Ketogenic Diet and Metabolic Health

Overview

This lecture covers the role of the ketogenic diet in managing obesity, type 1 and type 2 diabetes, and its impact on metabolic and cardiovascular risk factors, emphasizing glucose and insulin regulation as primary targets.

Metabolic Disease and Key Risk Factors

• Obesity, type 2 diabetes, and fatty liver disease are complex, progressive metabolic disorders influenced by genetics and environment.
• Key early signals: elevated insulin and reduced insulin sensitivity, especially in liver and muscle tissues.
• Fatty liver (now called metabolically associated steatotic liver disease, MASLD) and increased visceral fat are early signs of metabolic dysfunction.
• As these conditions progress, they lead to elevated fasting glucose, increased A1C, inflammation, and higher cardiovascular risk.
• Glycemic control (primarily HBA1C) and blood pressure are stronger predictors of cardiovascular events than LDL cholesterol in diabetes.

Understanding Key Biomarkers

• Fasting glucose: measures current blood glucose at a single point.
• Hemoglobin A1C (HBA1C): reflects average blood glucose over 2-3 months; key predictor of long-term cardiovascular risk.
• Insulin: chronic elevation indicates underlying metabolic dysfunction.
• LDL cholesterol, while associated with heart disease risk, is a lower priority risk factor in diabetics than glycemic control or blood pressure.

Ketogenic Diet: Mechanisms and Impact

• Ketogenic diet is very low in carbohydrates (<50g/day, ideally <30g), high in fat (≈70% of calories), moderate in protein (20-25%).
• Reduces glucose and insulin levels rapidly, shifting primary fuel from glucose to fat (increasing fat oxidation and ketone production).
• Shown in long-term studies (10 years) to maintain near-normal glycemic control and reduce insulin by 40% in type 1 diabetes, even with increased LDL.
• No adverse effects observed on kidney, liver, thyroid, or bone health over long-term ketogenic diet.

Cardiovascular Effects and LDL Cholesterol

• Despite doubling LDL cholesterol, long-term ketogenic diet did not cause vascular stiffening or heart dysfunction in high-risk patients.
• Overall cardiovascular function in ketogenic diet users was often superior to both diabetic and healthy non-diabetic controls.
• LDL increases primarily with more saturated fat intake, but glycemic control, blood pressure, and triglycerides are more significant for heart disease risk.

Ketogenic Diet Structure and Food Choices

• Standard ketogenic macros: 70% fat, 20-25% protein, <10% carbs.
• Example top foods: eggs, salmon or beef, broccoli, macadamia nuts, olives (for fiber, micronutrients, fat diversity).
• Well-rounded keto diet can include low-carb alternatives to common foods and is adaptable to individual preferences.

Who Should Avoid Ketogenic Diets

• Contraindicated in people with inborn errors of fat metabolism.
• Careful consideration needed for those with eating disorders, though evidence is evolving.
• Most healthy adults can consider keto, but individualization, guidance, and monitoring are key.

Physiological vs. Pathological Insulin Resistance

• “Physiological insulin resistance” on keto does not have the same risk as pathological insulin resistance from obesity/diabetes.
• Body remains capable of burning glucose and fat, shifting fuel preference based on availability (Randle cycle).
• Oral glucose tolerance tests are not valid when adapted to keto due to altered fuel metabolism.

Key Terms & Definitions

• Ketogenic Diet — Diet low in carbs, high in fat, moderate in protein, promoting ketosis.
• Insulin Resistance — Reduced response of cells to insulin, leading to elevated blood sugar and insulin.
• Hemoglobin A1C (HBA1C) — Average blood sugar over 2-3 months; main diabetes risk marker.
• Visceral Fat — Fat stored inside the abdomen, linked to higher disease risk.
• MASLD — Metabolically Associated Steatotic Liver Disease (fatty liver).
• LDL Cholesterol — "Bad" cholesterol, associated with cardiovascular disease risk, but less predictive in diabetes than glycemic control.
• Ketone Bodies — Molecules produced during fat metabolism in low-carb states, used for energy.
• Randle Cycle — Metabolic concept explaining preference for fat or glucose fuel use.

Action Items / Next Steps

• Review HBA1C, fasting glucose, and insulin as primary health markers over LDL.
• Consider ketogenic diet if battling obesity, type 2 or type 1 diabetes, under medical supervision.
• Explore low-carb food alternatives for favorite dishes to increase dietary sustainability.
• Read more about ketogenic diet safety and implementation, especially in special populations.