Philip Randle described the Randle Cycle (aka Randle Effect) in 1963 as an explanation of how the human physiology determines glucose or fat metabolism, which determined by the body being in either a fasted or fed state. When in insulin levels are low, the body is in a fasted state and conversely, when insulin levels are high, the body is in a fed state. When the body is in fed state, the mitochondria favour glucose metabolism and inhibits fat metabolism. When the body is in a fasted state, the body favours fat metabolism and inhibits glucose metabolism.
I became aware of the effect of the Randle Cycle after I stopped taking Dapagliflozin (Forxiga/Farxiga). After being off of Forxiga for two weeks, I noticed that the Dawn Phenomenon became more pronounced and took longer to wear off. Others on a fat-adapted (eg, ketogenic) diet have also reported a similar situation and some describe it as psysiological insulin resistance. This occurs because the liver responds to waking hormonal changes and "dumps" glucose into the bloodstream, which significantly boosts serum glucose. Dr Ben Bikman (see Diet Doctor Podcast #35 @ 13:04) states he believes this situation is "glucose intolerance" rather than insulin resistance because psysiologially the body will respond to an influx of insulin. With this glucose intolerance (aka carbohydrate intolerance), hyperinsulinemia is NOT present and the pancreas does not appear to be responding to the endogenous glucose produced by the liver. This has also been described as "Adaptive Glucose Sparing" because, although the liver raises serum glucose from the Dawn Phenomenon, tissues have been adapted to using ketones and no-longer require as much glucose for fuel. It appears that high morning glucose on a low-carb diet is normal and healthy.
- The Lancet: THE GLUCOSE FATTY-ACID CYCLE ITS ROLE IN INSULIN SENSITIVITY AND THE METABOLIC DISTURBANCES OF DIABETES MELLITUS
- The Randle cycle revisited: a new head for an old hat
- Resolving the Paradox of Hepatic Insulin Resistance
- High Glucose on Keto Diet - Adaptive Glucose Sparing
- Dr. Sarah Hallberg on the dawn phenomenon
- Dawn phenomenon: what is it, what causes it, and how do you fix it?
- Is your fasting blood glucose higher on low carb or keto? Five things to know
- Reduced Glucose Tolerance and Skeletal Muscle GLUT4 and IRS1 Content in Cyclists Habituated to a Long-Term Low-Carbohydrate, High-Fat Diet