Understanding Insulin Resistance

What is Insulin Resistance?

Insulin resistance occurs when the body’s cells—especially those in the muscles, fat, and liver—become less responsive to the effects of insulin, a hormone produced by the pancreas. Under normal circumstances, insulin helps cells absorb glucose (sugar) from the bloodstream to be used for energy or stored for future use. However, when cells become resistant to insulin, the pancreas compensates by producing more insulin to help glucose enter the cells. Over time, this can lead to elevated levels of insulin in the blood, known as hyperinsulinemia, and eventually, the pancreas may struggle to keep up, causing blood sugar levels to rise.

The consequences of insulin resistance are far-reaching. Persistent high blood sugar levels can lead to prediabetes and Type 2 diabetes, conditions that significantly increase the risk of heart disease, stroke, and other serious health problems. Additionally, insulin resistance is often associated with other metabolic issues, including obesity, high blood pressure, and abnormal cholesterol levels, collectively known as metabolic syndrome.

Symptoms and Risk Factors

Insulin resistance itself doesn’t usually cause noticeable symptoms, which is why it often goes undiagnosed until it leads to more serious conditions like Type 2 diabetes. However, certain signs and risk factors can indicate the presence of insulin resistance:

• Increased hunger and fatigue: When cells are resistant to insulin, they don’t get the energy they need, leading to increased hunger and fatigue.
• Weight gain, particularly around the abdomen: Insulin resistance is closely linked to obesity, especially the accumulation of fat around the midsection.
• Dark patches of skin (acanthosis nigricans): These velvety, darkened patches of skin, often found on the neck, armpits, or groin, can be a sign of insulin resistance.
• High blood pressure: Insulin resistance can contribute to hypertension, a major risk factor for cardiovascular disease.
• Elevated cholesterol and triglycerides: Insulin resistance often accompanies high levels of LDL (bad) cholesterol and triglycerides, as well as low levels of HDL (good) cholesterol.

Risk factors for insulin resistance include obesity, a sedentary lifestyle, a diet high in processed foods and sugars, and a family history of Type 2 diabetes. Certain ethnic groups, including Indigenous Canadians, African Canadians, and South Asian Canadians, are also at higher risk.

History and Development of Metformin

Metformin has a long history that dates back to the 1920s when researchers first identified its glucose-lowering properties in a plant called Galega officinalis, also known as French lilac. However, it wasn't until the 1950s that metformin was developed as a pharmaceutical drug. French physician Jean Sterne was the first to publish clinical evidence of metformin's efficacy in reducing blood sugar levels. Since then, it has become the most widely prescribed oral medication for Type 2 diabetes worldwide.

How Metformin Improves Insulin Sensitivity

Reduction of Hepatic Glucose Production

One of the key ways metformin improves insulin sensitivity is by targeting the liver, which plays a crucial role in glucose metabolism. In individuals with insulin resistance, the liver often produces excessive amounts of glucose, even when it's not needed, leading to elevated blood sugar levels. Metformin reduces this overproduction by inhibiting a process called hepatic gluconeogenesis (production of glucose from non-carbohydrate sources). This is achieved through the activation of an enzyme known as AMP-activated protein kinase (AMPK), which acts as an energy sensor in cells. When AMPK is activated, it suppresses the liver's glucose production, thereby lowering blood sugar levels and reducing the burden on the pancreas to produce excess insulin.

Enhancing Peripheral Glucose Uptake

Metformin also directly impacts how muscle and fat cells respond to insulin. In people with insulin resistance, these cells are less responsive to insulin, meaning they don't absorb glucose from the bloodstream as efficiently as they should. Metformin helps to reverse this by increasing the number and activity of insulin receptors on the surface of muscle and fat cells. This enhanced sensitivity allows these cells to take in more glucose, reducing blood sugar levels and improving overall metabolic control. Additionally, metformin increases the translocation of glucose transporters (such as GLUT4) to the cell membrane, which further facilitates the uptake of glucose into the cells.

Reduction of Intestinal Absorption of Glucose

Metformin also decreases the absorption of glucose from the intestines after meals, which helps to prevent spikes in blood sugar levels. The unabsorbed glucose is passed through the digestive tract then processed in the colon, where bacteria may ferment some of it, but the majority ends up being excreted in stool.

Improving Gut Microbiota

Recent research has uncovered a fascinating new mechanism by which metformin may improve insulin sensitivity—through its effects on the gut microbiota. The gut microbiota, a complex community of microorganisms living in the digestive tract, plays a significant role in metabolic health. Studies have shown that metformin can alter the composition of the gut microbiota in a way that enhances insulin sensitivity. For example, metformin has been found to increase the abundance of beneficial bacteria, such as Akkermansia muciniphila, which are associated with improved glucose metabolism and reduced inflammation. This interaction between metformin and the gut microbiota represents an exciting area of research, suggesting that metformin's benefits may extend beyond its direct effects on glucose metabolism.

