Background This study aimed to assess whether markers of diabetes severity could serve as predictors for foot amputation risk among patients with type 2 diabetes mellitus.
Methods We analyzed data from the nationally representative Korean National Health Insurance System database, tracking 2,544,077 patients with type 2 diabetes mellitus who participated in routine health check-ups between 2009 and 2012, with followup extending through the end of 2018. The parameters used to define the diabetes severity score encompassed diabetes duration, insulin usage, the number of oral glucose-lowering medications, the presence of chronic kidney disease, diabetic retinopathy, and cardiovascular disease. Each factor was assigned one point, yielding a cumulative severity score ranging from 0 to 6.
Results The risk of diabetic foot amputation was predominantly predicted by insulin therapy, diabetic retinopathy, and a prolonged duration of diabetes. The hazard ratios for foot amputation increased with the severity score as follows: 2.31 (95% confidence interval [CI], 2.15 to 2.47) for a score of 1, 4.73 (95% CI, 4.42 to 5.07) for a score of 2, 8.86 (95% CI, 8.24 to 9.53) for a score of 3, 16.95 (95% CI, 15.60 to 18.4) for a score of 4, 23.98 (95% CI, 21.25 to 27.05) for a score of 5, and 37.87 (95% CI, 28.93 to 49.57) for a score of 6.
Conclusion Specific markers of advanced diabetes effectively identified patients at an elevated risk for diabetic foot amputation.
Continuous glucose monitoring (CGM) has revolutionized diabetes management, significantly enhancing glycemic control across diverse patient populations. Recent evidence supports its effectiveness in both type 1 and type 2 diabetes management, with benefits extending beyond traditional glucose monitoring approaches. CGM has demonstrated substantial improvements in glycemic control across multiple metrics. Studies report consistent glycosylated hemoglobin reductions of 0.25%–3.0% and notable time in range improvements of 15%–34%. CGM effectively reduces hypoglycemic events, with studies reporting significant reductions in time spent in hypoglycemia. CGM also serves as an educational tool for lifestyle modification, providing real-time feedback that helps patients understand how diet and physical activity affect glucose levels. While skin-related complications remain a concern, technological advancements have addressed many initial concerns. High satisfaction rates and long-term use suggest that device-related issues are manageable with proper education and support. Despite high initial costs, CGM’s prevention of complications and hospitalizations ultimately reduces healthcare expenditures. With appropriate training and support, CGM represents a transformative technology for comprehensive diabetes care.
Background Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduces hyperglycemia and obesity by inhibiting renal glucose reabsorption. This post hoc study evaluated clinical factors influencing patient response to dapagliflozin.
Methods The analysis focused on patients treated with dapagliflozin (10 mg/day for 52 weeks) within the randomized, double-blind, parallel-group BEYOND trial. Adequate glycemic control (GC) was defined as a reduction in glycated hemoglobin (HbA1c) of ≥ 1.0% or the achievement of an HbA1c level <7.0% at week 52. Significant weight loss (WL) referred to a reduction in body weight of ≥3.0% at week 52. Participants were classified into four groups based on their GC and WL responses: GC+/WL+, GC+/WL−, GC−/WL+, and GC−/WL−.
Results Among dapagliflozin recipients (n=56), at 52 weeks, HbA1c had decreased by 1.0%±0.8% from baseline, while body weight had declined by 2.4±3.1 kg. Overall, 69.6% of participants achieved GC+, and 57.1% achieved WL+. Male sex and shorter diabetes duration were significantly associated with achieving GC+. Conversely, higher estimated glomerular filtration rate was significantly linked to WL+. The only factor significantly associated with both GC+ and WL+ was shorter diabetes duration (odds ratio, 0.81; 95% confidence interval, 0.68 to 0.97; P=0.023). The GC+ and WL+ groups exhibited favorable responses beginning soon after dapagliflozin therapy was initiated. Furthermore, HbA1c decline was more strongly associated with reduction in visceral fat than with WL.
