Diabetes & Metabolism Journal

Original Articles

Technology/Device
Current Status of Continuous Glucose Monitoring Use in South Korean Type 1 Diabetes Mellitus Population–Pronounced Age-Related Disparities: Nationwide Cohort Study: Ji Yoon Kim, Seohyun Kim, Jae Hyeon Kim; Received December 9, 2024 Accepted February 3, 2025 Published online April 28, 2025; DOI: https://doi.org/10.4093/dmj.2024.0804 [Epub ahead of print]

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Abstract PDF: Background
This study aims to identify the status of continuous glucose monitoring (CGM) use among individuals with type 1 diabetes mellitus (T1DM) in South Korea and to investigate whether age-related disparities exist.
Methods
Individuals with T1DM receiving intensive insulin therapy were identified from the Korean National Health Insurance Cohort (2019–2022). Characteristics of CGM users and non-users were compared, and the prescription rates of CGM and sensor- augmented pump (SAP) or automated insulin delivery (AID) systems according to age groups (<19, 19–39, 40–59, and ≥60 years) were analyzed using chi-square tests. Glycosylated hemoglobin (HbA1c) levels and coefficients of variation (CV) among CGM users were also examined.
Results
Among the 56,908 individuals with T1DM, 10,822 (19.0%) used CGM at least once, and 6,073 (10.7%) used CGM continuously. Only 241 (0.4%) individuals utilized either SAP or AID systems. CGM users were younger than non-users. The continuous prescription rate of CGM was highest among individuals aged <19 years (37.0%), followed by those aged 19–39 years (15.8%), 40–59 years (10.7%), and ≥60 years (3.9%) (P<0.001 for between-group differences). Among CGM users, HbA1c levels decreased from 8.7%±2.4% at baseline to 7.2%±1.2% at 24 months, and CV decreased from 36.6%±11.9% at 3 months to 34.1%±12.7% at 24 months.
Conclusion
Despite national reimbursement for CGM devices, the prescription rates of CGM remain low, particularly among older adults. Given the improvements in HbA1c and CV following CGM initiation, more efforts are needed to increase CGM utilization and reduce age-related disparities.

Basic Research
Effects of CXCR1/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in Rat: Serena Boccella, Andrea Maria Morace, Cristina Giorgio, Francesca Guida, Michela Perrone, Iolanda Manzo, Carmela Belardo, Meghan Jones, Sabatino Maione, Andrea Aramini, Marcello Allegretti, Livio Luongo, Laura Brandolini; Received August 25, 2024 Accepted November 15, 2024 Published online March 12, 2025; DOI: https://doi.org/10.4093/dmj.2024.0504 [Epub ahead of print]

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The CXC motif chemokine ligand 8 (CXCL8)-CXC motif chemokine receptor 1/2 (CXCR1/2) axis has been implicated in type 1 diabetes mellitus (T1DM). Its actions on non-immune cells may also contribute to T1DM-associated complications, including painful diabetic peripheral neuropathy (DPN) and diabetic retinopathy (DR).
Methods
We assessed the efficacy of early (4–8 weeks) or late (8–12 weeks) daily ladarixin (LDX) for the treatment of streptozotocin (STZ)-induced T1DM and the related complications of DPN or DR in male rats.
Results
Early LDX mitigated STZ-induced dysmetabolism (i.e., blood glucose, insulin), inflammation in dorsal root ganglion/ sciatic nerve (interleukin-1β and tumor necrosis factor-α expression) and mechanical allodynia and thermal hyperalgesia, indicative of DPN. Moreover, vitreous citrullinated histone H3 (CitH3) and plasma GRO/CINC1 (CXCL8) increase were attenuated. Late LDX failed to reverse STZ-induced changes in metabolic parameters (i.e., blood glucose, insulin, C-peptide, pancreatic β-cell number and function). Strikingly, even in the absence of an effect on glycemic control, late LDX mitigated STZ-induced mechanical allodynia and thermal hyperalgesia and vitreous (CXCL8, CitH3) and retinal (CXCL8, CXCR1/2, myeloperoxidase, CitH3) inflammatory/pro-angiogenic (vascular endothelial growth factor, CD34) signs of DR.
Conclusion
These data confirm the efficacy of LDX in STZ-induced T1DM and provide evidence of a protective effect also against DPN and onset of DR which is independent of its effect on β-cell functionality preservation and glycemic control.

