Diabetes & Metabolism Journal

Volume 46(4); July 2022

Reviews

Drug/Regimen
New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins: Kyuho Kim, Henry N. Ginsberg, Sung Hee Choi; Diabetes Metab J. 2022;46(4):517-532. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0198; Correction in: Diabetes Metab J 2022;46(5):817

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Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance in phase 2 trial, but the large clinical phase 3 trial (PROMINENT) was recently stopped for futility based on a late interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.

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Pathophysiology
Endoplasmic Reticulum Stress and Dysregulated Autophagy in Human Pancreatic Beta Cells: Seoil Moon, Hye Seung Jung; Diabetes Metab J. 2022;46(4):533-542. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0070

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Pancreatic beta cell homeostasis is crucial for the synthesis and secretion of insulin; disruption of homeostasis causes diabetes, and is a treatment target. Adaptation to endoplasmic reticulum (ER) stress through the unfolded protein response (UPR) and adequate regulation of autophagy, which are closely linked, play essential roles in this homeostasis. In diabetes, the UPR and autophagy are dysregulated, which leads to beta cell failure and death. Various studies have explored methods to preserve pancreatic beta cell function and mass by relieving ER stress and regulating autophagic activity. To promote clinical translation of these research results to potential therapeutics for diabetes, we summarize the current knowledge on ER stress and autophagy in human insulin-secreting cells.

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Pathophysiology
Renoprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors: Focusing on Renal Hemodynamics: Nam Hoon Kim, Nan Hee Kim; Diabetes Metab J. 2022;46(4):543-551. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0209

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Diabetic kidney disease (DKD) is a prevalent renal complication of diabetes mellitus that ultimately develops into end-stage kidney disease (ESKD) when not managed appropriately. Substantial risk of ESKD remains even with intensive management of hyperglycemia and risk factors of DKD and timely use of renin-angiotensin-aldosterone inhibitors. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce hyperglycemia primarily by inhibiting glucose and sodium reabsorption in the renal proximal tubule. Currently, their effects expand to prevent or delay cardiovascular and renal adverse events, even in those without diabetes. In dedicated renal outcome trials, SGLT2 inhibitors significantly reduced the risk of composite renal adverse events, including the development of ESKD or renal replacement therapy, which led to the positioning of SGLT2 inhibitors as the mainstay of chronic kidney disease management. Multiple mechanisms of action of SGLT2 inhibitors, including hemodynamic, metabolic, and anti-inflammatory effects, have been proposed. Restoration of tubuloglomerular feedback is a plausible explanation for the alteration in renal hemodynamics induced by SGLT2 inhibition and for the associated renal benefit. This review discusses the clinical rationale and mechanism related to the protection SGLT2 inhibitors exert on the kidney, focusing on renal hemodynamic effects.

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Others
Current Trends of Big Data Research Using the Korean National Health Information Database: Mee Kyoung Kim, Kyungdo Han, Seung-Hwan Lee; Diabetes Metab J. 2022;46(4):552-563. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0193

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Recently, medical research using big data has become very popular, and its value has become increasingly recognized. The Korean National Health Information Database (NHID) is representative of big data that combines information obtained from the National Health Insurance Service collected for claims and reimbursement of health care services and results obtained from general health examinations provided to all Korean adults. This database has several strengths and limitations. Given the large size, various laboratory data, and questionnaires obtained from medical check-ups, their longitudinal nature, and long-term accumulation of data since 2002, carefully designed studies may provide valuable information that is difficult to obtain from other forms of research. However, consideration of possible bias and careful interpretation when defining causal relationships is also important because the data were not collected for research purposes. After the NHID became publicly available, research and publications based on this database have increased explosively, especially in the field of diabetes and metabolism. This article reviews the history, structure, and characteristics of the Korean NHID. Recent trends in big data research using this database, commonly used operational diagnosis, and representative studies have been introduced. We expect further progress and expansion of big data research using the Korean NHID.

