Nguyen NTY, Tran HP, Luong TV, Nguyen DX, Tran DH, Hoai PHT, Lee MC, Dang HNN. From lipodystrophy to subcutaneous insulin depots: Overlooked mechanisms of glycemic variability in patients with diabetes. World J Diabetes 2026; 17(5): 114042 [DOI: 10.4239/wjd.v17.i5.114042]
Corresponding Author of This Article
Hai Nguyen Ngoc Dang, MD, Doctor, Menzies Institute for Medical Research, University of Tasmania, 1/17 Liverpool Street, Hobart 7000, Tasmania, Australia. ngochai123dc@gmail.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Minireviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. May 15, 2026; 17(5): 114042 Published online May 15, 2026. doi: 10.4239/wjd.v17.i5.114042
From lipodystrophy to subcutaneous insulin depots: Overlooked mechanisms of glycemic variability in patients with diabetes
Nhi Thi Y Nguyen, Hau Phuc Tran, Thang Viet Luong, Dat Xuan Nguyen, Duong Hung Tran, Phuong Ho Thi Hoai, Meng-Chi Lee, Hai Nguyen Ngoc Dang
Nhi Thi Y Nguyen, Hau Phuc Tran, Dat Xuan Nguyen, Duong Hung Tran, Phuong Ho Thi Hoai, University of Medicine and Pharmacy, Hue University, Hue 530000, Viet Nam
Thang Viet Luong, Hai Nguyen Ngoc Dang, Menzies Institute for Medical Research, University of Tasmania, Hobart 7000, Tasmania, Australia
Meng-Chi Lee, Department of Critical Care Medicine, Royal Hobart Hospital, Hobart 7000, Tasmania, Australia
Co-first authors: Nhi Thi Y Nguyen and Hau Phuc Tran.
Co-corresponding authors: Thang Viet Luong and Hai Nguyen Ngoc Dang.
Author contributions: Nguyen NTY conceptualized the study and prepared the original draft; Tran HP contributed to the literature search, evidence synthesis, and development of the manuscript; Luong TV provided guidance on the conceptual framework and critical intellectual input; Dang HNN ensured methodological consistency and coordinated communication with collaborators; Nguyen NTY, Tran HP, Luong TV, Nguyen DX, Tran DH, Hoai PHT, Lee MC, and Dang HNN contributed to reviewing and editing the manuscript and approved the final version. Nguyen NTY and Tran HP contributed equally to this work and are co-first authors. Luong TV and Dang HNN were designated as co-corresponding authors because of their supervisory roles.
AI contribution statement: We used ChatGPT solely as a tool for grammar checking and language polishing to improve the clarity and flow of the manuscript. No portion of the Main Text (Abstract, Introduction, Materials and Methods, Results, Discussion, and Conclusion) was AI-generated. The entire content and all original ideas were developed and written exclusively by the research team. The AI tool was used only for language polishing and stylistic improvements, sometimes for translation. It was not utilized for data analysis or any form of writing assistance. No AI tool participated in the design of the study or the interpretation of the research results. All figures in the manuscript were created using specialized professional software by the authors. We did not use AI to generate any Figures. All AI-generated outputs were critically reviewed and revised by the authors.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Corresponding author: Hai Nguyen Ngoc Dang, MD, Doctor, Menzies Institute for Medical Research, University of Tasmania, 1/17 Liverpool Street, Hobart 7000, Tasmania, Australia. ngochai123dc@gmail.com
Received: September 10, 2025 Revised: March 10, 2026 Accepted: March 26, 2026 Published online: May 15, 2026 Processing time: 243 Days and 16.3 Hours
Abstract
Lipohypertrophy (LH) is the most common complication of insulin injection therapy but remains underrecognized in routine care. Repeated injections into the same area promote subcutaneous fat hypertrophy and fibrosis, which can create insulin depot behavior and lead to delayed, blunted, and highly variable insulin absorption. As a result, patients may develop unexplained glycemic instability, including persistent postprandial hyperglycemia and late, unpredictable hypoglycemia that complicates insulin titration. Clinical inspection and palpation detect only a proportion of lesions, whereas high-frequency ultrasound can improve detection and lesion mapping, particularly when lesions are subtle or deep. This review synthesizes current evidence linking injection-site tissue remodeling to altered insulin pharmacokinetics and clinically meaningful glycemic variability and provides a practical pathway for diagnosis and management. Key elements include systematic injection-site assessment, structured technique education with site rotation, and intensified glucose monitoring with individualized dose adjustment when injections are switched away from the LH, as absorption may become faster and more predictable. Recognizing LH as a modifiable driver of insulin depot-related variability shifts clinical focus from repeated dose escalation to correcting injection-site factors, thereby improving the safety and effectiveness of insulin therapy.
Core Tip: Lipohypertrophy is a common but often overlooked cause of unstable insulin activity. Tissue hypertrophy and fibrosis at injection sites can create insulin depot behavior, leading to delayed and unpredictable absorption with both hyperglycemia and late hypoglycemia. A practical management pathway combines routine injection-site inspection with palpation (and ultrasound when needed), structured rotation and technique education, and close monitoring with individualized dose adjustment when patients are switched away from affected areas. Embedding injection-site care into routine insulin titration can reduce avoidable glycemic variability and improve insulin safety.
