Endocrinology and Metabolism

Namgok Lecture 2022

Diabetes, Obesity and Metabolism
Incretin and Pancreatic β-Cell Function in Patients with Type 2 Diabetes: Chang Ho Ahn, Tae Jung Oh, Se Hee Min, Young Min Cho; Endocrinol Metab. 2023;38(1):1-9. Published online February 13, 2023; DOI: https://doi.org/10.3803/EnM.2023.103

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To maintain normal glucose homeostasis after a meal, it is essential to secrete an adequate amount of insulin from pancreatic β-cells. However, if pancreatic β-cells solely depended on the blood glucose level for insulin secretion, a surge in blood glucose levels would be inevitable after the ingestion of a large amount of carbohydrates. To avoid a deluge of glucose in the bloodstream after a large carbohydrate- rich meal, enteroendocrine cells detect the amount of nutrient absorption from the gut lumen and secrete incretin hormones at scale. Since insulin secretion in response to incretin hormones occurs only in a hyperglycemic milieu, pancreatic β-cells can secrete a “Goldilocks” amount of insulin (i.e., not too much and not too little) to keep the blood glucose level in the normal range. In this regard, pancreatic β-cell sensitivity to glucose and incretin hormones is crucial for maintaining normal glucose homeostasis. In this Namgok lecture 2022, we review the effects of current anti-diabetic medications on pancreatic β-cell sensitivity to glucose and incretin hormones.

Citations

Citations to this article as recorded by

Initial Combination Therapy in Type 2 Diabetes
Ji Yoon Kim, Nam Hoon Kim
Endocrinology and Metabolism.2024; 39(1): 23. CrossRef

In Memoriam

Miscellaneous
In Memoriam: Remembering Professor Hun-Ki Min (1928–2021): Young Min Cho; Endocrinol Metab. 2021;36(2):207-208. Published online April 20, 2021; DOI: https://doi.org/10.3803/EnM.2021.204

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Review Article

Diabetes
Peptidyl and Non-Peptidyl Oral Glucagon-Like Peptide-1 Receptor Agonists: Hun Jee Choe, Young Min Cho; Endocrinol Metab. 2021;36(1):22-29. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.102

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Abstract PDF PubReader ePub

Glucagon-like peptide-1 (GLP-1) receptor agonists are efficacious glucose-lowering medications with salient benefits for body weight and cardiovascular events. This class of medications is now recommended as the top priority for patients with established cardiovascular disease or indicators of high risk. Until the advent of oral semaglutide, however, GLP-1 receptor agonists were available only in the form of subcutaneous injections. Aversion to needles, discomfort with self-injection, or skin problems at the injection site are commonly voiced problems in people with diabetes, and thus, attempts for non-invasive delivery strategies have continued. Herein, we review the evolution of GLP-1 therapy from its discovery and the development of currently approved drugs to the unprecedented endeavor to administer GLP-1 receptor agonists via the oral route. We focus on the pharmacokinetic and pharmacodynamic properties of the recently approved oral GLP-1 receptor agonist, oral semaglutide. Small molecule oral GLP-1 receptor agonists are currently in development, and we introduce how these chemicals have addressed the challenge posed by interactions with the large extracellular ligand binding domain of the GLP-1 receptor. We specifically discuss the structure and pharmacological properties of TT-OAD2, LY3502970, and PF-06882961, and envision an era where more patients could benefit from oral GLP-1 receptor agonist therapy.

