Endocrinology and Metabolism

Review Article

Glucagon-Like Peptide-1 Based Therapies: A New Horizon in Obesity Management: Jang Won Son, Soo Lim; Received January 18, 2024 Accepted February 15, 2024 Published online April 16, 2024; DOI: https://doi.org/10.3803/EnM.2024.1940 [Epub ahead of print]

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Abstract PDF PubReader ePub: Obesity is a significant risk factor for health issues like type 2 diabetes and cardiovascular disease. It often proves resistant to traditional lifestyle interventions, prompting a need for more precise therapeutic strategies. This has led to a focus on signaling pathways and neuroendocrine mechanisms to develop targeted obesity treatments. Recent developments in obesity management have been revolutionized by introducing novel glucagon-like peptide-1 (GLP-1) based drugs, such as semaglutide and tirzepatide. These drugs are part of an emerging class of nutrient-stimulated hormone-based therapeutics, acting as incretin mimetics to target G-protein–coupled receptors like GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon. These receptors are vital in regulating body fat and energy balance. The development of multiagonists, including GLP-1–glucagon and GIP–GLP-1–glucagon receptor agonists, especially with the potential for glucagon receptor activation, marks a significant advancement in the field. This review covers the development and clinical efficacy of various GLP-1-based therapeutics, exploring the challenges and future directions in obesity management.

Original Article

Effects of an Electronic Medical Records-Linked Diabetes Self-Management System on Treatment Targets in Real Clinical Practice: Retrospective, Observational Cohort Study: So Jung Yang, Sun-Young Lim, Yoon Hee Choi, Jin Hee Lee, Kun-Ho Yoon; Received November 10, 2023 Accepted January 22, 2024 Published online March 21, 2024; DOI: https://doi.org/10.3803/EnM.2023.1878 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
This study evaluated the effects of a mobile diabetes management program called “iCareD” (College of Medicine, The Catholic University of Korea) which was integrated into the hospital’s electronic medical records system to minimize the workload of the healthcare team in the real clinical practice setting.
Methods
In this retrospective observational study, we recruited 308 patients. We categorized these patients based on their compliance regarding their use of the iCareD program at home; compliance was determined through self-monitored blood glucose inputs and message subscription rates. We analyzed changes in the ABC (hemoglobin A1c, blood pressure, and low-density lipoprotein cholesterol) levels from the baseline to 12 months thereafter, based on the patients’ iCareD usage patterns.
Results
The patients comprised 92 (30%) non-users, 170 (55%) poor-compliance users, and 46 (15%) good-compliance users; the ABC target achievement rate showed prominent changes in good-compliance groups from baseline to 12 months (10.9% vs. 23.9%, P<0.05), whereas no significant changes were observed for poor-compliance users and non-users (13.5% vs. 18.8%, P=0.106; 20.7% vs. 14.1%, P=0.201; respectively).
Conclusion
Implementing the iCareD can improve the ABC levels of patients with diabetes with minimal efforts of the healthcare team in real clinical settings. However, the improvement of patients’ compliance concerning the use of the system without the vigorous intervention of the healthcare team needs to be solved in the future.

Namgok Lecture 2023

Diabetes, obesity and metabolism
Hypothalamic AMP-Activated Protein Kinase as a Whole-Body Energy Sensor and Regulator: Se Hee Min, Do Kyeong Song, Chan Hee Lee, Eun Roh, Min-Seon Kim; Endocrinol Metab. 2024;39(1):1-11. Published online February 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.1922

