1.A Longitudinal Increase in Serum Gamma-Glutamyl Transferase Levels, but Not in Alanine Aminotransferase Levels, Improves the Prediction of Risk of Impaired Fasting Glucose in Male
Jisoon IM ; Susie JUNG ; Yuri YANG ; Kyu-Nam KIM
Journal of Korean Medical Science 2025;40(6):e13-
Background:
Impaired fasting glucose (IFG), being a pre-diabetic condition, can increase the risk of overt diabetes; thus early detection and prediction of IFG are important to reduce the incidence of overt diabetes. Some predictive factors, including serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), have been reported in several studies, but none of the studies have investigated the effect of longitudinal changes in individual serum ALT and GGT levels on the risk of IFG.
Methods:
We aimed to investigate the association between changes in the serum ALT and GGT levels and the risk of IFG using a checkup database between 1999 and 2014.
Results:
A total of 3,598 males and 3,275 females were enrolled in the study. We performed a follow-up test of serum ALT or GGT in each individual, and classified the cases in which the serum ALT or GGT level was increased or decreased during the follow-up test compared to the baseline. According to the multivariate Cox proportional hazards model, the hazard ratio was 1.76 (95% confidence interval, 1.45–2.12; P < 0.001) in male subjects with an increased serum GGT level compared to male subjects with a decrease in the serum GGT level at followup compared to the baseline. However, the relationship between the serum ALT level and incidence of new-onset IFG was not statistically significant in both sexes; and in females, the relationship between the serum GGT level and incidence of new-onset IFG was also not statistically significant.
Conclusion
We revealed that a longitudinal increase in serum GGT levels was related to an increased risk of IFG in males. Therefore, monitoring the changes in serum GGT levels is important for predicting new-onset IFG, and it can be used as an early indicator of onset of overt diabetes in males.
2.A Longitudinal Increase in Serum Gamma-Glutamyl Transferase Levels, but Not in Alanine Aminotransferase Levels, Improves the Prediction of Risk of Impaired Fasting Glucose in Male
Jisoon IM ; Susie JUNG ; Yuri YANG ; Kyu-Nam KIM
Journal of Korean Medical Science 2025;40(6):e13-
Background:
Impaired fasting glucose (IFG), being a pre-diabetic condition, can increase the risk of overt diabetes; thus early detection and prediction of IFG are important to reduce the incidence of overt diabetes. Some predictive factors, including serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), have been reported in several studies, but none of the studies have investigated the effect of longitudinal changes in individual serum ALT and GGT levels on the risk of IFG.
Methods:
We aimed to investigate the association between changes in the serum ALT and GGT levels and the risk of IFG using a checkup database between 1999 and 2014.
Results:
A total of 3,598 males and 3,275 females were enrolled in the study. We performed a follow-up test of serum ALT or GGT in each individual, and classified the cases in which the serum ALT or GGT level was increased or decreased during the follow-up test compared to the baseline. According to the multivariate Cox proportional hazards model, the hazard ratio was 1.76 (95% confidence interval, 1.45–2.12; P < 0.001) in male subjects with an increased serum GGT level compared to male subjects with a decrease in the serum GGT level at followup compared to the baseline. However, the relationship between the serum ALT level and incidence of new-onset IFG was not statistically significant in both sexes; and in females, the relationship between the serum GGT level and incidence of new-onset IFG was also not statistically significant.
Conclusion
We revealed that a longitudinal increase in serum GGT levels was related to an increased risk of IFG in males. Therefore, monitoring the changes in serum GGT levels is important for predicting new-onset IFG, and it can be used as an early indicator of onset of overt diabetes in males.