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Editorial

Beyond Liver Disease: Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Kidney Disease: Eugene Han; Diabetes Metab J. 2022;46(4):564-566. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0203

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Original Articles

Cardiovascular Risk/Epidemiology
Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitor and Thiazolidinedione Treatment on Risk of Stroke among Patients with Type 2 Diabetes Mellitus: Seung Eun Lee, Hyewon Nam, Han Seok Choi, Hoseob Kim, Dae-Sung Kyoung, Kyoung-Ah Kim; Diabetes Metab J. 2022;46(4):567-577. Published online February 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0160

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Background
Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients.
Methods
Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF).
Results
After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease.
Conclusion
In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.

Citations

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Similar incidence of stroke with SGLT2 inhibitors and GLP-1 receptor agonists in real-world cohort studies among patients with type 2 diabetes
André J. Scheen
Diabetes Epidemiology and Management.2024; 13: 100179. CrossRef
Diabetes and Stroke: Impact of Novel Therapies for the Treatment of Type 2 Diabetes Mellitus
Inês Henriques Vieira, Tânia Santos Carvalho, Joana Saraiva, Leonor Gomes, Isabel Paiva
Biomedicines.2024; 12(5): 1102. CrossRef
Key results from observational studies and real‐world evidence of sodium‐glucose cotransporter‐2 inhibitor effectiveness and safety in reducing cardio‐renal risk
Thomas Nyström
Diabetes, Obesity and Metabolism.2024; 26(S5): 35. CrossRef
Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults
Jung-Joon Cha, Soon Jun Hong, Subin Lim, Ju Hyeon Kim, Hyung Joon Joo, Jae Hyoung Park, Cheol Woong Yu, Do-Sun Lim, Jang Young Kim, Jin-Ok Jeong, Jeong-Hun Shin, Chi Young Shim, Jong-Young Lee, Young-Hyo Lim, Sung Ha Park, Eun Joo Cho, Hasung Kim, Jungkuk
Korean Circulation Journal.2024; 54(9): 534. CrossRef
Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study
Joonsang Yoo, Jimin Jeon, Minyoul Baik, Jinkwon Kim
Cardiovascular Diabetology.2023;[Epub] CrossRef
Do SGLT2 inhibitors and GLP-1 receptor agonists modulate differently the risk of stroke ? Discordance between randomised controlled trials and observational studies
André J. Scheen
Diabetes & Metabolism.2023; 49(5): 101474. CrossRef

Metabolic Risk/Epidemiology
Reproductive Life Span and Severe Hypoglycemia Risk in Postmenopausal Women with Type 2 Diabetes Mellitus: Soyeon Kang, Yong-Moon Park, Dong Jin Kwon, Youn-Jee Chung, Jeong Namkung, Kyungdo Han, Seung-Hyun Ko; Diabetes Metab J. 2022;46(4):578-591. Published online January 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0135

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Background
Estrogen promotes glucose homeostasis, enhances insulin sensitivity, and maintains counterregulatory responses in recurrent hypoglycemia in women of reproductive age. Postmenopausal women with type 2 diabetes mellitus (T2DM) might be more vulnerable to severe hypoglycemia (SH) events. However, the relationship between reproductive factors and SH occurrence in T2DM remains unelucidated.
Methods
This study included data on 181,263 women with postmenopausal T2DM who participated in a national health screening program from January 1 to December 31, 2009, obtained using the Korean National Health Insurance System database. Outcome data were obtained until December 31, 2018. Associations between reproductive factors and SH incidence were assessed using Cox proportional hazards models.
Results
During the mean follow-up of 7.9 years, 11,279 (6.22%) postmenopausal women with T2DM experienced SH episodes. A longer reproductive life span (RLS) (≥40 years) was associated with a lower SH risk compared to a shorter RLS (<30 years) (adjusted hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.69 to 0.80; P for trend <0.001) after multivariable adjustment. SH risk decreased with every 5-year increment of RLS (with <30 years as a reference [adjusted HR, 0.91; 95% CI, 0.86 to 0.95; P=0.0001 for 30−34 years], [adjusted HR, 0.80; 95% CI, 0.76 to 0.84; P<0.001 for 35−39 years], [adjusted HR, 0.74; 95% CI, 0.68 to 0.81; P<0.001 for ≥40 years]). The use of hormone replacement therapy (HRT) was associated with a lower SH risk than HRT nonuse.
Conclusion
Extended exposure to endogenous ovarian hormone during lifetime may decrease the number of SH events in women with T2DM after menopause.

