Diabetes & Metabolism Journal

Original Article

Cardiovascular Risk/Epidemiology
Mean and Variability of Lipid Measurements and Risk for Development of Subclinical Left Ventricular Diastolic Dysfunction: Jiyun Park, Mira Kang, Jiyeon Ahn, Min Young Kim, Min Sun Choi, You-Bin Lee, Gyuri Kim, Kyu Yeon Hur, Jae Hyeon Kim, Jeong Hoon Yang, Sang-Man Jin; Diabetes Metab J. 2022;46(2):286-296. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0080

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Background
Subclinical left ventricular diastolic dysfunction (LVDD) is an emerging consequence of increased insulin resistance, and dyslipidemia is one of the few correctable risk factors of LVDD. This study evaluated the role of mean and visit-to-visit variability of lipid measurements in risk of LVDD in a healthy population.
Methods
This was a 3.7-year (interquartile range, 2.1 to 4.9) longitudinal cohort study including 2,817 adults (median age 55 years) with left ventricular ejection fraction >50% who underwent an annual or biannual health screening between January 2008 and July 2016. The mean, standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), non-HDL-C, and triglycerides were obtained from three to six measurements during the 5 years preceding the first echocardiogram.
Results
Among the 2,817 patients, 560 (19.9%) developed LVDD. The mean of no component of lipid measurements was associated with risk of LVDD. CV (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.10 to 1.67), SD (HR, 1.27; 95% CI, 1.03 to 1.57), and VIM (HR, 1.26; 95% CI, 1.03 to 1.55) of LDL-C and all the variability parameters of apoB were significantly associated with development of LVDD. The association between CV-LDL and risk of LVDD did not have significant interaction with sex, increasing/decreasing trend at baseline, or use of stain and/or lipid-modifying agents.
Conclusion
The variability of LDL-C and apoB, rather than their mean, was associated with risk for LVDD.

Citations

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Separate and Joint Associations of Remnant Cholesterol Accumulation and Variability With Carotid Atherosclerosis: A Prospective Cohort Study
Jinqi Wang, Rui Jin, Xiaohan Jin, Zhiyuan Wu, Haiping Zhang, Ze Han, Zongkai Xu, Yueruijing Liu, Xiaoyu Zhao, Xiuhua Guo, Lixin Tao
Journal of the American Heart Association.2023;[Epub] CrossRef
Variability of Metabolic Risk Factors: Causative Factor or Epiphenomenon?
Hye Jin Yoo
Diabetes & Metabolism Journal.2022; 46(2): 257. CrossRef

Review

Metabolic risk/Epidemiology
Obesity, Diabetes, and Increased Cancer Progression: Dae-Seok Kim, Philipp E. Scherer; Diabetes Metab J. 2021;45(6):799-812. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0077

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Rates of obesity and diabetes have increased significantly over the past decades and the prevalence is expected to continue to rise further in the coming years. Many observations suggest that obesity and diabetes are associated with an increased risk of developing several types of cancers, including liver, pancreatic, endometrial, colorectal, and post-menopausal breast cancer. The path towards developing obesity and diabetes is affected by multiple factors, including adipokines, inflammatory cytokines, growth hormones, insulin resistance, and hyperlipidemia. The metabolic abnormalities associated with changes in the levels of these factors in obesity and diabetes have the potential to significantly contribute to the development and progression of cancer through the regulation of distinct signaling pathways. Here, we highlight the cellular and molecular pathways that constitute the links between obesity, diabetes, cancer risk and mortality. This includes a description of the existing evidence supporting the obesity-driven morphological and functional alternations of cancer cells and adipocytes through complex interactions within the tumor microenvironment.

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Original Article

Metabolic Risk/Epidemiology
Sex Differences of Visceral Fat Area and Visceral-to-Subcutaneous Fat Ratio for the Risk of Incident Type 2 Diabetes Mellitus: Eun Hee Kim, Hong-Kyu Kim, Min Jung Lee, Sung-Jin Bae, Jaewon Choe, Chang Hee Jung, Chul-Hee Kim, Joong-Yeol Park, Woo Je Lee; Diabetes Metab J. 2022;46(3):486-498. Published online November 18, 2021; DOI: https://doi.org/10.4093/dmj.2021.0095