3.A Longitudinal Increase in Serum Gamma-Glutamyl Transferase Levels, but Not in Alanine Aminotransferase Levels, Improves the Prediction of Risk of Impaired Fasting Glucose in Male
Jisoon IM ; Susie JUNG ; Yuri YANG ; Kyu-Nam KIM
Journal of Korean Medical Science 2025;40(6):e13-
Background:
Impaired fasting glucose (IFG), being a pre-diabetic condition, can increase the risk of overt diabetes; thus early detection and prediction of IFG are important to reduce the incidence of overt diabetes. Some predictive factors, including serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), have been reported in several studies, but none of the studies have investigated the effect of longitudinal changes in individual serum ALT and GGT levels on the risk of IFG.
Methods:
We aimed to investigate the association between changes in the serum ALT and GGT levels and the risk of IFG using a checkup database between 1999 and 2014.
Results:
A total of 3,598 males and 3,275 females were enrolled in the study. We performed a follow-up test of serum ALT or GGT in each individual, and classified the cases in which the serum ALT or GGT level was increased or decreased during the follow-up test compared to the baseline. According to the multivariate Cox proportional hazards model, the hazard ratio was 1.76 (95% confidence interval, 1.45–2.12; P < 0.001) in male subjects with an increased serum GGT level compared to male subjects with a decrease in the serum GGT level at followup compared to the baseline. However, the relationship between the serum ALT level and incidence of new-onset IFG was not statistically significant in both sexes; and in females, the relationship between the serum GGT level and incidence of new-onset IFG was also not statistically significant.
Conclusion
We revealed that a longitudinal increase in serum GGT levels was related to an increased risk of IFG in males. Therefore, monitoring the changes in serum GGT levels is important for predicting new-onset IFG, and it can be used as an early indicator of onset of overt diabetes in males.
4.A Longitudinal Increase in Serum Gamma-Glutamyl Transferase Levels, but Not in Alanine Aminotransferase Levels, Improves the Prediction of Risk of Impaired Fasting Glucose in Male
Jisoon IM ; Susie JUNG ; Yuri YANG ; Kyu-Nam KIM
Journal of Korean Medical Science 2025;40(6):e13-
Background:
Impaired fasting glucose (IFG), being a pre-diabetic condition, can increase the risk of overt diabetes; thus early detection and prediction of IFG are important to reduce the incidence of overt diabetes. Some predictive factors, including serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), have been reported in several studies, but none of the studies have investigated the effect of longitudinal changes in individual serum ALT and GGT levels on the risk of IFG.
Methods:
We aimed to investigate the association between changes in the serum ALT and GGT levels and the risk of IFG using a checkup database between 1999 and 2014.
Results:
A total of 3,598 males and 3,275 females were enrolled in the study. We performed a follow-up test of serum ALT or GGT in each individual, and classified the cases in which the serum ALT or GGT level was increased or decreased during the follow-up test compared to the baseline. According to the multivariate Cox proportional hazards model, the hazard ratio was 1.76 (95% confidence interval, 1.45–2.12; P < 0.001) in male subjects with an increased serum GGT level compared to male subjects with a decrease in the serum GGT level at followup compared to the baseline. However, the relationship between the serum ALT level and incidence of new-onset IFG was not statistically significant in both sexes; and in females, the relationship between the serum GGT level and incidence of new-onset IFG was also not statistically significant.
Conclusion
We revealed that a longitudinal increase in serum GGT levels was related to an increased risk of IFG in males. Therefore, monitoring the changes in serum GGT levels is important for predicting new-onset IFG, and it can be used as an early indicator of onset of overt diabetes in males.
