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Review Article
Diabetes, obesity and metabolism
SGLT2 Inhibitors as Systemic Metabolic Modulators: Linking Glucose Excretion to Liver Function Restoration
Seung Wan Noh, Han Sol Ryu, Yong-Ho Kim, Byung-Chul Oh
Endocrinol Metab. 2025;40(6):851-865.   Published online December 24, 2025
DOI: https://doi.org/10.3803/EnM.2025.2786
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AbstractAbstract PDFPubReader   ePub   
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as paradigm-shifting therapeutics that extend beyond glycemic regulation, to conferring profound hepatometabolic benefits. This review delineates the multifaceted mechanisms underlying metabolic dysfunction-associated steatotic liver disease (MASLD), with an emphasis on systemic metabolic remodeling, mitochondrial protection, and intracellular calcium restoration. By promoting glucosuria-induced energy depletion, SGLT2 inhibition alleviates insulin resistance, suppresses hepatic lipogenesis, and activates adenosine monophosphate-activated protein kinase (AMPK)–sirtuin 1 (SIRT1)–peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α pathways that reprogram hepatocellular metabolism toward achieving lipid oxidation and autophagy. Mechanistically, SGLT2 inhibitors restore intracellular Ca2+ homeostasis via sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) activation, mitigating endoplasmic reticulum (ER) stress and normalizing Ca2+–phosphoinositide (PIP)–protein kinase B (AKT) signaling, collectively reinforcing insulin responsiveness and ER-mitochondrial crosstalk. Clinically, these effects translate into consistently reducing hepatic fat, aminotransferases, and fibrosis markers in both diabetic and nondiabetic patients with MASLD. Furthermore, SGLT2 inhibitors uniquely integrate renal energy regulation with hepatic resilience through the Ca2+–PIP–SERCA axis, positioning them as prototype systemic modulators of metabolic homeostasis. Future translational efforts should refine patient stratification using metabolomic and Ca2+-imaging biomarkers to delineate therapeutic responders and advance next-generation SGLT2 analogs targeting Ca2+-dependent metabolic signaling. Collectively, SGLT2 inhibitors represent a new metabolic therapeutic class that unify glucose, lipid, and Ca2+ regulation to restore hepatocellular functions in metabolic liver diseases.

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  • Immune Determinants of MASLD Progression: From Immunometabolic Reprogramming to Fibrotic Transformation
    Senping Xu, Zhaoshan Zhang, Zhongquan Zhou, Jiawei Guo
    Biology.2026; 15(2): 148.     CrossRef
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Original Articles
LGALS3BP Induces Insulin Resistance via TLR2-IKKα/β Pathway-Mediated IRS1 Serine Phosphorylation
Minjeong Sung, Dae-Hwan Kim, Eun-Gene Sun, Jun-Eul Hwang, Sang-Hee Cho, Ik-Joo Chung, Hyun-Jeong Shim, Woo Kyun Bae
Received May 12, 2025  Accepted July 10, 2025  Published online October 21, 2025  
DOI: https://doi.org/10.3803/EnM.2025.2448    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Insulin resistance (IR) disrupts hepatic glucose and lipid metabolism, contributing to metabolic dysfunction-associated steatotic liver disease (MASLD) and progression to severe liver complications. Galectin-3-binding protein (LGALS3BP) is a secreted glycoprotein implicated in inflammation and metabolic disorders. Elevated LGALS3BP levels are associated with MASLD and type 2 diabetes (T2D), but its role in IR remains unclear.
Methods
LGALS3BP-deficient models were used to investigate its role in IR and inflammation. Glucose metabolism and insulin signaling were assessed in high-fat diet (HFD)-fed mice. Hepatic cell lines were employed to evaluate the direct effects of LGALS3BP on insulin signaling and inflammation. Mechanistic insights were obtained through RNA sequencing, structural modeling, immunoprecipitation, and protein/gene expression analyses.
Results
LGALS3BP deficiency improved insulin sensitivity in HFD-fed mice by enhancing glucose tolerance, lowering serum glucose and insulin, and increasing hepatic insulin signaling, without altering lipid accumulation. In vitro, LGALS3BP deficiency enhanced insulin signaling and suppressed gluconeogenesis, whereas recombinant LGALS3BP impaired insulin signaling and upregulated gluconeogenesis. RNA sequencing revealed activation of Toll-like receptor 2 (TLR2) and nuclear factor-kappa B (NF-κB) pathways by LGALS3BP. Immunoprecipitation confirmed a direct interaction between LGALS3BP and TLR2, leading to inhibitor kappa kinase (IKK)/NF-κB activation and increased insulin receptor substrate-1 (IRS1) serine phosphorylation, a key inhibitory modification in IR. Furthermore, LGALS3BP deficiency attenuated hepatic fibrosis under chronic HFD, accompanied by downregulated inflammatory signaling pathways.
Conclusion
LGALS3BP contributes to IR through inflammatory responses, particularly via TLR2-IKKα/β signaling that regulates IRS1 serine phosphorylation. LGALS3BP deficiency improves insulin sensitivity and reduces inflammation, suggesting that targeting LGALS3BP may represent a potential therapeutic strategy for metabolic disorders such as T2D and MASLD.

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  • Correlation of Plasma and Liver Tissue Proteomics for Plasma Biomarkers in Metabolic Dysfunction-Associated Steatotic Liver Disease
    Achuthan Sourianarayanane, Ju-Seog Lee, Honsoul Kim, Brett S Phinney
    Journal of Proteome Research.2025;[Epub]     CrossRef
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Reduced Sphingosine-1-Phosphate Levels Exacerbate Type 2 Diabetes Mellitus and Associated Complications in a High-Fat Diet Mouse Model
Shih-Chang Hsu, Ching-Lu Chen, Chung Te Liu, Hung-Chieh Lo, Ying-Kuo Liu, Pei-Song Gao, Shau-Ku Huang, Chin-Wang Hsu
Received March 4, 2025  Accepted May 28, 2025  Published online August 5, 2025  
DOI: https://doi.org/10.3803/EnM.2025.2360    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Type 2 diabetes mellitus (T2DM) is increasingly prevalent and frequently associated with obesity, insulin resistance, nonalcoholic fatty liver disease, and chronic kidney disease. Emerging evidence suggests sphingosine-1-phosphate (S1P), a bioactive sphingolipid, plays a significant role in the pathogenesis of T2DM. This study aimed to investigate how reduced S1P levels impact T2DM development.
Methods
S1P lyase knock-in (S1PLC317A KI) mice, characterized by reduced S1P levels due to impaired S1P degradation, were compared with wild-type (WT) mice. Both groups were fed a high-fat diet (HFD) to induce T2DM. Parameters including body weight, insulin resistance, blood glucose levels, hepatic fat accumulation, and kidney pathology were evaluated. Next-generation sequencing was employed to identify differentially expressed genes.
Results
S1PLC317A KI mice exhibited greater body weight, more pronounced insulin resistance, and higher blood glucose levels compared to WT mice on an HFD. Increased hepatic fat deposition and worsened diabetic kidney disease were also observed in KI mice. Sequencing analysis identified 4,656 differentially expressed genes, notably enriched in mitochondrial and bioenergetic pathways, including 133 diabetes-related genes.
Conclusion
Reduced S1P levels exacerbate T2DM symptoms, indicating that therapeutic targeting of S1P pathways may offer promising strategies for treating T2DM and its related complications.
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Diabetes, obesity and metabolism
Big Data Articles (National Health Insurance Service Database)
The Triglyceride-Glucose Index and Risk of End-Stage Renal Disease across Different Durations of Type 2 Diabetes Mellitus: A Longitudinal Cohort Study
Mi-sook Kim, Kyu-Na Lee, Jeongmin Lee, Jeongeun Kwak, Seung-Hwan Lee, Hyuk-Sang Kwon, Jing Hughes, Kyung-Do Han, Eun Young Lee
Endocrinol Metab. 2025;40(5):718-726.   Published online May 19, 2025
DOI: https://doi.org/10.3803/EnM.2024.2271
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study investigated the association between the triglyceride-glucose (TyG) index, a marker of insulin resistance, and the risk of end-stage renal disease (ESRD) in individuals with type 2 diabetes mellitus (T2DM), focusing on variations by diabetes duration.
Methods
We analyzed 1,219,148 Korean adults with T2DM from National Health Insurance Service data who underwent biennial health evaluations (2015 to 2016). ESRD was defined using specific procedural codes (V codes), and Cox proportional hazard models were employed to estimate hazard ratios (HRs) for ESRD across TyG index quartiles and diabetes duration categories, adjusting for various confounders.
Results
Over 6,967,381 person-years of follow-up, 7,548 participants developed ESRD. Higher TyG index quartiles were independently associated with increased risk of ESRD, which was more pronounced with longer diabetes duration. The adjusted HR for ESRD in the highest TyG quartile (Q4) compared to the lowest quartile (Q1) was 1.235 (95% confidence interval [CI], 0.995 to 1.533) in new-onset diabetes, and 1.592 (95% CI, 1.465 to 1.730) in those with diabetes for ≥10 years. Compared to the lowest TyG quartile in new-onset diabetes, the adjusted HR for ESRD in the highest quartile with diabetes duration ≥10 years increased to 10.239 (95% CI, 8.440 to 12.422). Subgroup analysis revealed that a higher TyG index consistently increased the risk of ESRD, with stronger associations observed in younger individuals and those without comorbidities.
Conclusion
The TyG index is a significant predictor of ESRD in T2DM, particularly in those with prolonged diabetes duration. Targeting insulin resistance early may mitigate the risk of ESRD in this population.

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  • Association between TYG-BMI index and asthma in adults over 45 years of age: analysis of Global Burden of Disease 2021, China Health and Retirement Longitudinal Study, and National Health and Nutrition Examination Survey data
    Zhuolin Qin, Longqian Li, Cheng Wang
    Journal of Asthma.2026; 63(2): 214.     CrossRef
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Diabetes, obesity and metabolism
Antilipolytic Insulin Sensitivity Indices Measured during an Oral Glucose Challenge: Associations with Insulin-Glucose Clamp and Central Adiposity in Women without Diabetes
Foued Naimi, Christophe Richer dit Laflèche, Marie-Claude Battista, André C. Carpentier, Jean-Patrice Baillargeon
Endocrinol Metab. 2025;40(4):561-573.   Published online March 18, 2025
DOI: https://doi.org/10.3803/EnM.2024.2129
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AbstractAbstract PDFPubReader   ePub   
Background
Tissue overexposure to non-esterified fatty acids (NEFA) contributes to the development of metabolic conditions, with insulin-mediated suppression of lipolysis being an important mechanism in limiting this overexposure. We investigated which dynamic NEFA insulin-suppression indices derived from the oral glucose tolerance test (OGTT) were best associated with those derived from the insulin-glucose clamp, as well as with central adiposity and glucoregulatory parameters.
Methods
This cross-sectional study recruited 29 women without diabetes, 15 healthy women, and 14 women with polycystic ovary syndrome. The OGTT indices of NEFA insulin-suppression were the decremental NEFA area under the curve, negative log-linear NEFA slope, percentage of NEFA suppression (%NEFAsupp) and time to suppress NEFA levels by 50% (T50NEFA). The indices derived from the two-step euglycemic-hyperinsulinemic clamp (low-dose insulin step) were delta NEFA and %NEFAsupp.
Results
Among the OGTT and clamp indices, T50NEFA[OGTT] and %NEFAsupp[clamp] showed the closest associations in both subgroups (r=–0.58). Additionally, T50NEFA correlated significantly in all women with waist circumference (r=0.64), body fat percentage (r=0.60), fasting insulinemia (r=0.53), and M-value insulin sensitivity index (r=–0.45). Similarly, %NEFAsupp[clamp] correlated significantly in all women with waist circumference (r=–0.57), body fat percentage (r=–0.54), fasting insulinemia (r=–0.55), and M-value insulin sensitivity index (r=0.51). T50NEFA and %NEFAsupp[clamp] also correlated with other anthropometric and metabolic parameters associated with lipotoxicity.
Conclusion
For dynamic testing of NEFA insulin-suppression in women, T50NEFA was the OGTT-derived index best correlated with a clamp index (%NEFAsupp). These indices were also the most closely associated with anthropometric and glucoregulatory parameters. Thus, the OGTT-derived T50NEFA appears valid for assessing dynamic antilipolytic insulin action.

Citations

Citations to this article as recorded by  
  • Impact of a high dietary fiber cereal meal intervention on the progression of liver fibrosis in T2DM with MASLD
    Xi-Shuang Chen, Hui-Zhen Liu, Fang Huang, Jian Meng, Jing-Xian Fang, Yu Han, Hui-Ming Zou, Qing Gu, Xue Hu, Qian-Wen Ma, Yue-Xia Han, Sui-Jun Wang
    Frontiers in Endocrinology.2025;[Epub]     CrossRef
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Diabetes, obesity and metabolism
Big Data Articles (National Health Insurance Service Database)
Association between the Triglyceride-Glucose Index and Cardiovascular Risk and Mortality across Different Diabetes Durations: A Nationwide Cohort Study
Jeongeun Kwak, Kyung-Do Han, Eun Young Lee, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Jeongmin Lee
Endocrinol Metab. 2025;40(4):548-560.   Published online March 5, 2025
DOI: https://doi.org/10.3803/EnM.2024.2205
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We aimed to assess the association between triglyceride-glucose (TyG) index and cardiovascular disease (CVD) risk and mortality in a large cohort of diabetes patients.
Methods
A retrospective cohort study of 1,090,485 participants from the Korean National Health Insurance Service database was conducted. Participants were stratified into TyG quartiles.
Results
Higher TyG index quartiles were significantly associated with an increased CVD risk and mortality risk. In fully adjusted models, participants in the highest TyG quartile (Q4) had an 18% higher risk of CVD (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.13 to 1.23) and a 16% higher risk of mortality (HR, 1.16; 95% CI, 1.11 to 1.23) compared to those in the lowest quartile (Q1). The association was particularly pronounced in patients with fasting glucose ≥126 mg/dL (CVD [HR, 1.33; 95% CI, 1.29 to 1.37], mortality [HR, 1.23; 95% CI, 1.20 to 1.26]; P for interaction <0.001). Patients with a diabetes duration of ≥10 years showed the strongest association between the TyG index and CVD risk (HR, 1.44; 95% CI, 1.38 to 1.50), while the mortality risk was particularly elevated in those with a diabetes duration of less than 5 years (HR, 1.23; 95% CI, 1.18 to 1.30). Subgroup analyses revealed stronger associations between TyG index and CVD risk in younger participants, non-obese individuals, and non-smokers.
Conclusion
The TyG index is a significant predictor of CVD and mortality in diabetic patients, particularly in those with poor glycemic control or longer disease duration.

