Rethinking Insulin Resistance: An Overflow Paradigm
The Flaws of the Conventional View
The conventional view of insulin resistance focuses narrowly on glucose transport into cells, seeing it as a problem with the “locks and keys” that allow insulin to move glucose from the bloodstream into cells. However, this view struggles to explain paradoxes like continued high rates of fat storage and de novo lipogenesis (DNL) in insulin resistant tissues.
For example, in the insulin resistant liver, glucose uptake is supposedly hindered, yet DNL and triglyceride production remains elevated. If liver cells were truly “starving” internally due to insulin resistance, as the conventional paradigm states, how could they continue to incorporate glucose into triglycerides at high rates?
The conventional view struggles to explain such paradoxes, leading to the vague concept of “selective insulin resistance” to paper over the cracks. A new paradigm is needed to properly explain theclinical realities.
An Overflow Paradigm
Rather than an “underfill” problem where cells reject insulin’s signals, hyperinsulinemia and insulin resistance may reflect an “overflow” problem. Cells become overloaded with glucose from chronically excessive insulin, until they reach their maximum capacity to store it as glycogen and fat.
At this point, the cell is so full that incoming glucose simply has nowhere left to go, despite insulin signaling it to enter. The cell isn’t resistant to insulin per se, it simply has no more room for glucose. Meanwhile, insulin-driven processes like DNL and fat storage continue unchecked in the overloaded cell.
This paradigm neatly explains the paradoxes without evoking claims of selective resistance. The cells aren’t rejecting insulin signals, they are simply full. The core problem is chronic hyperinsulinemia flooding cells with too much glucose over time, not cellular resistance.
Hyperinsulinemia: The True Culprit
Viewing hyperinsulinemia rather insulin resistance as the core abnormality has profound implications for treatment. If insulin overload is the problem, continuing to inject even more insulin is illogical. It would be akin to dealing with overloaded suitcase by trying to cram yet more items inside.
Instead, the key is reducing the hyperinsulinemia to drain glucose out of overloaded cells. This brings insulin signaling back into a normal range so glucose transport resumes, rather than endlessly escalating insulin doses to overpower resistance.
This paradigm correctly predicts that we should see the greatest treatment benefits from lowering insulin itself, not just glucose. And therapies like intermittent fasting, low carb diets, SGLT2 inhibitors, and bariatric surgery do exactly that while improving metabolic health.
The overflow view also neatly explains the full spectrum of metabolic abnormalities. Hyperinsulinemia doesn’t just drive high blood glucose, but also broader symptoms like high triglycerides, low HDL, obesity, and hypertension that characterize metabolic syndrome.
Benefits of Therapeutic Fasting
Of available interventions, fasting is perhaps the most direct way to rapidly lower chronically high insulin. During a fast, glucose and glycogen stores quickly deplete, forcing cells to fat and protein for fuel.
This metabolic shift actively drains overloaded glucose from tissues like the liver, while ketones spare them from excessive protein breakdown. Fasting periods as short as 24-72 hours can dramatically reduce hyperinsulinemia, insulin resistance, and reverse type 2 diabetes.
Case studies have shown severely diabetic patients rapidly coming off all insulin and normalizing blood sugar in as little as 12 days of therapeutic fasting. Overloaded and failing beta cells have a chance to temporarily “rest” during fasting periods, and fat melts away from the pancreas and liver.
Fasting isn’t without challenges, of course – patients require medical monitoring, electrolyte management, community support, and managed refeeding. But risks are low compared to the lifelong burden of insulin dependence and diabetic complications.
Health Benefits of Periodic Fasting
While evidence is limited, periodic fasting may benefit healthy non-diabetic people as well. Most chronic diseases today involve some element of inappropriate growth signaling, which fasting powerfully curtails through effects on pathways like IGF-1, mTOR, and especially insulin.
Some clinicians argue for routine fasting periods – a popular approach is a low-calorie “fasting mimicking” diet for 3-5 days every 2-3 months. Evidence for such prescriptive protocols is scant but risks are similarly low.
One does not need flawless evidence to adopt a behavior with virtually no health risks but excellent potential upsides. Hence, occasional fasting periods seem advisable even for healthy people looking to promote long-term wellness.
