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Hypoglycemia

Metabolism and Endocrine Disease · NLM MeSH · updated 2026-11-04 · version 1

Citations verified against PubMedNot yet clinician-reviewed10 referencesApproximately 4 min read

A syndrome of abnormally low blood glucose level.

Table of Contents

1. Definition2. Research landscape3. Reading the evidence4. Open-access studies5. Key reviews6. References7. About this article

Definition and research guide

This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.

Content available: 4 complete abstracts (878 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.

Definition

A syndrome of abnormally low blood glucose level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the central nervous system resulting in hunger; sweating; paresthesia; impaired mental function; seizures; COMA; and even death.

Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.

Also known as: Fasting Hypoglycemia; Hypoglycemia, Fasting; Postabsorptive Hypoglycemia; Hypoglycemia, Postabsorptive; Postprandial Hypoglycemia; Hypoglycemia, Postprandial; Reactive Hypoglycemia; Hypoglycemia, Reactive.

Where it fits in the MeSH classification

Broader topics
Glucose Metabolism Disorders
Narrower topics
Congenital Hyperinsulinism; Insulin Coma

Related concepts

  • Blood Glucose
  • Central Nervous System
  • Hunger
  • Sweating
  • Paresthesia
  • Seizures
  • Death

Research landscape

PubMed indexes 34,179 records tagged with the MeSH heading “Hypoglycemia” (counts retrieved 2026-10-31). 5,828 of them (17.1%) were published from 2020 onward, and the busiest period so far is through 1999 with 14,360 records.

Reviews account for 4,805 records (14.1%) and meta-analyses for 510. Randomized controlled trials number 2,211 (6.5%) as a share of all records on the topic.

PubMed records by publication periodthrough 1999: 14,360 records; 2000-2009: 5,098 records; 2010-2019: 8,893 records; 2020 onward: 5,828 records14,360through 19995,0982000-20098,8932010-20195,8282020 onward
Records in PubMed indexed with this heading, by publication period. Real counts from NCBI E-utilities; the final period covers only part of the current year. Volume reflects how much has been published, not how strong the evidence is.
Show the data
PeriodRecords
through 199914,360
2000-20095,098
2010-20198,893
2020 onward5,828
Share of records by publication typeReviews: 14.1 percent; Meta-analyses: 1.5 percent; Randomized controlled trials: 6.5 percentReviews14.1% (4,805)Meta-analyses1.5% (510)Randomized controlled trials6.5% (2,211)
Share of all PubMed records on this heading that carry each publication type. Types overlap with other records, so the shares do not sum to 100%.
Publication-type chart data
Publication types among 34,179 PubMed records
TypeRecordsShare
Reviews4,80514.1%
Meta-analyses5101.5%
Randomized controlled trials2,2116.5%

Method: PubMed query "Hypoglycemia"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.

Reading the evidence in metabolism and endocrine disease

Studies of diabetes, obesity and hormone disorders often follow blood tests such as glucose, HbA1c or hormone levels, which are stand-ins for outcomes that matter more, such as complications. Lifestyle and diet research is largely observational, and weight and diabetes trials can differ in how long people were followed. Nothing on this page is advice about medicines, insulin or diet; talk to a qualified clinician about your own situation. Check whether the outcome was a lab value or a clinical event, and the type and duration of the condition studied.

Evidence from open-access studies

These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.

Study comparison — selected abstracts, not a systematic review
Study / authorsYearSource label / designEurope PMC citationsLicence / source
Non-coding cis-regulatory variants in HK1 cause congenital hyperinsulinism with variable disease severity
Bennett JJ, Saint-Martin C, Neumann B, Männistö JME, Houghton JAL, Empting S, et al.
2025Research article
Design not recorded in structured metadata
11cc by
PMID 40033430 · DOI · PMC11874398
The challenge of assessing impaired awareness of hypoglycaemia in diabetes in the era of continuous glucose monitoring: A narrative review of evidence and translation into clinical practice
Berry SA, Liarakos AL, Koutroukas V, Choudhary P, Wilmot EG, Iqbal A
2025Review article
Design not recorded in structured metadata
10cc by
PMID 39996361 · DOI · PMC11965031
Hypoglycemia incidence and behavioural adjustments during free-living unstructured physical activity in adults with type 1 diabetes using AID systems: Results from the RAPPID study
Joubert M, Meyer L, Bekka S, Rakotoarisoa L, Scheyer N, Dreves B, et al.
2025Research article
Design not recorded in structured metadata
8cc by
PMID 40926369 · DOI · PMC12587226
Accuracy and reliability of a continuous glucose monitoring system with a focus on hypoglycaemia
van Baal L, Raess L, Mathew A, Lahner H, Unger N, Fuhrer D
2026Research article
Design not recorded in structured metadata
4cc by
PMID 41448958 · DOI · PMC12890745