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Abstract PDF PubReader ePub: 5´-Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a cellular energy sensor, is an essential enzyme that helps cells maintain stable energy levels during metabolic stress. The hypothalamus is pivotal in regulating energy balance within the body. Certain neurons in the hypothalamus are sensitive to fluctuations in food availability and energy stores, triggering adaptive responses to preserve systemic energy equilibrium. AMPK, expressed in these hypothalamic neurons, is instrumental in these regulatory processes. Hypothalamic AMPK activity is modulated by key metabolic hormones. Anorexigenic hormones, including leptin, insulin, and glucagon-like peptide 1, suppress hypothalamic AMPK activity, whereas the hunger hormone ghrelin activates it. These hormonal influences on hypothalamic AMPK activity are central to their roles in controlling food consumption and energy expenditure. Additionally, hypothalamic AMPK activity responds to variations in glucose concentrations. It becomes active during hypoglycemia but is deactivated when glucose is introduced directly into the hypothalamus. These shifts in AMPK activity within hypothalamic neurons are critical for maintaining glucose balance. Considering the vital function of hypothalamic AMPK in the regulation of overall energy and glucose balance, developing chemical agents that target the hypothalamus to modulate AMPK activity presents a promising therapeutic approach for metabolic conditions such as obesity and type 2 diabetes mellitus.

Original Article

Diabetes, obesity and metabolism
Inhibition of Sodium-Glucose Cotransporter-2 during Serum Deprivation Increases Hepatic Gluconeogenesis via the AMPK/AKT/FOXO Signaling Pathway: Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Yu-Mi Lim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2024;39(1):98-108. Published online January 3, 2024; DOI: https://doi.org/10.3803/EnM.2023.1786

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Abstract PDF Supplementary Material PubReader ePub: Background
Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states.
Methods
Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco’s modified Eagle’s medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours.
Results
SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation.
Conclusion
These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.

Brief Report

Diabetes, obesity and metabolism
Partial Deletion of Perk Improved High-Fat Diet-Induced Glucose Intolerance in Mice: Jooyeop Lee, Min Joo Kim, Seoil Moon, Ji Yoon Lim, Kyong Soo Park, Hye Seung Jung; Endocrinol Metab. 2023;38(6):782-787. Published online November 13, 2023; DOI: https://doi.org/10.3803/EnM.2023.1738

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Abstract PDF Supplementary Material PubReader ePub: Although pancreatic endoplasmic reticulum kinase (PERK) is indispensable to beta cells, low-dose PERK inhibitor improved glucose- stimulated insulin secretion (GSIS) and hyperglycemia in diabetic mice. Current study examined if partial deletion of Perk (Perk^+/-) recapitulated the effects of PERK inhibitor, on the contrary to the complete deletion. Perk^+/- mice and wild-type controls were fed with a high-fat diet (HFD) for 23 weeks. Glucose tolerance was evaluated along with serum insulin levels and islet morphology. Perk^+/- mice on normal chow were comparable to wild-type mice in various metabolic features. HFD-induced obesity was not influenced by Perk reduction; however, HFD-induced glucose intolerance was significantly improved since 15-week HFD. HFD-induced compromises in GSIS were relieved by Perk reduction, accompanied by reductions in phosphorylated PERK and activating transcription factor 4 (ATF4) in the islets. Meanwhile, HFD-induced islet expansion was not significantly affected. In summary, partial deletion of Perk improved glucose tolerance and GSIS impaired by diet-induced obesity, without changes in body weights or islet mass.

Review Article

Diabetes, obesity and metabolism
The Benefits Of Continuous Glucose Monitoring In Pregnancy: Jee Hee Yoo, Jae Hyeon Kim; Endocrinol Metab. 2023;38(5):472-481. Published online October 11, 2023; DOI: https://doi.org/10.3803/EnM.2023.1805

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Abstract PDF PubReader ePub

Previous studies have consistently demonstrated the positive effects of continuous glucose monitoring (CGM) on glycemic outcomes and complications of diabetes in people with type 1 diabetes. Guidelines now consider CGM to be an essential and cost-effective device for managing type 1 diabetes. As a result, insurance coverage for it is available. Evidence supporting CGM continues to grow and expand to broader populations, such as pregnant people with type 1 diabetes, people with type 2 diabetes treated only with basal insulin therapy, and even type 2 diabetes that does not require insulin treatment. However, despite the significant risk of hyperglycemia in pregnancy, which leads to complications in more than half of affected newborns, CGM indications and insurance coverage for those patients are unresolved. In this review article, we discuss the latest evidence for using CGM to offer glycemic control and reduce perinatal complications, along with its cost-effectiveness in pregestational type 1 and type 2 diabetes and gestational diabetes mellitus. In addition, we discuss future prospects for CGM coverage and indications based on this evidence.