Citations

Citations to this article as recorded by  
  • Preoperative triglyceride–glucose index as a metabolic predictor of surgical site infection after posterior lumbar fusion
    Yu Hua, Shaoxing Li, Yuan Jiang, Jinwang Liu
    Journal of Orthopaedic Surgery.2026;[Epub]     CrossRef
  • Combined effect of triglyceride-glucose index and glucose disposal rate on cardio-cerebrovascular disease
    Hongfei Yang, Chao Sun, Ya Li, You Zhou, Rui Wang, Yingxue Li, Marwan Salih Al-Nimer
    PLOS One.2026; 21(2): e0342154.     CrossRef
  • The Triglyceride-Glucose Index: A Practical Tool for Enhanced Cardiovascular Risk Stratification in Type 2 Diabetes
    Jang Won Son
    Endocrinology and Metabolism.2025; 40(4): 545.     CrossRef
  • The association between triglyceride-glucose index and all-cause/cardiovascular mortality in patients with different glucose metabolism statuses
    Jiajun Liu, Jinhua Kang, Pengpeng Liang, Zhangxiao Song, Guiyun Li, Xueshan Jin, Hongyan Wu
    Cardiovascular Diabetology.2025;[Epub]     CrossRef
  • Standardized Triglyceride-Glucose and Plasma Atherogenic Indices as Predictors of Diabetic Nephropathy and Coronary Artery Disease in Patients with Type 1 Diabetes Mellitus
    Nazif Yalçın, Nizameddin Koca
    European Journal of Therapeutics.2025;[Epub]     CrossRef
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Review Article
Diabetes, obesity and metabolism
Evolving Characteristics of Type 2 Diabetes Mellitus in East Asia
Joonyub Lee, Kun-Ho Yoon
Endocrinol Metab. 2025;40(1):57-63.   Published online January 15, 2025
DOI: https://doi.org/10.3803/EnM.2024.2193
  • 6,189 View
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  • 3 Web of Science
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AbstractAbstract PDFPubReader   ePub   
In East Asians, type 2 diabetes mellitus (T2DM) is primarily characterized by significant defects in insulin secretion and comparatively low insulin resistance. Recently, the prevalence of T2DM has rapidly increased in East Asian countries, including Korea, occurring concurrently with rising obesity rates. This trend has led to an increase in the average body mass index among East Asian T2DM patients, highlighting the influence of insulin resistance in the development of T2DM within this group. Currently, the incidence of T2DM in Korea is declining, which may indicate potential adaptive changes in insulin secretory capacity. This review focuses on the changing epidemiology of T2DM in East Asia, with a particular emphasis on the characteristics of peak functional β-cell mass.

Citations

Citations to this article as recorded by  
  • Lobeglitazone improves glycaemic control as add‐on therapy to empagliflozin plus metformin in patients with type 2 diabetes mellitus: A double‐blind, randomised, placebo‐controlled trial
    Da Hea Seo, Kyung Wan Min, Ho Sang Sohn, Sang Yong Kim, In‐Kyung Jeong, Cheol‐Young Park, Kun‐Ho Yoon, So Hun Kim, Bong‐Soo Cha
    Diabetes, Obesity and Metabolism.2026; 28(1): 728.     CrossRef
  • Association of Insulin Resistance with Dysglycemia in Elder Koreans: Age- and Sex-Specific Cutoff Values
    Sang Min Yoon, Boyoung Park
    Journal of Personalized Medicine.2025; 15(9): 438.     CrossRef
  • Exploring Sex-Specific Mechanisms in Type 2 Diabetes Mellitus by Single-Cell Analysis in Pancreatic Islets
    Joonyub Lee
    Endocrinology and Metabolism.2025; 40(5): 699.     CrossRef
  • A phase 1 single and multiple ascending dose study of orforglipron in Japanese participants with type 2 diabetes
    Kenji Ohwaki, Chino Nakamura, Risa Nasu, Kazumasa Takenouchi, Tetsuaki Hirase
    Journal of Diabetes Investigation.2025;[Epub]     CrossRef
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Original Articles
Diabetes, obesity and metabolism
Metabolic Phenotypes of Women with Gestational Diabetes Mellitus Affect the Risk of Adverse Pregnancy Outcomes
Joon Ho Moon, Sookyung Won, Hojeong Won, Heejun Son, Tae Jung Oh, Soo Heon Kwak, Sung Hee Choi, Hak Chul Jang
Endocrinol Metab. 2025;40(2):247-257.   Published online November 28, 2024
DOI: https://doi.org/10.3803/EnM.2024.2089
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AbstractAbstract PDFPubReader   ePub   
Background
Gestational diabetes mellitus (GDM) affects women with diverse pathological phenotypes, but little is known about the effects of this variation on perinatal outcomes. We explored the metabolic phenotypes of GDM and their impact on adverse pregnancy outcomes.
Methods
Women diagnosed with gestational glucose intolerance or GDM were categorized into subgroups according to their prepregnancy body mass index (BMI) and the median values of the gestational Matsuda and Stumvoll indices. Logistic regression analysis was employed to assess the odds of adverse pregnancy outcomes, such as large-for-gestational age (LGA), small-for-gestational age, preterm birth, low Apgar score, and cesarean section.
Results
A total of 309 women were included, with a median age of 31 years and a median BMI of 22.3 kg/m2. Women with a higher pre-pregnancy BMI had a higher risk of LGA newborns (adjusted odds ratio [aOR] for pre-pregnancy BMI ≥25 kg/m2 compared to 20–23 kg/m2, 4.26; 95% confidence interval [CI], 1.99 to 9.12; P<0.001; P for trend=0.001), but the risk of other adverse pregnancy outcomes did not differ according to pre-pregnancy BMI. Women with insulin resistance had a higher risk of LGA (aOR, 1.88; 95% CI, 1.02 to 3.47; P=0.043) and cesarean section (aOR, 2.12; 95% CI, 1.29 to 3.50; P=0.003) than women in the insulin-sensitive group. In contrast, defective β-cell function did not affect adverse pregnancy outcomes.
Conclusion
Different metabolic phenotypes of GDM were associated with heterogeneous pregnancy outcomes. Women with obesity and those with insulin resistance are at greater risk of adverse outcomes and might need strict glycemic management during pregnancy.

Citations

Citations to this article as recorded by  
  • Gestational Diabetes Mellitus: Mechanisms Underlying Maternal and Fetal Complications
    Jooyeop Lee, Na Keum Lee, Joon Ho Moon
    Endocrinology and Metabolism.2025; 40(1): 10.     CrossRef
  • The Characteristics of Course of Pregnancy and Perinatal Outcomes in Women with Gestation Diabetes Mellitus (The Results of Ten-Years Research)
    N. V. Batrak, I. V. Ivanova
    Problems of Social Hygiene, Public Health and History of Medicine.2025; 33(6): 1414.     CrossRef
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Thyroid
Prevalence of Subclinical Hypothyroidism in a Non-Diabetic Young Female Population and Its Impact on Diabetes and Cardiometabolic Risk
Nawoda Hewage, Udaya Wijesekara, Rasika Perera
Endocrinol Metab. 2024;39(6):864-876.   Published online November 5, 2024
DOI: https://doi.org/10.3803/EnM.2024.2015
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AbstractAbstract PDFPubReader   ePub   
Background
We evaluated the influence of subclinical hypothyroidism (SCH) on insulin resistance (IR), cardiometabolic risk, and obesity in childbearing-age women without diabetes.
Methods
This cross-sectional investigation included 282 women, aged 18 to 35 years, from rural and suburban Sri Lanka. Anthropometric and biochemical parameters, including IR and lipid/thyroid profiles, were recorded. Data were compared between SCH and euthyroidism (EU) for controls (normal weight) and cases (overweight/obese).
Results
The overall rates of SCH, EU, IR, and metabolic syndrome (MetS) were 40.42%, 59.57%, 73.40%, and 24.46%, respectively. Both controls and cases included individuals with SCH; overall, 168 participants (59.57%) had EU, while 114 (40.42%) exhibited SCH. IR was significantly associated with SCH in both weight groups (P<0.05). Among those with SCH, the odds ratios (ORs) for IR were >2 (95% confidence interval [CI], 0.45 to 3.87) in controls and >6 (95% CI, 3.52 to 8.41) in cases. Similarly, the ORs for MetS were >1 (95% CI, 0.38 to 4.16) in controls and >11 (95% CI, 8.73 to 15.01) in cases. Dyslipidemia and hypertriglyceridemia were significantly more prevalent in the SCH group (P<0.05). Women with SCH exhibited higher mean values for all obesity indices compared to their EU counterparts, surpassing normal thresholds (P<0.05). Among obesity measures, visceral adiposity index (VAI) demonstrated the highest area under the curve and sensitivity for assessing SCH and cardiovascular disease (CVD) risk.
Conclusion
SCH must be identified and managed in young women to help prevent diabetes and cardiometabolic disorders. VAI may aid in precisely detecting SCH and CVD.

Citations

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  • Increased Serum Lipopolysaccharide Levels are Related to a Higher Prevalent Risk of Subclinical Hypothyroidism
    Xuan An, Xiaoyi Wang, Jin Zhang, Mingtong Xu, Muchao Wu, Suraiya Saleem
    International Journal of Endocrinology.2025;[Epub]     CrossRef
  • Incidence of Subclinical Hypothyroidism in Obese Adults and Its Metabolic Implications: A Prospective Cohort Study
    Umer Jameel, Obaidullah Durrani, Ahmad Munib, Amanullah Khan
    Cureus.2025;[Epub]     CrossRef
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Diabetes, obesity and metabolism
Insulin Resistance and Impaired Insulin Secretion Predict Incident Diabetes: A Statistical Matching Application to the Two Korean Nationwide, Population-Representative Cohorts
Hyemin Jo, Soyeon Ahn, Jung Hun Ohn, Cheol Min Shin, Eunjeong Ji, Donggil Kim, Sung Jae Jung, Joongyub Lee
Endocrinol Metab. 2024;39(5):711-721.   Published online August 30, 2024
DOI: https://doi.org/10.3803/EnM.2024.1986
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
To evaluate whether insulin resistance and impaired insulin secretion are useful predictors of incident diabetes in Koreans using nationwide population-representative data to enhance data privacy.
Methods
This study analyzed the data of individuals without diabetes aged >40 years from the Korea National Health and Nutrition Examination Survey (KNHANES) 2007–2010 and 2015 and the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Owing to privacy concerns, these databases cannot be linked using direct identifiers. Therefore, we generated 10 synthetic datasets, followed by statistical matching with the NHIS-HEALS. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were used as indicators of insulin resistance and insulin secretory function, respectively, and diabetes onset was captured in NHIS-HEALS.
Results
A median of 4,580 (range, 4,463 to 4,761) adults were included in the analyses after statistical matching of 10 synthetic KNHANES and NHIS-HEALS datasets. During a mean follow-up duration of 5.8 years, a median of 4.7% (range, 4.3% to 5.0%) of the participants developed diabetes. Compared to the reference low–HOMA-IR/high–HOMA-β group, the high–HOMA-IR/low– HOMA-β group had the highest risk of diabetes, followed by high–HOMA-IR/high–HOMA-β group and low–HOMA-IR/low– HOMA-β group (median adjusted hazard ratio [ranges]: 3.36 [1.86 to 6.05], 1.81 [1.01 to 3.22], and 1.68 [0.93 to 3.04], respectively).
Conclusion
Insulin resistance and impaired insulin secretion are robust predictors of diabetes in the Korean population. A retrospective cohort constructed by combining cross-sectional synthetic and longitudinal claims-based cohort data through statistical matching may be a reliable resource for studying the natural history of diabetes.

Citations

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  • Abnormal insulin metabolism and decreased levels of mindfulness in type 2 diabetes mellitus
    Xue Zhang, Rui Huang, Jiaxin Li, Mingyue Yang, Daowen Zhang, Cancan Liu, Kuanlu Fan
    Diabetology & Metabolic Syndrome.2025;[Epub]     CrossRef
  • Association of Insulin Resistance with Dysglycemia in Elder Koreans: Age- and Sex-Specific Cutoff Values
    Sang Min Yoon, Boyoung Park
    Journal of Personalized Medicine.2025; 15(9): 438.     CrossRef
  • Evaluating the utility of data integration with synthetic data and statistical matching
    Eunjeong Ji, Jung Hun Ohn, Hyemin Jo, Min-Jeong Park, Hang J. Kim, Cheol Min Shin, Soyeon Ahn
    Scientific Reports.2025;[Epub]     CrossRef
  • Neck to Waist Circumference Ratio and Insulin Resistance in Adult Korean Population Under 50 Years
    Kyu Rae Lee
    Metabolic Syndrome and Related Disorders.2025; 23(9): 422.     CrossRef
  • Combining Nationwide Cohorts to Unveil the Predictive Role of Insulin Resistance and Impaired Insulin Secretion in Diabetes
    Bukyung Kim
    Endocrinology and Metabolism.2024; 39(5): 699.     CrossRef
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Diabetes, obesity and metabolism
Amelioration of Insulin Resistance after Delivery Is Associated with Reduced Risk of Postpartum Diabetes in Women with Gestational Diabetes Mellitus
Heejun Son, Joon Ho Moon, Sung Hee Choi, Nam H. Cho, Soo Heon Kwak, Hak Chul Jang
Endocrinol Metab. 2024;39(5):701-710.   Published online August 21, 2024
DOI: https://doi.org/10.3803/EnM.2024.1974
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Identifying risk factors for postpartum type 2 diabetes in women with gestational diabetes mellitus (GDM) is crucial for effective interventions. We examined whether changes in insulin sensitivity after delivery affects the risk of type 2 diabetes in women with GDM.
Methods
This prospective cohort study included 347 women with GDM or gestational impaired glucose tolerance, who attended the follow-up visits at 2 months postpartum and annually thereafter. Changes in insulin sensitivity were calculated using the Matsuda index at GDM diagnosis and at 2 months postpartum (ΔMatsuda index). After excluding women with pregestational diabetes or those followed up only once, we analyzed the risk of postpartum type 2 diabetes based on the ΔMatsuda index tertiles.
Results
The incidence of type 2 diabetes at the two-month postpartum visit decreased with increasing ΔMatsuda index tertiles (16.4%, 9.5%, and 1.8%, P=0.001). During a 4.1-year follow-up, 26 out of 230 women who attended more than two follow-up visits (11.3%) developed type 2 diabetes. Compared to the lowest tertile, subjects in the highest ΔMatsuda index tertile showed a significantly reduced risk of type 2 diabetes (hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.93; P=0.036) after adjusting for confounders.
Conclusion
Improvement in insulin sensitivity after delivery is associated with a reduced risk of postpartum type 2 diabetes in women with GDM. Postpartum changes in insulin sensitivity could be a useful prediction for future type 2 diabetes development in women with GDM.