Conclusion A short duration of diabetes and early response to treatment appear to represent key factors in maximizing the benefits of dapagliflozin for blood glucose and weight management.
Background We aimed to assess the association between triglyceride-glucose (TyG) index and cardiovascular disease (CVD) risk and mortality in a large cohort of diabetes patients.
Methods A retrospective cohort study of 1,090,485 participants from the Korean National Health Insurance Service database was conducted. Participants were stratified into TyG quartiles.
Results Higher TyG index quartiles were significantly associated with an increased CVD risk and mortality risk. In fully adjusted models, participants in the highest TyG quartile (Q4) had an 18% higher risk of CVD (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.13 to 1.23) and a 16% higher risk of mortality (HR, 1.16; 95% CI, 1.11 to 1.23) compared to those in the lowest quartile (Q1). The association was particularly pronounced in patients with fasting glucose ≥126 mg/dL (CVD [HR, 1.33; 95% CI, 1.29 to 1.37], mortality [HR, 1.23; 95% CI, 1.20 to 1.26]; P for interaction <0.001). Patients with a diabetes duration of ≥10 years showed the strongest association between the TyG index and CVD risk (HR, 1.44; 95% CI, 1.38 to 1.50), while the mortality risk was particularly elevated in those with a diabetes duration of less than 5 years (HR, 1.23; 95% CI, 1.18 to 1.30). Subgroup analyses revealed stronger associations between TyG index and CVD risk in younger participants, non-obese individuals, and non-smokers.
Conclusion The TyG index is a significant predictor of CVD and mortality in diabetic patients, particularly in those with poor glycemic control or longer disease duration.
Background This study investigated the prevalence of diabetes mellitus (DM) and impaired fasting glucose, as well as their management and comorbidities among older Korean adults.
Methods Data from 269,447 individuals aged 65 years and older from the Korean National Health Insurance Service between 2000 and 2019 were analyzed to evaluate trends in DM prevalence, healthcare utilization, mortality, and complications.
Results Among 269,447 individuals, 18.6% (n=50,159/269,447) were diagnosed with DM and 27.0% (n=72,670/269,447) had impaired fasting glucose. The DM group had the highest body mass index, waist circumference, and prevalence of current smokers (P<0.001) but not the highest hypertension prevalence. From 2010 to 2019, the prevalence of DM and impaired fasting glucose increased from 15.5% to 21.9% and from 26.0% to 30.6%, respectively. Cancer-related mortality in DM was 1.15 times higher than in those with normal glucose tolerance (P<0.001), and cardiovascular disease-related mortality was 1.32 times higher (P<0.001); all mortalities were higher in female participants. Myocardial infarction (hazard ratio [HR], 1.34; P<0.001), stroke (HR, 1.24; P<0.001), and heart failure (HR, 1.13; P<0.001) were significantly higher in those with DM.
Conclusion This is the first study to investigate the prevalence of DM and related complications in older individuals based on longterm representative data in Korea. These results highlight the necessity for targeted interventions to enhance management and outcomes in this population.
Background We examined the distribution of time to insulin therapy (TIT) post-diabetes diagnosis and the hazard of severe hypoglycemia (SH) according to TIT in Korean adults initially diagnosed with type 2 diabetes (T2D) and who progressed to insulin therapy.
Methods Using data from the Korean National Health Insurance Service (2002 to 2018), we selected adult incident insulin users (initially diagnosed as T2D) who underwent health examinations between 2009 and 2012. The hazards of SH, recurrent SH, and problematic hypoglycemia were analyzed according to groups categorized using the TIT and clinical risk factors for SH (TIT ≥5 years with risk factors, TIT ≥5 years without risk factors, 3 ≤TIT <5 years, 1 ≤TIT <3 years, and TIT <1 year).
