Peter Attia MD - How to Get Your Insulin to a Normal Level | Ralph DeFronzo
The discussion highlights the impact of hyperinsulinemia on insulin resistance. It is noted that individuals with type 2 diabetes taking high doses of insulin should focus on nutrition, exercise, and medication to reduce insulin dosage. A study demonstrated that even healthy, lean individuals can develop insulin resistance within 48 to 72 hours when exposed to low doses of insulin infusion, raising their fasting insulin levels. This suggests that hyperinsulinemia downregulates the insulin signaling system, leading to insulin resistance. The findings emphasize the importance of managing insulin levels to prevent resistance, even in non-diabetic individuals. The conversation also touches on the genetic factors contributing to insulin resistance, noting that historical data shows insulin resistance existed even when diabetes prevalence was low, indicating a genetic component.
Key Points:
- Hyperinsulinemia can cause insulin resistance in healthy individuals within 48-72 hours.
- Reducing insulin dosage through lifestyle changes can help manage type 2 diabetes.
- Insulin resistance can be induced by downregulating the insulin signaling system.
- Genetic factors contribute to insulin resistance, not just obesity.
- Managing insulin levels is crucial to prevent resistance.
Details:
1. 🩺 Effective Insulin Management Strategies
1.1. Nutrition and Exercise for Insulin Reduction
1.2. Pharmacological Strategies for Insulin Management
2. 🔬 Understanding Hyperinsulinemia and Its Effects
- Increasing fasting insulin levels in healthy, lean individuals from 8 to 20 over 3 days can induce insulin resistance comparable to type 2 diabetes in just 48 to 72 hours, demonstrating the rapid impact of hyperinsulinemia.
- Hyperinsulinemia affects insulin signaling by downregulating key pathways such as IRS1, PI3 kinase, and AKT, which are crucial for insulin's action.
- The evidence for hyperinsulinemia inducing insulin resistance is robust, supported by consistent findings in both human and rodent studies.
- Understanding these mechanisms is essential for developing interventions to prevent insulin resistance and related metabolic disorders.
3. 🧪 Insights from Insulin Infusion Studies
- Normal volunteers with a fasting insulin of 8 and glucose of 90 were infused with insulin at a clinical research center, maintaining glucose levels constant.
- During the infusion, insulin levels were increased by 1.5 times, a much smaller increase compared to post-meal levels, yet constant at 20.
- Within 48 to 72 hours, participants developed insulin resistance comparable to type 2 diabetics.
- The model suggests that insulin resistance is primarily driven by insulin itself, downregulating the insulin signaling system, not by lipotoxicity or intramyocellular lipid accumulation.
- If the infusion was stopped after 72 hours, it is predicted that participants would return to normal insulin sensitivity within 24 to 48 hours.
- Prolonged exposure to increased insulin levels over several months could result in sustained insulin resistance.
4. 🧬 Exploring Genetic Causes of Insulin Resistance
- Insulin is absorbed by the liver via the portal vein, regulating glucose and insulin distribution, but type 1 diabetes treatment disrupts this with peripheral administration, causing imbalance.
- Excess peripheral insulin leads to resistance, especially in obese or type 2 diabetes patients already insulin resistant.
- Effective management tackles both low insulin production and resistance.
- Genetic factors are crucial; insulin resistance historically affected even lean individuals, showing genetics' role over lifestyle.
- Diabetes incidence was 1-2% in the 1950s and 1970s, despite lean individuals having resistance, emphasizing genetics.
- Specific genes, like IRS1 and PPARG, are linked to insulin resistance, highlighting the need for genetic screening and personalized treatment strategies.