Citations

Citations to this article as recorded by  
  • Gestational Diabetes Mellitus: Mechanisms Underlying Maternal and Fetal Complications
    Jooyeop Lee, Na Keum Lee, Joon Ho Moon
    Endocrinology and Metabolism.2025; 40(1): 10.     CrossRef
  • Evaluation of Maternal Factors Affecting Postpartum Insulin Resistance Markers in Mothers with Gestational Diabetes—A Case–Control Study
    Karolina Karcz, Paulina Gaweł, Barbara Królak-Olejnik
    Nutrients.2024; 16(22): 3871.     CrossRef
Close layer
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
  • 17,949 View
  • 345 Download
  • 32 Web of Science
  • 29 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

Citations

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Diabetes, Obesity and Metabolism
The Impact of Insulin Resistance on Hepatic Fibrosis among United States Adults with Non-Alcoholic Fatty Liver Disease: NHANES 2017 to 2018
Ji Cheol Bae, Lauren A. Beste, Kristina M. Utzschneider
Endocrinol Metab. 2022;37(3):455-465.   Published online June 21, 2022
DOI: https://doi.org/10.3803/EnM.2022.1434
  • 9,436 View
  • 174 Download
  • 19 Web of Science
  • 19 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We aimed to investigate the association of hepatic steatosis with liver fibrosis and to assess the interactive effects of hepatic steatosis and insulin resistance on liver fibrosis in a nationally representative sample of United States adults.
Methods
We conducted a cross-sectional analysis using data from National Health and Nutrition Examination Survey 2017 to 2018, which for the first time included transient elastography to assess liver stiffness and hepatic steatosis. We evaluated the association between hepatic steatosis (using controlled attenuation parameter [CAP]) and clinically significant liver fibrosis (defined as liver stiffness ≥7.5 kPa) using logistic regression with an interaction term for hepatic steatosis and insulin resistance (defined as homeostatic model assessment of insulin resistance ≥3.0).
Results
Among adults undergoing transient elastography (n=2,023), 45.9% had moderate or greater hepatic steatosis and 11.3% had clinically significant liver fibrosis. After adjustment for demographic and metabolic factors, the odds of significant liver fibrosis increased as CAP score rose (odds ratio, 1.35 per standard deviation increment; 95% confidence interval, 1.11 to 1.64). We detected a significant interaction effect between CAP score and insulin resistance on the probability of significant liver fibrosis (P=0.016 for interaction). The probability of significant liver fibrosis increased in the presence of insulin resistance with increasing CAP score, while those without insulin resistance had low probability of significant liver fibrosis, even with high CAP scores.
Conclusion
Individuals with hepatic steatosis had higher odds of fibrosis when insulin resistance was present. Our findings emphasize the importance of the metabolic aspects of the disease on fibrosis risk and suggest a need to better identify patients with metabolic associated fatty liver disease.

Citations

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Diabetes, Obesity and Metabolism
Changes in Insulin Resistance Index and the Risk of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease without Diabetes: Kangbuk Samsung Health Study
Dae-Jeong Koo, Mi Yeon Lee, Inha Jung, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
Endocrinol Metab. 2021;36(5):1016-1028.   Published online October 21, 2021
DOI: https://doi.org/10.3803/EnM.2021.1110
  • 7,621 View
  • 148 Download
  • 11 Web of Science
  • 14 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Fibrosis is the most important prognostic factor for nonalcoholic fatty liver disease (NAFLD). Insulin resistance plays a key role of fibrosis progression. We evaluated the association between changes in homeostasis model assessment of insulin resistance (HOMA-IR) values and changes in fibrosis status in NAFLD.
Methods
We analyzed the data of 15,728 participants with NAFLD (86% men, mean age 40.5 years) who had no diabetes at baseline and visited our centers for health check-ups both in 2012 and 2016. The participants were classified into four groups according to the degree of change in HOMA-IR values from baseline to the end of follow-up: G1 (<0), G2 (0–0.50), G3 (0.51–1.00), and G4 (>1.00). NAFLD was assessed by ultrasonography, and fibrosis status was evaluated by the NAFLD fibrosis score (NFS) and the aspartate aminotransferase to platelet ratio index (APRI).
Results
After the 4-year follow-up, the multivariable-adjusted odds ratio (OR) for progression of fibrosis probability increased with increasing HOMA-IR values (OR, 2.25; 95% confidence interval [CI], 1.87 to 2.71 for NFS; and OR, 2.55; 95% CI, 2.05 to 3.18 for APRI, G4). This tendency remained consistent throughout the subgroup analyses, except in those for female sex and a body mass index <25 kg/m2. The OR for regression of fibrosis probability decreased with increasing HOMA-IR values (OR, 0.33; 95% CI, 0.25 to 0.43 for NFS, G4).
Conclusion
Changes in HOMA-IR values were associated with changes in fibrosis status in patients with NAFLD without diabetes, which underscores the role of insulin resistance in liver fibrosis.

Citations

Citations to this article as recorded by  
  • Metabolic Dysfunction-Associated Steatotic Liver Disease: The Role of Hepatic Steatosis in Insulin Resistance and Metabolic Health
    Ji Cheol Bae
    Endocrinology and Metabolism.2025; 40(2): 304.     CrossRef
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    Mohammad E. Khamseh, Mojtaba Malek, Soodeh Jahangiri, Sohrab Nobarani, Azita Hekmatdoost, Marieh Salavatizadeh, Samira Soltanieh, Haleh Chehrehgosha, Hoda Taheri, Zeinab Montazeri, Fereshteh Attaran, Faramarz Ismail-Beigi, Fariba Alaei-Shahmiri
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    Inha Jung, Dae-Jeong Koo, Won-Young Lee
    Diabetes & Metabolism Journal.2024; 48(3): 327.     CrossRef
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    Takumi Kawaguchi, Kenta Murotani, Hiromitsu Kajiyama, Hitoshi Obara, Hironori Yamaguchi, Yuko Toyofuku, Fumi Kaneko, Yutaka Seino, Saeko Uchida
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    Ángel Arturo López-González, Bárbara Altisench Jané, Luis Masmiquel Comas, Sebastiana Arroyo Bote, Hilda María González San Miguel, José Ignacio Ramírez Manent
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    Jun-Hyuk Lee, Yu-Jin Kwon, Kyongmin Park, Hye Sun Lee, Hoon-Ki Park, Jee Hye Han, Sang Bong Ahn
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    Kexing Han, Kexuan Tan, Jiapei Shen, Yuting Gu, Zilong Wang, Jiayu He, Luyang Kang, Weijie Sun, Long Gao, Yufeng Gao
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Diabetes, Obesity and Metabolism
Musclin Is Related to Insulin Resistance and Body Composition, but Not to Body Mass Index or Cardiorespiratory Capacity in Adults
Yeliana L. Sánchez, Manuela Yepes-Calderón, Luis Valbuena, Andrés F. Milán, María C. Trillos-Almanza, Sergio Granados, Miguel Peña, Mauricio Estrada-Castrillón, Juan C. Aristizábal, Raúl Narvez-Sanchez, Jaime Gallo-Villegas, Juan C. Calderón
Endocrinol Metab. 2021;36(5):1055-1068.   Published online October 21, 2021
DOI: https://doi.org/10.3803/EnM.2021.1104
  • 9,789 View
  • 155 Download
  • 13 Web of Science
  • 13 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
We studied whether musclin function in humans is related to glycemic control, body composition, and cardiorespiratory capacity.
Methods
A cross-sectional study was performed in sedentary adults with or without metabolic syndrome (MS). Serum musclin was measured by enzyme-linked immunosorbent assay. Insulin resistance (IR) was evaluated by the homeostatic model assessment (HOMA-IR). Body composition was determined by dual-energy X-ray absorptiometry and muscle composition by measuring carnosine in the thigh, a surrogate of fiber types, through proton magnetic resonance spectroscopy. Cardiorespiratory capacity was assessed through direct ergospirometry.
Results
The control (n=29) and MS (n=61) groups were comparable in age (51.5±6.5 years old vs. 50.7±6.1 years old), sex (72.4% vs. 70.5% women), total lean mass (58.5%±7.4% vs. 57.3%±6.8%), and peak oxygen consumption (VOpeak) (31.0±5.8 mL O2./kg.min vs. 29.2±6.3 mL O2/kg.min). Individuals with MS had higher body mass index (BMI) (30.6±4.0 kg/m2 vs. 27.4± 3.6 kg/m2), HOMA-IR (3.5 [95% confidence interval, CI, 2.9 to 4.6] vs. 1.7 [95% CI, 1.1 to 2.0]), and musclin (206.7 pg/mL [95% CI, 122.7 to 387.8] vs. 111.1 pg/mL [95% CI, 63.2 to 218.5]) values than controls (P˂0.05). Musclin showed a significant relationship with HOMA-IR (β=0.23; 95% CI, 0.12 to 0.33; P˂0.01), but not with VOpeak, in multiple linear regression models adjusted for age, sex, fat mass, lean mass, and physical activity. Musclin was significantly associated with insulin, glycemia, visceral fat, and regional muscle mass, but not with BMI, VCO2peak, maximum heart rate, maximum time of work, or carnosine.
Conclusion
In humans, musclin positively correlates with insulinemia, IR, and a body composition profile with high visceral adiposity and lean mass, but low body fat percentage. Musclin is not related to BMI or cardiorespiratory capacity.

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    Ji Sun Nam, Eun-Suk Cho, Yu Rim Kwon, Jong Suk Park, YuSik Kim
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    YuSik Kim
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    Jorge L. Petro, Jaime Gallo-Villegas, Juan C. Calderón
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  • Musclin Mitigates the Attachment of HUVECs to THP-1 Monocytes in Hyperlipidemic Conditions through PPARα/HO-1-Mediated Attenuation of Inflammation
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    European Journal of Applied Physiology.2022; 122(2): 331.     CrossRef
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Diabetes, Obesity and Metabolism
Increased Risk of Nonalcoholic Fatty Liver Disease in Individuals with High Weight Variability
Inha Jung, Dae-Jeong Koo, Mi Yeon Lee, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
Endocrinol Metab. 2021;36(4):845-854.   Published online August 27, 2021
DOI: https://doi.org/10.3803/EnM.2021.1098
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Weight loss through lifestyle modification is recommended for patients with nonalcoholic fatty liver disease (NAFLD). Recent studies have suggested that repeated loss and gain of weight is associated with worse health outcomes. This study aimed to examine the association between weight variability and the risk of NAFLD in patients without diabetes.
Methods
We examined the health-checkup data of 30,708 participants who had undergone serial examinations between 2010 and 2014. Weight variability was assessed using coefficient of variation and the average successive variability of weight (ASVW), which was defined as the sum of absolute weight changes between successive years over the 5-year period divided by 4. The participants were classified according to the baseline body mass index and weight difference over 4 years.
Results
On dividing the participants into four groups according to ASVW quartile groups, those in the highest quartile showed a significantly increased risk of NAFLD compared to those in the lowest quartile (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.63 to 2.19). Among participants without obesity at baseline, individuals with high ASVW showed increased risk of NAFLD (OR, 1.80; 95% CI, 1.61 to 2.01). Participants with increased weight over 4 years and high ASVW demonstrated higher risk of NAFLD compared to those with stable weight and low ASVW (OR, 4.87; 95% CI, 4.29 to 5.53).
Conclusion
Regardless of participant baseline obesity status, high weight variability was associated with an increased risk of developing NAFLD. Our results suggest that further effort is required to minimize weight fluctuations after achieving a desirable body weight.

Citations

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    Nathalie C. Leite, Claudia R. L. Cardoso, Cristiane A. Villela‐Nogueira, Gil F. Salles
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    Inha Jung, Dae-Jeong Koo, Won-Young Lee
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    Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
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    Kyung‐Soo Kim, Sangmo Hong, Hong‐Yup Ahn, Cheol‐Young Park
    Obesity.2022; 30(6): 1279.     CrossRef
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    Mohammed Eslam, Hashem B. El-Serag, Sven Francque, Shiv K. Sarin, Lai Wei, Elisabetta Bugianesi, Jacob George
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    Ángel Arturo López-González, Bárbara Altisench Jané, Luis Masmiquel Comas, Sebastiana Arroyo Bote, Hilda María González San Miguel, José Ignacio Ramírez Manent
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    Yeoree Yang, Jae-Hyoung Cho
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    Inha Jung, Da Young Lee, Mi Yeon Lee, Hyemi Kwon, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Won-Young Lee, Sung-Woo Park, Se Eun Park
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Review Article
Diabetes
In Vivo and In Vitro Quantification of Glucose Kinetics: From Bedside to Bench
Il-Young Kim, Sanghee Park, Yeongmin Kim, Yewon Chang, Cheol Soo Choi, Sang-Hoon Suh, Robert R. Wolfe
Endocrinol Metab. 2020;35(4):733-749.   Published online December 23, 2020
DOI: https://doi.org/10.3803/EnM.2020.406
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AbstractAbstract PDFPubReader   ePub   
Like other substrates, plasma glucose is in a dynamic state of constant turnover (i.e., rates of glucose appearance [Ra glucose] into and disappearance [Rd glucose] from the plasma) while staying within a narrow range of normal concentrations, a physiological priority. Persistent imbalance of glucose turnover leads to elevations (i.e., hyperglycemia, Ra>Rd) or falls (i.e., hypoglycemia, Ra<Rd) in the pool size, leading to clinical conditions such as diabetes. Endogenous Ra glucose is divided into hepatic glucose production via glycogenolysis and gluconeogenesis (GNG) and renal GNG. On the other hand, Rd glucose, the summed rate of glucose uptake by tissues/organs, involves various intracellular metabolic pathways including glycolysis, the tricarboxylic acid (TCA) cycle, and oxidation at varying rates depending on the metabolic status. Despite the dynamic nature of glucose metabolism, metabolic studies typically rely on measurements of static, snapshot information such as the abundance of mRNAs and proteins and (in)activation of implicated signaling networks without determining actual flux rates. In this review, we will discuss the importance of obtaining kinetic information, basic principles of stable isotope tracer methodology, calculations of in vivo glucose kinetics, and assessments of metabolic flux in experimental models in vivo and in vitro.

