Literature on antiepileptic-induced iatrogenic hyperglyceamia is scanty. Due to its broad spectrum of activity and mechanisms of action, valproic acid (VPA), a fatty acid, is one of the most widely prescribed epilepsy treatments worldwide. Herein, we describe an adolesent epileptic patient, in whom persistent, otherwise unexplained, hyperglyceamia was most likely induced by VPA, as suggested by the VPA and glucose blood level normalcy after withdrawal. Indeed, no further hyperglyceamic episodes occurred after VPA discontinuation. This case supports the hypothesis that VPA may induce hyperglyceamia, due to still not well-defined metabolic mechanisms of action. Moreover, this emphasizes the need for more monitoring on paediatric patients on this medication, so as to be forestall complications, if it may arise.

• Seizure Disorder

• Sodium Valproate

• Insulin resistance

• Diabetes

• Diabetic Ketoacidosis

Oluwayemi IO, Oke JO, Adebisi AO, Ajibola AE, Ajayi TJ, et al. (2026) Anticonvulsant-Induced Diabetes Mellitus in a Nigerian Adolescent. J Endocrinol Diabetes Obes 12(1): 1129.

Sodium valproate (VPA), a broad-spectrum antiepileptic drug (AED), used widely in the treatment of epilepsy, bipolar disorder, and migraine prophylaxis [1-5]. Although its efficacy is well-established, VPA is associated with a variety of side effects, including weight gain, insulin resistance, and dyslipidemia. Recently, an increasing body of evidence has implicated VPA in the development of diabetes mellitus (DM), particularly type 2 diabetes mellitus (T2DM), raising concerns about long-term metabolic risks in patients receiving chronic therapy [1-3]. In this write up is we would see a female patient who was had been on oral sodium valproate for the management for generalized seizure presented in the children emergency with DKA.

The index patient was a 13-year-old female who presented at the children emergency department with clinical features suggestive of diabetic ketoacidosis (DKA). She had a history of epilepsy managed for approximately five years with carbamazepine, and sodium valproate was added to her regimen when seizure control became suboptimal. She remained on both medications for about five years at a private facility.

She presented with complaints of generalized body weakness, polyuria, polydipsia, and several generalized tonic-clonic seizures. The seizures, four in number, lasted approximately three minutes each, with no associated fecal or urinary incontinence, and resolved spontaneously. There were no accompanying symptoms such as fever, cough, sore throat, or dysuria.

On examination, she was afebrile (36.5°C), not pale or jaundiced, and had no cyanosis, lymphadenopathy, or pedal edema. Her sexual maturity rating was Tanner Stage 3. She weighed 37 kg (25th percentile) and was 150 cm tall (between 10th–25th percentile). Vital signs included a heart rate of 100 bpm and blood pressure of 100/65 mmHg. She was alert but weak and restless. Respiratory examination revealed acidotic breathing and a respiratory rate of 30 cpm with vesicular breath sounds.

A clinical diagnosis of DKA in a patient with suspected type 1 diabetes mellitus and underlying epilepsy was made. Her random blood glucose (RBG) level at presentation was unrecordably high. Initial resuscitation with normal saline was performed for two hours, followed by insulin infusion at a rate of 0.1 IU/kg/hour. The RBG decreased to 5.1 mmol/L within five hours. The patient became active and regained appetite.

Laboratory findings included

• Urinalysis: Glucose ++++, Ketones ++

• Full Blood Count: PCV 38%, WBC 8980/µL, Neutrophils 63%, Lymphocytes 28.05%, Monocytes 8.55%, Eosinophils 0.10%

• Serum Electrolytes and Creatinine: Sodium 139.1 mmol/L, Chloride 101.8 mmol/L, Potassium 4.81 mmol/L, Urea 4.4 mmol/L, Creatinine 101.3 µmol/L

She was commenced on intravenous ceftriaxone 1 g 12 hourly. Remarkable clinical improvement was observed within 24 hours. Insulin infusion was stopped, and she was transitioned to subcutaneous insulin therapy (NPH and Soluble insulin). Sodium valproate was discontinued. Nutritional counselling was initiated.

