Evidence map›Paper›PMID 30627753›Full record

ArticleDiabetologia2019

Carvedilol prevents counterregulatory failure and impaired hypoglycaemia awareness in non-diabetic recurrently hypoglycaemic rats.

Rawad Farhat, Gong Su, Anne-Sophie Sejling, Nicholas Knight, Simon J Fisher, Owen Chan

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetologia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

9 citing papers in PubMed, 12 citations in OpenAlex.

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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

6 authors at 3 institutions in 3 countries.

Rawad FarhatDivision of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, University of Utah, Department 15 North 2030 East, EIHG Building 533, Room 2420B, Salt Lake City, UT, 84112, USA.
Gong SuDivision of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, University of Utah, Department 15 North 2030 East, EIHG Building 533, Room 2420B, Salt Lake City, UT, 84112, USA.
Anne-Sophie SejlingNovo-Nordisk A/S, Søborg, Denmark.
Nicholas KnightDivision of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, University of Utah, Department 15 North 2030 East, EIHG Building 533, Room 2420B, Salt Lake City, UT, 84112, USA.
Simon J FisherDivision of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, University of Utah, Department 15 North 2030 East, EIHG Building 533, Room 2420B, Salt Lake City, UT, 84112, USA.
Owen ChanDivision of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, University of Utah, Department 15 North 2030 East, EIHG Building 533, Room 2420B, Salt Lake City, UT, 84112, USA. ochan@u2m2.utah.edu.
University of Utah · USCapital Medical University · CNNovo Nordisk (Denmark) · DK

Funding

Pharmacological Approach to the Restoration of Hypoglycemia AwarenessR01DK118082 · NIDDK · UNIVERSITY OF UTAH · PI FISHER, SIMON J · 2019 to 2023
$1.9M
MECHANISMS OF COUNTERREGULATORY FAILURER01DK099315 · NIDDK · YALE UNIVERSITY · PI CHAN, OWEN · 2013 to 2017
$1.8M
NIDDK NIH HHS R01 DK099315NIDDK NIH HHS R01 DK118082
6 · The paper itself

Abstract

aims/hypothesisThis study evaluates whether the non-selective β-blocker, carvedilol, can be used to prevent counterregulatory failure and the development of impaired awareness of hypoglycaemia (IAH) in recurrently hypoglycaemic rats.

methodsSprague Dawley rats were implanted with vascular catheters and intracranial guide cannulas targeting the ventromedial hypothalamus (VMH). These animals underwent either three bouts of insulin-induced hypoglycaemia or received three saline injections (control group) over 3 days. A subgroup of recurrently hypoglycaemic animals was treated with carvedilol. The next day, the animals underwent a hypoglycaemic clamp with microdialysis without carvedilol treatment to evaluate changes in central lactate and hormone levels. To assess whether carvedilol prevented IAH, we treated rats that had received repeated 2-deoxyglucose (2DG) injections to impair their awareness of hypoglycaemia with carvedilol and measured food intake in response to insulin-induced hypoglycaemia as a surrogate marker for hypoglycaemia awareness.

resultsCompared with the control group, recurrently hypoglycaemic rats had a ~1.7-fold increase in VMH lactate and this was associated with a 75% reduction in the sympathoadrenal response to hypoglycaemia. Treatment with carvedilol restored VMH lactate levels and improved the adrenaline (epinephrine) responses. In 2DG-treated rats compared with control animals receiving saline, food intake was reduced in response to hypoglycaemia and increased with carvedilol treatment. CONCLUSIONS/

interpretationWe conclude that carvedilol may be a useful therapy to prevent counterregulatory failure and improve IAH.

Indexed as

Adrenergic beta-1 Receptor AntagonistsAnimalsBlood GlucoseBody WeightCarvedilolCatheterizationDeoxyglucoseDisease Models, AnimalGlucose Clamp TechniqueHyperglycemiaHypoglycemiaHypoglycemic AgentsInsulinLactic AcidMaleRatsAdrenergic beta-1 Receptor AntagonistsBlood GlucoseCarvedilolDeoxyglucoseHypoglycemic AgentsInsulinLactic AcidCarvedilolCounterregulatory failureImpaired hypoglycaemia awarenessLactateRecurrent hypoglycaemiaVentromedial hypothalamus (VMH)β-blocker

Identifiers

PMID30627753
PMCPMC6403018
OpenAlexW2909500627

What OpenQuestion 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 OpenQuestion graph.