Introduction: Hypoglycemia, a frequent and potentially life-threatening consequence of anti-diabetic therapy, remains a major barrier to optimal glycemic control. Effective inpatient management depends on frontline staff knowledge and preparedness; thus, knowledge gaps may compromise patient safety. This audit evaluated staff knowledge of hypoglycemia management in a district hospital in Malaysia to identify areas for improvement. Methodology: A cross-sectional audit was conducted among healthcare staff in a district hospital. A structured, modified questionnaire based on the Malaysian MEMS Inpatient Glycemic Guidelines was used. The 10-item questionnaire assessed definition, initial and subsequent management, reassessment, escalation, and documentation, yielding scores from 0 to 10. Descriptive statistics were used for analysis. Conclusion Despite high overall knowledge, critical gaps remain in reassessment, drug-related risks, and stepwise management, warranting targeted education, protocol reinforcement, and re-audit to enhance patient safety.
Hospitals, District ; Hypoglycemia

Introduction: Clinically important drug–drug interactions are a frequently overlooked cause of severe hypoglycemia in patients with type 2 diabetes mellitus (T2DM). Gliclazide is primarily metabolized via cytochrome P450 2C9 (CYP2C9), while fluconazole is a potent inhibitor of this enzyme.1,2 Concomitant administrations markedly increase gliclazide plasma concentration and prolong its hypoglycemic effect, substantially increasing the risk of severe and prolonged hypoglycemia. In some cases of refractory sulfonylureainduced hypoglycemia, octreotide may need to be considered early. Case: A 63-year-old Malay female with a 15-year history of T2DM on maximum-dose gliclazide (320 mg/day) presented with syncope and recurrent severe hypoglycemia 5 days after receiving a single oral dose of fluconazole 150 mg for a superficial fungal skin infection. Her other antidiabetic medications included metformin 1 g twice daily and vildagliptin 50 mg once daily. Her blood pressure on presentation was 151/74 mmHg, and her glucose level was 2.8 mmol/L. Her presentation was compounded by community-acquired pneumonia and acute kidney injury (estimated glomerular filtration rate 52 mL/min/1.73 m²). Biochemical evaluation excluded adrenal insufficiency, with normal serum cortisol (1,098 µg/dL), serum sodium (141 mmol/L), and serum potassium (4.6 mmol/L). Thyroid and liver function tests were normal. Despite repeated boluses of 50% dextrose and continuous infusion of 20% dextrose, recurrent hypoglycemia persisted for up to 48 hours after discontinuation of gliclazide, with glucose ranging from 1.7 to 5.1 mmol/L, reflecting prolonged sulfonylurea activity. Conclusion This case highlights a clinically significant yet preventable interaction between fluconazole and gliclazide, mediated through CYP2C9 inhibition, resulting in sustained hyperinsulinemic hypoglycemia. Gliclazide should be reduced or withheld prior to initiating fluconazole, and medication review should be performed at every consultation.
Fluconazole ; Gliclazide ; Hypoglycemia

Introduction: Insulin autoimmune syndrome (IAS), or Hirata syndrome, is characterized by hyperinsulinemic hypoglycemia resulting from the presence of high titers of insulin autoantibodies (IAAs) in the absence of exogenous insulin. We present a rare case of IAS. Case: A 75-year-old female with underlying hypertension, dyslipidemia, and osteoporosis presented with symptoms suggestive of spontaneous hypoglycemia of 3 months duration. She was non-diabetic with no history of antidiabetic agents or exogenous insulin use. Notably, she had taken traditional medications 1 month prior to onset of symptoms. Her fasting blood glucose was 2 mmol/L. Serum insulin was significantly elevated at >1,000 iui/mL and serum C peptide was 2,950 pmol/L, consistent with hyperinsulinemic hypoglycemia. Blood sulfonylurea level was not available. Her complete blood count and renal and liver function were normal. Thyroid function test was normal, and a short corticotropin stimulation test showed adequate cortisol response. Computed tomography (CT) pancreas, endoscopic ultrasound and PET-CT scan with Galium-68 DOTATATE showed no evidence of insulinoma. Serum IAAs were raised at 175 IU/mL, which confirmed a diagnosis of IAS. The patient was managed with dietary modifications and advised for frequent, small meals with low glycemic index, incorporating oral raw cornstarch. She was also started on oral diazoxide 100 mg twice daily (3 mg/kg/day) due to persistent hypoglycemia. She responded well to diazoxide with no more spontaneous hypoglycemia, however, developed fluid retention which was managed with oral diuretics. Subsequently, we managed to taper and stop the diazoxide after 18 months of treatment. Patient remains well with no further episodes of hypoglycemia. Conclusion IAS may be triggered by medications or viral infections, occurs more frequently in people with autoimmune conditions, and shows genetic predisposition. However, as in our patient, IAS may be idiopathic, and the cause remains unknown. IAS is frequently self-limiting, and our patient experienced spontaneous remission with no further hypoglycemic episodes after discontinuation of treatment.
Hypoglycemia ; Insulins