5.Functional medicine perspectives on the evaluation and management of hypochlorhydria and achlorhydria
Journal of Korean Institute for Functional Medicine 2025;8(1):69-83
Hypochlorhydria and achlorhydria, a condition of abnormally low and no gastric acid secretion, are often underdiagnosed due to its nonspecific symptoms and limited clinical awareness. Gastric acid plays a critical role in protein digestion, micronutrient absorption, and microbial defense. Functional medicine approaches emphasize the upstream causes and systemic impacts of hypochlorhydria, identifying its contribution to nutritional deficiencies, small intestinal bacterial overgrowth, and chronic gastrointestinal symptoms. This review explores the pathophysiology, diagnostic strategies—including serologic, endoscopic, and microbiome-based assessments—and root causes such as Helicobacter pylori infection, autoimmune gastritis, and medication-induced hypochlorhydria. Functional medicine interventions such as the 5R framework (remove, replace, reinoculate, repair, rebalance) offer a holistic model to restore gastric function and systemic health. Particular attention is given to the role of nutrient supplementation, targeted microbial therapies, and acid replacement strategies like betaine HCl. In addition to diagnostic accuracy, therapeutic timing is crucial to prevent irreversible mucosal atrophy and micronutrient depletion. Clinical implications extend to anemia, osteoporosis, vitamin B12 deficiency, and impaired methylation pathways. Functional medicine offers a unique paradigm to address these interconnected systems, presenting opportunities for both disease management and prevention.
6.The effect of resistant starch on heart rate variability in women with metabolic risks: a subgroup analysis from a randomized, double-blind, clinical trial
Hyang-Rae LEE ; Kyu-Nam KIM ; Susie JUNG ; Soohwan JUNG ; Nam-Seok JOO
Journal of Korean Institute for Functional Medicine 2025;8(1):84-93
Heart rate variability (HRV) is a well-established marker of autonomic nervous system function and resistant starch (RS) is known to modulate gut microbiota and promote short-chain fatty acid production. This study aimed to investigate whether RS consumption improves HRV by modulating autonomic function in individuals with metabolic syndrome risks. Methods: This randomized controlled trial included 30 women with metabolic syndrome, recruited from a university hospital. Participants were randomly assigned to either the high-resistant starch (HRS) group or the low-resistant starch (LRS) group. The intervention lasted for 8 weeks. The primary analysis of this study focused on participants in the lower 50% of baseline total power (TP), assessing the differential effects of HRS intake on autonomic function in this subgroup. Statistical analyses, including the Wilcoxon rank-sum test, were performed to compare differences between groups. Results: In the subgroup with baseline TP in the lower 50%, the HRS group showed an increase in TP (median ΔTP: 435 ms², interquartile range [IQR]: 964 ms²), while the LRS group showed a decrease (-30.9 ms², IQR: 146 ms²). The between-group difference in TP change was statistically significant (P=0.03). Similarly, low frequency (LF) power increased significantly in the HRS group compared to the LRS group (P=0.03). Although high frequency and very low frequency also showed greater improvement in the HRS group, these changes did not reach statistical significance. Conclusion: RS intake was associated with significant improvements in TP and LF in individuals with lower baseline HRV, suggesting its potential role in autonomic nervous system modulation.
7.Entrustable Professional Activities in Family Medicine Residency Training between South Korea and Abroad: A Comparative Analysis
Korean Journal of Family Practice 2025;15(4):174-180
This study provides a comparative analysis of the Entrustable Professional Activities (EPAs) within family medicine residency training programs in South Korea, the United States, Canada, the United Kingdom, and Australia. As medical education shifts globally toward a competency-based paradigm, EPAs have become a crucial framework for defining and assessing a resident’s ability to perform essential clinical tasks independently. While this concept is utilized in all five countries to structure residents’ training, significant differences exist in their scope, philosophy, and assessment systems.South Korea has established 12 core EPAs reflecting its specific clinical environment, but currently lacks a systematic competency-based assessment methodology. By contrast, their international counterparts have more developed systems. The U.S. has recently evolved from 20 granular EPAs to 12 broader “Core Outcomes,” consequently focusing on the overall results of training. Canada integrates 35 EPAs into its CanMEDS competency framework to create a cohesive continuum from medical school through residency. The U.K. employs a functionally equivalent system of 13 “Professional Capabilities” supported by a robust workplace-based assessment system. Australia utilizes 13 EPAs assessed through a practical 4-level entrustment scale that is embedded in daily clinical practice. Key differences lie in the emphasis international programs place on broader professional roles, such as health equity, team leadership, and social accountability, and their sophisticated, integrated assessment tools. This study recommends that the Korean family medicine training system adopt a more holistic, outcome-based perspective, develop multifaceted assessment tools, and create a flexible framework to address the evolving demands of modern healthcare.