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Sulfobetaine modification of poly (D, L-lactide-co-glycolic acid) nanoparticles enhances mucus permeability and improves bioavailability of orally delivered liraglutide
Zhenyu Zhao, Ruihuan Ding, Yumei Wang, Ranran Yuan, Houqian Zhang, Tianyang Li, Wei Zheng, Entao Chen, Aiping Wang, Yanan Shi
Journal of Drug Delivery Science and Technology.2024; 93: 105437. CrossRef
Physiology and pharmacology of glucagon-like peptide-1 receptor
D. V. Kurkin, D. A. Bakulin, E. I. Morkovin, V. I. Petrov, A. V. Strygin, K. N. Koryanova, Yu. V. Gorbunova, Yu. A. Kolosov, O. V. Ivanova, E. V. Pavlova, M. A. Dzhavakhyan, A. V. Zaborovsky, V. B. Saparova, I. E. Makarenko, R. I. Drai, A. N. Chumachenko
Pharmacy & Pharmacology.2024; 11(4): 347. CrossRef
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Binbin Gong, Zhihong Yao, Chenxu Zhou, Wenxi Wang, Lidan Sun, Jing Han
European Journal of Medicinal Chemistry.2024; 269: 116342. CrossRef
Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition
Yaochen Xie, Qian Zhou, Qiaojun He, Xiaoyi Wang, Jincheng Wang
Acta Pharmaceutica Sinica B.2023; 13(6): 2383. CrossRef
Advances in GLP-1 receptor agonists for the treatment of type 2 diabetes
Shurui Hong, J. Xiao, Y. He
BIO Web of Conferences.2023; 61: 01006. CrossRef
Safety and efficacy of the new, oral, small-molecule, GLP-1 receptor agonists orforglipron and danuglipron for the treatment of type 2 diabetes and obesity: systematic review and meta-analysis of randomized controlled trials
Paschalis Karakasis, Dimitrios Patoulias, Konstantinos Pamporis, Panagiotis Stachteas, Konstantinos I. Bougioukas, Aleksandra Klisic, Nikolaos Fragakis, Manfredi Rizzo
Metabolism.2023; 149: 155710. CrossRef
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Reeju Amatya, Kyoung Ah Min, Meong Cheol Shin
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Harold E. Bays, Angela Fitch, Sandra Christensen, Karli Burridge, Justin Tondt
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Zhaotong Cong, Qingtong Zhou, Yang Li, Li-Nan Chen, Zi-Chen Zhang, Anyi Liang, Qing Liu, Xiaoyan Wu, Antao Dai, Tian Xia, Wei Wu, Yan Zhang, Dehua Yang, Ming-Wei Wang
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GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects
Xin Zhao, Minghe Wang, Zhitong Wen, Zhihong Lu, Lijuan Cui, Chao Fu, Huan Xue, Yunfeng Liu, Yi Zhang
Frontiers in Endocrinology.2021;[Epub] CrossRef
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Erratum

Erratum: Correction of Figure. Clinical Implications of Various Criteria for the Biochemical Diagnosis of Insulinoma: Chang Ho Ahn, Lee-Kyung Kim, Jie Eun Lee, Chan-Hyeon Jung, Se-Hee Min, Kyong Soo Park, Seong Yeon Kim, Young Min Cho; Endocrinol Metab. 2017;32(2):306. Published online June 23, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.2.306

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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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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
Journal of Diabetes Investigation.2019; 10(5): 1365. CrossRef
Articles inEndocrinology and Metabolismin 2016
Won-Young Lee
Endocrinology and Metabolism.2017; 32(1): 62. CrossRef
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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

Clinical Study
Clinical Characteristics of Subjects with Sulfonylurea-Dependent Type 2 Diabetes: Se Hee Min, Soo Heon Kwak, Young Min Cho, Kyong Soo Park, Hye Seung Jung; Endocrinol Metab. 2015;30(4):509-513. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.509

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Background

Even though several oral anti-diabetic drugs (OAD) with various modes of action are replacing sulfonylurea (SU), some patients seem to be dependent on SU for adequate glycemic control. Therefore, we evaluated the clinical characteristics of such patients.

