Bernt Johan von Scholten

Bio: Bernt Johan von Scholten is an academic researcher from Novo Nordisk. The author has contributed to research in topics: Type 2 diabetes & Liraglutide. The author has an hindex of 20, co-authored 64 publications receiving 1046 citations. Previous affiliations of Bernt Johan von Scholten include Steno Diabetes Center & Copenhagen University Hospital.

Global Changes in Food Supply and the Obesity Epidemic.

Abstract: Purpose of Review We explore how a global shift in the food system caused by global economic growth, increase in available food per capita and in food processing is a driver of the obesity epidemic.

Trimethylamine N-oxide (TMAO) as a New Potential Therapeutic Target for Insulin Resistance and Cancer.

Abstract: Background: The intake of animal products in food has been associated with both the development of insulin resistance and gastrointestinal cancers (GIC). Through the digestion of animal protein and other constituents of animal products, the commensal bacteria in the gut (the gut microbiota) forms metabolites that can contribute to the development of both insulin resistance and cancer. Trimethylamine-N-Oxide (TMAO) is such a molecule and has recently drawn a lot of attention as it may be a risk factor for - and a link between - the gut microbiota and cardiovascular and renal disease. Further, TMAO is anticipated to have significance as a biomarker of - or even an independent risk factor for - other undesirable conditions, including insulin resistance and GIC. TMAO originates from a precursor, trimethylamine (TMA) that is a metabolite of various precursors; mainly choline and carnitine from ingested foods. Methods: We review the literature on TMAO as a shared risk factor and/or pathway between insulin resistance and GIC risk and take the reader through the literature of interventions that could reduce formation of TMAO and thereby the risk of insulin resistance and GIC. The purpose of the work is to generate a hypothesis to be tested in preclinical and clinical studies. Results: TMAO seems to be associated with both insulin resistance and GIC risk and also with atherosclerotic cardiovascular disease. One shared pathway is the formation of N-Nitroso compounds, a group of metabolites that can cause DNA-damage and epigenetic changes. Levels of TMAO can be reduced by limiting the dietary intake of certain foods, most importantly animal products. Further, certain drugs, namely Meldonium and 3, 3-dimethyl-1-butanol, may inhibit the formation of TMAO by inhibiting bacterial enzymes. Conclusions: The TMAO pathway and its metabolites are possibly involved in the development of two major health problems: insulin resistance and cancer. Within these pathways novel therapeutic targets may be identified. Further research is needed in order to verify existing or develop new pharmacological agents that modify these pathways and reduce the risk of insulin resistance and GIC.

Effects of Liraglutide Versus Placebo on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease.

Abstract: Background: LEADER trial (Liraglutide Effect and Action in Diabetes: Evaluation of CV Outcome Results) results demonstrated cardiovascular benefits for patients with type 2 diabetes mellitus at hig...

The effect of liraglutide on renal function: A randomized clinical trial.

Abstract: Aims Patients with type 2 diabetes and albuminuria have high cardiorenal morbidity and mortality despite multifactorial treatment. Short-term reduction in albuminuria is considered suggestive of long-term renoprotective effects. We evaluated the renal effects of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on top of multifactorial care, including renin-angiotensin-system (RAS)-inhibition. Materials and methods Randomised, double-blind, placebo-controlled, cross-over trial including patients with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio > 30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. Patients received liraglutide (1.8 mg/d) and matched placebo for 12 weeks in random order. Primary endpoint was change in 24-h urinary albumin excretion rate (UAER). Results 32 patients were randomised, 27 completed the study. After placebo treatment, geometric mean (IQR) UAER was 199 (81-531) mg/24-h, mean (SD) measured GFR (mGFR) 75 (36) mL/min/1.73m2, 24-h blood pressure 145/80 (15/8) mmHg and HbA1c 61 (11) mmol/mol. Liraglutide reduced HbA1c by 8 (95% CI: 5;11) mmol/mol (p<0.001) and weight by 1.8 (95% CI: 0.2;3.4) kg (p=0.032) compared to placebo. Furthermore, liraglutide reduced UAER by 32 (95% CI: 7; 50) % (p=0.017) compared with placebo. Change in mGFR was -5 (95% CI: -11; 2) mL/min/1.73m2 (p=0.15), and change in 24-h systolic blood pressure was -5 (95% CI: -10;0) mmHg (p=0.07). In multivariate regression models, change in UAER was associated with change in 24-h systolic blood pressure (p=0.025) but not with change in HbA1c, weight or mGFR (p≥0.14), overall model R2=0.39. Conclusions Our placebo-controlled randomised trial suggests that liraglutide has renoprotective effects on top of multifactorial treatment, including RAS-inhibition, in patients with type 2 diabetes and albuminuria. Clinical trial registration ClinicalTrials.gov, NCT02545738.

Liraglutide and Renal Outcomes in Type 2 Diabetes

Abstract: BackgroundIn a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown. MethodsWe report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rat...