Evidence mapPaperPMID 38776413Full record

ArticleDiabetes2024

An E115A Missense Variant in CERS2 Is Associated With Increased Sleeping Energy Expenditure and Hepatic Insulin Resistance in American Indians.

Sascha Heinitz, Michael Traurig, Jonathan Krakoff, Philipp Rabe, Claudia Stäubert, Sayuko Kobes, Robert L Hanson, Michael Stumvoll, Matthias Blüher, Clifton Bogardus and 2 more

Abstract read
In one paragraph

Article in Diabetes, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
field-weighted citation impact
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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
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

12 authors.

Sascha HeinitzPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
Michael TraurigPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
Jonathan KrakoffPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
Philipp RabeFaculty of Medicine, Rudolf Schönheimer Institute of Biochemistry, Leipzig University, Leipzig, Germany.
Claudia StäubertFaculty of Medicine, Rudolf Schönheimer Institute of Biochemistry, Leipzig University, Leipzig, Germany.
Sayuko KobesPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
Robert L HansonPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
Michael StumvollDepartment of Internal Medicine, Clinic for Endocrinology, Nephrology and Rheumatology, University of Leipzig, Leipzig, Germany.
Matthias BlüherDepartment of Internal Medicine, Clinic for Endocrinology, Nephrology and Rheumatology, University of Leipzig, Leipzig, Germany.
Clifton BogardusPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
Leslie BaierPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.ORCID 0000-0002-8773-9670
Paolo PiaggiPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.ORCID 0000-0003-2774-9161

Funding

Genetic Epidemiology of Diabetes and ObesityZIADK069028 · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · 2025 to 2025
$699k
Risk Factors and Etiology of Obesity and Type 2 DiabetesZIADK069015 · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · 2025 to 2025
$364k
Follow-Up Studies of a Genome-Wide Association Analysis in Pima IndiansZIADK075012 · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · 2025 to 2025
$294k
Whole Genome and Whole Exome Sequencing to Identify Genes for Type 2 Diabetes and ObesityZIADK075058 · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · 2025 to 2025
$177k
Structural Analysis Of Candidate Genes For Type 2 Diabetes and ObesityZIADK069071 · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · 2025 to 2025
$118k
Etiology of obesity--Pathophysiological consequencesZ01DK069015 · DIABETES, DIGESTIVE, KIDNEY DISEASES · 1986 to 2005
Intramural NIH HHS Z01 DK069015NIDDK NIH HHS DK069015-36
6 · The paper itself

Abstract

Genetic determinants of interindividual differences in energy expenditure (EE) are largely unknown. Sphingolipids, such as ceramides, have been implicated in the regulation of human EE via mitochondrial uncoupling. In this study, we investigated whether genetic variants within enzymes involved in sphingolipid synthesis and degradation affect EE and insulin-related traits in a cohort of American Indians informative for 24-h EE and glucose disposal rates during a hyperinsulinemic-euglycemic clamp. Association analysis of 10,084 genetic variants within 28 genes involved in sphingolipid pathways identified a missense variant (rs267738, A>C, E115A) in exon 4 of CERS2 that was associated with higher sleeping EE (116 kcal/day) and increased rates of endogenous glucose production during basal (5%) and insulin-stimulated (43%) conditions, both indicators of hepatic insulin resistance. The rs267738 variant did not affect ceramide synthesis in HepG2 cells but resulted in a 30% decrease in basal mitochondrial respiration. In conclusion, we provide evidence that the CERS2 rs267738 missense variant may influence hepatic glucose production and postabsorptive sleeping metabolic rate. ARTICLE HIGHLIGHTS:

Indexed as

Energy MetabolismIndians, North AmericanInsulin ResistanceLiverMembrane ProteinsSphingosine N-AcyltransferaseAdultFemaleGlucose Clamp TechniqueHep G2 CellsHumansMaleMiddle AgedMutation, MissenseSleepTumor Suppressor ProteinsCERS2 protein, humanMembrane ProteinsSphingosine N-AcyltransferaseTumor Suppressor Proteins

Identifiers

PMID38776413
PMCPMC11262042

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.