Endocrinology and Metabolism

Original Articles

Diabetes, obesity and metabolism
Distinct Pituitary-Adrenal Responses to Hypoglycemia in Type 1 and Type 2 Diabetes: Yun Hu, Reng-na Yan, Ting-ting Cai, Xiao-wei Zhu, Jian-hua Ma, Bo Ding; Endocrinol Metab. 2026;41(1):162-173. Published online December 3, 2025; DOI: https://doi.org/10.3803/EnM.2025.2479

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Abstract PDF Supplementary Material PubReader ePub: Background
Hypoglycemia remains a major barrier to optimal glycemic control in diabetes. Counter-regulatory hormonal responses, particularly those involving the pituitary and adrenal systems, play a central role in mitigating hypoglycemia, yet differences between diabetes subtypes are not well characterized. We aimed to investigate pituitary-target gland responses to hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM).
Methods
We enrolled drug-naive patients with newly diagnosed T2DM or T1DM, along with controls who did not have diabetes. Participants with diabetes received insulin pump therapy until normoglycemia was achieved. Hyperinsulinemic euglycemic-hypoglycemic clamps were then performed in all participants. Hormonal profiles of the pituitary-adrenal axis and C-peptide were serially measured during the clamps.
Results
During hypoglycemic clamps, C-peptide, thyroid-stimulating hormone, estradiol, and testosterone decreased, whereas prolactin, adrenocorticotropic hormone (ACTH), cortisol, and growth hormone (GH) increased significantly according to repeatedmeasures analysis of variance (ANOVA) (P<0.05 for all). Compared to controls and T2DM, patients with T1DM exhibited elevated basal GH (P=0.002) and an exaggerated GH response to hypoglycemia (P=0.002), with earlier onset and sustained elevation. In contrast, patients with T2DM showed higher ACTH (P=0.024) and cortisol (P=0.043) levels during hypoglycemia compared to controls and T1DM. Relative to the T1DM group, the T2DM group demonstrated lower testosterone and higher estradiol levels during hypoglycemia (P<0.001 for both).
Conclusion
Distinct diabetes subtypes demonstrate divergent pituitary-adrenal counter-regulatory responses to hypoglycemia, suggesting unique pathogenic mechanisms contributing to glycemic variability. The exaggerated GH response in T1DM may aggravate glucose fluctuations, whereas elevated ACTH and cortisol in T2DM could perpetuate insulin resistance.

Diabetes, obesity and metabolism
Plasma C-Peptide Levels and the Continuous Glucose Monitoring-Defined Coefficient of Variation in Risk Prediction for Hypoglycemia in Korean People with Diabetes Having Normal and Impaired Kidney Function: So Yoon Kwon, Jiyun Park, So Hee Park, You-Bin Lee, Gyuri Kim, Kyu Yeon Hur, Jae Hyeon Kim, Sang-Man Jin; Endocrinol Metab. 2025;40(2):268-277. Published online February 27, 2025; DOI: https://doi.org/10.3803/EnM.2024.2083

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Background
We aimed to investigate the predictive values of plasma C-peptide levels and the continuous glucose monitoring (CGM)-defined coefficient of variation (CV) in risk prediction for hypoglycemia in Korean people with diabetes with normal and impaired kidney function.
Methods
We analyzed data from 1,185 participants diagnosed with type 1 and type 2 diabetes who underwent blinded professional CGM between January 2009 and May 2021 at outpatient clinics. We explored correlations among CGM-defined CV, plasma C-peptide levels, and time below range at <70 and 54 mg/dL across different kidney function categories.
Results
In patients with chronic kidney disease (CKD) stages 1–2 (n=934), 89.3% who had a random plasma C-peptide level higher than 600 pmol/L exhibited a CV of ≤36%. Among those in CKD stage 3 (n=161) with a random plasma C-peptide level exceeding 600 pmol/L, 66.7% showed a CV of ≤36%. In stages 4–5 of CKD (n=90), the correlation between random C-peptide levels and CV was not significant (r=–0.05, P=0.640), including cases with a CV greater than 36% despite very high random plasma C-peptide levels. Random plasma C-peptide levels and CGM-assessed CV significantly predicted hypoglycemia in CKD stages 1–2 and 1–5, respectively.
Conclusion
The established C-peptide criteria in Western populations are applicable to Korean people with diabetes for hypoglycemic risk prediction, unless kidney function is impaired equivalent to CKD stage 3–5. The CGM-defined CV is informative for hypoglycemic risk prediction regardless of kidney function.

Citations

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Continuous glucose monitoring in high-risk individuals
Zhiyue Chen, Yinbei Zhang, Lin Sun, Weiying Guo
Clinica Chimica Acta.2026; 580: 120733. CrossRef
The evolution of C-peptide's role in diabetes care
Laura Briggs, Alexander Read, Sarah Darch, Emma L. Williams, Wann Jia Loh, Julia S. Kenkre
Current Opinion in Endocrinology, Diabetes & Obesity.2026; 33(1): 16. CrossRef
Antidiabetic Potential of Brewed Arabica Coffee: Modulation of GLUT4, Insulin, and Glucagon in STZ‐Induced Rats
Yusni Yusni, Hanifah Yusuf, Said Usman, Iflan Nauval, Hasanuddin Hasanuddin, Fahmi Ichwansyah, Nurul Mahmudati, Eric Gumpricht
Journal of Nutrition and Metabolism.2026;[Epub] CrossRef
Recent Advances in the Application of C-Peptide in Type 2 Diabetes Management: From Biomarker to Clinical Decision Tool
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Advances in Clinical Medicine.2026; 16(04): 3314. CrossRef
Plasma C-Peptide Level and Continuous Glucose Monitoring-Derived Coefficient of Variation as a Predictable Risk Factor for Hypoglycemia in Koreans with Diabetes
Seung-Hyun Ko
Endocrinology and Metabolism.2025; 40(2): 198. CrossRef
Beneficial Role of Increased Glucose Infusion in Decompensated Type 2 Diabetes Patient
Marie Ticha, Ondrej Sobotka, Pavel Skorepa, Lubos Sobotka
Diabetology.2025; 6(6): 47. CrossRef

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Time to Insulin Therapy and Severe Hypoglycemia in Korean Adults Initially Diagnosed with Type 2 Diabetes: A Nationwide Study: You-Bin Lee, Kyungdo Han, Bongsung Kim, So Hee Park, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim, Sang-Man Jin; Endocrinol Metab. 2025;40(3):421-433. Published online February 4, 2025; DOI: https://doi.org/10.3803/EnM.2024.2082

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Abstract PDF Supplementary Material PubReader ePub: Background
We examined the distribution of time to insulin therapy (TIT) post-diabetes diagnosis and the hazard of severe hypoglycemia (SH) according to TIT in Korean adults initially diagnosed with type 2 diabetes (T2D) and who progressed to insulin therapy.
Methods
Using data from the Korean National Health Insurance Service (2002 to 2018), we selected adult incident insulin users (initially diagnosed as T2D) who underwent health examinations between 2009 and 2012. The hazards of SH, recurrent SH, and problematic hypoglycemia were analyzed according to groups categorized using the TIT and clinical risk factors for SH (TIT ≥5 years with risk factors, TIT ≥5 years without risk factors, 3 ≤TIT <5 years, 1 ≤TIT <3 years, and TIT <1 year).
Results
Among 41,637 individuals, 14,840 (35.64%) and 10,587 (25.43%) initiated insulin therapy within <5 and <3 years postdiabetes diagnosis, respectively. During a median 6.53 years, 3,406 SH events occurred. Compared to individuals with TIT ≥5 years and no risk factor for SH, individuals with TIT <3 years had higher outcome hazards in a graded manner (adjusted hazard ratio [95% confidence intervals] for any SH: 1.117 [0.967 to 1.290] in those with 3 ≤TIT <5 years; 1.459 [1.284 to 1.657] in those with 1 ≤ TIT <3 years; and 1.515 [1.309 to 1.754] in those with TIT <1 year). This relationship was more pronounced in the non-obese subpopulation.
Conclusion
Among adults who progressed to insulin therapy after being diagnosed with T2D, a shorter TIT was not uncommon and may predict an increased risk of SH, particularly in non-obese patients.

