Recurrent diabetic ketoacidosis associated with polysubstance performance-enhancing drug use in previously unrecognised insulin-deficient diabetes

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening metabolic emergency typically associated with type 1 diabetes but may also occur as the first presentation of previously unrecognised diabetes or in response to metabolic stressors. Performance-enhancing drugs (PEDs), including growth hormone secretagogues and anabolic agents, are increasingly used despite limited safety data and may adversely affect glucose metabolism.

Case Presentation: We report a case of recurrent DKA in a man in his 30s with previously unrecognised diabetes following prolonged use of multiple performance-enhancing substances, including Ibutamoren (MK-677) and other hormonal agents. Initial presentation demonstrated severe metabolic acidosis, marked hyperglycaemia (HbA1c 109 mmol/mol), and ketonemia. Autoimmune screening was negative, while follow-up testing revealed profoundly suppressed C-peptide levels, consistent with severe insulin deficiency. A prior episode of DKA had occurred several years earlier following anabolic steroid exposure.

Investigations and Management: There was no evidence of infection, pancreatitis, or other precipitating illness. The patient was managed with standard intravenous insulin therapy and fluid resuscitation, followed by transition to basal–bolus insulin. Despite initial stabilisation, recurrent ketosis occurred, requiring ongoing insulin therapy. Metformin was later added to assist glycaemic control.

Discussion: This case highlights diagnostic uncertainty regarding diabetes phenotype in the context of antibody-negative, insulin-deficient diabetes. Differential considerations included ketosis-prone diabetes, idiopathic type 1 diabetes (type 1B), and antibody-negative autoimmune diabetes. Growth hormone secretagogues and other PEDs may have contributed to insulin resistance and metabolic decompensation, although causality cannot be definitively established. Interpretation of C-peptide in the post-DKA setting is complex but persistent suppression supports significant beta-cell dysfunction.

Conclusion: Clinicians should consider unregulated performance-enhancing drug use as a potential contributor to metabolic decompensation in patients presenting with DKA. Careful assessment of diabetes phenotype, including antibody status and C-peptide measurement, is essential to guide long-term management.

Dr Awais Khan is an Internal Medicine Senior House Officer at St. Luke's General Hospital, Kilkenny, Ireland, where he has been working for the past three years. He has a strong interest in Diabetes and Endocrinology and intends to pursue specialist training in Endocrinology. During his rotation in the Endocrinology Department, he encountered a rare and clinically significant case of recurrent diabetic ketoacidosis associated with polysubstance performance-enhancing drug use. The uniqueness of the case and its important clinical implications inspired him to investigate it further and prepare it for presentation at the International Conference on Diabetes and Endocrinology.