Results Among 41,637 individuals, 14,840 (35.64%) and 10,587 (25.43%) initiated insulin therapy within <5 and <3 years postdiabetes diagnosis, respectively. During a median 6.53 years, 3,406 SH events occurred. Compared to individuals with TIT ≥5 years and no risk factor for SH, individuals with TIT <3 years had higher outcome hazards in a graded manner (adjusted hazard ratio [95% confidence intervals] for any SH: 1.117 [0.967 to 1.290] in those with 3 ≤TIT <5 years; 1.459 [1.284 to 1.657] in those with 1 ≤ TIT <3 years; and 1.515 [1.309 to 1.754] in those with TIT <1 year). This relationship was more pronounced in the non-obese subpopulation.
Conclusion Among adults who progressed to insulin therapy after being diagnosed with T2D, a shorter TIT was not uncommon and may predict an increased risk of SH, particularly in non-obese patients.
In East Asians, type 2 diabetes mellitus (T2DM) is primarily characterized by significant defects in insulin secretion and comparatively low insulin resistance. Recently, the prevalence of T2DM has rapidly increased in East Asian countries, including Korea, occurring concurrently with rising obesity rates. This trend has led to an increase in the average body mass index among East Asian T2DM patients, highlighting the influence of insulin resistance in the development of T2DM within this group. Currently, the incidence of T2DM in Korea is declining, which may indicate potential adaptive changes in insulin secretory capacity. This review focuses on the changing epidemiology of T2DM in East Asia, with a particular emphasis on the characteristics of peak functional β-cell mass.
Background Data on the carcinogenic potential of tirzepatide from randomized controlled trials (RCTs) are limited. Furthermore, no meta-analysis has included all relevant RCTs to assess the cancer risk associated with tirzepatide.
Methods RCTs involving patients receiving tirzepatide in the intervention arm and either a placebo or any active comparator in the control arm were searched through electronic databases. The primary outcome was the overall risk of any cancer, and secondary outcomes were the risks of specific types of cancer in the tirzepatide versus the control groups.
Results Thirteen RCTs with 13,761 participants were analyzed. Over 26 to 72 weeks, the tirzepatide and pooled control groups had identical risks of any cancer (risk ratio, 0.78; 95% confidence interval, 0.53 to 1.16; P=0.22). The two groups had comparable cancer risks in patients with and without diabetes. In subgroup analyses, the risks were also similar in the tirzepatide versus placebo, insulin, and glucagon-like peptide-1 receptor agonist groups. The overall cancer risk was also comparable for different doses of tirzepatide compared to the control groups; only a 10-mg tirzepatide dose had a lower risk of any cancer than placebo. Furthermore, compared to the control groups (pooled or separately), tirzepatide did not increase the risk of any specific cancer types. Despite greater increments in serum calcitonin with 10- and 15-mg tirzepatide doses than with placebo, the included RCTs reported no cases of papillary thyroid carcinoma.
Conclusion Tirzepatide use in RCTs over 26 to 72 weeks did not increase overall or specific cancer risk.
Background Achieving optimal glucose control is essential in the management of type 2 diabetes (T2D). This study aimed to evaluate the effectiveness and safety of oral quadruple combination therapy for the treatment of T2D.
Methods This meta-analysis reviewed original research on oral quadruple combination therapy for T2D, including both experimental and observational studies with a minimum duration of 12 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to follow-up. The secondary endpoint was the incidence rate of adverse events. Two investigators independently extracted data and assessed the risk of bias. Outcomes were pooled as the standardized mean difference (using Hedge’s g) and the risk ratio for adverse events in random-effects meta-analyses.
Results The meta-analysis included 17 studies. Oral quadruple combination therapy resulted in an additional mean reduction in HbA1c levels of 1.1% in patients who did not achieve glycemic control with oral triple combination therapy. Compared with switching to injectables, such as insulin or a glucagon-like peptide-1 receptor agonist–containing regimen, this therapy was non-inferior, even demonstrating a slightly superior glucose-lowering effect. Furthermore, it was determined to be safe, with an adverse event rate of 0.25, indicating no significant difference in safety compared with adding a placebo or switching to an injectable-containing regimen.
Conclusion Oral quadruple combination therapy is a valid option for patients with T2D who are unable to achieve glycemic targets with oral triple combination therapy, offering both effective glycemic control and a favorable safety profile.
