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Cited by 0Cardiac electrophysiology and arrhythmiasDiabetes Management and ResearchPotassium and Related Disorders

Effect of Hypoglycemia on QT Interval in Individuals With and Without Type 2 Diabetes: A Randomized Crossover Trial

Open access
Haas, Andrea V, Koefoed, Andrew W, Celli, Johanna, Bonyhay, Istvan, White, Jeffrey, Meyer, Kayla M, Easly-Merski, Rebecca M, Heydarpour, Mahyar +2 more·2025·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/clinem/dgae919PMC PMC12342361
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Abstract

BACKGROUND: Our goal was to determine in healthy individuals and individuals with type 2 diabetes the impact of repeated episodes of hypoglycemia on the corrected QT (QTc) interval and the time course for QTc recovery. Further, since hypoglycemia increases aldosterone and patients with primary aldosteronism have prolonged QTc, we also determined whether mineralocorticoid receptor blockade prevents hypoglycemia-induced QTc alterations. METHODS: Twenty-seven healthy participants completed a double-blinded crossover trial contrasting 3 experimental conditions: (1) euglycemia, (2) hypoglycemia, and (3) hypoglycemia with mineralocorticoid receptor blockade pretreatment. Sixteen participants with type 2 diabetes completed 1 condition, hypoglycemia. Hyperinsulinemic clamps were performed to induce the hypoglycemic and euglycemic conditions. Electrocardiograms were performed before, during, and after the clamps. RESULTS: Healthy participants had a significant (P < .0001) prolongation of QTc during both the morning and afternoon hypoglycemic clamps as compared with euglycemic clamps (morning hypoglycemia vs euglycemia: 439.06 ± 41.18 ms vs 406.96 ± 26.16 ms; afternoon hypoglycemia vs euglycemia: 441.50 ± 34.36 ms vs 407.78 ± 19.18 ms). Mineralocorticoid receptor (MR) blockade did not alter the response to hypoglycemia. Participants with diabetes achieved a significant prolongation of QTc during the afternoon hypoglycemia only (afternoon hypoglycemia vs morning baseline: 461.96 ± 49.14 vs 428.90 ± 28.54, P < .05). In both participant populations, QTc intervals were similar to baseline 90 minutes after return to euglycemia and the following day. CONCLUSION: Hypoglycemia prolonged QTc in healthy participants, and this was not altered by MR blockade. In individuals with type 2 diabetes, 2 hypoglycemic episodes were required to achieve prolongation. Reassuringly, in both study populations, hypoglycemia-induced QTc prolongation resolved quickly with no apparent residual effects the next day.

Integrity signals

Registry

Crossref · 10.1210/clinem/dgae919

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

26 of 44 cited sources checked · 15 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Impaired baroreflex sensitivity persists at least 16 hours after recovery from hypoglycemia.

    “whereas impaired baroreflex sensitivity persists at least 16 hours after recovery from hypoglycemia (12)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [12] Adler, 2009, Antecedent hypoglycemia impairs autonomic cardiovascular function: implications for rigorous glycemic control, Diabetes source
      Experimental — accuracy not yet measured
  • Premisecitation

    Hypoglycemia is a reported cause of increased QTc in healthy adults and individuals with diabetes.

    “Hypoglycemia is a reported cause of an increase in QTc in healthy adults and individuals with diabetes (7–11, 15).”
    Quote in the paperSubstantial claim3 of 6 sources checked
    • cites [7] Marques, 1997, Altered ventricular repolarization during hypoglycaemia in patients with diabetes, Diabet Med source
    • cites [8] Robinson, 2003, Mechanisms of abnormal cardiac repolarization during insulin-induced hypoglycemia, Diabetes source
    • cites [9] Landstedt-Hallin, 1999, Increased QT dispersion during hypoglycaemia in patients with type 2 diabetes mellitus, J Intern Med source
    • cites [10] Lee, 2005, Effect of atenolol on QTc interval lengthening during hypoglycaemia in type 1 diabetes, Diabetologia source
    • cites [11] Chow, 2017, Cardiac autonomic regulation and repolarization during acute experimental hypoglycemia in type 2 diabetes, Diabetes source
    • cites [15] Fitzpatrick, 2018, Association of hypoglycaemia and risk of cardiac arrhythmia in patients with diabetes mellitus: a systematic review and meta-analysis, Diabetes Obes Metab source

