Diabetes & Metabolism Journal

Original Articles

Technology/Device
Comparison of Real-Time and Intermittently-Scanned Continuous Glucose Monitoring for Glycemic Control in Type 1 Diabetes Mellitus: Nationwide Cohort Study: Ji Yoon Kim, Seohyun Kim, Jae Hyeon Kim; Received March 28, 2024 Accepted October 30, 2024 Published online February 27, 2025; DOI: https://doi.org/10.4093/dmj.2024.0160 [Epub ahead of print]

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This study compares the association between real-time continuous glucose monitoring (rtCGM) and intermittently- scanned CGM (isCGM) and glycemic control in individuals with type 1 diabetes mellitus (T1DM) in a real-world setting.
Methods
Using data from the Korean National Health Insurance Service Cohort, individuals with T1DM managed by intensive insulin therapy were followed at 3-month intervals for 2 years after the initiation of CGM. The glycosylated hemoglobin (HbA1c) levels and coefficients of variation (CVs) of rtCGM and isCGM users were compared using independent two-sample t-test and a linear mixed model.
Results
The analyses considered 7,786 individuals (5,875 adults aged ≥19 years and 1,911 children and adolescents aged <19 years). Overall, a significant reduction in HbA1c level was observed after 3 months of CGM, and the effect was sustained for 2 years. The mean HbA1c level at baseline was higher in rtCGM users than in isCGM users (8.9%±2.7% vs. 8.6%±2.2%, P<0.001). However, from 3 to 24 months, rtCGM users had lower HbA1c levels than isCGM users at every time point (7.1%±1.2% vs. 7.5%±1.3% at 24 months, P<0.001 for all time points). In both adults and children, the greater reduction in HbA1c with rtCGM remained significant after adjusting for the baseline characteristics of the users. The CV also showed greater decrease with rtCGM than with isCGM.
Conclusion
In this large nationwide cohort study, the use of rtCGM was associated with a greater improvement in glycemic control, including HbA1c reduction, than the use of isCGM in both adults and children with T1DM.

Drug/Regimen
Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial: Ji-Yeon Park, Joonyub Lee, Yoon-Hee Choi, Kyung Wan Min, Kyung Ah Han, Kyu Jeung Ahn, Soo Lim, Young-Hyun Kim, Chul Woo Ahn, Kyung Mook Choi, Kun-Ho Yoon, the Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) study investigators; Diabetes Metab J. 2024;48(5):915-928. Published online April 23, 2024; DOI: https://doi.org/10.4093/dmj.2023.0259

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Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy.
Methods
The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety.
Results
After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy.
Conclusion
Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

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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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.

Citations

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Flow and ischemic changes in retina and choroid across diabetic retinopathy spectrum: a SS-OCTA study
Qianhui Yang, Kelvin Y. C. Teo, Yueheng Hong, Bingyao Tan, Leopold Schmetterer, Chui Ming Gemmy Cheung, Tien Yin Wong, Gavin Tan Siew Wei
Eye.2025;[Epub] CrossRef

Metabolic Risk/Epidemiology
Glycemic Control Is Associated with Histological Findings of Nonalcoholic Fatty Liver Disease: Teruki Miyake, Shinya Furukawa, Bunzo Matsuura, Osamu Yoshida, Masumi Miyazaki, Akihito Shiomi, Ayumi Kanamoto, Hironobu Nakaguchi, Yoshiko Nakamura, Yusuke Imai, Mitsuhito Koizumi, Takao Watanabe, Yasunori Yamamoto, Yohei Koizumi, Yoshio Tokumoto, Masashi Hirooka, Teru Kumagi, Eiji Takesita, Yoshio Ikeda, Masanori Abe, Yoichi Hiasa; Diabetes Metab J. 2024;48(3):440-448. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0200