Type 1 Diabetes
Global Burden of Type 1 Diabetes Mellitus Related Chronic Kidney Disease among Adolescents and Young Adults, and Projections to 2035: Results from the Global Burden of Disease Study 2021: Xiaoli Qu, Chongbin Liu, Lin Sun, Zhifeng Sheng; Received September 4, 2024 Accepted December 12, 2024 Published online March 10, 2025; DOI: https://doi.org/10.4093/dmj.2024.0544 [Epub ahead of print]

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Type 1 diabetes mellitus related chronic kidney disease (T1DM-CKD) presents a global health challenge, with unclear trends and patterns among adolescents and young adults. This study analyzed the burden and risk factors of T1DM-CKD in individuals aged 15 to 39 from 1990 to 2021 and predicted future trends.
Methods
Using data from the Global Burden of Disease (GBD) study 2021, we analyzed the prevalence, incidence, mortality, disability-adjusted life years (DALYs), and average annual percentage change (AAPC) of T1DM-CKD among youth across gender, sociodemographic index (SDI) areas, and data from 21 regions and 204 countries and territories. Risk factors were assessed and future trends were projected.
Results
Between 1990 and 2021, the global prevalence of T1DM-CKD aged 15 to 39 increased by 107.5% to 3.32 million, with an age-standardized prevalence rate (ASPR) of 111.44 per 100,000 (AAPC 1.33%). Incidence rose by 165.4% to 14,200, with an agestandardized incidence rate of 0.48 per 100,000 (AAPC 2.19%). However, age-standardized mortality rate (0.50 per 100,000, AAPC –0.87%) and age-standardized DALYs rate (30.61 per 100,000, AAPC –0.83%) decreased. ASPR increased across all SDI regions, especially in high-SDI countries. High fasting glucose remained the major risk factor influencing DALYs. By 2035, T1DM-CKD prevalence was projected to decrease to 2.86 million (ASPR 89.67 per 100,000).
Conclusion
The research revealed a global increase in T1DM-CKD among youth, with a shift towards younger onset and significant variations based on gender and location, emphasizing the importance of early prevention and management strategies for this demographic.

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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Abstract PDF Supplementary Material PubReader ePub: Background
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.

Technology/Device
Efficacy and Safety of Automated Insulin Delivery Systems in Patients with Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis: Wenqi Fan, Chao Deng, Ruoyao Xu, Zhenqi Liu, Richard David Leslie, Zhiguang Zhou, Xia Li; Diabetes Metab J. 2025;49(2):235-251. Published online November 13, 2024; DOI: https://doi.org/10.4093/dmj.2024.0130

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Background
Automated insulin delivery (AID) systems studies are upsurging, half of which were published in the last 5 years. We aimed to evaluate the efficacy and safety of AID systems in patients with type 1 diabetes mellitus (T1DM).
Methods
We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov until August 31, 2023. Randomized clinical trials that compared AID systems with other insulin-based treatments in patients with T1DM were considered eligible. Studies characteristics and glycemic metrics was extracted by three researchers independently.
Results
Sixty-five trials (3,623 patients) were included. The percentage of time in range (TIR) was 11.74% (95% confidence interval [CI], 9.37 to 14.12; P<0.001) higher with AID systems compared with control treatments. Patients on AID systems had more pronounced improvement of time below range when diabetes duration was more than 20 years (–1.80% vs. –0.86%, P=0.031) and baseline glycosylated hemoglobin lower than 7.5% (–1.93% vs. –0.87%, P=0.033). Dual-hormone full closed-loop systems revealed a greater improvement in TIR compared with hybrid closed-loop systems (–19.64% vs. –10.87%). Notably, glycemia risk index (GRI) (–3.74; 95% CI, –6.34 to –1.14; P<0.01) was also improved with AID therapy.
Conclusion
AID systems showed significant advantages compared to other insulin-based treatments in improving glucose control represented by TIR and GRI in patients with T1DM, with more favorable effect in euglycemia by dual-hormone full closedloop systems as well as less hypoglycemia for patients who are within target for glycemic control and have longer diabetes duration.

