What Might Fasting Insulin Predict About Health?

fasting insulinIn the comment section of my recent Definitive Guide to Blood Sugar, someone asked about fasting insulin. What does it predict? Is it the preeminent health marker? Does it actually cause harm, or is it just an indicator? Great questions and a great idea, I thought. Let’s do it. Let’s dig in.

It looks like it’s all true. Elevated insulin is both a direct cause of certain unwanted health conditions and an indicator of several other unwanted health conditions.

There are difficulties inherent to insulin. It varies wildly. There is no universally-agreed-upon reference range for healthy and unhealthy insulin levels. In the studies that find connections between elevated insulin and disease, they use quantiles—breaking up the subjects into groups of low, medium, and high insulin levels. It’s all relative.

We need to figure out what normal looks like. We can’t measure the insulin levels of paleolithic hunter-gatherers (insulin degrades pretty quickly and cannot be recovered from fossils). We can look at extant hunter-gatherers, but those are slipping away with every passing year (and to my knowledge, no one has actually tested the Hadza or Tsimane). The best way do it would be to measure the fasting insulin in a healthy, non-industrialized population largely free of disease, like the Kitava of the South Pacific. Staffan Lindeberg did test their fasting insulin levels, finding them to be very low—an average range of 3-6 uIU/mL in both men and women of all ages. He then compared them to modern Swedes, whose insulin ranged from 4-11 uIU/mL and went up with age. The average American fasting insulin runs about 8.4 uIU/mL, which likely isn’t physiologically normal.

That the Kitavans’ fasting insulin was relatively low and consistent throughout their entire lives, and they were largely free of the degenerative diseases that plague industrialized societies, suggests that a fasting insulin somewhere between 3-6 uIU/mL is the physiological norm for humans. It’s what we should be walking around with.

What’s the problem, exactly, with hyperinsulinemia?

Insulin and Overweight

One primary function of insulin is to suppress lipolysis—the release of fatty acids from body fat to be burned. This makes sense. You eat carbohydrates, glucose goes up, and the glucose has to go somewhere. Insulin rises to help you dispose of the glucose and suppress the release of free fatty acids. It’s harder to burn fat when glucose is in the picture, and insulin keeps fat locked away so you can dispose of the glucose.

Studies as far back as the 80s are pretty clear that the higher your insulin level, the higher your hunger and the more you eat. These aren’t just observational, either. Researchers actually pushed subjects’ insulin higher or lower, both with and without increasing their glucose, and found that raising their insulin was the most reliable way to increase hunger, food intake, and junk food cravings.

So hyperinsulinemia hits you from two sides:

  • It prevents you from burning your own body fat.
  • It makes you hungrier than your energy stores would actually suggest you should be.

That’s probably why a recent study found that reducing insulin could reduce diet-induced weight gain.

Insulin and Cancer

Another major function of insulin is to make things grow. This is an important function that makes total sense in certain situations, like when you’re trying to gain muscle, heal a wound, or if you’re a toddler who needs to grow your skeleton and get taller. But there are times where cellular growth is unwanted. Consider cancer, a disease of unchecked cellular growth. It’s no surprise that hyperinsulinemia is a risk factor for most, if not all cancers. 

While insulin isn’t everything when it comes to cancer, the links are undeniable and myriad—and worrying.

The link between colon cancer and hyperinsulinemia likely involves the tendency of insulin to increase the availability and potency of insulin-like growth factor. Post-menopausal women with genetic variants related to insulin resistance and hyperinsulinemia have a greater risk of colorectal cancer, and colon cancer patients who eat the most insulinogenic foods have poorer outcomes.

In breast cancer, hyperglycemia increases the tumors’ resistance to chemotherapy. Fixing the hyperglycemia makes chemotherapy more effective.

People with a genetic predisposition toward hyperinsulinemia have a higher chance of developing pancreatic cancer.

Independent of bodyweight, hyperinsulinemia predicts endometrial cancer; so does a high postprandial insulin response.

Diabetics who use insulin therapy have an increased risk of liver cancer. One study of Taiwanese diabetics found that those on insulin therapy have an elevated risk of dying from cancer and from non-cancer.