Diabetes, obesity and metabolism
Efficacy and Safety of Omarigliptin, a Novel Once-Weekly Dipeptidyl Peptidase-4 Inhibitor, in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis: A.B.M. Kamrul-Hasan, Muhammad Shah Alam, Samir Kumar Talukder, Deep Dutta, Shahjada Selim; Endocrinol Metab. 2024;39(1):109-126. Published online January 23, 2024; DOI: https://doi.org/10.3803/EnM.2023.1839

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Background
No recent meta-analysis has holistically analyzed and summarized the efficacy and safety of omarigliptin in type 2 diabetes mellitus (T2DM). We conducted a meta-analysis to address this knowledge gap.
Methods
Electronic databases were searched to identify randomized controlled trials (RCTs) that included patients with T2DM who received omarigliptin in the intervention arm. The control arm consisted of either a placebo (passive control group [PCG]) or an active comparator (active control group [ACG]). The primary outcome assessed was changes in hemoglobin A1c (HbA1c), while secondary outcomes included variations in glucose levels, achievement of glycemic targets, adverse events (AEs), and hypoglycemic events.
Results
From 332 initially screened articles, data from 16 RCTs involving 8,804 subjects were analyzed. Omarigliptin demonstrated superiority over placebo in reducing HbA1c levels (mean difference, –0.58%; 95% confidence interval, –0.75 to –0.40; P<0.00001; I²=91%). Additionally, omarigliptin outperformed placebo in lowering fasting plasma glucose, 2-hour postprandial glucose, and in the percentage of participants achieving HbA1c levels below 7.0% and 6.5%. The glycemic efficacy of omarigliptin was similar to that of the ACG across all measures. Although the omarigliptin group experienced a higher incidence of hypoglycemic events compared to the PCG, the overall AEs, serious AEs, hypoglycemia, and severe hypoglycemia were comparable between the omarigliptin and control groups (PCG and ACG).
Conclusion
Omarigliptin has a favorable glycemic efficacy and safety profile for managing T2DM.

Citations

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Sanobia Yousuf, Muhammad Yakoob Ahmedani
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A.B.M. Kamrul-Hasan, Shahjada Selim, Faria Afsana, Lakshmi Nagendra, Rezwana Ahmed, Deep Dutta
Endocrine Practice.2025; 31(3): 315. CrossRef
Optimal Use of Once-Weekly Basal Insulin Efsitora Alfa in Type 1 and Type 2 Diabetes: A Systematic Review and Meta-Analysis
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Endocrine Practice.2025; 31(4): 471. CrossRef
Neuropsychiatric Effects of Tirzepatide: A Systematic Review and Meta-Analysis
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Renal effects and safety of tirzepatide in subjects with and without diabetes: A systematic review and meta-analysis
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Endocrinology and Metabolism.2025; 40(1): 112. CrossRef
Reasons for discontinuing tirzepatide in randomized controlled trials: A systematic review and meta-analysis
Abul Bashar Mohammad Kamrul-Hasan, Joseph M Pappachan, Deep Dutta, Lakshmi Nagendra, Mohammad Shafi Kuchay, Nitin Kapoor
World Journal of Diabetes.2025;[Epub] CrossRef
Effect of beinaglutide, a thrice-daily GLP-1 receptor agonist, on body weight and metabolic parameters: A systematic review and meta-analysis
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Omarigliptin ameliorates cisplatin-induced renal damage: Cross-talk between glucagon-like peptide-1, HMGB1/RAGE/TLR4 signaling, and TXNIP/NLRP3 inflammasome/gasdermin D axis
Shuruq E. Alsufyani, Hany H. Arab, Azza A.K. El-Sheikh, El-Shaimaa A. Arafa, Ahmed Fouad Hussein Hashad, Reham M. Goda, Tamer M. Naguib, Maaly A. Abd Elmaaboud, Mennatallah A. Elkady, Ahmed M. Kabel
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Thrice-Weekly Insulin Degludec Versus Once-Daily Insulin Glargine in Insulin-Naïve Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
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World Journal of Diabetes.2025;[Epub] CrossRef
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Abul Bashar Mohammad Kamrul-Hasan, Deep Dutta, Lakshmi Nagendra, Sindhu Doddabokikere Basavarajappa, Harish Bukkasagar Girijashankar, Ameya Joshi, Joseph M Pappachan
World Journal of Diabetes.2025;[Epub] CrossRef
Role of flibanserin in managing hypoactive sexual desire disorder in women: A systematic review and meta-analysis
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Medicine.2024; 103(25): e38592. CrossRef
Teneligliptin: A potential therapeutic approach for diabetic cardiomyopathy
Ashraf Al Madhoun
World Journal of Diabetes.2024; 15(8): 1654. CrossRef
Inhibition of Oxidative Stress and Related Signaling Pathways in Neuroprotection
Maja Jazvinšćak Jembrek
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Clinical Study Big Data Articles (National Health Insurance Service Database)
Effect of Teneligliptin versus Sulfonylurea on Major Adverse Cardiovascular Outcomes in People with Type 2 Diabetes Mellitus: A Real-World Study in Korea: Da Hea Seo, Kyoung Hwa Ha, So Hun Kim, Dae Jung Kim; Endocrinol Metab. 2021;36(1):70-80. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.777

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Background
Results regarding the cardiovascular (CV) effects of dipeptidyl peptidase-4 (DPP-4) inhibitors are inconsistent. This study aimed to assess the effects of teneligliptin, a DPP-4 inhibitor, on the risk of major CV outcomes in type 2 diabetes mellitus (T2DM) patients compared to sulfonylurea.
Methods
From January 1, 2015 to December 31, 2017, we conducted a retrospective cohort study using the Korean National Health Insurance Service database. A total of 6,682 T2DM patients who were newly prescribed DPP-4 inhibitors or sulfonylurea were selected and matched in a 1:1 ratio by propensity score. The hazard ratios (HRs) for all-cause mortality, hospitalization for heart failure (HHF), all-cause mortality or HHF, myocardial infarction (MI), stroke, and hypoglycemia were assessed.
Results
During 641 days of follow-up, the use of teneligliptin was not associated with an increased risk of all-cause mortality (HR, 1.00; 95% confidence interval [CI], 0.85 to 1.19), HHF (HR, 0.99; 95% CI, 0.86 to 1.14), all-cause mortality or HHF (HR, 1.02; 95% CI, 0.90 to 1.14), MI (HR, 0.90; 95% CI, 0.68 to 1.20), and stroke (HR, 1.00; 95% CI, 0.86 to 1.17) compared to the use of sulfonylurea. However, it was associated with a significantly lower risk of hypoglycemia (HR, 0.68; 95% CI, 0.49 to 0.94) compared to sulfonylurea therapy.
Conclusion
Among T2DM patients, teneligliptin therapy was not associated with an increased risk of CV events including HHF, but was associated with a lower risk of hypoglycemia compared to sulfonylurea therapy.