Citations

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Wearable devices for glucose monitoring: A review of state-of-the-art technologies and emerging trends
Mohammad Mansour, M. Saeed Darweesh, Ahmed Soltan
Alexandria Engineering Journal.2024; 89: 224. CrossRef

Original Articles

Diabetes, obesity and metabolism
Risk of Cause-Specific Mortality across Glucose Spectrum in Elderly People: A Nationwide Population-Based Cohort Study: Joonyub Lee, Hun-Sung Kim, Kee-Ho Song, Soon Jib Yoo, Kyungdo Han, Seung-Hwan Lee, Committee of Big Data, Korean Endocrine Society; Endocrinol Metab. 2023;38(5):525-537. Published online September 7, 2023; DOI: https://doi.org/10.3803/EnM.2023.1765

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Background
This study investigated the risk of cause-specific mortality according to glucose tolerance status in elderly South Koreans.
Methods
A total of 1,292,264 individuals aged ≥65 years who received health examinations in 2009 were identified from the National Health Information Database. Participants were classified as normal glucose tolerance, impaired fasting glucose, newly-diagnosed diabetes, early diabetes (oral hypoglycemic agents ≤2), or advanced diabetes (oral hypoglycemic agents ≥3 or insulin). The risk of system-specific and disease-specific deaths was estimated using multivariate Cox proportional hazards analysis.
Results
During a median follow-up of 8.41 years, 257,356 deaths were recorded. Diabetes was associated with significantly higher risk of all-cause mortality (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.57 to 1.60); death due to circulatory (HR, 1.49; 95% CI, 1.46 to 1.52), respiratory (HR, 1.51; 95% CI, 1.47 to 1.55), and genitourinary systems (HR, 2.22; 95% CI, 2.10 to 2.35); and neoplasms (HR, 1.30; 95% CI, 1.28 to 1.32). Diabetes was also associated with a significantly higher risk of death due to ischemic heart disease (HR, 1.70; 95% CI, 1.63 to 1.76), cerebrovascular disease (HR, 1.46; 95% CI, 1.41 to 1.50), pneumonia (HR, 1.69; 95% CI, 1.63 to 1.76), and acute or chronic kidney disease (HR, 2.23; 95% CI, 2.09 to 2.38). There was a stepwise increase in the risk of death across the glucose spectrum (P for trend <0.0001). Stroke, heart failure, or chronic kidney disease increased the risk of all-cause mortality at every stage of glucose intolerance.
Conclusion
A dose-dependent association between the risk of mortality from various causes and severity of glucose tolerance was noted in the elderly population.

Citations

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The Characteristics and Risk of Mortality in the Elderly Korean Population
Sunghwan Suh
Endocrinology and Metabolism.2023; 38(5): 522. CrossRef

Diabetes, obesity and metabolism
Triglyceride-Glucose Index Predicts Future Atherosclerotic Cardiovascular Diseases: A 16-Year Follow-up in a Prospective, Community-Dwelling Cohort Study: Joon Ho Moon, Yongkang Kim, Tae Jung Oh, Jae Hoon Moon, Soo Heon Kwak, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi, Nam H. Cho; Endocrinol Metab. 2023;38(4):406-417. Published online August 3, 2023; DOI: https://doi.org/10.3803/EnM.2023.1703

