Milionis C, Zoumakis E, Ilias I. Letter to the Editor: Endocrine determinants of diabetic ketoacidosis outcomes in type 2 diabetes and insights into Gymnema sylvestre actions. World J Exp Med 2026; 16(2): 121192 [DOI: 10.5493/wjem.v16.i2.121192]
Corresponding Author of This Article
Ioannis Ilias, MD, PhD, Director, Department of Endocrinology, Hippocration General Hospital, No. 63 Evrou Street, Athens 11527, Greece. iiliasmd@yahoo.com
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Endocrinology & Metabolism
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letter
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Milionis C, Zoumakis E, Ilias I. Letter to the Editor: Endocrine determinants of diabetic ketoacidosis outcomes in type 2 diabetes and insights into Gymnema sylvestre actions. World J Exp Med 2026; 16(2): 121192 [DOI: 10.5493/wjem.v16.i2.121192]
World J Exp Med. Jun 20, 2026; 16(2): 121192 Published online Jun 20, 2026. doi: 10.5493/wjem.v16.i2.121192
Letter to the Editor: Endocrine determinants of diabetic ketoacidosis outcomes in type 2 diabetes and insights into Gymnema sylvestre actions
Ioannis Ilias, Emmanouil Zoumakis, Charalampos Milionis
Charalampos Milionis, Department of Endocrinology, Diabetes and Metabolism, Elena Venizelou General Hospital, Athens 11521, Greece
Emmanouil Zoumakis, First Department of Pediatrics, University of Athens Medical School, Agia Sofia Hospital, Athens GR-11527, Greece
Ioannis Ilias, Department of Endocrinology, Hippocration General Hospital, Athens 11527, Greece
Author contributions: Milionis C, Zoumakis E and Ilias I searched the literature; Milionis C, Zoumakis E and Ilias I wrote the first draft; Milionis C, Zoumakis E and Ilias I wrote the final draft; and all authors report no conflict of interest; and all authors agreed for the submission of this work.
AI contribution statement: ChatGPT was used for language/syntax editing of this manuscript's drafts and final version. The manuscript content was all created without the use of AI software.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
Corresponding author: Ioannis Ilias, MD, PhD, Director, Department of Endocrinology, Hippocration General Hospital, No. 63 Evrou Street, Athens 11527, Greece. iiliasmd@yahoo.com
Received: March 18, 2026 Revised: March 31, 2026 Accepted: April 14, 2026 Published online: June 20, 2026 Processing time: 86 Days and 16 Hours
Abstract
We read with great interest the recent articles by Chandrabalan et al on diabetic ketoacidosis (DKA) in type 2 diabetes mellitus (T2DM) and by Kodiyatar et al on adjuvant herbal therapies. These articles provide important insights into DKA in T2DM, both at a clinical and experimental level. However, further endocrine aspects need to be addressed. In one study a paradoxical relationship between pre-admission metformin use and reduced in-hospital mortality from DKA was noted; this may be related to preserved beta-cell function and a more favorable incretin-glucagon axis rather than a pharmacological effect per se. However, important endocrine effectors such as C-peptide, glucagon, and incretin hormones were not measured. Furthermore, currently available antidiabetic agents, such as glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, have not been taken into account despite their possible effects on ketogenesis. An additional and underappreciated complexity is the concurrent occurrence of acute pancreatitis (AP) in DKA patients (DKA-AP), a complication that may affect at least 15% of DKA cases and that can neutralize key clinical and biochemical features of each condition, confounding diagnosis and worsening prognosis. At the same time, studies on Gymnema sylvestre have shown promising effects on glycemia and metabolism, while their endocrine effects have not been fully characterized. Recent data have shown possible effects of this herbal preparation on glucocorticoid receptors, suggesting a possible impact on the hypothalamus-pituitary-adrenal axis. We propose that future studies take into account detailed hormonal profiles and systematic screening for concurrent AP, which could help to further clarify the pathophysiology and mechanisms of currently available agents in T2DM-associated DKA.
Core Tip: Endocrine parameters - including beta-cell reserve, incretin signaling, and glucagon dynamics - are critical but underexplored determinants of diabetic ketoacidosis (DKA) outcomes in type 2 diabetes mellitus. The concurrent occurrence of acute pancreatitis in DKA, which may affect at least 15% of cases and substantially worsens prognosis, adds diagnostic complexity by masking hallmark features of both conditions and amplifying metabolic and hormonal dysregulation. The metabolic effects of Gymnema sylvestre also require deeper hormonal characterization to clarify its mechanism of action.
