Blue circle, the universal symbol for diabetes
Blue circle, the universal symbol for diabetes

Diabetes in modern usage means high blood glucose, with or without sugar in urine. Older "sugar disease" meant wasting with heavy sugar loss. Ideology treated sugar as the enemy. The working problem is failed oxidation of glucose inside cells, with free fatty acids blocking the path.

P. J. Randle (1963) showed free fatty acids block glucose oxidation. IV lipid emulsions raise blood sugar at once. Polyunsaturated free fats do the worst long-range damage.[1]

See Randle cycle, Free fatty acids, PUFA.

Sugar and protection

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Bernardo Houssay protected animals from experimental diabetes with sugar and coconut oil. Lard-heavy diets failed that protection.[2]

In 1927, an oral dextrose series in healthy medical students ranked prior diets by tolerance: two days of high sugar/starch carbohydrate produced the best curves; two days of high fat or of starvation produced the worst.[3]

High blood sugar can be the body pushing fuel through a fat block. Fighting the number alone without fixing free fatty acids and oxidation misses the mechanism. See Glucose.

In hyperglycemia, what you have is the body's adjustment to the inability of cells to get enough energy because they can't oxidize glucose because the fats are blocking it.

— Ray Peat[4]

In the Counterpoint trial, 11 people with established type 2 diabetes were put on a very-low-calorie diet (about 600 kcal/day); fasting blood glucose normalized within one week, driven by a rapid drop in liver fat and restored liver insulin sensitivity, and continued improvement in pancreatic fat and beta-cell function over eight weeks restored first-phase insulin response.[5]

Mechanism: PUFA, estrogen, and mitochondria

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Free fatty acids inhibit mitochondrial respiration; linoleic and linolenic acid act as intracellular regulators that stimulate the protein kinase C (PKC) system, the same system stimulated by estrogen and the cancer-promoting phorbol esters. PKC activation stimulates the cell while blocking the energy it needs.[6]

When the oral contraceptive pill was new (Enovid), it produced signs of diabetes, including decreased glucose tolerance. Spellacy and Carlson (1966): free fatty acids can block the Krebs cycle, with relative insulin action resistance resulting.[7][8]

Acute hypertriglyceridemia from Intralipid, with or without heparin-driven NEFA release, impaired oral glucose tolerance and insulin sensitivity in lean nondiabetic volunteers during a concurrent OGTT.[9]

Coconut oil, in diabetes as in other degenerative diseases, is highly protective.[10]

Beta cells are always tending to regenerate, but in diabetes they die quickly; lipid peroxidation seems to kill them as they are reborn, so lowering PUFA is key.[11] Animals whose beta cells had been killed with a poison sometimes recovered after supplemental DHEA, and their beta cells had regenerated.[12]

Undigested starch can sustain bacteria in the small intestine, and the resulting endotoxin, nitric oxide and serotonin can cause insulin resistance. Adequate calcium matters because parathyroid hormone and serotonin interact with stress and glucose metabolism.[13]

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Cells short on usable glucose convert less T4 to active T3. Low thyroid then deepens the stress. Active T3 reverses many "diabetic" breakdown signs once sugar burning returns.[14]

Human data support the pattern: patients over 50 with type 2 diabetes showed low T3 and elevated reverse T3 tracking with metabolic control rather than age itself,[15] and a cohort of newly-diagnosed hospitalized type 2 diabetics found reduced free T3 was strongly correlated with the presence of diabetic nephropathy.[16] In animal models, T3 treatment improved insulin signaling and reduced hyperglycemia, insulin resistance, and neurodegenerative-pathway activation in the hippocampus of diabetic rats and mice.[17][18]

See Thyroid, Stress.