Citations

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Diabetes Research and Clinical Practice.2024; 208: 111098. CrossRef
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Da Hea Seo, Mina Kim, Yongin Cho, Seong Hee Ahn, Seongbin Hong, So Hun Kim
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Assessment of cardiovascular risk with sulfonylurea use in type 2 diabetes mellitus: A retrospective cohort study
Jari Delbaere, Ewoud Deboever, Bert Vaes, Frank Nobels, Pavlos Mamouris, Geert Goderis
Primary Care Diabetes.2024; 18(6): 599. CrossRef
Systematic review and meta-analysis of teneligliptin for treatment of type 2 diabetes
R. Pelluri, S. Kongara, V. R. Nagasubramanian, S. Mahadevan, J. Chimakurthy
Journal of Endocrinological Investigation.2023; 46(5): 855. CrossRef
Finding the most cost-effective option from commonly used Dipeptidyl peptidase-4 inhibitors in India: a systematic study
Harmanjit Singh, Ekta Arora, Seerat Narula, Mandeep Singla, Armaan Otaal, Jatin Sharma
Expert Review of Endocrinology & Metabolism.2023; 18(4): 347. CrossRef
Association Between DPP4 Inhibitor Use and the Incidence of Cirrhosis, ESRD, and Some Cancers in Patients With Diabetes
Yewon Na, Soo Wan Kim, Ie Byung Park, Soo Jung Choi, Seungyoon Nam, Jaehun Jung, Dae Ho Lee
The Journal of Clinical Endocrinology & Metabolism.2022; 107(11): 3022. CrossRef

Case Reports

A Case with Isolated ACTH Deficiency.: Myoung Sik Kim, Byung Doo Lee, Sang Min Shin, Young Il Kim, Byung Oh Jeong, Hong Jib Choi, Phil Ho Kim, Kyung Soo Ko, Jae Hong Park; J Korean Endocr Soc. 1996;11(4):538-543. Published online November 7, 2019

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Abstract PDF: Isolated ACTH deficiency is a rare cause of secondary adrenocortical insufficiency. Adrenal crisis in isolated ACTH deficiency is less common compared to primary adrenal insufficiency, but isolated ACTH deficiency is an important cause of hypoglycemia. Recently we experienced a 41-year-old man admitted because of mental confusion. On admission, plasma glucose and sodium concentration were 1.7, 132 mmol/L, respectively. Basal plasma ACTH and cortisol levels were low and other pituitary hormone showed normal response to combined pituitary stimulation test except growth hormone. Plasma ACTH concentration remained low even after intravenous injection of ovine corticotropin releasing factor. It suggest that the defect of ACTH secretion was apparently due to intrinsic pituitary rather than hypothalamic disease. The sellar CT showed the fossa to be filled by cerebrospinal fluid. After treatment with glucocorticoid, he had no further evidence of hypoglycemia and hyponatremia. In conclusion, we report a case of isolated ACTH deficiency with empty sella.

Diffuse Nesidioblastosis of the Pancreasin Adult with Persistent Hyperinsulinemic Hypoglycemia.: Seoung Ha Lee, Kean Young Hyoung, Geom Seog Seo, Bong Joo Shin, Chung Gu Cho, Kwang Soo Yang, Kwon Mook Chae, Ki Jung Yun; J Korean Endocr Soc. 1996;11(2):247-253. Published online November 7, 2019

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Abstract PDF: Nesidioblastosis is a term that describes multifocal hyperplasia of all panereatic cell components and is characterized primarily by their disorganization and proliferation throughout the entire panaeas. Adult onset nesidioblastosis is an extremely rare entity associated with hypersecretion of insulin. The authors have recently experieneed a case of nesidioblastosis in an adult. A 41-year old man was admitted due to interrnittenr hypoglycemic symptoms, that had been relieved by carbohydrate ingestion. Hyperinsulinemic hypoglycemia was documented during prolonged fast. Under the presumptive diagnosis of insulinoma, abdominal CT, celiac angiogram and percutaneous transhepatic portal venous sampling were done but we could not find any definitive mass. Eight-five percent of the panacas was removed. Pathologic examination of the resected pancreas revealed irregularly sized islets and scattering of small endocrine cell clusters throughout the acinar tissue and ductuloinsular complex.

Two Cases of hypoglycemia in IDDM patients with insulin antibody.: G A Kim, K W Lee, M R Kim, Y J Kim, J N Jang, S K Bae, B G Son; J Korean Endocr Soc. 1996;11(2):240-246. Published online November 7, 2019

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Abstract PDF: Hirata et al. first described the association of insulin antibodies with hypoglycemia attacks and decreased glucose tolerance in a patient who had not previously received insulin injections. Since that time there have been additional reports in the Japanese literature. Insulin antibodies are present in most of the patients who received insulin for a period of time, usually exceeding six weeks. There were several reports of hypoglycemia in patients with non-insulin-dependent diabetes mellitus who had developed insulin antibody after insulin administration and also in patients with insulin dependent diabetes mellitus. It is well known that either insulin antibody to the lower affinity site or insulin receptor antibody can be a eause of hypoglycemia. Recently, we experienced two cases of hypoglycemia in patient with insulin dependent diabetes rnellitus and non- insulin- dependent diabetes mellitus who had developed insulin antibody after insulin administration. Hereby we present these cases with review of the literature.

A Case of Non - Islet Cell Tumor Hypoglycemia.: Moon Hee Lee, Seung Sik Kang, Jin Lee, Sung Hee Ihm, Jae Myung Yoo, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park; J Korean Endocr Soc. 1995;10(1):65-69. Published online November 6, 2019

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Abstract PDF: The association between non-islet cell tumors and fasting hypoglycemia has been recognized since 1929. The humoral mediator of this non-islet cell tumor hypoglycemia(NICTH) is now known as IGF-II. Hypoglycemia develops commonly in the course of hepatocellular carcinoma(HCC), mostly late in the course and usually mild to moderate in severity. Rarely, severe hypoglycemia occurs early in the course of HCC, suggesting NICTH. We report a case of HCC in which hypoglycemic coma due to NICTH was the presenting symptom.A 52-year-old man developed mental confusion and seizures in the early morning. At emergency room, he was found to have severe hypoglycemia. Circulating levels of insulin, C-peptide, insulinlike growth factor-I(IGF-I) and growth hormone were reduced during hypoglycemia. Diagnostic work-up revealed that he had unresectable HCC. During admission, infusion of more than 400g of dextrose per day in addition to meals was required to prevent hypoglycemia. Because the chemotherapy was refused, he was transferred to a local hospital to receive infusions of dextrose.

A Case of Nesidioblastosis in Adult with Hyperinsulinemic Hypoglycemia.: Young Kee Shong, Hong Kyu Kim, Young Joo Min, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee, Duck Jong Han, Ho Jeong Lee, Ghi Su Kim, Gyung Yub Gong; J Korean Endocr Soc. 1994;10(3):273-277. Published online November 6, 2019

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Abstract PDF: Nesidioblastosis is a primarily childhood disease which is often associated with hyperinsulinemic hypoglycemia. It is very rarely found in adults. Only a few well documented cases are found in the world interature. The authors have recently experienced a case of nesidioblastosis in an adult. A 55-year-old man was admitted due to repeated episodes of reversible loss of consciousness. Hyperinsulinemic hypoglycemia was documented. Under the presumptive diagnosis of insulinoma, localization procedures were done but no definite tumor was found. Only suspicious gradient in insulin concentration was found around the head of pancreas by percutaneous transhepatic portal venous sampling. Exploratory laparotomy was performed and Whipple's operation was done. Seventy percent of proximal pancreas was removed. Histomorphometric study of the resected specimen revealed uneven graded hyperplasia of the islet cells with the most profuse hyperplasia in the head region and progressive decrease in the degree of hyperplasia to the body and tail. The patient remains euglycemia until 6 months after operation since immediate postoperative period and can tolerate 24 hour fasting without any medication.

Original Articles

Clinical Study
Impaired Cortisol and Growth Hormone Counterregulatory Responses among Severe Hypoglycemic Patients with Type 2 Diabetes Mellitus: Young A Rhyu, Ju-Young Jang, Sooyoun Park, Jee Hyun An, Dong-Lim Kim, Suk Kyeong Kim, Kee-Ho Song; Endocrinol Metab. 2019;34(2):187-194. Published online June 24, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.2.187

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Background

Elevated levels of cortisol and growth hormone are critical counterregulatory responses to severe hypoglycemia. However, the proportion and clinical characteristics of patients with type 2 diabetes mellitus (DM) who fail to show appropriate cortisol and/or growth hormone secretion in response to severe hypoglycemia have not been investigated.

Methods

We measured plasma cortisol and growth hormone levels in type 2 DM patients with severe hypoglycemia who visited the emergency department between 2006 and 2015.