Methods

We selected the patients with type 2 diabetes who met following criteria from 2009 to 2014 at Seoul National University Hospital: glycated hemoglobin (HbA1c) was maintained below 7.5% for at least 6 months under small dose of SU (glimepiride ≤2 mg/day or equivalent dose); after discontinuation of SU, HbA1c increased ≥1.2% within 3 months or ≥1.5% within 6 months; and after resuming SU, HbA1c reduction was ≥0.8% or reduction of fasting plasma glucose was ≥40 mg/dL within 3 months. Patients with impaired hepatic or renal function, and steroid users were excluded.

Results

Nineteen subjects were enrolled: after averaged 4.8±1.5 months of SU-free period, HbA1c increased from 6.7%±0.4% to 8.8%±0.8% even though adding other OAD such as gliptins. However, HbA1c decreased to 7.4%±0.7% after resuming SU within 2.4±0.8 months. There was no sexual predominance. Despite their old age (67±11 years) and long duration of diabetes (18±10 years), fasting C-peptide was relatively well-reserved (3.9±2.6 ng/mL), and nephropathy was not observed (albumin-creatinine ratio 21.2±16.6 mg/g and estimated glomerular filtration rate 75.8±18.0 mL/min/1.73 m²). Strong family history was also noted (73.7%).

Conclusion

Despite hypoglycemia risk of SU, it seemed indispensable for a subset of patients with regard to insulin secretion. Genetic influences would be evaluated.

Citations

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Incident Hepatocellular Carcinoma Risk in Patients Treated with a Sulfonylurea: A Nationwide, Nested, Case-Control Study
Ji-Yeon Lee, Suk-Yong Jang, Chung Mo Nam, Eun Seok Kang
Scientific Reports.2019;[Epub] CrossRef
A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes
Eugene Han, Hye Sun Park, Obin Kwon, Eun Yeong Choe, Hye Jin Wang, Yong-ho Lee, Sang-Hak Lee, Chul Hoon Kim, Lee-Kyung Kim, Soo Heon Kwak, Kyong Soo Park, Chul Sik Kim, Eun Seok Kang
Medicine.2016; 95(44): e5155. CrossRef

Brief Report

Obesity and Metabolism
Glucagon-Like Peptide-1 Increases Mitochondrial Biogenesis and Function in INS-1 Rat Insulinoma Cells: Mi Yeon Kang, Tae Jung Oh, Young Min Cho; Endocrinol Metab. 2015;30(2):216-220. Published online June 30, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.2.216

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Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that increases glucose-stimulated insulin secretion in pancreatic β-cells. Since mitochondrial function is crucial to insulin secretion, we hypothesized that GLP-1 may increase mitochondrial biogenesis in pancreatic β-cells. We treated INS-1 rat insulinoma cells with GLP-1 or exendin-4 for 48 hours and measured mitochondrial mass and function. Both GLP-1 and exendin-4 increased mitochondrial mass by approximately 20%. The mitochondria/cytosol ratio was increased from 7.60±3.12% to 10.53±2.70% by exendin-4. In addition, GLP-1 increased the mitochondrial membrane potential and oxygen consumption. Proliferator-activated receptor-gamma coactivator 1α expression was increased approximately 2-fold by GLP-1 treatment. In conclusion, the present study presents evidence for a new mechanism of action by which GLP-1 improves pancreatic β-cell function via enhanced mitochondrial mass and performance.

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Original Articles

Obesity and Metabolism
Mitochondrial Complexes I and II Are More Susceptible to Autophagy Deficiency in Mouse β-Cells: Min Joo Kim, Ok Kyong Choi, Kyung Sil Chae, Min Kyeong Kim, Jung Hee Kim, Masaaki Komatsu, Keiji Tanaka, Hakmo Lee, Sung Soo Chung, Soo Heon Kwak, Young Min Cho, Kyong Soo Park, Hye Seung Jung; Endocrinol Metab. 2015;30(1):65-70. Published online March 27, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.1.65

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Background

Damaged mitochondria are removed by autophagy. Therefore, impairment of autophagy induces the accumulation of damaged mitochondria and mitochondrial dysfunction in most mammalian cells. Here, we investigated mitochondrial function and the expression of mitochondrial complexes in autophagy-related 7 (Atg7)-deficient β-cells.

