KES
Articles
- Page Path
- HOME > Endocrinol Metab > Volume 40(4); 2025 > Article
-
Original ArticleDiabetes, obesity and metabolism The Severity of Diabetes and the Risk of Diabetic Foot Amputation: A National Cohort Study
Keypoint
- This study aimed to assess whether markers of diabetes severity could predict foot amputation risk in patients with type 2 diabetes mellitus.
- The risk of diabetic foot amputation was predominantly predicted by insulin therapy, diabetic retinopathy, and a prolonged duration of diabetes.
- Increased diabetes severity correlates with higher amputation rates. -
Jin Yu1*
, Ji-Hyun Kim1*, Bongseong Kim2, Kyungdo Han2, Seung Hwan Lee1, Mee Kyoung Kim3 -
Endocrinology and Metabolism 2025;40(4):574-582.
DOI: https://doi.org/10.3803/EnM.2024.2266
Published online: April 15, 2025
1Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
2Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
3Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Corresponding author: Mee Kyoung Kim. Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 1021 Tongil-ro, Eunpyeong-gu, Seoul 03312, Korea Tel: +82-2-2030-4435, Fax:+82-2-780-3132, E-mail: makung@catholic.ac.kr
- These authors contributed equally to this work.
• Received: November 28, 2024 • Revised: January 17, 2025 • Accepted: February 4, 2025
Copyright © 2025 Korean Endocrine Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
-
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 follow-up 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.
- Individuals with diabetes mellitus (DM) who develop foot ulcers face a 10- to 20-fold increased risk of amputation compared to those without DM. Furthermore, diabetic patients with a history of foot ulcers that have led to amputation experience even higher mortality rates than those without such complications [1-3]. Given that a previous episode of diabetic foot complications predisposes patients to future re-ulceration and amputation [1-3], it is crucial to prevent foot ulcers from developing in the first place. Therefore, establishing risk profiles is essential to identify high-risk patients who have not yet experienced a foot ulcer or amputation.
- A systematic review examining risk factors for diabetic foot complications consistently found that male sex, peripheral neuropathy, retinopathy, nephropathy, inadequate glycemic control, insulin therapy, longer diabetes duration, smoking, and increased height were positively correlated with these complications [2]. Excluding gender, height, and smoking, these factors also serve as indicators of diabetes severity [3-5]. Recently, a diabetes severity index was introduced that integrates insulin use, duration of diabetes, treatment complexity, and the presence of diabetic complications [4,5]. This suggests that identifying patients at risk for diabetic foot complications might be more effective when using markers of severe diabetes rather than focusing solely on poor glycemic control. In fact, one study reported no significant association between glycemic control and wound outcomes in diabetic patients [6]; neither baseline levels nor changes in glycosylated hemoglobin A1c (HbA1c) were clinically linked with wound healing in cases of diabetic foot ulcers.
- The Korean National Health Information Database (NHID) is a comprehensive, prospective population-based cohort that includes detailed baseline biochemical measurements (e.g., fasting blood glucose [FBG], renal function) along with complete medical usage and prescription data for roughly five million individuals [7-10]. In this study, we utilized NHID data to examine the relationship between diabetes severity and the risk of diabetic foot amputation.
INTRODUCTION
- Study population
- The Korean National Health Insurance Service (NHIS) offers a single-payer insurance system covering all South Korean residents (approximately 50 million individuals) and provides free health examinations every 2 years. These examinations include anthropometric measurements, laboratory tests, health behavior surveys (covering smoking, alcohol consumption, and exercise habits), and medical as well as family histories, as previously described [7-10]. The NHID holds comprehensive health examination records for all insured individuals along with demographic details and diagnostic codes related to inpatient and outpatient services, which facilitates the evaluation of diabetes-related complications.
- We included patients with type 2 DM aged 20 years or older who participated in the NHIS health examinations between 2009 and 2012 (n=2,745,689). We excluded individuals with missing data (n=171,129), those with a history of foot amputations (n=3,947), and individuals who experienced an amputation event or died during the first year of follow-up (n=26,536). This process resulted in a final cohort of 2,544,077 participants (Fig. 1). The Institutional Review Board of Yeouido St. Mary’s Hospital, The Catholic University of Korea (No. SC23ZISE0043), approved this study. Anonymous and deidentified information was used for analysis and, therefore, informed consent was not obtained.
