Evidence map›Paper›PMID 41712301›Full record

ArticleThe Journal of clinical investigation2026

Disrupted neurovascular-endocrine coupling in type 1 diabetes with impaired awareness of hypoglycemia.

Pavel Filip, Antonietta Canna, Heidi Grohn, Amir A Moheet, Anjali F Kumar, Xiufeng Li, Yuan Zhang, Lynn E Eberly, Elizabeth R Seaquist, Silvia Mangia

2 registry-linked trialsAbstract readClinical Study
In one paragraph

Article in The Journal of clinical investigation, 2026. 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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

NCT02747680 nacompletednot on this map

Cerebral Responses to Insulin Induced Hypoglycemia

TypeinterventionalSponsorUniversity of MinnesotaRan2004 to 2020Enrolled266ConditionsType 1 Diabetes, Healthy, Hypoglycemia UnawarenessArmshypoglycemia (low blood sugar) in MRI
NCT02866435 early_phase1completednot on this map

Identifying the Brain Substrates of Hypoglycemia Unawareness in Type 1 Diabetes

TypeinterventionalSponsorUniversity of MinnesotaRan2016 to 2019Enrolled27ConditionsHypoglycemiaArmsInsulin, Glucose, Potassium phosphate
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. 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

10 authors.

Pavel FilipCenter for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, USA.
Antonietta CannaCenter for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, USA.
Heidi GrohnCenter for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, USA.
Amir A MoheetDepartment of Medicine and.
Anjali F KumarDepartment of Medicine and.
Xiufeng LiCenter for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, USA.
Yuan ZhangDivision of Biostatistics and Health Data Science, University of Minnesota, Minneapolis, Minnesota, USA.
Lynn E EberlyCenter for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, USA.
Elizabeth R SeaquistDepartment of Medicine and.
Silvia MangiaCenter for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota, USA.

Funding

Obtaining brain pCO2, pH and pO2 maps via measurements of neurovascular coupling: a novel non-invasive approach to identify the culprits of loss of brain functionDP1AG093028 · NIA · UNIVERSITY OF MINNESOTA · PI Silvia Mangia · 2024 to 2026
$3.2M
Identifying the Brain Substrates of Hypoglycemia Unawareness in Type 1 DiabetesR01DK099137 · NIDDK · UNIVERSITY OF MINNESOTA · PI MANGIA, SILVIA · 2014 to 2018
$2.5M
NIA NIH HHS DP1 AG093028NIDDK NIH HHS R01 DK099137
6 · The paper itself

Abstract

BACKGROUNDRecurrent hypoglycemia in type 1 diabetes (T1D) may culminate in impaired awareness of hypoglycemia (IAH). While neuroimaging studies identified affected brain regions, more complex perspectives integrating vascular dynamics with endocrine profile are needed.METHODSHere, 26 healthy adults, 30 T1D patients with normal hypoglycemia awareness (NAH), and 25 T1D patients with IAH underwent a hyperinsulinemic stepped clamp (euglycemia → hypoglycemia 50 mg/dL) combined with pseudo-continuous arterial spin-labeling MRI. Cerebral blood flow (CBF) and sympathetic vasomotor range (0.02-0.05 Hz) CBF oscillations were modeled against serially sampled plasma cortisol, epinephrine, norepinephrine, and glucagon.RESULTSIn healthy individuals treated as controls, hypoglycemia evoked robust thalamo-striatal and salience-interoceptive CBF increases (mean Cohen's d across significant clusters = 0.93) and suppression of vasomotor oscillations (d = 0.71). T1D retained CBF response but failed to attenuate oscillations (dT1D>controls = 0.43). IAH further blunted hypoglycemia-associated CBF increase, especially in thalamus, striatum, and insula (dNAH>IAH = 0.51). Hormone-CBF coupling differed quantitatively: cortisol/epinephrine-CBF correlations were positive in controls (r = 0.37/0.26), negative in NAH (-0.16/-0.40), and strongly positive in IAH (0.42/0.46).CONCLUSIONThus, our findings indicate that T1D disrupts dynamic, sympathetic modulation of CBF, whereas IAH additionally impairs perfusion reserve and shows maladaptive catecholamine-dependent CBF regulation, suggesting a qualitatively distinct neurovascular phenotype.TRIAL REGISTRATIONClinicalTrials.gov: NCT02747680 and NCT02866435.FUNDINGNIH (P41-EB-015894, P30-NS-076408, R01-DK-099137, R56-DK-099137, and DP1 AG093028); National Center for Advancing Translational Sciences of the NIH (KL2-TR-000113 and UL1-TR-000114); DP1 AG093028; Charles University, Czech Republic (Cooperatio Program, research area NEUR), Brain Dynamics (grant number CZ.02.01.01/00/22_008/0004643); General University Hospital in Prague (MH CZ-DRO-VFN64165).

Indexed as

Cerebrovascular CirculationDiabetes Mellitus, Type 1HypoglycemiaNeurovascular CouplingAdultEpinephrineFemaleGlucagonHumansMagnetic Resonance ImagingMaleMiddle AgedYoung AdultEpinephrineGlucagonDiabetesDiagnostic imagingEndocrinologyNeuroscience

Identifiers

PMID41712301
PMCPMC13078881

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.