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.

Ceramides as Risk Markers for Future Cardiovascular Events and All-Cause Mortality in Long-standing Type 1 Diabetes.

Unlabelled: Ceramides are lipid molecules involved in inflammation-related signaling. Recent studies have shown that higher amounts of specific circulating ceramides and their ratios are associated with future development of cardiovascular (CV) disease (CVD). We examined the associations between serum ceramide levels with CVD, kidney failure, and all-cause mortality in individuals with long-standing type 1 diabetes (T1D).

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.

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.

Circulating metabolites and molecular lipid species are associated with future cardiovascular morbidity and mortality in type 1 diabetes.

Background: Cardiovascular disease remains the leading cause of mortality in individuals with diabetes and improved understanding of its pathophysiology is needed. We investigated the association of a large panel of metabolites and molecular lipid species with future cardiovascular events in type 1 diabetes.

Methods: The study included 669 individuals with type 1 diabetes.

Cardiovascular autonomic neuropathy and the impact on progression of diabetic kidney disease in type 1 diabetes.

Introduction: We investigated the association between cardiovascular autonomic neuropathy (CAN) and decline in kidney function in type 1 diabetes.

Research Design And Methods: We included 329 persons with type 1 diabetes. CAN was assessed by cardiovascular reflex tests (CARTs): heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva maneuvre.

Endothelial glycocalyx and cardio-renal risk factors in type 1 diabetes.

Background: Glycocalyx lines the inner surface of the capillary endothelium. Capillaroscopy enables visualization of the sublingual capillaries and measurement of the Perfused Boundary Region (PBR) as an estimate of the glycocalyx. Novel software enables assessment of the PBR estimated at a fixed high flow level (PBR-hf) and an overall microvascular assessment by the MicroVascular Health Score (MVHS).

Faecal biomarkers in type 1 diabetes with and without diabetic nephropathy.

Gastrointestinal dysbiosis is common among persons with type 1 diabetes (T1D), but its potential impact on diabetic nephropathy (DN) remains obscure. We examined whether faecal biomarkers, previously associated with low-grade gastrointestinal inflammation, differ between healthy controls and T1D subjects with and without DN. Faecal samples were analyzed for levels of calprotectin, intestinal alkaline phosphatase (IAP), short-chain fatty acids (SCFA) and immunoglobulins in subjects with T1D (n = 159) and healthy controls (NDC; n = 50).

Plasma trimethylamine N-oxide and its metabolic precursors and risk of mortality, cardiovascular and renal disease in individuals with type 2-diabetes and albuminuria.

Aims: The trimethylamine N-oxide (TMAO) pathway is related to intestinal microbiota and has been associated to risk of cardiovascular disease (CVD). We investigated associations between four plasma metabolites in the TMAO pathway and risk of all-cause mortality, CVD and deterioration in renal function in individuals with type 2-diabetes (T2D) and albuminuria.

Materials And Methods: Plasma concentrations of TMAO, choline, carnitine, and betaine were measured by liquid chromatography-tandem mass spectrometry at baseline in 311 individuals with T2D and albuminuria.

Copeptin and renal function decline, cardiovascular events and mortality in type 1 diabetes.

Background: Plasma copeptin is a surrogate of arginine vasopressin (AVP) secretion and is associated with a risk of renal and cardiovascular disease. We investigated associations between copeptin and renal events, cardiovascular events and mortality in type 1 diabetes (T1D).

Methods: We conducted a prospective cohort study on 658 individuals with T1D from Steno Diabetes Center Copenhagen.

Assessment of the sublingual microcirculation with the GlycoCheck system: Reproducibility and examination conditions.

Background: The glycocalyx is an extracellular layer lining the lumen of the vascular endothelium, protecting the endothelium from shear stress and atherosclerosis and contributes to coagulation, immune response and microvascular perfusion. The GlycoCheck system estimates glycocalyx' thickness in vessels under the tongue from perfused boundary region (PBR) and microvascular perfusion (red blood cell (RBC) filling) via a camera and dedicated software.

Objectives: Evaluating reproducibility and influence of examination conditions on measurements with the GlycoCheck system.

Comparison of Natriuretic Peptides as Risk Markers for All-Cause Mortality and Cardiovascular and Renal Complications in Individuals With Type 1 Diabetes.

Objective: Few studies have compared midregional proatrial natriuretic peptide (MR-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP). We compared their value as risk markers for all-cause mortality and cardiovascular (CV) and renal complications in individuals with type 1 diabetes.

Research Design And Methods: MR-proANP and NT-proBNP were measured in 664 individuals.

Visit-to-visit variability of clinical risk markers in relation to long-term complications in type 1 diabetes.

Background: Clinical characteristics such as HbA , systolic blood pressure (SBP), albuminuria and estimated glomerular filtration rate (eGFR) are important when treating type 1 diabetes. We investigated the variability in these measures as risk markers for micro- and macrovascular complications.

Methods: This prospective study included 1062 individuals with type 1 diabetes.

Carotid-Femoral Pulse Wave Velocity as a Risk Marker for Development of Complications in Type 1 Diabetes Mellitus.

Background The value of carotid-femoral pulse wave velocity (cfPWV) as risk factor for development of complications in type 1 diabetes mellitus remains to be determined. We investigated associations between cfPWV and renal outcomes, cardiovascular events, and all-cause mortality in people with type 1 diabetes mellitus. Methods and Results cfPWV was measured with SphygmoCor in 633 people with type 1 diabetes mellitus.

Gut microbiota profile and selected plasma metabolites in type 1 diabetes without and with stratification by albuminuria.