These mechanisms make metformin particularly effective at lowering fasting blood glucose levels, which are critical in the management of Type 2 diabetes. Importantly, metformin does not cause hypoglycemia (dangerously low blood sugar levels) when used alone, which is a significant advantage over some other diabetes medications.

Benefits of Metformin Beyond Blood Sugar Control

Weight Management

One of the notable benefits of metformin is its potential role in weight management, particularly for individuals with Type 2 diabetes and insulin resistance. Unlike many other diabetes medications that can lead to weight gain, metformin is often associated with modest weight loss or at least weight neutrality. This effect is particularly valuable because excess weight, especially around the abdomen, is a major contributor to insulin resistance and the progression of Type 2 diabetes.

The weight loss effect of metformin is believed to be due to several factors. Firstly, metformin may reduce appetite and caloric intake, potentially by altering the production of hormones involved in hunger regulation, such as ghrelin. Secondly, metformin’s action on the gut microbiota, as discussed earlier, may also contribute to changes in metabolism and fat storage. Finally, by improving insulin sensitivity, metformin helps to reduce the storage of fat in the body, particularly in the liver and muscles.

Cardiovascular Protection

Beyond its effects on glucose metabolism, metformin has been shown to offer protective benefits for the cardiovascular system, a critical consideration for individuals with diabetes who are at increased risk of heart disease and stroke. Studies have demonstrated that metformin can lower the risk of cardiovascular events, such as heart attacks, in people with Type 2 diabetes. This protective effect is likely due to several mechanisms:

• Improvement in Lipid Profiles: Metformin has been shown to improve cholesterol levels, particularly by reducing LDL (bad) cholesterol and triglycerides while potentially increasing HDL (good) cholesterol. These changes in lipid profiles are beneficial for heart health.
• Reduction in Inflammation: Chronic low-grade inflammation is a key driver of atherosclerosis, the process that leads to the narrowing and hardening of arteries. Metformin has anti-inflammatory properties, which may help reduce the progression of atherosclerosis and lower cardiovascular risk.
• Improvement in Endothelial Function: The endothelium is the inner lining of blood vessels, and its proper functioning is crucial for maintaining vascular health. Metformin has been shown to improve endothelial function, which helps to reduce the risk of blood clots and maintain healthy blood pressure.

Anti-Aging Properties

Emerging research suggests that metformin may have anti-aging properties, making it a subject of interest beyond the management of diabetes. Some studies have indicated that metformin may extend lifespan and delay the onset of age-related diseases, such as cancer, Alzheimer's disease, and cardiovascular diseases. This potential anti-aging effect is thought to be related to metformin’s ability to activate AMPK, a key regulator of cellular energy balance that influences processes related to aging, such as inflammation, oxidative stress, and cellular repair.

In addition, metformin’s impact on reducing insulin levels and improving metabolic health may contribute to its potential in delaying age-related decline. While the research is still ongoing, and much of the evidence comes from animal studies, the possibility that metformin could serve as a longevity-promoting agent is an exciting area of scientific exploration.

Cancer Prevention

Another area where metformin has shown promise is in the prevention of certain types of cancer. Epidemiological studies have observed that individuals with Type 2 diabetes who take metformin have a lower incidence of several types of cancer, including breast, colorectal, and pancreatic cancer, compared to those who do not take the medication. The exact mechanisms are not fully understood, but potential explanations include:

• Reduction in Insulin Levels: High insulin levels are associated with increased cancer risk, possibly due to insulin’s role in promoting cell growth and proliferation. By lowering insulin levels, metformin may help reduce this risk.
• Inhibition of mTOR Pathway: The mTOR pathway is a cellular signaling pathway that plays a role in cell growth and survival. Metformin’s activation of AMPK can inhibit the mTOR pathway, potentially reducing the growth of cancer cells.
• Anti-Inflammatory and Antioxidant Effects: Metformin’s ability to reduce inflammation and oxidative stress may also contribute to its cancer-preventive properties.

Considerations for Canadians

Accessibility and Cost in Canada

In Canada, metformin is widely available and is considered a cornerstone of Type 2 diabetes treatment. The medication is covered by most provincial and territorial health plans such as OHIP, making it accessible to a large portion of the population. For those without prescription coverage, metformin is relatively affordable, especially in its generic form. However, the cost can vary depending on the pharmacy, the dosage, and whether it is purchased as a brand-name drug or a generic version.

For Canadian seniors, metformin is often covered under provincial pharmacare programs, reducing the financial burden associated with long-term medication use. Additionally, some private insurance plans may cover the full or partial cost of metformin, depending on the plan's details. Canadians should consult with their healthcare providers or pharmacists to explore options for obtaining metformin at the lowest possible cost, especially if they require long-term therapy.