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Background
This study aimed to determine the optimal cut-off values of visceral fat area (VFA) and visceral-to-subcutaneous fat ratio (VSR) for predicting incident type 2 diabetes mellitus (T2DM).
Methods
A total of 10,882 individuals (6,835 men; 4,047 women) free of T2DM at baseline aged between 30 and 79 years who underwent abdominal computed tomography scan between 2012 and 2013 as a part of routine health check-ups were included and followed. VFA, subcutaneous fat area, and VSR on L3 vertebral level were measured at baseline.
Results
During a median follow-up of 4.8 years, 730 (8.1% for men; 4.3% for women) incident cases of T2DM were identified. Receiver operating characteristic curve analysis showed that the optimal cut-off values of VFA and VSR for predicting incident T2DM were 130.03 cm² and 1.08 in men, respectively, and 85.7 cm² and 0.48 in women, respectively. Regardless of sex, higher VFA and VSR were significantly associated with a higher risk of incident T2DM. Compared with the lowest quartiles of VFA and VSR, the highest quartiles had adjusted odds ratios of 2.62 (95% confidence interval [CI], 1.73 to 3.97) and 1.55 (95% CI, 1.14 to 2.11) in men, respectively, and 32.49 (95% CI, 7.42 to 142.02) and 11.07 (95% CI, 3.89 to 31.50) in women, respectively.
Conclusion
Higher VFA and VSR at baseline were independent risk factors for the development of T2DM. Sex-specific reference values for visceral fat obesity (VFA ≥130 cm² or VSR ≥1.0 in men; VFA ≥85 cm² or VSR ≥0.5 in women) are proposed for the prediction of incident T2DM.

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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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Effectiveness and safety of the combination of sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies
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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
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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
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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)
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Durability of glucose-lowering effect of dulaglutide in patients with type 2 diabetes mellitus: A real-world data study
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Original Articles

Metabolic Risk/Epidemiology
Prevalence of Type 2 Diabetes Mellitus among Korean Children, Adolescents, and Adults Younger than 30 Years: Changes from 2002 to 2016: Yong Hee Hong, In-Hyuk Chung, Kyungdo Han, Sochung Chung, on Behalf of the Taskforce Team of the Obesity Fact Sheet of the Korean Society for the Study of Obesity; Diabetes Metab J. 2022;46(2):297-306. Published online October 26, 2021; DOI: https://doi.org/10.4093/dmj.2021.0038

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Background
Despite the importance of and social concern regarding prevention of diabetes at younger ages, limited data are available. This study sought to analyze changes in the prevalence of type 2 diabetes mellitus (T2DM) in Koreans younger than 30 years according to sex, age, and level of income.
Methods
The dataset analyzed in this study was derived from health insurance claims recorded in the National Health Insurance Service (NHIS) database. Participants’ level of income was categorized as low (quintile 1, <20% of insurance premium) or others (quintile 2–5).
Results
In males and females, the prevalence of T2DM per 10,000 people steadily increased from 2.57 in 2002 to 11.41 in 2016, and from 1.96 in 2002 to 8.63 in 2016. The prevalence of T2DM in girls was higher in the age group of 5 to 14 years. Even though the prevalence was higher among those older than 20 years, the increase had started earlier, in the early 2000s, in younger age group. Adolescents aged 10 to 19 years in low-income families showed a remarkable increase in prevalence of T2DM, especially in boys.
Conclusion
The prevalence of T2DM in young Koreans increased more than 4.4-fold from 2002 to 2016, and the increase started in the early 2000s in younger age groups and in low-income families. This is the first study to examine the trend in prevalence of T2DM in children, adolescents, and young adults in Korea. Future studies and collaborations with social support systems to prevent T2DM at an early age group should be performed.

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SCORE and SCORE2 in East Asian Population
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Glycemic control and complications of type 2 diabetes mellitus in children and adolescents during the COVID-19 outbreak
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Drug/Regimen
Comparison of Prevailing Insulin Regimens at Different Time Periods in Hospitalized Patients: A Real-World Experience from a Tertiary Hospital: Sun Joon Moon, Hun Jee Choe, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho; Diabetes Metab J. 2022;46(3):439-450. Published online October 20, 2021; DOI: https://doi.org/10.4093/dmj.2021.0065

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Abstract PDF Supplementary Material PubReader ePub: Background
Prevailing insulin regimens for glycemic control in hospitalized patients have changed over time. We aimed to determine whether the current basal-bolus insulin (BBI) regimen is superior to the previous insulin regimen, mainly comprising split-mixed insulin therapy.
Methods
This was a single tertiary center, retrospective observational study that included non-critically ill patients with type 2 diabetes mellitus who were treated with split-mixed insulin regimens from 2004 to 2007 (period 1) and with BBI from 2008 to 2018 (period 2). Patients from each period were analyzed after propensity score matching. The mean difference in glucose levels and the achievement of fasting and preprandial glycemic targets by day 6 of admission were assessed. The total daily insulin dose, incidence of hypoglycemia, and length of hospital stay were also evaluated.
Results
Among 244 patients from each period, both fasting glucose (estimated mean±standard error, 147.4±3.1 mg/dL vs. 129.4±3.2 mg/dL, P<0.001, day 6) and preprandial glucose (177.7±2.8 mg/dL vs. 152.8±2.8 mg/dL, P<0.001, day 6) were lower in period 2 than in period 1. By day 6 of hospital admission, 42.6% and 67.2% of patients achieved a preprandial glycemic target of <140 mg/dL in periods 1 and 2, respectively (relative risk, 2.00; 95% confidence interval, 1.54 to 2.59), without an increased incidence of hypoglycemia. Length of stay was shorter in period 2 (10.23±0.26 days vs. 8.70±0.26 days, P<0.001).
Conclusion
BBI improved glycemic control in a more efficacious manner than a split-mixed insulin regimen without increasing the risk of hypoglycemia in a hospital setting.

