97: “Fast” vs. “Slow” Insulin Resistance: The Two Paths Explained with Dr. Ben Bikman

He dedicates substantial time to this recommendation, citing studies where carb overfeeding for 6 days tripled fasting insulin and 3 days of high carbs increased oxidative stress driving insulin resistance. He contrasts the modern constant eating pattern — breakfast, mid-morning snack, lunch, afternoon snack, dinner, evening snacks — with the ancestral pattern of intermittent elevations. He emphasizes that even ‘healthy’ carbs like whole grains and fruit juice spike insulin. Lowering insulin improves appetite control and increases metabolic rate, so calorie restriction becomes unnecessary and counterproductive.

He mentions that epinephrine and cortisol can trigger insulin resistance within hours, and that just as rapidly, reducing them reverses the problem. He specifically names improving sleep and cutting caffeine as practical levers. The connection to his ceramide framework implies that stress-reduction also lowers ceramide accumulation, though he doesn’t spell out the intervening biochemistry in this section.

He highlights that when autoimmune disease is active, insulin resistance tracks it precisely. People wearing continuous glucose monitors often notice difficulty controlling blood glucose when they are about to fall ill, demonstrating the acute effect of inflammation on insulin resistance. Removing the inflammatory stimulus (e.g., treating the infection, eliminating an offending food) allows ceramides to drop and insulin sensitivity to return, consistent with the fast insulin resistance model.

Bikman explains that hypertrophic fat cells become insulin resistant as a protective mechanism, causing a harmful state of coexisting high insulin and high free fatty acids that promotes ectopic fat deposition and systemic inflammation. Traditional calorie cutting triggers hunger and metabolic adaptation. In contrast, lowering insulin first — through carb control — improves appetite regulation, increases energy expenditure (partly via ketone excretion), and allows a natural reduction in calorie intake without hunger. He emphasizes that insulin is the primary driver of fat cell growth; without it, excess calories cannot be stored. Thus, addressing insulin is the strategic first step to reversing slow insulin resistance.

He outlines that fast insulin resistance hits in hours: insulin infusion for 24 h reduced glucose uptake, carb overfeeding for 6 days tripled fasting insulin, epinephrine infusion caused rapid muscle insulin resistance in 1980, and cortisol did so in 6 h. All three converge on ceramide accumulation, which blocks AKT. Removing the stimulus clears ceramides and rapidly restores sensitivity. Slow insulin resistance stems from fat cells enlarging (hypertrophy) over years. When fat cells get too big, they become insulin resistant as a self-defense to stop growing further, downregulating insulin receptors and glucose transporters, and they become hypoxic, secreting inflammatory cytokines that cause systemic inflammation and further insulin resistance. This creates a unique metabolic mixture of high insulin and high free fatty acids, leading to ectopic fat storage. Reversing it requires sustained insulin lowering, not just calorie cutting, because hunger will sabotage a calorie deficit.

In the 2014 Journal of Diabetes Research paper, muscle cells treated with high insulin showed a 50% increase in ceramides. When the team blocked ceramide accumulation with a pharmacological inhibitor, insulin no longer impaired signaling, proving ceramides are the essential mediator. This finding underpins his argument that controlling carbohydrate intake — and thus insulin — is the most direct way to prevent ceramide-driven insulin resistance.

Referencing the Food and Agriculture Organization and global nutritional surveys, he paints a picture of a typical day: a bagel for breakfast, sandwich for lunch, sugary snacks, pasta for dinner, and evening snacks. Even supposedly healthy options like whole grains and fruit juice cause large glucose and insulin spikes. In lean, insulin-sensitive subjects, 300–400 g of carbs can keep insulin elevated for over 10 hours. With such a diet, insulin rarely returns to fasting levels, and cells get no chance to resensitize. This is the foundation of his advocacy for carbohydrate control as the primary dietary lever.

He cites Debert and DeFronzo (1980) showing epinephrine infusion rapidly reduced insulin-stimulated glucose uptake in muscle. Another group found that elevating cortisol in just 6 hours induced significant insulin resistance. He mentions Cushing syndrome (chronic cortisol excess) as a clinical example where insulin resistance is prominent. Both hormones are completely different structurally but unified in their goal to raise blood glucose, prompting the body to resist insulin to keep glucose available for fight-or-flight. Removing the stressor allows ceramide levels to drop and sensitivity to return quickly.