Trial reportThe Journal of clinical investigation2018
Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to hypoglycemia.
Trial report in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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.
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.
Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Effects of Intranasal Naloxone on Hypoglycemia-associated Autonomic Failure in Susceptible Individuals.The Journal of clinical endocrinology and metabolism · 2025Trial
- Trial
- Dynamic response of cerebral blood flow to insulin-induced hypoglycemia.Scientific reports · 2020Trial
- Feasibility of ConcurrentNMR in biomedicine · 2026Article
- Disrupted neurovascular-endocrine coupling in type 1 diabetes with impaired awareness of hypoglycemia.The Journal of clinical investigation · 2026Article
- Impaired awareness of hypoglycemia: can structured education address this persistent challenge?Frontiers in endocrinology · 2026Review
- Postprandial hypoglycaemia after gastric bypass in type 2 diabetes: pathophysiological mechanisms and clinical implications.Diabetologia · 2025Article
- Interoceptive Awareness Is Associated With Impaired Awareness of Hypoglycemia in Adults With Type 1 Diabetes.Diabetes care · 2025Article
- Brain Regulation of Cardiac Function during Hypoglycemia.Metabolites · 2023Review
- Osmotic Minipump Implantation for Increasing Glucose Concentration in Mouse Cerebrospinal Fluid.Journal of visualized experiments : JoVE · 2023Article
- Red blood cells as glucose carriers to the human brain: Modulation of cerebral activity by erythrocyte exchange transfusion in Glut1 deficiency (G1D).Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Preference for high-carbohydrate foods does not change for children and adolescents in insulin-induced hypoglycemia.BMJ open diabetes research & care · 2022Article
- Gradient variability coefficient: a novel method for assessing glycemic variability and risk of hypoglycemia.Endocrine · 2022Article
- Symptom Recognition as a Mediator in the Self-Care of Chronic Illness.Frontiers in public health · 2022Article
- New Fast Acting Glucagon for Recovery from Hypoglycemia, a Life-Threatening Situation: Nasal Powder and Injected Stable Solutions.International journal of molecular sciences · 2021Review
- Differential Expression of Inflammatory Markers in Hypoglycemia Unawareness Associated with Type 1 Diabetes: A Case Report.Brain sciences · 2020Article
- Hypoglycemia unawareness and autonomic dysfunction in diabetes: Lessons learned and roles of diabetes technologies.Journal of diabetes investigation · 2020Review
- Potential Biochemical Mechanisms of Brain Injury in Diabetes Mellitus.Aging and disease · 2020Review
- Differential Resting State Connectivity Responses to Glycemic State in Type 1 Diabetes.The Journal of clinical endocrinology and metabolism · 2020Observational
- Is the Brain a Key Player in Glucose Regulation and Development of Type 2 Diabetes?Frontiers in physiology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundAmong nondiabetic individuals, mild glucose decrements alter brain activity in regions linked to reward, motivation, and executive control. Whether these effects differ in type 1 diabetes mellitus (T1DM) patients with and without hypoglycemia awareness remains unclear.
methodsForty-two individuals (13 healthy control [HC] subjects, 16 T1DM individuals with hypoglycemia awareness [T1DM-Aware], and 13 T1DM individuals with hypoglycemia unawareness [T1DM-Unaware]) underwent blood oxygen level-dependent functional MRI brain imaging during a 2-step hyperinsulinemic euglycemic (90 mg/dl)-hypoglycemic (60 mg/dl) clamp for assessment of neural responses to mild hypoglycemia.
resultsMild hypoglycemia in HC subjects altered activity in the caudate, insula, prefrontal cortex, and angular gyrus, whereas T1DM-Aware subjects showed no caudate and insula changes, but showed altered activation patterns in the prefrontal cortex and angular gyrus. Most strikingly, in direct contrast to HC and T1DM-Aware subjects, T1DM-Unaware subjects failed to show any hypoglycemia-induced changes in brain activity. These findings were also associated with blunted hormonal counterregulatory responses and hypoglycemia symptom scores during mild hypoglycemia.
conclusionIn T1DM, and in particular T1DM-Unaware patients, there is a progressive blunting of brain responses in cortico-striatal and fronto-parietal neurocircuits in response to mild-moderate hypoglycemia. These findings have implications for understanding why individuals with impaired hypoglycemia awareness fail to respond appropriately to falling blood glucose levels.
fundingThis study was supported in part by NIH grants R01DK020495, P30 DK045735, K23DK109284, K08AA023545. The Yale Center for Clinical Investigation is supported by an NIH Clinical Translational Science Award (UL1 RR024139).
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.