Most cancer cells overexpress insulin receptors, suggesting a unique affinity of cancer for circulating insulin.

Across the board, in both obese and people of normal bodyweight, hyperinsulinemia, whether it’s genetic, simulated, or diet-driven, increases cancer incidence and mortality. 

Okay, okay. That’s all rather convincing, but there’s a chance that these are merely associations and some common factor is causing both the hyperinsulinemia/insulin resistance and the cancer. Right?

What seems to counter that hypothesis is the effect of metformin, an anti-diabetic drug, on cancer. Compared to other diabetic drugs, metformin reduces the risk of cancer in type 2 diabetics. Metformin’s mechanism of action? A reduction in insulin levels and improvement of insulin resistance.

Insulin and Heart Disease

As far as heart disease risk factors go, hyperinsulinemia might be the strongest one yet. Hyperinsulinemia predicts the risk of heart attack. And it’s an independent risk factor. That’s key. You can control for LDL cholesterol, LDL particle number, triglycerides, HDL cholesterol, and it doesn’t matter. You can control for blood pressure and family history of heart disease, and it doesn’t matter. Among middle-aged men who do not have heart disease, hyperinsulinemia remains a significant and independent predictor of their risk of having a heart attack.

What about ApoB, the lipoprotein biomarker that most of the top cardiovascular health experts are pointing to as “causative” of heart disease? It’s actually one of the better predictors of insulin resistance and hyperinsulinemia. Whichever way you approach heart disease, insulin keeps popping up. Can’t escape it.

These are association studies, but the mechanisms for causality exist. As far back as 1990, researchers had established the pro-atherogenic effects of elevated insulin levels. As a review from that year explains:

Long-term treatment with insulin results in lipid-containing lesions and thickening of the arterial wall in experimental animals. Insulin also inhibits regression of diet-induced experimental atherosclerosis, and insulin deficiency inhibits the development of arterial lesions.

Could what they call an “insulin deficiency” be physiologically-normal levels of insulin? Could we all use a little “insulin deficiency”?

Insulin and Hypertension

Elevated insulin levels lead to sodium retention and water retention, which increases blood pressure. Dropping insulin—like, say, by eating a low-carb or keto diet—will counteract this effect and reduce blood pressure.

That’s why hyperinsulinemia is a consistent and independent predictor of hypertension, especially in women. Controlling for BMI doesn’t affect this relationship.

Insulin and Arthritis

There is growing evidence that insulin has an inflammatory effect on joints, reducing collagen deposition and increasing collagen degeneration. That’s in vitro research, but it jibes with many hundreds of anecdotes from people who went keto or low-carb or carnivore, dropped their insulin, and improved their arthritis—and with the common experience of reintroducing carbs and seeing the pain return.

Insulin and Fatty Liver

Among patients with non-alcoholic fatty liver, insulin resistance is almost a law. It’s very rare to see fatty liver without elevated insulin levels. Cause or effect?

Well, one job of insulin is to shove glucose into cells. It does this quite well, so long as there are vacancies. If the cell is already loaded with glucose, the liver converts the glucose into fat in a process called de novo lipogenesis. Some of this fat is exported to other cells, but a large portion is stored in the liver, especially in hyperinsulinemia.

Insulin and Mortality

Mortality is the endpoint of all endpoints. When it comes down to it, we’re trying to avoid dying. We don’t hope to live forever, but we do hope to live long and well as late into the game as possible. One way to do it is to reduce our insulin levels.

In cancer patients, for example, those who eat the most insulin-producing foods have worse cancer and overall mortality.

In middle aged adults, hyperinsulinemia predicts cancer mortality, even when you control for diabetes, obesity, and metabolic syndrome.

In older adults with type 2 diabetes, insulin use predicts mortality.

You won’t find a dietary philosophy that promotes the “benefits of hyperinsulinemia.” At the very worst, you might find folks who think elevated insulin is merely an indicator, and not a cause of disease. But this is one of those areas where almost everyone agrees “less is better.”

