Diabetes & Metabolism Journal

Original Article

Pharmacotherapy
Glycemic Improvement with Low-Dose Dulaglutide Is Associated with Leptin and Obestatin Modulation in Type 2 Diabetes Mellitus: Inha Jung, Hangseok Choi, In Young Choi, Hyun Joo Cho, So Young Park, Da Young Lee, Ji A Seo, Nan Hee Kim, Ji Hee Yu; Received July 28, 2025 Accepted September 23, 2025 Published online November 24, 2025; DOI: https://doi.org/10.4093/dmj.2025.0681 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve glycemic control through insulinotropic and anorectic effects. However, the role of adipokines and appetite-related hormones in mediating the glycemic response remains unclear. This study evaluated changes in abdominal fat, food cravings, and circulating adipokines and gut hormones following dulaglutide treatment and identified predictors of glycemic improvement in type 2 diabetes mellitus (T2DM).
Methods
In this 24-week prospective observational study, 82 patients with T2DM and glycosylated hemoglobin (HbA1c) levels ≥7.0% despite standard therapy received dulaglutide 0.75 mg once weekly. Abdominal computed tomography, the General Food Cravings Questionnaire-Trait, and fasting levels of leptin, adiponectin, obestatin, ghrelin, and resistin were assessed at baseline and week 24. Glycemic responders were defined as those with an HbA1c reduction ≥0.5% and/or HbA1c <7.0% at 24 weeks. Multivariable regression analysis was performed to identify the factors associated with glycemic improvement.
Results
Among the 67 patients who completed the study, dulaglutide significantly reduced HbA1c, food cravings, leptin, and adiponectin levels. Obestatin levels increased modestly. Responders showed greater improvement in β-cell function and more pronounced reductions in food cravings. In the adjusted models, a decrease in leptin and an increase in obestatin were independently associated with HbA1c reduction, while decreased adiponectin was associated with poorer glycemic outcomes. Changes in body mass index or abdominal fat were not associated with glycemic improvement.
Conclusion
Dulaglutide improved glycemic control through mechanisms beyond weight reduction. Hormonal changes in leptin, adiponectin, and obestatin may help predict responses to GLP-1 RAs therapy.

Editorial

Navigating Ultra-Processed Foods with Insight: Ji A Seo; Diabetes Metab J. 2024;48(4):713-715. Published online July 26, 2024; DOI: https://doi.org/10.4093/dmj.2024.0316

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Original Articles

Guideline/Fact Sheet
2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association: Jun Sung Moon, Shinae Kang, Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, Yoon Ju Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae Jin Kim, Hyun Min Kim, Jung Hae Ko, Nam Hoon Kim, Chong Hwa Kim, Jeeyun Ahn, Tae Jung Oh, Soo-Kyung Kim, Jaehyun Kim, Eugene Han, Sang-Man Jin, Jaehyun Bae, Eonju Jeon, Ji Min Kim, Seon Mee Kang, Jung Hwan Park, Jae-Seung Yun, Bong-Soo Cha, Min Kyong Moon, Byung-Wan Lee; Diabetes Metab J. 2024;48(4):546-708. Published online July 26, 2024; DOI: https://doi.org/10.4093/dmj.2024.0249

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Complications
Association of Succinate and Adenosine Nucleotide Metabolic Pathways with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus: Inha Jung, Seungyoon Nam, Da Young Lee, So Young Park, Ji Hee Yu, Ji A Seo, Dae Ho Lee, Nan Hee Kim; Diabetes Metab J. 2024;48(6):1126-1134. Published online July 1, 2024; DOI: https://doi.org/10.4093/dmj.2023.0377

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Background
Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD.
Methods
We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573).
Results
Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria.
Conclusion
Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.

Citations

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Drug/Regimen
Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial: Jie-Eun Lee, Seung Hee Yu, Sung Rae Kim, Kyu Jeung Ahn, Kee-Ho Song, In-Kyu Lee, Ho-Sang Shon, In Joo Kim, Soo Lim, Doo-Man Kim, Choon Hee Chung, Won-Young Lee, Soon Hee Lee, Dong Joon Kim, Sung-Rae Cho, Chang Hee Jung, Hyun Jeong Jeon, Seung-Hwan Lee, Keun-Young Park, Sang Youl Rhee, Sin Gon Kim, Seok O Park, Dae Jung Kim, Byung Joon Kim, Sang Ah Lee, Yong-Hyun Kim, Kyung-Soo Kim, Ji A Seo, Il Seong Nam-Goong, Chang Won Lee, Duk Kyu Kim, Sang Wook Kim, Chung Gu Cho, Jung Han Kim, Yeo-Joo Kim, Jae-Myung Yoo, Kyung Wan Min, Moon-Kyu Lee; Diabetes Metab J. 2024;48(4):730-739. Published online May 20, 2024; DOI: https://doi.org/10.4093/dmj.2023.0077

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Background
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

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Real-world safety evaluation of atorvastatin: insights from the US FDA adverse event reporting system (FAERS)
Hongbing Wan, Xiuxiu Xu, Dasong Yi, Kexin Shuai
Expert Opinion on Drug Safety.2025; 24(3): 305. CrossRef
Exploration of metformin-based drug combination for mitigating diabetes-associated atherosclerotic diseases
Biao Qu, Zheng Li, Wei Hu
World Journal of Diabetes.2025;[Epub] CrossRef

Reviews

Pathophysiology
Attention to Innate Circadian Rhythm and the Impact of Its Disruption on Diabetes: Da Young Lee, Inha Jung, So Young Park, Ji Hee Yu, Ji A Seo, Kyeong Jin Kim, Nam Hoon Kim, Hye Jin Yoo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Nan Hee Kim; Diabetes Metab J. 2024;48(1):37-52. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2023.0193

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Novel strategies are required to reduce the risk of developing diabetes and/or clinical outcomes and complications of diabetes. In this regard, the role of the circadian system may be a potential candidate for the prevention of diabetes. We reviewed evidence from animal, clinical, and epidemiological studies linking the circadian system to various aspects of the pathophysiology and clinical outcomes of diabetes. The circadian clock governs genetic, metabolic, hormonal, and behavioral signals in anticipation of cyclic 24-hour events through interactions between a “central clock” in the suprachiasmatic nucleus and “peripheral clocks” in the whole body. Currently, circadian rhythmicity in humans can be subjectively or objectively assessed by measuring melatonin and glucocorticoid levels, core body temperature, peripheral blood, oral mucosa, hair follicles, rest-activity cycles, sleep diaries, and circadian chronotypes. In this review, we summarized various circadian misalignments, such as altered light-dark, sleep-wake, rest-activity, fasting-feeding, shift work, evening chronotype, and social jetlag, as well as mutations in clock genes that could contribute to the development of diabetes and poor glycemic status in patients with diabetes. Targeting critical components of the circadian system could deliver potential candidates for the treatment and prevention of type 2 diabetes mellitus in the future.