Nutrient support

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High-dose thiamine (vitamin B1) improved glucose tolerance in a randomized, double-blind cross-over trial in hyperglycemic adults.[19] Peat named niacinamide, thiamine, thyroid, and progesterone or pregnenolone among the supplements that most often help correct diabetes-like conditions.[20]

Potassium has an insulin-like action that promotes glucose disposal.[21] Brewers' yeast's traditional use for correcting diabetes may come from its high content of niacin and other B vitamins together with potassium.[20]

A single-blind randomized trial gave 320 adults with diabetes and insomnia placebo, magnesium, potassium, or both for two months; 290 completed the trial. The study reported changes in insomnia severity, serum cortisol, and serum melatonin.[22]

High-dose aspirin (salicylate) lowered fasting glucose and hepatic glucose output and improved peripheral insulin-stimulated glucose uptake in type 2 diabetics over two weeks, via inhibition of IKKβ; the effective dose in that trial was large (~7 g/day), well above standard analgesic dosing.[23]

In the Isfahan Cohort Study, the highest third of nut intake had lower odds of obesity than the lowest third. The same group had about twice the odds of diabetes. The study is observational and does not test cause.[24]

In a placebo-controlled trial in overweight men with type 2 diabetes taking metformin, 5 mg of folic acid a day for eight weeks lowered HbA1c, insulin, insulin resistance and homocysteine within the folic acid group, though at the end only HbA1c differed from placebo.[25] In an open-label trial in people with type 2 diabetes on oral drugs, adding 500 mcg of vitamin B12 a day for eight weeks, alone or with folic acid, improved HbA1c, insulin resistance and adiponectin compared with standard treatment.[26]

Tissue effects

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Non-diabetic apes given insulin treatments developed some of the same complications of diabetes seen in humans, and antibodies to insulin.[27]

In muscles, and probably other tissues, diabetics have capillaries more widely spaced, as if the basal oxidative requirement were lower than normal.[28] F. Z. Meerson's description of the stress-injured heart closely parallels the general changes seen in chronic diabetes.[29]

A diabetic foot ulcer with osteolytic second-toe metatarsophalangeal osteomyelitis regenerated a joint-like structure after months of daily artificial CO2 foot bathing plus povidone-iodine sugar ointment, without sequestrectomy or systemic antibiotics.[30]

Practice

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Lower seed-oil PUFA. Cook with coconut oil or butter. Keep regular carbohydrate so lipolysis stays low. Support thyroid. Fasting can drop the glucose number while raising free-fat stress; long-range repair means lower PUFA and steady fuel, not repeated fuel deprivation.[31]

See Intermittent fasting, Coconut oil, Saturated fat.

GLP-1 agonists and muscle loss

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GLP-1 receptor agonists in obese patients were associated with a higher risk of depression, anxiety, and suicidal behavior than in matched controls in a large post-marketing cohort.[32] GLP-1 receptor agonists in type 2 diabetes were associated with a modestly higher rate of new diabetic retinopathy but fewer sight-threatening complications, including blindness, in a large observational analysis.[33] Semaglutide can cause a loss of cardiac mass, which ketone therapy prevented in one study.[34] Weight loss induced by GLP-1 drugs also costs skeletal muscle.[35]

Metformin and muscle atrophy

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Metformin is widely prescribed for type 2 diabetes and is often described as an AMPK activator mimicking caloric restriction. Metformin increases phosphorylated AMPK and upregulates myostatin at the transcriptional level through an HDAC6-FoxO3a axis, promoting muscle wasting in rodent models; metformin-treated wild-type mice had smaller muscle fibres and lower serum myoglobin.[36] Metformin's glucose-lowering effect in diabetic mice may partially offset its muscle-wasting effect, complicating interpretation in clinical populations where most patients receive metformin.[36]

Ketogenic diet risks

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A state-of-the-art review finds ketogenic-diet weight loss is largely water and muscle with limited lasting cardiometabolic benefit.[37] Low-carbohydrate diets were associated with higher incident atrial fibrillation risk regardless of whether protein or fat replaced carbohydrate.[38] Long-term ketogenic feeding in mice produces hyperlipidemia, hepatic dysfunction, and glucose intolerance resembling type 1 diabetes-like metabolic failure.[39] Ketogenic (90% fat) feeding in mice raises triglycerides and cholesterol while normalizing glucose and insulin yet doubles breast-tumor growth in a mouse model; hyperlipidemia, not glycemia, tracks tumor acceleration.[40]

Oral glycine (5 g three times daily for 3 months) lowered A1C more than placebo in type 2 diabetes and shifted proinflammatory markers (lower TNF-receptor I; higher IFN-γ).[41]

