculated using automated software. Univariate and multivariate ordered logistic regression (OLR) models were used accordingly.

Venular oxygen saturation is increased in young patients with type 1 diabetes and mild nonproliferative diabetic retinopathy.

Purpose: To clarify how early in the development of diabetic retinopathy (DR) can oxygen (O ) saturation changes be detected.

Methods: Retinal oximetry was performed in a cross-sectional study, involving 14- to 30-year-old individuals: 185 with type 1 diabetes (T1D) and 94 controls. The subjects were divided into four groups according to the grade of DR.

Annexin V Microvesicles in Children and Adolescents with Type 1 Diabetes: A Prospective Cohort Study.

Background: Type 1 diabetes is a chronic disease including hyperglycemia and accelerated atherosclerosis, with high risk of micro- and macrovascular complications. Circulating microvesicles (cMVs) are procoagulant cell fragments shed during activation/apoptosis and discussed to be markers of vascular dysfunction and hypercoagulability. Limited knowledge exists on hypercoagulability in young diabetics.

Procoagulant activity in children and adolescents on intensive insulin therapy.

Background: Type 1 diabetes is associated with atherothrombosis, but limited data exist on procoagulant activity in the young. We investigated procoagulant activity in children/adolescents with type 1 diabetes using intensified insulin treatment compared with controls in a 5-year follow-up study, and further any associations with cardiovascular risk factors.

Methods: The study included 314 diabetes children/adolescents and 120 healthy controls.

Preserved endothelial function in young adults with type 1 diabetes.

Background And Aim: Endothelial dysfunction is involved in the pathogenesis of atherosclerosis and is typically present in older adults with type 1 diabetes (T1D). In young adults, we aimed to assess the impact of T1D on endothelial function as detected by digital peripheral arterial tonometry (PAT) and its relationship with cardiovascular risk factors and long term glycemic control.

Materials And Methods: Reactive hyperemia index (RHI) as a measure of endothelial function was assessed by PAT in 46 T1D patients and 32 healthy controls.

High-density lipoprotein function is associated with atherosclerotic burden and cardiovascular outcomes in type 2 diabetes.

Background And Aims: Measures of HDL function are emerging tools for assessing cardiovascular disease (CVD) event risk. HDL-apoA-I exchange (HAE) reflects HDL capacity for reverse cholesterol transport.

Methods: HAE was measured in 93 participants with type 2 diabetes (T2D) and at least one additional CVD risk factor in the Asker and Bærum Cardiovascular Diabetes study.

Increased arterial stiffness in childhood onset diabetes: a cardiovascular magnetic resonance study.

Aims: Arterial stiffness is a strong predictor of cardiovascular events. We aimed to assess the impact of type 1 diabetes (T1D) on arterial stiffness and cardiac function in young adults.

Methods And Results: Aortic pulse wave velocity (PWV), distensibility, left ventricular (LV) function and LV mass were measured by cardiovascular magnetic resonance imaging (CMR) in 47 T1D patients and 33 healthy controls.

Reduced HDL function in children and young adults with type 1 diabetes.

Background: Patients with type 1 diabetes (T1D) are at increased risk of cardiovascular disease (CVD). Measures of high-density lipoprotein (HDL) function provide a better risk estimate for future CVD events than serum levels of HDL cholesterol. The objective of this study was to evaluate HDL function in T1D patients shortly after disease onset compared with healthy control subjects.

Advanced glycation end products in children with type 1 diabetes and early reduced diastolic heart function.

Background: Reduced diastolic function is an early sign of diabetes cardiomyopathy in adults and is associated with elevated levels of HbA1c and advanced glycation end products (AGEs).

Objective: To assess the associations between early reduced diastolic function and elevated levels of HbA1c and AGEs in children and adolescents with type 1 diabetes (T1D).

Methods: One hundred fourty six T1D patients (age 8-18 years) without known diabetic complications were examined with tissue Doppler imaging and stratified into two groups according to diastolic function.

Soluble RAGE and atherosclerosis in youth with type 1 diabetes: a 5-year follow-up study.

Background: Advanced glycation end products (AGEs) play a role in the development of late complications and atherosclerosis in diabetes by engaging the receptor for advanced glycation end products, RAGE. Receptor binding leads to activation of the vascular endothelium and increased inflammation in the vessel wall. The soluble variants of the receptor, endogenous secretory RAGE (esRAGE) and the cleaved cell-surface part of RAGE, which together comprise soluble RAGE (sRAGE), are suggested to have a protective effect acting as decoys for RAGE.

The advanced glycation end product methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in childhood diabetes.

Background: Advanced protein glycation is an important mechanism for the development of late diabetic complications including atherosclerosis. Methylglyoxal-derived hydroimidazolone-1 is the most abundant advanced glycation end product in human plasma.

Aim: To investigate the relationship between methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in children and adolescents with type 1 diabetes and healthy controls.

Inflammation in childhood type 1 diabetes; influence of glycemic control.

Objective: Patients with type 1 diabetes have increased mortality from cardiovascular disease, and inflammation is important in the development of atherosclerosis. Our aim was to evaluate the extent of inflammation and the influence of glycemic control in the early phases of atherosclerosis in childhood type 1 diabetes.

Materials And Methods: A population based cohort representative of all children with type 1 diabetes in Norway was studied.