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Guideline/Fact Sheet
2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association: Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Nan Hee Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, YoonJu Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae Jin Kim, Hyun Min Kim, Jung Hae Ko, Nam Hoon Kim, Chong Hwa Kim, Jeeyun Ahn, Tae Jung Oh, Soo-Kyung Kim, Jaehyun Kim, Eugene Han, Sang-Man Jin, Won Suk Choi, Min Kyong Moon, Committee of Clinical Practice Guidelines, Korean Diabetes Association; Diabetes Metab J. 2023;47(5):575-594. Published online September 26, 2023; DOI: https://doi.org/10.4093/dmj.2023.0282

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In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.

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Islet transplantation in Korea
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Original Articles

Technology/Device
Clinical and Lifestyle Determinants of Continuous Glucose Monitoring Metrics in Insulin-Treated Patients with Type 2 Diabetes Mellitus: Da Young Lee, Namho Kim, Inha Jung, So Young Park, Ji Hee Yu, Ji A Seo, Jihee Kim, Kyeong Jin Kim, Nam Hoon Kim, Hye Jin Yoo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Sung-Min Park, Nan Hee Kim; Diabetes Metab J. 2023;47(6):826-836. Published online August 24, 2023; DOI: https://doi.org/10.4093/dmj.2022.0273

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Background
There was limited evidence to evaluate the association between lifestyle habits and continuous glucose monitoring (CGM) metrics. Thus, we aimed to depict the behavioral and metabolic determinants of CGM metrics in insulin-treated patients with type 2 diabetes mellitus (T2DM).
Methods
This is a prospective observational study. We analyzed data from 122 insulin-treated patients with T2DM. Participants wore Dexcom G6 and Fitbit, and diet information was identified for 10 days. Multivariate-adjusted logistic regression analysis was performed for the simultaneous achievement of CGM-based targets, defined by the percentage of time in terms of hyper, hypoglycemia and glycemic variability (GV). Intake of macronutrients and fiber, step counts, sleep, postprandial C-peptide-to-glucose ratio (PCGR), information about glucose lowering medications and metabolic factors were added to the analyses. Additionally, we evaluated the impact of the distribution of energy and macronutrient during a day, and snack consumption on CGM metrics.
Results
Logistic regression analysis revealed that female, participants with high PCGR, low glycosylated hemoglobin (HbA1c) and daytime step count had a higher probability of achieving all targets based on CGM (odds ratios [95% confidence intervals] which were 0.24 [0.09 to 0.65], 1.34 [1.03 to 1.25], 0.95 [0.9 to 0.99], and 1.15 [1.03 to 1.29], respectively). And participants who ate snacks showed a shorter period of hyperglycemia and less GV compared to those without.
Conclusion
We confirmed that residual insulin secretion, daytime step count, HbA1c, and women were the most relevant determinants of adequate glycemic control in insulin-treated patients with T2DM. In addition, individuals with snack consumption were exposed to lower times of hyperglycemia and GV.

Citations

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Utility of continuous glucose monitoring in people with type 2 diabetes on insulin-based regimens in clinical practice: A case series and expert opinion
Soo Lim, Rimei Nishimura, Jothydev Kesavadev, Alice Pik Shan Kong, Margaret J McGill, Horng-Yih Ou, Chun-Kwan O, Chun-Chuan Lee, Xiaomei Zhang, Linong Ji, Chih-Yuan Wang
Diabetes Research and Clinical Practice.2026; 233: 113054. CrossRef
Association of daytime circadian-aligned activity with glycemic control in type 2 diabetes: Insights from continuous glucose monitoring and wearable data
Da Young Lee, Jung-Been Lee, Inha Jung, So Young Park, Ji Hee Yu, Ji A Seo, Heon-Jeong Lee, Nan Hee Kim
Metabolism.2026; 179: 156570. CrossRef
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Jinjing Wan, Leiluo Geng, Yiwen Fu, Qianting Zhang, Gaopeng Guan, Xue Jiang, Aimin Xu, Ping Jin
Diabetes Research and Clinical Practice.2025; 225: 112262. CrossRef
Expanding the Use of Continuous Glucose Monitoring in Type 2 Diabetes Mellitus: Impact on Glycemic Control and Metabolic Health
Mi-Joon Lee, Bum-Jeun Seo, Jae-Hyoung Cho
Life.2025; 15(10): 1543. CrossRef
Explanatory variables of objectively measured 24-h movement behaviors in people with prediabetes and type 2 diabetes: A systematic review
Lotte Bogaert, Iris Willems, Patrick Calders, Eveline Dirinck, Manon Kinaupenne, Marga Decraene, Bruno Lapauw, Boyd Strumane, Margot Van Daele, Vera Verbestel, Marieke De Craemer
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Others
Fasting Glucose Variability and the Risk of Dementia in Individuals with Diabetes: A Nationwide Cohort Study: Da Young Lee, Jaeyoung Kim, Sanghyun Park, So Young Park, Ji Hee Yu, Ji A Seo, Nam Hoon Kim, Hye Jin Yoo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Kyungdo Han, Nan Hee Kim; Diabetes Metab J. 2022;46(6):923-935. Published online May 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0346

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Background
We investigated whether fasting glucose (FG) variability could predict the risk of dementia.
Methods
This cohort study analyzed data from Koreans with diabetes after at least three health examinations by the Korean National Health Insurance Corporation between 2005 and 2010, which included at least one examination between 2009 and 2010. A total of 769,554 individuals were included, excluding those aged <40 years and those with dementia. FG variability was measured using the variability independent of the mean (FG-VIM). The incidence of dementia was defined by the International Classification of Diseases 10th Revision codes and prescription of anti-dementia medication and was subdivided into Alzheimer’s disease (AD) and vascular dementia (VD).
Results
During the 6.9-year follow-up, 54,837, 41,032, and 6,892 cases of all-cause dementia, AD, and VD, respectively, were identified. Cox proportional regression analyses showed that as the FG-VIM quartile increased, the risk of dementia serially increased after adjustment for metabolic factors, income status, and diabetes-related characteristics, including the mean FG. Participants in FG-VIM quartile 4 showed a 18%, 19%, and 17% higher risk for all-cause dementia, AD, and VD, respectively, than those in quartile 1; this particularly included non-obese patients with a longer duration of diabetes, high FG levels, dyslipidemia, and those taking glucose-lowering medications. Conversely, the baseline FG status and dementia showed a U-shaped association.
Conclusion
Increased FG variability over 5 years can predict the risk of dementia in individuals with diabetes in Korea. This finding was more pronounced in patients with less favorable metabolic profiles.