Introduction: The Warburg effect refers to a metabolic shift in which cells preferentially utilize aerobic glycolysis rather than oxidative phosphorylation despite adequate oxygen availability. This phenomenon is increasingly recognized as the mechanism for tumor-associated hypoglycemia, or paraneoplastic syndromes such as insulin-like growth factor-2 (IGF-2)– mediated non-islet cell tumor hypoglycemia. We present a case of Warburg effect with management challenges. Case: A 47-year-old male with advanced, treatment-naive retroviral disease presented with chronic cough, progressive right thigh swelling, constitutional symptoms over several months, followed by reduced responsiveness for 2 days prior to admission. Clinically, he was delirious, cachectic with generalized lung crepitations and right thigh mass. He was diagnosed with smear-negative disseminated tuberculosis, and thigh mass was considered either a tuberculous granuloma or sarcoma. During hospitalization, he developed recurrent hypoglycemia with lactatemia despite intravenous dextrose, optimized enteral feeding and a 1-day course of intravenous octreotide. His blood investigations showed full blood count, renal function test, liver function test, and serum ketone within normal range. His arterial blood gas analysis showed type B lactic acidosis with persistent lactatemia. At the time of hypoglycemia (RBS: 3.1 mmol/L), his serum insulin was suppressed, C-peptide was low–normal, morning cortisol was elevated, and IGF-1 was markedly reduced suggestive of non-insulin-mediated hypoglycemia secondary to Warburg effect. Conclusion In patients with retroviral disease and tuberculosis, Warburg effect may lead to poorer clinical outcomes and management may be challenging. Thus, definitive antimicrobial therapy with second generation somatostatin analogues (Pasireotide) may be considered in selected cases to modulate dysregulated hormonal and metabolic pathways. Early identification and timely targeted intervention are crucial to improving outcomes in this high-risk population.
Persistent Infection ; Hypoglycemia

Introduction: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome caused by tumor secretion of insulin-like growth factor-2 (IGF-2), leading to recurrent hypoinsulinemic hypoglycemia. It is most commonly associated with large mesenchymal tumors, such as solitary fibrous tumor, particularly those arising from the pleura or lungs. This phenomenon, also known as Doege–Potter syndrome, may precede tumor detection or signal tumor recurrence. We report a striking case of late malignant recurrence presenting solely with hypoglycemia after a decade of remission. Case: A 68-year-old female was initially presented in 2016 with respiratory symptoms and recurrent symptomatic fasting and post-prandial hypoglycemia, and was found to have a large left upper lobe mass. Tumor resection in 2017 resulted in complete resolution of hypoglycemia. She remained asymptomatic for several years. In 2023, she developed recurrent hypoglycemia without respiratory or constitutional symptoms. Biochemical evaluation demonstrated hypoinsulinemic hypoglycemia with suppressed insulin and C-peptide, low IGF-1, and markedly elevated IGF-2, resulting in an IGF-2:IGF-1 ratio of 25, consistent with IGF-2-mediated NICTH. Computed tomography imaging revealed a large left thoracic mass with invasion into the intercostal muscles and diaphragm with extension toward the stomach, associated with contralateral lung nodules and possible liver metastases, suggesting recurrent malignant disease. Hypoglycemia improved with glucocorticoid therapy, and the patient was referred for oncological assessment. Despite initiation of systemic chemotherapy, her disease progressed and she succumbed during treatment. Conclusion This case highlights several important lessons: Firstly, recurrent hypoinsulinemic hypoglycemia warrants evaluation for NICTH even in the absence of tumor-related symptoms. Secondly, solitary fibrous tumors may recur or undergo malignant transformation after prolonged disease-free intervals; and glucocorticoids provide effective metabolic control but do not alter oncologic prognosis. Long-term surveillance should be considered in patients with prior solitary fibrous tumors due to the risk of delayed recurrence and paraneoplastic complications.
Insulin-Like Growth Factor II ; Hypoglycemia ; Neoplasms