Methods

To evaluate the effect of autophagy deficiency on mitochondrial function in pancreatic β-cells, we isolated islets from Atg7^F/F:RIP-Cre+ mice and wild-type littermates. Oxygen consumption rate and intracellular adenosine 5'-triphosphate (ATP) content were measured. The expression of mitochondrial complex genes in Atg7-deficient islets and in β-TC6 cells transfected with siAtg7 was measured by quantitative real-time polymerase chain reaction.

Results

Baseline oxygen consumption rate of Atg7-deficient islets was significantly lower than that of control islets (P<0.05). Intracellular ATP content of Atg7-deficient islets during glucose stimulation was also significantly lower than that of control islets (P<0.05). By Oxygraph-2k analysis, mitochondrial respiration in Atg7-deficient islets was significantly decreased overall, although state 3 respiration and responses to antimycin A were unaffected. The mRNA levels of mitochondrial complexes I, II, III, and V in Atg7-deficient islets were significantly lower than in control islets (P<0.05). Down-regulation of Atg7 in β-TC6 cells also reduced the expression of complexes I and II, with marginal significance (P<0.1).

Conclusion

Impairment of autophagy in pancreatic β-cells suppressed the expression of some mitochondrial respiratory complexes, and may contribute to mitochondrial dysfunction. Among the complexes, I and II seem to be most vulnerable to autophagy deficiency.

Citations

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Proteomic pathways to metabolic disease and type 2 diabetes in the pancreatic islet
Belinda Yau, Sheyda Naghiloo, Alexis Diaz-Vegas, Austin V. Carr, Julian Van Gerwen, Elise J. Needham, Dillon Jevon, Sing-Young Chen, Kyle L. Hoehn, Amanda E. Brandon, Laurence Macia, Gregory J. Cooney, Michael R. Shortreed, Lloyd M. Smith, Mark P. Keller,
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Natural compound oblongifolin C inhibits autophagic flux, and induces apoptosis and mitochondrial dysfunction in human cholangiocarcinoma QBC939 cells
Aiqing Zhang, Wei He, Huimin Shi, Xiaodan Huang, Guozhong Ji
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Min Joo Kim, Ok Kyong Choi, Kyung Sil Chae, Hakmo Lee, Sung Soo Chung, Dong-Sik Ham, Ji-Won Kim, Kun-Ho Yoon, Kyong Soo Park, Hye Seung Jung
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Obesity and Metabolism
Clinical Implications of Various Criteria for the Biochemical Diagnosis of Insulinoma: Chang Ho Ahn, Lee-Kyung Kim, Jie Eun Lee, Chan-Hyeon Jung, Se-Hee Min, Kyong Soo Park, Seong Yeon Kim, Young Min Cho; Endocrinol Metab. 2014;29(4):498-504. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.498

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Background

Among the various diagnostic criteria for insulinoma, the ratio criteria have been controversial. However, the amended insulin-glucose ratio exhibited excellent diagnostic performance in a recent retrospective cohort study, although it has not yet been validated in other patient cohorts. We examined the diagnostic performance of the current criteria of the Endocrine Society, insulin-glucose ratio, C-peptide-glucose ratio, and amended ratios in terms of differentiating insulinomas.

Methods

We reviewed the medical records of patients who underwent evaluation for hypoglycemia from 2000 to 2013. Fourteen patients with histopathologically confirmed insulinoma and 18 patients without clinical evidence of insulinoma were included. The results of a prolonged fast test were analyzed according to the abovementioned criteria.

Results

Fulfilling all three Endocrine Society criteria-plasma levels of glucose (<3.0 mmol/L), insulin (≥8 pmol/L), and C-peptide (≥0.2 nmol/L)-exhibited 100% sensitivity and 89% specificity. Fulfilling the glucose and C-peptide criteria showed 100% sensitivity and 83% specificity, while fulfilling the glucose and insulin criteria showed 100% sensitivity and 72% specificity. Among the ratio criteria, the insulin-glucose ratio [>24.0 (pmol/L)/(mmol/L)] gave the highest area under the receiver operating characteristic curve, with 93% sensitivity and 94% specificity.