Aims/hypothesis: Abnormal gut microbiota and blood metabolome profiles have been reported both in children and adults with uncomplicated type 1 diabetes as well as in adults with type 1 diabetes and advanced stages of diabetic nephropathy. In this study we aimed to investigate the gut microbiota and a panel of targeted plasma metabolites in individuals with type 1 diabetes of long duration without and with different levels of albuminuria.

Methods: In a cross-sectional study we included 161 individuals with type 1 diabetes and 50 healthy control individuals.

Relation of cardiac adipose tissue to coronary calcification and myocardial microvascular function in type 1 and type 2 diabetes.

Background: Cardiac adipose tissue may have local paracrine effects on epicardial arteries and the underlying myocardium, promoting calcification and affecting myocardial microcirculation. We explored whether the total amount of cardiac adipose tissue was associated with coronary artery calcium score (CAC) and myocardial flow reserve in persons with type 1 or type 2 diabetes and healthy controls.

Methods: We studied three groups: (1) 30 controls, (2) 60 persons with type 1 diabetes and (3) 60 persons with type 2 diabetes.

Metabolomic Assessment Reveals Alteration in Polyols and Branched Chain Amino Acids Associated With Present and Future Renal Impairment in a Discovery Cohort of 637 Persons With Type 1 Diabetes.

Improved understanding of the pathophysiology causing diabetic kidney disease (DKD) is imperative. The aim of this study was to uncover associations between serum metabolites and renal outcomes. Non-targeted serum metabolomics analyses were performed in samples from 637 persons with type 1 diabetes using two-dimensional gas chromatography coupled to time-of-flight mass-spectrometry.

Lipidomic analysis reveals sphingomyelin and phosphatidylcholine species associated with renal impairment and all-cause mortality in type 1 diabetes.

There is an urgent need for a better molecular understanding of the pathophysiology underlying development and progression of diabetic nephropathy. The aim of the current study was to identify novel associations between serum lipidomics and diabetic nephropathy. Non-targeted serum lipidomic analyses were performed with mass spectrometry in 669 individuals with type 1 diabetes.

Markers of Collagen Formation and Degradation Reflect Renal Function and Predict Adverse Outcomes in Patients With Type 1 Diabetes.

Objective: Patients with type 1 diabetes (T1D) have a higher risk of developing chronic kidney disease, cardiovascular events (CVEs), and mortality than the general population. We hypothesized that two previously published biomarkers, namely PRO-C6, a biomarker of collagen type VI formation, and C3M, a biomarker of collagen type III degradation, may be associated with impaired renal function and have prognostic value for adverse renal, CVE, and mortality in patients with T1D.

Research Design And Methods: PRO-C6 and C3M in serum (sPRO-C6, sC3M) and urine (uPRO-C6, uC3M) were measured by ELISA in 663 patients with T1D ranging from normoalbuminuric to macroalbuminuric.

Utility of Plasma Concentration of Trimethylamine N-Oxide in Predicting Cardiovascular and Renal Complications in Individuals With Type 1 Diabetes.

Objective: Trimethylamine N-oxide (TMAO) is suggested as an independent gut microbiota-derived risk factor for cardiovascular and renal disease. We investigated associations between plasma TMAO concentrations and cardio-renal outcomes in a prospective study of individuals with type 1 diabetes.

Research Design And Methods: Plasma TMAO was measured at baseline in 1,159 individuals with type 1 diabetes (58% male, mean ± SD age 46 ± 13 years).

Soluble Urokinase Plasminogen Activator Receptor Predicts Cardiovascular Events, Kidney Function Decline, and Mortality in Patients With Type 1 Diabetes.

Objective: Soluble urokinase plasminogen activator receptor (suPAR) is an important inflammatory biomarker implicated in endothelial and podocyte dysfunction. However, suPAR's predictive qualities for complications in type 1 diabetes have yet to be determined. We investigated the prognostic value of suPAR for the development of cardiovascular events, decline in renal function, and mortality in patients with type 1 diabetes.

Uric Acid Is an Independent Risk Factor for Decline in Kidney Function, Cardiovascular Events, and Mortality in Patients With Type 1 Diabetes.

Objective: Previous studies have provided inconclusive results on the role of uric acid (UA) in risk prediction. Here we aimed to improve the power and precision of the predictive value of UA for the risk of decline in kidney function, cardiovascular events (CVEs), and mortality in patients with type 1 diabetes (T1D).

Research Design And Methods: Plasma UA was measured in 670 patients with T1D and various degrees of albuminuria, ranging from normoalbuminuria to macroalbuminuria.

Cardiac Autonomic Function Is Associated With Myocardial Flow Reserve in Type 1 Diabetes.

The link between cardiac autonomic neuropathy and risk of cardiovascular disease is highlighted as an area in which research is needed. This study was undertaken to evaluate the association between measures of cardiac autonomic function and cardiac vascular function in type 1 diabetes using new and sensitive methods. This was a cross-sectional study in patients with type 1 diabetes, stratified by normoalbuminuria ( = 30) and macroalbuminuria ( = 30), and in healthy control subjects ( = 30).

Myocardial flow reserve assessed by cardiac 82Rb positron emission tomography/computed tomography is associated with albumin excretion in patients with Type 1 diabetes.

Aims: To evaluate myocardial flow reserve (MFR) and coronary artery calcium (CAC) in persons with Type 1 diabetes with or without albuminuria and in non-diabetic controls. MFR reflects the function of large epicardial arteries and myocardial microcirculation. CAC represents structural aspects of atherosclerosis.