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Background
While the triglyceride-glucose (TyG) index is a measure of insulin resistance, its association with cardiovascular disease (CVD) has not been well elucidated. We evaluated the TyG index for prediction of CVDs in a prospective large communitybased cohort.
Methods
Individuals 40 to 70 years old were prospectively followed for a median 15.6 years. The TyG index was calculated as the Ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. CVDs included any acute myocardial infarction, coronary artery disease or cerebrovascular disease. We used a Cox proportional hazards model to estimate CVD risks according to quartiles of the TyG index and plotted the receiver operating characteristics curve for the incident CVD.
Results
Among 8,511 subjects (age 51.9±8.8 years; 47.5% males), 931 (10.9%) had incident CVDs during the follow-up. After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, total cholesterol, smoking, alcohol, exercise, and C-reactive protein, subjects in the highest TyG quartile had 36% increased risk of incident CVD compared with the lowest TyG quartile (hazard ratio, 1.36; 95% confidence interval, 1.10 to 1.68). Carotid plaque, assessed by ultrasonography was more frequent in subjects in the higher quartile of TyG index (P for trend=0.049 in men and P for trend <0.001 in women). The TyG index had a higher predictive power for CVDs than the homeostasis model assessment of insulin resistance (HOMA-IR) (area under the curve, 0.578 for TyG and 0.543 for HOMA-IR). Adding TyG index on diabetes or hypertension alone gave sounder predictability for CVDs.
Conclusion
The TyG index is independently associated with future CVDs in 16 years of follow-up in large, prospective Korean cohort.

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Construction and validation of a nomogram for predicting diabetes remission at 3 months after bariatric surgery in patients with obesity combined with type 2 diabetes mellitus
Kaisheng Yuan, Bing Wu, Ruiqi Zeng, Fuqing Zhou, Ruixiang Hu, Cunchuan Wang
Diabetes, Obesity and Metabolism.2024; 26(1): 169. CrossRef
Association between the triglyceride glucose index and chronic total coronary occlusion: A cross-sectional study from southwest China
Kaiyong Xiao, Huili Cao, Bin Yang, Zhe Xv, Lian Xiao, Jianping Wang, Shuiqing Ni, Hui Feng, Zhongwei He, Lei Xv, Juan Li, Dongmei Xv
Nutrition, Metabolism and Cardiovascular Diseases.2024; 34(4): 850. CrossRef
The association between TyG and all-cause/non-cardiovascular mortality in general patients with type 2 diabetes mellitus is modified by age: results from the cohort study of NHANES 1999–2018
Younan Yao, Bo Wang, Tian Geng, Jiyan Chen, Wan Chen, Liwen Li
Cardiovascular Diabetology.2024;[Epub] CrossRef
Triglyceride-glucose index predicts type 2 diabetes mellitus more effectively than oral glucose tolerance test-derived insulin sensitivity and secretion markers
Min Jin Lee, Ji Hyun Bae, Ah Reum Khang, Dongwon Yi, Mi Sook Yun, Yang Ho Kang
Diabetes Research and Clinical Practice.2024; 210: 111640. CrossRef
Evaluation of the novel three lipid indices for predicting five- and ten-year incidence of cardiovascular disease: findings from Kerman coronary artery disease risk factors study (KERCADRS)
Alireza Jafari, Hamid Najafipour, Mitra Shadkam, Sina Aminizadeh
Lipids in Health and Disease.2023;[Epub] CrossRef

Diabetes, obesity and metabolism
Efficacy of Gemigliptin Add-on to Dapagliflozin and Metformin in Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Study (SOLUTION): Byung Wan Lee, KyungWan Min, Eun-Gyoung Hong, Bon Jeong Ku, Jun Goo Kang, Suk Chon, Won-Young Lee, Mi Kyoung Park, Jae Hyeon Kim, Sang Yong Kim, Keeho Song, Soon Jib Yoo; Endocrinol Metab. 2023;38(3):328-337. Published online June 28, 2023; DOI: https://doi.org/10.3803/EnM.2023.1688

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Abstract PDF Supplementary Material PubReader ePub: Background
This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin.
Methods
In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks.
Results
The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted.
Conclusion
Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

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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Abstract PDF PubReader ePub

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.