Non-coding cis-regulatory variants in HK1 cause congenital hyperinsulinism with variable disease severity [1]

Research article Bennett JJ, Saint-Martin C, Neumann B, Männistö JME, Houghton JAL, Empting S, et al. · · 2025 · cited 11 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
BackgroundWe recently reported non-coding variants in a cis-regulatory element of the beta-cell disallowed gene hexokinase 1 (HK1) as a novel cause of congenital hyperinsulinism.
Closing excerpt
Discovering variants in 89 families confirms HK1 as a major cause of hyperinsulinism and highlights the important role of the non-coding genome in human monogenic disease.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (269 words)

BackgroundWe recently reported non-coding variants in a cis-regulatory element of the beta-cell disallowed gene hexokinase 1 (HK1) as a novel cause of congenital hyperinsulinism. These variants lead to a loss of repression of HK1 in pancreatic beta-cells, causing insulin secretion during hypoglycaemia. In this study, we aimed to determine the prevalence, genetics, and phenotype of HK1-hyperinsulinism by screening a large international cohort of patients living with the condition.MethodsWe screened the HK1 cis-regulatory region in 1761 probands with hyperinsulinism of unknown aetiology who had been referred to one of three large European genomics laboratories.ResultsWe identified a HK1 variant in 89/1761 probands (5%) and 63 family members. Within the Exeter HI cohort, these variants accounted for 2.8% of all positive genetic diagnoses (n = 54/1913) establishing this as an important cause of HI. Individuals with a disease-causing variant were diagnosed with hyperinsulinism between birth and 26 years (median: 7 days) with variable response to treatment; 80% were medically managed and 20% underwent pancreatic surgery due to poor response to medical therapy. Glycaemic outcomes varied from spontaneous remission to hypoglycaemia persisting into adulthood. Eight probands had inherited the variant from a parent not reported to have hyperinsulinism (median current age: 39 years), confirming variable penetrance. Two of the 23 novel HK1 variants allowed us to extend the minimal cis-regulatory region from 42 to 46 bp.ConclusionsNon-coding variants within the HK1 cis-regulatory region cause hyperinsulinism of variable severity ranging from neonatal-onset, treatment-resistant disease to being asymptomatic into adulthood. Discovering variants in 89 families confirms HK1 as a major cause of hyperinsulinism and highlights the important role of the non-coding genome in human monogenic disease.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40033430 · DOI · PMC11874398

The challenge of assessing impaired awareness of hypoglycaemia in diabetes in the era of continuous glucose monitoring: A narrative review of evidence and translation into clinical practice [2]

Review article Berry SA, Liarakos AL, Koutroukas V, Choudhary P, Wilmot EG, Iqbal A · · 2025 · cited 10 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
Iatrogenic hypoglycaemia remains a major barrier in diabetes care.
Closing excerpt
We conclude that a clinical approach involving traditional questionnaires, or newer updated alternatives such as the Hypo A-Q awareness scale, combined with CGM metrics and clinical assessment of human factors is recommended in the absence of a clearly superior measure.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (248 words)

Iatrogenic hypoglycaemia remains a major barrier in diabetes care. Over time, and with repeated hypoglycaemic episodes, the physiological responses to hypoglycaemia can become blunted, resulting in impaired awareness of hypoglycaemia (IAH). In IAH, the onset of cognitive dysfunction precedes the onset of autonomic symptoms, often preventing appropriate self-treatment, thus increasing the frequency of severe hypoglycaemia (SH). Historically, IAH has been assessed with questionnaires, such as the Gold and Clarke scores, which were developed in the 1990s. A stepwise change in diabetes management in the last few decades has been the deployment of continuous glucose monitoring (CGM). CGM allows people with diabetes to set alarms that can warn them of hypoglycaemia or even impending hypoglycaemia, thus providing a degree of 'technological' awareness. This creates a challenge in assessing awareness status, as people may be alerted to low-sensor glucose events before they experience any symptoms. CGM also allows the introduction of new measures of hypoglycaemia exposure such as time below range, which might complement traditional methods of risk assessment. These changes in the field prompt a need for reassessment of the measures of IAH. This narrative review evaluates the current epidemiology of SH and IAH, explores different measures of IAH, and evaluates the relationship between CGM metrics, IAH and SH. We conclude that a clinical approach involving traditional questionnaires, or newer updated alternatives such as the Hypo A-Q awareness scale, combined with CGM metrics and clinical assessment of human factors is recommended in the absence of a clearly superior measure.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39996361 · DOI · PMC11965031