Citations

Citations to this article as recorded by

Transitioning between automated insulin delivery systems: A focus on personalisation
Pilar Isabel Beato-Víbora, Ana Chico, Jesus Moreno-Fernandez, Sharona Azriel-Mira, Lia Nattero-Chávez, Rosario Vallejo Mora, Núria Alonso-Carril, Olga Simó-Servat, Eva Aguilera-Hurtado, Luz María Reyes Céspedes, Marisol Ruiz de Adana, Marta Domínguez, Ros
Diabetes Research and Clinical Practice.2025; 222: 112070. CrossRef

Brief Report

Technology/Device
Effectiveness of Predicted Low-Glucose Suspend Pump Technology in the Prevention of Hypoglycemia in People with Type 1 Diabetes Mellitus: Real-World Data Using DIA:CONN G8: Jee Hee Yoo, Ji Yoon Kim, Jae Hyeon Kim; Diabetes Metab J. 2025;49(1):144-149. Published online August 28, 2024; DOI: https://doi.org/10.4093/dmj.2024.0039

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Abstract PDF Supplementary Material PubReader ePub: We evaluated the effectiveness of the predictive low-glucose suspend (PLGS) algorithm in the DIA:CONN G8. Forty people with type 1 diabetes mellitus (T1DM) who used a DIA:CONN G8 for at least 2 months with prior experience using pumps without and with PLGS were retrospectively analyzed. The objective was to assess the changes in time spent in hypoglycemia (percent of time below range [%TBR]) before and after using PLGS. The mean age, sensor glucose levels, glucose threshold for suspension, and suspension time were 31.1±22.8 years, 159.7±23.2 mg/dL, 81.1±9.1 mg/dL, and 111.9±79.8 min/day, respectively. Overnight %TBR <70 mg/dL was significantly reduced after using the algorithm (differences=0.3%, from 1.4%±1.5% to 1.1%±1.2%, P=0.045). The glycemia risk index (GRI) improved significantly by 4.2 (from 38.8±20.9 to 34.6±19.0, P=0.002). Using the PLGS did not result in a change in the hyperglycemia metric (all P>0.05). Our findings support the PLGS in DIA:CONN G8 as an effective algorithm to improve night-time hypoglycemia and GRI in people with T1DM.

Original Articles

Type 1 Diabetes
A New Tool to Identify Pediatric Patients with Atypical Diabetes Associated with Gene Polymorphisms: Sophie Welsch, Antoine Harvengt, Paola Gallo, Manon Martin, Dominique Beckers, Thierry Mouraux, Nicole Seret, Marie-Christine Lebrethon, Raphaël Helaers, Pascal Brouillard, Miikka Vikkula, Philippe A. Lysy; Diabetes Metab J. 2024;48(5):949-959. Published online March 22, 2024; DOI: https://doi.org/10.4093/dmj.2023.0166

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Abstract PDF Supplementary Material PubReader ePub: Background
Recent diabetes subclassifications have improved the differentiation between patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus despite several overlapping features, yet without considering genetic forms of diabetes. We sought to facilitate the identification of monogenic diabetes by creating a new tool that we validated in a pediatric maturity-onset diabetes of the young (MODY) cohort.
Methods
We first created the DIAgnose MOnogenic DIAbetes (DIAMODIA) criteria based on the pre-existing, but incomplete, MODY calculator. This new score is composed of four strong and five weak criteria, with patients having to display at least one weak and one strong criterion.
Results
The effectiveness of the DIAMODIA criteria was evaluated in two patient cohorts, the first consisting of patients with confirmed MODY diabetes (n=34) and the second of patients with T1DM (n=390). These DIAMODIA criteria successfully detected 100% of MODY patients. Multiple correspondence analysis performed on the MODY and T1DM cohorts enabled us to differentiate MODY patients from T1DM. The three most relevant variables to distinguish a MODY from T1DM profile were: lower insulin-dose adjusted A1c score ≤9, glycemic target-adjusted A1c score ≤4.5, and absence of three anti-islet cell autoantibodies.
Conclusion
We validated the DIAMODIA criteria, as it effectively identified all monogenic diabetes patients (MODY cohort) and succeeded to differentiate T1DM from MODY patients. The creation of this new and effective tool is likely to facilitate the characterization and therapeutic management of patients with atypical diabetes, and promptly referring them for genetic testing which would markedly improve clinical care and counseling, as well.