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Association between serum copper level and reproductive health of Women in the United States: a cross-sectional study
Yi Yuan, Tong-Yu Peng, Guang-Yuan Yu, Zhao Zou, Meng-Ze Wu, Ruofei Zhu, Shuang Wu, Zi Lv, Su-Xin Luo
International Journal of Environmental Health Research.2024; 34(6): 2441. CrossRef
Defining Continuous Glucose Monitor Time in Range in a Large, Community-Based Cohort Without Diabetes
Nicole L Spartano, Naznin Sultana, Honghuang Lin, Huimin Cheng, Sophia Lu, David Fei, Joanne M Murabito, Maura E Walker, Howard A Wolpert, Devin W Steenkamp
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Metabolic Risk/Epidemiology
Effect of Low-Dose Persistent Organic Pollutants on Mitochondrial Function: Human and in Vitro Evidence: Se-A Kim, Hoyul Lee, Sung-Mi Park, Mi-Jin Kim, Yu-Mi Lee, Young-Ran Yoon, Hyun-Kyung Lee, Hyo-Bang Moon, In-Kyu Lee, Duk-Hee Lee; Diabetes Metab J. 2022;46(4):592-604. Published online January 26, 2022; DOI: https://doi.org/10.4093/dmj.2021.0132

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Background
Chronic exposure to low-dose persistent organic pollutants (POPs) can induce mitochondrial dysfunction. This study evaluated the association between serum POP concentrations and oxygen consumption rate (OCR) as a marker of mitochondrial function in humans and in vitro cells.
Methods
Serum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in 323 adults. The OCRs of platelets and peripheral blood mononuclear cells (PBMCs) were assessed in 20 mL of fresh blood using a Seahorse XF analyzer. Additionally, the in vitro effects of Arochlor-1254, β-hexachlorocyclohexane, and p,p´-dichlorodiphenyltrichloroethane at concentrations of 0.1 pM to 100 nM were evaluated in human platelets, human PBMCs, and Jurkat T-cells.
Results
The association between serum POP concentrations and OCR differed depending on the cell type. As serum OCP concentrations increased, basal platelet OCR levels decreased significantly; according to the OCP quintiles of summary measure, they were 8.6, 9.6, 8.2, 8.0, and 7.1 pmol/min/μg (P trend=0.005). Notably, the basal PBMC OCR levels decreased remarkably as the serum PCB concentration increased. PBMC OCR levels were 46.5, 34.3, 29.1, 16.5, and 13.1 pmol/min/μg according to the PCB quintiles of summary measure (P trend <0.001), and this inverse association was consistently observed in all subgroups stratified by age, sex, obesity, type 2 diabetes mellitus, and hypertension, respectively. In vitro experimental studies have also demonstrated that chronic exposure to low-dose POPs could decrease OCR levels.
Conclusion
The findings from human and in vitro studies suggest that chronic exposure to low-dose POPs can induce mitochondrial dysfunction by impairing oxidative phosphorylation.

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Persistent Organic Pollutants released from decomposed adipose tissue affect mitochondrial enzyme function in the brain and eyes other than the liver
Dongshin Yang, Eun Ko, Hwayeon Lim, Hyojin Lee, Kitae Kim, Moonsung Choi, Sooim Shin
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Anita A. Waye, Elvis Ticiani, Zinat Sharmin, Vanessa Perez Silos, Thilini Perera, Alex Tu, Irina A. Buhimschi, Carlos A. Murga-Zamalloa, Ying S. Hu, Almudena Veiga-Lopez
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Can lipophilic pollutants in adipose tissue explain weight change‐related risk in type 2 diabetes mellitus?
Duk‐Hee Lee, In‐Kyu Lee
Journal of Diabetes Investigation.2023; 14(4): 528. CrossRef
Mitochondrial and metabolic features of salugenesis and the healing cycle
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Metabolic Risk/Epidemiology
Effect of Different Types of Diagnostic Criteria for Gestational Diabetes Mellitus on Adverse Neonatal Outcomes: A Systematic Review, Meta-Analysis, and Meta-Regression: Fahimeh Ramezani Tehrani, Marzieh Saei Ghare Naz, Razieh Bidhendi-Yarandi, Samira Behboudi-Gandevani; Diabetes Metab J. 2022;46(4):605-619. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0178