In the context of a global shortage of glucagon-like peptide-1 (GLP-1) receptor agonists, we assessed the impact of discontinuing dulaglutide on metabolic control in individuals with type 2 diabetes. Our analysis included data from 69 individuals and revealed a significant deterioration in glycemic control following the discontinuation. Specifically, the average hemoglobin A1c level increased from 7.0%±0.9% to 8.1%±1.4% (P<0.001), and fasting glucose levels rose from 129±31 to 156±50 mg/dL (P<0.001) within 3 months after stopping the medication. Alternative treatments such as dipeptidyl peptidase-4 inhibitors and sodium glucose cotransporter- 2 inhibitors were insufficient substitutes, highlighting the essential role of continuous GLP-1 receptor agonist therapy in maintaining metabolic health.
Original Articles
Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Background Intellectual disability (ID) may be associated with an increased risk of diabetes mellitus (DM). However, evidence from longitudinal studies is scarce, particularly in Asian populations.
Methods This retrospective cohort study used representative linked data from the Korea National Disability Registration System and the National Health Insurance Service database. Adults (≥20 years) who received a national health examination in 2009 (3,385 individuals with ID and 3,463,604 individuals without ID) were included and followed until 2020. ID was identified using legal registration information. Incident DM was defined by prescription records with relevant diagnostic codes. Multivariable-adjusted Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for DM risks in individuals with ID compared to those without ID.
Results Over a mean follow-up of 9.8 years, incident DM occurred in 302 (8.9%) individuals with ID and 299,156 (8.4%) individuals without ID. Having ID was associated with increased DM risk (aHR, 1.38; 95% CI, 1.23 to 1.55). Sensitivity analysis confirmed a higher DM risk in individuals with ID (aHR, 1.39; 95% CI, 1.24 to 1.56) than those with other disabilities (aHR, 1.11; 95% CI, 1.10 to 1.13) or no disability (reference). Stratified analysis showed higher DM risk in non-hypertensive subjects (aHR, 1.63; 95% CI, 1.43 to 1.86) compared to hypertensive subjects (aHR, 1.00; 95% CI, 0.80 to 1.26; P for interaction <0.001).
Conclusion Adults with ID have an increased risk of developing DM, highlighting the need for targeted public health strategies to promote DM prevention in this population.
Background This study investigated the prognostic importance of the hemoglobin glycation index (HGI) for macrovascular and microvascular outcomes, mortality, and hypoglycemia occurrence in a type 2 diabetes cohort and compared it to glycated hemoglobin (HbA1c).
Methods Baseline and mean first-year HGI and HbA1c, and the variability thereof, were assessed in 687 individuals with type 2 diabetes (median follow-up, 10.6 years). Multivariable Cox regression was conducted to evaluate the associations of HGI and HbA1c parameters with macrovascular (total and major cardiovascular events) and microvascular outcomes (microalbuminuria, advanced renal failure, retinopathy, and peripheral neuropathy), mortality (all-cause and cardiovascular), and moderate/severe hypoglycemia occurrence.
Results During follow-up, there were 215 total cardiovascular events (176 major) and 269 all-cause deaths (131 cardiovascular). Microalbuminuria developed in 126 patients, renal failure in 104, retinopathy in 161, and neuropathy in 177. There were 90 hypoglycemia episodes. Both HGI and HbA1c predicted all adverse outcomes, except microalbuminuria and hypoglycemia. Their adjusted risks were roughly equivalent for all outcomes. For example, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), estimated for 1 standard deviation increments, of mean first-year HGI were 1.23 (1.05 to 1.44), 1.20 (1.03 to 1.38), 1.36 (1.11 to 1.67), 1.28 (1.09 to 1.67), and 1.29 (1.09 to 1.54), respectively, for cardiovascular events, all-cause mortality, renal failure, retinopathy, and neuropathy; whereas the respective HRs (95% CIs) of mean HbA1c were 1.31 (1.12 to 1.53), 1.28 (1.11 to 1.48), 1.36 (1.11 to 1.67), 1.33 (1.14 to 1.55), and 1.29 (1.09 to 1.53).
