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Diabetes Metab J. 2025;49(6):1141-1154.

Defining Severe Diabetes Mellitus: A Consensus Framework for Grading and Staging Diabetes Based on Pathophysiology and Complications.

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제1저자 배재현, 최훈지 · 교신저자 조영민

PMID 41153071 PMC12620694 DOI 10.4093/dmj.2025.0739 IF 8.2 내분비대사내과
소속 (14)
  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
  2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
  3. Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, College of Medicine, Hallym University, Hwaseong, Korea.
  4. Department of Medicine, Seoul National University College of Medicine, Seoul, Korea.
  5. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
  6. Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.
  7. Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
  8. Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  9. Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University Hospital, Chosun University College of Medicine, Gwangju, Korea.
  10. Department of Internal Medicine, Friend Dr. Han Clinic, Daegu, Korea.
  11. Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
  12. Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.
  13. Division of Endocrinology and Metabolism, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.
  14. Division of Endocrinology and Metabolism, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Abstract

Diabetes mellitus comprises a heterogeneous group of metabolic disorders differing in etiology, clinical course, and outcomes. Traditional classifications, such as type 1 and type 2 diabetes mellitus, fail to capture the full heterogeneity, including variation in insulin deficiency, insulin resistance, and complication burden. To address these limitations, we propose the Diabetes Grade-Stage Classification, an integrated system that combines pathophysiology-based grading with complication-based staging. Grading quantifies metabolic dysfunction through the assessment of insulin deficiency and insulin resistance. In parallel, staging assesses the extent of target organ damage, particularly in the cardiovascular, renal, ocular, and nervous systems. Together, this framework enables a comprehensive assessment of disease status, identification of vulnerable or high-risk phenotypes, and implementation of risk-adapted management strategies. Clinically, it facilitates personalized care, promotes collaborative coordination, and strengthens physician-patient communication. Furthermore, this framework provides a scalable structure for integrating disease severity into both individual- and population-level interventions. Although the current criteria for grading and staging are based on expert consensus and selected clinical indicators, such as low C-peptide levels and advanced complications, further validation and refinement are needed. In conclusion, the grading and staging system provides an operational tool for classifying the severity of diabetes mellitus and has the potential to extend life expectancy and improve quality of life for people living with diabetes mellitus.

Keywords

ClassificationDiabetes complicationsDiabetes mellitusDisease managementInsulin resistanceInsulin secretion

Figures

Fig. 1.
Fig. 1. Heterogeneity of complication profiles in people with diabetes mellitus. (A, B, C) Radar charts depicting diverse complication profiles for three hypothetical patients. Each axis represents a major domain of diabetes-related complications: atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD), retinopathy, and neuropathy. Severity within each domain is scored from 1 (at risk) to 4 (advanced disease). The resulting polygons illustrate the distinct and heterogeneous burden of target organ damage, demonstrating that patients with the same type of diabetes mellitus can present with markedly different clinical phenotypes. These findings underscore the value of complication-based staging in capturing individual disease burden.
Fig. 2.
Fig. 2. The Diabetes Grade–Stage Classification (DGSC): Integrated severity matrix for diabetes mellitus. A two-dimensional matrix conceptualizing overall diabetes severity by integrating pathophysiology-based grading (horizontal axis, grades 1–4) and complication-based staging (vertical axis, stages 1–4). The horizontal axis reflects progressive metabolic dysfunction, whereas the vertical axis represents the increasing burden of cumulative target organ damage. The color gradient from green (mild severity) to red (very high severity) qualitatively depicts the combined disease burden. The DGSC provides a holistic framework for classifying distinct clinical phenotypes and facilitating risk-adapted management strategies. aAlthough color intensity qualitatively indicates overall severity, each metabolic domain is graded separately according to defined criteria, and each organ system is staged independently to reflect domain-specific complication burden.
Fig. 3.
Fig. 3. Clinical pathway for comprehensive assessment and specialist referral. Flowchart depicting the proposed clinical decision-making process. Comprehensive assessment, including medical history, physical examination, and laboratory tests, feeds into two parallel evaluation pathways: pathophysiology-based grading (insulin deficiency and insulin resistance) and complication-based staging (atherosclerotic cardiovascular disease [ASCVD], heart failure [HF], chronic kidney disease [CKD], retinopathy, and neuropathy). Patients with a metabolic grade ≥3 or a complication stage ≥3 are classified as having severe diabetes mellitus. For these patients, a secondary assessment determines the need for specialist referral, guided by two key factors: difficulty in glycemic control (hyperglycemia, catabolic features, hypoglycemia, and high glycemic variability) and evidence of disease progression (glycemic deterioration and complication progression). Significant challenges in either area warrant referral to an endocrinologist or diabetes specialist.

그림 출처: PubMed Central 공개 논문 (PMC12620694)

Conflict of interest statement

CONFLICTS OF INTEREST . Jae Hyun Bae has been a managing editor of the Diabetes & Metabolism Journal since 2024. Kyung-Soo Kim has been a associate editor of the Diabetes & Metabolism Journal since 2024. They were not involved in the review process of this article. Otherwise, there was no conflict of interest.

그 밖의 정보
출판 형태
Journal Article, Review, Consensus Statement
저널
Diabetes & metabolism journal · eISSN 2233-6087
전자 출판
2025-10-28
MeSH
Humans · Diabetes Complications* / physiopathology / diagnosis · Diabetes Mellitus* / physiopathology / classification / diagnosis · Diabetes Mellitus, Type 1* / complications / physiopathology · Diabetes Mellitus, Type 2* / complications / physiopathology · Insulin Resistance · Severity of Illness Index*
참고문헌
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