Evidence map›Paper›PMID 39656436›Full record

ArticleJournal of endocrinological investigation2025

Metabolic, genetic and immunological features of relatives of type 1 diabetes patients with elevated insulin resistance.

V Codazzi, V Salvatore, F Ragogna, I Marzinotto, A Anselmo, N Baldoni, M R Pastore, S Martinenghi, A Stabilini, E Bosi and 9 more

Abstract read
In one paragraph

Article in Journal of endocrinological investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  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

19 authors.

V CodazziIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.ORCID http://orcid.org/0009-0000-7489-4439
V SalvatoreIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
F RagognaIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
I MarzinottoIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
A AnselmoIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
N BaldoniIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
M R PastoreIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
S MartinenghiIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
A StabiliniIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
E BosiIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
A GiustinaIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
L PiemontiIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
I LibmanUPMC Children's Hospital of Pittsburgh, Pittsburgh, USA.
H M IsmailIndiana University School of Medicine, Indianapolis, USA.
M J RedondoTexas Children's Hospital, Baylor College of Medicine, Houston, USA.
V LampasonaIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
P MontiIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
A GiovenzanaIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy.
A PetrelliIRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132, Italy. alessandra.petrelli@unimi.it.ORCID http://orcid.org/0000-0002-5639-9415

Funding

Type 1 Diabetes Genetic Risk Score in TrialNetR01DK121843 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI REDONDO, MARIA JOSE · 2019 to 2023
$2.4M
Juvenile Diabetes Research Foundation International 3-APF-2019-744-ANNIDDK NIH HHS R01 DK121843
6 · The paper itself

Abstract

purposeInsulin resistance plays a pivotal role in the preclinical stages of type 1 diabetes (T1D).

objectiveThis study aims at exploring the genetic, metabolic, and immunological features associated with insulin resistance among individuals at risk of developing T1D.

methodsWe retrospectively selected relatives of individuals with T1D from participants in the TrialNet Pathway to Prevention study. They were categorized into two groups: high-H (n = 27) and low-H (n = 30), based on the upper and lower quartiles of insulin resistance assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Genetic predisposition was determined using the T1D Genetic Risk Score 1 (GRS1). Additionally, glucose control was evaluated through an oral glucose tolerance test and levels of metabolic hormones and inflammatory cytokines were measured in the serum. Flow cytometry analysis was employed to assess frequency and phenotype of islet-specific CD8 T cells.

resultsWhile GRS1 were similar between the low-H and high-H groups, high-H individuals displayed a distinct metabolic profile, characterized by compensatory hyperinsulinemia, even while maintaining normoglycemia. Circulating cytokine levels were similar between the two groups. However, immune profiling revealed a central memory and activated profile of GAD65-specific CD8 T cells, along with an increased frequency of insulin-specific CD8 T cells in high-H individuals. The enrichment in insulin-specific CD8 T cells was independent of body mass.

conclusionThese findings highlight the intricate interplay between insulin resistance, genetic factors, and immune activation in the context of T1D susceptibility, indicating potential connections between insulin resistance and immune responses specific to islet cells.

Indexed as

BiomarkersDiabetes Mellitus, Type 1Genetic Predisposition to DiseaseInsulin ResistanceAdolescentAdultBlood GlucoseCD8-Positive T-LymphocytesCytokinesFamilyFemaleFollow-Up StudiesGlucose Tolerance TestHumansMaleMiddle AgedBiomarkersBlood GlucoseCytokinesInsulin resistanceMetabolic hormonesT1D genetic risk scoreT cellsType 1 diabetes

Identifiers

PMID39656436
PMCPMC11876269

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Registered trials

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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.