Conclusion HGI was no better than HbA1c as a predictor of adverse outcomes in individuals with type 2 diabetes, and its clinical use cannot be currently advised.
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Diabetes is a serious public health concern that significantly contributes to the global burden of disease. In Korea, the prevalence of diabetes is 12.5% among individuals aged 19 and older, and 14.8% among individuals aged 30 and older as of 2022. The total number of people with diabetes among those aged 19 and older is estimated to be 5.4 million. The incidence of diabetes decreased from 8.1 per 1,000 persons in 2006 to 6.3 per 1,000 persons in 2014, before rising again to 7.5 per 1,000 persons in 2019. Meanwhile, the incidence of type 1 diabetes increased significantly, from 1.1 per 100,000 persons in 1995 to 4.8 per 100,000 persons in 2016, with the prevalence reaching 41.0 per 100,000 persons in 2017. Additionally, the prevalence of gestational diabetes saw a substantial rise from 4.1% in 2007 to 22.3% in 2023. These changes have resulted in increases in the total medical costs for diabetes, covering both outpatient and inpatient services. Therefore, effective diabetes prevention strategies are urgently needed.
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Background We examined the impact of gout on the end-stage renal disease (ESRD) risk in patients with type 2 diabetes mellitus (T2DM) and determined whether this association differs according to chronic kidney disease (CKD) status.
Methods Using the Korean National Health Insurance Service, this nationwide cohort study enrolled 847,884 patients with T2DM who underwent health checkups in 2009. Based on the presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) and gout (two outpatient visits or one hospitalization within 5 years), patients were classified into four groups: CKD−Gout−, CKD− Gout+, CKD+Gout−, and CKD+Gout+. Patients with incident ESRD were followed up until December 2018.
Results Among 847,884 patients, 11,825 (1.4%) experienced progression to ESRD. ESRD incidence increased in the following order: 0.77 per 1,000 person-years (PY) in the CKD−Gout− group, 1.34/1,000 PY in the CKD−Gout+ group, 8.20/1,000 PY in the CKD+Gout− group, and 23.06/1,000 PY in the CKD+Gout+ group. The presence of gout modified the ESRD risk in a status-dependent manner. Hazard ratios (HR) were 1.49 (95% confidence interval [CI], 1.32 to 1.69) and 2.24 (95% CI, 2.09 to 2.40) in patients without and with CKD, respectively, indicating a significant interaction (P<0.0001). The CKD+Gout+ group had a markedly higher risk of developing ESRD (HR, 18.9; 95% CI, 17.58 to 20.32) than the reference group (CKD−Gout−).
Conclusion Gout substantially enhances the risk of ESRD, even in the absence of CKD. Concurrent CKD and gout synergistically increase the risk of ESRD. Therefore, physicians should carefully screen for hyperuricemia to prevent progression to ESRD.
Prior research has highlighted poor clinical outcomes in coronavirus disease 2019 (COVID-19)-infected patients with diabetes; however, susceptibility to COVID-19 infection in patients with diabetes has not been extensively studied. Participants aged ≥30 years who underwent COVID-19 testing from December 2019 to April 2020 were analyzed using the National Health Insurance Service data in South Korea. In a cohort comprising 29,433 1:1 propensity score-matched participants, COVID-19 positivity was significantly higher in participants with diabetes than in those without diabetes (512 [3.5%] vs. 395 [2.7%], P<0.001). Logistic regression analysis indicated that diabetes significantly increased the risk of COVID-19 test positivity (odds ratio, 1.307; 95% confidence interval, 1.144 to 1.493; P<0.001). Patients with diabetes exhibited heightened COVID-19 infection rates compared to individuals without diabetes, and diabetes increased the susceptibility to COVID-19, reinforcing the need for heightened preventive measures, particularly considering the poor clinical outcomes in this group.