      The Results (Accepted Article; page unavailable) report that hypoglycaemia was associated with significant QTc prolongation compared with euglycaemia in the pooled studies. The Materials and Methods specify that the review included adults with diabetes and extracted only their data when studies also included people without diabetes. Thus this source supports the claim for people with diabetes, but not its extension to healthy adults or a definitive causal interpretation. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
  • Premisecitation

    A recent meta-analysis did not demonstrate a significant association between QTc prolongation and hypoglycemia in type 2 diabetes.

    “a recent meta-analysis examining this relationship in patients with type 1 and type 2 diabetes did not demonstrate a significant association between QTc prolongation and hypoglycemia in type 2 diabetes (15).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [15] Fitzpatrick, 2018, Association of hypoglycaemia and risk of cardiac arrhythmia in patients with diabetes mellitus: a systematic review and meta-analysis, Diabetes Obes Metab source
  • Premisecitation

    Experimental hypoglycemia using hyperinsulinemic clamp protocols impairs cardiac repolarization.

    “Studies of experimentally induced hypoglycemia using hyperinsulinemic clamp protocols have shown hypoglycemia-induced impairments in cardiac repolarization (7–11)”
    Quote in the paperSubstantial claim2 of 5 sources checked
    • cites [7] Marques, 1997, Altered ventricular repolarization during hypoglycaemia in patients with diabetes, Diabet Med source
    • cites [8] Robinson, 2003, Mechanisms of abnormal cardiac repolarization during insulin-induced hypoglycemia, Diabetes source
    • cites [9] Landstedt-Hallin, 1999, Increased QT dispersion during hypoglycaemia in patients with type 2 diabetes mellitus, J Intern Med source
    • cites [10] Lee, 2005, Effect of atenolol on QTc interval lengthening during hypoglycaemia in type 1 diabetes, Diabetologia source
    • cites [11] Chow, 2017, Cardiac autonomic regulation and repolarization during acute experimental hypoglycemia in type 2 diabetes, Diabetes source
  • Premisecitation

    QTc values > 500 ms have been associated with an increased prevalence of torsades de pointes and other arrhythmias.

    “This is clinically relevant as QTc values > 500 ms have been associated with an increased prevalence of torsades de pointes and other arrhythmias (34).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [34] Drew, 2010, Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology foundation, Circulation source

      The “Premonitory ECG Signs of TdP” section states that QTc >500 ms is associated with a two- to threefold higher risk of torsades de pointes in congenital long-QT syndrome studies, with similar increased risk described in drug-induced cases. The copy does not establish that this threshold is associated with increased prevalence of other arrhythmias; the Summary lists other ventricular events as warning signs for torsades, not as outcomes associated with QTc >500 ms. Page numbers were not available in the supplied copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • May combine two claims. 18
  • Classified as probably not a substantial claim. 12
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    High aldosterone-to-renin ratios are associated with increased QTc, and QTc intervals are longer in patients with primary aldosteronism.

    “Specifically, high aldosterone-to-renin ratios are associated with increased QTc, and QTc intervals are longer in patients with primary aldosteronism (18, 19).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [18] Maule, 2006, QT interval in patients with primary aldosteronism and low-renin essential hypertension, J Hypertens source
    • cites [19] Grubler, 2016, Aldosterone-to-renin ratio is associated with reduced 24-hour heart rate variability and QTc prolongation in hypertensive patients, Medicine (Baltimore) source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Hypoglycemia releases IL-6 and other inflammatory cytokines.

