Via Research Recognition Day Program VCOM-Carolinas 2025

Case Reports

Thiamine Deficiency Mistaken for Diabetic Ketoacidosis: A Case Report Madison Benefield, OMS-III 1 , Hannah Sanders, OMS-IV 1 , George Mitchell, DO, FACOI, FACP, FCCP 2 . 1. Edward Via College of Osteopathic Medicine Carolinas Campus, Spartanburg, South Carolina. 2. Cleveland Clinic Indian River Hospital, Vero Beach, Florida.

Discussion

Introduction

Report of Case

A 42-year-old female presented to the emergency department (ED) due to a decreased level of consciousness. She complained of lower extremity pain, abdominal pain, and back pain, but was noted to be a poor historian. Medical history: Diabetes mellitus, alcohol use disorder, unspecified gastrointestinal bleed, pancreatic pseudocyst, and chronic pancreatitis. Medications: Acamprosate DR, insulin aspart, insulin glargine, lipase-protease amylase, ondansetron, calcium carbonate, and thiamine. Patient admitted to not taking some of her medications due to cost. Social history: Endorsed alcohol consumption but self-reported to not be in excess, and denied smoking, tobacco, or illicit drug use. Initial vital signs: BP: 113/62mmHg, Pulse: 101 bpm, Temperature: 96.9 ℉ , Respirations: 22 breaths/min, SpO2: 100% on room air, weight: 54.9kg. Physical exam: Acute distress and ill-appearing. Lethargic but maintained a Glasgow coma scale (GCS) of 15 with no cranial nerve or sensory deficit and normal deep tendon reflexes. No other abnormalities noted. Initial laboratory tests: beta-hydroxybutyrate of 7.2, lactic acid of 14.5 mmol/L, positive acetone, chloride of 97 mmol/L, CO2 <5, creatinine of 1.01 mg/dL, glucose of 187 mg/dL, calcium of 7.4 mg/dL, albumin of 3.8 g/dL, alkaline phosphatase of 144 U/L, AST of 295 U/L, anion gap >40 mmol/L, EtOH of 172, positive benzodiazepine on toxicology, RBC of 3.27 m/uL, hemoglobin of 9.8 g/dL, hematocrit of 34.5%, MCV of 105.5 fL, MCHC of 28.4, RDW-CV of 18.1%, pH <7.00, pCO2 <16mmHg, pO2 of 165mmHg, bicarbonate of 1 mmol/L, and 1+ hemoglobin, ketones, and protein in the urine. Imaging: No abnormalities on chest radiography or computed tomography of the brain. Electrocardiogram revealed normal sinus rhythm. The working diagnosis in the ED was diabetic ketoacidosis. Patient received fluid resuscitation with intravenous normal saline and sodium bicarbonate. She was started on insulin and thiamine 500mg once a day and admitted to the surgical intensive care unit. She was evaluated by the ICU team several hours later. Discrepancies between the patient’s lab work and the diagnosis of diabetic ketoacidosis were noted, including low urine ketones at 1+ and a lactic acid of 14.5 mmol/L. Upon questioning, the patient endorsed consuming vodka regularly, with her last consumption being four shots the afternoon prior to arrival at the ED. This led to strong consideration of thiamine deficiency as the cause of the patient’s lactic acidosis. The new plan included discontinuing the insulin infusion and initiating insulin sliding scale as her glucose had remained stable, changing the thiamine dosage from 500mg once daily to 500mg three times a day, discontinuing the IV fluids but continuing the sodium bicarbonate, discontinuing prophylactic pantoprazole, and repeating the patient’s CBC and BMP. Repeat lab values included a potassium of 3.2 mmol/L, BUN of 4 mg/dL, calcium 8.2 mg/dL, and phosphorus of 1.9 mg/dL. Her creatinine had lowered to 0.60 mg/dL, her glucose was 90 mg/dL, and her anion gap normalized at 10. Within 12 hours of starting treatment the lactate level had decreased from 15.2 mmol/L to 7.8 mmol/L, and within 24 hours it had normalized at 2.6 mmol/L. The patient’s lethargy and confusion improved, and she was discharged the following day on 100 mg oral thiamine daily.