Side Effects and Management

While metformin is generally well-tolerated, some Canadians may experience side effects, particularly when they first start taking the medication. The most common side effects include gastrointestinal issues such as nausea, diarrhea, and stomach discomfort. These side effects are usually temporary and can often be managed by starting with a low dose and gradually increasing it, as recommended by healthcare providers.

For those who continue to experience gastrointestinal discomfort, taking metformin with meals or switching to an extended-release (ER) formulation may help alleviate symptoms. The extended-release version of metformin releases the medication more slowly in the body, which can reduce the likelihood of gastrointestinal issues. It’s important for Canadians to communicate with their healthcare providers if they experience persistent side effects, as there may be alternative strategies to improve tolerance.

A rare but serious side effect of metformin is lactic acidosis, a condition where lactic acid builds up in the bloodstream faster than it can be removed. This is more likely to occur in individuals with kidney impairment, liver disease, or those who consume excessive alcohol. Canadians with these conditions should discuss the risks with their healthcare provider before starting metformin and may require regular monitoring of kidney function while on the medication.

Interactions with Other Medications

Canadians taking metformin should be aware of potential drug interactions, particularly with other medications commonly prescribed for managing chronic conditions. For example, certain blood pressure medications (such as ACE inhibitors and diuretics), corticosteroids, and other diabetes medications (like insulin) can interact with metformin, affecting its efficacy or increasing the risk of side effects.

It’s essential for Canadians to inform their healthcare providers of all medications they are taking, including over-the-counter drugs and supplements, to avoid harmful interactions. Regular monitoring of blood sugar levels, kidney function, and overall health is recommended for anyone on metformin, especially when other medications are involved.

Special Considerations for Indigenous and Rural Communities

For Indigenous Canadians and those living in rural or remote areas, accessing healthcare services and medications like metformin can present unique challenges. Limited access to pharmacies, healthcare providers, and diabetes education resources can make managing Type 2 diabetes more difficult. Telemedicine services, which have become more widespread in Canada, offer an important solution by providing remote consultations and prescriptions, reducing the need for travel.

Indigenous communities may also benefit from culturally tailored diabetes management programs that incorporate traditional practices and foods while promoting the use of medications like metformin. Organizations such as Diabetes Canada and various provincial health programs offer resources specifically designed to address the needs of Indigenous populations, emphasizing community-based approaches to diabetes care.

Monitoring and Regular Check-ups

Effective management of Type 2 diabetes and insulin resistance hinges on consistent monitoring and routine check-ups. At TeleTest, we prescribe metformin as well as continuous glucose monitors (CGMs) for those with diabetes or simply want to better manage blood sugar. Regular self-monitoring is key, allowing individuals to track how well their medication and lifestyle changes are working. Collaborating closely with healthcare providers helps determine optimal blood glucose targets and testing frequency. The increasing availability of CGMs across Canada provides real-time insights, enhancing overall diabetes management.

In addition to glucose monitoring, annual check-ups remain critical for evaluating the long-term effectiveness of metformin and adjusting treatment as necessary. Routine blood tests to monitor kidney function, cholesterol levels, and blood pressure are essential to safeguarding cardiovascular health.

FAQ

What happens if you eat a lot of sugar while taking metformin?

While consuming excessive sugar while taking metformin is generally better than doing so without the drug, eating a lot of sugar can negatively impact the medication's effectiveness. High sugar intake can contribute to increased blood sugar levels, which may make metformin less efficient at controlling these levels due to increased insulin resistance

Can Metformin cause too much insulin?

Metformin does not typically cause an overproduction or excess of insulin. Instead, it works primarily by improving insulin sensitivity in cells, particularly in the liver and muscles, and by reducing the amount of glucose produced by the liver. This helps the body utilize insulin more effectively, which in turn lowers blood sugar levels.

Can Metformin Cause Low Blood Sugar (Hypoglycemia)?

Unlike some other diabetes medications, metformin does not usually cause hypoglycemia when taken on its own. Its primary action is to improve insulin sensitivity and reduce glucose production in the liver, rather than increase insulin production. Hypoglycemia is more likely to occur when metformin is combined with other diabetes medications, such as insulin or sulfonylureas.

Does Metformin increase your metabolism to burn more calories?

Metformin can increase your metabolism in specific ways related to energy use, but it does not necessarily lead to a significant increase in calorie burning in the way that something like exercise or thermogenic drugs might. It primarily shifts your metabolism towards more efficient energy use (especially of fats and glucose) rather than increasing the basal metabolic rate so its impact on total daily calorie burning is relatively modest.

Can Metformin Alone Manage Diabetes?

While metformin is highly effective, it is not a substitute for a healthy lifestyle. Combining metformin with dietary changes, physical activity, and weight management is essential for achieving the best possible outcomes in managing insulin resistance and Type 2 diabetes.

Disclaimer: This blog post is intended for educational purposes only and should not be taken as medical advice. Always consult your healthcare provider for personal health concerns.