Evidence mapPaperPMID 34718628Full record

Trial reportThe Journal of clinical endocrinology and metabolism2022

Long-Term Effects of Metreleptin in Rabson-Mendenhall Syndrome on Glycemia, Growth, and Kidney Function.

Marinna C Okawa, Elaine Cochran, Marissa Lightbourne, Rebecca J Brown

Open access · bronzeAbstract readClinical Trial, Phase IIControlled Clinical Trial
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 30% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Observational
  3. Article
  4. Article
  5. Article
  6. Article
  7. A Novel Mutation in theInternational journal of molecular sciences · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. 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

4 authors at 1 institution in 1 country.

Marinna C OkawaDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Elaine CochranDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Marissa LightbourneDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0001-5498-0452
Rebecca J BrownDiabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-2589-7382
National Institutes of Health · US

Funding

Molecular and Clinical Studies of Insulin ResistanceZIADK047050 · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · 2025 to 2025
$833k
Clinical utility of leptin therapy in syndromic forms of insulin resistance.ZIADK047052 · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · 2025 to 2025
$417k
NIDDK NIH HHS
6 · The paper itself

Abstract

contextRabson-Mendenhall syndrome (RMS) is caused by biallelic pathogenic variants in the insulin receptor gene (INSR) leading to insulin-resistant diabetes, microvascular complications, and growth hormone resistance with short stature. Small, uncontrolled studies suggest that 1-year treatment with recombinant leptin (metreleptin) improves glycemia in RMS.

objectiveThis study aimed to determine effects of long-term metreleptin in RMS on glycemia, anthropometrics, the growth hormone axis, and kidney function.

methodsWe compared RMS patients during nonrandomized open-label treatment with metreleptin (≥ 0.15 mg/kg/day) vs no metreleptin over 90 months (5 subjects in both groups at different times, 4 only in metreleptin group, 2 only in control group). Main outcome measures were A1c; glucose; insulin; 24-hour urine glucose; standard deviation scores (SDS) for height, weight, body mass index (BMI), and insulin-like growth factor 1 (IGF-1); growth hormone; and estimated glomerular filtration rate.

resultsOver time, metreleptin-treated subjects maintained 1.8 percentage point lower A1c vs controls (P = 0.007), which remained significant after accounting for changes in insulin doses. Metreleptin-treated subjects had a reduction in BMI SDS, which predicted decreased A1c. Growth hormone increased after metreleptin treatment vs control, with no difference in SDS between groups for IGF-1 or height. Reduced BMI predicted higher growth hormone, while reduced A1c predicted higher IGF-1.

conclusionMetreleptin alters the natural history of rising A1c in RMS, leading to lower A1c throughout long-term follow-up. Improved glycemia with metreleptin is likely attributable to appetite suppression and lower BMI SDS. Lower BMI after metreleptin may also worsen growth hormone resistance in RMS, resulting in a null effect on IGF-1 and growth despite improved glycemia.

Indexed as

Antigens, CDBlood GlucoseBody HeightBody Mass IndexBody WeightDonohue SyndromeGlomerular Filtration RateGlycated HemoglobinHuman Growth HormoneHumansInsulinInsulin-Like Growth Factor IKidneyLeptinReceptor, InsulinTreatment OutcomeAntigens, CDBlood GlucoseGlycated Hemoglobinhemoglobin A1c protein, humanHuman Growth HormoneIGF1 protein, humanINSR protein, humanInsulinInsulin-Like Growth Factor ILeptinmetreleptinReceptor, InsulinA1cgrowth hormone resistanceinsulin receptorleptinRabson-Mendenhall syndrome

Identifiers

PMID34718628
PMCPMC8852213
OpenAlexW3209331199

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.