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Background
Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD.
Methods
This observational study included 331 patients diagnosed with NAFLD by liver biopsy. Effects of the glycemic control status on histological findings of NAFLD were evaluated by comparing the following four glycemic status groups defined by the glycosylated hemoglobin (HbA1c) level at the time of NAFLD diagnosis: ≤5.4%, 5.5%–6.4%, 6.5%–7.4%, and ≥7.5%.
Results
Compared with the lowest HbA1c group (≤5.4%), the higher HbA1c groups (5.5%–6.4%, 6.5%–7.4%, and ≥7.5%) were associated with advanced liver fibrosis and high NAFLD activity score (NAS). On multivariate analysis, an HbA1c level of 6.5%– 7.4% group was significantly associated with advanced fibrosis compared with the lowest HbA1c group after adjusting for age, sex, hemoglobin, alanine aminotransferase, and creatinine levels. When further controlling for body mass index and uric acid, total cholesterol, and triglyceride levels, the higher HbA1c groups were significantly associated with advanced fibrosis compared with the lowest HbA1c group. On the other hand, compared with the lowest HbA1c group, the higher HbA1c groups were also associated with a high NAS in both multivariate analyses.
Conclusion
Glycemic control is associated with NAFLD exacerbation, with even a mild deterioration in glycemic control, especially a HbA1c level of 6.5%–7.4%, contributing to NAFLD progression.

Citations

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The association between glycemic state, R factor and Steatosis-Associated Fibrosis Estimator score in advanced liver fibrosis in patients with diabetes mellitus
Mohammadjavad Sotoudeheian, Seyed-Mohamad-Sadegh Mirahmadi, Reza Azarbad
Obesity Medicine.2025; 53: 100575. CrossRef
Combined effect of histological findings and diabetes mellitus on liver‐related events in patients with metabolic dysfunction‐associated steatotic liver disease
Akihito Shiomi, Teruki Miyake, Shinya Furukawa, Bunzo Matsuura, Osamu Yoshida, Takao Watanabe, Ayumi Kanamoto, Masumi Miyazaki, Hironobu Nakaguchi, Yoshio Tokumoto, Masashi Hirooka, Masanori Abe, Yoichi Hiasa
Hepatology Research.2024; 54(11): 1016. CrossRef
Overweight Impacts Histological Disease Activity of De Novo Metabolic Dysfunction‐Associated Steatotic Liver Disease After Liver Transplantation
Alejandro Campos‐Murguia, Lea Guetzlaff, Emily Bosselmann, Bastian Engel, Björn Hartleben, Heiner Wedemeyer, Elmar Jaeckel, Richard Taubert, Katharina Luise Hupa‐Breier
Clinical Transplantation.2024;[Epub] CrossRef

Drug/Regimen
Two-Year Therapeutic Efficacy and Safety of Initial Triple Combination of Metformin, Sitagliptin, and Empagliflozin in Drug-Naïve Type 2 Diabetes Mellitus Patients: Young-Hwan Park, Minji Sohn, So Yeon Lee, Soo Lim; Diabetes Metab J. 2024;48(2):253-264. Published online January 26, 2024; DOI: https://doi.org/10.4093/dmj.2023.0128

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Background
We investigated the long-term efficacy and safety of initial triple therapy using metformin, a dipeptidyl peptidase-4 inhibitor, and a sodium-glucose cotransporter-2 inhibitor, in patients with type 2 diabetes mellitus.
Methods
We enrolled 170 drug-naïve patients with glycosylated hemoglobin (HbA1c) level >7.5% who had started triple therapy (metformin, sitagliptin, and empagliflozin). Glycemic, metabolic, and urinary parameters were measured for 24 months.
Results
After 24 months, HbA1c level decreased significantly from 11.0%±1.8% to 7.0%±1.7%. At 12 and 24 months, the rates of achievement of the glycemic target goal (HbA1c <7.0%) were 72.5% and 61.7%, respectively, and homeostasis model assessment of β-cell function and insulin resistance indices improved. Whole-body fat percentage decreased by 1.08%, and whole-body muscle percentage increased by 0.97% after 24 months. Fatty liver indices and albuminuria improved significantly. The concentration of ketone bodies was elevated at the baseline but decreased after 24 months. There were no serious adverse events, including ketoacidosis.
Conclusion
Initial triple combination therapy with metformin, sitagliptin, and empagliflozin led to achievement of the glycemic target goal, which was maintained for 24 months without severe hypoglycemia but with improved metabolic function and albuminuria. This combination therapy may be a good strategy for drug-naïve patients with type 2 diabetes mellitus.

