Identification of possible adverse drug reactions in clinical notes: The case of glucose-lowering medicines.

Objective: Through manual review of clinical notes for patients with type 2 diabetes mellitus attending a Danish diabetes center, the aim of the study was to identify adverse drug reactions (ADRs) associated with three classes of glucose-lowering medicines: "Combinations of oral blood-glucose lowering medicines" (A10BD), "dipeptidyl peptidase-4 (DDP-4) inhibitors" (A10BH), and "other blood glucose lowering medicines" (A10BX). Specifically, we aimed to describe the potential of clinical notes to identify new ADRs and to evaluate if sufficient information can be obtained for causality assessment.

Methods: For observed adverse events (AEs) we extracted time to onset, outcome, and suspected medicine(s).

Glucagon-like peptide 1 receptor agonist (GLP-1 RA): long-term effect on kidney function in patients with type 2 diabetes.

Aims: In a short-term study including 31 patients with type 2 diabetes, glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment was associated with a significant reversible decline in GFR. Twenty-three patients re-initiated GLP-1 RA treatment after the primary study, and the aim was to investigate the long-term effect on kidney function.

Methods: We included 30 patients in a one-year extension study, all initially treated with liraglutide for seven weeks.

The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers.

Aims: Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals.

Genetic risk factors affecting mitochondrial function are associated with kidney disease in people with Type 1 diabetes.

Aim: To evaluate the association with diabetic kidney disease of single nucleotide polymorphisms (SNPs) that may contribute to mitochondrial dysfunction.

Methods: The mitochondrial genome and 1039 nuclear genes that are integral to mitochondrial function were investigated using a case (n = 823 individuals with diabetic kidney disease) vs. control (n = 903 individuals with diabetes and no renal disease) approach.

Pulse pressure is not an independent predictor of outcome in type 2 diabetes patients with chronic kidney disease and anemia--the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT).

Pulse pressure (PP) remains an elusive cardiovascular risk factor with inconsistent findings. We clarified the prognostic value in patients with type 2 diabetes, chronic kidney disease (CKD) and anemia in the Trial to Reduce cardiovascular Events with Aranesp (darbepoetin alfa) Therapy. In 4038 type 2 diabetes patients, darbepoetin alfa treatment did not affect the primary outcome.

Global longitudinal strain is not impaired in type 1 diabetes patients without albuminuria: the Thousand & 1 study.

Objectives: The purpose of this study was to investigate if systolic myocardial function is reduced in all patients with type 1 diabetes (T1DM) or only in patients with albuminuria.

Background: Heart failure is a common cause of mortality in T1DM, and a specific diabetic cardiomyopathy has been suggested. It is not known whether myocardial dysfunction is a feature of T1DM per se or primarily associated with diabetes with albuminuria.

Rationale, design, and baseline characteristics of ARTS-DN: a randomized study to assess the safety and efficacy of finerenone in patients with type 2 diabetes mellitus and a clinical diagnosis of diabetic nephropathy.

Background/aims: Finerenone decreases albuminuria in patients having heart failure with reduced ejection fraction and mild-to-moderate (stage 2-3) chronic kidney disease. The MinerAlocorticoid Receptor Antagonist Tolerability Study-Diabetic Nephropathy (ARTS-DN; NCT01874431) is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b study. ARTS-DN investigated whether the mineralocorticoid receptor antagonist finerenone reduces albuminuria without causing major alterations in serum potassium levels in patients with type 2 diabetes mellitus and a clinical diagnosis of DN who were receiving a renin-angiotensin-system (RAS) inhibitor.

Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides.

Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin.

Diabetic kidney disease.

The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality.

Diabetic nephropathy in 2014: improved cardiorenal prognosis in diabetic nephropathy.

In 2014, key studies in the field of diabetic nephropathy highlighted the importance of albuminuria as a predictor of cardiovascular risk and showed that the incidence of renal and cardiovascular complications is decreasing. Promising efficacy data were obtained with atrasentan, whereas a trial of bardoxolone methyl led to safety concerns.