    “A novel potential mechanism for hypoglycemia-induced QTc prolongation is the release of IL-6 and other inflammatory cytokines during hypoglycemia (28, 29).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [28] Ratter, 2017, Proinflammatory effects of hypoglycemia in humans with or without diabetes, Diabetes source
    • cites [29] Joy, 2010, Effects of acute hypoglycemia on inflammatory and pro-atherothrombotic biomarkers in individuals with type 1 diabetes and healthy individuals, Diabetes Care source

  • May combine two claims.

    Premisecitation

    A recent prospective analysis of individuals with type 2 diabetes in the ACCORD study showed that those who experienced severe hypoglycemia during 5-year follow-up had a 66% higher risk of QTc prolongation, with risk increasing if they had 2 or more episodes.

    “A recent prospective analysis of individuals with type 2 diabetes that were part of the ACCORD study showed that those who had experienced severe hypoglycemia (defined as a blood sugar < 50 mg/dL requiring medical assistance) at any point during a 5 year follow-up had a 66% higher risk of QTc prolonga-ion and the risk increased if an individual had 2 or more episodes of severe hypoglycemia (24).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [24] Kaze, 2022, Severe hypoglycemia and incidence of QT interval prolongation among adults with type 2 diabetes, J Clin Endocrinol Metab source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Rigorous glycemic control is a primary focus of diabetes management but can increase the risk of hypoglycemia.

    “Rigorous glycemic control is a primary focus of diabetes management but can increase the risk of hypoglycemia (1).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [1] Cryer PE, American Diabetes Association, 2016 source

      The available passages are unnumbered front matter, not a discussion of glycemic control. Searches for rigorous or intensive glycemic control and hypoglycemia risk returned only that front matter, so our copy does not establish the attributed claim. (LLM, conf=0.72)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Other adverse physiologic effects of hypoglycemia, such as attenuation of baroreflex sensitivity and hyperalgesia, persist even after resolution of hypoglycemia.

    “Other adverse physiologic effects of hypoglycemia such as attenuation of baroreflex sensitivity (12) and hyperalgesia (37) persist even after resolution of hypoglycemia.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [12] Adler, 2009, Antecedent hypoglycemia impairs autonomic cardiovascular function: implications for rigorous glycemic control, Diabetes source
    • cites [37] Gibbons, 2012, Experimental hypoglycemia is a human model of stress-induced hyperalgesia, Pain source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Increased IL-6 levels are associated with prolonged QTc in patients with inflammatory conditions such as rheumatoid arthritis and infections including HIV and SARS-CoV-2.

    “Increased levels of IL-6 are associated with prolonged QTc in patients with inflammatory conditions such as rheumatoid arthritis and infections including HIV and SARS-CoV-2 (30–33).”
    Quote in the paperNot a substantial claim3 of 4 sources checked
    • cites [30] Adlan, 2015, Association between corrected QT interval and inflammatory cytokines in rheumatoid arthritis, J Rheumatol source
    • cites [31] Wu, 2019, Predictors of electrocardiographic QT interval prolongation in men with HIV, Heart source

      The Results (page not provided) report that higher IL-6 levels were associated with longer QTc in a cohort that included men with HIV. The Discussion links systemic inflammation more generally—not IL-6 specifically—to longer QTc in rheumatoid arthritis. The paper does not address SARS-CoV-2, so it does not support the full sentence. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [32] Lazzerini, 2020, Cardiac arrest risk during acute infections: systemic inflammation directly prolongs QTc interval via cytokine-mediated effects on potassium channel expression, Circ Arrhythm Electrophysiol source
    • cites [33] Rubin, 2021, Cardiac corrected QT interval changes among patients treated for COVID-19 infection during the early phase of the pandemic, JAMA Netw Open source

      The Results report that a subset analysis suggested an association between IL-6 and prolonged QTc in patients with COVID-19. The Discussion also reports an association between elevated IL-6 and QT prolongation in HIV. Our copy does not state that association for patients with rheumatoid arthritis; it mentions rheumatoid arthritis only in a reference title. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Studies in healthy individuals and individuals with type 1 diabetes have shown that beta-adrenergic receptor blockade can prevent QTc prolongation during hypoglycemia.

