Endocrinology and Metabolism

Original Article

Diabetes, obesity and metabolism
Impact of Chronic Kidney Disease and Gout on End-Stage Renal Disease in Type 2 Diabetes: Population-Based Cohort Study: Inha Jung, Da Young Lee, Seung Min Chung, So Young Park, Ji Hee Yu, Jun Sung Moon, Ji A Seo, Kyungdo Han, Nan Hee Kim; Endocrinol Metab. 2024;39(5):748-757. Published online August 30, 2024; DOI: https://doi.org/10.3803/EnM.2024.2020

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Abstract PDF Supplementary Material PubReader ePub: Background
We examined the impact of gout on the end-stage renal disease (ESRD) risk in patients with type 2 diabetes mellitus (T2DM) and determined whether this association differs according to chronic kidney disease (CKD) status.
Methods
Using the Korean National Health Insurance Service, this nationwide cohort study enrolled 847,884 patients with T2DM who underwent health checkups in 2009. Based on the presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m²) and gout (two outpatient visits or one hospitalization within 5 years), patients were classified into four groups: CKD⁻Gout⁻, CKD⁻ Gout⁺, CKD⁺Gout⁻, and CKD⁺Gout⁺. Patients with incident ESRD were followed up until December 2018.
Results
Among 847,884 patients, 11,825 (1.4%) experienced progression to ESRD. ESRD incidence increased in the following order: 0.77 per 1,000 person-years (PY) in the CKD⁻Gout⁻ group, 1.34/1,000 PY in the CKD⁻Gout⁺ group, 8.20/1,000 PY in the CKD⁺Gout⁻ group, and 23.06/1,000 PY in the CKD⁺Gout⁺ group. The presence of gout modified the ESRD risk in a status-dependent manner. Hazard ratios (HR) were 1.49 (95% confidence interval [CI], 1.32 to 1.69) and 2.24 (95% CI, 2.09 to 2.40) in patients without and with CKD, respectively, indicating a significant interaction (P<0.0001). The CKD⁺Gout⁺ group had a markedly higher risk of developing ESRD (HR, 18.9; 95% CI, 17.58 to 20.32) than the reference group (CKD⁻Gout⁻).
Conclusion
Gout substantially enhances the risk of ESRD, even in the absence of CKD. Concurrent CKD and gout synergistically increase the risk of ESRD. Therefore, physicians should carefully screen for hyperuricemia to prevent progression to ESRD.

Brief Report

Diabetes, obesity and metabolism
Performance of Simple Fibrosis Score in Non-Alcoholic Fatty Liver Disease with and without Type 2 Diabetes: Seung Min Chung, Min Kyu Kang, Jun Sung Moon, Jung Gil Park; Endocrinol Metab. 2023;38(2):277-281. Published online March 13, 2023; DOI: https://doi.org/10.3803/EnM.2022.1635

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This cross-sectional study enrolled 267 patients with metabolic risk factors and established non-alcoholic fatty liver disease in the prospective cohort. The performance of fibrosis-4 (FIB-4) score (≥1.3) to diagnose advanced fibrosis using transient elastography (liver stiffness measurement [LSM] ≥8 kPa) was analyzed. Comparing patients with type 2 diabetes (T2D, n=87) and without (n=180), not FIB-4, but LSM was significantly higher in T2D (P=0.026). The prevalence of advanced fibrosis was 17.2% in T2D and 12.8% in non-T2D. FIB-4 exhibited higher proportion of false negatives in T2D patients (10.9%) than those without (5.2%). The diagnostic performance of FIB-4 was suboptimal in T2D (area under curve [AUC], 0.653; 95% confidence interval [CI], 0.462 to 0.844) compared to that in non-T2D (AUC, 0.826; 95% CI, 0.724 to 0.927). In conclusion, patients with T2D might be beneficial to conduct transient elastography without screening to avoid missing advanced fibrosis.

