ArticleThe Journal of clinical endocrinology and metabolism2019
Mild Physiologic Hyperglycemia Induces Hepatic Insulin Resistance in Healthy Normal Glucose-Tolerant Participants.
Article in The Journal of clinical endocrinology and metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- The optimal exercise modality and dose for glycemic control in older adults with type 2 diabetes mellitus: a systematic review and network meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Continuous glucose monitor overestimates glycemia, with the magnitude of bias varying by postprandial test and individual - a randomized crossover trial.The American journal of clinical nutrition · 2025Trial
- β-Cell function and body mass index are predictors of exercise response in elderly patients with prediabetes.Journal of diabetes investigation · 2022Trial
- Impact of prolonged fasting on insulin secretion, insulin action, and hepatic versus whole body insulin secretion disposition indices in healthy young males.American journal of physiology. Endocrinology and metabolism · 2021Trial
- Exercise-Induced Improvements in Postprandial Glucose Response Are Blunted by Pre-Exercise Hyperglycemia: A Randomized Crossover Trial in Healthy Individuals.Frontiers in endocrinology · 2020Trial
- Insulin Resistance and Cutaneous Squamous Cell Carcinoma: A Narrative Review of Molecular Mechanisms.Iranian journal of medical sciences · 2026Review
- Incidence of Cardiovascular Events in Hypertensive Patients Based on the Quantity of Major Risk Factors According to the Isfahan Cohort Study.International journal of hypertension · 2025Article
- Normoglycemia and physiological cortisone level maintain glucose homeostasis in a pancreas-liver microphysiological system.Communications biology · 2024Article
- Comprehensive analysis of the association between triglyceride-glucose index and coronary artery disease severity across different glucose metabolism states: a large-scale cross-sectional study from an Asian cohort.Cardiovascular diabetology · 2024Article
- Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity.Cell metabolism · 2024Article
- New Insights into Cardiovascular Diseases Treatment Based on Molecular Targets.International journal of molecular sciences · 2023Review
- Hexokinase-linked glycolytic overload and unscheduled glycolysis in hyperglycemia-induced pathogenesis of insulin resistance, beta-cell glucotoxicity, and diabetic vascular complications.Frontiers in endocrinology · 2023Article
- Effects of Sustained Hyperglycemia on Skeletal Muscle Lipids in Healthy Subjects.The Journal of clinical endocrinology and metabolism · 2022Article
- Ten things to know about ten cardiovascular disease risk factors - 2022.American journal of preventive cardiology · 2022Review
- Impaired Suppression of Glucagon in Obese Subjects Parallels Decline in Insulin Sensitivity and Beta-Cell Function.The Journal of clinical endocrinology and metabolism · 2021Article
- Ten things to know about ten cardiovascular disease risk factors.American journal of preventive cardiology · 2021Review
- Data mining: The association of 2-h postprandial plasma glucose with the fasting plasma glucose in a large Chinese population.Journal of clinical laboratory analysis · 2020Article
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- Uncontrolled Diabetes as an Associated Factor with Dynapenia in Adults Aged 50 Years or Older: Sex Differences.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
contextChronic hyperglycemia worsens skeletal muscle insulin resistance and β-cell function. However, the effect of sustained physiologic hyperglycemia on hepatic insulin sensitivity is not clear.
objectiveTo examine the effect of sustained physiologic hyperglycemia (similar to that observed in patients with type 2 diabetes) on endogenous (primarily reflecting hepatic) glucose production (EGP) in healthy individuals.
designVolunteers participated in a three-step hyperinsulinemic (10, 20, 40 mU/m2 per minute) euglycemic clamp before and after a 48-hour glucose infusion to increase plasma glucose concentration by ∼40 mg/dL above baseline. EGP was measured with 3-3H-glucose before and after chronic glucose infusion.
participantsSixteen persons with normal glucose tolerance [eight with and eight without a family history (FH) of diabetes] participated in the study.
main outcome measureEGP.
resultsBasal EGP increased following 48 hours of glucose infusion (from a mean ± SEM of 2.04 ± 0.08 to 3.06 ± 0.29 mg/kgffm⋅ min; P < 0.005). The hepatic insulin resistance index (basal EGP × fasting plasma insulin) markedly increased following glucose infusion (20.1 ± 1.8 to 51.7 ± 6.6; P < 0.005) in both FH+ and FH- subjects.
conclusionSustained physiologic hyperglycemia for as little as 48 hours increased the rate of basal hepatic glucose production and induced hepatic insulin resistance in health persons with normal glucose tolerance, providing evidence for the role of glucotoxicity in the increase in hepatic glucose production in type 2 diabetes.
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