    “For example, studies in healthy individuals and individuals with type 1 diabetes have shown that blockade of the β-adrenergic receptor is capable of preventing QTc prolongation during hypoglycemia (8, 10).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [8] Robinson, 2003, Mechanisms of abnormal cardiac repolarization during insulin-induced hypoglycemia, Diabetes source
    • cites [10] Lee, 2005, Effect of atenolol on QTc interval lengthening during hypoglycaemia in type 1 diabetes, Diabetologia source

      The Introduction reports that atenolol largely prevented hypoglycaemic QTc lengthening in non-diabetic subjects. In this study’s type 1 diabetic adults, the Discussion says QTc increases were only partially prevented, so the claim overstates prevention in that group. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Hypoglycemia activates the renin-angiotensin-aldosterone system, increasing aldosterone levels in a dose-dependent manner.

    “Hypoglycemia activates the renin-angiotensin-aldosterone system, increasing aldosterone levels in a dose-dependent manner (17).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [17] Adler, 2010, Hypoglycaemia increases aldosterone in a dose-dependent fashion, Diabet Med source

      The Discussion reports that hypoglycaemia increased plasma renin activity and that the aldosterone rise depended on the depth of hypoglycaemia. Its Conclusions describe activation of the renin–angiotensin–aldosterone system as a likely explanation, alongside increased ACTH; the claim presents that mechanism as established. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Cardiac arrhythmia is thought to be a key mechanism underlying hypoglycemia-associated death.

    “Cardiac arrhythmia is thought to be a key mechanism underlying hypoglycemia-associated death (4).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [4] Investigators, 2013, Does hypoglycaemia increase the risk of cardiovascular events? A report from the ORIGIN trial, Eur Heart J source

      The Introduction (page unavailable) identifies ventricular arrhythmias as a possible effect of hypoglycaemia that may contribute to cardiovascular events. The Discussion (page unavailable) also considers other mechanisms and says hypoglycaemia may be a marker, rather than a cause, of adverse outcomes. The paper does not establish or single out arrhythmia as a key mechanism of hypoglycaemia-associated death. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    In participants with type 2 diabetes, average glucose was 2.85 ± 0.23 mmol/L during the morning clamp target period and 2.87 ± 0.26 mmol/L during the afternoon clamp target period, with no significant difference between morning and afternoon hypoglycemic clamps.

    “Average glucose was 2.85 ± 0.23 mmol/L during the morning clamp target glucose period and 2.87 ± 0.26 mmol/L during the afternoon clamp target glucose period (Fig. 3D). There was no significant difference in glucose levels between the morning and afternoon hypoglycemic clamps.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Average baseline QTc was 401.89 ms in healthy participants and 426.31 ms in participants with type 2 diabetes.

    “Average baseline QTc (average of measurements obtained prior to clamp study and spironolactone administration) was 401.89 ms in healthy participants and 426.31 ms in participants with type 2 diabetes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In healthy participants, at an individual level, QTc was longer with spironolactone 44.6% of the time and longer with placebo 55.4% of the time (P = .84).

    “In further support of the lack of effect of spironolactone on QTc, we found that at an individual level 44.6% of the time QTc was longer with spironolactone and 55.4% of the time QTc was longer with placebo (P-value .84).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The spironolactone regimen used in the healthy participant study produced effective acute mineralocorticoid receptor blockade.

  • The quote only partly states this claim.

    Findingown data

    In participants with type 2 diabetes, QTc prolongation versus baseline did not reach statistical significance during morning hypoglycemia (P = .06).

    “In participants with diabetes, QTc prolongation vs baseline did not reach statistical significance during the morning hypoglycemia (P = .06).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In a model corrected for age, BMI, and blood pressure, sex and disease status predicted baseline QTc; sex predicted 21.8 ms longer QTc in females than males, and type 2 diabetes predicted 26.0 ms longer QTc than healthy status.