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    Doron Goldberg, Isaac Bentwich, Yossi Haran, Tamar Getter
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Original Articles
Clinical Study
Changes in Glucose Metabolism after Adrenalectomy or Treatment with a Mineralocorticoid Receptor Antagonist for Primary Aldosteronism
Yu-Fang Lin, Kang-Yung Peng, Chia-Hui Chang, Ya-Hui Hu, Vin-Cent Wu, Shiu-Dong Chung, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group
Endocrinol Metab. 2020;35(4):838-846.   Published online December 2, 2020
DOI: https://doi.org/10.3803/EnM.2020.797
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AbstractAbstract PDFPubReader   ePub   
Background
Data on the effects of excess aldosterone on glucose metabolism are inconsistent. This study compared the changes in glucose metabolism in patients with primary aldosteronism (PA) after adrenalectomy or treatment with a mineralocorticoid receptor antagonist (MRA).
Methods
Overall, 241 patients were enrolled; 153 underwent adrenalectomy and 88 received an MRA. Fasting glucose, homeostatic model assessment of insulin resistance (HOMA-IR), and homeostatic model assessment of β-cell function (HOMA-β) were compared between the treatment groups after 1 year. Plasma aldosterone concentration (PAC) and factors determining HOMA-IR and PAC were evaluated.
Results
No baseline differences were observed between the groups. Fasting insulin, HOMA-IR, and HOMA-β increased in both groups and there were no significant differences in fasting glucose following treatment. Multiple regression analysis showed associations between PAC and HOMA-IR (β=0.172, P=0.017) after treatment. Treatment with spironolactone was the only risk factor associated with PAC >30 ng/dL (odds ratio, 5.2; 95% confidence interval [CI], 2.7 to 10; P<0.001) and conferred a 2.48-fold risk of insulin resistance after 1 year compared with surgery (95% CI, 1.3 to 4.8; P=0.007).
Conclusion
Spironolactone treatment might increase insulin resistance in patients with PA. This strengthened the current recommendation that adrenalectomy is the preferred strategy for patient with positive lateralization test. Achieving a post-treatment PAC of <30 ng/dL for improved insulin sensitivity may be appropriate.

Citations

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  • Comparative Outcomes of Adrenalectomy, Mineralocorticoid Receptor Antagonist, and Percutaneous Adrenal Ablation for Primary Aldosteronism: A Systematic Review and Network Meta-Analysis
    Liyuan Yuan, Xinyi Li, Fang Sun, Yi Tang, Wuhao Wang, Wei Liu, Xiaona Sun, Yushuang Luo, Xiaona Bu, Zongshi Lu, Daoyan Liu, Qiang Li, Zhiming Zhu
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    Magdoleen H Farah, Moustafa Hegazi, Mohammed Firwana, Mohamed Abusalih, Samer Saadi, Mohammad Al-Kordi, Arwa Elsheikh, Zhen Wang, Leslie Hassett, Irina Bancos, M Hassan Murad
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    Jin-Ying Lu, Yi-Yao Chang, Ting-Wei Lee, Ming-Hsien Wu, Zheng-Wei Chen, Yen-Ta Huang, Tai-Shuan Lai, Leay Kiaw Er, Yen-Hung Lin, Vin-Cent Wu, Hao-Min Cheng, Hsien-Li Kao, Charles Jia-Yin Hou, Kwan-Dun Wu, Szu-Tah Chen, Feng-Hsuan Liu
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    Stella Bernardi, Valerio Velardi, Federica De Luca, Giulia Zuolo, Veronica Calabrò, Riccardo Candido, Bruno Fabris
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    M. Araujo-Castro, M. Paja Fano, B. Pla Peris, M. González Boillos, E. Pascual-Corrales, A. M. García Cano, P. Parra Ramírez, P. Martín Rojas-Marcos, J. G. Ruiz-Sanchez, A. Vicente Delgado, E. Gómez Hoyos, R. Ferreira, I. García Sanz, M. Recasens Sala, R.
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    Jia-Yuh Sheu, Shuo-Meng Wang, Vin-Cent Wu, Kuo-How Huang, Chi-Shin Tseng, Yuan-Ju Lee, Yao-Chou Tsai, Yen-Hung Lin, Jeff S. Chueh
    Journal of Hypertension.2023; 41(9): 1401.     CrossRef
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    Namki Hong, Kyoung Jin Kim, Min Heui Yu, Seong Ho Jeong, Seunghyun Lee, Jung Soo Lim, Yumie Rhee
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    Melpomeni Moustaki, Stavroula A. Paschou, Eleni C. Vakali, Andromachi Vryonidou
    Endocrine.2022; 79(1): 17.     CrossRef
  • Serum Cystatin C Levels Could Predict Rapid Kidney Function Decline in A Community-Based Population
    Wei-Ching Fang, Hsing-Yu Chen, Shao-Chi Chu, Po-Hsi Wang, Chin-Chan Lee, I-Wen Wu, Chiao-Yin Sun, Heng-Jung Hsu, Chun-Yu Chen, Yung-Chang Chen, Vin-Cent Wu, Heng-Chih Pan
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    Yu Liu, Lede Lin, Chi Yuan, Sikui Shen, Yin Tang, Zhihong Liu, Yuchun Zhu, Liang Zhou
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Close layer
Clinical Study
Cross-Sectional and Longitudinal Examination of Insulin Sensitivity and Secretion across Puberty among Non-Hispanic Black and White Children
Shannon E. Marwitz, Megan V. Gaines, Sheila M. Brady, Sarah J. Mi, Miranda M. Broadney, Susan Z. Yanovski, Van S. Hubbard, Jack A. Yanovski
Endocrinol Metab. 2020;35(4):847-857.   Published online November 18, 2020
DOI: https://doi.org/10.3803/EnM.2020.771
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Few studies using criterion measures of insulin sensitivity (SI) and insulin secretory capacity (ISC) have been conducted across puberty to adulthood. We examined how SI and ISC change from pre-puberty through adulthood.
Methods
Hyperglycemic clamp studies were performed in a convenience sample of non-Hispanic Black (NHB) and White children evaluated at age 6 to 12 years and at approximately 5-year intervals into adulthood (maximum age 27 years). SI and ISC (first-phase and steady-state insulin secretion) were determined cross-sectionally in 133 unique participants across puberty and in adulthood. Additionally, longitudinal changes in SI and ISC were compared at two timepoints among three groups defined by changes in pubertal development: pre-pubertal at baseline and late-pubertal at follow-up (n=27), early-pubertal at baseline and late-pubertal at follow-up (n=27), and late-pubertal at baseline and adult at follow-up (n=24).
Results
Cross-sectionally, SI was highest in pre-puberty and early puberty and lowest in mid-puberty (analysis of covariance [ANCOVA] P=0.001). Longitudinally, SI decreased from pre-puberty to late puberty (P<0.001), then increased somewhat from late puberty to adulthood. Cross-sectionally, first-phase and steady-state ISC increased during puberty and decreased in adulthood (ANCOVA P<0.02). Longitudinally, steady-state and first-phase ISC increased from pre-puberty to late puberty (P<0.007), and steady-state ISC decreased from late puberty to adulthood. The NHB group had lower SI (P=0.003) and greater first-phase and steady-state ISC (P≤0.001), independent of pubertal development.
Conclusion
This study confirms that SI decreases and ISC increases transiently during puberty and shows that these changes largely resolve in adulthood.

Citations

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  • The relationship of changes in insulin demand and insulin adequacy over the life course
    Yingchai Zhang, Claudia H. T. Tam, Eric S. H. Lau, Noel Y. H. Ng, Aimin Yang, Baoqi Fan, Hongjiang Wu, Cadmon K. P. Lim, Elaine Y. K. Chow, Andrea O. Y. Luk, Alice P. S. Kong, Wing Hung Tam, Juliana C. N. Chan, Ronald C. W. Ma
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    Jody Beth Grundman, Elizabeth Estrada, Rachel Longendyke, Stephanie T. Chung
    Journal of Clinical Medicine.2025; 14(22): 7995.     CrossRef
  • Exploratory Longitudinal Analysis of the Circulating CHIT1 Activity in Pediatric Patients with Obesity
    Ioana Țaranu, Nicoleta Răcătăianu, Cristina Drugan, Cristina-Sorina Cătană, Andreea-Manuela Mirea, Diana Miclea, Sorana D. Bolboacă
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    Sonia M. Najjar, Sonia Caprio, Amalia Gastaldelli
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    Esther A. Kwarteng, Lisa M. Shank, Loie M. Faulkner, Lucy K. Loch, Syeda Fatima, Suryaa Gupta, Hannah E. Haynes, Kaitlin L. Ballenger, Megan N. Parker, Sheila M. Brady, Anna Zenno, Marian Tanofsky-Kraff, Jack A. Yanovski
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    Andrea Foppiani, Fabiana Ciciriello, Arianna Bisogno, Silvia Bricchi, Carla Colombo, Federico Alghisi, Vincenzina Lucidi, Maria Catena, Mariacristina Lucanto, Andrea Mari, Giorgio Bedogni, Alberto Battezzati
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  • Fat-free/lean body mass in children with insulin resistance or metabolic syndrome: a systematic review and meta-analysis
    Diana Paola Córdoba-Rodríguez, Iris Iglesia, Alejandro Gomez-Bruton, Gerardo Rodríguez, José Antonio Casajús, Hernan Morales-Devia, Luis A. Moreno
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  • Evaluating Triglyceride and Glucose Index as a Simple and Easy-to-Calculate Marker for All-Cause and Cardiovascular Mortality
    Kyung-Soo Kim, Sangmo Hong, You-Cheol Hwang, Hong-Yup Ahn, Cheol-Young Park
    Journal of General Internal Medicine.2022; 37(16): 4153.     CrossRef
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    Veronica Maria Tagi, Sona Samvelyan, Francesco Chiarelli
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    Stephanie T. Chung, Sheela N. Magge
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Close layer
Clinical Study
Serum Transferrin Predicts New-Onset Type 2 Diabetes in Koreans: A 4-Year Retrospective Longitudinal Study
Jong Dai Kim, Dong-Mee Lim, Keun-Young Park, Se Eun Park, Eun Jung Rhee, Cheol-Young Park, Won-Young Lee, Ki Won Oh
Endocrinol Metab. 2020;35(3):610-617.   Published online September 22, 2020
DOI: https://doi.org/10.3803/EnM.2020.721
  • 7,230 View
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AbstractAbstract PDFPubReader   ePub   
Background
It is well known that high serum ferritin, a marker of iron storage, predicts incident type 2 diabetes. Limited information is available on the association between transferrin, another marker of iron metabolism, and type 2 diabetes. Thus, we investigated the association between transferrin and incident type 2 diabetes.
Methods
Total 31,717 participants (mean age, 40.4±7.2 years) in a health screening program in 2005 were assessed via cross-sectional analysis. We included 30,699 subjects who underwent medical check-up in 2005 and 2009 and did not have type 2 diabetes at baseline in this retrospective longitudinal analysis.
Results
The serum transferrin level was higher in the type 2 diabetes group than in the non-type 2 diabetes group (58.32±7.74 μmol/L vs. 56.17±7.96 μmol/L, P<0.001). Transferrin correlated with fasting serum glucose and glycosylated hemoglobin in the correlational analysis (r=0.062, P<0.001 and r=0.077, P<0.001, respectively) after full adjustment for covariates. Transferrin was more closely related to homeostasis model assessment of insulin resistance than to homeostasis model assessment of β cell function (r=0.042, P<0.001 and r=–0.019, P=0.004, respectively) after full adjustment. Transferrin predicted incident type 2 diabetes in non-type 2 diabetic subjects in a multivariate linear regression analysis; the odds ratio (95% confidence interval [CI]) of the 3rd tertile compared to that in the 1st tertile of transferrin for incident diabetes was 1.319 (95% CI, 1.082 to 1.607) after full adjustment (P=0.006).
Conclusion
Transferrin is positively associated with incident type 2 diabetes in Koreans.

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Review Articles
Obesity and Metabolism
Metabolically Healthy and Unhealthy Normal Weight and Obesity
Norbert Stefan
Endocrinol Metab. 2020;35(3):487-493.   Published online August 20, 2020
DOI: https://doi.org/10.3803/EnM.2020.301
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AbstractAbstract PDFPubReader   ePub   
Increased fat mass is an established risk factor for the cardiometabolic diseases type 2 diabetes and cardiovascular disease (CVD) and is associated with increased risk of all-cause and CVD mortality. However, also very low fat mass associates with such an increased risk. Whether impaired metabolic health, characterized by hypertension, dyslipidemia, hyperglycemia, insulin resistance, and subclinical inflammation, may explain part of the elevated risk of cardiometabolic diseases that is found in many subjects with very low fat mass, as it does in many obese subjects, is unknown. An important pathomechanism of impaired metabolic health is disproportionate fat distribution. In this article the risk of cardiometabolic diseases and mortality in subjects with metabolically healthy and unhealthy normal weight and obesity is summarized. Furthermore, the change of metabolic health during a longer period of follow-up and its impact on cardiometabolic diseases is being discussed. Finally, the implementation of the concept of metabolic health in daily clinical practice is being highlighted.

