Root Causes of Insulin Resistance & Type 2 Diabetes: Could Thiamine Deficiency Be Part of the Picture?

Early on in my career, a mentor and long-time functional medicine practitioner encouraged me to study each micronutrient in depth. I spent years digging through research, synthesizing studies, and learning how nutrients impact the body long before AI tools existed to speed up the process. I was recently reminded about a key b-vitamin I had studied but been overlooking in my clients with insulin resistance.

Now, as someone who gets to see the full picture, client labs, dietary intake, stress levels, symptoms, and medical histories, I’m continually making new connections between micronutrient status and chronic health conditions.

Looking Beyond Food and Exercise

Most conversations about insulin resistance focus on diet, exercise, GLP-1s, Metformin and body weight. While these factors certainly matter, blood sugar regulation is also a cellular process.

Recently, a post from naturopathic doctor, Sheila Kenneally caught my attention. She shared that blood sugar issues are not solely a food and exercise problem, they can also be influenced by micronutrient deficiencies, sunlight exposure, and inflammatory conditions such as mast cell activation.

She specifically highlighted thiamine as one of the most important nutrients for blood sugar regulation and noted that thiamine stores can be depleted by:

• SIBO

• Low stomach acid

• Candida overgrowth

• Mycotoxin exposure

• Chronic stress

• Coffee consumption

• Alcohol intake

• High carbohydrate intake without adequate B-vitamin intake

In other words, many of the things modern humans are exposed to regularly.

While addressing these underlying root causes is important, ensuring adequate thiamine intake may be a simple, safe, and relatively inexpensive strategy worth exploring for individuals experiencing insulin resistance or blood sugar dysregulation.

She also highlighted several key thiamine cofactors:

• Magnesium

• Potassium

• Phosphorus

• Riboflavin (Vitamin B2)

Like many nutrients, thiamine doesn’t work in isolation.

Why Thiamine Matters

Thiamine is often recognized for its role in preventing severe deficiency diseases such as beriberi, but its day-to-day functions are far more extensive.

Thiamine plays important roles in:

• Blood sugar regulation

• Energy production

• Cognitive function

• Nervous system health

• Circulation

• Neurotransmitter production

At the cellular level, thiamine serves as a cofactor for multiple enzymes involved in carbohydrate metabolism. In simple terms, it helps convert the carbohydrates you eat into usable cellular energy.

Without adequate thiamine, glucose metabolism becomes less efficient.

Thiamine and Energy Production

One of thiamine’s most important jobs is supporting ATP production, the body’s primary energy currency.

Thiamine is involved in:

• Glycolysis (glucose metabolism)

• The Krebs cycle (cellular energy production)

• Ribose and DNA synthesis

• NAD production

• Neurotransmitter synthesis

Because of its role in these pathways, inadequate thiamine can affect nearly every organ system, particularly those with high energy demands such as the brain, nerves, and heart.

Signs of Thiamine Insufficiency

While severe deficiency is uncommon in developed countries, functional insufficiency may be more common than many practitioners realize.

Potential signs include:

• Fatigue

• Loss of appetite

• Blood sugar imbalances

• Anxiety

• Depression

• Brain fog

• Irritability

• Digestive issues

• Muscle weakness

• Tingling or numbness

• Increased inflammation

Thiamine needs may also increase during:

• Pregnancy and lactation

• Alcohol use

• Liver disease

• Small intestinal disorders

• Malabsorption conditions

• Chronic illness

• High-stress periods

The Diabetes Connection

Research has consistently found that thiamine deficiency is more common in people with Type 2 diabetes.

Scientists believe this may be due to increased urinary losses of thiamine as blood sugar levels rise. Over time, this can create a vicious cycle where impaired thiamine status further compromises glucose metabolism.

Thiamine deficiency has also been linked to several diabetes-related complications, including:

• Peripheral neuropathy

• Oxidative stress

• Endothelial dysfunction

• Inflammation

One reason researchers are interested in thiamine is its ability to reduce the formation of Advanced Glycation End Products (AGEs).

AGEs are harmful compounds formed when excess glucose binds to proteins and fats in the body. Elevated AGE production contributes to:

• Accelerated aging

• Oxidative stress

• Nerve damage

• Vascular damage

• Diabetes complications

Benfotiamine: A More Bioavailable Form

Much of the recent research has focused on benfotiamine, a fat-soluble derivative of vitamin B1.

Benfotiamine has been shown in multiple clinical trials to:

• Improve neuropathy symptoms

• Support endothelial function

• Reduce oxidative stress

• Improve cellular glucose metabolism

• Reduce AGE formation

Researchers have traditionally attributed these benefits to enhanced transketolase activity and improved glucose handling. More recent evidence suggests thiamine and benfotiamine may also influence metabolic and inflammatory pathways through mechanisms involving PPAR-gamma signaling. While more research is needed, these findings suggest thiamine’s impact may extend well beyond simply preventing deficiency.

Genetics Matter Too

Several genes influence thiamine transport and metabolism, including:

• SLC19A2

• SLC19A3

• TPK1

Variations in these genes can impair thiamine utilization and increase the need for supplementation.

Alcohol appears to significantly interfere with thiamine metabolism by suppressing the activity of certain thiamine transporters. Additionally, some medications may inhibit thiamine transport, potentially increasing the risk of deficiency in susceptible individuals.

The Bigger Picture

It’s important to remember that insulin resistance is rarely caused by a single nutrient deficiency.

Factors such as:

• Diet quality

• Sleep

• Stress

• Physical activity

• Inflammation

• Gut health

• Environmental exposures

• Micronutrient status

all interact to influence blood sugar regulation.

However, thiamine represents an interesting piece of the puzzle because it sits at the center of glucose metabolism itself.

While most studies have focused on individuals with Type 2 diabetes rather than earlier-stage insulin resistance, the research suggests that ensuring adequate thiamine status may support healthy glucose metabolism, nerve function, and protection against long-term complications.

As always, supplementation works best when paired with a comprehensive approach that addresses the root causes contributing to blood sugar dysfunction in the first place. We also offer in depth micronutrient testing with Vibrant America’s Micronutrient Panel. Taking a multivitamin can be helpful, but individuals with more severe deficiencies may need higher doses and more holistic healing plans.

Sometimes the missing piece isn’t another restrictive diet or more exercise. Sometimes it’s making sure the cells have the nutrients they need to do their job.