Thiamine as Adjunctive Therapy for Diabetic Ketoacidosis

Thiamine (vitamin B1) is a water-soluble vitamin that plays a key role in aerobic glucose
metabolism. Thiamine is a cofactor of pyruvate dehydrogenase (PDH), an enzyme that must be
activated for entry into the Krebs Cycle for aerobic metabolism. PDH activity is reduced in
thiamine deficient states, resulting in a shift in pyruvate metabolism to the anaerobic
pathway. This leads to increased lactate production and acidosis. Thiamine loss in the urine,
with consequent thiamine deficiency, is not uncommon in diabetes. The investigators'
preliminary studies have found that thiamine deficiency in occurs in as many as 39% of
patients with DKA, and that thiamine levels are inversely associated with lactate and
acidosis. The investigator hypothesizes that treating DKA patients with intravenous thiamine
will lead to faster resolution of acidosis and improved aerobic metabolism. The
investigator's secondary hypothesis is that thiamine treatment will shorten stays in the ICU
and hospital and lead to utilization of fewer hospital resources.

In this randomized, double-blind, placebo-controlled trial, patients admitted to the hospital
with DKA who are enrolled in the study will be randomized to either intravenous thiamine
(200mg in 0.9% saline) twice daily for two days or an identical volume of 0.9% saline on the
same schedule. The investigator's primary outcome is change in bicarbonate over the 24 hours
following enrollment, with measurements at 0, 6, 12, 18, 24 hours, using a linear
mixed-effects model. Secondarily, patients will be stratified by Type I and Type II DM.
Additionally, a pre-planned sub-analysis of thiamine deficient subjects will be performed.

Inclusion Criteria:

- Bicarbonate ≤15 mEq/L

- Anion gap > 12 mEq/L

- Blood pH≤ 7.24 (if already obtained by clinical team)

- Urine ketones (qualitative) or serum ketones (β-hydroxybutyric acid) > 3 mmol/L

- Enrollment within 6 hours of presentation

Exclusion Criteria:

- Current thiamine supplementation ≥ 6 milligrams per day (i.e., more than a
multivitamin)

- Competing causes of severe acidosis including seizure, carbon monoxide poisoning,
cyanide toxicity, cardiac arrest, liver dysfunction (specifically defined as known
cirrhosis)

- Known allergy to thiamine

- Competing indication for thiamine administration as judged by the clinical team (e.g.,
alcoholic)

- Research-protected populations (pregnant women, prisoners, the intellectually
disabled)

- Patient enrolled previously in same study

- Code status of Do Not Resuscitate/Do Not Intubate (DNR/DNI) or Comfort Measures Only
(CMO)