- Data collection and definitions
- Covariate information was obtained from the health examinations conducted between 2009 and 2012 and encompassed variables such as age, sex, socioeconomic status (determined by income level), body mass index (BMI in kg/m2), current smoking status, alcohol use, exercise habits (yes/no), and both systolic and diastolic blood pressure (measured in mm Hg). Blood samples for serum glucose and creatinine levels were collected after an overnight fast. Glucose-lowering medications were categorized into six classes: insulin, sulfonylureas, metformin, thiazolidinediones, dipeptidyl-peptidase-4 inhibitors, and alpha-glucosidase inhibitors. Prescription details—including drug class, prescription date, duration of supply, and quantity dispensed—were also retrieved.
- Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. Cardiovascular disease (CVD) was identified as a history of myocardial infarction or stroke, confirmed by one or more inpatient or outpatient International Statistical Classification of Diseases 10th Revision (ICD-10) codes within the 3 years preceding the index date [4,5,7,8]. Diabetic retinopathy was determined by the presence of the relevant ICD-10 code during hospitalization or by recording this code at least twice in an outpatient setting for patients with type 2 DM within 3 years prior to the index date [8].
- Definition of parameters comprising the diabetes severity score
- The components of the diabetes severity score in this study included the complexity of diabetes medications (specifically, insulin use or the use of multiple oral glucose-lowering drugs [GLDs]), an extended duration of diabetes, the presence of diabetic retinopathy, diabetes-associated renal complications (i.e., CKD), and the presence of CVD [4,5]. Each factor was assigned one point, resulting in a cumulative diabetes severity score ranging from 0 to 6. For example, if a patient was taking three or more oral GLDs, they were assigned one point; similarly, a diabetes duration of 5 years or more contributed one point. Thus, a patient on insulin with diabetic retinopathy and a diabetes duration of at least 5 years would have a severity score of 3.
- Definition of diabetic foot amputation
- The primary endpoint of the study was the occurrence of a new, nontraumatic foot amputation, identified using ICD-10 codes N0562, N0564-6, and N0571-5 [11]. Participants who did not undergo foot amputation were censored at the time of death or at the study’s end, whichever occurred first. Follow-up continued from baseline until the date of death, foot amputation, or December 31, 2018, whichever came first. The median follow-up period was 7.17 years, with an interquartile range of 6.02 to 8.10 years.
- Statistical analysis
- All statistical analyses were conducted with SAS software version 9.4 (SAS Institute, Cary, NC, USA), considering a P value below 0.05 as statistically significant. Baseline characteristics are reported as mean±standard deviation or as counts (number) and percentages. Participants were categorized into seven groups based on their diabetes severity score. The incidence rate of foot amputations was determined by dividing the number of new cases by 1,000 person-years. Unadjusted Kaplan–Meier curves illustrated the cumulative incidence of the primary outcome by diabetes severity score, and differences between groups were assessed using the log-rank test. Cox proportional hazard models were utilized to explore the relationship between the diabetes severity score (and its individual components) and the incidence of foot amputation, yielding hazard ratios (HRs) with 95% confidence intervals (CIs). Model 1 adjusted for age and sex, while model 2 further adjusted for smoking status, alcohol consumption, regular exercise, BMI, hypertension, dyslipidemia, and depression. Potential effect modification by age, sex, and obesity was examined through stratified analyses and interaction testing using a likelihood ratio test.
METHODS
- Baseline characteristics
- Patients who experienced foot amputations were older, predominantly male, and had higher rates of current smoking compared to those who did not undergo amputation (Table 1). Among type 2 DM patients, those who developed foot amputations exhibited higher FBG levels, reduced eGFR values, and a greater prevalence of CKD, diabetic retinopathy, and CVD. They were also more likely to be treated with insulin or to be on multiple oral GLDs.
- Risk of diabetic foot amputation according to the clinical characteristics of type 2 DM
- Table 2 presents the incremental risk of foot amputation corresponding to the presence or absence of each component of the DM severity score. All factors remained significantly associated with an elevated risk of foot amputation even after adjusting for confounding variables (Table 2). Among these, insulin use emerged as the strongest predictor (HR, 5.43; 95% CI, 5.18 to 5.69), followed by diabetic retinopathy (HR, 4.03; 95% CI, 3.84 to 4.23). A longer duration of diabetes was also an independent risk factor (HR, 3.79; 95% CI, 3.62 to 3.97) (Table 2). Both CKD and the use of three or more GLDs were linked to more than a 2-fold increase in foot amputation risk.