Hypoglycemia incidence and behavioural adjustments during free-living unstructured physical activity in adults with type 1 diabetes using AID systems: Results from the RAPPID study [3]

Research article Joubert M, Meyer L, Bekka S, Rakotoarisoa L, Scheyer N, Dreves B, et al. · · 2025 · cited 8 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
AimsTo assess the frequency and management of hypoglycaemia during unstructured physical activity (PA) in adults with type 1 diabetes (T1D) using automated insulin delivery (AID) systems in real-life settings.
Closing excerpt
Individualised education remains essential to enhance safety.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (172 words)

AimsTo assess the frequency and management of hypoglycaemia during unstructured physical activity (PA) in adults with type 1 diabetes (T1D) using automated insulin delivery (AID) systems in real-life settings.Materials and methodsRAPPID is a prospective, multicenter, observational study conducted over 1 month in four French tertiary care centres. Adults with T1D using one of three AID systems (MiniMed 780G, Tandem t:slim X2 with Control-IQ, or Ypsopump with CamAPS FX) and performing ≥2 unstructured PA sessions per week were included. Participants completed paper logbooks documenting each PA session (type, intensity, hypoglycemia, adjustments). Continuous glucose monitoring (CGM) and pump data were downloaded. Glycaemic control was assessed using CGM-derived metrics within predefined peri-exercise time windows.ResultsEighty-six participants (mean age 42.5 ± 14.3 years; 43% women; diabetes duration 23.6 ± 13.1 years; mean HbA1c 52 ± 7 mmol/mol (6.9% ± 0.6%)) reported 954 PA sessions (73% aerobic; 61% moderate intensity). TBR (ConclusionsHypoglycemia remains common during and after PA in AID users. Suboptimal adjustment strategies and impaired symptom awareness contribute to risk. Individualised education remains essential to enhance safety.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40926369 · DOI · PMC12587226

Accuracy and reliability of a continuous glucose monitoring system with a focus on hypoglycaemia [4]

Research article van Baal L, Raess L, Mathew A, Lahner H, Unger N, Fuhrer D · · 2026 · cited 4 times (Europe PMC)

Abstract reading summary — source excerpts
Opening excerpt
AimsGlucose monitoring is increasingly based on continuous glucose monitoring (CGM) systems.
Closing excerpt
While it remains acceptable in people with diabetes receiving subcutaneous insulin therapy and people with insulinoma, it appears to be inaccurate for glucose monitoring during ITT.
Interpretation limits
Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (189 words)

AimsGlucose monitoring is increasingly based on continuous glucose monitoring (CGM) systems. However, data on the accuracy of CGM within the hypoglycaemic range is sparse. This study investigated CGM accuracy within the hypoglycaemic range in three different clinical settings of hypoglycaemia.Materials and methodsNinety-two people with various causes of hypoglycaemia were analysed: (i) people during insulin tolerance testing (ITT) (n = 63); (ii) people with insulinoma (n = 16); and (iii) people with diabetes receiving subcutaneous insulin therapy (n = 13). CGM accuracy was evaluated for subgroups and different glucose rates of change (RoC) using mean absolute relative difference (MARD), percentage of glucose values within ±20 mg/dL of point-of-care glucose (%20/20), diabetes technology society error grid and Bland-Altman analysis (BAA).ResultsFour hundred sixty-four CGM/POC glucose pairs were obtained (39.7% level 1, 60.3% level 2 hypoglycaemia). CGM accuracy decreased from people with diabetes receiving subcutaneous insulin therapy (MARD: 13.9%; %20/20: 81.5%) to those with ITT (MARD: 50.8%; p ConclusionCGM accuracy can vary in different clinical hypoglycaemia scenarios. While it remains acceptable in people with diabetes receiving subcutaneous insulin therapy and people with insulinoma, it appears to be inaccurate for glucose monitoring during ITT.

Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41448958 · DOI · PMC12890745

Key reviews and meta-analyses

The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.