Citations

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Successful portosystemic shunt embolization resolves hepatic encephalopathy and enhances hepatic function and glycemic control in MASH-related cirrhosis: a case report
Yoshiaki Kobayashi, Takanobu Iwadare, Hiroyuki Kobayashi, Takefumi Kimura, Yoshiki Ozawa, Ryo Kodama, Masahiro Kurozumi, Yayoi Yamazaki, Yuki Yamashita, Takeji Umemura
Clinical Journal of Gastroenterology.2025; 18(1): 137. CrossRef
Mechanistic insights and therapeutic potential of astilbin and apigenin in diabetic cardiomyopathy
Sachin Dhiman, Sanchit Dhankhar, Anjali Garg, Manni Rohilla, Monika Saini, Thakur Gurjeet Singh, Samrat Chauhan, Samy Selim, Soad K. Al Jaouni, Sabina Yasmin, Naseem Begum, Aziza Alshahrani, Mohammad Yousuf Ansari
Heliyon.2024; 10(21): e39996. CrossRef

Metabolic Risk/Epidemiology
Association of Measures of Glucose Metabolism with Colorectal Cancer Risk in Older Chinese: A 13-Year Follow-up of the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy and Meta-Analysis: Shu Yi Wang, Wei Sen Zhang, Chao Qiang Jiang, Ya Li Jin, Tong Zhu, Feng Zhu, Lin Xu; Diabetes Metab J. 2024;48(1):134-145. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2022.0383

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Background
Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis.
Methods
Participants (n=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk.
Results
During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies.
Conclusion
Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.

Citations

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Association between accelerated biological aging and colorectal cancer: a cross-sectional study
Sai Wang, Keyu Wang, Xiu Wang
Frontiers in Medicine.2025;[Epub] CrossRef
Relationship Between Aspirin Use and Site-Specific Colorectal Cancer Risk Among Individuals With Metabolic Comorbidity
Seokyung An, Madhawa Gunathilake, Jeonghee Lee, Minji Kim, Jae Hwan Oh, Hee Jin Chang, Dae Kyung Sohn, Aesun Shin, Jeongseon Kim
Journal of Korean Medical Science.2024;[Epub] CrossRef
Associations between blood glucose and early- and late-onset colorectal cancer: evidence from two prospective cohorts and Mendelian randomization analyses
Chenyu Luo, Jiahui Luo, Yuhan Zhang, Bin Lu, Na Li, Yueyang Zhou, Shuohua Chen, Shouling Wu, Qingsong Zhang, Min Dai, Hongda Chen
Journal of the National Cancer Center.2024; 4(3): 241. CrossRef

Cardiovascular Risk/Epidemiology
Glycemic Control and Adverse Clinical Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus: Results from KNOW-CKD: Ga Young Heo, Hee Byung Koh, Hyung Woo Kim, Jung Tak Park, Tae-Hyun Yoo, Shin-Wook Kang, Jayoun Kim, Soo Wan Kim, Yeong Hoon Kim, Su Ah Sung, Kook-Hwan Oh, Seung Hyeok Han; Diabetes Metab J. 2023;47(4):535-546. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0112

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Background
The optimal level of glycosylated hemoglobin (HbA1c) to prevent adverse clinical outcomes is unknown in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM).
Methods
We analyzed 707 patients with CKD G1-G5 without kidney replacement therapy and T2DM from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD), a nationwide prospective cohort study. The main predictor was time-varying HbA1c level at each visit. The primary outcome was a composite of development of major adverse cardiovascular events (MACEs) or all-cause mortality. Secondary outcomes included the individual endpoint of MACEs, all-cause mortality, and CKD progression. CKD progression was defined as a ≥50% decline in the estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease.
Results
During a median follow-up of 4.8 years, the primary outcome occurred in 129 (18.2%) patients. In time-varying Cox model, the adjusted hazard ratios (aHRs) for the primary outcome were 1.59 (95% confidence interval [CI], 1.01 to 2.49) and 1.99 (95% CI, 1.24 to 3.19) for HbA1c levels of 7.0%–7.9% and ≥8.0%, respectively, compared with <7.0%. Additional analysis of baseline HbA1c levels yielded a similar graded association. In secondary outcome analyses, the aHRs for the corresponding HbA1c categories were 2.17 (95% CI, 1.20 to 3.95) and 2.26 (95% CI, 1.17 to 4.37) for MACE, and 1.36 (95% CI, 0.68 to 2.72) and 2.08 (95% CI, 1.06 to 4.05) for all-cause mortality. However, the risk of CKD progression did not differ between the three groups.
Conclusion
This study showed that higher HbA1c levels were associated with an increased risk of MACE and mortality in patients with CKD and T2DM.

