Evidence mapPaperPMID 39758010Full record

Observational studyThe Journal of clinical endocrinology and metabolism2025

Abnormal Glucagon Secretion Contributes to a Longitudinal Decline in Glucose Tolerance.

Sneha Mohan, Hannah E Christie, Marcello C Laurenti, Aoife M Egan, Kent R Bailey, Claudio Cobelli, Chiara Dalla Man, Adrian Vella

Abstract readObservational Study
In one paragraph

Observational study in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
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

5 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Modeling the effect of glucagon on endogenous glucose production in healthy individuals under meal-like conditions.American journal of physiology. Regulatory, integrative and comparative physiology · 2025
    Article
  5. Abnormal Glucagon Secretion Contributes to a Longitudinal Decline in Glucose Tolerance.The Journal of clinical endocrinology and metabolism · 2025
    Observational
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Sneha MohanDivision of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.ORCID 0000-0002-4840-1802
Hannah E ChristieDivision of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.ORCID 0000-0002-0606-6778
Marcello C LaurentiDivision of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Aoife M EganDivision of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.ORCID 0000-0003-0379-9279
Kent R BaileyDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA.
Claudio CobelliDepartment of Women and Children's Health, University of Padova, Via Giustiniani, 3, 35128 Padova, Italy.ORCID 0000-0002-0169-6682
Chiara Dalla ManDepartment of Information Engineering, University of Padova, Via G. Gradenigo 6/b, 35131 Padova, Italy.ORCID 0000-0002-4908-0596
Adrian VellaDivision of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.ORCID 0000-0001-6493-7837

Funding

The effect of endogenous GLP-1 secretion on islet function in vivoR01DK126206 · MAYO CLINIC ROCHESTER · 2025 to 2025
$743k
The regulation of fasting glucose metabolism in people with and without prediabetesR01DK078646 · MAYO CLINIC ROCHESTER · 2025 to 2025
$667k
Glucagon secretion and action in humansR01DK116231 · MAYO CLINIC ROCHESTER · 2025 to 2025
$520k
Elucidating the Pathophysiology of Gestational Diabetes MellitusK23DK134767 · MAYO CLINIC ROCHESTER · 2025 to 2025
$191k
Mayo Clinic General Clinical Research Center DK116231Mayo Clinic General Clinical Research Center DK126206Mayo Clinic General Clinical Research Center DK78646Mayo Clinic General Clinical Research Center DK TR000135MIUR (Italian Minister for EducationNCATS NIH HHS UL1 TR000135NIDDK NIH HHS K23 DK134767NIDDK NIH HHS R01 DK078646NIDDK NIH HHS R01 DK116231NIDDK NIH HHS R01 DK126206
6 · The paper itself

Abstract

contextDefects in insulin secretion and action contribute to the progression of prediabetes to diabetes. However, the contribution of α-cell dysfunction to this process has been unclear.

objectiveThis work aimed to understand the relative contributions of α-cell and β-cell dysfunction to declining glucose tolerance.

methodsA longitudinal, community-based observational study was conducted at a clinical research unit at an academic medical center. We studied 96 individuals without diabetes (age 55 ± 1 years; body mass index 27.7 ± 0.4) on 2 occasions, 3 years apart using an oral 75-g glucose challenge. Indices for insulin secretion and action were estimated using the oral minimal model. Glucagon secretion rate (GSR) was estimated by deconvolution from peripheral glucagon concentrations. Main outcome measures included glucose tolerance status (categorical variable) and then symmetrical percentage change in peak and 120-minute glucose (post oral glucose tolerance test) concentrations (continuous variables).

resultsA total of 32 individuals progressed from normal to impaired glucose tolerance (IGT) or from IGT to type 2 diabetes. The disposition index (DI) declined in the progressors (568 ± 98 vs 403 ± 65 10-4 dL/kg/min per μU/mL, baseline vs 3 years; P = .04). α-Cell suppression by glucose (δGSR/δglucose) did not change in the nonprogressors (1.5 ± 0.1 vs 1.3 ± 0.1 nmol/min/L; P = .37) but decreased (1.0 ± 0.2 vs 0.8 ± 0.2 nmol/min/L; P < .01) in those who progressed. Analysis of the entire cohort showed that DI and δGSR/δglucose were independently and inversely correlated with an increase in glycemic excursion.

conclusionThese data show that α-cell dysfunction accompanies a decline in β-cell function as IGT or overt type 2 diabetes develops.

Indexed as

Diabetes Mellitus, Type 2GlucagonGlucagon-Secreting CellsGlucose IntolerancePrediabetic StateAdultAgedBlood GlucoseDisease ProgressionFemaleGlucose Tolerance TestHumansInsulin-Secreting CellsInsulin SecretionLongitudinal StudiesMaleBlood GlucoseGlucagonglucagon suppressioninsulin secretionprediabetesα-cell functionβ-cell function

Identifiers

PMID39758010
PMCPMC12434210

What Socratic holds

Textmetadata
LicenceTDM
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.