The patient has since been on regular follow-up in both the pediatric neurology and endocrinology clinics, and her blood glucose has remained within normal limits.

Sodium valproate (VPA) is the most widely prescribe antiepileptic drug (AED). It has wide pharmacological effects with a variety of mechanisms, from increasing gamma-aminobutyric acid (GABA)-ergic transmission to reduce release and/or effects of excitatory amino acids, blockade of voltage-gated sodium channels and modulation of dopaminergic and serotoninergic transmission [5], it is almost completely metabolized in the liver, mainly by glucuronidation. It then undergoes further metabolism with oxidation, which is complex and involves several cytochrome P450 enzyme systems. It has multiple metabolites which may contribute to both its efficacy and toxicity. [6,7].

So how does sodium valproate work and what are the mechanisms linking it to diabetes mellitus?

VPA acts primarily by increasing brain levels of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter, through inhibition of GABA transaminase and increased synthesis of GABA. It also affects voltage-gated sodium and calcium channels. While its neurological effects are central to its therapeutic action, VPA also exerts effects on hepatic enzymes, lipid metabolism, and endocrine systems [8].

Pathophysiological Mechanisms Linking VPA to Diabetes Mellitus: Several mechanisms have been proposed to explain the diabetogenic effects of VPA [1-7].

Weight gain is one of the most common adverse effects of VPA, particularly in adolescents and women. Obesity is a major risk factor for insulin resistance and T2DM. Studies suggest that VPA may alter hypothalamic appetite regulation or interfere with leptin signaling, leading to increased appetite and weight gain [1].

Insulin Resistance

VPA has been shown to impair insulin sensitivity. In animal models and human studies, VPA treatment has resulted in increased fasting insulin levels and decreased glucose tolerance. Mechanistically, VPA may interfere with insulin receptor signaling or promote lipotoxicity and ectopic fat deposition [2].

Pancreatic β-Cell Dysfunction

Experimental studies have indicated that VPA might have direct toxic effects on pancreatic β-cells, possibly through mitochondrial dysfunction, oxidative stress, or interference with cellular calcium homeostasis, which could impair insulin secretion [3].

Mitochondrial Toxicity

VPA is known to inhibit mitochondrial β-oxidation of fatty acids, leading to fat accumulation and energy metabolism disturbances. Mitochondrial dysfunction has been associated with insulin resistance and β-cell failure, key features of T2DM [4].

Risk Factors for VPA-Induced Diabetes

Risk factors include pediatric and adolescent age, female sex, prolonged treatment duration, high dosage, and pre-existing obesity or metabolic syndrome [2-9]. Conditions such as polycystic ovary syndrome (PCOS) further increase susceptibility [5]. In the case discussed, the patient met many of these criteria—being female, adolescent, and having received VPA therapy for over five years.

Despite the proposed mechanisms, sodium valproate remains one of the most used oral anticonvulsants in resource-limited settings. Healthcare providers should recognize its adverse metabolic effects, screen for family history of diabetes, and routinely monitor blood glucose during follow-up visits [10]. This approach is essential to prevent or detect early complications in patients on long term VPA therapy [10].

Sodium valproate remains an effective treatment for epilepsy and other neurological conditions due to its broad-spectrum anticonvulsant properties?. However, increasing evidence links its long-term use to metabolic side effects, particularly weight gain, insulin resistance, and even overt diabetes mellitus [1-4].

Clinicians must be vigilant about the possibility of VPA-induced metabolic complications, especially in pediatric and adolescent patients, where the risks may be amplified due to hormonal changes, body composition, and developmental factors [9]. Our case illustrates how VPA can precipitate DKA in a previously undiagnosed diabetic patient and reinforces the importance of routine blood glucose monitoring during VPA therapy.

Clinicians must be vigilant about the possibility of VPA-induced metabolic complications, especially in pediatric and adolescent patients, where the risks may be amplified due to hormonal changes, body composition, and developmental factors [9]. Our case illustrates how VPA can precipitate DKA in a previously undiagnosed diabetic patient and reinforces the importance of routine blood glucose monitoring during VPA therapy.

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