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Obesity and Metabolism
Nonalcoholic Fatty Liver Disease and Diabetes: An Epidemiological Perspective
Eun-Jung Rhee
Endocrinol Metab. 2019;34(3):226-233.   Published online September 26, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.3.226
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  • 366 Download
  • 82 Web of Science
  • 87 Crossref
AbstractAbstract PDFPubReader   ePub   

Nonalcoholic fatty liver disease (NAFLD) is thought to stem from the body's inability to store excess energy in adipocytes; as such, it is commonly viewed as the hepatic manifestation of metabolic syndrome. The pathogenesis of NAFLD involves ectopic fat accumulation, which also takes place in the liver, muscle and visceral fat. NAFLD is rapidly becoming more widespread in Korea, with an estimated prevalence of 30% in adults. Type 2 diabetes mellitus (T2DM) and NAFLD share insulin resistance as a common pathophysiological mechanism, and each of these two diseases affects the development of the other. Recent studies have suggested that NAFLD is often present as a comorbidity in T2DM patients. The mutual interrelationship between these conditions is shown by findings suggesting that T2DM can exacerbate NAFLD by promoting progression to nonalcoholic hepatosteatosis or fibrosis, while NAFLD causes the natural course of diabetic complications to worsen in T2DM patients. It remains unknown whether one disease is the cause of the other or vice versa. In this review, I would like to discuss current epidemiological data on the associations between NAFLD and T2DM, and how each disease affects the course of the other.

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Close layer
Original Article
Clinical Study
Triglyceride Glucose Index Is Superior to the Homeostasis Model Assessment of Insulin Resistance for Predicting Nonalcoholic Fatty Liver Disease in Korean Adults
Sang Bae Lee, Min Kyung Kim, Shinae Kang, Kahui Park, Jung Hye Kim, Su Jung Baik, Ji Sun Nam, Chul Woo Ahn, Jong Suk Park
Endocrinol Metab. 2019;34(2):179-186.   Published online May 20, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.2.179
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AbstractAbstract PDFPubReader   ePub   
Background

Recently, the triglyceride glucose (TyG) index has been considered a surrogate marker of insulin resistance which is a well-known pathogenic factor in nonalcoholic fatty liver disease (NAFLD). However, few studies have investigated the relationship between the TyG index and NAFLD. Thus, we investigated the relationship between the TyG index and NAFLD and the effectiveness of the TyG index compared with the homeostasis model assessment of insulin resistance (HOMA-IR) in identifying NAFLD in Korean adults.

Methods

Participants of 4,986 who underwent ultrasonography in a health promotion center were enrolled. The TyG index was calculated as ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2], and HOMA-IR was estimated. NAFLD was diagnosed by ultrasonography.

Results

Significant differences were observed in metabolic parameters among the quartiles of the TyG index. The prevalence of NAFLD significantly increased with increment in the TyG index. After adjusting for multiple risk factors, a logistic regression analysis was performed. When the highest and lowest quartiles of the TyG index and HOMA-IR were compared, the odds ratios for the prevalence of NAFLD were 2.94 and 1.93 (95% confidence interval, 2.32 to 3.72 and 1.43 to 2.61; both P for trend <0.01), respectively. According to the receiver operating characteristic analysis, the TyG index was superior to HOMA-IR in predicting NAFLD.

Conclusion

The TyG index and prevalence of NAFLD were significantly related and the TyG index was superior to HOMA-IR in predicting NAFLD in Korean adults.

Citations

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  • Association of HOMA-IR Versus TyG Index with Diabetes in Individuals Without Underweight or Obesity
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  • The Triglyceride-Glucose Index is Associated with Vitamin D Status in Metabolic-Associated Fatty Liver Disease
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  • The triglyceride and glucose index and risk of nonalcoholic fatty liver disease: A dose–response meta-analysis
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Close layer
Review Articles
Obesity and Metabolism
Myths about Insulin Resistance: Tribute to Gerald Reaven
Sun H. Kim, Fahim Abbasi
Endocrinol Metab. 2019;34(1):47-52.   Published online March 21, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.47
  • 11,694 View
  • 188 Download
  • 3 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   ePub   

Gerald Reaven was often called the “father of insulin resistance.” On the 1-year anniversary of his death in 2018, we challenge three myths associated with insulin resistance: metformin improves insulin resistance; measurement of waist circumference predicts insulin resistance better than body mass index; and insulin resistance causes weight gain. In this review, we highlight Reaven's relevant research that helped to dispel these myths associated with insulin resistance.

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Close layer
Obesity and Metabolism
Implications of Mitochondrial Unfolded Protein Response and Mitokines: A Perspective on Fatty Liver Diseases
Hyon-Seung Yi
Endocrinol Metab. 2019;34(1):39-46.   Published online March 21, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.39
  • 9,866 View
  • 160 Download
  • 36 Web of Science
  • 36 Crossref
AbstractAbstract PDFPubReader   ePub   

The signaling network of the mitochondrial unfolded protein response (UPRmt) and mitohormesis is a retrograde signaling pathway through which mitochondria-to-nucleus communication occurs in organisms. Recently, it has been shown that the UPRmt is closely associated with metabolic disorders and conditions involving insulin resistance, such as alcoholic and non-alcoholic fatty liver and fibrotic liver disease. Scientific efforts to understand the UPRmt and mitohormesis, as well as to establish the mitochondrial proteome, have established the importance of mitochondrial quality control in the development and progression of metabolic liver diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this review, we integrate and discuss the recent data from the literature on the UPRmt and mitohormesis in metabolic liver diseases, including NAFLD/NASH and fibrosis.

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Close layer
Original Article
Obesity and Metabolism
Metabolic Syndrome and Insulin Resistance Syndrome among Infertile Women with Polycystic Ovary Syndrome: A Cross-Sectional Study from Central Vietnam
Minh Tam Le, Vu Quoc Huy Nguyen, Quang Vinh Truong, Dinh Duong Le, Viet Nguyen Sa Le, Ngoc Thanh Cao
Endocrinol Metab. 2018;33(4):447-458.   Published online November 30, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.4.447
  • 8,129 View
  • 102 Download
  • 12 Web of Science
  • 15 Crossref
AbstractAbstract PDFPubReader   ePub   
Background

Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies among reproductive-age women. Its metabolic features often overlap with those associated with metabolic syndrome (MS) and insulin resistance syndrome (IRS). The objective of this study was to determine the prevalence and predictors of MS and IRS in infertile Vietnamese women with PCOS.

Methods

A cross-sectional study was conducted at a tertiary fertility centre at Hue University Hospital from June 2016 to November 2017. A total of 441 infertile women diagnosed with PCOS based on the revised 2003 Rotterdam consensus criteria were enrolled. MS and IRS were defined based on the National Heart, Lung, and Blood Institute/American Heart Association Adult Treatment Panel III 2005 and American College of Endocrinology IRS 2003 criteria, respectively. Complete clinical and biochemical measurements of 318 women were available for analysis. Independent predictors of MS and IRS were identified using multivariate logistic regression.

Results

The overall prevalence of MS and IRS in women with PCOS was 10.4% and 27.0%, respectively. We identified older age (>30 years) and obesity as independent predictors of MS and IRS. Elevated anti-Müllerian hormone levels increased the risk of IRS, but not that of MS.

Conclusion

MS and IRS are prevalent disorders among infertile Vietnamese women with PCOS. PCOS is not solely a reproductive problem. Screening and early intervention for MS and/or IRS based on anthropometric, metabolic, and reproductive hormone risk factors should be an integral part of fertility care.

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Close layer
Review Articles
Diabetes
Latent Autoimmune Diabetes in Adults: Current Status and New Horizons
Paolo Pozzilli, Silvia Pieralice
Endocrinol Metab. 2018;33(2):147-159.   Published online June 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.147
  • 25,665 View
  • 578 Download
  • 66 Web of Science
  • 65 Crossref
AbstractAbstract PDFPubReader   ePub   

Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes in adults (LADA). This condition is more heterogeneous than young-onset autoimmune diabetes and shares clinical and metabolic characteristics with both type 2 and type 1 diabetes. Patients with LADA are considered by having highly variable β-cell destruction, different degrees of insulin resistance and heterogeneous titre and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. To date the heterogeneity of LADA does not allow to establish a priori treatment algorithm and no specific guidelines for LADA therapy are available. These subjects are mostly treated as affected by type 2 diabetes, a factor that might lead to the progression to insulin-dependency quickly. A personalised medicine approach is necessary to attain optimal metabolic control and preserve β-cell function to decrease the risk of long-term diabetes complications. Recent data concerning the use of oral antidiabetic agents as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up-and-coming results in term of protect C-peptide levels and improving glycaemic control. This review summarises current knowledge on LADA, emphasising controversies regarding its pathophysiology and clinical features. Moreover, we discuss data available about novel therapeutic approaches that can be considered for prevention of β-cell loss in LADA.

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Close layer
Diabetes
Pathophysiology of Type 2 Diabetes in Koreans
Soo Heon Kwak, Kyong Soo Park
Endocrinol Metab. 2018;33(1):9-16.   Published online March 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.1.9
  • 9,462 View
  • 137 Download
  • 20 Web of Science
  • 18 Crossref
AbstractAbstract PDFPubReader   ePub   

The pathophysiology of type 2 diabetes is characterized by variable degrees of insulin resistance and impaired insulin secretion. Both genetic and environmental factors serve as etiologic factors. Recent genetic studies have identified at least 83 variants associated with diabetes. A significant number of these loci are thought to be involved in insulin secretion, either through β-cell development or β-cell dysfunction. Environmental factors have changed rapidly during the past half century, and the increased prevalence of obesity and diabetes can be attributed to these changes. Environmental factors may affect epigenetic changes and alter susceptibility to diabetes. A recent epidemiologic study revealed that Korean patients with type 2 diabetes already had impaired insulin secretion and insulin resistance 10 years before the onset of diabetes. Those who developed diabetes showed impaired β-cell compensation with an abrupt decrease in insulin secretion during the last 2 years before diabetes developed. The retrograde trajectory of the disposition index differed according to the baseline subgroups of insulin secretion and insulin sensitivity. We hope that obtaining a more detailed understanding of the perturbations in the major pathophysiologic process of diabetes on the individual level will eventually lead to the implementation of precision medicine and improved patient outcomes.

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Close layer
Original Articles
Clinical Study
A Novel Index Using Soluble CD36 Is Associated with the Prevalence of Type 2 Diabetes Mellitus: Comparison Study with Triglyceride-Glucose Index
Ho Jin Kim, Jun Sung Moon, Il Rae Park, Joong Hee Kim, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee
Endocrinol Metab. 2017;32(3):375-382.   Published online September 18, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.3.375
  • 8,685 View
  • 58 Download
  • 15 Web of Science
  • 18 Crossref
AbstractAbstract PDFPubReader   
Background

Plasma soluble cluster determinant 36 (sCD36) level is closely related with insulin resistance and atherosclerosis, but little is known whether it could be a surrogate for estimating risk of developing diabetes or not. To address this, we evaluated association between sCD36 index, the product of sCD36 and fasting plasma glucose (FPG), and the prevalence of type 2 diabetes mellitus (T2DM), and then compared with triglyceride-glucose (TyG) index which has been suggested simple index for insulin resistance.

Methods

This was cross-sectional study, and participants were classified as normal glucose tolerance (NGT), prediabetes, and T2DM according to glucose tolerance. The formula of TyG index was ‘ln [FPG (mg/dL)×triglyceride (mg/dL)/2],’ and the sCD36 index was ‘ln [sCD36 (pg/mL)×FPG (mg/dL)/2].’

Results

One hundred and fifty-five subjects (mean age, 55.2 years) were enrolled, and patients with T2DM were 75. Both indexes were significantly increased in prediabetes and T2DM rather than NGT, and sCD36 index was positively correlated with both glycosylated hemoglobin and homeostasis model assessment of insulin resistance (r=0.767 and r=0.453, respectively; P<0.05) and negatively with homeostasis model assessment estimate of β-cell function (r=−0.317). The odds ratio (OR) of sCD36 index for T2DM was 4.39 (95% confidential interval, 1.51 to 12.77) after adjusting age, gender, blood pressure, smoking, alcohol, non-high density lipoprotein cholesterol and high-sensitivity C-reactive protein. However, OR of TyG index did not remained significance after adjustment.

Conclusion

sCD36 index has an independent association with the risk of T2DM, and showed better correlation than TyG index. These results suggest sCD36 index might be useful surrogate marker for the risk of diabetes.

Citations

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    Austin Dada, Javad Habibi, Huma Naz, Dongqing Chen, Guido Lastra, Brian P. Bostick, Adam Whaley-Connell, Michael A. Hill, James R. Sowers, Guanghong Jia
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Close layer
Clinical Study
Leu72Met and Other Intronic Polymorphisms in the GHRL and GHSR Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population
Faris Elbahi Joatar, Ali Ahmed Al Qarni, Muhalab E. Ali, Abdulaziz Al Masaud, Abdirashid M. Shire, Nagalla Das, Khalid Gumaa, Hayder A. Giha
Endocrinol Metab. 2017;32(3):360-369.   Published online September 18, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.3.360
  • 7,347 View
  • 51 Download
  • 9 Web of Science
  • 13 Crossref
AbstractAbstract PDFPubReader   
Background

Ghrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associations raise the issue of ‘which SNPs in which populations.’ The aim of this study was to investigate whether SNPs in GHRL and/or GHSR genes were associated with T2DM, IR, or plasma GHRL levels among Arab Saudis.

Methods

Blood was collected from 208 Saudi subjects with (n=107) and without (n=101) T2DM. DNA samples from these subjects were analyzed by real-time polymerase chain reaction to genotype five intronic SNPs in the GHRL (rs696217 TG, rs27647 CT, rs2075356 CT, and rs4684677 AT) and GHSR (rs509030 GC) genes. In addition, plasma GHRL levels were measured by a radioimmunoassay.

Results

None of the SNPs were associated with T2DM, IR, or plasma GHRL levels. The frequencies of the alleles, genotypes, and haplotypes of the five SNPs were comparable between the T2DM patients and the non-diabetic subjects. A large number of the GHRL haplotypes indicates the molecular heterogeneity of the preproghrelin gene in this region.

Conclusion

Neither the Leu72Met polymorphism nor the other intronic GHRL and GHSR SNPs were associated with T2DM, IR, or GHRL levels. Further investigations should be carried out to explain the molecular basis of the association of the GHRL peptide with T2DM and IR.