Thymoquinone and glycine, combined

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In streptozotocin-induced diabetic rats, combining thymoquinone (from Nigella sativa/black seed oil) with the amino acid glycine normalized fasting blood glucose, reversed insulin resistance (HOMA-IR), restored beta-cell function (HOMA-%B), and protected pancreatic tissue more effectively than either compound alone; the combination surpassed even healthy controls on several markers including glutathione and insulin sensitivity.[42]

Sunlight

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In UK Biobank data, recent sunlight (UVA) exposure went with lower blood glucose, most strongly in winter, and solarium users had a lower risk of type 2 diabetes than non-users.[43] See Sunlight.

In healthy adults, 15 minutes of deep red light (670 nm) before a glucose drink made the blood sugar rise over the next two hours about a quarter smaller than without the light; the peak itself dropped only slightly.[44] The trial did not include anyone with diabetes, and it used a single red light source, not sunlight. See Red light.

Metabolic syndrome

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Metabolic syndrome is the modern clinical cluster of abdominal obesity, insulin resistance, hypertension, and abnormal blood lipids, diagnosed when at least 3 of 5 harmonized criteria are met: triglycerides ≥150 mg/dL, HDL cholesterol below 40 mg/dL (men) or 50 mg/dL (women), blood pressure ≥130/85 mmHg, fasting glucose ≥100 mg/dL, and elevated waist circumference by regional cutoffs.[45] "Metabolic syndrome" itself is not a term Ray Peat used; his own framework addressed the same cluster through PUFA, thyroid, and insulin resistance directly rather than as a named syndrome.

A shared mechanism across the syndrome's components

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Peat identified free PUFA as a common driver behind several pieces of this cluster at once, not a coincidental co-occurrence of separate problems. Free fatty acids block the Krebs cycle to produce insulin resistance, and the same fatty acids directly stress the pancreatic beta cells that secrete insulin (see Pancreas for the full citations and quotes).[46]

In this framework, low thyroid function compounds the problem: it raises circulating free fatty acids (poor fat clearance), which then worsens insulin resistance and blood pressure regulation together, rather than each component of the "syndrome" having an independent cause.

Highest versus lowest dietary calcium intake was associated with about 20% lower odds of metabolic syndrome in a meta-analysis of cross-sectional estimates.[47]

Practice (Metabolic syndrome)

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Reducing PUFA intake and supporting thyroid function address the shared mechanism directly, rather than treating blood pressure, blood sugar, and weight as three unrelated problems needing three separate interventions. See Pancreas, Insulin resistance, PUFA, Thyroid.

Metformin

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Metformin is the first-line drug for type 2 diabetes. It lowers blood sugar mainly by reducing liver glucose output (gluconeogenesis) and improving insulin sensitivity.

Mechanism and context

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Metformin was criticized because its predecessor was phenformin: "Phenformin was the first form of that used widely in the 50s and 60s, but it was killing a very high proportion of people. They were dying much earlier than they would have with no treatment at all. It was causing lactic acidosis by causing the mitochondria to be unable to oxidize glucose, which was exactly the problem of diabetes." Metformin replaced phenformin on the claim that it would not cause the same lactic acidosis. The cited account notes over 100 PubMed articles warning about lactic acidosis with the drug: "It works partly by poisoning the mitochondria so that the cells are forced to produce lactic acid. It lowers blood sugar by wasting the glucose, turning it into lactic acid."[48]

Metformin's mechanism is partial inhibition of Complex I of the mitochondrial electron transport chain, which activates AMPK and shifts cells toward glycolysis and away from oxidative respiration.[49] This lowers blood sugar, but by making cells less efficient at oxidative energy production, not more, the same direction Peat criticized in phenformin.

A recognized risk is lactic acidosis, particularly with impaired kidney function, reflecting the shift toward glycolytic (lactate-producing) metabolism.[50] Long-term use is also associated with reduced vitamin B12 absorption.

Ozempic

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Ozempic (semaglutide) is a GLP-1 receptor agonist prescribed for type 2 diabetes and, at higher doses (Wegovy), for weight loss. It suppresses appetite and slows gastric emptying, producing sustained calorie reduction.