Results

Of 112 hypoglycemic patients, 23 (20.5%) had an impaired cortisol response (<18 µg/dL) and 82 patients (73.2%) had an impaired growth hormone response (<5 ng/mL). Nineteen patients (17.0%) had impaired responses to both cortisol and growth hormone. The patients with impaired responses of cortisol, growth hormone, and both hormones were significantly older and more likely to be female, and had higher admission rates, lower growth hormone levels, and lower adrenocorticotropic hormone levels than the patients with a normal hormonal response. Multivariate logistic regression analysis indicated that an impaired growth hormone response was significantly associated with advanced age, shorter DM duration, a higher admission rate, and a higher body mass index (BMI). An impaired cortisol response was significantly associated with growth hormone levels. Patients with an impaired growth hormone response had higher admission rates than patients with a normal response.

Conclusion

A considerable number of type 2 DM patients had impaired cortisol and/or growth hormone responses to severe hypoglycemia. Advanced age, shorter DM duration, and higher BMI were independently associated with an abnormal growth hormone response.

Citations

Citations to this article as recorded by

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Indian Journal of Endocrinology and Metabolism.2026; 30(1): 85. CrossRef
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Abdulbasit Amin, Toyin Mohammed Salman
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Rana A. Ali, Eatemad A. Awadalla, Yahia A. Amin, Samer S. Fouad, Maha Abd-El Baki Ahmed, Mohammed H. Hassan, Emaad Abdel-Kahaar, Rehab H. Abdel-Aziz
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Diagnostic Modalities, Management Considerations, and Outcomes of Insulinoma: A Case Series from a Tertiary Care Centre
Anirudh J. Shetty, Liza Das, Satyam S. Jayant, Sanjay K. Bhadada, Rajender Kumar, Ajay Gulati, Surinder S. Rana, Harmandeep Singh, Uma N. Saikia, Arunanshu Behera, Bhagwant R. Mittal, Rama Walia, Pinaki Dutta
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Prediabetes and mild hepatosteatosis are associated with blunted cortisol response to glucagon but not to growth hormone
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Endocrinología, Diabetes y Nutrición (English ed.).2023; 70(10): 634. CrossRef
Cerebrospinal fluid levels of hypothalamic-pituitary-adrenal axis hormones in MCI and dementia due to Alzheimer’s disease: a systematic review
Felipe Duarte-Zambrano, Jorge A. Barrero, Ismena Mockus
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Maria Crespo-Masip, Aurora Pérez-Gómez, Carla Guzmán, Sandra Rayego, Nuria Doladé, Alicia García-Carrasco, Ramiro Jover, José Manuel Valdivielso
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Predetermined Anti-Diabetic Drug Regimen Adjustments during Ramadan Fasting: An Observational Study of Safety: Abdallah M. Beano, Mohammad A. Zmaili, Zaid H. Gheith, Ahmad M. Naser, Munther S. Momani, Al-Motassem F. Yousef, Ayman A. Zayed; Endocrinol Metab. 2017;32(2):265-273. Published online June 23, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.2.265

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Background

Many Muslim type 2 diabetes mellitus (T2DM) patients choose to fast the month of Ramadan despite the possible adverse health effects brought about by the change in dietary habits, among other things. Clinical data regarding the safety of multi-drug regimens during fasting are particularly scarce. The aim of the study was to evaluate the safety of a drug protocol devised by the authors to accommodate Ramadan's dietary changes, involving dose adjustments of four anti-diabetic drug regimens in T2DM patients fasting Ramadan.

Methods

In this prospective, observational, open-label study, 301 T2DM patients who wished to fast Ramadan were followed during Ramadan and the preceding month. The incidence of hypoglycemia, diabetic ketoacidosis (DKA) and non-ketotic hyperosmolar state (NKHS) was monitored. Patients were classified into four groups: A group (those taking metformin, sulfonylurea and insulin [n=33]); B group (metformin and sulfonylurea [n=89]); C group (metformin and insulin [n=96]); and D group (premixed 70/30, glargine or regular insulin [n=82]). During Ramadan, drug doses were adjusted as percentages of their pre-Ramadan values: 75% for sulfonylureas, 75% for glargine, 75% for premixed insulin 70/30 in two doses, and 75% for regular insulin. Metformin was adjusted to a twice-daily regimen.

Results

No cases of DKA or NKHS were reported. Hypoglycemia occurred at a lower rate than pre-Ramadan values in groups C, and D; and a similar rate in groups A, and B.

Conclusion

The data suggested that using the above protocol to adjust the doses of anti-diabetic drugs is safe in T2DM patients in regards to hypoglycemia, DKA, and NKHS.

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The physiological changing and the recommended management plans for the diabetic patient during Ramadan fasting; A review article
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A Systematic Review of Insulin Management Recommendations to Improve Glycemic Control and Reduce Hypoglycemic Events During Ramadan Fasting in Patients With Insulin-Requiring Type 2 Diabetes
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Review Articles

Hypoglycemia and Dementia: Sang Youl Rhee; Endocrinol Metab. 2017;32(2):195-199. Published online June 23, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.2.195

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Recently, cardiovascular morbidity and mortality have been continuously reduced in people with diabetes through the intensive management of multiple risk factors. However, contrary to this trend, the prevalence and clinical significance of neurodegenerative disorders are steadily increasing. In previous studies, diabetes mellitus has been found to play an important role in increasing the risk of dementia and cognitive dysfunction through various mechanisms. In particular, hypoglycemia is a frequent clinical situation in the strict management of diabetes and is well known as an important factor that directly affects the risk of dementia and cognitive impairment. This article describes the occurrence of hypoglycemia in patients with diabetes, and summarizes the resultant risks of dementia and cognitive dysfunction.

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Stepwise Approach to Problematic Hypoglycemia in Korea: Educational, Technological, and Transplant Interventions: Sang-Man Jin; Endocrinol Metab. 2017;32(2):190-194. Published online June 23, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.2.190

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Impaired awareness of hypoglycemia has been found to be prevalent in 20% to 40% of people with type 1 diabetes. If a similar prevalence exists in Koreans with type 1 diabetes, at a minimum, thousands of people with type 1 diabetes suffer at least one unpredicted episode of severe hypoglycemia per year in Korea. For patients with problematic hypoglycemia, an evidence-based stepwise approach was suggested in 2015. The first step is structured education regarding multiple daily injections of an insulin analog, and the second step is adding a technological intervention, such as continuous subcutaneous insulin infusion or real-time continuous glucose monitoring. The next step is a sensor-augmented pump, preferably with a low glucose suspension feature or very frequent contact, and the final step is islet or pancreas transplantation. In Korea, however, none of these treatments are reimbursed by the National Health Insurance, and thus have not been widely implemented. The low prevalence of type 1 diabetes means that Korean physicians are relatively unfamiliar with the new technologies in this field. Therefore, the roles of new technologies and pancreas or islet transplantation in the treatment of problematic hypoglycemia need to be defined in the current clinical setting of Korea.

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Protective and risk factors of impaired awareness of hypoglycemia in patients with type 1 diabetes: a cross-sectional analysis of baseline data from the PR-IAH study
Naoki Sakane, Ken Kato, Sonyun Hata, Erika Nishimura, Rika Araki, Kunichi kouyama, Masako Hatao, Yuka Matoba, Yuichi Matsushita, Masayuki Domichi, Akiko Suganuma, Seiko Sakane, Takashi Murata, Fei Ling Wu
Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef
A 4-Week, Two-Center, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of EOPatch in Well-Controlled Type 1 Diabetes Mellitus
Jiyun Park, Nammi Park, Sangjin Han, You-Bin Lee, Gyuri Kim, Sang-Man Jin, Woo Je Lee, Jae Hyeon Kim
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Original Articles

Clinical Study
1,5-Anhydro-D-Glucitol Could Reflect Hypoglycemia Risk in Patients with Type 2 Diabetes Receiving Insulin Therapy: Min Kyeong Kim, Hye Seung Jung, Soo Heon Kwak, Young Min Cho, Kyong Soo Park, Seong Yeon Kim; Endocrinol Metab. 2016;31(2):284-291. Published online May 27, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.284

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Background

The identification of a marker for hypoglycemia could help patients achieve strict glucose control with a lower risk of hypoglycemia. 1,5-Anhydro-D-glucitol (1,5-AG) reflects postprandial hyperglycemia in patients with well-controlled diabetes, which contributes to glycemic variability. Because glycemic variability is related to hypoglycemia, we aimed to evaluate the value of 1,5-AG as a marker of hypoglycemia.

