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Review
. 2025 Jun 20;14(13):4393.
doi: 10.3390/jcm14134393.

Non-Diabetic Hypoglycemia: Evaluation and Management in Adults

Eugene Looi  1 , Helen M Lawler  1
Affiliations
Review

Non-Diabetic Hypoglycemia: Evaluation and Management in Adults

Eugene Looi et al. J Clin Med. .

Abstract

Hypoglycemia is defined by the presence of Whipple's triad, which is (1) low plasma glucose concentration, (2) neurogenic and neuroglycopenic symptoms and/or signs, and (3) their resolution with normalization of plasma glucose concentration. Hypoglycemia in adult patients without diabetes is rare and much less common compared to patients with diabetes. Because of its rarity in the general adult population, recognition and treatment may be delayed. Our review provides a comprehensive summary of non-insulin-mediated and insulin-mediated hypoglycemia in adult patients without diabetes. It explores the pathophysiology of various causes of hypoglycemia and reviews diagnostic approaches such as clinical history, key biochemical findings, and other relevant diagnostic modalities that aid in distinguishing among the different causes, from non-insulin-mediated (e.g., critical illness) to insulin-mediated causes (e.g., post-bariatric hypoglycemia). Our aim is to present the most up-to-date information regarding the diagnosis and management of non-diabetic hypoglycemia to increase awareness and understanding of the condition and promote prompt recognition in patients to expedite diagnosis and treatment.

Keywords: Whipple’s triad; insulin-mediated hypoglycemia; non-diabetic hypoglycemia; non-diabetic medications; non-insulin-mediated hypoglycemia.

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Conflict of interest statement

Eugene Looi has no competing financial interests or personal relationships to disclose. Helen M. Lawler received funding as a principal investigator for Vogenx, Inc. and served as an advisory board member for Amylyx Pharmaceuticals.

Figures

Figure 1
Figure 1
Diagnostic algorithm for non-diabetic hypoglycemia. See Supplemental Figure S1 for detailed step-by-step diagnostic algorithm.
See this image and copyright information in PMC

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