Endocrine Abstracts

Background: DNA mismatch repair (MMR) maintains genomic integrity and stability. Inactivation of the MMR genes MLH1, PMS2, MSH2, and MSH6 by somatic or germline variants or gene methylation causes MMR deficiency (dMMR) leading to microsatellite instability (MSI) and high tumour mutational burden. In many tumour entities, patients with dMMR/MSI respond well to immune checkpoint inhibitor (ICI) therapy. The clinical relevance of dMMR and MSI i...

In 1996, we showed that GLP-1 is a satiety hormone in humans, and increased post-prandial GLP-1 levels following high protein meals have shown to be at least partially responsible for the high satiating effect of protein. The natural ligands to stimulate GLP-1 release seem to be peptide fragments and monoacylglycerides.The once-daily GLP-1 analogue liraglutide at doses up to 3.0 mg was compared with placebo or orlistat over 104 weeks as adjunct to diet a...

Impaired 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2)-dependent cortisol inactivation can lead to electrolyte dysbalance, hypertension and cardiometabolic disease. Furthermore, placental 11β-HSD2 essentially protects the fetus from high maternal glucocorticoid levels, and its impaired function has been associated with altered fetal growth and a higher risk for cardio-metabolic diseases in later life. Despite its important role, 11β-HSD2 is not include...

Objective: The exopeptidase dipeptidyl peptidase 4 (Dpp4) selectively cleaves N-terminal dipeptides from several substrates, including cytokines, growth factors, neuropeptides, and the incretin hormones. The systemic inhibition of Dpp4 by the so-called gliptins (oral Dpp4 inhibitors) represents an effective and established treatment option for type 2 diabetes (T2D). In the current study we investigated in healthy as well as in obese and diabetic mice if a liver selective knock...

Class 2a HDACs (i.e. HDAC 4, 5, 7 and 9) are involved in the regulation of gluconeogenesis and accordingly, their inhibition has been shown to result in lower blood glucose and improved pyruvate tolerance in diabetic mice. However, pan-inhibition of HDACs is not a viable approach for chronic treatment of type 2 diabetes (T2D) due to induction of severe side effects in various tissues. We now have investigated in vitro and in vivo efficacy and safety of a live...

Background: Many studies in Norway have found inadequate iodine status in pregnant and lactating women, but no studies have been undertaken in a random, population-based sample. Globally, the main strategy to eliminate iodine deficiency is iodization of salt. However, this is not compulsory in Norway, where the current legislation only permits iodization up to 5 μg per gram of salt. To reach the Nordic Nutrition Recommendation (NNR) of 200 μg/day iodine, supplements ...

Background: Familial resemblance was shown for body composition and risk factors in several studies. In twin studies which are powerful tool to assess genetically mediated traits significant resemblance was found in twins reared apart. In pairs of monozygotic twins was found significant resemblance in response to positive and negative energy balance. Aim of the study was to evaluate relationship of anthropometric parameters of parents and socioeconomic characteristics of famil...

Aims/objectives: Obesity and prediabetes are risk factors for developing T2D. 5–10% weight-loss can reduce risk of developing T2D by >50%. The 3-year part of this phase 3 trial investigated effects of liraglutide 3.0 mg, as adjunct to diet+exercise, in delaying onset of T2D over 3 years, body-weight and cardiometabolic risk factors in adults with obesity or overweight with comorbidities, and diagnosed with prediabetes at screening.Methods: Indiv...

Background: Cardiovascular safety is important for antidiabetic agents. This study followed the ICH E14 guideline to examine the effect of the oral dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin on the cardiac QT interval in healthy volunteers.Methods: This thorough QT study of linagliptin was performed in healthy subjects, using 5 mg (therapeutic dose) and 100 mg. The randomised, single-dose, placebo-controlled, double-blind, four-way crossover st...

Study objective: To study blood pressure (BP) levels and aortic dimensions in women with Turner syndrome (TS).Materials and methods: 102 women with TS (mean age 37.7 years; 18–62 years). 24 hour ambulatory BP measurement and echocardiography was performed on participants.Results: Mean BP systolic (sys) and diastolic (dia) values were (±SD): sysBPday 128.0±15.3; diaBPday 81.6±11.8; sysBPnight 110.4...