Context

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Ray Peat died in November 2022, shortly before semaglutide's rapid rise to mainstream weight-loss use, so there is no direct Peat commentary on it. Applying his general framework: appetite suppression by slowing digestion is a mechanical override rather than a fix for whatever is driving overeating or poor metabolism in the first place, and rapid, sustained calorie reduction runs the same starvation-adjacent risks he associated with any aggressive calorie restriction: muscle loss, lowered thyroid output, and stress hormone elevation.

Documented adverse effects include gallbladder disease, gastroparesis, and intestinal blockage;[51] bone loss and rapid regain after discontinuation are also reported.[52]

Practice (Ozempic)

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If prescribed, protein intake and metabolic support (adequate food, salt, thyroid status) matter more, not less, given the drug's own appetite suppression. It is a medical tool with real risks, not a substitute for addressing why appetite or weight is a problem in the first place.

GLP-1

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GLP-1 is an incretin hormone that raises insulin secretion and slows gastric emptying. Drugs such as semaglutide mimic it for diabetes and weight loss. Signaling from the body's own GLP-1 is brief and meal-linked, while a drug agonist acts continuously, and the gastroparesis-like side effects listed above follow from that sustained slowing of the stomach. See Appetite, Digestion and Blood sugar.

See also

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References

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  1. ↑ Ray Peat, "Glucose and sucrose for diabetes," raypeat.com.
  2. ↑ Ray Peat, "Glycemia, starch, and sugar in context," raypeat.com.
  3. ↑ Sweeney JS. "Dietary Factors That Influence the Dextrose Tolerance Test," Arch Intern Med. 1927;40(6):818-830. doi:10.1001/archinte.1927.00130120077005.
  4. ↑ Ask the Herb Doctor: Diabetes I
  5. ↑ Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. "Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol," Diabetologia. 2011;54(10):2506-2514. doi:10.1007/s00125-011-2204-7. PMID 21656330.
  6. ↑ Ray Peat, "Diabetes, scleroderma, oils and hormones," raypeat.com.
  7. ↑ Ray Peat, "Diabetes, scleroderma, oils and hormones," raypeat.com.
  8. ↑ Ray Peat, "Diabetes, scleroderma, oils and hormones," raypeat.com.
  9. ↑ Tricò D, Rebelos E, Astiarraga B, et al. "Effects of Hypertriglyceridemia With or Without NEFA Elevation on β-cell Function and Insulin Clearance and Sensitivity," J Clin Endocrinol Metab. 2025. doi:10.1210/clinem/dgae276. PMID 38635405.
  10. ↑ Ray Peat, "Diabetes, scleroderma, oils and hormones," raypeat.com.
  11. ↑ Ray Peat, "Ask the Herb Doctor: Rheumatoid Arthritis", KMUD, 47:40
  12. ↑ Ray Peat, "Glucose and sucrose for diabetes," raypeat.com.
  13. ↑ Ray Peat, Ephemera: Emails & Exchanges from the Archives (2012-2024).
  14. ↑ Ray Peat, "Ask the Herb Doctor: Diabetes I", KMUD
  15. ↑ Kabadi UM, Premachandra BN. "Low triiodothyronine and raised reverse triiodothyronine levels in patients over fifty years of age who have type II diabetes mellitus: influence of metabolic control, not age," J Am Geriatr Soc. 1984;32(5):353-356. PMID 6715765.
  16. ↑ Li Y, Yi M, Deng X. "Evaluation of the Thyroid Characteristics and Correlated Factors in Hospitalized Patients with Newly Diagnosed Type 2 Diabetes," Diabetes Metab Syndr Obes. 2022. PMID 35340987.