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Background
Evidence supporting various diagnostic criteria for diagnose gestational diabetes mellitus (GDM) are consensus-based, needs for additional evidence related to outcomes. Therefore, the aim of this systematic-review and meta-analysis was to assess the impact of different GDM diagnostic-criteria on the risk of adverse-neonatal-outcomes.
Methods
Electronic databases including Scopus, PubMed, and Web of Sciences were searched to retrieve English original, population-based studies with the universal GDM screening approach, up to January-2020. GDM diagnostic criteria were classified in seven groups and International Association of the Diabetes and Pregnancy Study Groups (IADPSG) was considered as reference one. We used the Mantel–Haenszel method to calculate the pooled odds of events. The possibility of publication bias was examined by Begg’s test.
Results
A total of 55 population-based studies consisting of 1,604,391 pregnant women with GDM and 7,770,855 non-GDM counterparts were included. Results showed that in all diagnostic-criteria subgroups, the risk of adverse neonatal outcomes including macrosomia, hyperbilirubinemia, respiratory distress syndrome, neonatal hypoglycemia, neonatal intensive care unit admission, preterm birth, and birth-trauma were significantly higher than the non-GDM counterparts were significantly higher than non-GDM counterparts. Meta-regression analysis revealed that the magnitude of neonatal risks in all diagnostic-criteria subgroups are similar.
Conclusion
Our results showed that the risk of adverse-neonatal-outcome increased among women with GDM, but the magnitude of risk was not different among those women who were diagnosed through more or less intensive strategies. These findings may help health-care-providers and policy-makers to select the most cost-effective approach for the screening of GDM among pregnant women.

Citations

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Hyperglycemia in pregnancy did not worsen the short-term outcomes of very preterm infants: a propensity score matching study
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Cintia Gomes, Itamar D. Futterman, Olivia Sher, Bracha Gluck, Teresa A. Hillier, Fahimeh Ramezani Tehrani, Nadim Chaarani, Nelli Fisher, Vincenzo Berghella, Rodney A. McLaren
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Fahimeh Ramezani Tehrani, Ali Sheidaei, Maryam Rahmati, Farshad Farzadfar, Mahsa Noroozzadeh, Farhad Hosseinpanah, Mehrandokht Abedini, Farzad Hadaegh, Majid Valizadeh, Farahnaz Torkestani, Davood Khalili, Faegheh Firouzi, Masoud Solaymani-Dodaran, Afshin
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Complications
Prevalence of Diabetic Retinopathy in Undiagnosed Diabetic Patients: A Nationwide Population-Based Study: Han Na Jang, Min Kyong Moon, Bo Kyung Koo; Diabetes Metab J. 2022;46(4):620-629. Published online February 23, 2022; DOI: https://doi.org/10.4093/dmj.2021.0099

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Background
We investigated the prevalence of diabetic retinopathy (DR) in patients with undiagnosed diabetes through a nationwide survey, compared to those with known diabetes.
Methods
Among the participants of the Korean National Health and Nutrition Examination Surveys (KNHANES) from 2017 to 2018, individuals aged ≥40 years with diabetes and fundus exam results were enrolled. Sampling weights were applied to represent the entire Korean population. Newly detected diabetes patients through KNHANES were classified under “undiagnosed diabetes.”
Results
Among a total of 9,108 participants aged ≥40 years, 951 were selected for analysis. Of them, 31.3% (standard error, ±2.0%) were classified under “undiagnosed diabetes.” The prevalence of DR in patients with known and undiagnosed diabetes was 24.5%±2.0% and 10.7%±2.2%, respectively (P<0.001). The DR prevalence increased with rising glycosylated hemoglobin (HbA1c) levels in patients with known and undiagnosed diabetes (P for trend=0.001 in both). Among those with undiagnosed diabetes, the prevalence of DR was 6.9%±2.1%, 8.0%±3.4%, 5.6%±5.7%, 16.7%±9.4%, and 42.6%±14.8% for HbA1c levels of <7.0%, 7.0%–7.9%, 8.0%–8.9%, 9.0%–9.9%, and ≥10.0% respectively. There was no difference in the prevalence of hypertension, dyslipidemia, hypertriglyceridemia, or obesity according to the presence or absence of DR.
Conclusion
About one-third of patients with diabetes were unaware of their diabetes, and 10% of them have already developed DR. Considering increasing the prevalence of DR according to HbA1c level was found in patients with undiagnosed diabetes like those with known diabetes, screening and early detection of diabetes and DR are important.