Methods

We enrolled 18 adults with type 2 diabetes mellitus (T2DM) receiving insulin therapy and assessed the occurrence of hypoglycemia within a 3-month period. We measured 1,5-AG level, performed a survey to score the severity of hypoglycemia, and applied a continuous glucose monitoring system (CGMS).

Results

1,5-AG was significantly lower in the high hypoglycemia-score group compared to the low-score group. Additionally, the duration of insulin treatment was significantly longer in the high-score group. Subsequent analyses were adjusted by the duration of insulin treatment and mean blood glucose, which was closely associated with both 1,5-AG level and hypoglycemia risk. In adjusted correlation analyses, 1,5-AG was negatively correlated with hypoglycemia score, area under the curve at 80 mg/dL, and low blood glucose index during CGMS (P=0.068, P=0.033, and P=0.060, respectively).

Conclusion

1,5-AG level was negatively associated with hypoglycemia score determined by recall and with documented hypoglycemia after adjusting for mean glucose and duration of insulin treatment. As a result, this level could be a marker of the risk of hypoglycemia in patients with well-controlled T2DM receiving insulin therapy.

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Neurological dysfunction screening in a cohort of adolescents with type 1 diabetes: a six-year follow-up
Davide Tinti, Carlotta Canavese, Cecilia Nobili, Daniele Marcotulli, Erika Daniele, Ivana Rabbone, Luisa de Sanctis
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The progress of clinical research on the detection of 1,5-anhydroglucitol in diabetes and its complications
Huijuan Xu, Junhua Pan, Qiu Chen
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Mobile Healthcare System Provided by Primary Care Physicians Improves Quality of Diabetes Care
Tae Jung Oh, Jie-Eun Lee, Seok Kim, Sooyoung Yoo, Hak Chul Jang
CardioMetabolic Syndrome Journal.2021; 1(1): 88. CrossRef
Effects of mobile phone application combined with or without self‐monitoring of blood glucose on glycemic control in patients with diabetes: A randomized controlled trial
Yuan Yu, Qun Yan, Huizhi Li, Hongmei Li, Lin Wang, Hua Wang, Yiyun Zhang, Lei Xu, Zhaosheng Tang, Xinfeng Yan, Yinghua Chen, Huili He, Jie Chen, Bo Feng
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Articles inEndocrinology and Metabolismin 2016
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Scientific Reports.2017;[Epub] CrossRef
Low and exacerbated levels of 1,5-anhydroglucitol are associated with cardiovascular events in patients after first-time elective percutaneous coronary intervention
Shuhei Takahashi, Kazunori Shimada, Katsumi Miyauchi, Tetsuro Miyazaki, Eiryu Sai, Manabu Ogita, Shuta Tsuboi, Hiroshi Tamura, Shinya Okazaki, Tomoyuki Shiozawa, Shohei Ouchi, Tatsuro Aikawa, Tomoyasu Kadoguchi, Hamad Al Shahi, Takuma Yoshihara, Makoto Hi
Cardiovascular Diabetology.2016;[Epub] CrossRef

Obesity and Metabolism
Optimal Candidates for the Switch from Glimepiride to Sitagliptin to Reduce Hypoglycemia in Patients with Type 2 Diabetes Mellitus: Hyun Min Kim, Jung Soo Lim, Byung-Wan Lee, Eun-Seok Kang, Hyun Chul Lee, Bong-Soo Cha; Endocrinol Metab. 2015;30(1):84-91. Published online March 27, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.1.84

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Background

Sitagliptin is a novel antidiabetic agent with a low risk for hypoglycemia. We investigated the efficacy and safety of sitagliptin when patients switched from a sulfonylurea to sitagliptin and identified good candidates for the switch.

Methods

Sixty-one patients with type 2 diabetes switched from glimepiride with metformin to sitagliptin with metformin due to clinical hypoglycemia. Serum glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and 2-hour postprandial plasma glucose (2h-PPG) before and 12 and 24 weeks after the drug switch were checked.

Results

HbA1c and FPG levels did not change 12 or 24 weeks after the switch; however, the 2h-PPG level decreased from 218.0±67.5 mg/dL at baseline to 197.1±69.9 mg/dL at 12 weeks and 192.3±67.4 mg/dL at 24 weeks after switching drugs (P=0.045, P=0.018, respectively). All but one patient no longer experienced hypoglycemia after discontinuing glimepiride. In a multivariate logistic regression analysis, a high homeostasis model assessment of insulin resistance and low baseline HbA1c level were independent predictors of an HbA1c ≤7% after switching to sitagliptin.

Conclusion

Glycemic control was not aggravated in patients 24 weeks after the drug switch, and symptomatic hypoglycemia decreased significantly. Patients with dominant insulin resistance may be good candidates for switching from a sulfonylurea to sitagliptin to reduce hypoglycemia.

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Case Report

Obesity and Metabolism
Recurrent Hypoglycemia Triggered by Sorafenib Therapy in a Patient with Hemangiopericytoma: Si Won Lee, Eun Kyung Lee, Tak Yun, Young-Woong Won, Eun Jeong Ko, Mihong Choi, Sang Il Choi, Sun Seob Park, Eun Kyung Hong; Endocrinol Metab. 2014;29(2):202-205. Published online June 26, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.2.202

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Targeted therapy has been proven to be one of the most effective cancer treatments. However, some endocrine disorders can occur during treatment with targeted agents. We report the case of a patient who exhibited a wax and wane pattern of hypoglycemia that was attributed to sorafenib therapy. A 32-year-old woman with metastatic hemangiopericytoma visited the emergency department in a stuporous state. Nonhyperinsulinemic hypoglycemia was diagnosed, was exacerbated shortly after sorafenib therapy, and was improved by the cessation of sorafenib with additional glucocorticoid therapy. Patients with metastatic hemangiopericytoma should be carefully monitored with particular attention to hypoglycemia when sorafenib therapy is initiated.

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Case report of severe Cushing’s syndrome in medullary thyroid cancer complicated by functional diabetes insipidus, aortic dissection, jejunal intussusception, and paraneoplastic dysautonomia: remission with sorafenib without reduction in cortisol concentr
Muhammad M. Hammami, Najla Duaiji, Ghazi Mutairi, Sabah Aklabi, Nasser Qattan, Mohei El-Din M. Abouzied, Mohamed W. Sous
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Review Article

Obesity and Metabolism
Neurocognitive Changes and Their Neural Correlates in Patients with Type 2 Diabetes Mellitus: Junghyun H Lee, Yera Choi, Chansoo Jun, Young Sun Hong, Han Byul Cho, Jieun E Kim, In Kyoon Lyoo; Endocrinol Metab. 2014;29(2):112-121. Published online June 26, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.2.112

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As the prevalence and life expectancy of type 2 diabetes mellitus (T2DM) continue to increase, the importance of effective detection and intervention for the complications of T2DM, especially neurocognitive complications including cognitive dysfunction and dementia, is receiving greater attention. T2DM is thought to influence cognitive function through an as yet unclear mechanism that involves multiple factors such as hyperglycemia, hypoglycemia, and vascular disease. Recent developments in neuroimaging methods have led to the identification of potential neural correlates of T2DM-related neurocognitive changes, which extend from structural to functional and metabolite alterations in the brain. The evidence indicates various changes in the T2DM brain, including global and regional atrophy, white matter hyperintensity, altered functional connectivity, and changes in neurometabolite levels. Continued neuroimaging research is expected to further elucidate the underpinnings of cognitive decline in T2DM and allow better diagnosis and treatment of the condition.