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Paul Nichol G Gonzales, Encarnita R Ampil, Joseree-Ann S Catindig-Dela Rosa, Steven G Villaraza, Ma. Lourdes C Joson
Cureus.2024;[Epub] CrossRef
The Association of Glucose Variability and Dementia Incidence in Latinx Adults with Type 2 Diabetes: A Retrospective Study
Heather Cuevas, Elizabeth Muñoz, Divya Nagireddy, Jeeyeon Kim, Grace Ganucheau, Fathia Alomoush
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Sunyoung Cho, Choon Ok Kim, Bong-soo Cha, Eosu Kim, Chung Mo Nam, Min-Gul Kim, Min Soo Park
Diabetes Research and Clinical Practice.2023; 201: 110721. CrossRef
Physiological Mechanisms Inherent to Diabetes Involved in the Development of Dementia: Alzheimer’s Disease
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Short Communication

Technology/Device
Comparison of Laser and Conventional Lancing Devices for Blood Glucose Measurement Conformance and Patient Satisfaction in Diabetes Mellitus: Jung A Kim, Min Jeong Park, Eyun Song, Eun Roh, So Young Park, Da Young Lee, Jaeyoung Kim, Ji Hee Yu, Ji A Seo, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo, Nan Hee Kim; Diabetes Metab J. 2022;46(6):936-940. Published online March 30, 2022; DOI: https://doi.org/10.4093/dmj.2021.0293

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Self-monitoring of capillary blood glucose is important for controlling diabetes. Recently, a laser lancing device (LMT-1000) that can collect capillary blood without skin puncture was developed. We enrolled 150 patients with type 1 or 2 diabetes mellitus. Blood sampling was performed on the same finger on each hand using the LMT-1000 or a conventional lancet. The primary outcome was correlation between glucose values using the LMT-1000 and that using a lancet. And we compared the pain and satisfaction of the procedures. The capillary blood sampling success rates with the LMT-1000 and lancet were 99.3% and 100%, respectively. There was a positive correlation (r=0.974, P<0.001) between mean blood glucose levels in the LMT-1000 (175.8±63.0 mg/dL) and conventional lancet samples (172.5±63.6 mg/dL). LMT-1000 reduced puncture pain by 75.0% and increased satisfaction by 80.0% compared to a lancet. We demonstrated considerable consistency in blood glucose measurements between samples from the LMT-1000 and a lancet, but improved satisfaction and clinically significant pain reduction were observed with the LMT-1000 compared to those with a lancet.

Citations

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Pete Gregory
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Comparison between a laser-lancing device and automatic incision lancet for capillary blood sampling from the heel of newborn infants: a randomized feasibility trial
Chul Kyu Yun, Eui Kyung Choi, Hyung Jin Kim, Jaeyoung Kim, Byung Cheol Park, Kyuhee Park, Byung Min Choi
Journal of Perinatology.2024; 44(8): 1193. CrossRef
Comparison of laser and traditional lancing devices for capillary blood sampling in patients with diabetes mellitus and high bleeding risk
Min Jeong Park, Soon Young Hwang, Ahreum Jang, Soo Yeon Jang, Eyun Song, So Young Park, Da Young Lee, Jaeyoung Kim, Byung Cheol Park, Ji Hee Yu, Ji A Seo, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo, Nan Hee Kim
Lasers in Medical Science.2024;[Epub] CrossRef

Response

Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study (Diabetes Metab J 2021;45:368-78): Kyoung Jin Kim, Jimi Choi, Jae Hyun Bae, Kyeong Jin Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2021;45(4):617-618. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0152

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Editorial

Skeletal Muscle Should Not Be Overlooked: Ji A Seo; Diabetes Metab J. 2021;45(2):173-174. Published online March 25, 2021; DOI: https://doi.org/10.4093/dmj.2021.0024

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Original Articles

Complications
Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study: Kyoung Jin Kim, Jimi Choi, Jae Hyun Bae, Kyeong Jin Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2021;45(3):368-378. Published online October 20, 2020; DOI: https://doi.org/10.4093/dmj.2020.0046

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub

Background
To evaluate the association of time to reach the target glycosylated hemoglobin (HbA1c) level with long-term durable glycemic control and risk of diabetic complications in patients with newly diagnosed type 2 diabetes mellitus (T2DM).
Methods
In a longitudinal observational cohort, 194 patients with T2DM newly diagnosed between January 2011 and March 2013 were followed up over 6 years. Patients were classified according to the time needed to reach the target HbA1c (<7.0%): <3, 3 to 6 (early achievement group), and ≥6 months (late achievement group). Risks of microvascular complications including diabetic retinopathy, nephropathy, and neuropathy as well as macrovascular events including ischemic heart disease, ischemic stroke, and peripheral arterial disease were assessed by multivariable Cox proportional hazards analysis.
Results
During a median follow-up of 6.53 years, 66 microvascular and 14 macrovascular events occurred. Maintenance of durable glycemic control over 6 years was more likely in the early achievement groups than in the late achievement group (34.5%, 30.0%, and 16.1% in <3, 3 to 6, and ≥6 months, respectively, P=0.039). Early target HbA1c achievement was associated with lower risk of composite diabetic complications (adjusted hazard ratio [HR, 0.47; 95% confidence interval [CI], 0.26 to 0.86 in <3 months group) (adjusted HR, 0.50; 95% CI, 0.23 to 1.10 in 3 to 6 months group, in reference to ≥6 months group). Similar trends were maintained for risks of microvascular and macrovascular complications, although statistical significance was not reached for macrovascular complications.
Conclusion
Early target HbA1c achievement was associated with long-term durable glycemic control and reduced risk of diabetic complications in newly diagnosed T2DM.

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Metabolic Risk/Epidemiology
Age- and Sex-Related Differential Associations between Body Composition and Diabetes Mellitus: Eun Roh, Soon Young Hwang, Jung A Kim, You-Bin Lee, So-hyeon Hong, Nam Hoon Kim, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo; Diabetes Metab J. 2021;45(2):183-194. Published online June 16, 2020; DOI: https://doi.org/10.4093/dmj.2019.0171

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Background

The age- and sex-related differences on the impacts of body composition on diabetes mellitus (DM) remain uncertain.

Methods

The fourth and fifth Korea National Health and Nutrition Examination Survey included 15,586 subjects over 30 years of age who completed dual-energy X-ray absorptiometry. We conducted a cross-sectional study to investigate whether muscle mass index (MMI), defined as appendicular skeletal muscle divided by body mass index (BMI), and fat mass index (FMI), defined as trunk fat mass divided by BMI, were differently associated with DM according to age and sex.

Results

In multivariate logistic regression, the risk for DM significantly increased across quartiles of FMI in men aged ≥70. Meanwhile, MMI showed a protective association with DM in men of the same age. The odds ratios (ORs) for the highest quartile versus the lowest quartile of FMI and MMI were 3.116 (95% confidence interval [CI], 1.405 to 6.914) and 0.295 (95% CI, 0.157 to 0.554), respectively. In women, the ORs of DM was significantly different across FMI quartiles in those over age 50. The highest quartile of FMI exhibited increased ORs of DM in subjects aged 50 to 69 (OR, 1.891; 95% CI, 1.229 to 2.908) and ≥70 (OR, 2.275; 95% CI, 1.103 to 4.69) compared to lowest quartile. However, MMI was not significantly associated with DM in women of all age groups.