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Unveiling the utility of artificial intelligence for prediction, diagnosis, and progression of diabetic kidney disease: an evidence-based systematic review and meta-analysis
Sagar Dholariya, Siddhartha Dutta, Amit Sonagra, Mehul Kaliya, Ragini Singh, Deepak Parchwani, Anita Motiani
Current Medical Research and Opinion.2024; 40(12): 2025. CrossRef
Non-Alcoholic Fatty Liver Disease and Its Association with Kidney and Cardiovascular Outcomes in Moderate to Advanced Chronic Kidney Disease
Cheol Ho Park, Hyunsun Lim, Youn Nam Kim, Jae Young Kim, Hyung Woo Kim, Tae Ik Chang, Seung Hyeok Han
American Journal of Nephrology.2024; : 1. CrossRef
The Beneficial Effect of Glycemic Control against Adverse Outcomes in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease
Dong-Hwa Lee
Diabetes & Metabolism Journal.2023; 47(4): 484. CrossRef
Prevalence and predictors of chronic kidney disease among type 2 diabetic patients worldwide, systematic review and meta-analysis
Eneyew Talie Fenta, Habitu Birhan Eshetu, Natnael Kebede, Eyob Ketema Bogale, Amare Zewdie, Tadele Derbew Kassie, Tadele Fentabil Anagaw, Elyas Melaku Mazengia, Sintayehu Shiferaw Gelaw
Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef
Efficacy and safety of teneligliptin in patients with type 2 diabetes mellitus: a Bayesian network meta-analysis
Miao Zhu, Ruifang Guan, Guo Ma
Frontiers in Endocrinology.2023;[Epub] CrossRef

Type 1 Diabetes
Abnormal Responses in Cognitive Impulsivity Circuits Are Associated with Glycosylated Hemoglobin Trajectories in Type 1 Diabetes Mellitus and Impaired Metabolic Control: Helena Jorge, Isabel C. Duarte, Sandra Paiva, Ana Paula Relvas, Miguel Castelo-Branco; Diabetes Metab J. 2022;46(6):866-878. Published online March 22, 2022; DOI: https://doi.org/10.4093/dmj.2021.0307

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Background
Risky health decisions and impulse control profiles may impact on metabolic control in type 1 diabetes mellitus (T1DM). We hypothesize that the neural correlates of cognitive impulsivity and decision-making in T1DM relate to metabolic control trajectories.
Methods
We combined functional magnetic resonance imaging (fMRI), measures of metabolic trajectories (glycosylated hemoglobin [HbA1c] over multiple time points) and behavioral assessment using a cognitive impulsivity paradigm, the Balloon Analogue Risk Task (BART), in 50 participants (25 T1DM and 25 controls).
Results
Behavioral results showed that T1DM participants followed a rigid conservative risk strategy along the iterative game. Imaging group comparisons showed that patients showed larger activation of reward related, limbic regions (nucleus accumbens, amygdala) and insula (interoceptive saliency network) in initial game stages. Upon game completion differences emerged in relation to error monitoring (anterior cingulate cortex [ACC]) and inhibitory control (inferior frontal gyrus). Importantly, activity in the saliency network (ACC and insula), which monitors interoceptive states, was related with metabolic trajectories, which was also found for limbic/reward networks. Parietal and posterior cingulate regions activated both in controls and patients with adaptive decision-making, and positively associated with metabolic trajectories.
Conclusion
We found triple converging evidence when comparing metabolic trajectories, patients versus controls or risk averse (non-learners) versus patients who learned by trial and error. Dopaminergic reward and saliency (interoceptive and error monitoring) circuits show a tight link with impaired metabolic trajectories and cognitive impulsivity in T1DM. Activity in parietal and posterior cingulate are associated with adaptive trajectories. This link between reward-saliency-inhibition circuits suggests novel strategies for patient management.