Corrigendum

Time in Range from Continuous Glucose Monitoring: A Novel Metric for Glycemic Control: Jee Hee Yoo, Jae Hyeon Kim; Diabetes Metab J. 2021;45(5):795-795. Published online September 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0256; Corrects: Diabetes Metab J 2020;44(6):828

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Erratums

MondoA Is Required for Normal Myogenesis and Regulation of the Skeletal Muscle Glycogen Content in Mice: Hui Ran, Yao Lu, Qi Zhang, Qiuyue Hu, Junmei Zhao, Kai Wang, Xuemei Tong, Qing Su; Diabetes Metab J. 2021;45(5):797-797. Published online September 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0251; Corrects: Diabetes Metab J 2021;45(3):439

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Response

Increased Risk of Cardiovascular Disease and Mortality in Patients with Diabetes and Coexisting Depression: A Nationwide Population-Based Cohort Study (Diabetes Metab J 2021;45:379-89): Inha Jung, Eun-Jung Rhee, Won-Young Lee; Diabetes Metab J. 2021;45(5):793-794. Published online September 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0222

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Review

Technology/Device
Assessment of Insulin Secretion and Insulin Resistance in Human: So Young Park, Jean-François Gautier, Suk Chon; Diabetes Metab J. 2021;45(5):641-654. Published online September 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0220

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The impaired insulin secretion and increased insulin resistance (or decreased insulin sensitivity) play a major role in the pathogenesis of all types of diabetes mellitus (DM). It is very important to assess the pancreatic β-cell function and insulin resistance/ sensitivity to determine the type of DM and to plan an optimal management and prevention strategy for DM. So far, various methods and indices have been developed to assess the β-cell function and insulin resistance/sensitivity based on static, dynamic test and calculation of their results. In fact, since the metabolism of glucose and insulin is made through a complex process related with various stimuli in several tissues, it is difficult to fully reflect the real physiology. In order to solve the theoretical and practical difficulties, research on new index is still in progress. Also, it is important to select the appropriate method and index for the purpose of use and clinical situation. This review summarized a variety of traditional methods and indices to evaluate pancreatic β-cell function and insulin resistance/sensitivity and introduced novel indices.

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Letter

Increased Risk of Cardiovascular Disease and Mortality in Patients with Diabetes and Coexisting Depression: A Nationwide Population-Based Cohort Study (Diabetes Metab J 2021;45:379-89): Jin Hwa Kim; Diabetes Metab J. 2021;45(5):789-790. Published online September 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0212

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Sulwon Lecture 2020

Pathophysiology
Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases: Inês Sousa-Lima, Hyun Jeong Kim, John Jones, Young-Bum Kim; Diabetes Metab J. 2021;45(5):655-674. Published online September 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0197

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Nonalcoholic fatty liver disease (NAFLD) is a major public health problem and the most common form of chronic liver disease, affecting 25% of the global population. Although NAFLD is closely linked with obesity, insulin resistance, and type 2 diabetes mellitus, knowledge on its pathogenesis remains incomplete. Emerging data have underscored the importance of Rho-kinase (Rho-associated coiled-coil-containing kinase [ROCK]) action in the maintenance of normal hepatic lipid homeostasis. In particular, pharmacological blockade of ROCK in hepatocytes or hepatic stellate cells prevents the progression of liver diseases such as NAFLD and fibrosis. Moreover, mice lacking hepatic ROCK1 are protected against obesity-induced fatty liver diseases by suppressing hepatic de novo lipogenesis. Here we review the roles of ROCK as an indispensable regulator of obesity-induced fatty liver disease and highlight the key cellular pathway governing hepatic lipid accumulation, with focus on de novo lipogenesis and its impact on therapeutic potential. Consequently, a comprehensive understanding of the metabolic milieu linking to liver dysfunction triggered by ROCK activation may help identify new targets for treating fatty liver diseases such as NAFLD.

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Clinical Impact of Dysglycemia in Patients with an Acute Myocardial Infarction (Diabetes Metab J 2021;45:270-4): Chan-Hee Lee; Diabetes Metab J. 2021;45(5):791-792. Published online September 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0190

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The History of Insulin Therapy in Korea: Jun Sung Moon, Jong Chul Won, Young Min Cho; Diabetes Metab J. 2021;45(5):623-628. Published online September 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0171

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