Conclusion

Both FMI and MMI were independent risk factors for DM in men aged 70 years or more. In women over 50 years, FMI was independently associated with DM. There was no significant association between MMI and DM in women.

Citations

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Yiseul Lee, Nam-Kyoo Lim, Hyun-Young Park
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Clinical Complications
Incidence and Risk Factors for Dementia in Type 2 Diabetes Mellitus: A Nationwide Population-Based Study in Korea: Ji Hee Yu, Kyungdo Han, Sanghyun Park, Hanna Cho, Da Young Lee, Jin-Wook Kim, Ji A Seo, Sin Gon Kim, Sei Hyun Baik, Yong Gyu Park, Kyung Mook Choi, Seon Mee Kim, Nan Hee Kim; Diabetes Metab J. 2020;44(1):113-124. Published online November 12, 2019; DOI: https://doi.org/10.4093/dmj.2018.0216

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Abstract PDF Supplementary Material PubReader ePub

Background

Diabetes mellitus is associated with an increased risk of dementia. We aimed to comprehensively analyze the incidence and risk factors for dementia and young-onset dementia (YOD) in diabetic patients in Korea using the National Health Insurance Service data.

Methods

Between January 1, 2009 and December 31, 2012, a total of 1,917,702 participants with diabetes were included and followed until the date of dementia diagnosis or until December 31, 2015. We evaluated the incidence and risk factors for all dementia, Alzheimer's disease (AD), and vascular dementia (VaD) by Cox proportional hazards analyses. We also compared the impact of risk factors on the occurrence of YOD and late-onset dementia (LOD).

Results

During an average of 5.1 years of follow-up, the incidence of all types of dementia, AD, or VaD was 9.5, 6.8, and 1.3/1,000 person-years, respectively, in participants with diabetes. YOD comprised 4.8% of all dementia occurrence, and the ratio of AD/VaD was 2.1 for YOD compared with 5.5 for LOD. Current smokers and subjects with lower income, plasma glucose levels, body mass index (BMI), and subjects with hypertension, dyslipidemia, vascular complications, depression, and insulin treatment developed dementia more frequently. Vascular risk factors such as smoking, hypertension, and previous cardiovascular diseases were more strongly associated with the development of VaD than AD. Low BMI and a history of stroke or depression had a stronger influence on the development of YOD than LOD.

Conclusion

The optimal management of modifiable risk factors may be important for preventing dementia in subjects with diabetes mellitus.

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Editorial

Clinical Diabetes & Therapeutics
An Age of Sodium-Glucose Cotransporter-2 Inhibitor Priority: Are We Ready?: Ji A Seo; Diabetes Metab J. 2019;43(5):578-581. Published online October 24, 2019; DOI: https://doi.org/10.4093/dmj.2019.0173

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Original Articles

Obesity and Metabolic Syndrome
Proportion and Characteristics of the Subjects with Low Muscle Mass and Abdominal Obesity among the Newly Diagnosed and Drug-Naïve Type 2 Diabetes Mellitus Patients: Jung A Kim, Soon Young Hwang, Hye Soo Chung, Nam Hoon Kim, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo; Diabetes Metab J. 2019;43(1):105-113. Published online September 28, 2018; DOI: https://doi.org/10.4093/dmj.2018.0036

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Background

Sarcopenic obesity (SO) is a serious public health concern, few studies have examined the clinical implications of SO in newly-diagnosed type 2 diabetes mellitus (T2DM) patients. We evaluated the prevalence of the newly diagnosed, drug-naïve T2DM patients with low muscle mass with abdominal obesity and its association with insulin resistance and other diabetic complications.

Methods

We classified 233 drug-naïve T2DM subjects into four groups according to abdominal obesity (waist circumference ≥90 cm in men and ≥85 cm in women) and low muscle mass status (appendicular skeletal muscle <7.0 kg/m² for men and <5.4 kg/m² for women).

Results

The proportion of the subjects with low muscle mass and abdominal obesity among the newly diagnosed, drug-naïve T2DM patients was 8.2%. Homeostasis model assessment of insulin resistance (HOMA-IR) increased linearly according to body composition group from normal to abdominal obesity to both low muscle mass and abdominal obesity. The multiple logistic regression analysis indicated that subjects with low muscle mass and abdominal obesity (odds ratio [OR], 9.39; 95% confidence interval [CI], 2.41 to 36.56) showed a higher risk for insulin resistance, defined as HOMA-IR ≥3, than those with abdominal obesity (OR, 5.36; 95% CI, 2.46 to 11.69), even after adjusting for other covariates. However, there were no differences in lipid profiles, microalbuminuria, or various surrogate markers for atherosclerosis among the four groups.

Conclusion

Subjects with both low muscle mass and abdominal obesity had a higher risk of insulin resistance than those with low muscle mass or abdominal obesity only.

Citations

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Epidemiology
Ten-Year Mortality Trends for Adults with and without Diabetes Mellitus in South Korea, 2003 to 2013: Kyeong Jin Kim, Tae Yeon Kwon, Sungwook Yu, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Sin Gon Kim, Yousung Park, Nam Hoon Kim; Diabetes Metab J. 2018;42(5):394-401. Published online April 26, 2018; DOI: https://doi.org/10.4093/dmj.2017.0088

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Background

To estimate and compare the trends of all-cause and cause-specific mortality rates for subjects with and without diabetes in South Korea, from 2003 to 2013.

Methods

Using a population-based cohort (2003 to 2013), we evaluated annual mortality rates in adults (≥30 years) with and without diabetes. The number of subjects in this analysis ranged from 585,795 in 2003 to 670,020 in 2013.

Results

Age- and sex-adjusted all-cause mortality rates decreased consistently in both groups from 2003 to 2013 (from 14.4 to 9.3/1,000 persons in subjects with diabetes and from 7.9 to 4.4/1,000 persons in those without diabetes). The difference in mortality rates between groups also decreased (6.61 per 1,000 persons in 2003 to 4.98 per 1,000 persons in 2013). The slope associated with the mortality rate exhibited a steeper decrease in subjects with diabetes than those without diabetes (regression coefficients of time: −0.50 and −0.33, respectively; P=0.004). In subjects with diabetes, the mortality rate from cardiovascular disease decreased by 53.5% (from 2.73 to 1.27 per 1,000 persons, P for trend <0.001). Notably, the decrease in mortality from ischemic stroke (79.2%, from 1.20 to 0.25 per 1,000 persowns) was more profound than that from ischemic heart disease (28.3%, from 0.60 to 0.43 per 1,000 persons).

Conclusion

All-cause and cardiovascular mortality rates decreased substantially from 2003 to 2013, and the decline in ischemic stroke mortality mainly contributed to the decreased cardiovascular mortality in Korean people with diabetes.

