Evidence map›Paper›PMID 21660636›Full record

Trial reportDiabetologia2011

Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans.

K N Aronis, K N Diakopoulos, C G Fiorenza, J P Chamberland, C S Mantzoros

2 registry-linked trialsOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 10 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
0.8field-weighted citation impact, top 34% 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.

NCT00130117 phase2completednot on this map

Randomized, Double-blind, Placebo-controlled Trial of Human Recombinant Leptin (r-metHuLeptin) for the Treatment of Hypothalamic (Exercise-Induced) Amenorrhea

TypeinterventionalSponsorBeth Israel Deaconess Medical CenterRan2010 to 2016Enrolled20ConditionsAmenorrheaArmsr-metHuLeptin, Oral Contraceptive Pills (OCPs), Placebo
NCT00140205 phase1completednot on this map

Pharmacokinetics of Leptin Administration During Fasting

TypeinterventionalSponsorBeth Israel Deaconess Medical CenterRan2001 to 2016Enrolled15ConditionsEnergy Deficiency Due to Short-term FastingArmsr-metHuLeptin
3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. The role of leptin and low testosterone in obesity.International journal of impotence research · 2022
    Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Leptin in human physiology and pathophysiology.American journal of physiology. Endocrinology and metabolism · 2011
    Review
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

5 authors at 1 institution in 1 country.

K N AronisDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
K N Diakopoulos
C G Fiorenza
J P Chamberland
C S Mantzoros
Harvard University · US

Funding

HARVARD CLINICAL AND TRANSLATIONAL SCIENCE CENTER (UL1)UL1RR025758 · NCRR · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2008 to 2011
$91.4M
ZINC STATUS AND T CELL DISORDER IN MILD HUMAN ZINC DEFICIENCYM01RR001032 · NCRR · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SUKHATME, VIKAS P · 1985 to 2008
$32.3M
Role of Leptin in the Neuroendocrine Response to FastingR01DK058785 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI MANTZOROS, CHRISTOS S · 2001 to 2011
$4.0M
Physical Health in Midlife:Influences of adversities and relationshipsR01AG032030 · NIA · JUDGE BAKER CHILDREN'S CENTER · PI CROWELL, JUDITH A · 2009 to 2013
$3.1M
The Role of Leptin in the Maintenance of a Reduced Body WeightR01DK079929 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI MANTZOROS, CHRISTOS S · 2008 to 2012
$1.8M
Leptin and Adipokine PhysiologyK24DK081913 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI MANTZOROS, CHRISTOS S · 2008 to 2020
$1.5M
NCRR NIH HHS M01 RR001032NCRR NIH HHS M01-RR-01032NCRR NIH HHS UL1 RR025758NIA NIH HHS AG032030NIA NIH HHS R01 AG032030NIDDK NIH HHS K24 DK081913NIDDK NIH HHS R01 DK058785NIDDK NIH HHS R01 DK079929PHS HHS 58785PHS HHS 79929PHS HHS 81913
6 · The paper itself

Abstract

aim/hypothesisLeptin has been shown to regulate angiogenesis in animal and in vitro studies by upregulating the production of several pro-angiogenic factors, but its role in regulating angiogenesis has never been studied in humans.

methodsThe potential angiogenic effect of two doses of metreleptin (50 and 100 ng/ml) was evaluated in vitro, using a novel three-dimensional angiogenesis assay. Fifteen healthy, normoleptinaemic volunteers were administered both a physiological (0.1 mg/kg) and a pharmacological (0.3 mg/kg) single dose of metreleptin, in vivo, on two different inpatient admissions separated by 1-12 weeks. Serum was collected at 0, 6, 12 and 24 h after metreleptin administration. Twenty lean women, with leptin levels <5 ng/ml, were randomised in a 1:1 fashion to receive either physiological replacement doses of metreleptin (0.04-0.12 mg/kg q.d.) or placebo for 32 weeks. Serum was collected at 0, 8, 20 and 32 weeks after randomisation. Proteomic angiogenesis array analysis was performed to screen for angiogenic factors. Circulating concentrations of angiogenin, angiopoietin-1, platelet derived endothelial factor (PDGF)-AA, matrix metalloproteinase (MMP) 8 and 9, endothelial growth factor (EGF) and vascular EGF (VEGF) were also measured.

resultsBoth metreleptin doses failed to induce angiogenesis in the in vitro model. Although leptin levels increased significantly in response to both short-term and long-term metreleptin administration, circulating concentrations of angiogenesis markers did not change significantly in vivo. CONCLUSIONS/INTERPRETATIONS: This is the first study that examines the effect of metreleptin administration in angiogenesis in humans. Metreleptin administration does not regulate circulating angiogenesis related factors in humans. CLINICAL

trial registrationClinicalTrials.gov NCT00140205 and NCT00130117.

fundingThis study was supported by National Institutes of Health-National Center for Research Resources grant M01-RR-01032 (Harvard Clinical and Translational Science Center) and grant number UL1 RR025758. Funding was also received from the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785, 79929 and 81913, and AG032030.

Indexed as

AdolescentAdultAngiogenesis Inducing AgentsAngiopoietin-1Dose-Response Relationship, DrugEndothelial Growth FactorsFemaleHumansInjections, SubcutaneousLeptinMaleMatrix Metalloproteinase 8Matrix Metalloproteinase 9Neovascularization, PhysiologicPlatelet-Derived Growth FactorRibonuclease, PancreaticAngiogenesis Inducing AgentsangiogeninAngiopoietin-1Endothelial Growth FactorsLeptinMatrix Metalloproteinase 8Matrix Metalloproteinase 9metreleptinPlatelet-Derived Growth Factorplatelet-derived growth factor ARibonuclease, PancreaticVascular Endothelial Growth Factor A

Identifiers

PMID21660636
PMCPMC3733553
OpenAlexW2042057695

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.