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Symptom perception in adults with chronic physical disease: A systematic review of insular impairments
Giulia Locatelli, Austin Matus, Chin-Yen Lin, Ercole Vellone, Barbara Riegel
Heart & Lung.2025; 70: 122. CrossRef
Editorial: Translational neuroeconomic approach: from economic decision making to neuropsychological disorders
Mrinalini Srivastava, S. Senthil Kumaran, Achal Kumar Srivastava, Sanjay Singh
Frontiers in Neurology.2025;[Epub] CrossRef
Neuroeconomically dissociable forms of mental accounting are altered in a mouse model of diabetes
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Communications Biology.2025;[Epub] CrossRef
Glycated hemoglobin, type 2 diabetes, and poor diabetes control are positively associated with impulsivity changes in aged individuals with overweight or obesity and metabolic syndrome
Carlos Gómez‐Martínez, Nancy Babio, Lucía Camacho‐Barcia, Jordi Júlvez, Stephanie K. Nishi, Zenaida Vázquez, Laura Forcano, Andrea Álvarez‐Sala, Aida Cuenca‐Royo, Rafael de la Torre, Marta Fanlo‐Maresma, Susanna Tello, Dolores Corella, Alejandro Arias Vás
Annals of the New York Academy of Sciences.2024;[Epub] CrossRef
The usefulness of an intervention with a serious video game as a complementary approach to cognitive behavioural therapy in eating disorders: A pilot randomized clinical trial for impulsivity management
Cristina Vintró‐Alcaraz, Núria Mallorquí‐Bagué, María Lozano‐Madrid, Giulia Testa, Roser Granero, Isabel Sánchez, Janet Treasure, Susana Jiménez‐Murcia, Fernando Fernández‐Aranda
European Eating Disorders Review.2023; 31(6): 781. CrossRef
Adaptations of the balloon analog risk task for neuroimaging settings: a systematic review
Charline Compagne, Juliana Teti Mayer, Damien Gabriel, Alexandre Comte, Eloi Magnin, Djamila Bennabi, Thomas Tannou
Frontiers in Neuroscience.2023;[Epub] CrossRef
Trust-based health decision-making recruits the neural interoceptive saliency network which relates to temporal trajectories of Hemoglobin A1C in Diabetes Type 1
Helena Jorge, Isabel C. Duarte, Miguel Melo, Ana Paula Relvas, Miguel Castelo-Branco
Brain Imaging and Behavior.2023; 18(1): 171. CrossRef

Short Communication

Technology/Device
A 4-Week, Two-Center, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of EOPatch in Well-Controlled Type 1 Diabetes Mellitus: Jiyun Park, Nammi Park, Sangjin Han, You-Bin Lee, Gyuri Kim, Sang-Man Jin, Woo Je Lee, Jae Hyeon Kim; Diabetes Metab J. 2022;46(6):941-947. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0299

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This study evaluated the safety and efficacy of tubeless patch pump called EOPatch in patients with well-controlled type 1 diabetes mellitus (T1DM). This 4-week, two-center, open-label, single-arm study enrolled 10 adult patients diagnosed with T1DM with glycosylated hemoglobin less than 7.5%. The co-primary end points were patch pump usage time for one attachment and number of serious adverse events related to the patch pump. The secondary end points were total amount of insulin injected per patch and changes in glycemic parameters including continuous glucose monitoring data compared to those at study entry. The median usage time per patch was 84.00 hours (interquartile range, 64.50 to 92.50). Serious adverse events did not occur during the trial. Four weeks later, time in range 70 to 180 mg/dL was significantly improved (70.71%±17.14 % vs. 82.96%±9.14%, P=0.01). The times spent below range (<54 mg/dL) and above range (>180 mg/dL) also improved (All P<0.05). Four-week treatment with a tubeless patch pump was safe and led to clinical improvement in glycemic control.