  • Research article Continuous glucose monitoring and metrics for clinical trials: an international consensus statement [5]
    Battelino T, Alexander CM, Amiel SA, Arreaza-Rubin G, Beck RW, Bergenstal RM, et al. · Lancet Diabetes Endocrinol · 2023 · cited 696 times (Europe PMC)
  • Research article 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes-2024 [6]
    American Diabetes Association Professional Practice Committee · Diabetes Care · 2024 · cited 386 times (Europe PMC)
  • Research article Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysis [7]
    Goto A, Arah OA, Goto M, Terauchi Y, Noda M · BMJ · 2013 · cited 344 times (Europe PMC)
  • Research article 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes-2025 [8]
    American Diabetes Association Professional Practice Committee · Diabetes Care · 2025 · cited 326 times (Europe PMC)
  • Research article Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis [9]
    Bekiari E, Kitsios K, Thabit H, Tauschmann M, Athanasiadou E, Karagiannis T, et al. · BMJ · 2018 · cited 306 times (Europe PMC)
  • Research article A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin [10]
    Gangji AS, Cukierman T, Gerstein HC, Goldsmith CH, Clase CM · Diabetes Care · 2007 · cited 200 times (Europe PMC)

References

  1. Bennett JJ, Saint-Martin C, Neumann B, Männistö JME, Houghton JAL, Empting S, et al.. Non-coding cis-regulatory variants in HK1 cause congenital hyperinsulinism with variable disease severity. . 2025. PMID 40033430 · DOI · PMC11874398
  2. Berry SA, Liarakos AL, Koutroukas V, Choudhary P, Wilmot EG, Iqbal A. The challenge of assessing impaired awareness of hypoglycaemia in diabetes in the era of continuous glucose monitoring: A narrative review of evidence and translation into clinical practice. . 2025. PMID 39996361 · DOI · PMC11965031
  3. Joubert M, Meyer L, Bekka S, Rakotoarisoa L, Scheyer N, Dreves B, et al.. Hypoglycemia incidence and behavioural adjustments during free-living unstructured physical activity in adults with type 1 diabetes using AID systems: Results from the RAPPID study. . 2025. PMID 40926369 · DOI · PMC12587226
  4. van Baal L, Raess L, Mathew A, Lahner H, Unger N, Fuhrer D. Accuracy and reliability of a continuous glucose monitoring system with a focus on hypoglycaemia. . 2026. PMID 41448958 · DOI · PMC12890745
  5. Battelino T, Alexander CM, Amiel SA, Arreaza-Rubin G, Beck RW, Bergenstal RM, et al.. Continuous glucose monitoring and metrics for clinical trials: an international consensus statement. Lancet Diabetes Endocrinol. 2023. PMID 36493795 · DOI
  6. American Diabetes Association Professional Practice Committee. 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes-2024. Diabetes Care. 2024. PMID 38078586 · DOI · PMC10725808
  7. Goto A, Arah OA, Goto M, Terauchi Y, Noda M. Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysis. BMJ. 2013. PMID 23900314 · DOI
  8. American Diabetes Association Professional Practice Committee. 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes-2025. Diabetes Care. 2025. PMID 39651981 · DOI · PMC11635034
  9. Bekiari E, Kitsios K, Thabit H, Tauschmann M, Athanasiadou E, Karagiannis T, et al.. Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis. BMJ. 2018. PMID 29669716 · DOI · PMC5902803
  10. Gangji AS, Cukierman T, Gerstein HC, Goldsmith CH, Clase CM. A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin. Diabetes Care. 2007. PMID 17259518 · DOI

About this article

Sources
NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
Verification
Every reference was resolved against PubMed on 2026-11-04; title, year and DOI matched.
Review state
automated source verified; no human expert review has been recorded yet.
Version
1, last updated 2026-11-04.

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Related research topics

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All 77 articles in Metabolism and Endocrine Disease →

At a glance

34,179
PubMed records on this heading
17%
published since 2020
4,805
review articles
2,211
randomized trials
10
verified references below

Counts come from PubMed on 2026-10-31; they show how much has been written, not how strong the evidence is.

Related topics See all →

  • Glucose Metabolism DisordersMetabolism and Endocrine Disease
  • Glucose IntoleranceMetabolism and Endocrine Disease
  • GlycosuriaMetabolism and Endocrine Disease
  • Type 1 Diabetes MellitusMetabolism and Endocrine Disease
  • Type 2 Diabetes MellitusMetabolism and Endocrine Disease

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