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Does Fasting Cause Insulin Resistance? Yes, Briefly, and That Is the Point

Does Fasting Cause Insulin Resistance? Yes, Briefly, and That Is the Point

Fast for a day and your muscles stop taking up glucose the way they did yesterday. Measure insulin sensitivity that morning and it reads worse. So the honest answer to "does fasting cause insulin resistance" is yes, for as long as the fast lasts, and then it goes away the day you eat.

That temporary state confuses a lot of people, including people reading their own lab reports. Here is what is actually happening, what the trials say about fasting as a treatment for insulin resistance, and the two ways a fast will make your bloodwork lie to you.

Two different things share one name

Insulin resistance, the disease, is what happens when muscle, liver, and fat cells need more and more insulin to move the same glucose. It builds over years, it shows up first as a high fasting insulin, and it drives type 2 diabetes, fatty liver, and heart disease.

Insulin resistance, the fuel switch, is what happens inside a fast. When you stop eating, insulin falls, fat cells release fatty acids, and the body burns fat so that the little glucose it makes goes to the brain. Muscle deliberately ignores insulin during this window so it does not steal glucose the brain needs. George Cahill, who ran the classic starvation studies, laid out this fuel logic in a 2006 review in the Annual Review of Nutrition: the shift to fatty acids and ketones is what lets a human survive prolonged starvation.

The first kind is a problem. The second kind, physiological insulin resistance, is physiology working as designed. The trouble is that a blood test cannot tell them apart.

What a 24-hour and a 60-hour fast do to insulin sensitivity

Two controlled studies in healthy people show the size of the effect.

In a 2009 study in the American Journal of Physiology: Endocrinology and Metabolism, Salgin and colleagues fasted 14 healthy young adults for 24 hours and then ran an intravenous glucose tolerance test. Overnight free fatty acids rose almost threefold, insulin sensitivity fell by more than half, and the first-phase insulin response dropped as well. When they blocked fat release with a drug called acipimox during the same fast, the loss was partly undone, which points at the fatty acids as part of the cause.

Hoeks and colleagues went further in a 2010 study in the journal Diabetes. Twelve healthy men spent 60 hours fasting inside a respiration chamber, then had their insulin sensitivity measured by the gold-standard clamp. Fatty acids were about nine times higher than in the fed state, fat had accumulated inside muscle fibers, and muscle insulin sensitivity was down. The authors used the fast precisely because it produces insulin resistance in healthy people with low glucose and low insulin, which let them show that mitochondrial slowdown follows insulin resistance rather than causing it.

Neither study followed anyone after the fast ended, so they say nothing about the week after. Both found that a long fast makes a healthy person look insulin resistant while the fast is on.

What happens when you eat again

The fuel switch flips back with the first meal. Fatty acids fall, insulin rises, and muscle resumes glucose uptake. I know of no study showing that a fast leaves a healthy person more insulin resistant a week later than they were before.

I see the same mechanism in people on very low-carbohydrate diets who fail a glucose tolerance test. Their muscles have been running on fat for weeks and are not primed for a sudden 75 grams of glucose. It is the fuel switch again, not the disease, and it resolves with a few days of normal carbohydrate intake before the test.

Does intermittent fasting improve insulin resistance over months?

This is the question most people actually mean, and the evidence is more modest than the podcasts suggest.

Patikorn and colleagues published an umbrella review in JAMA Network Open in 2021 covering 11 meta-analyses and 130 randomized trials of intermittent fasting. Fasting was associated with lower fasting glucose, fasting insulin, and HOMA-IR, but the review graded 93% of the associations it examined as low or very low quality evidence. The single high-quality finding was that modified alternate-day fasting for one to two months lowers body mass index. The review also flagged that intermittent fasting was associated with loss of fat-free mass.

The trials that compared fasting head to head with plain calorie restriction mostly found a tie:

  • A 2017 trial in JAMA Internal Medicine by Trepanowski and colleagues randomized 100 adults with obesity to alternate-day fasting, daily calorie restriction, or nothing for one year. Weight loss was the same in both diet groups, and there were no differences in fasting glucose, fasting insulin, or insulin resistance at 6 or 12 months. The fasting group had the highest dropout, 38%, and higher LDL at one year.
  • Liu and colleagues randomized 139 adults with obesity to calorie restriction with or without an 8 a.m. to 4 p.m. eating window for 12 months in a 2022 trial in the New England Journal of Medicine. The time-restricted group lost 8.0 kg and the calorie-restriction group lost 6.3 kg, a difference that was not statistically significant, and metabolic risk factors moved the same way in both groups.
  • Khalafi and colleagues pooled 14 trials in 1,101 adults with prediabetes or type 2 diabetes in a 2024 meta-analysis in Diabetes, Obesity and Metabolism. Against a control diet, fasting lowered weight by 4.6 kg, A1c by 0.8 points, and fasting glucose, but did not significantly lower insulin. Against calorie restriction, fasting won on weight and on nothing else.