Thiamine, vitamin B1, is a water-soluble vitamin that is essential for normal aerobic metabolism and normal glucose metabolism, serving as the cofactor for three important enzymes: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase² , ³. In thiamine deficiency, pyruvate is unable to undergo the conversion to acetyl coenzyme A, leading to its accumulation and subsequent conversion to lactic acid. Thiamine deficiency can cause substantial morbidity and mortality, including Wernicke-Korsakoff syndrome, wet beriberi, and dry beriberi, but should also be included in the differential diagnosis for lactic acidosis 1 , as lactic acidosis related to thiamine deficiency can cause vasogenic cerebral edema, disruption of the blood brain barrier, and glial swelling 4 . Lactic acidosis is defined as acidosis with a serum lactate level of ⋝ 4 mmol/L, and occurs when the production of lactate exceeds the liver’s ability to metabolize it 5 . It is the most common cause of metabolic acidosis in hospitalized patients 1 . The differential diagnoses of lactic acidosis have historically been classified into two groups. Type A involves tissue hypoperfusion and reduced arterial oxygen content due to hypoperfusion, sepsis, cardiac failure, pulmonary disease, severe anemia, or carbon monoxide. Type B includes liver failure, renal failure, cancer, strenuous exercise, seizure, ingestion of a large amount of alcohol in an undernourished patient, toxicity due to biguanide therapy, and thiamine deficiency 6 . Individuals at risk for thiamine deficiency include those with chronic, excessive alcohol consumption, those who are malnourished, patients receiving dialysis, and those who require parenteral nutrition 1 . However, thiamine levels are negatively correlated with lactic acidosis in critically patients without liver dysfunction 7 . There are multiple instances where the thiamine requirement is increased. One case series noted three cases of patients who were receiving total parenteral nutrition (TPN) without vitamin supplementation due to lack of availability of parenteral vitamins. Patients were being monitored in the intensive care unit for various conditions. Several days after starting TPN, the patients presented with tachycardia, hypotension, renal impairment, diaphoresis, altered mental status and metabolic acidosis. Once the availability of parenteral vitamins was restored, the three patients showed rapid improvement in acidosis and lactate levels, reaching normal acid base balance and clinical improvement within 12 hours 2 . Another scenario demanding an increase in thiamine requirement includes situations with a high glucose load. In our patient with poorly managed diabetes mellitus, the increase in metabolic demand for thiamine furthered her already increased requirement secondary to long-term, heavy alcohol consumption.

• Historically, thiamine deficiency is associated with low- and middle-income countries whose populations depend on foods with low thiamine content. Insufficient dietary intake of thiamine can also be found in high-income countries in those who do not receive enough dietary intake for various reasons. • Ethanol intake can affect thiamine status in three main ways: Dietary intake in alcoholics is often low in thiamine, alcohol can inhibit intestinal ATPase involved in thiamine absorption, and thiamine requirement is increased in patients with a high glucose load. In our patient with poorly managed diabetes mellitus and medication noncompliance, the increase in metabolic demand for thiamine furthered her already increased requirement secondary to long-term, heavy alcohol consumption. • Hyperglycemia in thiamine deficiency may not only be explained by impaired utilization of glucose at the level of pyruvate dehydrogenase, but also by an inability of the pancreatic beta cells to produce enough insulin to restore euglycemia. In true diabetic ketoacidosis, one would expect the lactate level to be only mildly elevated, and urine ketones to be greater than 1+. • Alcoholic ketoacidosis was considered in this patient’s differential diagnosis. Alcoholic ketoacidosis is caused by the metabolism of alcohol is acetaldehyde and acetate, which increases the ratio of NADH to NAD+ and leads to preferential formation of B hydroxybutyric acid. Peripheral tissues can still oxidize lactic acid, so lactic acidosis tends to be milder than was seen in this patient. However, this could account for the elevated B-hydroxybutyrate seen in the patient’s blood on admission. • In previously documented cases of lactic acidosis secondary to thiamine deficiency, the acidosis persisted despite sodium bicarbonate administration but resolved rapidly with administration of thiamine. This pattern was seen in our patient, with her clinical symptoms resolving completely within 24 hours after increasing her dose of thiamine. • Although the cause of our patient’s lactic acidosis may have been multifactorial, thiamine deficiency was considered to be the leading contributor due to significant clinical improvement with thiamine supplementation • More research is needed to determine the optimal dose and duration of thiamine supplementation in patients with lactic acidosis secondary to thiamine deficiency.

Conclusion

Thiamine deficiency is an underappreciated cause of lactic acidosis that should be considered when a patient presents with metabolic acidosis and a severely elevated lactate level, coupled with risk factors for thiamine deficiency. Once thiamine deficiency is recognized as the cause of lactic acidosis, it can be quickly corrected with thiamine administration, and patients will show rapid improvement in clinical and lab manifestations of metabolic acidosis.

This project was supported by Cleveland Clinic Indian River Hospital Critical Care Department. References and Acknowledgements

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