Citations

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  • Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis
    Anca Moțățăianu, Ion Bogdan Mănescu, Georgiana Șerban, Laura Bărcuțean, Valentin Ion, Rodica Bălașa, Sebastian Andone
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    May Salem Al-Nbaheen
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    Monika Buraczynska, Jakub Golacki, Wojciech Zaluska
    Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 557.     CrossRef
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    Hayder A. Giha, Faris E. Joatar, Dhuha M. B. AlDehaini, Zainab H. A. Malalla, Muhalab E. Ali, Ali A. Al Qarni
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    Esma SELÇUK, Uğur ŞAHİN, Didem ÖZKAHRAMAN, Mustafa CALAPOĞLU, Nilüfer ŞAHİN CALAPOĞLU
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    Mohammad Muzaffar Mir, Rashid Mir, Mushabab Ayed Abdullah Alghamdi, Javed Iqbal Wani, Zia Ul Sabah, Mohammed Jeelani, Vijaya Marakala, Shahzada Khalid Sohail, Mohamed O’haj, Muffarah Hamid Alharthi, Mohannad Mohammad S. Alamri
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Close layer
Association of Plasma Ghrelin Levels with Insulin Resistance in Type 2 Diabetes Mellitus among Saudi Subjects
Ali Ahmed Al Qarni, Faris Elbahi Joatar, Nagalla Das, Mohamed Awad, Mona Eltayeb, Ahmed Gasim Al-Zubair, Muhalab E. Ali, Abdulaziz Al Masaud, Abdirashid M. Shire, Khalid Gumaa, Hayder A. Giha
Endocrinol Metab. 2017;32(2):230-240.   Published online May 29, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.2.230
  • 8,993 View
  • 77 Download
  • 22 Web of Science
  • 21 Crossref
AbstractAbstract PDFPubReader   
Background

Although the exact mechanism of insulin resistance (IR) has not yet been established, IR is the hallmark characteristic of type 2 diabetes mellitus (T2DM). The aim of this study was to examine the relationship between plasma ghrelin levels and IR in Saudi subjects with T2DM.

Methods

Patients with T2DM (n=107, cases) and non-diabetic apparently healthy subjects (n=101, controls) from Saudi Arabia were included in this study. The biochemical profiles and plasma insulin levels of all subjects were analyzed, and IR was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Active ghrelin levels in plasma were measured using the radioimmunoassay technique.

Results

Only 46.7% (50 of 107) of the T2DM subjects had IR, including 26% (28 of 107) with severe IR (HOMA-IR ≥5), while 5.9% (six of 101) of the controls had moderate IR (3 ≤HOMA-IR <5). HOMA-IR values were not associated with age, disease duration, or gender. Importantly, T2DM itself and the co-occurrence of IR with T2DM were significantly associated with low plasma ghrelin levels. However, ghrelin levels were inversely correlated with the HOMA-IR index, body weight, and fasting plasma insulin levels, mainly in the control subjects, which was indicative of the breakdown of metabolic homeostasis in T2DM.

Conclusion

The prevalence of IR was relatively low, and IR may be inversely associated with plasma ghrelin levels among Saudi patients with T2DM.

Citations

Citations to this article as recorded by  
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Close layer
Review Articles
The SCAP/SREBP Pathway: A Mediator of Hepatic Steatosis
Young-Ah Moon
Endocrinol Metab. 2017;32(1):6-10.   Published online January 19, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.1.6
  • 13,593 View
  • 261 Download
  • 91 Web of Science
  • 90 Crossref
AbstractAbstract PDFPubReader   

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance, obesity, and dyslipidemia. NAFLD encompasses a wide range of states from the simple accumulation of triglycerides in the hepatocytes to serious states accompanied by inflammation and fibrosis in the liver. De novo lipogenesis has been shown to be a significant factor in the development of hepatic steatosis in insulin-resistant states. Sterol regulatory element binding protein-1c (SREBP-1c) is the main transcription factor that mediates the activation of lipogenesis, and SREBP cleavage activating protein (SCAP) is required for the activation of SREBPs. Here, recent animal studies that suggest SCAP as a therapeutic target for hepatic steatosis and hypertriglyceridemia are discussed.

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Obesity and Metabolism
Insulin Secretory Capacity and Insulin Resistance in Korean Type 2 Diabetes Mellitus Patients
Jong-Dai Kim, Won-Young Lee
Endocrinol Metab. 2016;31(3):354-360.   Published online August 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.3.354
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AbstractAbstract PDFPubReader   

It is well known that many Korean patients with type 2 diabetes mellitus (T2DM) were non-obese and had decreased insulin secretion in past. However, during the past three decades, lifestyles in Korea have been westernized. As a result, the prevalence of obesity, the main cause of diabetes has increased. Thus, there is still a question as to whether the main pathophysiology of current Korean T2DM is insulin resistance or an insulin secretion defect. Because various anti-diabetes medications having different mechanisms of action are currently used as therapeutics, it is important to understand which of these factors is the main physiology in the development of diabetes in Koreans. In this review, we review changes in obesity prevalence, insulin resistance and insulin secretion defects in Korean T2DM during three decades.

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Namgok Lecture 2015
Obesity and Metabolism
The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis
Kyung Mook Choi
Endocrinol Metab. 2016;31(1):1-6.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.1
  • 9,061 View
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AbstractAbstract PDFPubReader   

Immoderate energy intake, a sedentary lifestyle, and aging have contributed to the increased prevalence of obesity, sarcopenia, metabolic syndrome, type 2 diabetes, and cardiovascular disease. There is an urgent need for the development of novel pharmacological interventions that can target excessive fat accumulation and decreased muscle mass and/or strength. Adipokines, bioactive molecules derived from adipose tissue, are involved in the regulation of appetite and satiety, inflammation, energy expenditure, insulin resistance and secretion, glucose and lipid metabolism, and atherosclerosis. Recently, there is emerging evidence that skeletal muscle and the liver also function as endocrine organs that secrete myokines and hepatokines, respectively. Novel discoveries and research into these organokines (adipokines, myokines, and hepatokines) may lead to the development of promising biomarkers and therapeutics for cardiometabolic disease. In this review, I summarize recent data on these organokines and focus on the role of adipokines, myokines, and hepatokines in the regulation of insulin resistance, inflammation, and atherosclerosis.

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Close layer
Original Article
Obesity and Metabolism
Serum Concentrations of Ghrelin and Leptin according to Thyroid Hormone Condition, and Their Correlations with Insulin Resistance
Kyu-Jin Kim, Bo-Yeon Kim, Ji-Oh Mok, Chul-Hee Kim, Sung-Koo Kang, Chan-Hee Jung
Endocrinol Metab. 2015;30(3):318-325.   Published online May 18, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.3.318
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AbstractAbstract PDFPubReader   
Background

Thyroid hormones can influence energy metabolism and insulin sensitivity via their interaction with adipocytokines and gut hormones. The aims of this study were to evaluate differences in serum ghrelin and leptin concentrations according to thyroid hormone levels, and to investigate the correlation of insulin resistance.

Methods

A total of 154 patients (57 hyperthyroid patients, 61 euthyroid patients, and 36 hypothyroid patients; mean age, 47.9 years) were enrolled. Serum leptin, ghrelin, and insulin levels were measured and insulin resistance was calculated using the formula of the homeostasis model assessment of insulin resistance (HOMA-IR).

Results

There were no differences in mean concentrations of ghrelin or leptin among the three groups. There were no significant differences in insulin levels between the groups (P=0.06), although hyperthyroid patients had borderline statistically significantly higher levels of insulin than did euthyroid subjects by post hoc test (26.4 µIU/mL vs. 16.1 µIU/mL, P=0.057). Regarding HOMA-IR index, the mean levels were highest in the hyperthyroid group among those of the three groups (hyperthyroid vs. euthyroid vs. hypothyroid, 6.7 vs. 3.8 vs. 4.4, P=0.068). Plasma levels of ghrelin were significantly negatively correlated with age, insulin, glucose, body mass index (BMI), and HOMA-IR. Plasma levels of leptin showed significant positive correlation with BMI and triglyceride. There were no significant correlations among thyroid hormone, thyrotropin, ghrelin, leptin, or insulin.

Conclusion

The present study found that serum ghrelin, leptin, and insulin levels didn't differ according to thyroid function conditions. Further studies with larger numbers of patients are required to establish a direct relationship between plasma ghrelin, leptin, and thyroid hormone.

Citations

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Close layer
Review Article
Obesity and Metabolism
Transcriptional Regulation of Fibroblast Growth Factor 21 Expression
Kwi-Hyun Bae, Jung-Guk Kim, Keun-Gyu Park
Endocrinol Metab. 2014;29(2):105-111.   Published online June 26, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.2.105
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  • 75 Download
  • 28 Web of Science
  • 26 Crossref
AbstractAbstract PDFPubReader   

Fibroblast growth factor 21 (FGF21) is an attractive target for treating metabolic disease due to its wide-ranging beneficial effects on glucose and lipid metabolism. Circulating FGF21 levels are increased in insulin-resistant states; however, endogenous FGF21 fails to improve glucose and lipid metabolism in obesity, suggesting that metabolic syndrome is an FGF21-resistant state. Therefore, transcription factors for FGF21 are potential drug targets that could increase FGF21 expression in obesity and reduce FGF21 resistance. Despite many studies on the metabolic effects of FGF21, the transcriptional regulation of FGF21 gene expression remains controversial and is not fully understood. As the FGF21 transcription factor pathway is one of the most promising targets for the treatment of metabolic syndrome, further investigation of FGF21 transcriptional regulation is required.

Citations

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Close layer
Original Articles
Obesity and Metabolism
Adiposity in the Relationship between Serum Vitamin D Level and Insulin Resistance in Middle-Aged and Elderly Korean Adults: The Korea National Health and Nutrition Examination Survey 2008
Ji Hyun Kang, Sang Soo Kim, Seung Su Moon, Won Jin Kim, Min Jung Bae, Bo Gwang Choi, Yun Kyung Jeon, Bo Hyun Kim, Yong Ki Kim, In Joo Kim
Endocrinol Metab. 2013;28(2):96-102.   Published online June 18, 2013
DOI: https://doi.org/10.3803/EnM.2013.28.2.96
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  • 17 Web of Science
  • 18 Crossref
AbstractAbstract PDFPubReader   
Background

The role of adiposity in the relationship between serum vitamin D levels and insulin resistance has not yet been fully studied. This aim of this study is to clarify the role of adiposity in the relationship between serum vitamin D level and insulin resistance among middle-aged and elderly Korean adults.

Methods

We used data from 2,710 individuals aged ≥50 years based on national data from a representative sample of the fourth Korea National Health and Nutrition Examination Survey IV-2 in 2008.

Results

After adjustment for potential confounders, body mass index (BMI) was significantly associated with 25(OH) vitamin D (P=0.008). However, waist circumference was not significantly associated with 25(OH) vitamin D. In the stratified analyses, 25(OH) vitamin D was found to be negatively associated with fasting insulin and homeostasis model assessment estimate of insulin resistance (HOMA-IR) in participants with BMIs ≥25 kg/m2 (P=0.003 for both insulin and HOMR-IR) but was not found to be associated in those with BMIs <23 kg/m2. However, we observed a significant inverse in the association of 25(OH) vitamin D with fasting insulin and HOMA-IR in both the normal (P=0.001 and P<0.001 and the abdominally obese group (P=0.010 and P=0.009) in the stratified analyses according to abdominal obesity.

Conclusion

Our results support that the idea that endogenously-produced vitamin D might be stored in subcutaneous fat deposits. In addition, the association of vitamin D with insulin resistance in middle-aged and elderly Korean adults was stronger when it was stratified by BMI than when abdominal obesity status.

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Close layer
Obesity and Metabolism
Association between Serum Albumin, Insulin Resistance, and Incident Diabetes in Nondiabetic Subjects
Ji Cheol Bae, Sung Hwan Seo, Kyu Yeon Hur, Jae Hyeon Kim, Myung-Shik Lee, Moon Kyu Lee, Won Young Lee, Eun Jung Rhee, Ki Won Oh
Endocrinol Metab. 2013;28(1):26-32.   Published online March 25, 2013
DOI: https://doi.org/10.3803/EnM.2013.28.1.26
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  • 64 Download
  • 51 Crossref
AbstractAbstract PDFPubReader   
Background

Serum albumin has been suggested to be associated with insulin resistance. We evaluated the association between serum albumin concentration and insulin resistance. We also investigated whether serum albumin level has an independent effect on the development of diabetes.

Methods

In our study, 9,029 subjects without diabetes, who underwent comprehensive health check-ups annually for 5 years, were categorized into tertiles based on their serum albumin levels at baseline. The odds ratio (OR) for the prevalence of insulin resistance, defined as the top quartile of homeostasis model assessment of insulin resistance and the presence of impaired fasting glucose and nonalcoholic fatty liver disease, was evaluated cross-sectionally. Also, the hazard ratio (HR) for incident diabetes was estimated longitudinally, according to the baseline albumin tertiles using Cox proportional hazard analysis respectively.

Results

From the lowest to the highest tertile of albumin, the multivariable-adjusted ORs of insulin resistance increased significantly in both men and women. During the mean follow-up period of nearly 4 years, 556 (6.1%) subjects progressed to diabetes. The multivariable-adjusted HR (95% confidence interval [CI]) of diabetes in men were 1, 1.09 (95% CI, 0.86 to 1.40), and 1.10 (95% CI, 0.86 to 1.41), respectively, from the lowest to the highest tertiles of baseline albumin. Corresponding values for women were 1, 1.21 (95% CI, 0.66 to 2.21), and 1.06 (95% CI, 0.56 to 2.02), respectively.

Conclusion

Our study showed that increased serum albumin level was associated with insulin resistance. However, serum albumin did not have an independent effect on the development of diabetes.