Citations

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Risk factors of peripheral occlusive arterial disease in patients with diabetic retinopathy due to type 2 diabetes
Milos Maksimovic
Srpski arhiv za celokupno lekarstvo.2024; 152(1-2): 50. CrossRef
Gene Expression Analysis in T2DM and Its Associated Microvascular Diabetic Complications: Focus on Risk Factor and RAAS Pathway
Laxmipriya Jena, Prabhsimran Kaur, Tashvinder Singh, Kangan Sharma, Sushil Kotru, Anjana Munshi
Molecular Neurobiology.2024;[Epub] CrossRef
Trends and Barriers in Diabetic Retinopathy Screening: Korea National Health and Nutritional Examination Survey 2016–2021
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Jonghwa Jin, Hyein Woo, Youngeun Jang, Won-Ki Lee, Jung-Guk Kim, In-Kyu Lee, Keun-Gyu Park, Yeon-Kyung Choi
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Archives of Osteoporosis.2023;[Epub] CrossRef

Complications
Advanced Liver Fibrosis Is Associated with Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease: Da Hea Seo, Young Ju Suh, Yongin Cho, Seong Hee Ahn, Seongha Seo, Seongbin Hong, Yong-ho Lee, Young Ju Choi, Eunjig Lee, So Hun Kim; Diabetes Metab J. 2022;46(4):630-639. Published online January 26, 2022; DOI: https://doi.org/10.4093/dmj.2021.0130

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Background
Nonalcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). However, the causal relationship between NAFLD and CKD is uncertain, particularly in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the association between the presence and severity of NAFLD and incident CKD in patients with T2DM.
Methods
In this longitudinal cohort study of patients with T2DM, 3,188 patients with preserved renal function were followed up for the occurrence of incident CKD. NAFLD was defined as the presence of hepatic steatosis on ultrasonography, without any other causes of chronic liver disease. Advanced liver fibrosis of NAFLD was defined as a fibrosis-4 index ≥2.67. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m².
Results
At baseline, 1,729 (54.2%) patients had NAFLD, of whom 94 (5.4%) had advanced liver fibrosis. During the follow-up of 8.3±3.6 years, 472 (14.8%) patients developed incident CKD: 220 (15.1%) in the non-NAFLD group, 231 (14.1%) in the NAFLD without advanced fibrosis group and 28 (31.1%) in the NAFLD with advanced fibrosis group. There was no increased risk of incident CKD in the NAFLD group compared to the non-NAFLD group (P=0.435). However, among patients with NAFLD, advanced liver fibrosis was associated with an increased risk of CKD (adjusted hazard ratio, 1.75; 95% confidence interval, 1.15 to 2.66; P=0.009).
Conclusion
Advanced liver fibrosis in patients with NAFLD is independently associated with an increased risk of incident CKD in patients with T2DM.