- We further evaluated foot amputation risk in relation to the presence of peripheral artery disease (PAD), which has been recognized in earlier studies as a key factor in diabetic foot [2]. Both PAD (HR, 1.59; 95% CI, 1.51 to 1.67) and prior CVD (HR, 1.56; 95% CI, 1.47 to 1.66) were similarly associated with an elevated risk. Because CVD was already included in our analysis, PAD was not incorporated into the severity score.
- Risk of diabetic foot amputation according to diabetes severity score
- The foot amputation incidence rate was 0.173 per 1,000 person-years among patients with a diabetes severity score of zero. This rate increased progressively, reaching 1.576 per 1,000 person-years in patients with three severity factors and 6.546 per 1,000 person-years in those with all six factors (Table 3, Fig. 2). After adjusting for potential confounders, the HR for foot amputation rose with the number of severity parameters: 2.31 (95% CI, 2.15 to 2.47) for one parameter, 4.73 (95% CI, 4.42 to 5.07) for two, 8.86 (95% CI, 8.24 to 9.53) for three, 16.95 (95% CI, 15.60 to 18.4) for four, 23.98 (95% CI, 21.25 to 27.05) for five, and 37.87 (95% CI, 28.93 to 49.57) for six, relative to individuals with a severity score of zero.
- Effect of FBG level on the risk of diabetic foot amputation in patients with type 2 DM
- FBG was measured once during the baseline health check-ups conducted between 2009 and 2012. A J-shaped relationship emerged between glycemic control and foot amputation risk (Table 4), with the lowest risk occurring in the 120 to 139 mg/dL FBG range. In comparison, an FBG level below 100 mg/dL was associated with a higher risk (HR, 2.14; 95% CI, 1.94 to 2.35) relative to the 120 to 129 mg/dL range. Similarly, an FBG level of 180 to 189 mg/dL corresponded to nearly a 3-fold increase in risk (HR, 2.94; 95% CI, 2.58 to 3.35).
- Subgroup analyses
- Across all subgroups, a higher number of diabetes severity indicators was linked to an elevated risk of foot amputation (Supplemental Fig. S1). Notably, the association between the diabetes severity score and foot amputation risk was more pronounced in younger individuals (<65 years), women, and obese patients (all P values for interaction <0.001).
RESULTS
- This study demonstrated that patients with a diabetes severity score of zero had a low foot amputation incidence rate of 0.173 per 1,000 person-years. In contrast, the rate increased to 1.576 per 1,000 person-years in those with three severity factors and reached 6.546 per 1,000 person-years in patients with all six factors. A diabetes severity score of 3 or higher elevated the risk of diabetic foot amputation by nearly 9-fold compared to those with a score of zero, while a score of 6 was associated with an almost 40-fold increased risk. Readily available clinical information—such as insulin use, treatment complexity, diabetes duration, and the presence of diabetic retinopathy or nephropathy—can thus aid in predicting the development of foot amputation in type 2 DM patients. Notably, the diabetes severity risk score can be derived from clinical data alone without additional laboratory tests. Additionally, our findings indicate that both hyperglycemia and hypoglycemia contribute to an increased risk of foot amputation, with the lowest risk observed in the FBG range of 120 to 139 mg/dL.
- Insulin therapy often reflects the severity of diabetes because patients who cannot achieve glycemic control through lifestyle modifications or oral GLDs are typically transitioned to insulin. Although the link between age and foot complications is somewhat variable, the association between diabetes duration and foot complications remains consistently positive—even after adjustment for age [2]. This indicates that cumulative exposure to hyperglycemia over time may be more critical in developing diabetic foot complications than age per se.
- Although one might expect a strong correlation between poor glycemic control and diabetes complications, existing findings are inconsistent. Recent reports have shown that patients undergoing major amputations spent significantly less time within the target glucose range (70 to 180 mg/dL) and more time below range (<70 mg/dL) [12]. Inpatient hypoglycemia has also been identified as an independent risk factor for amputations in patients with diabetic foot ulcers [13]. Our results indicate that both low (<100 mg/dL) and high (>140 mg/dL) FBG levels are linked to an elevated risk of diabetic foot amputation, underscoring the importance of optimal glycemic management. Although an FBG level below 100 mg/dL likely reflects mild hypoglycemia, the absence of data on severe hypoglycemia (e.g., <70 mg/dL) limits our ability to assess its impact. Future research incorporating more detailed glucose measurements and records of hypoglycemic episodes is needed to better understand this relationship. Hypoglycemia might simply indicate a more severe underlying illness, predisposing patients to a higher risk of amputation. For instance, one study found that hospitalized patients who experienced hypoglycemia were more frequently on dialysis for end-stage renal disease, had PAD, and were receiving insulin therapy [13]. Additionally, other research did not find a clinically significant association between baseline or changes in HbA1c and wound healing in diabetic foot ulcer patients [6]—possibly because HbA1c does not capture the nuances of hyperglycemia, hypoglycemia, or glucose variability as effectively as continuous glucose monitoring.