8.Clinical evaluation and treatment of hypercortisolism that functional medicine practitioners should consider
Journal of Korean Institute for Functional Medicine 2024;7(1):40-52
Hypercortisolism is a phenomenon identified in traditional medicine for Cushing's syndrome, an endocrine disease, but is commonly discovered during clinical evaluation in functional medicine. Endogenous Cushing's syndrome itself is an uncommon disease, but if not properly evaluated, it can cause various complications in patients, so early detection and treatment are important. Additionally, pseudo-Cushing's syndrome, which may appear to be Cushing's syndrome, is often closely related to mental illness and stress reactions. As a functional medicine physician, it is important to understand cortisol metabolism and testing methods to evaluate hypercortisolism, and it is necessary to consider various patient’s conditions and solutions when hypercortisolism is confirmed.
9.Functional medicine approach to functional dyspepsia: a case of brain-gut axis imbalance and 2 cases of hypochlorhydria
Journal of Korean Institute for Functional Medicine 2024;7(2):89-108
Functional dyspepsia is a common gastrointestinal disorder typically treated with proton pump inhibitors or gastrointestinal motility agents. However, these treatments can sometimes be ineffective or even worsen symptoms. Therefore, it may be more beneficial to identify and address the root causes of the symptoms rather than relying solely on standard treatments. Addressing the root issues of functional dyspepsia can be more effective than merely using gastrointestinal medications. First, gastrointestinal symptoms may arise from hormonal imbalances, autonomic nervous system dysfunctions, and neurotransmitter imbalances, all of which indicate imbalances of brain-gut axis. Correcting these imbalances can significantly alleviate symptoms. Second, a comprehensive approach to functional medicine in gastrointestinal health should include not only hyperacidity and hypersensitivity but also conditions like hypochlorhydria, along with associated nutritional deficiencies and small intestinal bacterial overgrowth. Integrating clinical nutritional treatments alongside these considerations can further enhance symptom relief. This paper reviewed the related literature and reported three related cases.
10.Serum Homocysteine and Vascular Calcification: Advances in Mechanisms, Related Diseases, and Nutrition
Susie JUNG ; Beom-Hee CHOI ; Nam-Seok JOO
Korean Journal of Family Medicine 2022;43(5):277-289
Identifying and preventing modifiable risk factors for cardiovascular disease is very important. Vascular calcification has been studied clinically as an asymptomatic preclinical marker of atherosclerosis and a risk factor for cardio-cerebrovascular disease. It is known that higher homocysteine levels are associated with calcified plaques and the higher the homocysteine level, the higher the prevalence and progression of vascular calcification. Homocysteine is a byproduct of methionine metabolism and is generally maintained at a physiological level. Moreover, it may increase if the patient has a genetic deficiency of metabolic enzymes, nutritional deficiencies of related cofactors (vitamins), chronic diseases, or a poor lifestyle. Homocysteine is an oxidative stress factor that can lead to calcified plaques and trigger vascular inflammation. Hyperhomocysteinemia causes endothelial dysfunction, transdifferentiation of vascular smooth muscle cells, and the induction of apoptosis. As a result of transdifferentiation and cell apoptosis, hydroxyapatite accumulates in the walls of blood vessels. Several studies have reported on the mechanisms of multiple cellular signaling pathways that cause inflammation and calcification in blood vessels. Therefore, in this review, we take a closer look at understanding the clinical consequences of hyperhomocysteinemia and apply clinical approaches to reduce its prevalence.

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