The pattern: intermittent fasting improves insulin resistance to the extent that it makes you eat less and lose weight. One way to create a deficit. Not a separate mechanism that fixes insulin resistance on its own.

Timing matters more than the fast

Two trials suggest the clock is doing real work.

Sutton and colleagues ran the cleanest test in a 2018 study in Cell Metabolism. Men with prediabetes ate all their food in a six-hour window that ended before 3 p.m., for five weeks, with meals provided so that nobody lost weight. Insulin sensitivity, beta-cell responsiveness, and blood pressure all improved with no weight loss at all. Early eating did something that the calorie count could not explain.

Jamshed and colleagues then tested an early window outside the lab in a 2022 trial in JAMA Internal Medicine: 90 adults with obesity, all on a calorie-restricted diet, randomized to eat only between 7 a.m. and 3 p.m. or over 12 or more hours, for 14 weeks. The early group lost an extra 2.3 kg and dropped diastolic blood pressure by 4 points, but other cardiometabolic markers, including insulin, ended up the same in both groups.

Now the other side. Lowe and colleagues gave 116 adults a noon-to-8 p.m. window with no calorie target in the TREAT trial, published in JAMA Internal Medicine in 2020. Twelve weeks later, weight loss was not different from the control group, and fasting insulin, fasting glucose, and A1c did not change. The only thing the late window moved was lean mass in the arms and legs, which went down.

And in people who already have type 2 diabetes, Andriessen and colleagues found in a 2022 trial in Diabetologia that three weeks of a 10-hour eating window improved 24-hour glucose control but did not improve insulin sensitivity on a clamp in 14 adults. Better glucose, same insulin resistance.

The practical read: an early eating window, dinner done by mid-afternoon or early evening, does more for insulin than a late one. Outside a supervised feeding study like Sutton's, no window has done much without a calorie deficit, and none protects muscle without strength training.

Does fasting cause insulin resistance on your lab report?

This is the part I want every reader to remember. If you get blood drawn after a 24-hour or longer fast, or in the middle of a multi-day fast, your glucose tolerance and your insulin sensitivity will read worse than they are. The two studies above measured that drop in healthy people with an intravenous glucose test and a clamp. A glucose tolerance test after a long fast, or after weeks of very low carbohydrate, can flag prediabetes in someone who does not have it.

For fasting insulin, fasting glucose, or a HOMA-IR calculation, fast 10 to 12 hours, not 24. A longer fast pushes the other way: insulin and glucose both drop, HOMA-IR flatters you, and the number is no more your baseline than the glucose tolerance test that reads too high. Water is fine. Skip the coffee until after the draw. Eat normally, including carbohydrate, for three days before a glucose tolerance test. If you are in the middle of an extended fast, wait until you have been eating normally for a few days before you draw the labs you plan to make decisions on. What insulin does hour by hour through a fast is laid out in insulin levels during fasting.

Who should not fast

Anyone on insulin or a sulfonylurea, because the drugs keep working while the food stops. Anyone on an SGLT2 inhibitor such as empagliflozin, dapagliflozin, or canagliflozin, because a long fast on those drugs can tip you into ketoacidosis with a normal glucose reading. Anyone pregnant or breastfeeding. Anyone with a history of an eating disorder. Anyone with type 1 diabetes. People over 65 and anyone who already has low muscle mass should be careful, because the fat-free mass loss in the trials above is not trivial and it is harder to rebuild at that age in my experience. If you take blood pressure medication, a fast can drop your pressure further than you want.

What I tell members

If fasting helps you eat less and you can keep it up, use it. Put the window early. Keep protein at 30 grams per meal inside the window and lift weights three times a week so the weight you lose is fat. Then retest fasting insulin at 12 weeks and let the number tell you whether it worked. All seven steps are in how to lower fasting insulin, and the food side is in the insulin resistance diet.

If fasting makes you binge, wrecks your sleep, or costs you strength in the gym, drop it. In the year-long head-to-head trial, plain calorie restriction produced the same change in fasting insulin and insulin resistance as fasting did, and the 12-month time-restricted trial found the same for every metabolic marker it measured. Add the same protein and the same lifting and you lose nothing by skipping the fast.

Get the number, then get a plan

Rebel Health Alliance members start with an initial panel of more than 100 biomarkers, drawn from more than 3,000 available, that includes fasting insulin, fasting glucose, A1c, hs-CRP, and ApoB. A physician you can message any time reads the whole thing, tells you which kind of insulin resistance you are looking at, and retests on a schedule that shows whether it is working. Rebel Peak members add a dietitian and strength coach who build the eating window and the training around your week. See how it works, book a 20-minute call, or read the FAQ.