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Salvador Benlloch, Francesc Moncho, Jose Luis Górriz
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Longitudinal Outcomes Associated With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Meta-analysis of 129 Studies
Kai En Chan, Elden Yen Hng Ong, Charlotte Hui Chung, Christen En Ya Ong, Benjamin Koh, Darren Jun Hao Tan, Wen Hui Lim, Jie Ning Yong, Jieling Xiao, Zhen Yu Wong, Nicholas Syn, Apichat Kaewdech, Margaret Teng, Jiong-Wei Wang, Nicholas Chew, Dan Yock Young
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Association of NAFLD/NASH, and MAFLD/MASLD with chronic kidney disease: an updated narrative review
Amedeo Lonardo
Metabolism and Target Organ Damage.2024;[Epub] CrossRef
Targeting metabolic-associated fatty liver disease in diabetic kidney disease: A call to action
Salvador Benlloch, Francesc Moncho, Jose Luis Górriz
Nefrología (English Edition).2024; 44(2): 129. CrossRef
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
Impact of dietary fiber intake on non-alcoholic fatty liver disease risk in Korean patients with obesity and type 2 diabetes mellitus
Ji-Sook Park, Hina Akbar, Young-Seol Kim, Jung-Eun Yim
Journal of Nutrition and Health.2024; 57(3): 282. CrossRef
Digestive system diseases and a chronic kidney disease — the two sides of the healthcare global problems
A.M. Osadchuk, I.D. Loranskaya, M.A. Osadchuk
Russian Journal of Preventive Medicine.2024; 27(7): 108. CrossRef
MAFLD and NAFLD in the prediction of incident chronic kidney disease
So Yoon Kwon, Jiyun Park, So Hee Park, You-Bin Lee, Gyuri Kim, Kyu Yeon Hur, Janghyun Koh, Jae Hwan Jee, Jae Hyeon Kim, Mira Kang, Sang-Man Jin
Scientific Reports.2023;[Epub] CrossRef
Associations of non-invasive indices of liver steatosis and fibrosis with progressive kidney impairment in adults with type 2 diabetes
Mei Chung Moh, Sharon Li Ting Pek, Kenny Ching Pan Sze, Serena Low, Tavintharan Subramaniam, Keven Ang, Wern Ee Tang, Simon Biing Ming Lee, Chee Fang Sum, Su Chi Lim
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Rudi Supriyadi, Theo Audi Yanto, Timotius Ivan Hariyanto, Ketut Suastika
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Therese Adrian, Mads Hornum, Filip Krag Knop, Karl Bang Christensen, Thomas Almdal, Peter Rossing, Lisa Í Lídaa, Niels Søndergaard Heinrich, Vincent Oltman Boer, Anouk Marsman, Esben Thade Petersen, Hartwig Roman Siebner, Bo Feldt-Rasmussen
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Complications
Fatty Acid-Binding Protein 4 in Patients with and without Diabetic Retinopathy: Ping Huang, Xiaoqin Zhao, Yi Sun, Xinlei Wang, Rong Ouyang, Yanqiu Jiang, Xiaoquan Zhang, Renyue Hu, Zhuqi Tang, Yunjuan Gu; Diabetes Metab J. 2022;46(4):640-649. Published online April 28, 2022; DOI: https://doi.org/10.4093/dmj.2021.0195

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Background
Fatty acid-binding protein 4 (FABP4) has been demonstrated to be a predictor of early diabetic nephropathy. However, little is known about the relationship between FABP4 and diabetic retinopathy (DR). This study explored the value of FABP4 as a biomarker of DR in patients with type 2 diabetes mellitus (T2DM).
Methods
A total of 238 subjects were enrolled, including 20 healthy controls and 218 T2DM patients. Serum FABP4 levels were measured using a sandwich enzyme-linked immunosorbent assay. The grade of DR was determined using fundus fluorescence angiography. Based on the international classification of DR, all T2DM patients were classified into the following three subgroups: non-DR group, non-proliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. Multivariate logistic regression analyses were employed to assess the correlation between FABP4 levels and DR severity.
Results
FABP4 correlated positively with DR severity (r=0.225, P=0.001). Receiver operating characteristic curve analysis was used to assess the diagnostic potential of FABP4 in identifying DR, with an area under the curve of 0.624 (37% sensitivity, 83.6% specificity) and an optimum cut-off value of 76.4 μg/L. Multivariate logistic regression model including FABP4 as a categorized binary variable using the cut-off value of 76.4 μg/L showed that the concentration of FABP4 above the cut-off value increased the risk of NPDR (odds ratio [OR], 3.231; 95% confidence interval [CI], 1.574 to 6.632; P=0.001) and PDR (OR, 3.689; 95% CI, 1.306 to 10.424; P=0.014).
Conclusion
FABP4 may be used as a serum biomarker for the diagnosis of DR.