Citations

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Editorial

Clinical Diabetes & Therapeutics
Changes in the Bone Mineral Density of Femur Neck and Total Hip Over a 52-Week Treatment with Lobeglitazone: Da Young Lee, Ji A Seo; Diabetes Metab J. 2017;41(5):374-376. Published online October 24, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.5.374

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Original Articles

Increased Selenoprotein P Levels in Subjects with Visceral Obesity and Nonalcoholic Fatty Liver Disease: Hae Yoon Choi, Soon Young Hwang, Chang Hee Lee, Ho Cheol Hong, Sae Jeong Yang, Hye Jin Yoo, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi, Kyung Mook Choi; Diabetes Metab J. 2013;37(1):63-71. Published online February 15, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.1.63

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Background

Selenoprotein P (SeP) has recently been reported as a novel hepatokine that regulates insulin resistance and systemic energy metabolism in rodents and humans. We explored the associations among SeP, visceral obesity, and nonalcoholic fatty liver disease (NAFLD).

Methods

We examined serum SeP concentrations in subjects with increased visceral fat area (VFA) or liver fat accumulation measured with computed tomography. Our study subjects included 120 nondiabetic individuals selected from participants of the Korean Sarcopenic Obesity Study. In addition, we evaluated the relationship between SeP and cardiometabolic risk factors, including homeostasis model of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hsCRP), adiponectin values, and brachial-ankle pulse wave velocity (baPWV).

Results

Subjects with NAFLD showed increased levels of HOMA-IR, hsCRP, VFA, and several components of metabolic syndrome and decreased levels of adiponectin and high density lipoprotein cholesterol than those of controls. Serum SeP levels were positively correlated with VFA, hsCRP, and baPWV and negatively correlated with the liver attenuation index. Not only subjects with visceral obesity but also those with NAFLD exhibited significantly increased SeP levels (P<0.001). In multiple logistic regression analysis, the subjects in the highest SeP tertile showed a higher risk for NAFLD than those in the lowest SeP tertile, even after adjusting for potential confounding factors (odds ratio, 7.48; 95% confidence interval, 1.72 to 32.60; P=0.007).

Conclusion

Circulating SeP levels were increased in subjects with NAFLD as well as in those with visceral obesity and may be a novel biomarker for NAFLD.

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Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats: Jae Hee Ahn, Ho Cheol Hong, Myong Jin Cho, Yoon Jung Kim, Hae Yoon Choi, Chai Ryoung Eun, Sae Jeong Yang, Hye Jin Yoo, Hee Young Kim, Ji A Seo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Nan Hee Kim; Diabetes Metab J. 2012;36(2):128-135. Published online April 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.2.128

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Background

Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats.

Methods

Animals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks.

Results

Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-β1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups.

Conclusion

Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug.

Citations

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Editorial

Fibroblast Growth Factor 21: A Novel Metabolic Regulator: Ji A Seo, Nan Hee Kim; Diabetes Metab J. 2012;36(1):26-28. Published online February 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.1.26

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Original Article

Relationship Between Metabolic Syndrome and Risk of Chronic Complications in Koreans with Type 2 Diabetes.: Hye Soo Chung, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Doo Man Kim, Choon Hee Chung, Dong seop Choi; Korean Diabetes J. 2009;33(5):392-400. Published online October 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.5.392

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Abstract PDF

BACKGROUND
We examined the relationships between components of metabolic syndrome at the time of diagnosis of type 2 diabetes, and the development of chronic complications in Korean patients with type 2 diabetes. METHODS: The medical records of patients with type 2 diabetes who had undergone treatment for at least five years prior were collected from 10 general hospitals in Korea. Among a total of 1,418 patients reviewed for possible inclusion in this study, 603 patients were selected, and the occurrence of complications among these patients was evaluated. RESULTS: Among the 603 patients (male, 253; female, 350), 154 males (60.8%) and 266 females (76.0%) were diagnosed with metabolic syndrome at the time of initial diagnosis of type 2 diabetes. The incidence of chronic complications (average follow-up 15.2 +/- 4.9 years) included 60 cases of coronary artery disease (CAD), 57 cases of cerebrovascular accident (CVA), 268 cases of diabetic retinopathy (DR), 254 cases of diabetic nephropathy (DN), and 238 cases of diabetic peripheral neuropathy (DPN). As compared to patients without metabolic syndrome, the adjusted relative risks (95% CI) of incidental diabetic complications in patients with metabolic syndrome were 3.28 (1.40~7.71) for CAD, 2.04 (0.86~4.82) for CVA, 1.53 (1.10~2.14) for DR, 1.90 (1.29~2.80) for DN, and 1.51, (1.06~2.14) for DPN. With the addition of just one constituent of metabolic syndrome, the relative risk of developing CAD, CVD, DR, DN, and DPN increased by 2.08 (95% CI, 1.27~3.40), 1.16 (0.80~1.66), 1.09 (0.93~1.26), 1.29 (1.06~1.57) and 1.06 (0.87~1.26), respectively. CONCLUSION: Metabolic syndrome in Korean patients with type 2 diabetes increases the risk of developing both macrovascular and microvascular complications.

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Clinical Trial

The Effect of Cellular Phone-Based Telemedicine on Glycemic Control in Type 2 Diabetes Patients Using Insulin Therapy.: Yun Jeong Lee, Mi Hyun Jeong, Joo Hyung Kim, Juri Park, Hee Young Kim, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2009;33(3):232-240. Published online June 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.3.232

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Abstract PDF

BACKGROUND
Cellular phones are extremely prevalent in modern society and they enable appropriate feedback mechanisms through real time monitoring and short message services regarding blood glucose levels. We investigated whether cellular phone-based telemedicine support system could improve blood glucose control in type 2 diabetes patients who were in inadequate glycemic control regardless of insulin therapy. METHODS: A randomized, controlled clinical trial was conducted involving 74 type 2 diabetic patients with suboptimal glycemic control (HbA1c levels > 7%) regardless of insulin therapy. The intervention (cellular phone-based telemedicine) group managed their blood glucose using a cellular phone for 3 months, while the control (self monitoring of blood glucose) group managed their blood glucose with a standard glucometer for the same period. RESULTS: Three months later, HbA1c levels were decreased in both groups. However, the decrease in the control group from 8.37% to 8.20% was only 0.20% (P = 0.152) which was not significant. In contrast, the intervention group had a significant reduction of 0.61% from 8.77% to 8.16% (P < 0.001). Moreover, among patients with a baseline > or = 8%, the patients in the intervention group showed a significant reduction of 0.81% from 9.16% to 8.34% (P < 0.001). CONCLUSION: HbA1c levels were significantly decreased in the cellular phone-based telemedicine group compared with the control group after 3 months. This study suggests that cellular phone-based telemedicine is helpful for better glucose control in type 2 diabetes patients who previously were unable to control glucose levels adequately with insulin therapy.