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Case Reports

Transformation of Nonfunctioning Pancreatic Neuroendocrine Carcinoma Cells into Insulin Producing Cells after Treatment with Sunitinib: Jung Hun Ohn, Yeong Gi Kim, Se-Hoon Lee, Hye Seung Jung; Endocrinol Metab. 2013;28(2):149-152. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.149

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We report a rare case of severe hypoglycemia after sunitinib treatment for pancreatic neuroendocrine carcinoma. We describe the initial clinical presentation, laboratory results, pathologic findings, and managment in a patient with a nonfunctioning pancreatic neuroendocrine carcinoma with liver metastases who developed life threatening hypoglycemia after 2 months of sunitinib therapy. A 46-year-old woman presented to the emergency department with loss of consciousness from hypoglycemia. Serum C-peptide and insulin levels at fasting state revealed that the hypoglycemia resulted from endogenous hyperinsulinemia. She had been diagnosed with nonfunctioning pancreatic neuroendocrine carcinoma based on a biopsy of metastatic cervical lymph node and was being treated with sunitinib, a small molecule tyrosine kinase inhibitor. Immunohistochemical stain of the metastatic liver mass demonstrated that the initially nonfunctioning neuroendocrine carcinoma cells had changed into insulin-producing cells after sunitinib therapy. Transarterial chemoembolization of the liver masses and systemic chemotherapy with streptozotocin/adriamycin relieved the hypoglycemia. A nonfunctioning pancreatic neuroendocrine carcinoma was transformed into an insulin-producing tumor after treatment with sunitinib, causing endogenous hyperinsulinemia and severe hypoglycemia.

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Annals of Surgical Oncology.2026; 33(1): 609. CrossRef
Medical Management of Well-Differentiated Pancreatic Neuroendocrine Tumors: From Conventional Therapies to Emerging Strategies
Min Je Sung, Namyoung Park
Journal of Clinical Medicine.2026; 15(5): 1713. CrossRef
Systemic Therapy of Unresectable Non-functioning Pancreatic Neuroendocrine Tumor: Focusing on Grade 1–2
Namyoung Park, Min Je Sung
Journal of Digestive Cancer Research.2025; 13(2): 131. CrossRef
Small Insulinoma Followed-up as an Indolent Pancreatic Tumor
Hiroki Sato, Shozaburo Fujii, Tetsuhiro Okada, Hidemasa Kawabata, Yuki Kamikokura, Mikihiro Fujiya
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A Case of a Metastatic Pancreatic Neuroendocrine Tumor: A Surgical Conundrum Wrapped in Functionality's Embrace
Adam Mylonakis, Michail Vailas, Panagiotis Sakarellos, Lysandros Karydakis, Eleandros Kyros, Spyridon Davakis, Alexandros Papalampros, Evaggelos Felekouras
Cureus.2024;[Epub] CrossRef
Malignant Insulinoma Arising From Nonfunctioning Pancreatic Neuroendocrine Tumor
Ritodhi Chatterjee, Basim Ali, Son H. Nguyen, Rui Chen, Yvonne H. Sada
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Case Report: Giant insulinoma, a very rare tumor causing hypoglycemia
Georges Tarris, Alexia Rouland, Kévin Guillen, Romaric Loffroy, Anne-Cécile Lariotte, Patrick Rat, Benjamin Bouillet, Haingo Andrianiaina, Jean-Michel Petit, Laurent Martin
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Transformation of a non-secretory neuroendocrine tumor to insulinoma after treatment with Sunitinib: A case report and review of the literature
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Georgios K Dimitriadis, Martin O Weickert, Harpal S Randeva, Gregory Kaltsas, Ashley Grossman
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Severe resistant hypoglycemia in a patient with a pancreatic neuroendocrine tumor on sunitinib treatment
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Spontaneous Hypoglycemia due to Insulin Antibody after Insulin Treatment of Diabetic Ketoacidosis.: Jin Ook Chung, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung; Endocrinol Metab. 2010;25(3):217-220. Published online September 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.3.217

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Abstract PDF

Hypoglycemia in diabetic patients is usually caused by excessive exogenous insulin or the administration of an insulin secretagogue relative to the prevailing glucose concentration. Thus, the clinical manifestations of hypoglycemia are usually not observed in diabetic patients after either insulin or an oral hypoglycemic agent is discontinued. In contrast, diabetic ketoacidosis results from relative or absolute insulin deficiency. Although about 40% of diabetic patients who inject human insulin have insulin antibodies, these antibodies seldom significantly affect the glycemic control. It has not been reported in the literature that insulin antibody in the setting of human insulin therapy is associated with diabetic ketoacidosis and subsequent hypoglycemia. We describe here a rare case of spontaneous hypoglycemia due to insulin antibody after the improvement of diabetic ketoacidosis in a patient with type 2 diabetes mellitus and who had been treated with human insulin.

Citations

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Type 1 diabetes complicated with cyclic vomiting syndrome and exogenous insulin antibody syndrome: A case report
Leiluo Geng, Xue Diao, Hao Han, Ying Lin, Wei Liang, Aimin Xu
Frontiers in Endocrinology.2022;[Epub] CrossRef
Insulin Glulisine May Cause a Disease Resembling Insulin Autoimmune Syndrome: Case Report
Maki Kawasaki, Yoichi Oikawa, Takeshi Katsuki, Yusuke Kabeya, Masuomi Tomita, Mari Okisugi, Akira Shimada
Diabetes Care.2013; 36(12): e195. CrossRef
Insulin Autoimmune Syndrome with Diabetic Ketoacidosis
Yeong Geol Jo, Young Il Kim, Su Jin Lee, Ki Won Kim, Sung Wan Chun, Yeo Joo Kim, Sang Jin Kim
Journal of Korean Diabetes.2012; 13(2): 105. CrossRef

A Case of Gastrointestinal Stromal Tumor with Recurrent Hypoglycemia.: Sun Hee Ko, Seok Hwan Kim, Il Ho Maeng, Koon Soon Kim, Yi Sun Jang, Hye Soo Kim, Jong Min Lee, Suk Young Park, Sang Bum Kang; Endocrinol Metab. 2010;25(2):125-130. Published online June 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.2.125

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Abstract PDF

Non-islet cell tumor induced hypoglycemia (NICTH) is attributable to overproduction of insulin-like growth factor-II (IGF-II) by solid tumors, and these tumors usually originate from mesenchymal or epithelial cells. Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor and most commonly find in the gastrointestinal tract. It is usually expresses the CD117 (stem cell factor receptor, c-kit) detected by immunohistochemistry. Hypoglycemia associated with GIST is very rare and this has not yet been reported in Korea. A 72-year-old man was hospitalized due to frequent episodes of confusion. It was observed that non-hyperinsulinemic hypoglycemia, an elevated serum IGF-II level and a huge liver mass. The histology of liver mass showed c-kit (CD117) positivity, which was consistent with GIST, but it was surgically unresectable. He was treated with imatinib mesylate. Although he recieved palliative treatment, he still experienced intermittent fasting hypoglycemia. After 2 months, the serum IGF-II level was even higher than before. We changed imatinib mesylate to sunitinib malate and performed radiotherapy on the liver mass. Although the change of the liver mass was not significant, he did not suffer from hypoglycemia for three months afterwards.

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Impact of Hypoglycemia on Morbidity, Mortality, and Resource Utilization in Gastrointestinal Stromal Tumor: A Nationwide Analysis
Manasa Ginjupalli, Jayalekshmi Jayakumar, Arnold Forlemu, Anuj Raj Sharma, Praneeth Bandaru, Vikash Kumar, Kameswara Santosh Dheeraj Nalluri, Madhavi Reddy
Gastroenterology Insights.2025; 16(4): 36. CrossRef

A Case of Prolonged Hypoglycemia Post Topiramate Treatment an Anti-convulsant, in a Type 2 Diabetic Patient.: Myung Jun Lee, Yoon Shick Yom, Hyun woo Lim, Sung Tae Kim, Yu Mi Lee, Youn Zoo Cho, Kang Woo Lee, Byung Joon Kim, Keun Young Park, Dong Mee Lim; J Korean Endocr Soc. 2009;24(4):277-280. Published online December 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.4.277

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Abstract PDF: Topiramate is a drug used to treat epilepsy, and is known for its effects including reduced appetite resulting in lower body weight, and the lowering of neutral fat. In addition, topiramate is known to reduce blood sugar levels by increasing insulin sensitivity and by increasing insulin secretion by glucose stimulation. The authors report a case of persistent hypoglycemia, in a patient who had been administrating topiramate, as a treatment for epilepsy following an episode of cerebral infarction.