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Comparison between a tubeless, on-body automated insulin delivery system and a tubeless, on-body sensor-augmented pump in type 1 diabetes: a multicentre randomised controlled trial
Ji Yoon Kim, Sang-Man Jin, Eun Seok Kang, Soo Heon Kwak, Yeoree Yang, Jee Hee Yoo, Jae Hyun Bae, Jun Sung Moon, Chang Hee Jung, Ji Cheol Bae, Sunghwan Suh, Sun Joon Moon, Sun Ok Song, Suk Chon, Jae Hyeon Kim
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Advancements in Insulin Pumps: A Comprehensive Exploration of Insulin Pump Systems, Technologies, and Future Directions
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A true continuous healthcare system for type 1 diabetes
Jiyong Kim, Salman Khan, Eun Kyu Kim, Hye-Jun Kil, Bo Min Kang, Hyo Geon Lee, Jin-Woo Park, Jun Young Yoon, Woochul Kim
Nano Energy.2023; 113: 108553. CrossRef

Original Articles

Drug/Regimen
Effects of Teneligliptin on HbA1c levels, Continuous Glucose Monitoring-Derived Time in Range and Glycemic Variability in Elderly Patients with T2DM (TEDDY Study): Ji Cheol Bae, Soo Heon Kwak, Hyun Jin Kim, Sang-Yong Kim, You-Cheol Hwang, Sunghwan Suh, Bok Jin Hyun, Ji Eun Cha, Jong Chul Won, Jae Hyeon Kim; Diabetes Metab J. 2022;46(1):81-92. Published online June 16, 2021; DOI: https://doi.org/10.4093/dmj.2021.0016

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Background
To evaluate the effects of teneligliptin on glycosylated hemoglobin (HbA1c) levels, continuous glucose monitoring (CGM)-derived time in range, and glycemic variability in elderly type 2 diabetes mellitus patients.
Methods
This randomized, double-blinded, placebo-controlled study was conducted in eight centers in Korea (clinical trial registration number: NCT03508323). Sixty-five participants aged ≥65 years, who were treatment-naïve or had been treated with stable doses of metformin, were randomized at a 1:1 ratio to receive 20 mg of teneligliptin (n=35) or placebo (n=30) for 12 weeks. The main endpoints were the changes in HbA1c levels from baseline to week 12, CGM metrics-derived time in range, and glycemic variability.
Results
After 12 weeks, a significant reduction (by 0.84%) in HbA1c levels was observed in the teneligliptin group compared to that in the placebo group (by 0.08%), with a between-group least squares mean difference of –0.76% (95% confidence interval [CI], –1.08 to –0.44). The coefficient of variation, standard deviation, and mean amplitude of glycemic excursion significantly decreased in participants treated with teneligliptin as compared to those in the placebo group. Teneligliptin treatment significantly decreased the time spent above 180 or 250 mg/dL, respectively, without increasing the time spent below 70 mg/dL. The mean percentage of time for which glucose levels remained in the 70 to 180 mg/dL time in range (TIR70–180) at week 12 was 82.0%±16.0% in the teneligliptin group, and placebo-adjusted change in TIR70–180 from baseline was 13.3% (95% CI, 6.0 to 20.6).
Conclusion
Teneligliptin effectively reduced HbA1c levels, time spent above the target range, and glycemic variability, without increasing hypoglycemia in our study population.