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

Review Articles

Diabetes, Obesity and Metabolism
Recent Updates to Clinical Practice Guidelines for Diabetes Mellitus: Jin Yu, Seung-Hwan Lee, Mee Kyoung Kim; Endocrinol Metab. 2022;37(1):26-37. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.105

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Guidelines for the management of patients with diabetes have become an important part of clinical practice that improve the quality of care and help establish evidence-based medicine in this field. With rapidly accumulating evidence on various aspects of diabetes care, including landmark clinical trials of treatment agents and newer technologies, timely updates of the guidelines capture the most current state of the field and present a consensus. As a leading academic society, the Korean Diabetes Association publishes practice guidelines biennially and the American Diabetes Association does so annually. In this review, we summarize the key changes suggested in the most recent guidelines. Some of the important updates include treatment algorithms emphasizing comorbid conditions such as atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease in the selection of anti-diabetic agents; wider application of continuous glucose monitoring (CGM), insulin pump technologies and indices derived from CGM such as time in range; more active screening of subjects at high-risk of diabetes; and more detailed individualization in diabetes care. Although there are both similarities and differences among guidelines and some uncertainty remains, these updates provide a good approach for many clinical practitioners who are battling with diabetes.

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Qiong Zeng, Xiao-Jing Chen, Yi-Ting He, Ze-Ming Ma, Yi-Xi Wu, Kun Lin
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Diabetes, Obesity and Metabolism
Homeostatic Regulation of Glucose Metabolism by the Central Nervous System: Jong Han Choi, Min-Seon Kim; Endocrinol Metab. 2022;37(1):9-25. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1364

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Evidence for involvement of the central nervous system (CNS) in the regulation of glucose metabolism dates back to the 19th century, although the majority of the research on glucose metabolism has focused on the peripheral metabolic organs. Due to recent advances in neuroscience, it has now become clear that the CNS is indeed vital for maintaining glucose homeostasis. To achieve normoglycemia, specific populations of neurons and glia in the hypothalamus sense changes in the blood concentrations of glucose and of glucoregulatory hormones such as insulin, leptin, glucagon-like peptide 1, and glucagon. This information is integrated and transmitted to other areas of the brain where it eventually modulates various processes in glucose metabolism (i.e., hepatic glucose production, glucose uptake in the brown adipose tissue and skeletal muscle, pancreatic insulin and glucagon secretion, renal glucose reabsorption, etc.). Errors in these processes lead to hyper- or hypoglycemia. We here review the current understanding of the brain regulation of glucose metabolism.

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Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 2939. CrossRef

Original Articles

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Frequency of Exposure to Impaired Fasting Glucose and Risk of Mortality and Cardiovascular Outcomes: Seung-Hwan Lee, Kyungdo Han, Hyuk-Sang Kwon, Mee Kyoung Kim; Endocrinol Metab. 2021;36(5):1007-1015. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1218

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Background
Metabolic abnormalities, such as impaired fasting glucose (IFG), are dynamic phenomena; however, it is unclear whether the timing of IFG exposure and cumulative exposure to IFG are related to cardiovascular disease (CVD) and mortality risk.
Methods
Data were extracted from a nationwide population-based cohort in South Korea for adults (n=2,206,679) who were free of diabetes and had 4 years of consecutive health examination data. Fasting blood glucose levels of 100 to 125 mg/dL were defined as IFG, and the number of IFG diagnoses for each adult in the 4-year period was tabulated as the IFG exposure score (range, 0 to 4). Adults with persistent IFG for the 4-year period received a score of 4.
Results
The median follow-up was 8.2 years. There were 24,820 deaths, 13,502 cases of stroke, and 13,057 cases of myocardial infarction (MI). IFG exposure scores of 1, 2, 3, and 4 were associated with all-cause mortality (multivariable-adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.08 to 1.15; aHR, 1.16; 95% CI, 1.12 to 1.20; aHR, 1.20; 95% CI, 1.15 to 1.25; aHR, 1.18; 95% CI, 1.11 to 1.25, respectively) compared with an IFG exposure score of 0. Adjusting for hypertension and dyslipidemia attenuated the slightly increased risk of MI or stroke associated with high IFG exposure scores, but significant associations for allcause mortality remained.
Conclusion
The intensity of IFG exposure was associated with an elevated risk of all-cause mortality, independent of cardiovascular risk factors. The association between IFG exposure and CVD risk was largely mediated by the coexistence of dyslipidemia and hypertension.