Conclusion

Fulfilling the glucose, insulin, and C-peptide criteria of the Endocrine Society guidelines exhibited the best diagnostic performance for insulinoma. Nonetheless, the insulin-glucose ratio may still have a role in the biochemical diagnosis of insulinoma.

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Kálmán Bódis, Martin Schön, Laura Dauben, Miriam Wilker, Klaus Strassburger, Volker Burkart, Michael Roden, Karsten Müssig
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Feng Wang, Zhe Yang, XiuBing Chen, Yiling Peng, HaiXing Jiang, ShanYu Qin
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Comparison of the diagnostic accuracy of the current guidelines for detecting insulinoma
Laura Dauben, Marie-Christine Simon, Klaus Strassburger, Volker Burkart, Katharina S Weber, Sven Schinner, Michael Roden, Karsten Müssig
European Journal of Endocrinology.2019; 180(6): 381. CrossRef
EUS-guided lauromacrogol ablation of insulinomas: a novel treatment
Shanyu Qin, Yongru Liu, Hongjian Ning, Lin Tao, Wei Luo, Donghong Lu, Zuojie Luo, Yingfen Qin, Jia Zhou, Junqiang Chen, Haixing Jiang
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Diagnosis of insulinoma using the ratios of serum concentrations of insulin and C-peptide to glucose during a 5-hour oral glucose tolerance test
Xu Li, Feng Zhang, Haibing Chen, Haoyong Yu, Jian Zhou, Ming Li, Qing Li, Lianxi Li, Jun Yin, Fang Liu, Yuqian Bao, Junfeng Han, Weiping Jia
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C. Binici, S. Plog, O. Kershaw, M. Schmicke, J.H. van der Kolk, K.E. Müller
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Kelsee Halpin, Ryan McDonough, Patria Alba, Jared Halpin, Vivekanand Singh, Yun Yan
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Won-Young Lee
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Obesity and Metabolism
A Novel Mutation in the Von Hippel-Lindau Tumor Suppressor Gene Identified in a Patient Presenting with Gestational Diabetes Mellitus: Yun Hyi Ku, Chang Ho Ahn, Chan-Hyeon Jung, Jie Eun Lee, Lee-Kyung Kim, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho; Endocrinol Metab. 2013;28(4):320-325. Published online December 12, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.4.320

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Background

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited, multisystemic tumor syndrome caused by mutations in the VHL gene. To date, more than 1,000 germline and somatic mutations of the VHL gene have been reported. We present a novel mutation in the VHL tumor suppressor gene that presented with gestational diabetes mellitus.

Methods

A 30-year-old woman presented with gestational diabetes mellitus. She sequentially showed multiple pancreatic cysts, spinal cord hemangioblastoma, cerebellar hemangioblastoma, and clear cell type renal cell carcinomas. Also, her father and brother had brain hemangioblastomas. Each of the three exons of the VHL gene was individually amplified by polymerase chain reaction and direct sequencing was performed using an ABI 3730 DNA analyzer.

Results

DNA sequence analysis to determine the presence of VHL mutation in her family revealed del291C, a novel frameshift mutation.

Conclusion

We found a novel mutation in the VHL tumor suppressor gene that presented with gestational diabetes mellitus.

