This FoundMyFitness podcast features an extensive interview with Dr. Ben Bikman, a professor of cell biology specializing in metabolic disorders. The conversation explores the root causes of insulin resistance, its connection to various chronic diseases, and effective strategies for reversal, including dietary changes, exercise, and sleep optimization. The discussion also delves into the use and potential drawbacks of GLP-1 agonist drugs for weight loss.
Insulin resistance is a common root cause of many chronic diseases: Insulin resistance, even with normal glucose levels, contributes to type 2 diabetes, obesity, Alzheimer's, fatty liver disease, infertility, and certain cancers. This is because insulin affects every cell in the body.
Measuring insulin levels is crucial for early detection: Current clinical practice focuses primarily on glucose levels, overlooking elevated insulin as an early sign of insulin resistance. Continuous Glucose Monitors (CGMs) can help track dynamic glucose changes, indicating potential issues.
Dietary strategies for reversing insulin resistance: Controlling carbohydrate intake, prioritizing whole foods and minimizing refined starches and sugars, and including adequate protein and healthy fats are key. The impact of saturated fats depends on carbohydrate intake; they become more problematic in high-carb diets.
Exercise and strength training's role in insulin sensitivity: While diet is paramount, exercise (especially strength training) significantly improves insulin sensitivity by increasing muscle mass and glucose uptake. Strength training is recommended even for limited time availability.
GLP-1 agonists: benefits and concerns: GLP-1 agonist drugs can be effective for weight loss, but the high doses commonly used may have long-term negative consequences. Microdosing and cycling could mitigate these risks, focusing on habit change rather than solely on weight loss.
Dr. Bikman highlights fasting insulin as the best single biomarker, but also mentions the triglyceride to HDL ratio as a strong surrogate marker for metabolic and cardiometabolic health, and uric acid as another predictor of longevity and healthspan, based on studies like the Amore study from Sweden. He also notes that while HbA1c and APOB (particularly considering particle size) are valuable, the triglyceride-to-HDL ratio is a more readily accessible and practical indicator.
High glucose levels damage cells through two primary mechanisms: glycation and sorbitol pathway activation. Glycation irreversibly alters molecules, reducing their function and increasing inflammation. When glucose overwhelms glycolysis, it's shunted to the sorbitol pathway, causing sorbitol accumulation, increased osmotic pressure, cellular swelling, and potentially cell bursting. This is implicated in conditions like macular degeneration, retinopathies, and nephropathies.
Dr. Bikman explains that a low-carb diet offers a metabolic advantage by lowering insulin levels. This leads to a higher metabolic rate (up to 800 calories/day), increased fat burning, and ketone excretion (ketones being calories). The body's "engine" revs higher, burning more energy as heat and expelling calories, resulting in weight loss even with increased calorie intake. This contrasts with high-carb diets which often result in insulin spikes, increased hunger, and less metabolic flexibility.
High doses of GLP-1 agonist drugs, while effective for weight loss, carry several potential long-term risks. The podcast mentions a study showing a more than doubled risk of blindness in users. Another study revealed a tripled risk of major depression and a doubled risk of suicidal behavior in those who used the drugs for two years. Additionally, the slowed gastric emptying and intestinal peristalsis can lead to discomfort (nausea, burping), affect drug and nutrient absorption, and possibly contribute to muscle loss due to poor digestion and nutrient uptake.
The video explores the following topics related to insulin resistance and metabolic health:
Insulin Resistance as a Root Cause of Chronic Disease: The pervasive role of insulin resistance in various health problems, including type 2 diabetes, obesity, Alzheimer's disease, fatty liver disease, infertility, and certain cancers.
Early Detection of Insulin Resistance: The limitations of focusing solely on glucose levels and the importance of measuring insulin levels for early detection. The use of CGMs for monitoring dynamic glucose response is discussed.
Dietary Strategies to Reverse Insulin Resistance: The impact of carbohydrate intake (refined vs. whole), the role of saturated fats (in relation to carb intake), the importance of protein, and the benefits of a low-carb approach.
Exercise and Insulin Sensitivity: The role of exercise, particularly strength training, in improving insulin sensitivity, increasing muscle mass, and improving glucose uptake.
Meal Frequency and Timing: The effects of meal frequency, late-night eating, and the impact of meal timing on insulin levels and sleep quality.
Environmental Toxins and Insulin Resistance: The potential impact of air pollution and other environmental toxins on metabolic health and insulin resistance.
Medications and Metabolic Health: The effects of commonly prescribed medications, such as statins and antidepressants, on weight gain and metabolic health.
GLP-1 Agonist Drugs: The mechanisms of action, benefits (weight loss, appetite regulation), risks, and potential long-term consequences of GLP-1 agonist drugs. Microdosing and cycling strategies are explored.
