Letter to the Editor: Endocrine determinants of diabetic ketoacidosis outcomes in type 2 diabetes and insights into Gymnema sylvestre actions.

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.