SORBS1 gene, a new candidate for diabetic nephropathy: results from a multi-stage genome-wide association study in patients with type 1 diabetes.

Aims/hypothesis: The genetic determinants of diabetic nephropathy remain poorly understood. We aimed to identify novel susceptibility genes for diabetic nephropathy.

Methods: We performed a genome-wide association study using 1000 Genomes-based imputation to compare type 1 diabetic nephropathy cases with proteinuria and with or without renal failure with control patients who have had diabetes for more than 15 years and no evidence of renal disease.

Increased plasma concentrations of midregional proatrial natriuretic Peptide is associated with risk of cardiorenal dysfunction in type 1 diabetes.

Background: To examine possible associations between midregional proatrial natriuretic peptide (MR-proANP) and diabetic complications at baseline and risk of mortality and end-stage renal disease (ESRD) during follow-up in type 1 diabetes.

Methods: Observational study including 667 patients, with plasma MR-proANP measured at baseline. Complications were defined as micro- (n = 168) or macroalbuminuria (n = 190) (urinary albumin excretion rate (UAER) 30-299 or ≥ 300 mg/24h), previous cardiovascular disease (CVD) (n = 143), cardiac autonomic dysfunction (heart rate variability < 11 beats/min) (n = 369), and retinopathy (n = 523).

Microalbuminuria: a parameter that has changed diabetes care.

Diabetic nephropathy is characterised by persistent albuminuria, elevated blood pressure, relentless decline in GFR and enhanced fatal and nonfatal cardiovascular diseases. Microalbuminuria has been central to the development of clinical practise in prevention and treatment of diabetic nephropathy and cardiovascular disease. Treatment-induced and spontaneous remission of microalbuminuria has been reported both in type 1 and type 2 diabetic patients, underlining the importance of sustained elevation of urinary albumin excretion.

Retinopathy and clinical outcomes in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia.

Objective: Retinopathy is an established microvascular complication of type 2 diabetes mellitus (T2DM), but its independent relationship with macrovascular and other microvascular complications is less well defined across the spectrum of kidney disease in T2DM. We examined the prognostic value of retinopathy in assessing the risk of developing end-stage renal disease (ESRD), cardiovascular morbidity or death among patients in the Trial to Reduce cardiovascular Events with Aranesp Therapy (TREAT).

Design: TREAT enrolled 4038 patients with T2DM, chronic kidney disease (CKD) and moderate anemia.

Urinary alpha- and pi-glutathione s-transferases in adult patients with type 1 diabetes.

Background/aims: Glutathione S-transferases (GSTs) are cytosolic enzymes excreted from renal tubules following tubular damage. α-GST primarily originates from proximal tubules, while π-GST from distal tubules and collecting ducts. We investigated if GST levels are associated with renal function in patients with type 1 diabetes.

Vitamin D analogue therapy, cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy: a randomized trial.

Aim: To evaluate the effects of therapy with the vitamin D analogue paricalcitol on markers of cardiovascular risk and kidney function in people with Type 1 diabetes mellitus and diabetic nephropathy.

Methods: In a double-blind, randomized placebo-controlled, crossover trial, 48 participants on stable renin angiotensin aldosterone system blockade and diuretics were assigned, in random order, to 12 weeks of paricalcitol and 12 weeks of placebo therapy, separated by a 4-week washout period. Primary and secondary endpoints were changes in plasma N-terminal probrain natriuretic peptide and urinary albumin excretion rate obtained before and after each intervention.

Effects of 12 weeks of treatment with fermented milk on blood pressure, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind placebo-controlled study.

Objective: Studies have indicated a blood pressure (BP)-lowering effect of milk-derived peptides in non-diabetic individuals, but the cardiometabolic effects of such peptides in patients with type 2 diabetes (T2D) are not known. We investigated the effect of milk fermented with Lactobacillus helveticus on BP, glycaemic control and cardiovascular risk factors in T2D.