Frequently asked questions

Does fasting cause insulin resistance?
Temporarily, yes. During a fast of 24 hours or more, fatty acids rise and muscle responds far less to insulin so that glucose is saved for the brain. Controlled studies in healthy people show this clearly. It goes away when you eat again and is not the same as the chronic insulin resistance that leads to diabetes.

Can intermittent fasting reverse insulin resistance?
It can improve it, mostly by helping you eat less and lose weight. In a year-long trial against plain calorie restriction, fasting produced the same changes in fasting insulin and insulin resistance, not better ones.

Why do my labs look different after a long fast?
Fatty acids blunt insulin's effect in muscle, so any test that challenges you with glucose reads worse than your baseline. The static numbers go the other way: fasting insulin and fasting glucose both fall during a long fast, so a HOMA-IR drawn mid-fast looks better than it is. Neither is your true baseline. Fast 10 to 12 hours for labs.

Is early or late time-restricted eating better for insulin?
Early. A six-hour window ending before 3 p.m. improved insulin sensitivity without weight loss in men with prediabetes. A noon-to-8 p.m. window with no calorie target changed nothing except lean mass, which went down.

Who should not try fasting?
Anyone on insulin, a sulfonylurea, or an SGLT2 inhibitor, anyone pregnant or breastfeeding, anyone with type 1 diabetes or a history of disordered eating, and anyone with low muscle mass, without a physician involved.


Dr. Alec Weir is the Chief Medical Officer at Rebel Health Alliance (https://rebelhealthalliance.io), a 100% virtual, physician-led longevity practice in all 50 states. This article is for education only and is not medical advice. Talk to your physician before changing medication, diet, or exercise.

Sources
  1. Cahill GF. Fuel metabolism in starvation. Annu Rev Nutr. 2006;26:1-22. doi:10.1146/annurev.nutr.26.061505.111258 PubMed
  2. Salgin B, Marcovecchio ML, Humphreys SM, et al. Effects of prolonged fasting and sustained lipolysis on insulin secretion and insulin sensitivity in normal subjects. Am J Physiol Endocrinol Metab. 2009;296(3):E454-61. doi:10.1152/ajpendo.90613.2008 PubMed
  3. Hoeks J, van Herpen NA, Mensink M, et al. Prolonged fasting identifies skeletal muscle mitochondrial dysfunction as consequence rather than cause of human insulin resistance. Diabetes. 2010;59(9):2117-25. doi:10.2337/db10-0519 PubMed
  4. Patikorn C, Roubal K, Veettil SK, et al. Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials. JAMA Netw Open. 2021;4(12):e2139558. doi:10.1001/jamanetworkopen.2021.39558 PubMed
  5. Trepanowski JF, Kroeger CM, Barnosky A, et al. Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA Intern Med. 2017;177(7):930-938. doi:10.1001/jamainternmed.2017.0936 PubMed
  6. Liu D, Huang Y, Huang C, et al. Calorie Restriction with or without Time-Restricted Eating in Weight Loss. N Engl J Med. 2022;386(16):1495-1504. doi:10.1056/NEJMoa2114833 PubMed
  7. Khalafi M, Habibi Maleki A, Symonds ME, et al. The effects of intermittent fasting on body composition and cardiometabolic health in adults with prediabetes or type 2 diabetes: A systematic review and meta-analysis. Diabetes Obes Metab. 2024;26(9):3830-3841. doi:10.1111/dom.15730 PubMed
  8. Sutton EF, Beyl R, Early KS, et al. Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Cell Metab. 2018;27(6):1212-1221.e3. doi:10.1016/j.cmet.2018.04.010 PubMed
  9. Jamshed H, Steger FL, Bryan DR, et al. Effectiveness of Early Time-Restricted Eating for Weight Loss, Fat Loss, and Cardiometabolic Health in Adults With Obesity: A Randomized Clinical Trial. JAMA Intern Med. 2022;182(9):953-962. doi:10.1001/jamainternmed.2022.3050 PubMed
  10. Lowe DA, Wu N, Rohdin-Bibby L, et al. Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial. JAMA Intern Med. 2020;180(11):1491-1499. doi:10.1001/jamainternmed.2020.4153 PubMed
  11. Andriessen C, Fealy CE, Veelen A, et al. Three weeks of time-restricted eating improves glucose homeostasis in adults with type 2 diabetes but does not improve insulin sensitivity: a randomised crossover trial. Diabetologia. 2022;65(10):1710-1720. doi:10.1007/s00125-022-05752-z PubMed
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