- Our study also revealed a strong association between diabetic retinopathy and the risk of foot amputation, possibly attributable to a shared physiological basis. Diabetic neuropathy, like retinopathy and nephropathy, is a microvascular complication resulting from damage to small blood vessels [2,14]. Nevertheless, diabetic retinopathy exhibited a much stronger association with foot amputation risk compared to diabetic nephropathy. Previous longitudinal studies have linked poor vision to an increased likelihood of developing diabetic foot ulcers and subsequent amputations [3]. Inadequate perfusion in small blood vessels—closely associated with retinopathy—can hinder the healing of minor wounds, eventually leading to foot ulcers independent of neuropathy and macrovascular disease.
- Could the occurrence of one diabetes complication predict the occurrence of another diabetic complication? Microvascular and macrovascular complications frequently coexist and share common risk factors and pathological mechanisms. However, the influence of macrovascular disease on the occurrence of microvascular events remains less clear. In type 2 DM patients, both microvascular and macrovascular diseases independently predict a 10-year risk of mortality, major adverse cardiovascular events, and significant clinical microvascular outcomes (such as end-stage renal disease or the need for retinal photocoagulation) [15]. The simultaneous presence of these conditions corresponds to the highest risk levels [15]. It appears that macrovascular disease exerts a weaker influence on major microvascular events than microvascular disease does on cardiovascular risk. Diabetic foot, regarded as a macrovascular complication secondary to arterial insufficiency, typically develops following foot ulceration or injury from diabetic neuropathy. In our analysis, diabetes severity—reflected by treatment complexity, diabetes duration, and the presence of diabetic retinopathy, nephropathy, and CVD—was robustly associated with an increased risk of foot amputation.
- Our findings further indicate that the relationship between increasing diabetes severity and foot amputation risk was more consistent in younger individuals. This suggests that, in younger patients, diabetes itself may be the primary contributor to foot complications, whereas in older patients, other comorbid conditions might also influence the risk. Young-onset diabetes is often characterized by higher obesity rates, poorer adherence to treatment, a more rapid decline in beta-cell function, and earlier initiation of insulin therapy compared to later-onset type 2 DM [16,17]. Consequently, the adverse impact of diabetes on both morbidity and mortality is most pronounced in those diagnosed at a younger age [16,17].
- This study has several limitations. First, as an observational investigation, the associations observed between severity parameters and outcomes may not imply causation. Second, we were unable to accurately assess the impact of diabetic neuropathy because the insurance claim database lacks precise diagnostic data for this condition. Third, data on HbA1c and postprandial glucose levels were not analyzed, as it is challenging to perform these tests on all participants in a mass screening context. Finally, although we classified the complexity of oral GLDs, we could not examine specific insulin regimens (e.g., basal-only vs. basal-bolus therapy) due to insufficient detailed data. Given that insulin dosing is often tailored dynamically to individual needs, consistent classification is further complicated. It is also important to note that individuals with type 1 DM were excluded from our study.
- In summary, diabetic foot ulcers and subsequent amputations represent some of the most severe yet preventable complications of diabetes. In addition to regular foot examinations, enhanced strategies for prevention and early detection are imperative. A crucial component of prevention is the early identification of severe diabetes, enabling clinicians to pinpoint patients at high risk for foot complications [18]. We are confident that the diabetes severity score proposed in this study will prove valuable in this effort.
DISCUSSION
Supplementary Material
Supplemental Fig. S1.
-
CONFLICTS OF INTEREST
Mee Kyoung Kim is a deputy editor of the journal. But she was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
-
ACKNOWLEDGMENTS
This research was supported by grant from the Institute of Clinical Medicine Research in the Yeouido St. Mary’s Hospital, The Catholic University of Korea. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. We would like to thank the Medical Library of the Catholic University of Korea for assisting with the manuscript formatting and the Research Support Team of the Catholic University of Korea for providing English proofreading support.