Citations

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Eun-Jung Rhee
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Inha Jung, Dae-Jeong Koo, Won-Young Lee
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Epidemiology, screening, and co-management of type 2 diabetes mellitus and metabolic dysfunction–associated steatotic liver disease
Xiaolong Qi, Jie Li, Cyrielle Caussy, Gao-Jun Teng, Rohit Loomba
Hepatology.2024;[Epub] CrossRef
Prevalence of High and Moderate Risk of Liver Fibrosis Among Patients With Diabetes at a Noncommunicable Diseases (NCD) Clinic in a Primary Healthcare Center in Northern India
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Special Article

Miscellaneous
Immune Checkpoint Inhibitors and Endocrine Disorders: A Position Statement from the Korean Endocrine Society: Hyemi Kwon, Eun Roh, Chang Ho Ahn, Hee Kyung Kim, Cheol Ryong Ku, Kyong Yeun Jung, Ju Hee Lee, Eun Heui Kim, Sunghwan Suh, Sangmo Hong, Jeonghoon Ha, Jun Sung Moon, Jin Hwa Kim, Mi-kyung Kim, The Committee of Clinical Practice Guideline of the Korean Endocrine Society; Endocrinol Metab. 2022;37(6):839-850. Published online December 26, 2022; DOI: https://doi.org/10.3803/EnM.2022.1627

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Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

Citations

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Patterns of hormonal changes in hypophysitis by immune checkpoint inhibitor
Hyunji Sang, Yun Kyung Cho, Sang-hyeok Go, Hwa Jung Kim, Eun Hee Koh
The Korean Journal of Internal Medicine.2024; 39(5): 801. CrossRef
Pembrolizumab plus lenvatinib for radically unresectable or metastatic renal cell carcinoma in the Japanese population
Ryo Fujiwara, Takeshi yuasa, kenichi kobayashi, tetsuya yoshida, susumu kageyama
Expert Review of Anticancer Therapy.2023; 23(5): 461. CrossRef
Incidence of Endocrine-Related Dysfunction in Patients Treated with New Immune Checkpoint Inhibitors: A Meta-Analysis and Comprehensive Review
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Endocrinology and Metabolism.2023; 38(6): 750. CrossRef

Original Article

Diabetes, Obesity and Metabolism
High Fibrosis-4 Index Is Related with Worse Clinical Outcome in Patients with Coronavirus Disease 2019 and Diabetes Mellitus: A Multicenter Observational Study: Sung-Woo Kim, Jae-Han Jeon, Jun Sung Moon, Mi Kyung Kim; Endocrinol Metab. 2021;36(4):800-809. Published online August 20, 2021; DOI: https://doi.org/10.3803/EnM.2021.1040

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Background
Based on recent evidence on the importance of the presence of diabetes mellitus (DM) and fibrosis-4 (FIB-4) index in coronavirus disease 2019 (COVID-19) mortality, we analyzed whether these factors could additively predict such mortality.
Methods
This multicenter observational study included 1,019 adult inpatients admitted to university hospitals in Daegu. The demographic and laboratory findings, mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM and/or a high FIB-4 index. The mortality risk and corresponding hazard ratio (HR) were analyzed using the Kaplan-Meier method and Cox proportional hazard models.
Results
The patients with DM (n=217) exhibited significantly higher FIB-4 index and mortality compared to those without DM. Although DM (HR, 2.66; 95% confidence interval [CI], 1.63 to 4.33) and a high FIB-4 index (HR, 4.20; 95% CI, 2.21 to 7.99) were separately identified as risk factors for COVID-19 mortality, the patients with both DM and high FIB-4 index had a significantly higher mortality (HR, 9.54; 95% CI, 4.11 to 22.15). Higher FIB-4 indices were associated with higher mortality regardless of DM. A high FIB-4 index with DM was more significantly associated with a severe clinical course with mortality (odds ratio, 11.24; 95% CI, 5.90 to 21.41) than a low FIB-4 index without DM, followed by a high FIB-4 index alone and DM alone. The duration of quarantine and hospital stay also tended to be longer in those with both DM and high FIB-4 index.
Conclusion
Both DM and high FIB-4 index are independent and additive risk factors for COVID-19 mortality.

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Special Article

Miscellaneous
COVID-19 Vaccination for Endocrine Patients: A Position Statement from the Korean Endocrine Society: Cheol Ryong Ku, Kyong Yeun Jung, Chang Ho Ahn, Jun Sung Moon, Ju Hee Lee, Eun Heui Kim, Hyemi Kwon, Hee Kyung Kim, Sunghwan Suh, Sangmo Hong, Jeonghoon Ha, Eun Roh, Jin Hwa Kim, Mi-kyung Kim, the Committee of Clinical Practice Guideline of the Korean Endocrine Society; Endocrinol Metab. 2021;36(4):757-765. Published online August 17, 2021; DOI: https://doi.org/10.3803/EnM.2021.404

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Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients’ health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.