Type 1 Diabetes
Optimal Coefficient of Variance Threshold to Minimize Hypoglycemia Risk in Individuals with Well-Controlled Type 1 Diabetes Mellitus: Jee Hee Yoo, Seung Hee Yang, Sang-Man Jin, Jae Hyeon Kim; Diabetes Metab J. 2024;48(3):429-439. Published online March 4, 2024; DOI: https://doi.org/10.4093/dmj.2023.0083

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Abstract PDF Supplementary Material PubReader ePub: Background
This study investigated the optimal coefficient of variance (%CV) for preventing hypoglycemia based on real-time continuous glucose monitoring (rt-CGM) data in people with type 1 diabetes mellitus (T1DM) already achieving their mean glucose (MG) target.
Methods
Data from 172 subjects who underwent rt-CGM for at least 90 days and for whom 439 90-day glycemic profiles were available were analyzed. Receiver operator characteristic analysis was conducted to determine the cut-off value of %CV to achieve time below range (%TBR)^{<54 mg/dL} <1 and =0.
Results
Overall mean glycosylated hemoglobin was 6.8% and median %TBR^{<54 mg/dL} was 0.2%. MG was significantly higher and %CV significantly lower in profiles achieving %TBR^{<54 mg/dL} <1 compared to %TBR^{<54 mg/dL} ≥1 (all P<0.001). The cut-off value of %CV for achieving %TBR^{<54 mg/dL} <1 was 37.5%, 37.3%, and 31.0%, in the whole population, MG >135 mg/dL, and ≤135 mg/dL, respectively. The cut-off value for %TBR^{<54 mg/dL}=0% was 29.2% in MG ≤135 mg/dL. In profiles with MG ≤135 mg/dL, 94.2% of profiles with a %CV <31 achieved the target of %TBR^{<54 mg/dL} <1, and 97.3% with a %CV <29.2 achieved the target of %TBR<54 mg/ dL=0%. When MG was >135 mg/dL, 99.4% of profiles with a %CV <37.3 achieved %TBR^{<54 mg/dL} <1.
Conclusion
In well-controlled T1DM with MG ≤135 mg/dL, we suggest a %CV <31% to achieve the %TBR^{<54 mg/dL} <1 target. Furthermore, we suggest a %CV <29.2% to achieve the target of %TBR^{<54 mg/dL} =0 for people at high risk of hypoglycemia.

Complications
Does the Relationship of the Autonomic Symptoms Questionnaire COMPASS 31 with Cardiovascular Autonomic Tests Differ between Type 1 and Type 2 Diabetes Mellitus?: Ilenia D’Ippolito, Marika Menduni, Cinzia D’Amato, Aikaterini Andreadi, Davide Lauro, Vincenza Spallone; Diabetes Metab J. 2024;48(6):1114-1125. Published online February 26, 2024; DOI: https://doi.org/10.4093/dmj.2023.0301