Citations

Citations to this article as recorded by

A nationwide cohort study on diabetes severity and risk of Parkinson disease
Kyungdo Han, Bongsung Kim, Seung Hwan Lee, Mee Kyoung Kim
npj Parkinson's Disease.2023;[Epub] CrossRef
Diabetes severity is strongly associated with the risk of active tuberculosis in people with type 2 diabetes: a nationwide cohort study with a 6-year follow-up
Ji Young Kang, Kyungdo Han, Seung-Hwan Lee, Mee Kyoung Kim
Respiratory Research.2023;[Epub] CrossRef
Construction and Validation of a Model for Predicting Impaired Fasting Glucose Based on More Than 4000 General Population
Cuicui Wang, Xu Zhang, Chenwei Li, Na Li, Xueni Jia, Hui Zhao
International Journal of General Medicine.2023; Volume 16: 1415. CrossRef
Factors Affecting High Body Weight Variability
Kyungdo Han, Mee Kyoung Kim
Journal of Obesity & Metabolic Syndrome.2023; 32(2): 163. CrossRef
Exposure to perfluoroalkyl and polyfluoroalkyl substances and risk of stroke in adults: a meta-analysis
Min Cheol Chang, Seung Min Chung, Sang Gyu Kwak
Reviews on Environmental Health.2023;[Epub] CrossRef
Cumulative effect of impaired fasting glucose on the risk of dementia in middle-aged and elderly people: a nationwide cohort study
Jin Yu, Kyu-Na Lee, Hun-Sung Kim, Kyungdo Han, Seung-Hwan Lee
Scientific Reports.2023;[Epub] CrossRef
A Longitudinal Retrospective Observational Study on Obesity Indicators and the Risk of Impaired Fasting Glucose in Pre- and Postmenopausal Women
Myung Ji Nam, Hyunjin Kim, Yeon Joo Choi, Kyung-Hwan Cho, Seon Mee Kim, Yong-Kyun Roh, Kyungdo Han, Jin-Hyung Jung, Yong-Gyu Park, Joo-Hyun Park, Do-Hoon Kim
Journal of Clinical Medicine.2022; 11(10): 2795. CrossRef
Current Trends of Big Data Research Using the Korean National Health Information Database
Mee Kyoung Kim, Kyungdo Han, Seung-Hwan Lee
Diabetes & Metabolism Journal.2022; 46(4): 552. CrossRef
Lipid cutoffs for increased cardiovascular disease risk in non-diabetic young people
Mee Kyoung Kim, Kyungdo Han, Hun-Sung Kim, Kun-Ho Yoon, Seung-Hwan Lee
European Journal of Preventive Cardiology.2022; 29(14): 1866. CrossRef
Low-Density Lipoprotein Cholesterol Level, Statin Use and Myocardial Infarction Risk in Young Adults
Heekyoung Jeong, Kyungdo Han, Soon Jib Yoo, Mee Kyoung Kim
Journal of Lipid and Atherosclerosis.2022; 11(3): 288. CrossRef
Additive interaction of diabetes mellitus and chronic kidney disease in cancer patient mortality risk
Seohyun Kim, Gyuri Kim, Jae Hyeon Kim
Scientific Reports.2022;[Epub] CrossRef

Diabetes, Obesity and Metabolism
How Can We Adopt the Glucose Tolerance Test to Facilitate Predicting Pregnancy Outcome in Gestational Diabetes Mellitus?: Kyeong Jin Kim, Nam Hoon Kim, Jimi Choi, Sin Gon Kim, Kyung Ju Lee; Endocrinol Metab. 2021;36(5):988-996. Published online October 15, 2021; DOI: https://doi.org/10.3803/EnM.2021.1107