Where people disagree is on how to reduce hyperinsulinemia and maintain a healthy insulin level. That’s a post for another time.

Thanks for reading, everyone. Take care and be well, and may your insulin levels approach that of a Kitavan!

References

Chakrabarti P, Kim JY, Singh M, et al. Insulin inhibits lipolysis in adipocytes via the evolutionarily conserved mTORC1-Egr1-ATGL-mediated pathway. Mol Cell Biol. 2013;33(18):3659-66.

Rodin J, Wack J, Ferrannini E, Defronzo RA. Effect of insulin and glucose on feeding behavior. Metab Clin Exp. 1985;34(9):826-31.

Kaur P, Choudhury D. Insulin Promotes Wound Healing by Inactivating NFk?P50/P65 and Activating Protein and Lipid Biosynthesis and alternating Pro/Anti-inflammatory Cytokines Dynamics. Biomol Concepts. 2019;10(1):11-24.

Jung SY, Rohan T, Strickler H, et al. Genetic variants and traits related to insulin-like growth factor-I and insulin resistance and their interaction with lifestyles on postmenopausal colorectal cancer risk. PLoS ONE. 2017;12(10):e0186296.

Yuan C, Bao Y, Sato K, et al. Influence of dietary insulin scores on survival in colorectal cancer patients. Br J Cancer. 2017;117(7):1079-1087.

Al qahtani A, Holly J, Perks C. Hypoxia negates hyperglycaemia-induced chemo-resistance in breast cancer cells: the role of insulin-like growth factor binding protein 2. Oncotarget. 2017;8(43):74635-74648.

Carreras-torres R, Johansson M, Gaborieau V, et al. The Role of Obesity, Type 2 Diabetes, and Metabolic Factors in Pancreatic Cancer: A Mendelian Randomization Study. J Natl Cancer Inst. 2017;109(9)

Nead KT, Sharp SJ, Thompson DJ, et al. Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis. J Natl Cancer Inst. 2015;107(9)

Liu XL, Wu H, Zhao LG, Xu HL, Zhang W, Xiang YB. Association between insulin therapy and risk of liver cancer among diabetics: a meta-analysis of epidemiological studies. Eur J Gastroenterol Hepatol. 2018;30(1):1-8.

Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. 2006;29(2):254-8.

Baghbani-oskouei A, Tohidi M, Hasheminia M, Azizi F, Hadaegh F. Impact of 3-year changes in fasting insulin and insulin resistance indices on incident hypertension: Tehran lipid and glucose study. Nutr Metab (Lond). 2019;16:76.

Qiao L, Li Y, Sun S. Insulin Exacerbates Inflammation in Fibroblast-Like Synoviocytes. Inflammation. 2020;

Yuan C, Bao Y, Sato K, et al. Influence of dietary insulin scores on survival in colorectal cancer patients. Br J Cancer. 2017;117(7):1079-1087.

Perseghin G, Calori G, Lattuada G, et al. Insulin resistance/hyperinsulinemia and cancer mortality: the Cremona study at the 15th year of follow-up. Acta Diabetol. 2012;49(6):421-8.

Damluji AA, Cohen ER, Moscucci M, et al. Insulin provision therapy and mortality in older adults with diabetes mellitus and stable ischemic heart disease: Insights from BARI-2D trial. Int J Cardiol. 2017;241:35-40.

 

TAGS:  fasting, insulin

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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31 thoughts on “What Might Fasting Insulin Predict About Health?”

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  1. Just got off the phone with a good friend whose wife was diagnosed with stage 4 adrenal cancer months ago. Prior to the last round of chemo, she went fully ketogenic. During the scan yesterday, her doctors expressed astonishment that her liver had cleared completely. They admitted that they had not expected her results to be so good. Admittedly, this is multifactorial and we can’t know why this occurred. But it sure didn’t hurt!

      1. The tumor was attached to the adrenal gland and was just removed. it had spread to liver, lymphs, and kidney. Chem (plus keto?) seems to have cleared the liver. One kidney was also removed.