-
AUTHOR CONTRIBUTIONS
Conception or design: J.H.K., M.K.K. Acquisition, analysis, or interpretation of data: J.Y., J.H.K., B.K., K.H., S.H.L., M.K.K. Drafting the work or revising: J.Y., J.H.K., M.K.K. Final approval of the manuscript: J.Y., J.H.K., B.K., K.H., S.H.L., M.K.K.
Article information
Fig. 2.Kaplan–Meier estimates of the cumulative incidence of diabetic foot amputation according to the diabetes severity score (0–6).
Table 1.Baseline Characteristics of the Study Participants
Table 2.Risk of Diabetic Foot Amputation by Diabetes Characteristics Indicative of Severity
Table 3.Risk of Diabetic Foot Amputation according to Diabetes Severity Score
Table 4.The Risk of Diabetic Foot Amputation by Fasting Blood Glucose Category in Patients with Type 2 Diabetes Mellitus
- 1. Birmpili P, Li Q, Johal AS, Atkins E, Waton S, Chetter I, et al. Outcomes after minor lower limb amputation for peripheral arterial disease and diabetes: population-based cohort study. Br J Surg 2023;110:958–65.ArticlePubMedPMCPDF
- 2. Rossboth S, Lechleitner M, Oberaigner W. Risk factors for diabetic foot complications in type 2 diabetes: a systematic review. Endocrinol Diabetes Metab 2020;4:e00175.ArticlePubMedPMCPDF
- 3. Boyko EJ, Ahroni JH, Stensel V, Forsberg RC, Davignon DR, Smith DG. A prospective study of risk factors for diabetic foot ulcer. The Seattle Diabetic Foot Study. Diabetes Care 1999;22:1036–42.ArticlePubMedPDF
- 4. Kang JY, Han K, Lee SH, Kim MK. Diabetes severity is strongly associated with the risk of active tuberculosis in people with type 2 diabetes: a nationwide cohort study with a 6-year follow-up. Respir Res 2023;24:110.ArticlePubMedPMCPDF
- 5. Han K, Kim B, Lee SH, Kim MK. A nationwide cohort study on diabetes severity and risk of Parkinson disease. NPJ Parkinsons Dis 2023;9:11.ArticlePubMedPMCPDF
- 6. Fesseha BK, Abularrage CJ, Hines KF, Sherman R, Frost P, Langan S, et al. Association of hemoglobin A1c and wound healing in diabetic foot ulcers. Diabetes Care 2018;41:1478–85.ArticlePubMedPMCPDF
- 7. Cho SW, Kim JH, Choi HS, Ahn HY, Kim MK, Rhee EJ. Big data research in the field of endocrine diseases using the Korean National Health Information Database. Endocrinol Metab (Seoul) 2023;38:10–24.ArticlePubMedPMCPDF
- 8. Kim MK, Han K, Lee SH. Current trends of big data research using the Korean National Health Information Database. Diabetes Metab J 2022;46:552–63.ArticlePubMedPMCPDF
- 9. Kim MK, Han K, Kwon HS, Yoo SJ. Risk of pancreatic cancer and use of dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes: a propensity score-matching analysis. Endocrinol Metab (Seoul) 2023;38:426–35.ArticlePubMedPMCPDF
- 10. Jin EH, Han K, Shin CM, Lee DH, Kang SJ, Lim JH, et al. Sex and tumor-site differences in the association of alcohol intake with the risk of early-onset colorectal cancer. J Clin Oncol 2023;41:3816–25.ArticlePubMedPMC
- 11. Lee YJ, Han KD, Kim JH. Association among current smoking, alcohol consumption, regular exercise, and lower extremity amputation in patients with diabetic foot: nationwide population-based study. Endocrinol Metab (Seoul) 2022;37:770–80.ArticlePubMedPMCPDF
- 12. Yin X, Zhu W, Liu C, Yao H, You J, Chen Y, et al. Association of continuous glucose monitoring-derived time in range with major amputation risk in diabetic foot osteomyelitis patients undergoing amputation. Ther Adv Endocrinol Metab 2022;13:20420188221099337.ArticlePubMedPMCPDF
- 13. Peled S, Pollack R, Elishoov O, Haze A, Cahn A. Association of inpatient glucose measurements with amputations in patients hospitalized with acute diabetic foot. J Clin Endocrinol Metab 2019;104:5445–52.ArticlePubMedPDF
- 14. Selby JV, Zhang D. Risk factors for lower extremity amputation in persons with diabetes. Diabetes Care 1995;18:509–16.ArticlePubMedPDF