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Background
We investigated how 100-g oral glucose tolerance test (OGTT) results can be used to predict adverse pregnancy outcomes in gestational diabetes mellitus (GDM) patients.
Methods
We analyzed 1,059 pregnant women who completed the 100-g OGTT between 24 and 28 weeks of gestation. We compared the risk of adverse pregnancy outcomes according to OGTT patterns by latent profile analysis (LPA), numbers to meet the OGTT criteria, and area under the curve (AUC) of the OGTT graph. Adverse pregnancy outcomes were defined as a composite of preterm birth, macrosomia, large for gestational age, low APGAR score at 1 minute, and pregnancy-induced hypertension.
Results
Overall, 257 participants were diagnosed with GDM, with a median age of 34 years. An LPA led to three different clusters of OGTT patterns; however, there were no significant associations between the clusters and adverse pregnancy outcomes after adjusting for confounders. Notwithstanding, the risk of adverse pregnancy outcome increased with an increase in number to meet the OGTT criteria (P for trend=0.011); odds ratios in a full adjustment model were 1.27 (95% confidence interval [CI], 0.72 to 2.23), 2.16 (95% CI, 1.21 to 3.85), and 2.32 (95% CI, 0.66 to 8.15) in those meeting the 2, 3, and 4 criteria, respectively. The AUCs of the OGTT curves also distinguished the patients at risk of adverse pregnancy outcomes; the larger the AUC, the higher the risk (P for trend=0.007).
Conclusion
The total number of abnormal values and calculated AUCs for the 100-g OGTT may facilitate tailored management of patients with GDM by predicting adverse pregnancy outcomes.

Citations

Citations to this article as recorded by

Risk factors combine in a complex manner in assessment for macrosomia
Yi-Wen Wang, Yan Chen, Yong-Jun Zhang
BMC Public Health.2023;[Epub] CrossRef
Association of the Severity of Hypertensive Disorders in Pregnancy with Birthweight, Childhood Obesity, and Blood Pressure at Age 7
Yan Chen, Yiwen Wang, Yanjun Li, Guodong Ding, Yongjun Zhang
Nutrients.2023; 15(14): 3104. CrossRef

Diabetes, Obesity and Metabolism
Role of TRPV4 Channel in Human White Adipocytes Metabolic Activity: Julio C. Sánchez, Aníbal Valencia-Vásquez, Andrés M. García; Endocrinol Metab. 2021;36(5):997-1006. Published online October 14, 2021; DOI: https://doi.org/10.3803/EnM.2021.1167

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122 Download
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Abstract PDF PubReader ePub

Background
Intracellular calcium (Ca²⁺) homeostasis plays an essential role in adipocyte metabolism and its alteration is associated with obesity and related disorders. Transient receptor potential vanilloid 4 (TRPV4) channels are an important Ca²⁺ pathway in adipocytes and their activity is regulated by metabolic mediators such as insulin. In this study, we evaluated the role of TRPV4 channels in metabolic activity and adipokine secretion in human white adipocytes.
Methods
Human white adipocytes were freshly cultured and the effects of the activation and inhibition of TRPV4 channels on lipolysis, glucose uptake, lactate production, and leptin and adiponectin secretion were evaluated.
Results
Under basal and isoproterenol-stimulated conditions, TRPV4 activation by GSK1016709A decreased lipolysis whereas HC067047, an antagonist, increased lipolysis. The activation of TRPV4 resulted in increased glucose uptake and lactate production under both basal conditions and insulin-stimulated conditions; in contrast HC067047 decreased both parameters. Leptin production was increased, and adiponectin production was diminished by TRPV4 activation and its inhibition had the opposite effect.
Conclusion
Our results suggested that TRPV4 channels are metabolic mediators involved in proadipogenic processes and glucose metabolism in adipocyte biology. TRPV4 channels could be a potential pharmacological target to treat metabolic disorders.

Citations

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Yibing Wang
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Xi-Ding Yang, Xing-Cheng Ge, Si-Yi Jiang, Yong-Yu Yang
Frontiers in Endocrinology.2022;[Epub] CrossRef
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Joseph C. Galley, Shubhnita Singh, Wanessa M.C. Awata, Juliano V. Alves, Thiago Bruder-Nascimento
Biochemical Pharmacology.2022; 206: 115324. CrossRef

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