Diabetes & Metabolism Journal

Original Articles

Complications
Glycemic Control and Retinal Microvascular Changes in Type 2 Diabetes Mellitus Patients without Clinical Retinopathy: Kangmin Lee, Ga Hye Lee, Seung Eun Lee, Jee Myung Yang, Kunho Bae; Diabetes Metab J. 2024;48(5):983-992. Published online March 13, 2024; DOI: https://doi.org/10.4093/dmj.2023.0149

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Abstract PDF Supplementary Material PubReader ePub: Background
To investigate the association of glycemic control and retinal microvascular changes in patients with type 2 diabetes mellitus (T2DM) without diabetic retinopathy (DR).
Methods
This retrospective, observational, cohort study included patients with T2DM without DR. The patients were categorized into intensive control (IC; mean glycosylated hemoglobin [HbA1c] ≤7.0%) and moderate control (MC; mean HbA1c >7.0%) groups. Optical coherence tomography (OCT) and swept-source OCT angiography (OCTA) image parameters were compared between three groups, including healthy controls.
Results
In total, 259 eyes of 259 participants (88 IC, 81 MC, and 90 controls) were included. The foveal avascular zone area was significantly larger in the MC group than IC and control groups (all P<0.05). The IC group had lower vessel density in the superficial retinal layer and deep retinal layer than the controls (all P<0.05). The choriocapillaris (CC) flow deficit (FD) was significantly greater in the MC group than in the IC and control groups (18.2%, 16.7%, and 14.2%, respectively; all P<0.01). In multivariate regression analysis, CC-FD was associated with the mean HbA1c level (P=0.008). There were no significant differences in OCT parameters among the groups.
Conclusion
OCTA revealed that early CC impairment is associated with HbA1c levels; the CC changes precede clinically apparent DR. The OCTA parameters differed among the groups according to the degree of glycemic control. Our results suggest that microvascular changes precede DR and are closely related to glycemic control.

Cardiovascular Risk/Epidemiology
Two-Year Changes in Diabetic Kidney Disease Phenotype and the Risk of Heart Failure: A Nationwide Population-Based Study in Korea: Seung Eun Lee, Juhwan Yoo, Han Seok Choi, Kyungdo Han, Kyoung-Ah Kim; Diabetes Metab J. 2023;47(4):523-534. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0096

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Background
Diabetic kidney disease (DKD) is a risk factor for hospitalization for heart failure (HHF). DKD could be classified into four phenotypes by estimated glomerular filtration rate (eGFR, normal vs. low) and proteinuria (PU, negative vs. positive). Also, the phenotype often changes dynamically. This study examined HHF risk according to the DKD phenotype changes across 2-year assessments.
Methods
The study included 1,343,116 patients with type 2 diabetes mellitus (T2DM) from the Korean National Health Insurance Service database after excluding a very high-risk phenotype (eGFR <30 mL/min/1.73 m2) at baseline, who underwent two cycles of medical checkups between 2009 and 2014. From the baseline and 2-year eGFR and PU results, participants were divided into 10 DKD phenotypic change categories.
Results
During an average of 6.5 years of follow-up, 7,874 subjects developed HHF. The cumulative incidence of HHF from index date was highest in the eGFR^lowPU– phenotype, followed by eGFR^norPU⁺ and eGFR^norPU^–. Changes in DKD phenotype differently affect HHF risk. When the persistent eGFR^norPU^– category was the reference, hazard ratios for HHF were 3.10 (95% confidence interval [CI], 2.73 to 3.52) in persistent eGFR^norPU⁺ and 1.86 (95% CI, 1.73 to 1.99) in persistent eGFR^lowPU^–. Among altered phenotypes, the category converted to eGFR^lowPU⁺ showed the highest risk. In the normal eGFR category at the second examination, those who converted from PU^– to PU⁺ showed a higher risk of HHF than those who converted from PU⁺ to PU^–.
Conclusion
Changes in DKD phenotype, particularly with the presence of PU, are more likely to reflect the risk of HHF, compared with DKD phenotype based on a single time point in patients with T2DM.