Introduction: Uterine fibroids are common in reproductive-age women and are associated with obstetric complications. Their potential contribution to maternal metabolic disturbances is poorly described. We report a case of maternal hypoglycemia in the setting of a large uterine fibroid and fetal overgrowth, suggesting a possible endocrine–metabolic interaction. Case: A 39-year-old multiparous female with no history of diabetes or endocrine disease had a large lower-segment uterine fibroid measuring 8 × 10 cm. Pregnancy was otherwise uncomplicated until 39 weeks, when she underwent classical Caesarean section for transverse lie and delivered a large-for-gestational-age infant. Postpartum, she developed recurrent symptomatic hypoglycemia despite normal hemoglobin A1c (5.0%) and preserved thyroid and adrenal function. There was no evidence of sepsis, liver disease, medication exposure, or insulinoma. Hypoglycemia resolved spontaneously following delivery. Postnatal imaging showed persistence of the fibroid (6 × 9 cm). She remains under follow-up, considering interval laparoscopic myomectomy with bilateral tubal ligation. The coexistence of maternal hypoglycemia and fetal overgrowth raises the possibility of altered maternal– fetal glucose dynamics. Large mesenchymal tumors may produce insulin-like growth factor 2 (IGF-2), causing non–islet cell tumor hypoglycemia. Fibroid-related uteroplacental hemodynamic changes or increased fetal glucose demand may also contribute. While causality cannot be established, the temporal resolution post-delivery suggests a contributory role of the fibroid in metabolic disturbance. Conclusion This case highlights a rare but clinically relevant association between a large uterine fibroid, maternal hypoglycemia, and fetal overgrowth. In pregnant patients with unexplained hypoglycemia, uterine fibroids may represent an overlooked factor. Multidisciplinary follow-up and further research into IGF signaling and placental–tumor interactions are warranted.
Diabetes, Gestational ; Fetal Macrosomia ; Leiomyoma ; Hypoglycemia

Introduction: Insulinoma during pregnancy is exceedingly rare, with fewer than 30 cases reported worldwide. Diagnosis is often delayed due to overlapping physiological and gestational symptoms, posing significant risks to both mother and fetus. Case: We report a case of a 36-year-old G4P2 + 1 female presenting at 7 weeks’ gestation with recurrent symptomatic hypoglycemia initially suspected due to poor oral intake. She returned at 12 weeks with persistent neuroglycopenic symptoms and weight loss. Biochemical evaluation demonstrated inappropriately non-suppressed insulin and C-peptide levels during hypoglycemia, raising suspicion for endogenous hyperinsulinemia. Imaging with magnetic resonance imaging identified a 2.3 × 2.5 cm pancreatic lesion consistent with insulinoma. A multidisciplinary team (MDT) approach involving Internal Medicine, Endocrinology, Obstetrics and Gynecology (Maternal-Fetal Medicine), Hepatobiliary Surgery, and Radiology guided management. Due to concerns regarding surgical and ablative risks during pregnancy, medical therapy with octreotide was initiated, achieving partial glycemic control. The pregnancy was complicated by fetal growth restriction, necessitating delivery at 34 weeks. Postpartum, the patient underwent endoscopic ultrasoundguided radiofrequency ablation (EUS-RFA), requiring two sessions before achieving glycemic stabilization. Conclusion This case highlights the diagnostic challenges of insulinoma in pregnancy and underscores the importance of MDTguided individualized management. It also illustrates the limitations of EUS-RFA and medical therapy, particularly in larger tumors, and raises important considerations regarding fetal outcomes.
Female ; Pregnancy ; Insulinoma ; Hypoglycemia

Introduction: Diazoxide is an effective treatment for hyperinsulinemic hypoglycemia (HH), though its dosage for the transient form of HH is not well established. Recently, a Singapore cohort reported effective low-dose diazoxide in treating HH secondary to small for gestational age (SGA). We aim to study the effectiveness and safety of this low-dose regimen in transient HH. Methodology: This was a retrospective cohort study. All infants diagnosed with transient HH and treated with diazoxide between 1 January 2024 and 31 December 2025 were included. The primary objective was to determine the effective diazoxide dose in maintaining euglycemia (blood glucose ≥3.5 mmol/L). The secondary objective was to monitor complications following diazoxide usage. Results: A total of 21 infants were recruited with a median gestational age of 37 weeks (IQR: 35–37.5) and a median birth weight of 1,980 grams (IQR: 1,670–2,340). The risk factors were SGA (71.4%, n = 15), infants of diabetic mothers (19%, n = 4), and others (14%, n = 3). A median glucose infusion rate of 12.6 (IQR: 10.4–14.5) mg/kg/minute was required to treat the hypoglycemia. Eleven infants (52.3%) required adjunct glucagon therapy before transitioning to diazoxide therapy, with a median dose of 8 mcg/kg/hour (IQR: 7–12). Diazoxide was initiated at a median of 20 days of life (IQR: 14–30), with a median starting dose of 3.0 mg/kg/day (IQR: 3.0–3.55). Euglycemia was fully achieved in 95.2% (n = 20) of infants within a median of 5 days (IQR: 3–9) post diazoxide initiation. At discharge, the median diazoxide dose was 3.3 mg/kg/day (IQR: 3.0–4.8). Adverse events occurred in five cases (23.8%), primarily limited to transient fluid retention (n = 4) and gastrointestinal symptoms (n = 1). None developed echocardiography-proven pulmonary hypertension in this cohort. Conclusion Low-dose diazoxide (3–5 mg/kg/day) is effective and well-tolerated for managing the transient form of HH in our setting. This benefit appears not to be limited to babies born with SGA, but may extend to other risk factors as well.
Diazoxide ; Hypoglycemia