- 15. Mohammedi K, Woodward M, Marre M, Colagiuri S, Cooper M, Harrap S, et al. Comparative effects of microvascular and macrovascular disease on the risk of major outcomes in patients with type 2 diabetes. Cardiovasc Diabetol 2017;16:95.ArticlePubMedPMCPDF
- 16. Al-Saeed AH, Constantino MI, Molyneaux L, D’Souza M, Limacher-Gisler F, Luo C, et al. An inverse relationship between age of type 2 diabetes onset and complication risk and mortality: the impact of youth-onset type 2 diabetes. Diabetes Care 2016;39:823–9.ArticlePubMedPDF
- 17. Baek HS, Park JY, Yu J, Lee J, Yang Y, Ha J, et al. Characteristics of glycemic control and long-term complications in patients with young-onset type 2 diabetes. Endocrinol Metab (Seoul) 2022;37:641–51.ArticlePubMedPMC
- 18. Zghebi SS, Panagioti M, Rutter MK, Ashcroft DM, van Marwijk H, Salisbury C, et al. Assessing the severity of type 2 diabetes using clinical data-based measures: a systematic review. Diabet Med 2019;36:688–701.ArticlePubMedPDF
References
Figure & Data
References
Citations
Citations to this article as recorded by 
- Costos directos y determinantes de las amputaciones en pacientes diabéticos en un hospital de Nicaragua en el año 2024.
Sidley Irania Hurtado Alvarado, Sheila Karina Valdivia Quiroz
Revista Multidisciplinaria Voces de América y el Caribe.2026; 3(1): 12. CrossRef - Nationwide Big Data Studies of Endocrine Diseases Using the Korean National Health Information Database: Research Trends and Standardization of Operational Definitions
Sun Wook Cho, Jung Hee Kim, Kyoung Jin Kim, Beom-Jun Kim, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2026; 41(1): 86. CrossRef - Cardiovascular outcomes with thiazolidinediones and sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus undergoing peripheral artery revascularization
Ji Woong Roh, Jimin Jeon, Joonsang Yoo, Minyoul Baik, Seok-Jae Heo, Deok-Kyu Cho, Jinkwon Kim
Diabetes Research and Clinical Practice.2026; 236: 113281. CrossRef - Diabetes progression and its association with fracture risk in type 2 diabetes
Bongsung Kim, Kyu-Na Lee, Kyungdo Han, Mee Kyoung Kim
Osteoporosis International.2026;[Epub] CrossRef - Development, validation, and pilot implementation of a prognostic model to predict future foot complications among people with diabetes recently discharged from hospital
Surain B. Roberts, Anne Löffler, Dhanesh Ramachandram, Javier Garay-Fernandez, Maia Norman, Conrad Pow, Fahad Razak, Amol A. Verma, Charles de Mestral
Journal of Clinical Epidemiology.2026; 195: 112295. CrossRef - Hemoglobin-albumin-lymphocyte-platelet score associated with diabetic foot severity, unlike modified systemic immune-inflammatory index and modified systemic inflammatory response index
Weiyu Pan, Zhaoyuan Nie, Qizhi Tang, Ling Zhao
Frontiers in Endocrinology.2026;[Epub] CrossRef - Diabetes Progression and Its Impact on Kidney Cancer Risk: Insights From a Longitudinal Korean Cohort Study
Jin Yu, Bongseong Kim, Kyungdo Han, Mee Kyoung Kim
The Journal of Clinical Endocrinology & Metabolism.2025; 111(1): e125. CrossRef - Association of high-density lipoprotein-related inflammatory indicators with diabetic foot ulcer in patients with diabetes: a population-based study
Renhe Deng, Ruyi Tao, Huiyi Luo, Yueqi Gu, Mengyu Yang, Chaoqi Yin
Diabetology & Metabolic Syndrome.2025;[Epub] CrossRef
PubReader
ePub Link
Cite
XML DownloadThe Severity of Diabetes and the Risk of Diabetic Foot Amputation: A National Cohort Study
Fig. 1. Study flow chart.
Fig. 2. Kaplan–Meier estimates of the cumulative incidence of diabetic foot amputation according to the diabetes severity score (0–6).
Graphical abstract
Fig. 1.
Fig. 2.