  17. ↑ Prieto-Almeida F, et al. "Thyroid hormone improves insulin signaling and reduces the activation of neurodegenerative pathway in the hippocampus of diabetic adult male rats," Life Sci. 2018. PMID 29132997.
  18. ↑ Lin Y, Sun Z. "Thyroid hormone potentiates insulin signaling and attenuates hyperglycemia and insulin resistance in a mouse model of type 2 diabetes," Br J Pharmacol. 2011. PMID 20883475.
  19. ↑ Alaei Shahmiri F, Soares MJ, Zhao Y, Sherriff J. "High-dose thiamine supplementation improves glucose tolerance in hyperglycemic individuals: a randomized, double-blind cross-over trial," Eur J Nutr. 2013;52(7):1821-1824. PMID 23715873.
  20. ↑ 20.0 20.1 Ray Peat, "Glucose and sucrose for diabetes," raypeat.com.
  21. ↑ Ray Peat, "Politics & Science: Biochemical Health", KMUD
  22. ↑ Khalid S, Bashir S, Mehboob R, Anwar T, Ali M, Hashim M, Waseem H and Basharat S. "Effects of magnesium and potassium supplementation on insomnia and sleep hormones in patients with diabetes mellitus." Front Endocrinol (Lausanne). 2024;15:1370733. doi:10.3389/fendo.2024.1370733. PMID 39534260. Full text.
  23. ↑ Hundal RS, Petersen KF, Mayerson AB, et al. "Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes," J Clin Invest. 2002;109(10):1321-1326. PMID 12021247.
  24. ↑ Mohammadifard N, Haghighatdoost F, Mansourian M, Hassannejhad R, Sadeghi M, Roohafza H, et al. "Long-term association of nut consumption and cardiometabolic risk factors," Nutr Metab Cardiovasc Dis. 2019;29(9):972-982. doi:10.1016/j.numecd.2019.04.014. PMID 31248717. 1,387 adults, 12 years; obesity adjusted OR 0.67; diabetes adjusted OR 2.23.
  25. ↑ Gargari BP et al. 2011. "Effect of folic acid supplementation on biochemical indices in overweight and obese men with type 2 diabetes," Diabetes Res Clin Pract. 2011;94(1):33-38. 48 men on metformin of at least 1500 mg/day; within the folic acid group HbA1c fell 8%, insulin 16.2%, HOMA-IR 20.5% and homocysteine 21.2%; between groups at 8 weeks only HbA1c differed (p=0.014; HOMA-IR p=0.393). doi:10.1016/j.diabres.2011.07.003. PMID 21802161.
  26. ↑ Satapathy S et al. 2020. "Folic acid and vitamin B12 supplementation in subjects with type 2 diabetes mellitus: A multi-arm randomized controlled clinical trial," Complement Ther Med. 2020;53:102526. 80 patients in four arms of 20; median HbA1c change -1.2% with B12 (p=0.04) and -1.5% with B12 plus folic acid (p=0.02) versus standard treatment. doi:10.1016/j.ctim.2020.102526. PMID 33066869.
  27. ↑ Ray Peat, "Diabetes, scleroderma, oils and hormones," raypeat.com.
  28. ↑ Ray Peat, "Diabetes, scleroderma, oils and hormones," raypeat.com.
  29. ↑ Ray Peat, "Diabetes, scleroderma, oils and hormones," raypeat.com.
  30. ↑ Hihara M, Fukui M, Mitsui T, Kakudo N, Kuro A. "Osteolytic metatarsal osteomyelitis regenerated by combined treatment of artificial carbon dioxide foot bathing and povidone-iodine sugar ointment: a case report," J Med Case Rep. 2022;16:434. PMID 36404336.
  31. ↑ Ray Peat, "Ask the Herb Doctor: September 2021", KMUD
  32. ↑ Kornelius E, Huang JY, Lo SC, Huang CN, Yang YS. "The risk of depression, anxiety, and suicidal behavior in patients with obesity on glucagon like peptide-1 receptor agonist therapy," Sci Rep. 2024;14(1):24433. doi:10.1038/s41598-024-75965-2. PMID 39424950. 162,253 matched patients; 98% higher risk of any psychiatric disorder, 195% higher major depression, 108% anxiety, 106% suicidal behavior.
