Salivary proteomics and metaproteomics identifies distinct molecular and taxonomic signatures of type-2 diabetes.

Background: Saliva is a protein-rich body fluid for noninvasive discovery of biomolecules, containing both human and microbial components, associated with various chronic diseases. Type-2 diabetes (T2D) imposes a significant health and socio-economic burden. Prior research on T2D salivary microbiome utilized methods such as metagenomics, metatranscriptomics, 16S rRNA sequencing, and low-throughput proteomics.

A genetic exploration of the relationship between posttraumatic stress disorder and cardiovascular diseases.

Experiencing a traumatic event may lead to Posttraumatic Stress Disorder (PTSD), including symptoms such as flashbacks and hyperarousal. Individuals suffering from PTSD are at increased risk of cardiovascular disease (CVD), but it is unclear why. This study assesses shared genetic liability and potential causal pathways between PTSD and CVD.

Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes.

Introduction: Diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality.

Research Design And Methods: In adults with type 1 diabetes, 49 metabolites previously associated with either DR or DKD were assessed in relation to presence of DSPN. Metabolites overlapping in significance with presence of all three complications were assessed in relation to microvascular burden severity (additive number of complications-ie, presence of DKD±DR±DSPN) using linear regression models.

Randomized Trial of SGLT2 Inhibitor Identifies Target Proteins in Diabetic Kidney Disease.

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as novel therapeutics to treat diabetic kidney disease (DKD). Although the beneficial effects of SGLT2i have been demonstrated, their target mechanisms on kidney function are unknown. The current study aimed to elucidate these mechanisms by studying SGLT2i-induced changes in the urinary proteome of persons with type 2 diabetes (T2D) and DKD.

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel).

Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis.

Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n ~ 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance.

Dissecting the causal association between inflammation and post-traumatic stress disorder: A bidirectional Mendelian randomization study.

Background: Accumulating evidence showed a bidirectional association between post-traumatic stress disorder and inflammation. However, whether the association is causal remains unclear. We aimed to evaluate the causal relationships between inflammatory cytokines and post-traumatic stress disorder using two-sample bi-directional Mendelian randomization analysis.

Circulating Metabolomic and Lipidomic Signatures Identify a Type 2 Diabetes Risk Profile in Low-Birth-Weight Men with Non-Alcoholic Fatty Liver Disease.

The extent to which increased liver fat content influences differences in circulating metabolites and/or lipids between low-birth-weight (LBW) individuals, at increased risk of type 2 diabetes (T2D), and normal-birth-weight (NBW) controls is unknown. The objective of the study was to perform untargeted serum metabolomics and lipidomics analyses in 26 healthy, non-obese early-middle-aged LBW men, including five men with screen-detected and previously unrecognized non-alcoholic fatty liver disease (NAFLD), compared with 22 age- and BMI-matched NBW men (controls). While four metabolites (out of 65) and fifteen lipids (out of 279) differentiated the 26 LBW men from the 22 NBW controls ( ≤ 0.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.

Multiomics signatures of type 1 diabetes with and without albuminuria.

Aims/hypothesis: To identify novel pathophysiological signatures of longstanding type 1 diabetes (T1D) with and without albuminuria we investigated the gut microbiome and blood metabolome in individuals with T1D and healthy controls (HC). We also mapped the functional underpinnings of the microbiome in relation to its metabolic role.

Methods: One hundred and sixty-one individuals with T1D and 50 HC were recruited at the Steno Diabetes Center Copenhagen, Denmark.

Dapagliflozin Improves the Urinary Proteomic Kidney-Risk Classifier CKD273 in Type 2 Diabetes with Albuminuria: A Randomized Clinical Trial.

Objective: To evaluate the effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on the kidney-risk urinary proteomic classifier (CKD273) in persons with type 2 diabetes (T2D) and albuminuria.

Research Design And Methods: In a double-blind, randomized, controlled, crossover trial, we assigned participants with T2D and urinary albumin to creatinine ratio (UACR) ≥30 mg/g to receive dapagliflozin or matching placebo added to guideline-recommended treatment (ClinicalTrial.gov identifier NCT02914691).

A genome-wide association study of total child psychiatric problems scores.

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium.

Non-dipping and higher nocturnal blood pressure are associated with risk of mortality and development of kidney disease in type 1 diabetes.

Aims: People with type 1 diabetes have increased risk of cardiovascular (CV) and kidney disease. A 24-hour ambulatory blood pressure (BP) measurement (ABPM) examines diurnal variations in BP. We aimed to determine the prognostic significance of blunted decrease in nocturnal systolic BP of <10 % (non-dipping of nocturnal BP) for CV- and kidney disease and all-cause mortality in type 1 diabetes.