Graphical abstract
The Severity of Diabetes and the Risk of Diabetic Foot Amputation: A National Cohort Study
| Characteristic | Diabetic foot amputation |
P value | |
|---|---|---|---|
| No | Yes | ||
| Number | 2,535,606 | 8,471 | |
| Age, yr | 57.35±12.33 | 61.53±10.81 | <0.001 |
| Male sex | 1,518,886 (59.9) | 6,497 (76.7) | <0.001 |
| Body mass index, kg/m2 | 25.07±3.4 | 23.97±3.34 | <0.001 |
| Smoking | <0.001 | ||
| Non-smoker | 1,411,607 (55.67) | 3,987 (47.07) | |
| Ex-smoker | 468,160 (18.46) | 1,595 (18.83) | |
| Current smoker | 655,839 (25.87) | 2,889 (34.1) | |
| Alcohol drinking | 251,574 (9.92) | 975 (11.51) | <0.001 |
| Regular exercise | 522,473 (20.61) | 1,595 (18.83) | 0.014 |
| Income (lower 25%) | 531,196 (20.95) | 2,128 (25.12) | <0.001 |
| Systolic BP, mm Hg | 129.03±15.82 | 131.51±18.34 | <0.001 |
| Diastolic BP, mm Hg | 79.05±10.27 | 78.8±11.12 | 0.022 |
| Fasting glucose, mg/dL | 144.57±46.65 | 176.12±82.17 | <0.001 |
| eGFR, mL/min/1.73 m2 | 85.01±36.26 | 77.49±45.64 | <0.001 |
| Baseline TC, mg/dL | 196.52±42.45 | 194.21±46.51 | <0.001 |
| Dyslipidemia | 1,057,535 (41.71) | 3,694 (43.61) | <0.001 |
| Hypertension | 1,434,044 (56.56) | 5,908 (69.74) | <0.001 |
| Chronic kidney disease | 288,637 (11.38) | 2,237 (26.41) | <0.001 |
| Diabetic retinopathy | 202,504 (7.99) | 2,433 (28.72) | <0.001 |
| Myocardial infarction | 54,920 (2.17) | 371 (4.38) | <0.001 |
| Stroke | 179,052 (7.06) | 1,183 (13.97) | <0.001 |
| Depression | 253,386 (9.99) | 1,221 (14.41) | <0.001 |
| Duration of diabetes ≥5 years | 774,843 (30.56) | 5,608 (66.2) | <0.001 |
| Pharmacologic therapy for DM | |||
| Insulin | 200,181 (7.89) | 2,882 (34.02) | <0.001 |
| No. of oral GLDs ≥3 | 337,701 (13.32) | 2,431 (28.7) | <0.001 |
| Medication | |||
| Metformin | 1,049,731 (41.4) | 4,957 (58.52) | <0.001 |
| Sulfonylurea | 987,882 (38.96) | 5,243 (61.89) | <0.001 |
| DPP4-inhibitors | 157,885 (6.23) | 577 (6.81) | 0.026 |
| Thiazolidinedione | 156,608 (6.18) | 772 (9.11) | <0.001 |
| Alpha-glucosidase inhibitors | 281,430 (11.1) | 2,310 (27.27) | <0.001 |
| Variable | No. of events | Incidence rate, /1,000 person-yr | HR (95% CI) |
|
|---|---|---|---|---|
| Model 1 | Model 2 | |||
| Duration of diabetes, yr | ||||
| <5 | 2,863 | 0.236 | 1 (ref) | 1 (ref) |
| ≥5 | 5,608 | 1.045 | 4.03 (3.84–4.22) | 3.79 (3.62–3.97) |
| No. of oral glucose-lowering drugs | ||||
| <3 | 6,040 | 0.399 | 1 (ref) | 1 (ref) |
| ≥3 | 2,431 | 1.026 | 2.40 (2.29–2.51) | 2.21 (2.11–2.32) |
| Use of insulin | ||||
| No | 5,589 | 0.345 | 1 (ref) | 1 (ref) |
| Yes | 2,882 | 2.151 | 6.02 (5.75–6.30) | 5.43 (5.18–5.69) |
| Chronic kidney disease | ||||
| No | 6,234 | 0.400 | 1 (ref) | 1 (ref) |
| Yes | 2,237 | 1.157 | 2.57 (2.44–2.70) | 2.48 (2.36–2.61) |
| Cardiovascular disease | ||||
| No | 7,026 | 0.438 | 1 (ref) | 1 (ref) |
| Yes | 1,445 | 0.984 | 1.78 (1.68–1.89) | 1.56 (1.47–1.66) |