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Background
The aim was to investigate if autonomic symptoms questionnaire Composite Autonomic Symptom Score (COMPASS) 31 has different association with cardiovascular autonomic neuropathy (CAN) and diagnostic performance between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).
Methods
Seventy-nine participants with T1DM and 140 with T2DM completed COMPASS 31 before cardiovascular reflex tests (CARTs) for CAN, and assessment of symptoms, signs, vibration, and thermal perception thresholds for diabetic polyneuropathy (DPN) diagnosis.
Results
COMPASS 31 total weighted score (TWS) was similar in the two groups, but significantly associated with confirmed CAN only in T1DM (P=0.0056) and not T2DM group (P=0.1768) and correlated with CARTs score more strongly in T1DM (rho=0.356, P=0.0016) than in T2DM group (rho=0.084, P=0.3218) (P=0.016). Only in T1DM and not T2DM group, the area under the receiver operating characteristic curve (AUC) reached a fair diagnostic accuracy (>0.7) for confirmed CAN (0.73±0.07 vs. 0.61±0.08) and DPN (0.75±0.06 vs. 0.68±0.05), although without a significant difference. COMPASS 31 TWS (cut-off 16.44) reached acceptable diagnostic performance in T1DM, with sensitivity for confirmed CAN 81.2% and sensitivity and specificity for DPN 76.3% and 78%, compared to T2DM group (all <70%). AUC for DPN of orthostatic intolerance domain was higher in T1DM compared to T2DM group (0.73±0.05 vs. 0.58±0.04, P=0.027).
Conclusion
COMPASS 31 is more weakly related to CAN in T2DM than in T1DM, with a fair diagnostic accuracy for confirmed CAN only in T1DM. This difference supports a multifactorial origin of symptoms and should be considered when using COMPASS 31.

Citations

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Corneal confocal microscopy identifies early and definite diabetic cardiac autonomic neuropathy
Shazli Azmi, Maryam Ferdousi, Alise Kalteniece, Ioannis N Petropoulos, Uazman Alam, Georgios Ponirakis, Omar Asghar, Andrew Marshall, Andrew JM Boulton, Nathan Efron, Rayaz A Malik
Diabetes Research and Clinical Practice.2025; 224: 112172. CrossRef
Frequency and severity of autonomic dysfunction assessed by objective hemodynamic responses and patient-reported symptoms in individuals with myasthenia gravis
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Frontiers in Neuroscience.2024;[Epub] CrossRef

Review

Pathophysiology
Immune-Checkpoint Inhibitors-Induced Type 1 Diabetes Mellitus: From Its Molecular Mechanisms to Clinical Practice: Yun Kyung Cho, Chang Hee Jung; Diabetes Metab J. 2023;47(6):757-766. Published online July 24, 2023; DOI: https://doi.org/10.4093/dmj.2023.0072

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With the increasing use of immune-checkpoint inhibitors (ICIs), such as anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and anti-programmed cell death-1 (PD-1), for the treatment of malignancies, cases of ICI-induced type 1 diabetes mellitus (ICI-T1DM) have been reported globally. This review focuses on the features and pathogenesis of this disease. T1DM is an immune-related adverse event that occurs following the administration of anti-PD-1 or anti-programmed death ligand-1 (PDL1) alone or in combination with anti-CTLA-4. More than half of the reported cases presented as abrupt-onset diabetic ketoacidosis. The primary mechanism of ICI-T1DM is T-cell stimulation, which results from the loss of interaction between PD-1 and PD-L1 in pancreatic islet. The similarities and differences between ICI-T1DM and classical T1DM may provide insights into this disease entity. ICI-T1DM is a rare but often life-threatening medical emergency that healthcare professionals and patients need to be aware of. Early detection of and screening for this disease is imperative. At present, the only known treatment for ICI-T1DM is insulin injection. Further research into the mechanisms and risk factors associated with ICI-T1DM development may contribute to a better understanding of this disease entity and the identification of possible preventive strategies.

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Original Articles

Lifestyle
Clinical Effects of a Home Care Pilot Program for Patients with Type 1 Diabetes Mellitus: A Retrospective Cohort Study: Sejeong Lee, KyungYi Kim, Ji Eun Kim, Yura Hyun, Minyoung Lee, Myung-Il Hahm, Sang Gyu Lee, Eun Seok Kang; Diabetes Metab J. 2023;47(5):693-702. Published online June 22, 2023; DOI: https://doi.org/10.4093/dmj.2022.0170