    “Sex (P = .0008) and disease status (diabetes or no diabetes; P = .008) predict baseline QTc in a model corrected for age, BMI, and blood pressure. Sex predicts a 21.8 ms longer QTc in females compared with males, and disease status predicts a 26.0 ms longer QTc in individuals with type 2 diabetes compared with healthy individuals.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In a model predicting maximum QTc during hypoglycemia for both groups, baseline QTc predicted maximum QTc (P = .005), while sex, age, disease status, BMI, blood pressure, potassium, insulin, glucose, heart rate variability, and Valsalva ratio did not.

    “In a model to predict the maximum QTc during hypoglycemia for both healthy individuals and those with type 2 diabetes, baseline QTc predicted maximum QTc (P = .005), but sex, age, disease status, BMI, blood pressure, potassium, insulin, glucose, heart rate variability, and Valsalva ratio did not predict maximum QTc.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Randomization for the healthy participant study was performed by the Investigational Drug Services at Brigham and Women's Hospital.

    “Randomization was determined by the Investigational Drug Services at Brigham and Women’s Hospital.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Interobserver differences in QT measurement were 12.7 ± 10.2 ms (3.3%) for healthy participants and 17.4 ± 11.6 ms (4.4%) for participants with type 2 diabetes.

    “The mean interobserver difference for the healthy participants was 12.7 ± 10.2 ms or 3.3% and 17.4 ± 11.6 ms or 4.4% for participants with type 2 diabetes.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    Healthy participants were studied in a three-arm, randomized, double-blinded crossover trial comparing hypoglycemic clamp with placebo, euglycemic clamp with placebo, and hypoglycemic clamp with spironolactone.

    “Healthy individuals participated in a 3-arm, randomized, double-blinded, crossover study (ClinicalTrials.gov NCT03429946) (Fig. 1). The 3 treatments were hypoglycemic-hyperinsulinemic clamp with placebo, euglycemic-hyperinsulinemic clamp with placebo, and hypoglycemic-hyperinsulinemic clamp with spironolactone.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The three treatments in healthy participants were given in random order and separated by at least four weeks.

    “The 3 treatments were performed in random order and separated by at least 4 weeks.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    In 7 of 16 participants with type 2 diabetes, continuous glucose monitoring before admission confirmed absence of hypoglycemia, with less than 2% of glucose values below 3.88 mmol/L.

    “prior to the inpatient visit, 7 out of 16 participants had a continuous glucose monitor placed to verify absence of hypoglycemic episodes. For the 7 participants who had a continuous glucose monitor, all were confirmed to be free of hypoglycemia (<2% of blood glucose values <3.88 mmol/L).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    QT intervals were measured manually by two independent readers, with discrepancies greater than 2 SDs remeasured and persistent discrepancies resolved by a senior investigator blinded to treatment.

    “Repolarization analysis and measurement of the QT interval were completed manually by 2 independent readers using digital calipers (Mitutoyo, ABSOLUTE Digimatic Caliper Series 500, Aurora, IL).”
    • Also stated in: § ECG and Repolarization (QTc) Measurements · plain
      “In cases of persistent discrepancy, a senior investigator, blinded to treatment, reevaluated the ECG traces to resolve the discrepancy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Hypoglycemia prolonged QTc in healthy participants, and MR blockade did not alter this prolongation.

    “Hypoglycemia prolonged QTc in healthy participants, and this was not altered by MR blockade.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The spironolactone regimen used in the healthy participant study produced effective acute mineralocorticoid receptor blockade.

  • May combine two claims.

    Interpretationown data

    Baseline QTc predicts maximum QTc during hypoglycemia, indicating that those with the longest baseline QTc are at greatest risk during hypoglycemia.

    “Maximum QTc during hypoglycemia is predicted by baseline QTc, indicating that those who have the longest QTc at baseline are at the greatest risk during hypoglycemia.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    In both study populations, hypoglycemia-induced QTc prolongation resolved quickly, with no apparent residual effects the next day.