| Diabetic retinopathy | ||||
| No | 6,038 | 0.375 | 1 (ref) | 1 (ref) |
| Yes | 2,433 | 1.739 | 4.34 (4.14–4.55) | 4.03 (3.84–4.23) |
| Total | No. of events | Incidence rate, /1,000 person-yr | HR (95% CI) |
||
|---|---|---|---|---|---|
| Model 1 | Model 2 | ||||
| 0 | 1,380,356 | 1,647 | 0.173 | 1 (ref) | 1 (ref) |
| 1 | 598,973 | 1,706 | 0.409 | 2.30 (2.15–2.46) | 2.31 (2.15–2.47) |
| 2 | 337,767 | 1,979 | 0.851 | 4.83 (4.52–5.17) | 4.73 (4.42–5.07) |
| 3 | 155,387 | 1,648 | 1.576 | 9.19 (8.56–9.87) | 8.86 (8.24–9.53) |
| 4 | 56,318 | 1,083 | 2.986 | 17.87 (16.49–19.36) | 16.95 (15.60–18.4) |
| 5 | 13,785 | 352 | 4.178 | 25.69 (22.83–28.91) | 23.98 (21.25–27.05) |
| 6 | 1,491 | 56 | 6.546 | 41.59 (31.83–54.36) | 37.87 (28.93–49.57) |
| Fasting blood glucose, mg/dL | No. of events | Incidence rate, /1,000 person-yr | HR (95% CI) |
|
|---|---|---|---|---|
| Model 1 | Model 2 | |||
| <100 | 1,110 | 0.668 | 2.39 (2.17–2.63) | 2.14 (1.94–2.35) |
| 100–109 | 410 | 0.364 | 1.33 (1.17–1.50) | 1.25 (1.10–1.41) |
| 110–119 | 548 | 0.416 | 1.52 (1.36–1.70) | 1.46 (1.30–1.64) |
| 120–129 | 677 | 0.242 | 1 (ref) | 1 (ref) |
| 130–139 | 733 | 0.218 | 0.94 (0.84–1.04) | 0.95 (0.85–1.05) |
| 140–149 | 562 | 0.285 | 1.20 (1.07–1.34) | 1.20 (1.07–1.34) |
| 150–159 | 516 | 0.407 | 1.70 (1.52–1.91) | 1.69 (1.51–1.90) |
| 160–169 | 401 | 0.467 | 1.96 (1.73–2.21) | 1.92 (1.70–2.18) |
| 170–179 | 378 | 0.609 | 2.57 (2.26–2.91) | 2.51 (2.21–2.85) |
| 180–189 | 335 | 0.711 | 3.03 (2.66–3.45) | 2.94 (2.58–3.35) |
| 190–199 | 277 | 0.759 | 3.28 (2.85–3.77) | 3.17 (2.75–3.64) |
| ≥200 | 2,524 | 1.479 | 6.80 (6.24–7.40) | 6.27 (5.76–6.83) |
Table 1. Baseline Characteristics of the Study Participants
Values are expressed as mean±standard deviation or number (%). BP, blood pressure; eGFR, estimated glomerular filtration rate; TC, total cholesterol; DM, diabetes mellitus; GLD, glucose-lowering drug; DPP4, dipeptidyl-peptidase 4.
Table 2. Risk of Diabetic Foot Amputation by Diabetes Characteristics Indicative of Severity
Model 1: adjusted for age and sex; Model 2: adjusted for age, sex, smoking, alcohol drinking, regular exercise, body mass index, hypertension, dyslipidemia, and depression history. HR, hazard ratio; CI, confidence interval.
Table 3. Risk of Diabetic Foot Amputation according to Diabetes Severity Score
Model 1: adjusted for age and sex; Model 2: adjusted for age, sex, smoking, alcohol drinking, regular exercise, body mass index, hypertension, dyslipidemia, and depression history. HR, hazard ratio; CI, confidence interval.
Table 4. The Risk of Diabetic Foot Amputation by Fasting Blood Glucose Category in Patients with Type 2 Diabetes Mellitus
Model 1: adjusted for age and sex; Model 2: adjusted for age, sex, smoking, alcohol drinking, regular exercise, body mass index, hypertension, dyslipidemia, and depression history. HR, hazard ratio; CI, confidence interval.