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Telemedicine-Supported Intervention Versus Standard Care for Managing Cardiovascular Risk Factors in a Socially Deprived Urban Population: A Prospective Study
Angelica Gherman, Codrina Mihaela Levai, Ovidiu Alin Haţegan, Călin Marius Popoiu, Emil Robert Stoicescu, Anca Laura Maghiari
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A Survey on Ubiquitous Healthcare Service Demand among Diabetic Patients
Soo Lim, So-Youn Kim, Jung Im Kim, Min Kyung Kwon, Sei Jin Min, Soo Young Yoo, Seon Mee Kang, Hong Il Kim, Hye Seung Jung, Kyong Soo Park, Jun Oh Ryu, Hayley Shin, Hak Chul Jang
Diabetes & Metabolism Journal.2011; 35(1): 50. CrossRef

Original Articles

Effect of Valsartan on Blood Pressure and Urinary Albumin Excretion in Hypertensive Type 2 Diabetic Patients: An Open-Label, Multicenter Study.: Se Jun Park, Dae Jung Kim, Hae Jin Kim, Soo Yeon Park, Ji A Seo, Nan Hee Kim, Sung Hee Choi, Soo Lim, Hak Chul Jang, Seung Hyun Ko, Ki Ho Song, Yu Bae Ahn, Soo Kyoung Kim, Yong Wook Cho, Jun Goo Kang, Sung Hee Ihm, Cheol Young Park, Sung Woo Park, Dong Hyun Shin, Yong Hyun Kim, Kwan Woo Lee; Korean Diabetes J. 2008;32(6):513-521. Published online December 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.6.513

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Abstract PDF: BACKGROUND
Activation of renin-angiotensin system (RAS) has been an important mechanism of microvascular and macrovascular complications in diabetic patients. It has been reported that RAS blockades reduce the development and progression of diabetic nephropathy. The aim of this study was to evaluate whether valsartan, an angiotensin II receptor blocker (ARB), reduced blood pressure and urinary albumin excretion rate (UAER) in hypertensive type 2 diabetic patients. METHOD: Three hundred forty-seven hypertensive type 2 diabetic patients who had not taken angiotensin converting enzyme inhibitors or ARB for 6 months prior to this study were enrolled. We measured blood pressure and UAER before and after 24 weeks of valsartan treatment. RESULT: Baseline mean systolic and diastolic blood pressure was 143 +/- 15 and 87 +/- 11 mmHg, respectively and the median albumin excretion rate was 27 ug/mg. Reduction in systolic and diastolic blood pressure was 16 mmHg/10 mmHg and the median UAER was 19.3 ug/mg after 24 weeks (P < 0.01, respectively). When we divided the subjects into three groups according to the UAER (normoalbuminuria, microalbuminuria and macroalbuminuria), significant changes were reported in the microalbuminuria and the macroalbuminuria groups. Thirty-eight (42%) patients with microalbuminuria improved to normoalbuminuria and twelve (41%) patients with macroalbuminuria improved to microalbuminuria. We found an association between the improvement of blood pressure and UAER (R = 0.165, P = 0.015). CONCLUSION: We concluded that valsartan reduces urinary albumin excretion and blood pressure in hypertensive type 2 diabetic patients.

Effects of Comprehensive Support on Glycemic Control Using Community Networks in Low- Income Elderly Patients with Diabetes.: Nam Hoon Kim, Yun Jeong Lee, Hye Ok Kim, Cho Rong Oh, Ju Ri Park, Soo Yoen Park, Hee Young Kim, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Sin Gon Kim; Korean Diabetes J. 2008;32(5):453-461. Published online October 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.5.453

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Abstract PDF

BACKGROUND
Diabetes is common among elderly, and low-income is associated with poor adherence to treatment and increased mortality. We evaluated whether comprehensive support using community networks improves glycemic control among low-income elderly patients with diabetes. METHODS: A total of 49 low-income elderly patients with type 2 diabetes, mean age 73 years, were enrolled. For 1 year, study subjects underwent various lifestyle modification programs provided by community networks. The biochemical data including glycemic markers and anthropometric data were obtained at the baseline and at the end of the study. Also, the patients were asked to complete a questionnaire about their quality of life, self-confidence and self-care behavior. RESULTS: After lifestyle modification program, overall changes of fasting plasma glucose, HbA1c, blood pressure, body weight, and other biochemical markers were not significantly different. In a subgroup analysis of 21 patients with poorly controlled diabetes (fasting glucose > 140 mg/dL or HbA1c > 7.5%), fasting plasma glucose was significantly reduced (P = 0.030). Among patients with baseline HbA1c level > or = 8%, HbA1c levels after intervention decreased from 9.33 +/- 1.07% to 8.27 +/- 1.15% (P = 0.092). The results of the questionnaires revealed significant increases in the scores of quality of life, self-confidence and self-care behavior (P < 0.05). CONCLUSION: Among low-income, elderly patients with type 2 diabetes, lifestyle modification through community networks showed no significant changes in glycemic control markers. More intensive and precise interventions using community networks are needed for the glycemic control of low-income, elderly patients with type 2 diabetes.

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The Effects of a Health Mentoring Program in Community-dwelling Vulnerable Elderly Individuals with Diabetes
Ki wol Sung, Hye Seung Kang, Ji Ran Nam, Mi Kyung Park, Ji Hyeon Park
Journal of Korean Academy of Nursing.2018; 48(2): 182. CrossRef
Development of a scale to measure diabetes self‐management behaviors among olderKoreans with type 2 diabetes,based on the seven domains identified by theAmericanAssociation ofDiabetesEducators
Kyoungsan Seo, Misoon Song, Suyoung Choi, Se‐an Kim, Sun Ju Chang
Japan Journal of Nursing Science.2017; 14(2): 161. CrossRef
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Seung Hye Yang
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Randomized Controlled Trial

Effects of Telmisartan Compared with Valsartan on Plasma Adiponectin Levels and Arterial Stiffness in Patients with Type 2 Diabetes: A Pilot Study.: Soo Yeon Park, Sin Gon Kim, Juri Park, Yun Jeong Lee, Hee Young Kim, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2008;32(3):236-242. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2006.32.3.236

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Abstract PDF: BACKGROUND
Telmisartan, used for the treatment of hypertension, has been shown to function as a partial agonist of peroxime proliferative activated receptor-nu (PPAR-nu). Theoretically, telmisartan which simultaneously blocks the angiotensin II receptor and activates PPAR-nu should be more effective in improving atherosclerotic surrogate markers than angiotensin II receptor blockers alone. Therefore, this pilot study was designed to evaluate and compare the efficacy of telmisartan and valsartan on plasma adiponectin levels and pulse wave velocity as a marker of arterial stiffness in patients with type 2 diabetes. METHODS: Thirty two patients with type 2 diabetes (mean duration 7.6 +/- 5.1 years) taking oral hypoglycemic agents were randomly assigned to receive telmisartan or valsartan for 12 weeks. RESULTS: Telmisartan and valsartan treatment significantly increased circulating adiponectin levels (P = 0.013 and P = 0.013, respectively) and reduced systolic (P = 0.001 and P = 0.002, respectively) and diastolic blood pressure (P = 0.001 and P < 0.001, respectively), and brachial-ankle PWV (P = 0.019 and P = 0.002, respectively), without significant differences between the two treatments. Before and after treatment, the fasting plasma glucose, interleukin-6, homeostasis model of assessment insulin resistance (HOMAIR) levels and lipid profile were unchanged in both treatment groups. CONCLUSION: Contrary to our expectation, telmisartan, even with its partial PPAR-nu activity, is not superior to valsartan in improving plasma adipocytokine levels and arterial stiffness in patients with type 2 diabetes. These data suggest that the partial PPAR-nu activity of telmisartan beyond valsartan may have less significant therapeutic implications than expected in treating patients with type 2 diabetes.