    “Reassuringly, in both study populations, hypoglycemia-induced QTc prolongation resolved quickly with no apparent residual effects the next day.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Individuals with type 2 diabetes and women may be at increased risk of reaching concerningly long QTc intervals during hypoglycemia.

    “This suggests that individuals with type 2 diabetes and women, who have longer baseline QTc as observed in this study and by others (35, 36), may be at increased risk of reaching concerningly long QTc intervals during hypoglycemia.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [35] Vink, 2018, Effect of age and gender on the QTc-interval in healthy individuals and patients with long-QT syndrome, Trends Cardiovasc Med source
    • cites [36] Veglio, 2002, Prevalence of increased QT interval duration and dispersion in type 2 diabetic patients and its relationship with coronary heart disease: a population-based cohort, J Intern Med source
25 of 25

  • The paper relies on this without support.

    The spironolactone regimen used in the healthy participant study produced effective acute mineralocorticoid receptor blockade.

    “Healthy participants received treatment with 2 doses of 100 mg spironolactone or placebo: 1 dose at 7:00 PM on day 1 and 1 dose at 6:00 AM on day 2.”

  • The paper relies on this without support.

    In participants with type 2 diabetes, the afternoon QTc prolongation observed without a euglycemic control condition is attributable to hypoglycemia rather than to time, order, or repeated clamp effects.

    “In order to increase recruitment of individuals with type 2 diabetes, this population was exposed to hypoglycemic clamps without euglycemic control clamps, which is a limitation.”

  • The paper relies on this without support.

    All participants with type 2 diabetes were free of recent hypoglycemia before the study, despite continuous glucose monitoring being performed in only 7 of 16.

    “prior to the inpatient visit, 7 out of 16 participants had a continuous glucose monitor placed to verify absence of hypoglycemic episodes.”
3 of 3

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Age adjustment conflicts with the listed baseline model

    Minor

    The specified variables for the baseline-QTc regression omit age, but the results describe its baseline-QTc estimates as corrected for age.

  • Diabetes group is described as having a euglycemic clamp

    Minor

    The text says both groups underwent hypoglycemic and euglycemic clamps, but the methods say participants with type 2 diabetes completed only the hypoglycemic condition. This changes whether that group had a euglycemic control.

  • Healthy-participant study size differs across sections

    Minor

    The abstract says 27 healthy participants completed the crossover trial, while the discussion says the studies were performed in 24. The text does not explain why these counts differ.

3 of 3

Cites

Flagged first, then by citations

Related

Authors
Haas, A. V., Koefoed, A. W., Celli, J., Bonyhay, I., White, J., Meyer, K. M., Easly-Merski, R. M., Heydarpour, M., Adler, G. K., & Freeman, R.
Affiliations
  • Brigham and Women's Hospital (US)
  • Beth Israel Deaconess Medical Center (US)
Corresponding author
Haas, Andrea V
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2025-01-09
Volume
110
Issue
9
Pages
e2908-e2917
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/clinem/dgae919
PMC
PMC12342361
OpenAlex
W4406212624
Cited by
0
References
38
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
Funders
National Institutes of Health (K23HL155076, R01HL109634, R01HL111465, K24HL103845, NCT03429946, NCT03422471)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Potassium and Related Disorders
Keywords
hypoglycemia, QTc interval, type 2 diabetes, mineralocorticoid receptor blockade, aldosterone, primary aldosteronism, hyperinsulinemic-euglycemic clamp, cardiac repolarization, normoglycemia, electrolytes, magnesium, sodium, dietary magnesium, dietary calcium
MeSH terms
Adult, Aged, Mineralocorticoid Receptor Antagonists, Blood Glucose, Diabetes Mellitus, Type 2, Double-Blind Method, Electrocardiography, Female, Humans, Hypoglycemia, Long QT Syndrome, Male, Middle Aged, Glucose Clamp Technique, Cross-Over Studies

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Claims read under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

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