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Time in range—A new gold standard in type 2 diabetes research?
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Potential approaches using teneligliptin for the treatment of type 2 diabetes mellitus: current status and future prospects
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Mechanism of molecular interaction of sitagliptin with human DPP4 enzyme - New Insights
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A prospective multicentre open label study to assess effect of Teneligliptin on glycemic control through parameters of time in range (TIR) Metric using continuous glucose monitoring (TOP-TIR study)
Banshi Saboo, Suhas Erande, A.G. Unnikrishnan
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2022; 16(2): 102394. CrossRef
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Diabetes & Metabolism Journal.2022; 46(1): 49. CrossRef

Drug/Regimen
Increasing Age Associated with Higher Dipeptidyl Peptidase-4 Inhibition Rate Is a Predictive Factor for Efficacy of Dipeptidyl Peptidase-4 Inhibitors: Sangmo Hong, Chang Hee Jung, Song Han, Cheol-Young Park; Diabetes Metab J. 2022;46(1):63-70. Published online April 19, 2021; DOI: https://doi.org/10.4093/dmj.2020.0253

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Background
It is not known which type 2 diabetes mellitus (T2DM) patients would most benefit from dipeptidyl peptidase-4 (DPP-4) inhibitor treatment. We aimed to investigate the predictors of response to DPP-4 inhibitors considering degree of DPP-4 inhibition.
Methods
This study is a post hoc analysis of a 24-week, randomized, double-blind, phase III trial that compared the efficacy and safety of a DPP-4 inhibitor (gemigliptin vs. sitagliptin) in patients with T2DM. Subjects were classified into tertiles of T1 <65.26%, T2=65.26%–76.35%, and T3 ≥76.35% by DPP-4 inhibition. We analyzed the change from baseline in glycosylated hemoglobin (HbA1c) according to DPP-4 inhibition with multiple linear regression adjusting for age, ethnicity, body mass index, baseline HbA1c, and DPP-4 activity at baseline.
Results
The mean age was greater in the high tertile group compared with the low tertile group (T1: 49.8±8.3 vs. T2: 53.1±10.5 vs. T3: 55.3±9.5, P<0.001) of DPP-4 inhibition. Although HbA1c at baseline was not different among tertiles of DPP-4 inhibition (P=0.398), HbA1c after 24-week treatment was lower in the higher tertile compares to the lower tertile (T1: 7.30%±0.88% vs. T2: 7.12%±0.78% vs. T3: 7.00%±0.78%, P=0.021). In multiple regression analysis, DPP-4 enzyme inhibition rate was not a significant determent for HbA1c reduction due to age. In subgroup analysis by tertile of DPP-4 inhibition, age was the only significant predictor and only in the highest tertile (R²=0.281, B=–0.014, P=0.024).
Conclusion
This study showed that HbA1c reduction by DPP-4 inhibitor was associated with increasing age, and this association was linked with higher DPP-4 inhibition.

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Comparative efficacy and safety of sitagliptin or gliclazide combined with metformin in treatment-naive patients with type 2 diabetes: A single-center, prospective, randomized, controlled, noninferiority study with genetic polymorphism analysis
Min Qin, Lingxi Chao, Shiqun Liu
Medicine.2025; 104(2): e41061. CrossRef
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Che Mohd Nasril Che Mohd Nassir, Muhammad Danial Che Ramli, Usman Jaffer, Hafizah Abdul Hamid, Muhammad Zulfadli Mehat, Mazira Mohamad Ghazali, Ebrahim Nangarath Kottakal Cheriya
Current Issues in Molecular Biology.2024; 46(12): 13565. CrossRef

Review

Type 1 Diabetes
Time in Range from Continuous Glucose Monitoring: A Novel Metric for Glycemic Control: Jee Hee Yoo, Jae Hyeon Kim; Diabetes Metab J. 2020;44(6):828-839. Published online December 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0257; Correction in: Diabetes Metab J 2021;45(5):795

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Glycosylated hemoglobin (HbA1c) has been the sole surrogate marker for assessing diabetic complications. However, consistently reported limitations of HbA1c are that it lacks detailed information on short-term glycemic control and can be easily interfered with by various clinical conditions such as anemia, pregnancy, or liver disease. Thus, HbA1c alone may not represent the real glycemic status of a patient. The advancement of continuous glucose monitoring (CGM) has enabled both patients and healthcare providers to monitor glucose trends for a whole single day, which is not possible with HbA1c. This has allowed for the development of core metrics such as time spent in time in range (TIR), hyperglycemia, or hypoglycemia, and glycemic variability. Among the 10 core metrics, TIR is reported to represent overall glycemic control better than HbA1c alone. Moreover, various evidence supports TIR as a predictive marker of diabetes complications as well as HbA1c, as the inverse relationship between HbA1c and TIR reveals. However, there are more complex relationships between HbA1c, TIR, and other CGM metrics. This article provides information about 10 core metrics with particular focus on TIR and the relationships between the CGM metrics for comprehensive understanding of glycemic status using CGM.