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Review Article

Obesity and Metabolism
Clinical Application of Glucagon-Like Peptide 1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: Young Min Cho, Rhonda D. Wideman, Timothy J. Kieffer; Endocrinol Metab. 2013;28(4):262-274. Published online December 12, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.4.262

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Glucagon-like peptide 1 (GLP-1) is secreted from enteroendocrine L-cells in response to oral nutrient intake and elicits glucose-stimulated insulin secretion while suppressing glucagon secretion. It also slows gastric emptying, which contributes to decreased postprandial glycemic excursions. In the 1990s, chronic subcutaneous infusion of GLP-1 was found to lower blood glucose levels in patients with type 2 diabetes. However, GLP-1's very short half-life, arising from cleavage by the enzyme dipeptidyl peptidase 4 (DPP-4) and glomerular filtration by the kidneys, presented challenges for clinical use. Hence, DPP-4 inhibitors were developed, as well as several GLP-1 analogs engineered to circumvent DPP-4-mediated breakdown and/or rapid renal elimination. Three categories of GLP-1 analogs, are being developed and/or are in clinical use: short-acting, long-acting, and prolonged-acting GLP-1 analogs. Each class has different plasma half-lives, molecular size, and homology to native GLP-1, and consequently different characteristic effects on glucose metabolism. In this article, we review current clinical data derived from each class of GLP-1 analogs, and consider the clinical effects reported for each category in recent head to head comparison studies. Given the relatively brief clinical history of these compounds, we also highlight several important efficacy and safety issues which will require further investigation.

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Original Article

Obesity and Metabolism
Hemoglobin A1c Is Positively Correlated with Framingham Risk Score in Older, Apparently Healthy Nondiabetic Korean Adults: Ji Hye Shin, Ji In Kang, Yun Jung, Young Min Choi, Hyun Jung Park, Jung Hae So, Jin Hwa Kim, Sang Yong Kim, Hak Yeon Bae; Endocrinol Metab. 2013;28(2):103-109. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.103

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Background

Several studies have suggested that elevated levels of hemoglobin A1c (HbA1c) are associated with cardiovascular disease (CVD) in nondiabetic individuals. However, it is unclear whether HbA1c levels can serve as a simple screening marker for increased CVD risk in nondiabetic individuals. Our objective was to evaluate the relationship between HbA1c levels and CVD risk using the Framingham risk score (FRS) in older, apparently healthy nondiabetic Korean adults.

Methods

We retrospectively studied 2,879 Korean adults between the ages of 40 and 79 who underwent voluntary health check-ups at the Health Promotion Center of our hospital from July 2009 to June 2011. Subjects were subdivided based on their HbA1c levels into four groups: tertiles within the HbA1c normal tolerance range and a group for subjects with an increased risk for diabetes (IRD).

Results

The mean FRS for the upper tertile (9.6±3.8) group was significantly higher than that of the middle tertile (8.4±4.0) and lower tertile (7.6±3.8) groups. In addition, FRS was highest in the IRD group (10.5±3.7). Multiple linear regression analysis demonstrated that HbA1c levels exhibited a significant positive correlation with FRS when adjusted for confounding variables in all subjects (β±standard error [SE], 0.018±0.002; R², 0.131), women (β±SE, 0.023±0.003; R², 0.170), and men (β±SE, 0.016±0.004; R², 0.109).

Conclusion

HbA1c levels were positively correlated with FRS in older, apparently healthy nondiabetic Korean adults. We propose that HbA1c levels may reflect CVD risk in nondiabetic individuals.

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Case Reports

Thyroid
Two Cases of Methimazole-Induced Insulin Autoimmune Syndrome in Graves' Disease: Eun Roh, Ye An Kim, Eu Jeong Ku, Jae Hyun Bae, Hye Mi Kim, Young Min Cho, Young Joo Park, Kyong Soo Park, Seong Yeon Kim, Soo Heon Kwak; Endocrinol Metab. 2013;28(1):55-60. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.55

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Abstract PDF PubReader

We report here the cases of two females with Graves' disease who developed insulin autoimmune syndrome after treatment with methimazole. The patients exhibited a sudden altered mental state after treatment with methimazole for approximately 4 weeks. Patients had hypoglycemia with serum glucose below 70 mg/dL, and laboratory findings showed both high levels of serum insulin and high titers of insulin autoantibodies. The two women had never been exposed to insulin or oral antidiabetic agents, and there was no evidence of insulinoma in imaging studies. After glucose loading, serum glucose, and total insulin levels increased abnormally. One of the patient was found to have HLA-DRB1*0406, which is known to be strongly associated with methimazole-induced insulin autoimmune syndrome. After discontinuation of methimazole, hypoglycemic events disappeared within 1 month. Insulin autoantibody titer and insulin levels decreased within 5 months and there was no further development of hypoglycemic events. We present these cases with a review of the relevant literature.