Design: A randomised, double-blinded, prospective, placebo-controlled study.

Pulse wave reflection is associated with diabetes duration, albuminuria and cardiovascular disease in type 1 diabetes.

Aims: We investigate associations between the pulse-wave-derived measures augmentation pressure (AP) and augmentation index, and diabetic complications in type 1 diabetes.

Methods: This cross-sectional study from 2009-2011 included 676 type 1 diabetes patients. SphygmoCor (Atcor Medical, Australia) measured AP and heart rate-adjusted augmentation index (AI75).

Treatment with continuous subcutaneous insulin infusion is associated with lower arterial stiffness.

Aims: To investigate the relationship between arterial stiffness and insulin treatment mode [continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI)] in type 1 diabetes patients.

Methods: Cross-sectional study, from 2009 to 2011, including 601 Caucasian type 1 diabetes patients, 58 and 543 treated with CSII and MDI, respectively. Arterial stiffness was measured as pulse wave velocity (PWV) (SphygmoCor, AtCor Medical).

Time course and mechanisms of the anti-hypertensive and renal effects of liraglutide treatment.

Aims: Glucagon-like peptide-1 receptor agonist studies have revealed clinically significant reductions in systolic blood pressure (SBP). The aim was to investigate the time course of the anti-hypertensive effect of liraglutide treatment and potential underlying mechanisms.

Methods: We used an open-label, single-centre trial; 31 participants with Type 2 diabetes and hypertension completed the study.

Association of the pattern recognition molecule H-ficolin with incident microalbuminuria in an inception cohort of newly diagnosed type 1 diabetic patients: an 18 year follow-up study.

Aims/hypothesis: Increasing evidence links complement activation through the lectin pathway to diabetic nephropathy. Adverse complement recognition of proteins modified by glycation has been suggested to trigger complement auto-attack in diabetes. H-ficolin (also known as ficolin-3) is a pattern recognition molecule that activates the complement cascade on binding to glycated surfaces, but the role of H-ficolin in diabetic nephropathy is unknown.

Improved prognosis of diabetic nephropathy in type 1 diabetes.

The natural history of diabetic nephropathy offered an average survival of only 5-7 years. During the past decades, multiple changes in therapy and lifestyle have occurred. The prognosis of diabetic nephropathy after implementing stricter control of blood pressure (including increased use of long-term renin-angiotensin system inhibition), lipids, and glycemia, along with less smoking and other lifestyle and treatment advancements, is inadequately analyzed.

Soluble urokinase plasminogen activator receptor levels are elevated and associated with complications in patients with type 1 diabetes.

Objectives: Soluble urokinase plasminogen activator receptor (suPAR) is a marker of inflammation and endothelial dysfunction. We investigated the associations between suPAR and diabetes, including diabetes duration and complications, in patients with type 1 diabetes.

Design, Setting And Subjects: From 2009 to 2011, 667 patients with type 1 diabetes and 51 nondiabetic control subjects were included in a cross-sectional study at Steno Diabetes Center, Gentofte, Denmark.

Cause-specific mortality according to urine albumin creatinine ratio in the general population.

Background: Urine albumin creatinine ratio, UACR, is positively associated with all-cause mortality, cardiovascular disease and diabetes in observational studies. Whether a high UACR is also associated with other causes of death is unclear. We investigated the association between UACR and cause-specific mortality.

Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with Type 2 diabetes mellitus.

Aims: Early detection of individuals with Type 2 diabetes mellitus or hypertension at risk for micro- or macroalbuminuria may facilitate prevention and treatment of renal disease. We aimed to discover plasma and urine metabolites that predict the development of micro- or macroalbuminuria.

Methods: Patients with Type 2 diabetes (n = 90) and hypertension (n = 150) were selected from the community-cohort 'Prevention of REnal and Vascular End-stage Disease' (PREVEND) and the Steno Diabetes Center for this case-control study.