Original Articles

VEGF-Angiopoietin-Tie2 System in Diabetic Retinopathy.: Nan Hee Kim, Hee Young Kim, Ji A Seo, Kye Won Lee, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Yoon Shin Park, Inho Jo, Dong Seop Choi; Korean Diabetes J. 2005;29(2):122-132. Published online March 1, 2005

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Abstract PDF: BACKGROUND
Ischemia-induced neovascularization can cause the loss of vision in retinal disorders such as diabetic retinopathy. Recent studies have shown that the angiopoietin-Tie2 system is a major regulator of vascular integrity and it is involved in pathologic angiogenesis. However, its role in the pathophysiology of diabetic retinopathy is not yet known. We examined the regulation of the VEGF-angiopoietin-Tie2 system in both in vitro and in vivo studies to discover their possible role in diabetic retinopathy. METHODS: We investigated the effects of a well-known angiogenic stimulus, hypoxia(2% O2 concentration) and vascular endothelial growth factor(VEGF, 10 ng/mL) on the expression of the angiopoietin-Tie2 mRNA in bovine retinal pericytes(BRP) and bovine aortic endothelial cells(BAEC). We also examined the expressions of VEGF-angiopoietin-Tie2 mRNA in retinas of type 2 diabetic OLETF(Otsuka-Long-Evans-Tokushima-Fatty) rats at 30 and 50 weeks. We also investigated the effect of angiotensin II receptor type 1(AT1) antagonist on the VEGFangiopoietin-Tie2 expression. RESULTS: Hypoxia and VEGF treatment significantly increased angiopoietin-1(Ang1) mRNA expression in the BRPs. In contrast, the angiopoietin-2(Ang2) mRNA expression was unaltered in the BRPs treated with hypoxia and VEGF. Significant up-regulation of Tie2 mRNA expression was found and this lasted up to 12 h. However, using BAECs, we found that only the Ang2 expression responded to these two angiogenic stimuli. In OLETF rats, the Ang-Tie2 expression patterns were similar with those of the BAECs. Ang2 and VEGF mRNA were increased at 30 and 50 weeks for the OLETF rats, whereas the Ang1 expression was not changed. The up-regulation of Ang2 and VEGF was decreased with the losartan treatment, an AT1 receptor antagonist. Tie2 mRNA expression was increased only at 50 weeks and it did not show any decrement by the losartan treatment. CONCLUSION: Our data suggest that hypoxia and VEGF treatment differentially regulate the angiopoietin-Tie2 system in the two vascular cells. Ang2 and VEGF expressions were predominantly increased in type 2 diabetic rats, and the unopposed action of Ang2 with VEGF might be involved in the development of diabetic retinopathy. The renin-angiotensin system may be a potential mechanism for the up-regulated VEGF-Ang2 system

Correlation of C-reactive Protein with Components of Metabolic Syndrome in Elderly Korean Women with Normal or Impaired Glucose Tolerance.: Soon Beom Kwon, Kyung Mook Choi, Soo Yeon Park, Hye Jin Yoo, Ohk Hyun Ryu, Sang Soo Park, Hee Young Kim, Kye Won Lee, Ji A Seo, Jeong Heon Oh, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2004;28(5):432-440. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Previous studies have reported that type 2 diabetes is associated with the increased blood concentrations of markers for the acute phase response, such as C-reactive protein (CRP), serum sialic acid and fibrinogen. The purpose of this study was to verify whether the pro-inflammatory cytokine- induced acute-phase response is a major pathogenic mechanism for type 2 diabetes in elderly Korean women. METHODS: We randomly selected a total of 232 non-smoking and non-diabetic female subjects among a total of 1,737 elderly subjects aged over 60 years who had participated in a population based study in Seoul, Korea (SWS Study 1999). We compared concentrations of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), as well as the acute-phase reactant C-reactive protein (CRP), between the subjects with normal glucose tolerance (NGT) and the subjects with impaired glucose tolerance (IGT). RESULTS: The IGT group showed higher serum high-sensitivity CRP (hs-CRP) concentrations than did the NGT group (the median was 1.2 versus 0.9, respectively, p<0.05). Moreover, a close relationship between serum hs-CRP concentrations and many components of the metabolic syndrome was found. However, serum concentrations of pro-inflammatory cytokines, IL-6 and TNF-alpha were not increasedin the IGT group, and they were not closely correlated with the components of metabolic syndrome. Multiple regression analysis using a stepwise selection method showed that the white blood cell counts, body mass index (BMI), fasting insulin, post-load 2h glucose, hematocrit and LDL cholesterol were associated with hs-CRP. CONCLUSIONS: The present study confirms the relationship between C-reactive protein, impaired glucose tolerance and metabolic syndrome in elderly Korean women.

Serum CRP levels are associated with Estradiol levels and Insulin Resistance Syndrome in Korean Women.: Kwon Beom Kim, Hee Young Kim, Kye Won Lee, Ji A Seo, Jeong Heon Oh, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Chol Shin, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2004;28(4):324-337. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Several reports have recently suggested a positive correlation between components of metabolic syndrome (MS) or insulin resistance syndrome (IRS) and markers of the acute-phase response, including C-reactive protein (CRP). These results imply that MS and type 2 diabetes are the results of ongoing inflammatory process. Whether estrogen plays a beneficial role in preventing atherosclerosis has been a matter of controversy. The objective of this study was to evaluate the relationship between the serum levels of estradiol (E2) and the components of the MS and CRP in nondiabetic subjects of Ansan Health Study (AHS). METHODS: Eight-hundred and ninety-one healthy non-diabetic women aged over 18 years were enrolled. After measurements of the anthropometric and metabolic parameters, correlation and multiple linear regression analyses were performed with regard to the CRP level, as a dependent variable, and with regards to age, blood pressure (BP), body mass index (BMI), lipid profiles, fasting plasma glucose levels, HOMA-IR and fat content as independent variables. RESULTS: In the multiple linear regression analysis, the CRP concentration was found to be independently associated with the E2 level, total fat content, leukocyte counts, and total cholesterol level in all subjects and the serum E2 levels was correlated with age, HOMA-IR, total cholesterol and the CRP level. When subjects were grouped according to their number of MS or IRS components, the CRP levels were found to show statistically significant differences between the MS and IRS groups. CONCLUSION: As a marker of chronic inflammation, the serum CRP level was independently associated with the components of MS and IRS. Also, the serum CRP and E2 levels were positively correlated. These results suggest that estrogen and CRP might play some independent roles in chronic inflammation which is a part of MS and IRS.

