Overview
Insulin is treated by mainstream medicine as the central hormone of blood sugar regulation, but its real function is to lay down fat in adipose tissue and store glycogen in the liver. Type 2 diabetes is not a disease of insulin deficiency; the great majority of diabetics have normal or high insulin, and the actual problem is that free fatty acids, especially polyunsaturated ones, are blocking glucose from being oxidized in the cells. The Randle effect, established in the 1960s, shows that an excess of fatty acids in the blood prevents the use of sugar regardless of how much insulin is present. Insulin itself accounts for only about eight percent of the insulin-like activity in the blood, with potassium, leucine, and exercise providing most of the rest. The whole concept of insulin resistance falls apart on close inspection because every tissue responds differently.
Key Points
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Insulin's primary function is to store fat and glycogen, not to "lower blood sugar" as commonly described. A major function of insulin is to lay down fat in the adipose tissue and glycogen in the liver. When insulin is high from quickly digested starch or pure glucose, the liver gets overwhelmed and the excess turns into stored fat. This is why eating starches and pure glucose tends to make people fatter than eating sucrose, even at the same calorie level, because the fructose half of the sucrose molecule does not stimulate insulin and instead promotes glycogen storage.
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Free fatty acids, especially polyunsaturated ones, block the cell's ability to oxidize glucose. This is the Randle effect. P.J. Randle observed in 1963 or 1964 that increased fatty acids in the blood would block glucose oxidation. When hospitals began giving intravenous fatty emulsions to patients, blood glucose would shoot up about 15 minutes after the injection. Polyunsaturated fatty acids are the most damaging because they create long-range damage that keeps the Randle effect going.
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Insulin accounts for only about eight percent of the insulin-like activity in the blood. Several other things imitate the function of insulin. Potassium is probably the largest single factor, which is why fruits, with their high potassium content, smoothly handle a sugar load with very little stimulation of pancreatic insulin secretion. Leucine, an amino acid found in chocolate and meat, also acts like insulin. Exercise increases the cell's ability to take up glucose by an insulin-like mechanism, and magnesium also helps regulate glucose.
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Type 2 diabetes is not a problem of insulin deficiency. When doctors looked for more ways to sell insulin, they noticed that lots of people who weren't wasting away also had very high blood sugar, but their blood had a normal amount of insulin in it. About 95 percent of people now diagnosed with diabetes are overweight and have plenty of insulin. The actual problem is that free fatty acids prevent the cells from using glucose, so the liver responds by making more glucose to try to overcome the block, stuffing more glucose into the blood.
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Cortisol and insulin always travel together, and cortisol is the main driver of fasting blood glucose in type 2 diabetics. About 80 percent of the high blood glucose in type 2 diabetes comes from gluconeogenesis in the liver, not from the diet, and cortisol is the primary driver of that pathway. People with Cushing syndrome, who over-produce cortisol, are almost universally insulin resistant or diabetic. Studies using the cortisol blocker mifepristone (RU-486) reversed insulin resistance and produced sustained weight loss in Cushing patients without any change in diet, which strongly suggests cortisol drives the disease in non-Cushing diabetics too.
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Beta cells in the pancreas constantly regenerate. Polyunsaturated fats kill them. Glucose stimulates the renewal of beta cells (insulin-producing) from stem cells, with the alpha cells (glucagon-producing) maturing into beta cells as they differentiate. Polyunsaturated fats and the prostaglandins they form are toxic to the beta cells, killing them as fast as they regenerate. In experiments, putting lab animals on a fat-free diet or one with only saturated fats made them resistant to all the standard methods of inducing diabetes by poisoning beta cells.
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Starches stimulate insulin much more powerfully than sucrose, glucose, or fructose alone. {rotein is also a strong insulin stimulant. Starches are pure chains of glucose and hit the bloodstream as a powerful insulin trigger. Sucrose, half fructose and half glucose, gives a smaller insulin response because fructose is metabolized without insulin and sometimes inhibits insulin production. Amino acids from protein also strongly stimulate insulin secretion, so eating a big protein meal without sugar can drop blood sugar and trigger cortisol or adrenaline.
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The combination of insulin and sugar is anti-inflammatory. Insulin lowers free fatty acids, which are major inflammatory drivers, and the combination of sugar and insulin suppresses inflammatory mediators like nitric oxide. Diabetics, who cannot oxidize sugar, and hypoglycemics, who do not have enough sugar, both have increased inflammation. The standard hospital treatment for a heart attack, called MAGIK (magnesium, glucose, insulin, and potassium), works because both glucose and insulin lower the free fatty acids that drive heart attack damage and let the heart use glucose.
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Aspirin and niacinamide improve insulin sensitivity by reducing free fatty acid liberation. Aspirin acts on at least two lipase enzymes including the adipose hormone-sensitive lipase that insulin controls, so insulin deficiency itself liberates more free fatty acids. Niacinamide inhibits the lipase that liberates fats from fat stores. By cutting the supply of free fatty acids in the blood, both compounds remove the block on glucose oxidation. For chronic problems, doses of 300 to 500 milligrams of aspirin daily provide systemic protection, with vitamin K supplementation to offset the bleeding risk.