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    BMJ Open Diabetes Research & Care.2021; 9(2): e002039.     CrossRef
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    Samuel Seidu, Setor K. Kunutsor, Kamlesh Khunti
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Review Articles
Reproduction and Metabolism: Insights from Polycystic Ovary Syndrome.
Prathima Jasti, Andrea Dunaif
Endocrinol Metab. 2012;27(3):180-190.   Published online September 19, 2012
DOI: https://doi.org/10.3803/EnM.2012.27.3.180
  • 3,308 View
  • 32 Download
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AbstractAbstract PDF
Until the 1980s, polycystic ovary syndrome (PCOS) was considered to be a poorly defined reproductive disorder. During that decade, it was recognized that PCOS was associated with profound insulin resistance and a substantially increased risk for type 2 diabetes mellitus in young women. Accordingly, the mechanisms linking the reproductive and metabolic features of the syndrome became the subject of intense investigation. Insulin is now recognized as a reproductive as well as a metabolic hormone and insulin signaling in the central nervous system participates in normal reproductive function. These insights have been directly translated into a novel therapy for PCOS with insulin sensitizing drugs. Androgens also have reversible metabolic actions to decrease insulin sensitivity and increase visceral fat. Prenatal androgen administration to non-human primates, sheep and rodents produces reproductive and metabolic features of PCOS suggesting that the disorder also has developmental origins. PCOS is highly heritable and male as well as female relatives have reproductive and metabolic phenotypes. A number of confirmed genetic susceptibility loci have now been mapped for PCOS and genes in well-known as well as novel biologic pathways have been implicated in disease pathogenesis.

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  • The Role of Foxo3 in Leydig Cells
    Young Suk Choi, Joo Eun Song, Byung Soo Kong, Jae Won Hong, Silvia Novelli, Eun Jig Lee
    Yonsei Medical Journal.2015; 56(6): 1590.     CrossRef
  • FoxO1 Is a Negative Regulator of FSHβ Gene Expression in Basal and GnRH-Stimulated Conditions in Female
    Young-Suk Choi, Hyeon Jeong Lee, Cheol Ryong Ku, Yoon Hee Cho, Mi Ran Seo, Yoo Jeoung Lee, Eun Jig Lee
    Endocrinology.2014; 155(6): 2277.     CrossRef
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Mechanism of Lipid Induced Insulin Resistance: An Overview.
Samir Bhattacharya, Rakesh Kundu, Suman Dasgupta, Sushmita Bhattacharya
Endocrinol Metab. 2012;27(1):12-19.   Published online March 1, 2012
DOI: https://doi.org/10.3803/EnM.2012.27.1.12
  • 5,223 View
  • 46 Download
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AbstractAbstract PDF
Type 2 diabetes (T2D) is rapidly spreading throughout the world. It's an insidious disease and still treated in an indirect manner without having specific drug target. In majority cases T2D is treated with drugs that address type 1 diabetes, majority of drugs aim to increase insulin release although the root cause for T2D is not the dearth of insulin release, it occurs in the later stage of disease development. T2D silently progressed in the patient; it begins with insulin resistance that takes place due to the loss of insulin sensitivity. Though insulin resistance is the centre of pathogenesis, our treatment of the disease has not yet addressed it. It is now a fact that insulin resistance is manifested by lipid and fatty acids (FAs) play a critical role in blunting insulin sensitivity. Our understanding is still poor in deciphering how lipid impose insulin insensitivity, majority of workers suggest it is because of insulin signaling defects which implements insulin function in inhibiting glucose to the cell from circulation. Number of long chain saturated FA has been shown to produce insulin signaling defects. However, we really need further investigation to find specific target(s) for FA induced damage. In addition to these information, a new dimension of T2D is getting attractive is fetuin-A/alpha2-Heremans-Schmid Glycoprotein, a secretary protein from liver. Its gene locus has been identified as T2D susceptible. Fetuin-A's excess expression occurs by FA and it disrupts adipocyte function. It has been shown to be associated with T2D especially in obesity. In this review, we briefly discuss the present status on the mechanistic understanding of lipid induced insulin resistance that leads to T2D. More we understand the mechanism; opportunity to fight the battle with T2D will be increasing. Since, this field is now vast; we covered a few major events.

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  • Abnormal Fetuin-A levels in obese horses are associated with activated TLR4/NF-ƙB/MAPK axis and depleted FBXW7 E3 ubiquitin ligase
    Lynda Bourebaba, Mikołaj Panek, Lilibeth Carolina Cárdenas Piedra, Nabila Bourebaba
    Veterinary Research Communications.2025;[Epub]     CrossRef
  • The SWGEDWGEIW from Soybean Peptides Reduces Insulin Resistance in 3T3-L1 Adipocytes by Activating p-Akt/GLUT4 Signaling Pathway
    Guofu Yi, Xia Sang, Yuxia Zhu, Di Zhou, Shuibing Yang, Yue Huo, Yang Liu, Bushra Safdar, Xianyong Bu
    Molecules.2023; 28(7): 3001.     CrossRef
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Case Report
A Case of the Type B Insulin Resistance Syndrome with Chronic Hepatitis B.
Hyun Seok Choi, Byoung Ho Choi, Seok Hoo Jeong, Shung Han Choi, Dong Su Shin, Sei hyun Kim, Young Sil Eom, Sihoon Lee, Yeun Sun Kim, Ie Byung Park, Ki Young Lee
Endocrinol Metab. 2011;26(4):360-363.   Published online December 1, 2011
DOI: https://doi.org/10.3803/EnM.2011.26.4.360
  • 2,958 View
  • 24 Download
AbstractAbstract PDF
Type B insulin resistance syndrome is rare autoimmune disease that is characterized by various abnormalities of glycemic homeostasis, from hyperglycemia caused by extreme insulin resistance to fasting hypoglycemia. It can combine with other autoimmune diseases, most commonly systemic lupus erythematosus. It usually occurs in women and accompanies acanthosis nigricans, hyperandrogenism, and, in many cases, ovary dysfunction. The diagnosis of type B insulin resistance syndrome is based largely on the presence of insulin receptor autoantibodies and hyperglycemia, or hypoglycemia and hyperinsulinemia. In some cases, patients with the type B insulin resistance have been successfully treated with immunosuppressive therapy and plasmapheresis. We experienced type B insulin resistance syndrome in a patient with chronic hepatitis B and used only plasmapheresis for treatment. The immunosuppressive therapy was omitted due to the state of activation of chronic hepatitis B. We present this case with a review of relevant literature.
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Original Articles
Prevalence and Characteristics of Metabolically Obese but Normal Weight and Metabolically Healthy but Obese in Middle-aged Koreans: the Chungju Metabolic Disease Cohort (CMC) Study.
Seung Hwan Lee, Hee Sung Ha, Young Jun Park, Jin Hee Lee, Hyeon Woo Yim, Kun Ho Yoon, Moo Il Kang, Won Chul Lee, Ho Young Son, Yong Moon Park, Hyuk Sang Kwon
Endocrinol Metab. 2011;26(2):133-141.   Published online June 1, 2011
DOI: https://doi.org/10.3803/EnM.2011.26.2.133
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AbstractAbstract PDF
BACKGROUND
We attempted to determine the prevalence and characteristics of metabolically obese but normal weight (MONW) and metabolically healthy but obese (MHO) individuals in a large cohort of middle-aged Koreans. METHODS: 8,987 non-diabetic subjects were selected from the Chungju Metabolic disease Cohort Study performed in 2003-2006. MONW was defined as a body mass index (BMI) > or = 18.5 and < 23 kg/m2 with a homeostasis model assessment of insulin resistance (HOMA-IR) in the highest quartile. MHO was defined as BMI > or = 25 kg/m2 with HOMA-IR in the lowest quartile. RESULTS: The mean age of the subjects was 62.3 +/- 10.5 years (men 40.4%). The age-adjusted prevalence of MONW and MHO were 4.3% (5.3% men, 3.7% women) and 5.6% (3.6% men, 7.0% women), respectively. 14.2% of men and 12.9% of women were classified as MONW among the normal weight population, whereas 10.7% of men and 14.5% of women were classified as MHO among the obese subjects. The prevalence of prediabetes was significantly higher in the MONW group than in the MHO group (34.7 vs. 12.5%, P < 0.0001 in men; 23.1 vs. 8.8%, P < 0.0001 in women). The MONW group evidenced an equivalent risk of coronary heart disease (CHD) relative to the MHO group (10.77 +/- 0.68 vs. 10.22 +/- 0.90% in men; 7.02 +/- 0.34 vs. 7.26 +/- 0.26% in women, means +/- standard error [SE]). CONCLUSION: The subjects in the MONW group are characterized by a high risk of diabetes and CHD, despite their normal weights. Their substantial prevalence in the population emphasizes the importance of identifying subjects in the MONW group, and warrants more intensive risk management.

Citations

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  • Obesity, metabolic health, and mortality in adults: a nationwide population-based study in Korea
    Hae Kyung Yang, Kyungdo Han, Hyuk-Sang Kwon, Yong-Moon Park, Jae-Hyoung Cho, Kun-Ho Yoon, Moo-Il Kang, Bong-Yun Cha, Seung-Hwan Lee
    Scientific Reports.2016;[Epub]     CrossRef
  • The Definition of Metabolically Healthy Obesity
    Hae Kyung Yang, Seung-Hwan Lee
    The Journal of Korean Diabetes.2014; 15(1): 17.     CrossRef
Close layer
Gly1057Asp Polymorphism of the Insulin Receptor Substrate-2 Genes May Not Have a Significant Impact on Insulin Resistance in Korean Women with Polycystic Ovary Syndrome.
Ji Young Oh, Jee Young Oh, Yeon Ah Sung, Hye Jin Lee, Hye Won Chung
J Korean Endocr Soc. 2009;24(2):100-108.   Published online June 1, 2009
DOI: https://doi.org/10.3803/jkes.2009.24.2.100
  • 2,746 View
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  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Insulin resistance is a key factor in the pathogenesis of polycystic ovary syndrome (PCOS), and several candidate genes involved in insulin action such as insulin receptor or insulin recpetor substrate (IRS) have been investigated. In this study, we examined the genetic effects of the IRS-1 and IRS-2 genes on the metabolic and reproductive features in women with PCOS. METHODS: 125 patients with PCOS and 344 regular cycling controls were enrolled. Analysis of the polymorphisms of Gly972Arg in the IRS-1 gene and Gly1057Asp in the IRS-2 gene was performed and oral glucose tolerance tests and hyperinsulinemic euglycemic clamp tests were done. RESULTS: The genotype frequencies of the Gly972Arg polymorphism in the IRS-1 gene and the Gly1057Asp polymorphism in the IRS-2 gene were not significantly different between the women with PCOS and the controls. Gly972Arg polymorphism of the IRS-1 gene was extremely rare in both groups. PCOS women with the IRS-2 Asp1057Asp genotype showed significantly higher hirsutism scores, higher levels of free testosterone and higher post-load 60, 90, and 120 min plasma glucose levels compared to those women with the Gly1057Gly or Gly1057Asp genotype. In contrast, the control women with the Asp1057Asp genotype showed significantly lower post-load 60, 90, and 120 min plasma glucose levels compared with those women with the Gly1057Gly or Gly1057Asp genotype. CONCLUSION: Gly972Arg polymorphism of the IRS-1 gene was extremely rare in Korean women. Gly1057Asp polymorphism of the IRS-2 gene was associated with the phenotypic features of PCOS such as hirsutism, hyperandrogenemia and hyperglycemia, but it was not associated with the insulin sensitivity index. In conclusion, Gly1057Asp polymorphism of the IRS-2 gene may not have a significant impact on insulin resistance in Korean women with PCOS.

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  • Insulin Receptor Substrate 1 Gly972Arg (rs1801278) Polymorphism Is Associated with Obesity and Insulin Resistance in Kashmiri Women with Polycystic Ovary Syndrome
    Shayaq Ul Abeer Rasool, Mudasar Nabi, Sairish Ashraf, Shajrul Amin
    Genes.2022; 13(8): 1463.     CrossRef
Close layer
Calpain-10 Polymorphism in Korean Women with Polycystic Ovary Syndrome.
Hye jin Lee, Gun Woo Pyun, Eun Kyung Byun, Ji Young Oh, Jee Young Oh, Youngsun Hong, Yeon Ah Sung, Hye Won Chung
J Korean Endocr Soc. 2008;23(5):319-326.   Published online October 1, 2008
DOI: https://doi.org/10.3803/jkes.2008.23.5.319
  • 2,904 View
  • 33 Download
  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Polycystic ovary syndrome (PCOS) is characterized by chronic anovulation, hyperandrogenism and insulin resistance, and PCOS is known to be associated with an increased risk of type 2 diabetes mellitus (DM). PCOS has also been proposed to share a common genetic background with type 2 DM. The calpain 10 (CAPN10) gene is known to be associated with type 2 DM in several different population. We examined the association of CAPN10 gene polymorphisms and their influence on the metabolic abnormalities in Korean women who suffer with PCOS. METHODS: One hundred sixty four women with PCOS and 325 control women were studied. The CAPN10 gene polymorphisms were genotyped by amplifying the genomic DNA. Anthropometric measures, a 75g oral glucose tolerance test and measurement of insulin sensitivity by the euglycemic hyperinsulinemic clamp technique were performed. RESULTS: The frequencies of CAPN10 UCSNP-43, UCSNP-19, UCSNP-63 and the haplotype combinations were not different between the women with PCOS and the control subjects. In the women with PCOS and who had the UCSNP-43 GA genotype, the post-load 90 minute plasma glucose level was significantly greater and the HDL cholesterol and insulin mediated glucose uptake were significantly lower compared to the women with PCOS and who had the GG genotype. CONCLUSION: The CAPN10 UCSNP-43 genotype might be responsible for insulin resistance, yet further study is required to confirm the role of this genetic polymorphism in the development of PCOS and the presentation of its disease features.