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Circulating AFABP, FGF21, and PEDF Levels as Prognostic Biomarkers of Sight-threatening Diabetic Retinopathy
Chi-Ho Lee, David Tak-Wai Lui, Chloe Yu-Yan Cheung, Carol Ho-Yi Fong, Michele Mae-Ann Yuen, Yu-Cho Woo, Wing-Sun Chow, Ian Yat-Hin Wong, Aimin Xu, Karen Siu-Ling Lam
The Journal of Clinical Endocrinology & Metabolism.2023; 108(9): e799. CrossRef
A Prediction Model for Sight-Threatening Diabetic Retinopathy Based on Plasma Adipokines among Patients with Mild Diabetic Retinopathy
Yaxin An, Bin Cao, Kun Li, Yongsong Xu, Wenying Zhao, Dong Zhao, Jing Ke, Takayuki Masaki
Journal of Diabetes Research.2023; 2023: 1. CrossRef

Others
Development of Various Diabetes Prediction Models Using Machine Learning Techniques: Juyoung Shin, Jaewon Kim, Chanjung Lee, Joon Young Yoon, Seyeon Kim, Seungjae Song, Hun-Sung Kim; Diabetes Metab J. 2022;46(4):650-657. Published online March 11, 2022; DOI: https://doi.org/10.4093/dmj.2021.0115

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Background
There are many models for predicting diabetes mellitus (DM), but their clinical implication remains vague. Therefore, we aimed to create various DM prediction models using easily accessible health screening test parameters.
Methods
Two sets of variables were used to develop eight DM prediction models. One set comprised 62 easily accessible examination results of commonly used variables from a tertiary university hospital. The second set comprised 27 of the 62 variables included in the national routine health checkups. Gradient boosting and random forest algorithms were used to develop the models. Internal validation was performed using the stratified 10-fold cross-validation method.
Results
The area under the receiver operating characteristic curve (ROC-AUC) for the 62-variable DM model making 12-month predictions for subjects without diabetes was the largest (0.928) among those of the eight DM prediction models. The ROC-AUC dropped by more than 0.04 when training with the simplified 27-variable set but still showed fairly good performance with ROC-AUCs between 0.842 and 0.880. The accuracy was up to 11.5% higher (from 0.807 to 0.714) when fasting glucose was included.
Conclusion
We created easily applicable diabetes prediction models that deliver good performance using parameters commonly assessed during tertiary university hospital and national routine health checkups. We plan to perform prospective external validation, hoping that the developed DM prediction models will be widely used in clinical practice.

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Predictive modeling for the development of diabetes mellitus using key factors in various machine learning approaches
Marenao Tanaka, Yukinori Akiyama, Kazuma Mori, Itaru Hosaka, Kenichi Kato, Keisuke Endo, Toshifumi Ogawa, Tatsuya Sato, Toru Suzuki, Toshiyuki Yano, Hirofumi Ohnishi, Nagisa Hanawa, Masato Furuhashi
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Validation of the Framingham Diabetes Risk Model Using Community-Based KoGES Data
Hye Ah Lee, Hyesook Park, Young Sun Hong
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Integrated Embedded system for detecting diabetes mellitus using various machine learning techniques
Rishita Konda, Anuraag Ramineni, Jayashree J, Niharika Singavajhala, Sai Akshaj Vanka
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Predicting diabetes in adults: identifying important features in unbalanced data over a 5-year cohort study using machine learning algorithm
Maryam Talebi Moghaddam, Yones Jahani, Zahra Arefzadeh, Azizallah Dehghan, Mohsen Khaleghi, Mehdi Sharafi, Ghasem Nikfar
BMC Medical Research Methodology.2024;[Epub] CrossRef
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Ji-Won Chun, Hun-Sung Kim
Journal of Korean Medical Science.2023;[Epub] CrossRef
Machine learning for predicting diabetic metabolism in the Indian population using polar metabolomic and lipidomic features
Nikita Jain, Bhaumik Patel, Manjesh Hanawal, Anurag R. Lila, Saba Memon, Tushar Bandgar, Ashutosh Kumar
Metabolomics.2023;[Epub] CrossRef
Retrospective cohort analysis comparing changes in blood glucose level and body composition according to changes in thyroid‐stimulating hormone level
Hyunah Kim, Da Young Jung, Seung‐Hwan Lee, Jae‐Hyoung Cho, Hyeon Woo Yim, Hun‐Sung Kim
Journal of Diabetes.2022; 14(9): 620. CrossRef
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Juyoung Shin, Joonyub Lee, Taehoon Ko, Kanghyuck Lee, Yera Choi, Hun-Sung Kim
Journal of Personalized Medicine.2022; 12(11): 1899. CrossRef