Citations

Citations to this article as recorded by

Persistent proteinuria is associated with the occurrence of cardiovascular disease: a nationwide population-based cohort study
Ho Geol Woo, Moo-Seok Park, Tae-Jin Song
Scientific Reports.2024;[Epub] CrossRef

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

Citations to this article as recorded by

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
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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
A Green Approach: Optimization of the UPLC Method Using DoE Software for Concurrent Quantification of Pioglitazone and Dapagliflozin in a SNEDDS Formulation for the Treatment of Diabetes
Ehab M. Elzayat, Abdelrahman Y. Sherif, Mohamed W. Attwa, Mohammad A. Altamimi
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Cardiovascular Disease & Diabetes Statistics in Korea: Nationwide Data 2010 to 2019
Jin Hwa Kim, Junyeop Lee, Kyungdo Han, Jae-Taek Kim, Hyuk-Sang Kwon
Diabetes & Metabolism Journal.2024; 48(6): 1084. 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
Insulin Resistance Increases Serum Immunoglobulin E Sensitization in Premenopausal Women: Seung Eun Lee, Ji Yeon Baek, Kyungdo Han, Eun Hee Koh; Diabetes Metab J. 2021;45(2):175-182. Published online April 14, 2020; DOI: https://doi.org/10.4093/dmj.2019.0150

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Graphical Abstract Abstract PDF PubReader ePub

Background

Although studies have shown that obesity is associated with aeroallergen sensitization (atopy), controversy still exists. We aimed to investigate the association between metabolic status, obesity, and atopy stratified by sex and menopausal status.

Methods

A total of 1,700 adults from the 2010 Korean National Health and Nutrition Examination Survey were classified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) by body mass index and insulin resistance. Atopy was defined as a positive response to at least one aeroallergen. Multiple regression analysis was used to evaluate the risk of immunoglobulin E (IgE) elevation or atopy in relation to the degree of metabolic abnormality and obesity.

Results

In premenopausal women, total IgE was positively correlated with obesity and insulin resistance. MUNO participants had a higher risk of having elevated total IgE compared to MHNO participants (odds ratio [OR], 2.271; 95% confidence interval [CI], 1.201 to 4.294), while MHO participants did not show a significant difference (OR, 1.435; 95% CI, 0.656 to 3.137) in premenopausal women. MUNO, but not MHO was also associated with atopy (OR, 2.157; 95% CI, 1.284 to 3.625). In men and postmenopausal women, there was no significant difference between metabolic status, obesity, and atopy among groups.

Conclusion

Increased insulin resistance is associated with total IgE and atopy in premenopausal women but not in postmenopausal women or men.

Citations

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Sulwon Lecture 2018

Pathophysiology
Mitochondrial Dysfunction in Adipocytes as a Primary Cause of Adipose Tissue Inflammation: Chang-Yun Woo, Jung Eun Jang, Seung Eun Lee, Eun Hee Koh, Ki-Up Lee; Diabetes Metab J. 2019;43(3):247-256. Published online March 27, 2019; DOI: https://doi.org/10.4093/dmj.2018.0221

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Abstract PDF PubReader

Adipose tissue inflammation is considered a major contributing factor in the development of obesity-associated insulin resistance and cardiovascular diseases. However, the cause of adipose tissue inflammation is presently unclear. The role of mitochondria in white adipocytes has long been neglected because of their low abundance. However, recent evidence suggests that mitochondria are essential for maintaining metabolic homeostasis in white adipocytes. In a series of recent studies, we found that mitochondrial function in white adipocytes is essential to the synthesis of adiponectin, which is the most abundant adipokine synthesized from adipocytes, with many favorable effects on metabolism, including improvement of insulin sensitivity and reduction of atherosclerotic processes and systemic inflammation. From these results, we propose a new hypothesis that mitochondrial dysfunction in adipocytes is a primary cause of adipose tissue inflammation and compared this hypothesis with a prevailing concept that “adipose tissue hypoxia” may underlie adipose tissue dysfunction in obesity. Recent studies have emphasized the role of the mitochondrial quality control mechanism in maintaining mitochondrial function. Future studies are warranted to test whether an inadequate mitochondrial quality control mechanism is responsible for mitochondrial dysfunction in adipocytes and adipose tissue inflammation.