Original Article

Glucose Counterregulatory Hormone Response During Hypoglycemia due to Endogenous Hyperinsulinemia.: Jin Ook Chung, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung; J Korean Endocr Soc. 2009;24(3):174-180. Published online September 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.3.174

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Abstract PDF

BACKGROUND
In patients with hypoglycemia due to endogenous hyperinsulinemia such as insulinoma or insulin autoimmune syndrome, little is known about the counterregulatory hormone response to spontaneous hypoglycemia. We therefore compared hormone responses during spontaneous hypoglycemia due to endogenous hyperinsulinemia with those at the end of a 72-hour fast. METHODS: We measured glucagon, epinephrine, cortisol, and growth hormone responses during spontaneous hypoglycemia in 8 patients with insulinoma and 18 patients with insulin autoimmune syndrome. We also assessed these responses in 13 normal control subjects who underwent a 72-hour fast. RESULTS: In patients with insulinoma (median serum glucose level, 35.0 mg/dL), plasma glucagon levels (median, 42.9 vs. 76.2 pg/mL, respectively; P < 0.05) were lower than those in control subjects (serum glucose level, 62.5 mg/dL), whereas, there were no statistically significant differences in the other hormone responses between the two groups. In contrast, in the patients with insulin autoimmune syndrome (median serum glucose level, 34.5 mg/dL), plasma glucagon levels (median, 73.7 vs. 76.2 pg/mL, respectively) were lower than those in the control subjects, but there was no statistically significant difference between the two groups. There were no statistically significant differences in counterregulatory hormone responses during spontaneous hypoglycemia between patients with insulinoma and patients with insulin autoimmune syndrome. CONCLUSION: Our results suggest that defective glucagon secretion in patients with insulinoma rather than insulin autoimmune syndrome may contribute to hypoglycemia in addition to hyperinsulinemia.

Citations

Citations to this article as recorded by

Glycogenic hepatopathy in a Korean girl with poorly controlled type 1 diabetes mellitus
Hwal Rim Jeong, Young Seok Shim, Young Bae Kim, Hae Sang Lee, Jin Soon Hwang
Annals of Pediatric Endocrinology & Metabolism.2014; 19(1): 49. CrossRef
Glucose Counterregulatory Hormone Response During Hypoglycemia due to Endogenous Hyperinsulinemia
Jung Guk Kim
Journal of Korean Endocrine Society.2009; 24(3): 162. CrossRef

Case Reports

A Case of Epithelioid Hemangioendothelioma of the Pelvic Retroperitoneum with Hypoglycemia.: Ji Ryang Kim, Yun Kyung Jeun, Kee Tae Park, Yang Ho Kang, Seok Man Son, In Ju Kim, Yong Ki Kim, Kyung Un Choi, Kwang Jae Lee; J Korean Endocr Soc. 2007;22(6):440-445. Published online December 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.6.440

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Abstract PDF: Hypoglycemia caused by a non-islet cell tumor (NICT) is a rare condition. The mechanism of NICT-induced hypoglycemia is still unclear, but insulin-like growth factor-II (IGF-II) has been thought to play a major role in its development. NICT is usually of mesenchymal or epithelial cell origin, but reports on NICT of an endothelial cell origin, which causes hypoglycemia, have yet to surface. Here, we report on a case of a 63-year-old female patient who was diagnosed with epithelioid hemangioendothelioma-induced hypoglycemia. Epithelioid hemangioendothelioma is a borderline malignant vascular tumor that is of endothelial cell origin and usually occurs in soft tissue, skin, lung, and liver. It was observed that serum insulin, C-peptide, and IGF-I were reduced, but the IGF-II level was elevated in hypoglycemia. The PET-CT showed no abnormal glucose metabolism in the tumor. Dextrose fluid was administered to the patient to control hypoglycemia until the operation. For treatment and diagnosis, surgical resection of the tumor and total hysterectomy were performed. The specimen was noted to have epithelioid hemangioendothelioma. Hypoglycemia-related symptoms disappeared after surgical resection was performed.

A Case of Autoimmune Hypoglycemia due to Insulin Antibody in Patient with End Stage Renal Disease.: Ji Ye Jung, Eun Seok Kang, Beom Seok Kim, Sung Wan Chun, Yumie Rhee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Hyun Chul Lee; J Korean Endocr Soc. 2006;21(6):536-541. Published online December 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.6.536

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Abstract PDF: Fasting hypoglycemia results from several mechanisms. Autoimmune hypoglycemia is one of the rare causes of hypoglycemia, and characterized by hyperinsulinemia, fasting hypoglycemia and the presence of autoantibodies to insulin or insulin receptor. We report here on a 64-year-old male patient with autoimmune hypoglycemia with end stage renal disease. He had no history of diabetes or insulin use. He had experienced several severe hypoglycemic events. The serum C-peptide level was 7.48 ng/mL and the insulin concentration was 115.4 micro U/mL when the fasting plasma glucose level was 88 mg/dL. The insulin to glucose ratio was 5.42, which suggested the presence of insulinoma. Yet the radiologic studies, including magnetic resonance cholangiopancreatography, endoscopic ultrasonography and selective calcium stimulated venous sampling revealed no evidence of insulinoma. The insulin autoantibody level was 62 micro U/mL. Therefore, we could diagnosis the autoimmune hypoglycemia. The hypoglycemia was treated with prednisolone and the patient recovered from this. His insulin level decreased to 21.11 micro U/mL and the insulin autoantibody level decreased to 34 micro U/mL. Hypoglycemia in the hemodialysis patients is not uncommon. One should bear in mind autoimmune hypoglycemia as one of the causes of hypoglycemia in patients with no history of diabetes.

A Case of Non-islet Cell Tumor Hypoglycemia.: Yun Tae Chae, Il Jun Hwang, Kyung Hee Ryu, Eun Hyang Ko, Jung Im Rue, Soo Kyung Kim, Seok Won Park, Yoo Ri Kim, Yong Wook Cho, Young Kil Choi, Sang Jong Lee; J Korean Endocr Soc. 2006;21(1):74-78. Published online February 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.1.74

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Abstract PDF

Mesenchymal tumors including hemangiopericytomas, hepatocellular tumors, adrenal carcinomas, and a variety of other large tumors have been reported to produce excessive amounts of insulin-like growth factor (IGF) type II precursor, which binds weakly to insulin receptors and strongly to IGF-I receptors, leading to insulin like actions. In addition to increased IGF-II production, IGF-II bioavailability is increased due to complex alterations in circulating binding proteins. The authors of this article diagnosed non-islet cell tumor hypoglycemia from an 81-year-old male patient suffering from repetitive fasting hypoglycemia while he has not received any treatment for pulmonary hemangiopericytoma diagnosed in the past. Moreover, this topic is getting reported as the authors have experienced a significant improvement of catamnesis by a treatment with glucocorticoid.