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  • Comments on the latest meta-analysis of CAPN10 polymorphism associations with polycystic ovary syndrome
    Sidra Raihan, Dawood Shariff, Sami Bizzari
    Gene.2019; 717: 144006.     CrossRef
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Effects of Alpha-lipoic Acid on SREBP-1c Expression in HepG2 Cells.
Tae Sung Yun, Ae Kyung Min, Nam Kyung Kim, Mi Kyung Kim, Ho Chan Cho, Hye Soon Kim, Jae Seok Hwang, Seong Yeol Ryu, Keun Gyu Park, In Kyu Lee
J Korean Endocr Soc. 2008;23(1):27-34.   Published online February 1, 2008
DOI: https://doi.org/10.3803/jkes.2008.23.1.27
  • 3,720 View
  • 52 Download
  • 2 Crossref
AbstractAbstract PDF
BACKGROUND
Non-alcoholic fatty liver disease is common in patients with insulin resistance. Sterol regulatory element binding protein-1c (SREBP-1c) is a member of a family of transcription factors that have been recognized as key regulators for lipid accumulation in the liver that activate enzymes involved in the fatty acid biosynthetic pathway. This study was designed to evaluate whether alpha-lipoic acid (ALA) inhibits insulin-stimulated SREBP-1c expression. METHODS: We investigated the effects of ALA on insulin-stimulated SREBP-1c expression in a human hepatoma cell line (HepG2 cells) using Northern and Western blot analysis. We also examined the effect of ALA on the promoter activity of the SREBP-1c gene to examine whether ALA can affect SREBP-1c expression at the transcriptional level. To discern the mechanism by which ALA inhibits SREBP-1c expression, we examined the role of AMP-activated protein kinase (AMPK). RESULTS: Insulin increased the expression of SREBP-1c mRNA and protein in HepG2 cells in a dose depended manner. Co-treatment with ALA inhibited the insulin increased SREBP-1c expression in a dose-dependent manner. ALA also inhibited insulin-stimulated activation of the SREBP-1c promoter activity, indicating that ALA inhibited SREBP-1c expression at the transcriptional level. ALA increased phosphorylation of AMPK in HepG2 cells. Inhibition of the AMPK activity by compound C markedly reversed the inhibitory effects of ALA for insulin-stimulated SREBP-1c expression. These results suggest that ALA-induced suppression of SREBP-1c expression is at least in part mediated via AMPK activation. CONCLUSION: The present study suggests that ALA has an inhibitory effect on insulin-stimulated SREBP-1c expression. Therefore, further studies on the effects of ALA on hepatic steatosis in an animal model need to be performed.

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  • Effects of an aqueous extract of purple sweet potato on nonalcoholic fatty liver in high fat/cholesterol-fed mice
    You Jin Lee, Yoon Kyoung Yang, You Jin Kim, Oran Kwon
    Journal of Nutrition and Health.2015; 48(1): 1.     CrossRef
  • Effects of an aqueous extract of purple sweet potato on nonalcoholic fatty liver in high fat/cholesterol-fed mice
    You Jin Lee, Yoon Kyoung Yang, You Jin Kim, Oran Kwon
    Journal of Nutrition and Health.2015; 48(1): 1.     CrossRef
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The Effect of Fenofibrate and Exercise on Metabolic Syndrome and Hepatic Steatosis in OLETF Rats.
Kyung II Lee, Ji Min Kim, Ja Young Park, Ja Won Kim, Ji Young Mok, Mi Kyoung Park, Hye Jeong Lee, Sook Hee Hong, Wenjun Li, Duk Kyu Kim
J Korean Endocr Soc. 2007;22(3):192-202.   Published online June 1, 2007
DOI: https://doi.org/10.3803/jkes.2007.22.3.192
  • 3,557 View
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  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
The aim of this study is to verify the effects of fenofibrate monotherapy and fenofibrate combined with exercise for improving metabolic syndrome and hepatic steatosis. METHODS: Thirty-four weeks old OLETF rats (Otsuka Long-Evans Tokushima Fatty Rats, n = 20) were divided four groups: the regular diet group (n = 5, DD group), the exercise group (n = 5, DE group), the fenofibrate (100 mg/kg) treated group (n = 5, DF group) and the combination treatment group {fenofibrate and exercise (n = 5, EF group)}. After 5 weeks of treatment, blood was drawn for measuring the blood glucose, insulin, lipid and leptin levels. All the subjects were sacrificed for assessment of their body adiposity and hepatic steatosis. RESULTS: The total amount of food intake, body weight and total body weight of the rat were significantly decreased in the EF and DF groups compared to the DD group. The plasma triglyceride and glucose levels were significantly decreased in the EF and DF groups compared to the DD group. The HOMA-IR of EF, DF and DE groups were significantly decreased compared with that of the DD group. The plasma leptin levels of the EF and DF groups were significantly decreased compared with those of the DD and DE groups. The hepatic steatosis index was significantly decreased in the EF and DF groups compared to the DD and DE groups. CONCLUSION: Fenofibrate monotherapy was effective to control three major components (obesity, hypertriglyceridemia and hyperglycemia) of metabolic syndrome and hepatic steatosis in OLETF rats. Exercise combined with fenofibrate treatment showed an additional effect compared to that of fenofibrate monotherapy.

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  • Effect of Fenofibrate and Exercise on Metabolic Syndrome and Hepatic Steatosis
    Bong Soo Cha, Jae Hyuk Lee
    Journal of Korean Endocrine Society.2007; 22(3): 188.     CrossRef
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Role of Thigh Muscle in the Carotid artery Intima-Media Thickness and Insulin resistance.
ll Jun Hwang, Kyung Sun Park, Yun Tae Chae, Kyeh Dong Shi, Soo Kyung Kim, Seok Won Park, Yu Lee Kim, Yong Wook Cho, Young Kil Choi, Sang Jong Lee
J Korean Endocr Soc. 2005;20(5):452-459.   Published online October 1, 2005
DOI: https://doi.org/10.3803/jkes.2005.20.5.452
  • 2,753 View
  • 18 Download
  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
There have been recent reports that the fat distribution within skeletal muscle and the amount of muscle mass are associated with insulin resistance and the development of type 2 diabetes mellitus (T2DM). This study evaluated the impacts of visceral fat and thigh muscle from patients with T2DM and healthy subjects on atherosclerosis and insulin resistance. METHODS: Forty-two patients with newly-developed T2DM and 11 healthy subjects were selected for the study. The diabetic patients were subdivided into two groups, those under 40 years of age, as the young T2DM (n=21) group, and 40 years-old or greater, as the old T2DM (n=21) group. CT scans were obtained for all patients at the L4-L5 level and at the mid-portion between the greater trochanter and upper margin patella. The carotid intima-media thickness (IMT) was also measured using high resolution B-mode ultrasonography. RESULTS: The mean visceral fat area (VFA) in the old T2DM group was 169.4+/-13.2cm2, which was significantly greater than that found in the healthy subjects (67.9+/-7.92cm2, P<0.001) and young T2DM group (127.1+/-10.4cm2, P<0.05). The mean visceral fat to normal density muscle area ratio (VMNR) in the old T2DM group was 1.50+/-0.19, which was greater than in the healthy subjects (0.46+/-0.52, P<0.001) and young T2DM group (1.01+/-0.10, P<0.05). The total thigh muscle areas in the young and old T2DM groups were smaller than that in the healthy subjects, but without statistical significance. VMNR showed a positive correlation with the IMT and HOMA-IR. However, the total thigh muscle area was negatively correlated with the IMT. The normal density muscle area also showed significant negative correlations with the IMT and HOMA-IR. In a multiple regression analysis, age and VMNR were the most important independent risk factors of an increased carotid IMT. CONCLUSION: This study showed that the role of thigh muscle, as well as that of visceral fat, played a very important role in the occurrence of atherosclerosis. VMNR was found to be an especially important independent factor for an increased carotid IMT.

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  • High fat stores in ectopic compartments in men with newly diagnosed type 2 diabetes: an anthropometric determinant of carotid atherosclerosis and insulin resistance
    S-K Kim, S-W Park, I-J Hwang, Y-K Lee, Y-W Cho
    International Journal of Obesity.2010; 34(1): 105.     CrossRef
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The Relation of Serum Adiponectin and Resistin Concentrations with Metabolic Risk Factors.
Seong Tae Ryu, Seok O Park, Se Hwa Kim
J Korean Endocr Soc. 2005;20(5):444-451.   Published online October 1, 2005
DOI: https://doi.org/10.3803/jkes.2005.20.5.444
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  • 5 Crossref
AbstractAbstract PDF
BACKGROUND
Adiponectin is a fat cell-secreted cytokine, which has been reported to improve insulin sensitivity and have antiatherogenic properties. However, it is still unclear whether resistin plays a significant role in the development of insulin resistance in humans. The aim of this study was to investigate the relationship of the adiponectin and resistin concentrations with insulin resistance, metabolic markers and adiposity in healthy and type 2 diabetic subjects. METHODS: Eighty-three type 2 diabetic and 139 healthy subjects were studied. Blood samples were drawn after fasting to determine the fasting plasma glucose, insulin, resistin, adiponectin, total cholesterol, triglyceride and HDL-cholesterol levels. The subcutaneous and visceral fat areas were measured at the umbilical level using computed tomography. RESULTS: The serum adiponectin concentrations were significantly lower in the diabetic(6.7+/-2.3microgram/mL) than in the obese(8.2+/-2.4microgram/mL, P<0.01) and non-obese subjects(9.9+/-4.5microgram/mL, P<0.01). The serum resistin concentrations were Similar between the non-obese, obese and type 2 diabetic subjects. From a multiple regression analysis, the fasting glucose, HDL-cholesterol and HOMA-IR were found to be independent determinants of the log of the adiponectin level in the diabetes group. In healthy subjects, the gender, BMI, HOMA-IR, visceral fat area and HDL-cholesterol were associated with the log of the adiponectin level. However, the log of the resistin level was not associated with the markers of insulin resistance and obesity. CONCLUSION: This study showed that the serum adiponectin concentration was closely related to the insulin resistance marker in both healthy and type 2 diabetic subjects. However, the resistin concentration was not associated with the markers of insulin resistance and/or obesity.

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  • Effect of Simvastatin on induced apical periodontitis in rats: a tomographic and biochemical analysis
    Jussara Machado PEREIRA, Alex SEMENOFF-SEGUNDO, Natalino Francisco da SILVA, Álvaro Henrique BORGES, Tereza Aparecida Delle Vedove SEMENOFF
    Revista de Odontologia da UNESP.2016; 45(4): 189.     CrossRef
  • Relationships among Serum Adiponectin, Leptin and Vitamin D Concentrations and the Metabolic Syndrome in Farmers
    Seo-Eun Yeon, Hee-Ryoung Son, Jung-Sook Choi, Eun-Kyung Kim
    Korean Journal of Community Nutrition.2014; 19(1): 12.     CrossRef
  • Comparison of Serum Adiponectin Levels According to Body Mass Index and Dietary Behaviors of Female University Students in Seoul
    Mi Joung Kim, Hyun Young Jun, Hye Bog Rha
    Korean Journal of Community Nutrition.2013; 18(4): 354.     CrossRef
  • The Effects of 12-Weeks Intensive Intervention Program on Cardiovascular Risk Factors, Adipocytokines and Nutrients Intakes in Industrial Male Workers
    Kieun Moon, Ill Keun Park, Yeon Sang Jo, Yun Kyun Chang, Yun Mi Paek, Tae In Choi
    The Korean Journal of Nutrition.2011; 44(4): 292.     CrossRef
  • The Effects of D-Chiro-Inositol on Glucose Metabolism in 3T3-L1 Cells
    Kang Seo Park, Jae Min Lee, Bon Jeong Ku, Young Suk Jo, Seong Kyu Lee, Kyung Wan Min, Kyung Ah Han, Hyo Jeong Kim, Hyun Jin Kim
    Korean Diabetes Journal.2008; 32(3): 196.     CrossRef
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Relationship between Serum Adiponectin and Development of the Metabolic Syndrome.
S S Park, K M Choi, S B Kwon, O H Ryu, H J Ryu, S Y Park, H Y Kim, J A Seo, K W Lee, S G Kim, N H Kim, D S Choi, S H Baik
J Korean Endocr Soc. 2004;19(5):492-500.   Published online October 1, 2004
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AbstractAbstract PDF
BACKGROUND
We investigated whether low serum adiponectin concentrations are able to predict the future development of type 2 diabetes and metabolic syndrome. METHODS: This was a prospective cohort study, which included 372 elderly Koreans that participated in the South-West Seoul (SWS) study, conducted in 1999 and 2002 in Seoul, Korea. Fasting and post-challenge 2-hour plasma glucose, body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, lipid profiles, and serum adiponectin data were examined. RESULTS: Adiponectin concentrations obtained in 1999 and 2002 were highly correlated (r = 0.63, P < 0.0001), and the three-year within-person variation of the adiponectin concentrations was not significant (P=0.61). The serum adiponectin level was closely correlated with metabolic syndrome; negatively with BMI, WHR, blood pressure, triglyceride and blood glucose, and positively with HDL cholesterol. Subjects with metabolic syndrome showed lower serum adiponectin concentrations than those without (P < 0.0001). The baseline adiponectin levels were found to be correlated with subsequent changes in the WHR, LDL cholesterol, and fasting and post-load 2h glucose over the 3-year period, after adjusting the baseline values. A multiple logistic regression analysis showed that lower baseline serum adiponectin concentrations were significantly associated with the developments of type 2 diabetes and the metabolic syndrome after adjusting for age, gender, obesity, history of impaired fasting glucose or impaired glucose tolerance, hypertension and dyslipidemia. CONCLUSION: Reduced concentrations of adiponectin were found to be independently associated with increase risks of both type 2 diabetes and metabolic syndrome in elderly Koreans
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Case Report
Diabetic Ketoacidosis in a Patient with Acromegaly.
Eun Hee Koh, Min Kyung Kim, Jin Tae Park, Il Seong Nam-Goong, Joong Yeol Park, Ki Up Lee, Min Seon Kim
J Korean Endocr Soc. 2004;19(4):393-398.   Published online August 1, 2004
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AbstractAbstract PDF
Acromegaly is a chronic, debilitating condition caused by excessive secretion of growth hormone (GH). Impaired glucose tolerance is present in about 20-40% of acromegaly, with diabetes mellitus developing in about 10~15% of patients, but diabetic ketoacidosis is a rare association. Herein is reported a case of diabetic ketoacidosis in a 33 year-old female, with a 4 year history of typical acromegaly features. She presented with severe hyperglycemia and ketoacidosis, but with no other cause for this metabolic derangement. She had elevated plasma GH (50 ng/mL) and IGF-1 (1533 ng/mL) levels, and a pituitary macroadenoma. About 200 units of insulin per day were required for her glycemic control. However, the serum IGF-1 level and daily insulin requirement were significantly tapered after a transsphenoidal adenomectomy and long acting somatostatin analogue treatment. There was a good correlation with the daily insulin requirement and plasma IGF-1 level. This case demonstrates that severe GH excess can cause diabetic ketoacidosis, and that its successful treatment improves glucose metabolism.
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Endocrinol Metab : Endocrinology and Metabolism
© Korean Endocrine Society.
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