The majority of T2DM adults show thiamine (vitamin B1) deficiency which may contribute to impaired function. This study will examine patients with T2DM through brain MRI scans, cognition assessments, blood tests, and questionnaires. Our goal is to see if a thiamine treatment (taking vitamin B1 capsules) can improve function. Patients will be asked to come to UCLA two times three months apart and each visit will last about 2.5-3 hours.

Type 2 diabetes mellitus (T2DM) makes up 90-95% of all diagnosed diabetes mellitus, and is a serious health issue in the United States.1 T2DM adults show significant mood and cognitive deficits, symptoms that are associated with higher morbidity and mortality, poor self-care, and decreased quality of life, and the condition is linked with early dementia and Alzheimer's disease. Brain structural changes emerge in T2DM adults in sites that exert major influence on cognition and mood functions, potentially resulting from impaired blood brain barrier function (BBB). However, it is unclear whether BBB function can be repaired in T2DM adults, reducing impaired cognition and mood functions and early risks of dementia and Alzheimer's disease in the condition.

Several pre-clinical studies suggest the possibility for BBB function repair, including low-cost thiamine intervention. Thiamine is an essential co-factor for carbohydrate metabolism and adequate or higher levels promote aerobic metabolism and reduce neural injury. In addition, reduced thiamine levels are shown contributing to impaired endothelial cell functions and higher doses of thiamine treatment improve endothelial functions. Thus, lower thiamine levels can contribute to neural, as well as endothelial cell dysfunctions, resulting to impaired BBB function. The majority of T2DM adults show thiamine deficiency, which may contribute to impaired BBB function, but it is unclear if the thiamine treatment can improve BBB function in T2DM adults. The investigators hypothesize that thiamine intervention (3-months) will reduce impaired BBB function and will improve cognition and mood functions in T2DM adults with thiamine treatment compared to non-treated T2DM adults.

In summary, the investigators propose that low-cost thiamine treatment for 3-months in T2DM adults will repair BBB dysfunction and improve mood and cognition functions. If studies successful, the findings from this clinical trial might serve as a novel and innovative treatment strategy to repair BBB function, affecting less cognition and mood function, and hence better outcomes in T2DM adults, as well as in other adult conditions with impaired BBB function. This R21 exploratory clinical trial study will provide required data regarding the benefits of a low-cost thiamine intervention that could be implemented on a large-scale clinical trial to repair BBB function in T2DM adults, as congruent to the National Institutes of Health mission, and thus, decrease early risks of dementia and Alzheimer's disease, reduce morbidity and mortality, and increase quality of life in this serious and common T2DM patient population.

Inclusion Criteria:

• Diagnosed T2DM
• Outpatient status
• Able to lay flat for imaging

Exclusion Criteria:

• A previous history of stroke
• Current in-take of thiamine
• Known thiamine allergy
• Seizure disorder
• Head trauma
• Myocardial infarction
• Current pregnancy (if female)
• Diagnosed neuropsychiatric disorders (clinical depression, schizophrenia, manic-depression)
• Diagnosed dementia
• Sleep disordered breathing
• Airway or chest deformities that would interfere with breathing
• Chronic obstructive pulmonary disease
• Cystic fibrosis
• Presence of brain mass lesions
• Any history of drug abuse (e.g., cocaine, tobacco, or cannabis)
• Renal failure (requiring dialysis)
• All T2DM adults with metallic and electronic implants (phrenic or cardiac pacemakers; although some pacemakers and cardioverter defibrillators are safe at a low magnetic field, they are not safe at 3.0-Tesla scanner)
• Non-removable insulin pump/glucose sensor
• Braces
• Body weight more than 300 pounds (weight and height will be used to calculate BMI to determine if the patient will fit in the scanner and stay within parameters of size restrictions of MRI scanner table)
• Any other contraindications to MRI, such as claustrophobia, or metallic-based tattoos, as per MRI safety website suggestions, will also be excluded.

The investigator will make every effort to publish data in a timely manner. Once the findings related to changes in blood brain barrier based on brain MRI data before and after thiamine intervention have been published or by the end of award performance period, whichever is sooner, the MRI data, demographics, mood and cognition, and clinical data (devoid of individual identifiers) will be deposited in NIH supported domain-specific data sharing repository (NIMH Data Archive). All data will be labeled with consistent unique identifiers that will make it easily findable in data repository to interested research investigators. Data will be available forever after sharing with data repository to other investigators for secondary analyses.

Once the findings related to changes in blood brain barrier based on brain MRI data before and after thiamine intervention have been published or by the end of award performance period, whichever is sooner.

Any research investigator

Participants will be assigned a number to be used instead of their names with double-blind randomization until visits are complete and data is analyzed.