Notable Quotes
"Fat people became something like 95% of the patients for treatment for high blood glucose. So it definitely isn't a problem of insulin deficiency for the great majority of people who are diagnosed with diabetes."
[Ray Peat — Diabetes (KMUD, February 2014)]
"You have to talk about what you mean by insulin resistance and that really isn't a very good concept because for every tissue you look at, it's going to have its own particular meaning"
[Ray Peat — The Estrogen Industry, the Magic of Progesterone and the Importance of Thyroid]
"The combination of sugar and insulin is definitely anti-inflammatory"
[Ray Peat — Questions and Answers (KMUD, January 2014)]
"Aspirin improves insulin sensitivity"
[Ray Peat — Rheumatoid Arthritis (KMUD, October 2016)]
"The cell can only do what the environment allows it to do and what has been set up to do naturally. So which means I can only oxidize either carbs or fats. If you're giving me fats all the time, I cannot metabolize those carbs."
[Georgi Dinkov — On the Randle Cycle and Insulin Resistance]
"It's not a sugar-driven disease. In fact, it's just fat that's causing it."
[Georgi Dinkov — Bioenergetic View on Type 2 Diabetes]
"When a biomarker becomes a target, it ceases to be a (useful) biomarker."
[Georgi Dinkov — On Metformin and Chasing Blood Glucose]
Important Things To Consider
Eating protein without carbohydrate causes a sharp drop in blood sugar. Amino acids strongly stimulate insulin secretion, and without sugar to balance them, the insulin lowers blood glucose, triggering adrenaline or cortisol. Cortisol then breaks down the protein you just ate to make sugar, so the meal becomes self-defeating. People eating a couple of pounds of meat a day can show signs of protein deficiency and gain fat because of this.
Ketogenic and very low-carb diets are diabetes-promoting. The stress of going into ketosis elevates free fatty acids in the blood, and free fatty acids are precisely what blocks glucose oxidation. People who go keto for an extended period can end up with insulin resistance or even type 2 diabetes diagnoses. The hydroxybutyrate generated in ketosis is technically an alcohol rather than a ketone and has been shown to stimulate cancer growth and other stress-related processes.
Starches drive insulin spikes that crash blood sugar and trigger cortisol. Each crash provokes a cortisol surge, which then breaks down protein and stores fat in the trunk and face area, the Cushing's pattern. Sucrose with fruit produces a far smaller insulin reaction because the fructose half does not stimulate insulin and the potassium content acts insulin-like.
The introduction of insulin in the 1950s was associated with rising diabetes death rates. This was possibly due to it being made from pig pancreas, but the broader point is that supplementing insulin does not address the underlying free-fatty-acid problem. The first oral non-insulin drug, phenformin, was withdrawn in the 1960s because it caused fatal lactic acidosis by poisoning mitochondria. Metformin works by a similar mechanism and carries similar warnings about lactic acidosis.
Reducing dietary fat is more useful than cutting carbs in already insulin-resistant people. If a 2000-calorie diet is currently 50 percent fat, 40 percent carbs, and 10 percent protein, the fix is to bring fat down toward 30 percent and let carbs rise. Going to zero on either end is not the goal; the cell needs both, just not in the wrong ratio. Obese people in particular are already supplying themselves with fat from their own tissue, so dietary fat just adds to the flood.
The transition from low-carb to higher-carb has to be gradual. Adding sugar on top of a high-fat diet without first reducing the fat will produce weight gain, because the cells cannot oxidise the glucose and cortisol will route it into fat synthesis through fatty acid synthase. Lower fat first, then bring carbs up slowly, while testing free fatty acids and blood glucose to see whether the underlying insulin resistance is improving.
Even with supplemented insulin, type 1 diabetics still develop nerve and circulation damage. Neuropathy, retinopathy, and circulation damage often appear before blood sugar even rises. The damage comes from polyunsaturated fatty acid breakdown into prostaglandins and lipid peroxides, not from glucose itself. Aspirin and niacinamide help by lowering free fatty acid release. Active T3 (thyroid hormon)e has been used to reverse severe diabetic foot rot in cases where lowering blood sugar alone failed.
Type 1 and type 2 diabetes can converge. Untreated type 2 diabetes can progress to type 1, because the same elevated free fatty acids that block the insulin receptor will eventually destroy the pancreatic beta cells. Kidney damage in diabetes, traditionally blamed on high blood sugar, is now attributed primarily to PUFA-derived metabolites such as 4-hydroxynonenal.
The standard medical concept of "insulin resistance" does not hold up when tissues are examined separately. Estrogen and cortisol both act as pro-insulin in fat tissue, with estrogen depositing fat in the hips and thighs and cortisol depositing it in the belly, chest, and face, while simultaneously antagonizing insulin elsewhere. Calling this all "resistance" conflates contradictory effects across different tissues.
Aspirin requires vitamin K supplementation if taken long-term. When using aspirin daily for insulin sensitivity, around 1 milligram of vitamin K per 325 milligram aspirin tablet is a workable ratio to avoid any excess blood thinning. Cooked greens like kale, liver, and certain cheeses are good food sources of Vitamin K.