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Background
Given the importance of continuous self-care for people with type 1 diabetes mellitus (T1DM), the Ministry of Health and Welfare of Korea launched a pilot program for chronic disease management. Herein, we applied a home care pilot program to people with T1DM to investigate its effects.
Methods
This retrospective cohort study was conducted at a single tertiary hospital (January 2019 to October 2021). A multidisciplinary team comprising doctors, nurses, and clinical nutritionists provided specialized education and periodically assessed patients’ health status through phone calls or text messages. A linear mixed model adjusting for age, sex, and body mass index was used to analyze the glycemic control changes before and after implementing the program between the intervention and control groups.
Results
Among 408 people with T1DM, 196 were enrolled in the intervention group and 212 in the control group. The reduction in glycosylated hemoglobin (HbA1c) after the program was significantly greater in the intervention group than in the control group (estimated marginal mean, –0.57% vs. –0.23%, P=0.008); the same trend was confirmed for glycoalbumin (GA) (–3.2% vs. –0.39%, P<0.001). More patients achieved the target values of HbA1c (<7.0%) and GA (<20%) in the intervention group than in the control group at the 9-month follow-up (34.5% vs. 19.6% and 46.7% vs. 28.0%, respectively).
Conclusion
The home care program for T1DM was clinically effective in improving glycemic control and may provide an efficient care option for people with T1DM, and positive outcomes are expected to expand the program to include more patients.

Citations

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Glycemic outcomes and patient satisfaction and self-management improves in transition from standard to virtual multidisciplinary care
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Diabetes Research and Clinical Practice.2024; 209: 111587. CrossRef

Guideline/Fact Sheet
Insulin Fact Sheet in Type 1 and 2 Diabetes Mellitus and Trends of Antidiabetic Medication Use in Insulin Users with Type 2 Diabetes Mellitus: 2002 to 2019: Jiyun Park, Gyuri Kim, Bong-Sung Kim, Kyung-Do Han, So Yoon Kwon, So Hee Park, You-Bin Lee, Sang-Man Jin, Jae Hyeon Kim; Diabetes Metab J. 2023;47(2):211-219. Published online February 7, 2023; DOI: https://doi.org/10.4093/dmj.2022.0346

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Background
This study investigated the trends of insulin use among Korean patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Changes in prescription of antidiabetic medications in T2DM patients taking insulin therapy were evaluated.
Methods
We analyzed data from the National Health Insurance Service database in Korea to evaluate the prevalence of insulin users and trends of insulin use in T1DM and T2DM patients from January 2002 to December 2019. We also investigated numbers and types of antidiabetic medications in insulin users with T2DM.
Results
The overall total number of insulin users increased from 2002 to 2019, reaching 348,254 for T2DM and 20,287 for T1DM in 2019 compared with 109,974 for T2DM and 34,972 for T1DM in 2002. The proportion of patients using basal analogs and short acting analogs have increased and those using human insulin, premixed insulin, or biphasic human insulin have decreased (rapid acting analogs: 71.85% and 24.12% in T1DM and T2DM, respectively, in 2019; basal analogs: 76.75% and 75.09% in T1DM and T2DM, respectively, in 2019). The use of other antidiabetic medication in addition to insulin increased for T2DM, especially in dual therapy, reaching up to 52.35% in 2019 compared with 16.72% in 2002.
Conclusion
The proportion of the patients using basal or rapid acting analogs increased among all insulin users in both T1DM and T2DM patients. Among patients with T2DM, the proportion of patients using antidiabetic medications in addition to insulin was significantly increased compared to those who used insulin alone.

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Review

Technology/Device
Advances in Continuous Glucose Monitoring and Integrated Devices for Management of Diabetes with Insulin-Based Therapy: Improvement in Glycemic Control: Jee Hee Yoo, Jae Hyeon Kim; Diabetes Metab J. 2023;47(1):27-41. Published online January 12, 2023; DOI: https://doi.org/10.4093/dmj.2022.0271

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Continuous glucose monitoring (CGM) technology has evolved over the past decade with the integration of various devices including insulin pumps, connected insulin pens (CIPs), automated insulin delivery (AID) systems, and virtual platforms. CGM has shown consistent benefits in glycemic outcomes in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) treated with insulin. Moreover, the combined effect of CGM and education have been shown to improve glycemic outcomes more than CGM alone. Now a CIP is the expected future technology that does not need to be worn all day like insulin pumps and helps to calculate insulin doses with a built-in bolus calculator. Although only a few clinical trials have assessed the effectiveness of CIPs, they consistently show benefits in glycemic outcomes by reducing missed doses of insulin and improving problematic adherence. AID systems and virtual platforms made it possible to achieve target glycosylated hemoglobin in diabetes while minimizing hypoglycemia, which has always been challenging in T1DM. Now fully automatic AID systems and tools for diabetes decisions based on artificial intelligence are in development. These advances in technology could reduce the burden associated with insulin treatment for diabetes.