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Original Articles

Clinical Study
Fasting Plasma Glucose Level Independently Predicts the Mortality of Patients with Coronavirus Disease 2019 Infection: A Multicenter, Retrospective Cohort Study: Min Cheol Chang, Jong-Moon Hwang, Jae-Han Jeon, Sang Gyu Kwak, Donghwi Park, Jun Sung Moon; Endocrinol Metab. 2020;35(3):595-601. Published online August 26, 2020; DOI: https://doi.org/10.3803/EnM.2020.719

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Background
Coronavirus disease 2019 (COVID-19) has become a global pandemic, which prompts a consensus for the necessity to seek risk factors for this critical disease. Risk factors affecting mortality of the disease remain elusive. Diabetes and hyperglycemia are known to negatively affect a host’s antiviral immunity. We evaluated the relationship between a history of diabetes, fasting plasma glucose (FPG) levels and mortality among severely ill patients with COVID-19.
Methods
This was a retrospective cohort study that assessed 106 adult inpatients (aged ≥18 years) from two tertiary hospitals in Daegu, South Korea. The participants were transferred to tertiary hospitals because their medical condition required immediate intensive care. The demographic and laboratory data were compared between COVID-19 patients who survived and those who did not.
Results
Compared with the survivor group, age, and the proportions of diabetes, chronic lung disease and FPG were significantly higher in the deceased group. In the Cox proportional hazards regression model for survival analysis, FPG level and age were identified as significant predictors of mortality (P<0.05). The threshold values for predicting high mortality were age >68 years and FPG of 168 mg/dL, respectively. Among those without diabetes, high FPG remained a significant predictor of mortality (P<0.04).
Conclusion
High FPG levels significantly predicted mortality in COVID-19, regardless of a known history of diabetes. These results suggest intensive monitoring should be provided to COVID-19 patients who have a high FPG level.

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Testing AI predictions that hyperglycemia-induced non-enzymatic glycation of immune system proteins impairs diabetic immunity
Thomas Turkette, Andrew Decker, Robert Root-Bernstein
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Fasting Plasma Glucose Levels at the Time of Admission Predict 90-Day Mortality in Patients with Viral Pneumonia. A Prospective Study
Jie Xu, Jianyu Zhao, Liyuan Wu, Xinxin Lu
Experimental and Clinical Endocrinology & Diabetes.2023; 131(05): 290. CrossRef
Influence of Fasting Plasma Glucose Level on Admission of COVID-19 Patients: A Retrospective Study
Yingying Zhao, Huichun Xing, Yong Xu
Journal of Diabetes Research.2022; 2022: 1. CrossRef
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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

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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.

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Miriam Beatrís Reckziegel, Patrik Nepomuceno, Tania Machado, Jane Dagmar Pollo Renner, Hildegard Hedwig Pohl, Carlos Alberto Nogueira-de-Almeida, Elza Daniel de Mello
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Obesity and Metabolism
Variation in Serum Creatinine Level Is Correlated to Risk of Type 2 Diabetes: Jun Sung Moon, Ji Eun Lee, Ji Sung Yoon; Endocrinol Metab. 2013;28(3):207-213. Published online September 13, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.3.207

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Abstract PDF PubReader

Background

Skeletal muscle is well established as a major target organ of insulin action, and is associated with the pathogenesis of type 2 diabetes. Therefore, we attempted to determine whether a variation in serum creatinine is related to the development of type 2 diabetes and other risk factors for diabetes.

Methods

A total of 2,676 nondiabetic subjects with stable and normal renal function (estimated glomerular filtration rate >60 mL/min/1.73 m²) were followed up for approximately 4.5 years. New onset diabetes was defined as fasting plasma glucose (FPG) ≥7.0 mmol/L, glycated hemoglobin (HbA1c) ≥6.5%, or subjects taking antidiabetic agents. Variation of serum creatinine (ΔCre) was defined as a difference between follow-up and baseline creatinine. In subgroup analysis, body composition was examined by bioelectric impedance analysis method.

Results

A total of 106 subjects were diagnosed with new-onset diabetes during the follow-up period. Baseline serum creatinine was not different between the new-onset diabetes and no diabetes groups. Negative ΔCre (ΔCre <0) showed an association with increased risk of type 2 diabetes after adjusting for age, sex, body mass index, systolic blood pressure, FPG, HbA1c, triglyceride, high density lipoprotein cholesterol, and γ-glutamyl transpeptidase (odds ratio, 1.885; 95% confidence interval, 1.127 to 3.153). Serum creatinine level demonstrated positive correlation with muscle mass and negative correlation with percentage of body fat in body composition analysis.

Conclusion

Serum creatinine reflected body muscle mass and the decrease of serum creatinine might be regarded as a risk factor for type 2 diabetes.

Citations

Citations to this article as recorded by

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