Introduction: Hyperinsulinemic hypoglycemia of infancy may be congenital or acquired, and rarely due to factitious hypoglycemia imposed by another. A thorough medical and social history, critical sampling, and screening for inborn errors of metabolism are crucial. Case: A 5-month-old, ex-29 weeker, twin female infant, born to a non-consanguineous couple was admitted at 4 months with severe refractory hypoglycemia and seizures requiring a glucose infusion rate (GIR) of 16 mg/kg/min. Critical sampling suggested hypoglycemia due to exogenous insulin: glucose 1.1 mmol/L, ketones 0.2 mmol/L, insulin 1,208 pmol/L (17.8–173), and C-peptide 18.2 pmol/L (366– 1,466). Free fatty acids were not raised; growth hormones were 2.223 µg/L (0.14–6.27) and cortisol >1,000 nmol/L (145.4–619.4). Metabolic and genetic testing excluded glycogen storage disorder. Two months prior, she was admitted with a severe human metapneumovirus and parainfluenza infection, hypoglycemia, lactic acidosis and left ventricular hypertrophy. Her twin had died of sudden infant death syndrome. Examination revealed a small puncture mark on the abdomen, but otherwise it was unremarkable. The GIR dropped dramatically over 3 days and the intravenous dextrose was discontinued. Normoglycemia was maintained on 3-hourly feeds and she tolerated an age-appropriate fast before discharge. No hypoglycemic episodes were reported. Of note, the mother suffered from bipolar disorder and had access to insulin for gestational diabetes mellitus. The infant is currently in foster care, is scheduled to have neuroimaging and continues to have growth and developmental follow-up. Conclusion Factitious hypoglycemia should be suspected when there are red flags in the clinical history and critical sampling demonstrates high insulin levels, suppressed C-peptide in the face of hypoglycem ia with low ketones and low free fatty acids. A multidisciplinary approach involving paediatrics, psychiatry, and child protective services is mandatory
Infant ; Hypoglycemia

Introduction: Beckwith–Wiedemann syndrome (BWS) is a congenital overgrowth disorder associated with dysregulation of genes on chromosome 11p15.5. Infants with BWS can present with hyperinsulinemic hypoglycemia. There are also distinctive clinical features including macrosomia, macroglossia and visceromegaly that may raise suspicion of this diagnosis. Case: A preterm female infant of 30 weeks gestation with a birth weight of 1.87 kg (97th centile) had recurrent hypoglycemia in the neonatal period, requiring escalation to a maximum glucose infusion rate of 17.6 mg/kg/min. Hypoglycemia only resolved after starting intravenous glucagon infusion. Critical sampling during hypoglycemia revealed serum insulin 3.9 µU/mL (3–25 µU/mL), serum ketone 0.2 mmol/L, cortisol 3,053 nmol/L and growth hormone 16.2 ng/mL. These findings supported the diagnosis of non-ketotic hyperinsulinemic hypoglycemia. She was commenced on oral diazoxide with resolution of hypoglycemia and discontinuation of glucagon. Examination at birth revealed macroglossia, hepatomegaly and ballotable kidneys. An initial US abdomen at birth revealed bilateral enlarged kidneys but normal liver. An initial chromosomal study revealed karyotype 46, XX. Over time, additional clinical features became evident fulfilling the diagnostic criteria for BWS, that is, polyhydramnios, large for gestational age, transient hypoglycemia, hyperinsulinism, macroglossia, hemihypertrophy, facial nevi, bilateral ear creases, hepatomegaly and ballotable kidney. A repeat US abdomen surveillance at 4 months old revealed a heterogeneous liver mass with marked vascularity, prompting a diagnosis of hepatic hemangioma. She was commenced on oral propranolol, with reduction in the size and vascularity of the liver hemangioma and decline in alpha-fetoprotein levels. Conclusion The clinical features of BWS may not be recognizable in a preterm baby in early neonatal period. Careful clinical examination should be done in a baby with persistent hyperinsulinemic hypoglycemia for underlying syndromal causes. US surveillance should also be carried out due to increased risk of hepatoblastoma or liver hemangioma in BWS, as was seen in this case.
Infant, Newborn ; Infant ; Beckwith-Wiedemann Syndrome ; Infant, Premature ; Hypoglycemia