Citations

Citations to this article as recorded by

A Case of Epithelioid Hemangioendothelioma of the Pelvic Retroperitoneum with Hypoglycemia
Ji Ryang Kim, Yun Kyung Jeun, Kee Tae Park, Yang Ho Kang, Seok Man Son, In Ju Kim, Yong Ki Kim, Kyung Un Choi, Kwang Jae Lee
Journal of Korean Endocrine Society.2007; 22(6): 440. CrossRef

A Case of Malignant Insulinoma Metastasized to Liver after Partial Pancreatectomy due to Insulinoma 10 Years before.: Yang Il Kang, Byung Hyuk Yang, Suk Chon, Seungjoon Oh, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Ju Hie Lee, Kwanpyo Koh; J Korean Endocr Soc. 2006;21(1):68-73. Published online February 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.1.68

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Abstract PDF: Malignant insulinomas are very rare endocrine tumours with a variable clinical course. Here, a case of a malignant insulinoma, resected from the tail of the pancreas 10 years previously, which was found to have hepatic metastasis, is reported. A pancreatic mass, without evidence of metastasis, has been found using an abdominal CT scan and intra-operative ultrasonography 10 years previously. Recently, the patient has suffered from dizziness, sweating and an altered mentality. Hyperinsulinemia was diagnosed from the biochemical laboratory finding. An abdominal CT scan and intra-operative abdominal sonography showed multiple hepatic metastasis, without local recurrence in pancreas. Therefore, a partial hepatic segmentectomy was performed. Immunohistochemical staining of the postoperative specimen was strongly positive for insulin. The postoperative biochemical response was normalized, and the patient experienced no further hypoglycemic symptom.

A Case of Masked Hypoglycemia during Lactic Acidosis.: Hee Seon Kim, Ho Sung Yoon, Chang Ok Koh, Hyeon Kyu Kim, Choel Young Park, Seong Jin Lee, Gi Weon Oh, In Kyung Jeong, Eun Gyung Hong, Cheol Soo Choi, Doo Man Kim, Sung Hee Ihm, Jae Myung Yu, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park, Dong Jin Oh; J Korean Endocr Soc. 2004;19(4):406-410. Published online August 1, 2004

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Abstract PDF: Severe hypoglycemia induces neuroglycopenic symptoms, including mental alteration, as glucose is the exclusive fuel for the central nervous system. However, some reports have shown that non-glucose fuels, like lactates and ketones, could be utilized by the brain during severe hypoglycemia. Herein, a case of extreme hypoglycemia in a 44-year old woman, subsequently diagnosed as congestive heart failure accompanied by ischemic hepatitis and lactic acidosis, is presented. In two episodes of extreme hypoglycemia, she was fully alert without obvious neurological deficits. In this unusual case, an increased supply of lactate might have maintained the cerebral function and prevented cerebral injury during the hypoglycemia that was induced as a result of starvation and hepatic and cardiac dysfunctions

A Case of Lymphocytic Hypophysitis Presented with Hypoglycemia after Delivery.: Jang Myung Son, Seung Hyun Ko, Yu Bae Ahn, Kang Ju, Jeong Rok Lee, Seong Eun Yang, Ki Ho Song, Ho Young Son, Jeong Su Jun; J Korean Endocr Soc. 2003;18(3):325-331. Published online June 1, 2003

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Abstract PDF: Lymphocytic hypophysitis, an inflammatory disease of the pituitary gland that is often associated with pregnancy, is caused by autoimmune destruction of the pituitary gland evidenced by diffuse inflammatory cell infiltration of the pituitary gland and some kinds of detectable autoantibodies. We report a case of lymphocytic hypophysitis in a 31-year-old woman presenting with severe hypoglycemia and hyponatremia after delivery. Hormonal study revealed panhypopituitarism and magnetic resonance imaging with enhancement showed the bulging contour of the right side pituitary gland with an ill-defined mass-like lesion and nodular thickening of the stalk. The patient's symptoms and biochemical data improved greatly with replacement of L-thyroxine and glucocorticoid. Partial recovery of panhypopituitarism was also seen. The follow-up tests revealed dramatic resolution of the pituitary lesion.

Two Cases of Autoimmune Insulin Syndrome with Hypoglycemia.: See Hyung Park, Shin Won Lee, Gui Hwa Jeong, Chang Hoon Choi, Soon Hee Lee, Jeung Hoon Han, Jeong Guk Kim, Seong Woo Ha, Bo Wan Kim; J Korean Endocr Soc. 2001;16(4-5):508-513. Published online October 1, 2001

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Abstract PDF: Autoimmune insulin syndrome is characterized by insulin autoantibody, hyperinsulinemia, and fasting hypoglycemia without previous insulin immunization. This syndrome shows discordant levels between immunoreactive insulin and C-peptide. Negative results of an anatomic study of the pancreas and an inability to reproduce hypoglycemia during a prolonged fast may be helpful in excluding insulinoma. Symptomatic hypoglycemia usually develops during an oral glucose tolerance test. This syndrome is a self-limited disorder. Recently, we experienced one case that developed symptomatic hypoglycemia during both the fasting & oral glucose tolerance test, and another that developed symptomatic hypoglycemia during the oral glucose tolerance test but not the fasting test. Hereby, we present these cases with a review of the literature.

A Case of non-islet Cell Tumor Hypoglycemia Due to Gepatoma-increased serum subfraction of big insulin-like growth factor II.: Kwan Woo Lee, Hyun Soo Kim, Yun Suk Chung, Hyun Man Kim, Myung Ho Yoon, Joon Ho Ko, Hyo Chul Kim, Young Soo Kim, Sung Won Cho; J Korean Endocr Soc. 1997;12(4):667-671. Published online January 1, 2001

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Abstract PDF: Hypoglycemia due to non-islet cell tumor is usually associated with hypersecretion of big insulin-like growth factor II (IGF-II). This big IGF-II cannot form ternary IGF complex, and is biologically more active in peripheral tissue, inducing increased glucose utilization and hypoglycemia. A 57-year-old man developed severe hypoglycemia due to hepatocellular carcinoma. To control hypoglycemia, the patient required continuous glucose infusion. The circulating levels of cortisol and free T4 were in the normal range. The plasma levels of insulin, C-peptide, IGF-I, IGF binding protein-3 (IGFBP-3), and total IGF-II levels were decreased. Radioimmunoassay of IGF-II revealed that big IGF-II immunoreactivity markedly increased compared to that of normal control. In this patient, it was strongly suggested that big IGF-II might be a cause of severe intractable hypoglycemia.

Original Article

Nesidioblastosis in an Elderly Patient with Hyperinsulinemic Hypoglycemia.: Ye Kyung Seo, Jik Hwa Nam, Byung Ho Sin, Jung Guk Kim, Sung Woo Ha, Bo Whn Kim, Sang Won Jung, Young Guk Yun, In Su Seo, Chang Ho Cho; J Korean Endocr Soc. 1997;12(3):485-492. Published online January 1, 2001

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Abstract PDF: Nesidioblastosis is characterized by a diffuse proliferation of islet cells arising from pancreatic ducts and is the most common cause of hyperinsulinemic hypoglycemia in newborns and infantile. It is exceedingly rare in adults and no concensus regarding its diagnosis and management is available. We herein describe an elderly man with fasting hypoglycemia, inappropriate insulin hypersecretion. And pathologic examination of his pancreas revealed the characteristic finding of nesidioblastosis confirmed by immunohistochemical stain.

Case Report

A Case of Isolated ACTH Deficiency Manifestated by Atrial Fibrillation and Hypoglycemia.: Won Seob Kim, Ki Se Lee, Sun Kyung Song, In Suk Seo, Soo Jin Choi, Dong Yoon Kim; J Korean Endocr Soc. 1998;13(4):646-651. Published online January 1, 2001

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Abstract PDF: Isolated ACTH deficiency is a rare cause of secondary adrenocortical insufficiency caused by the defect of synthesis or release of ACTH in pituitary gland. The clinical presentation can be simiilar to that of primary adrenal insufficiency, but there is a greater tendency for hypoglycemia and absence of hyperpigmentation. The patient, 80 year-old female, was admitted in chief complaint of deteriorated mental states. On admission, serum sodium was 127mEq/L, potassium 4.4mEq/L, blood glucose 27mg/dL and on routine E.C.G. was atrial fibrillation was revealed. The basal morning serum cortisol level was 9.97 pg/dL it dosent respond to insulin-induced hypoglycemia enoughly, but other pituitary functions were intact in pituitary cocktail stimulation test. In CRH stimulation test, there was no remarkable response in serum ACTH and cortisol level. Brain MRI failed to reveal any anatomic abnormalities of the sellar or suprasellar area consistent with the defect of pituitary ACTH secretion. This case was a isolated ACTH deficiency, So, we conclude that associated with atrail fibrillation and hypoglycemia.

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