  33. ↑ Ramsey DJ, et al. "GLP-1 receptor agonists and sight-threatening ophthalmic complications in patients with type 2 diabetes," JAMA Netw Open. 2025;8(8):e2526321. doi:10.1001/jamanetworkopen.2025.26321. PMID 40788647. 185,066 matched patients; retinopathy HR 1.07; blindness HR 0.77 (0.73-0.82).
  34. ↑ Schmidt MA, Abuetabh Y, Naganuma M, et al. "Ketone therapy prevents semaglutide-induced loss of cardiac mass," Eur J Prev Cardiol. 2026;33(1):148-150. doi:10.1093/eurjpc/zwaf605. PMID 41026893.
  35. ↑ Prado CM, Phillips SM, Gonzalez MC, Heymsfield SB. "Muscle matters: the effects of medically induced weight loss on skeletal muscle," Lancet Diabetes Endocrinol. 2024;12(11):785-787. doi:10.1016/S2213-8587(24)00272-9. PMID 39265590.
  36. ↑ 36.0 36.1 Kang MJ, et al. "Metformin induces muscle atrophy by transcriptional regulation of myostatin via HDAC6 and FoxO3a," J Cachexia Sarcopenia Muscle. 2022;13(1):302-315. PMID 34725961.
  37. ↑ Popiolek-Kalisz J. "Ketogenic diet and cardiovascular risk - state of the art review," Curr Probl Cardiol. 2024. PMID 38232923.
  38. ↑ Zhang S, et al. "Low-Carbohydrate Diets and Risk of Incident Atrial Fibrillation: A Prospective Cohort Study," J Am Heart Assoc. 2019. PMID 31020911.
  39. ↑ Gallop A, et al. "Long-term ketogenic diet metabolic harm," Sci Adv. 2025. doi:10.1126/sciadv.adx2752.
  40. ↑ Vieira RFL, et al. "Hyperlipidemia drives tumor growth in a mouse model of obesity-accelerated breast cancer growth," Cancer Metab. 2025. doi:10.1186/s40170-025-00407-0.
  41. ↑ Cruz M, Maldonado-Bernal C, Mondragón-Gonzalez R, et al. "Glycine treatment decreases proinflammatory cytokines and increases interferon-gamma in patients with type 2 diabetes," J Endocrinol Invest. 2008;31(8):694-699. PMID 18852529.
  42. ↑ "Optimized renal protection with combined thymoquinone and glycine treatment: synergistic management of streptozotocin-induced nephropathy," Sci Rep. 2026.
  43. ↑ Stevenson AC, Weller RB, Lindqvist P, Dibben C. "Sunlight exposure is associated with lower blood glucose levels and type 2 diabetes," Sci Rep. 2026. doi:10.1038/s41598-026-66100-4. Winter 7-day UVA: 0.027 mmol/L lower glucose per W/m2 vs 0.007 in spring; frequent solarium use HR 0.77.
  44. ↑ Powner MB, Jeffery G. "Light stimulation of mitochondria reduces blood glucose levels," J Biophotonics. 2024;17(5):e202300521. doi:10.1002/jbio.202300521. PMID 38378043. Oral glucose tolerance test in healthy volunteers without diabetes; integrated 2-h glucose rise 27.7% lower, maximum spike 7.5% lower. Single exposure; diabetic patients not tested.
  45. ↑ Alberti KG, Eckel RH, Grundy SM, et al., "Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity," Circulation. 2009;120(16):1640-5. PMID 19805654.
  46. ↑ Ray Peat, "Diabetes, scleroderma, oils and hormones," raypeat.com.
  47. ↑ Cheng L, Hu D, Jiang W. "Dietary calcium intake and the risk of metabolic syndrome: evidence from observational studies," Public Health Nutr. 2019;22(11):2055-2062. PMID 30846011. 15 cross-sectional estimates; OR 0.80.
  48. ↑ Ray Peat, "Ask the Herb Doctor: Diabetes I", KMUD, 18:52
  49. ↑ Rena G, Hardie DG, Pearson ER. "The mechanisms of action of metformin," Diabetologia. 2017;60(9):1577-1585.
  50. ↑ DeFronzo R, et al. "Metformin-associated lactic acidosis: current perspectives on causes and risk," Metabolism. 2016;65(2):20-29.
  51. ↑ FDA prescribing information for Ozempic, accessed via fda.gov.
  52. ↑ Discussion collected on Ray Peat Forum, "Ozempic (semaglutide)" — forum discussion, not a primary/clinical source; included as an anecdotal caution, not established fact.