Evidence map›Paper›PMID 26385462›Full record

ArticleDiabetologia2015

Endogenous GLP-1 mediates postprandial reductions in activation in central reward and satiety areas in patients with type 2 diabetes.

Jennifer S ten Kulve, Dick J Veltman, Liselotte van Bloemendaal, Frederik Barkhof, Carolyn F Deacon, Jens J Holst, Robert J Konrad, John H Sloan, Madeleine L Drent, Michaela Diamant and 1 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03361098 (Combined Effects of SGLT2 Inhibition and GLP-1 Receptor Agonism on Food Intake, Body Weight and Central Satiety and Reward Circuits in Obese T2DM Patients), which is not on this map. Cited by 51 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 3 pooled it
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03361098 phase4completedstarted 2017, after this paper: background citation

Combined Effects of SGLT2 Inhibition and GLP-1 Receptor Agonism on Food Intake, Body Weight and Central Satiety and Reward Circuits in Obese T2DM Patients

Ran2017Enrolled65Registered outcomes18Posted comparisons0ConditionsObesity, Type 2 Diabetes MellitusArmsDapagliflozin 10mg, exenatide, placebo dapagliflozin, placebo exenatide
PMID 26769912PMID 27651331PMID 24463454PMID 25943756PMID 25071023PMID 24323912PMID 22402735PMID 22332246PMID 26403227PMID 26331843PMID 26180105PMID 26094857other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 3 syntheses or guidelines pooled it, 107 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 3 countries.

Jennifer S ten KulveDepartment of Internal Medicine, Diabetes Center, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. js.tenkulve@vumc.nl.
Dick J VeltmanDepartment of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
Liselotte van BloemendaalDepartment of Internal Medicine, Diabetes Center, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
Frederik BarkhofDepartment of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
Carolyn F DeaconThe NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Jens J HolstThe NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Robert J KonradLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
John H SloanLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
Madeleine L DrentDepartment of Internal Medicine/Endocrine Section, VU University Medical Center, Amsterdam, the Netherlands.
Michaela DiamantDepartment of Internal Medicine, Diabetes Center, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
Richard G IJzermanDepartment of Internal Medicine, Diabetes Center, VU University Medical Center, de Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
Amsterdam UMC Location VUmc · NLEli Lilly (United States) · USUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisThe central nervous system (CNS) is a major player in the regulation of food intake. The gut hormone glucagon-like peptide-1 (GLP-1) has been proposed to have an important role in this regulation by relaying information about nutritional status to the CNS. We hypothesised that endogenous GLP-1 has effects on CNS reward and satiety circuits.

methodsThis was a randomised, crossover, placebo-controlled intervention study, performed in a university medical centre in the Netherlands. We included patients with type 2 diabetes and healthy lean control subjects. Individuals were eligible if they were 40-65 years. Inclusion criteria for the healthy lean individuals included a BMI <25 kg/m(2) and normoglycaemia. Inclusion criteria for the patients with type 2 diabetes included BMI >26 kg/m(2), HbA1c levels between 42 and 69 mmol/mol (6.0-8.5%) and treatment for diabetes with only oral glucose-lowering agents. We assessed CNS activation, defined as blood oxygen level dependent (BOLD) signal, in response to food pictures in obese patients with type 2 diabetes (n = 20) and healthy lean individuals (n = 20) using functional magnetic resonance imaging (fMRI). fMRI was performed in the fasted state and after meal intake on two occasions, once during infusion of the GLP-1 receptor antagonist exendin 9-39, which was administered to block actions of endogenous GLP-1, and on the other occasion during saline (placebo) infusion. Participants were blinded for the type of infusion. The order of infusion was determined by block randomisation. The primary outcome was the difference in BOLD signal, i.e. in CNS activation, in predefined regions in the CNS in response to viewing food pictures.

resultsAll patients were included in the analyses. Patients with type 2 diabetes showed increased CNS activation in CNS areas involved in the regulation of feeding (insula, amygdala and orbitofrontal cortex) in response to food pictures compared with lean individuals (p ≤ 0.04). Meal intake reduced activation in the insula in response to food pictures in both groups (p ≤ 0.05), but this was more pronounced in patients with type 2 diabetes. Blocking actions of endogenous GLP-1 significantly prevented meal-induced reductions in bilateral insula activation in response to food pictures in patients with type 2 diabetes (p ≤ 0.03). CONCLUSIONS/

interpretationOur findings support the hypothesis that endogenous GLP-1 is involved in postprandial satiating effects in the CNS of obese patients with type 2 diabetes.

trial registrationClinicalTrials.gov NCT 01363609. Funding The study was funded in part by a grant from Novo Nordisk.

Indexed as

Postprandial PeriodRewardSatiety ResponseAdultAgedCross-Over StudiesDiabetes Mellitus, Type 2FemaleFoodGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsGlycated HemoglobinHumansMagnetic Resonance ImagingMaleexendin (9-39)GLP1R protein, humanGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsGlycated HemoglobinOxygenPeptide FragmentsfMRIFood intakeGLP-1NeuroimagingObesityType 2 diabetes

Identifiers

PMID26385462
PMCPMC4630252
OpenAlexW1783116048

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.