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Original Articles

Clinical Diabetes & Therapeutics
Asian Subpopulations May Exhibit Greater Cardiovascular Benefit from Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A Meta-Analysis of Cardiovascular Outcome Trials: Yu Mi Kang, Yun Kyung Cho, Jiwoo Lee, Seung Eun Lee, Woo Je Lee, Joong-Yeol Park, Ye-Jee Kim, Chang Hee Jung, Michael A. Nauck; Diabetes Metab J. 2019;43(4):410-421. Published online December 27, 2018; DOI: https://doi.org/10.4093/dmj.2018.0070

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Abstract PDF Supplementary Material PubReader

Background

Based on reported results of three large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), we aimed to investigate the overall effect of GLP-1 RAs on major adverse cardiovascular events (MACEs) and to identify subpopulations exhibiting the greatest cardiovascular (CV) benefit.

Methods

Three CVOTs reporting effects of long-acting GLP-1 RAs were included: LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide once weekly). In all studies, the primary endpoint was three-point MACE, comprising CV death, non-fatal myocardial infarction, and non-fatal stroke. Overall effect estimates were calculated as hazard ratios and 95% confidence intervals (CIs) using the random-effects model; subgroup analyses reported in the original studies were similarly analyzed.

Results

Overall, statistically significant risk reductions in MACE and CV death were observed. Subgroup analysis indicated a significant racial difference with respect to CV benefit (P for interaction <0.001), and more substantial risk reductions were observed in subjects of African origin (relative risk [RR], 0.78; 95% CI, 0.60 to 0.99) and in Asians (RR, 0.35; 95% CI, 0.09 to 1.32). However, post hoc analysis (Bonferroni method) revealed that only Asians exhibited a significantly greater CV benefit from treatment, compared with white subjects (P<0.0001).

Conclusion

Long-acting GLP-1 RAs reduced risks of MACE and CV deaths in high-risk patients with type 2 diabetes mellitus. Our findings of a particularly effective reduction in CV events with GLP-1 RA in Asian populations merits further exploration and dedicated trials in specific populations.

Citations

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Association of Adiponectin and Hepatic Steatosis in Adults with Normal Transaminase Levels.: Jeong Hyun Mun, Seung Eun Lee, Ji Hyun Ahn, Soon Hyun Shinn; Korean Diabetes J. 2008;32(2):149-156. Published online April 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.2.149

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Abstract PDF

BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome including insulin resistance, hypertension, dyslipidemia, central obesity, type 2 diabetes, and cardiovascular disease. In NAFLD, insulin resistance plays an important role in the progression of liver damage. In this study, we evaluated insulin resistance, plasma adiponectin, hepatic steatosis, and their association in adults with normal liver transaminase concentrations. METHODS: We analyzed 111 subjects, aged over 20 years old, who visited the Health Management Center at Chung-Ang University Hospital between May 2006 and August 2006. They had neither history nor clinical evidence of diabetes, cardiovascular or liver disease. They were divided into three groups by the degree of hepatic steatosis based on ultrasound findings. Anthropometric parameters were measured and blood samples were drawn after eight hours of fasting. RESULTS: Hepatic steatosis had a positive correlation with body mass index, waist circumference, blood pressure, triglycerides, HOMA-IR, and QUICKI. Moreover, it had a negative correlation with high-density lipoprotein cholesterol and adiponectin. Triglycerides, Adiponectin, and QUICKI were independent variables in predicting the degree of hepatic steatosis. CONCLUSION: This finding suggests that triglycerides and plasma adiponectin are independent predictors of hepatic steatosis in adults with normal liver transaminase concentrations.

Citations

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Jae-Hwan Cho, Jang-Sun Namgung, Jin Lee, Deog-Hwan Moon, Hae-Kag Lee
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