Plasma and urinary Vascular Endothelial Growth Factor and Diabetic Nephropathy in Type 2 Diabetes Mellitus.: Jeong Heon Oh, Hye Jin Yoo, Soo Yeon Park, Ohk Hyun Ryu, Sang Soo Park, Soon Beom Kwon, Hee Young Kim, Ji A Seo, Kye Won Lee, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Dae Ryong Cha, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2004;28(2):111-121. Published online April 1, 2004

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Abstract PDF: BACKGROUND
VEGF(vascular endothelial growth factor) has been implicated in the pathogenesis of neovascularization and endothelial dysfunction in diabetes mellitus. However, its precise role in diabetic nephropathy is still unknown. Our aims were to determine whether alterations of plasma and urinary VEGF levels were related to diabetic microvascular complications, especially nephropathy in type 2 diabetic patients. METHODS: 107 type 2 diabetic patients, without non-diabetic kidney diseases, and 47 healthy control subjects were studied. The urinary albumin excretion was defined as the albumin-to-creatinine ratio(ACR) in 24 hour urine samples. The study subjects were divided into four groups: a nondiabetic healthy control group(n=47), a normoalbuminuric diabetic group(ACR <30mug/mg, n=37), a microalbuminuric diabetic group(ACR 30~299mug/mg, n=37) and an overt proteinuric diabetic group(ACR=300mug/mg, n=33). The plasma and urinary VEGF levels were measured in these subjects by enzyme-linked immunosorbent assays. RESULTS: 1) The urinary VEGF concentrations were significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage(log VEGF/Cr, normoalbuminuria; 4.33+/-1.06 vs. control; 3.53+/-0.79, p=0.009). The levels of urinary VEGF excretions increased with advancing diabetic nephropathy stage. 2) The plasma and urinary VEGF levels were higher in the hypertensive diabetic than the normotensive diabetic patients. 3) In the diabetic patients, the level of plasma VEGF was positively correlated with the BUN(r=0.398, p=0.039) and urinary ACR (r=0.251, p=0.044). The level of urinary VEGF was positively correlated with the urinary ACR(r=0.645, p<0.001), and creatinine(r=0.336, p=0.009), but negatively correlated with the level of serum albumin(r=-0.557, p<0.001). Both the levels of urinary VEGF and serum creatinine were independently correlated with the urinary ACR. CONCLUSIONS: The excretion of urinary VEGF increased at a relatively earlier stage in diabetic nephropathy and was significantly correlated with the excretion of urinary albumin. These results suggested the possibility of urinary VEGF as a sensitive marker or the detection of diabetic nephropathy and in predicting disease progression.

Brachial-ankle Pulse Wave Velocity in Koreans with the Metabolic Syndrome.: Kyung Mook Choi, Kye Won Lee, Sul Hye Ryoung, Ji A Seo, Jeong Heon Oh, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2004;28(1):36-44. Published online February 1, 2004

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Abstract PDF: BACKGROUND
The clustering of cardiovascular risk factors is known as metabolic syndrome. In this study, the association between the brachial-ankle pulse wave velocity(baPWV), a novel non-invasive means of measuring atherosclerosis, and the cardiovascular risk factors of the metabolic syndrome were investigated. METHODS: The study group comprised 460 non-diabetic Koreans, male:female ratio 158:302, with a mean age of 52.4+/-11.3 years. The anthropometric parameters, blood pressure, fasting blood glucose(FBG), lipid profiles, ankle-brachial pressure index(ABI) and baPWV were measured in each subject. RESULTS: The ABI and baPWV levels were significantly higher in the men than the women. In both the men and women, the baPWV was closely associated with the cardiovascular risk factors of the metabolic syndrome. Those who had more metabolic syndrome components showed higher baPWV levels. Women with metabolic syndrome showed higher baPWV levels compared to those without (1517+/-281 vs. 1336+/-250, P<0.001). A multiple regression analysis showed the baPWV to be significantly associated with systolic blood pressure, age, gender, body mass index (BMI) and FBG (adjusted R-square 0.554). CONCLUSIONS: The present study shows that the baPWV was significantly associated with the features of metabolic syndrome, including the FBG, in non-diabetic Koreans.

Relations between Insulin Resistance and Hematologic Parameters in Elderly Koreans: Southwest Seoul (SWS) Study.: Kye Won Lee, Hye Jin Yoo, Soo Yeon Park, Ohk Hyun Ryu, Sang Soo Park, Soon Beom Kwon, Hee Young Kim, Ji A Seo, Jeong Heon Oh, Dong Hyun Shin, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Hyoung Jin Kim; Korean Diabetes J. 2003;27(4):352-361. Published online August 1, 2003

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Abstract PDF: BACKGROUND
The clustering of cardiovascular risk factors is known as insulin resistance syndrome. Hyperinsulinemia has been suggested as a cardiovascular risk factor due to the capacity of insulin to induce vascular endothelial proliferation and atherosclerosis. Insulin also has been shown to stimulate erythroid colony formation independently of erythropoietin. WBC count is one of the major components of the inflammatory process and is increased by IL-6, which is high in those with features of insulin resistance. In this study, we investigated whether insulin resistance affects hematological parameters. METHODS: In this study, 1,314, randomly selected, non-diabetic, elderly subjects over 60 years living in the southwest area of Seoul were recruited. Subjects underwent 75 g OGTT and careful physical examinations during evaluation, and were interviewed using a standardized questionnaire. Biochemical data and hematologic parameters were also measured. Insulin resistance was calculated by HOMA (homeostasis model assessment) method. Analysis of variance, Duncan's multiple comparisons and multiple linear regression analysis were carried out. RESULTS: In the male non-smoking group we found a correlation between insulin resistance and hemoglobin concentration (r=0.20, p=0.0186). In the female non- smoking group we found correlations between insulin resistance and both hemoglobin concentration (r=0.10, p=0.0017) and white blood cell (WBC) count (r=0.15, p=0.001). Hemoglobin concentration and WBC count were also correlated with BMI, systolic and diastolic blood pressure, lipid profiles and fasting insulin levels in female non-smokers. In multiple regression analysis, using HOMA IR as a dependent variable, we found significance in the variables of hemoglobin concentration, WBC count, age, BMI and triglyceride level. CONCLUSION: Our study provided evidence for a relation between insulin resistance and hematological parameters such as hemoglobin concentration and WBC count in elderly Koreans. This suggests that increased hemoglobin level and WBC count could be considered as novel aspects of the met.

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