Short Communication

Drug/Regimen
Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study: Hwi Seung Kim, Taekwan Yoon, Chang Hee Jung, Joong-Yeol Park, Woo Je Lee; Diabetes Metab J. 2022;46(4):658-662. Published online November 8, 2021; DOI: https://doi.org/10.4093/dmj.2021.0232

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Sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are novel anti-diabetic drugs whose glucose-lowering effect and cardiovascular and renal benefits were evidenced in clinical trials. We investigated the real-world efficacy and safety of the combination of SGLT2i and GLP-1RA in patients with type 2 diabetes mellitus in Korea. The medical records of 104 patients who maintained the combination for at least 1 year were retrospectively reviewed. The change in glycosylated hemoglobin (HbA1c) after 6 months and 1 year of treatment was evaluated. The mean age was 51 years, and 41% were female. The mean baseline HbA1c, body mass index, and duration of diabetes were 9.0%, 28.8 kg/m², and 11.7 years, respectively. Compared with baseline, the HbA1c decreased by 1.5% (95% confidence interval [CI], 1.27 to 1.74; P<0.001) after 6 months and by 1.4% (95% CI, 1.19 to 1.70; P<0.001) after 1 year. Over 1 year, the bodyweight change was −2.8 kg (95% CI, −4.21 to −1.47; P<0.001). The combination of SGLT2i and GLP-1RA is effective and tolerable in type 2 diabetes mellitus patients in real-world practice.

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Aftab Ahmad, Hani Sabbour
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Fernando Cortés-Camacho, Oscar René Zambrano-Vásquez, Elena Aréchaga-Ocampo, Jorge Ismael Castañeda-Sánchez, José Guillermo Gonzaga-Sánchez, José Luis Sánchez-Gloria, Laura Gabriela Sánchez-Lozada, Horacio Osorio-Alonso
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Eun Roh, Kyung Mook Choi
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All‐cause mortality and cardiovascular outcomes with sodium‐glucose Co‐transporter 2 inhibitors, glucagon‐like peptide‐1 receptor agonists and with combination therapy in people with type 2 diabetes
David R. Riley, Hani Essa, Philip Austin, Frank Preston, Isatu Kargbo, Gema Hernández Ibarburu, Ramandeep Ghuman, Daniel J. Cuthbertson, Gregory Y. H. Lip, Uazman Alam
Diabetes, Obesity and Metabolism.2023; 25(10): 2897. CrossRef
The Efficacy and Safety of the Combination Therapy With GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis
Chen Li, Jie Luo, Mingyan Jiang, Keke Wang
Frontiers in Pharmacology.2022;[Epub] CrossRef
Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study (Diabetes Metab J 2022;46: 658-62)
Hwi Seung Kim, Woo Je Lee
Diabetes & Metabolism Journal.2022; 46(4): 665. CrossRef
Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study (Diabetes Metab J 2022;46: 658-62)
Tomoyuki Kawada
Diabetes & Metabolism Journal.2022; 46(4): 663. CrossRef
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Frontiers in Endocrinology.2022;[Epub] CrossRef

Letter

Clinical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes Mellitus: Real-World Study (Diabetes Metab J 2022;46: 658-62): Tomoyuki Kawada; Diabetes Metab J. 2022;46(4):663-664. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0131; [Original]

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