Fat Storage and Metabolism: The different types of fat storage (subcutaneous vs. visceral), the implications of fat cell size (hypertrophy vs. hyperplasia), and the role of linoleic acid and seed oils.
Biomarkers of Aging and Metabolic Health: Key biomarkers indicative of biological aging, such as fasting insulin, triglyceride to HDL ratio, and uric acid levels.
Insulin's Role in Aging: The mechanisms by which insulin can accelerate aging, including its effects on mTOR, autophagy, and stress response pathways. The damaging effects of high glucose (glycation and sorbitol pathways) are also discussed.
Practical Strategies for Improving Metabolic Health: Simple, actionable steps for improving insulin sensitivity and metabolic health, such as modifying breakfast habits, mindful eating, and incorporating exercise.
Based solely on the provided transcript, the risks associated with GLP-1 agonist drugs discussed include:
Weight regain after cessation: If lifestyle changes aren't made alongside medication, weight is often regained once the drug is stopped.
Increased risk of major depression: A study showed a three-fold increase in the risk of major depression in users after two years of use (at higher doses).
Increased risk of suicidal behavior: A two-fold increase in the risk of suicidal behavior was also observed in a study of users after two years on higher doses.
Increased risk of anxiety: A study showed a 106% increased risk of anxiety in users after two years on the higher dose.
Increased risk of blindness: A recent study indicated more than double the risk of developing blindness in individuals using high doses of GLP-1 agonists.
Gastrointestinal distress: The mechanism of action (delayed gastric emptying and slowed peristalsis) can cause discomfort, including nausea, burping, and changes in nutrient absorption. This can, in turn, lead to nutritional deficiencies.
Muscle loss: While not definitively determined to be a direct effect of the drug, the significant fat-free mass loss observed in some studies is attributed partly to the drug's effects on the gastrointestinal tract (affecting nutrient absorption) and partly to inadequate protein intake and lack of resistance training during rapid weight loss.
The transcript emphasizes that these risks are more pronounced with the higher doses currently used clinically for weight loss, suggesting that lower doses may mitigate some of these side effects.
The transcript highlights several risks associated with different aspects of metabolic health and the interventions discussed:
Regarding Insulin Resistance and its Consequences:
Development of chronic diseases: Insulin resistance, even without high glucose levels, significantly increases the risk of developing various chronic diseases, including type 2 diabetes, obesity, Alzheimer's disease, fatty liver disease, infertility, and certain cancers.
Cardiovascular disease: High levels of insulin and the resulting metabolic dysregulation increase the risk of cardiovascular events, including stroke. Visceral fat, often associated with insulin resistance, contributes to this risk.
Accelerated aging: Chronic high insulin levels inhibit processes like autophagy, impacting cellular repair and contributing to accelerated aging. High glucose levels also damage cells through glycation and sorbitol pathway activation, further accelerating aging.
Regarding Dietary Choices:
Overeating due to insulin spikes: Consuming refined carbohydrates can lead to insulin spikes, followed by hypoglycemia and increased hunger, potentially causing a cycle of overeating.
Metabolic problems from combining high saturated fat with high carbohydrates: Although saturated fat itself is not definitively shown to be a primary driver of insulin resistance, combining a high saturated fat diet with a high-carbohydrate diet can significantly worsen insulin resistance and cardiometabolic health.
Regarding GLP-1 Agonist Drugs:
Weight regain upon discontinuation: Without accompanying lifestyle changes, weight is often regained after ceasing GLP-1 agonist treatment.
Mental health issues: Studies indicate increased risks of major depression, suicidal behavior, and anxiety with long-term high-dose use.
Vision problems: High doses are linked to an increased risk of blindness.
Gastrointestinal problems: The drugs can cause significant gastrointestinal distress due to the changes in gastric emptying and intestinal motility.
Potential muscle loss: Significant fat-free mass loss is observed in some studies, which may be partly due to the drugs' effects on digestion and nutrient absorption, but also due to insufficient protein intake and lack of resistance training.
Regarding Lack of Sleep:
Increased insulin resistance: Even one night of poor sleep can lead to insulin resistance due to elevated stress hormones (cortisol and epinephrine).
Disrupted melatonin rhythm: Hypoglycemia from late-night eating can disrupt melatonin production, further worsening sleep quality.
It is crucial to note that the video emphasizes that many of these risks are more significant with high doses of GLP-1 agonists and unhealthy dietary habits, and that many can be mitigated through healthy lifestyle choices.
The transcript mentions a study showing that the risk of blindness more than doubled in people using high doses of GLP-1 agonists. However, the study is described as correlational, meaning it shows an association but doesn't definitively prove that the drug causes blindness. Other factors in the lives of the study participants could be contributing to the increased risk.