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Diabetic Ketoacidosis Associated with Emphysematous Gastritis: A Case Report.: Young Min Choi, Jun Won Seo, Woo Jin Lee, Hyeong Jin Park, Ji Hye Shin, Seung Bum Kang, Jun Lee, Jin Hwa Kim, Sang Yong Kim, Hak Yeon Bae; Endocrinol Metab. 2011;26(4):355-359. Published online December 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.4.355

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Abstract PDF: Diabetic ketoacidosis is a serious and demanding medical emergency for the field of endocrinology, and the identification and correction of the precipitating factors is equally important. Many patients of diabetic ketoacidosis show gastrointestinal symptoms as an initial presentation, and coincidental gastrointestinal diseases can be neglected or misdiagnosed. Emphysematous gastritis is a rare and lethal disease in which gas bubbles form in the stomach wall. The predisposing factors include ingestion of corrosive substances, alcohol abuse, diabetes, and immunosuppressive therapy. Thus, it may be difficult to detect emphysematous gastritis early, especially when it is developed in conjunction with diabetic ketoacidosis. We report a case of diabetic ketoacidosis associated with emphysematous gastritis in a young male without medical history.

Original Article

Six Cases of Congenital Adrenal Hyperplasia That Were Due to 17alpha-hydroxylase/17,20-lyase Deficiency.: Dong Hoon Shin, Sung Hoon Yu, Young Min Choi, Jung Gu Kim, Sang Wan Kim, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim; J Korean Endocr Soc. 2009;24(2):109-115. Published online June 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.2.109

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Abstract PDF

17alpha-hydroxylase/17,20-lyase deficiency is a rare phenotype of congenital adrenal hyperplasia (CAH), and this is characterized by hyporeninemic hypertension, primary amenorrhea and abnormality of the secondary sexual characteristics (pseudohermaphroditism in men). This type of CAH is usually misdiagnosed at first as mineralocorticoid induced hypertension with primary aldosteronism, but primary amenorrhea with deficient sex hormone is a clue for making the correct diagnosis. The authors experienced 6 cases of 17alpha-hydroxylase/17,20-lyase deficiency in patients who ranged from 15 to 42 years of age. 4 cases were diagnosed according to the investigation of their mineralocorticoid-induced hypertension and 2 cases their primary amenorrhea and sexual infantilism. All of them had hypokalemia, hyporeninemic hypertension and an atrophied uterus and ovaries. In the genotypic male (46 XY), the testicles were atrophied in the abdominal cavity. The levels of cortisol, estrogen and dehydroepiandrosterone sulfate (DHEAS) were low, but the levels of progesterone and 11-deoxycorticosterone were high. Therefore, the diagnosis of 17alpha-hydroxylase/17,20-lyase deficiency should be considered in female patients who present with both sexual infantilism and mineralocorticoid hypertension. We report on these cases with a brief review of the literature.

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Functional Identification of Compound Heterozygous Mutations in the CYP17A1 Gene Resulting in Combined 17α-Hydroxylase/17,20-Lyase Deficiency
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17α-hydroxylase Deficiency Mimicking Hyperaldosteronism by Aldosterone-producing Adrenal Adenoma
Yun Kyung Cho, Hyeseon Oh, Sun-myoung Kang, Sujong An, Jin-Young Huh, Ji-Hyang Lee, Woo Je Lee
The Korean Journal of Medicine.2016; 91(2): 191. CrossRef

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