2 research outputs found
Effect of sitagliptin on energy metabolism and brown adipose tissue in overweight individuals with prediabetes:a randomised placebo-controlled trial
Aims/hypothesis: The aim of this study was to evaluate the effect of sitagliptin on glucose tolerance, plasma lipids, energy expenditure and metabolism of brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle in overweight individuals with prediabetes (impaired glucose tolerance and/or impaired fasting glucose). Methods: We performed a randomised, double-blinded, placebo-controlled trial in 30 overweight, Europid men (age 45.9 \xc2\xb1 6.2\xc2\xa0years; BMI 28.8 \xc2\xb1 2.3\xc2\xa0kg/m2) with prediabetes in the Leiden University Medical Center and the Alrijne Hospital between March 2015 and September 2016. Participants were initially randomly allocated to receive sitagliptin (100\xc2\xa0mg/day) (n = 15) or placebo (n = 15) for 12\xc2\xa0weeks, using a randomisation list that was set up by an unblinded pharmacist. All people involved in the study as well as participants were blinded to group assignment. Two participants withdrew from the study prior to completion (both in the sitagliptin group) and were subsequently replaced with two new participants that were allocated to the same treatment. Before and after treatment, fasting venous blood samples and skeletal muscle biopsies were obtained, OGTT was performed and body composition, resting energy expenditure and [18F] fluorodeoxyglucose ([18F]FDG) uptake by metabolic tissues were assessed. The primary study endpoint was the effect of sitagliptin on BAT volume and activity. Results: One participant from the sitagliptin group was excluded from analysis, due to a distribution error, leaving 29 participants for further analysis. Sitagliptin, but not placebo, lowered glucose excursion (\xe2\x88\x9240%; p < 0.003) during OGTT, accompanied by an improved insulinogenic index (+38%; p < 0.003) and oral disposition index (+44%; p < 0.003). In addition, sitagliptin lowered serum concentrations of triacylglycerol (\xe2\x88\x9229%) and very large (\xe2\x88\x9246%), large (\xe2\x88\x9235%) and medium-sized (\xe2\x88\x9224%) VLDL particles (all p < 0.05). Body weight, body composition and energy expenditure did not change. In skeletal muscle, sitagliptin increased mRNA expression of PGC1\xce\xb2 (also known as PPARGC1B) (+117%; p < 0.05), a main controller of mitochondrial oxidative energy metabolism. Although the primary endpoint of change in BAT volume and activity was not met, sitagliptin increased [18F] FDG uptake in subcutaneous WAT (sWAT; +53%; p < 0.05). Reported side effects were mild and transient and not necessarily related to the treatment. Conclusions/interpretation: Twelve weeks of sitagliptin in overweight, Europid men with prediabetes improves glucose tolerance and lipid metabolism, as related to increased [18F] FDG uptake by sWAT, rather than BAT, and upregulation of the mitochondrial gene PGC1\xce\xb2 in skeletal muscle. Studies on the effect of sitagliptin on preventing or delaying the progression of prediabetes into type 2 diabetes are warranted. Trial registration: ClinicalTrials.gov NCT02294084. Funding: This study was funded by Merck Sharp & Dohme Corp, Dutch Heart Foundation, Dutch Diabetes Research Foundation, Ministry of Economic Affairs and the University of Granada
The effect of mirabegron on energy expenditure and brown adipose tissue in healthy lean South Asian and Europid men
Aim: To compare the effects of cold exposure and the β3-adrenergic receptor agonist
mirabegron on plasma lipids, energy expenditure and brown adipose tissue (BAT)
activity in South Asians versus Europids.
Materials and Methods: Ten lean Dutch South Asian (aged 18-30 years; body mass
index [BMI] 18-25 kg/m2
) and 10 age- and BMI-matched Europid men participated in
a randomized, double-blinded, cross-over study consisting of three interventions:
short-term (~ 2 hours) cold exposure, mirabegron (200 mg one dose p.o.) and placebo. Before and after each intervention, we performed lipidomic analysis in serum,
assessed resting energy expenditure (REE) and skin temperature, and measured BAT
fat fraction by magnetic resonance imaging.
Results: In both ethnicities, cold exposure increased the levels of several serum lipid
species, whereas mirabegron only increased free fatty acids. Cold exposure increased
lipid oxidation in both ethnicities, while mirabegron increased lipid oxidation in
Europids only. Cold exposure and mirabegron enhanced supraclavicular skin temperature in both ethnicities. Cold exposure decreased BAT fat fraction in both
ethnicities. After the combination of data from both ethnicities, mirabegron
decreased BAT fat fraction compared with placebo.
Conclusions: In South Asians and Europids, cold exposure and mirabegron induced
beneficial metabolic effects. When combining both ethnicities, cold exposure and
mirabegron increased REE and lipid oxidation, coinciding with a higher supraclavicular
skin temperature and lower BAT fat fraction.Diabetes Research Foundation Fellowship
2015.81.1808Netherlands CardioVascular Research Initiative: 'the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences'
CVON2014-02 ENERGISE
CVON2017-20 GENIUS-IIEuropean Union (EU)
602485European Research Council (NOMA-MRI) PCNR is an Established Investigator of the Netherlands Heart Foundation
2009T03