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Original Articles

Type 1 Diabetes
Performance of Fast-Acting Aspart Insulin as Compared to Aspart Insulin in Insulin Pump for Managing Type 1 Diabetes Mellitus: A Meta-Analysis: Deep Dutta, Ritin Mohindra, Kunal Mahajan, Meha Sharma; Diabetes Metab J. 2023;47(1):72-81. Published online June 24, 2022; DOI: https://doi.org/10.4093/dmj.2022.0035

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Background
No meta-analysis has analysed efficacy and safety of fast-acting aspart insulin (FIAsp) with insulin pump in type 1 diabetes mellitus (T1DM).
Methods
Electronic databases were searched for randomised controlled trials (RCTs) involving T1DM patients on insulin pump receiving FIAsp in intervention arm, and placebo/active comparator insulin in control arm. Primary outcome was to evaluate changes in 1- and 2-hour post-prandial glucose (1hPPG and 2hPPG). Secondary outcomes were to evaluate alterations in percentage time with blood glucose <3.9 mmol/L (hypoglycaemia), time in range (TIR) blood glucose 3.9 to 10 mmol/L, insulin requirements and adverse events.
Results
Data from four RCTs involving 640 patients was analysed. FIAsp use in insulin pump was associated with significantly greater lowering of 1hPPG (mean difference [MD], –1.35 mmol/L; 95% confidence interval [CI], –1.72 to –0.98; P<0.01; I²=63%) and 2hPPG (MD, –1.19 mmol/L; 95% CI, –1.38 to –1.00; P<0.01; I²=0%) as compared to controls. TIR was comparable among groups (MD, 1.06%; 95% CI, –3.84 to 5.96; P=0.67; I²=70%). Duration of blood glucose <3.9 mmol/L was lower in FIAsp group, approaching significance (MD, –0.91%; 95% CI, –1.84 to 0.03; P=0.06; I²=0%). Total hypoglycaemic episodes (risk ratio [RR], 1.35; 95% CI, 0.55 to 3.31; P=0.51; I²=0%), severe hypoglycaemia (RR, 2.26; 95% CI, 0.77 to 6.66; P=0.14), infusion site reactions (RR, 1.35; 95% CI, 0.63 to 2.93; P=0.77; I²=0%), and treatment-emergent adverse events (RR, 1.13; 95% CI, 0.80 to 1.60; P=0.50; I²=0%) were comparable.
Conclusion
FIAsp use in insulin pump is associated with better post-prandial glycaemic control with no increased hypoglycaemia or glycaemic variability.

Citations

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Sergio Di Molfetta, Antonio Rossi, Roberta Assaloni, Roberto Franceschi, Valeria Grancini, Vincenzo Guardasole, Andrea Enzo Scaramuzza, Antonietta Maria Scarpitta, Maddalena Trombetta, Angela Zanfardino, Riccardo Candido, Angelo Avogaro, Valentino Cherubi
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Type 1 Diabetes
Identification of Key Genes and Pathways in Peripheral Blood Mononuclear Cells of Type 1 Diabetes Mellitus by Integrated Bioinformatics Analysis: Xing Li, Mingyu Liao, Jiangheng Guan, Ling Zhou, Rufei Shen, Min Long, Jiaqing Shao; Diabetes Metab J. 2022;46(3):451-463. Published online April 1, 2022; DOI: https://doi.org/10.4093/dmj.2021.0018

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Background
The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM.
Methods
Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb).
Results
We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM.
Conclusion
These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications.

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