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Short Communication

COVID-19
Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus: Sung-Don Park, Sung-Woo Kim, Jun Sung Moon, Yin Young Lee, Nan Hee Cho, Ji-Hyun Lee, Jae-Han Jeon, Yeon-Kyung Choi, Mi Kyung Kim, Keun-Gyu Park; Diabetes Metab J. 2021;45(1):109-114. Published online December 4, 2020; DOI: https://doi.org/10.4093/dmj.2020.0226

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This study investigated the impact of social distancing due to coronavirus disease 2019 (COVID-19) on glycemic control in people with type 2 diabetes mellitus (T2DM). We retrospectively analyzed the change in glycosylated hemoglobin level (ΔHbA1c) in people with T2DM who undertook social distancing because of COVID-19. We compared the ΔHbA1c between COVID-19 and non-COVID-19 cohorts that were enrolled at the same time of year. The ΔHbA1c of the COVID-19 cohort was significantly higher than that of two non-COVID-19 cohorts. Subgroup analysis according to age and baseline HbA1c level showed that social distancing significantly increased the mean HbA1c level of participants of <50 years. The ΔHbA1c of participants of <50 years and with HbA1c <7.0% in the COVID-19 cohort showed larger changes than other subgroups. In adjusted model, adjusted ΔHbA1c levels in the COVID-19 cohort remained significantly higher than those in the two other cohorts. Social distancing negatively impacts blood glucose control in people with T2DM, especially those who are younger and have good blood glucose control.

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Brief Report

Drug/Regimen
Long-Term Glycaemic Durability of Early Combination Therapy Strategy versus Metformin Monotherapy in Korean Patients with Newly Diagnosed Type 2 Diabetes Mellitus: Soon-Jib Yoo, Sang-Ah Chang, Tae Seo Sohn, Hyuk-Sang Kwon, Jong Min Lee, Sungdae Moon, Pieter Proot, Päivi M Paldánius, Kun Ho Yoon; Diabetes Metab J. 2021;45(6):954-959. Published online November 12, 2020; DOI: https://doi.org/10.4093/dmj.2020.0173

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub

We assessed the glycaemic durability with early combination (EC; vildagliptin+metformin [MET], n=22) versus MET monotherapy (n=17), among newly-diagnosed type 2 diabetes mellitus (T2DM) enrolled (between 2012 and 2014) in the VERIFY study from Korea (n=39). Primary endpoint was time to initial treatment failure (TF) (glycosylated hemoglobin [HbA1c] ≥7.0% at two consecutive scheduled visits after randomization [end of period 1]). Time to second TF was assessed when both groups were receiving and failing on the combination (end of period 2). With EC the risk of initial TF significantly reduced by 78% compared to MET (n=3 [15%] vs. n=10 [58.7%], P=0.0228). No secondary TF occurred in EC group versus five patients (29.4%) in MET. Patients receiving EC treatment achieved consistently lower HbA1c levels. Both treatment approaches were well tolerated with no hypoglycaemic events. In Korean patients with newly diagnosed T2DM, EC treatment significantly and consistently improved the long-term glycaemic durability as compared with MET.

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Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial
Ji-Yeon Park, Joonyub Lee, Yoon-Hee Choi, Kyung Wan Min, Kyung Ah Han, Kyu Jeung Ahn, Soo Lim, Young-Hyun Kim, Chul Woo Ahn, Kyung Mook Choi, Kun-Ho Yoon
Diabetes & Metabolism Journal.2024; 48(5): 915. CrossRef
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 J
Diabetes & Metabolism Journal.2023; 47(5): 575. CrossRef
2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
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Diabetes & Metabolism Journal.2021; 45(4): 461. CrossRef

Original Article

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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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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