        1. My dad has just been diagnosed with stage 4 cancer of the oesophagus which has also spread to the lungs and liver. The cancer diet he’s been advised to go on is high carb, high calorie. I’ve tried to get him on keto in the past, but him (and my mum who’s the cook) don’t understand or ‘get it’. Makes me so sad that this area of nutrition is overlooked as this could be such a simple and effective way of improving cancer outcomes combined with the standard chemo/radiation.

  2. Mark, this was great. And you are so right about arthritis pain returning when you reintroduce carbs. I found that out for 2 or 3 days following Christmas after having eaten apple pie, pecan pie, sweetened cranberry sauce and conventional stuffing.

    1. That’s because you don’t have enzymes in your body to digest carbs properly. The pain will go away if you do it often. Just like it took you time to adjust to low carb as wel, it’s the same. Tried and tested. But it’s no excuse to eat wrong. But Insulin is higher with protein than carbs. And you had carbs plus fat, so your blood sugar wasn’t spiked as much as you think

  3. My fasting insulin has consistently been <2. Way under the reference range according to the lab. But A1c is always 4.6 and glucose less than 90. Still seems too low to me? I wonder what this means

    1. Excelente, mesmo que Glicose perto de 90, pois este é o que menos importa.

      1. MattK, a normal A1c is between 4.2 and 4.6 for adults. Your number is perfect. Being a type 1, I would love to have that A1c every time I go in for blood work. Mine tends between 4.7 and 4.9 while eating low carb… now for 22 years.
        Sure, I used to cheat a bit, but now maintain the low 30 grams a day and my blood sugars are near normal. So, don’t listen to the mainstream med types, and just keep doing what you’re doing. Andrew

  4. Wow the articles on insulinogenic foods found that red meat can raise insulin as much, or more, than carbohydrates. Sort of surprising.

    1. Not just red meat. Protein in general. Depending on the body’s need.

    2. Hey Jeff,
      Mark has done a number of posts / articles on red meat studies. Check ’email out …

    3. That may not be fasting insulin. Insulin spikes are likely not a problem and may be necessary for some signaling functions of insulin. From what I’ve heard the carnivore people have very low fasting insulin.

      1. Agreed.

        On low carb, one can also increase insulin resistance. It’s not all glory either.

  5. I’m surprised you didn’t list the big cause of elevated fasting insulin – the disregulation of gluconeogenesis that comes with NAFLD and insulin resistance.

  6. just read “The Obesity Code” basically, it’s all about insulin control great read and written by an MD

  7. Thank you for a very informative article on insulin. I was hoping you would touch on gestational diabetes. Is this preventable through diet, fasting? What causes it?

  8. Hi, how would this article content relate to type 1 diabetics, which are on insulin therapy for the rest of their life?
    Thank you

    1. I remember hearing on one of the Peter Attia interviews that there is a tendency for doing too much insulin and that one can reduce the amount of used once you have a better understanding how it works, it’s dynamics in your body.

      It seems that a continuous glucose monitor is the first step. Start there if not equipped.

      1. Hi loana, having been diagnosed with Type 1 Diabetes in 1997, I can say that low carb is the way to go for a type 1. It is the only way to “normalize” my blood sugar and has allowed me to avoid the dreaded diabetic complications that plague most diabetics. So, yes, Marks article touches on what I learned early in my diagnosis. Not from local doctors, mind you. I had to search and read just about everything I could get my hands on in order to make any sense of this mess I was in. The info is good and spot on.

  9. Okay, color me blonde, but how do you convert uIU/mL to mg/dl (which is what my glucose meter uses). And yes, I tried Googling it but the results I got were confusing.

    1. I went that way first too, as I was thinking of the mg/dl as blood glucose, but he is talking about insulin levels (which is new information for me) and that’s where the other measure comes from.

  10. What are the most insulinogenic foods? The link doesn’t appear to be correct.

  11. Thank you! I watched a friend die because her insulin levels were very high, she was only 72. I’m on day 24 of the primal eating plan and I love it! I feel amazing and I don’t crave food.

  12. Ideally, insulin is pulsatile, so measurements can be variable day to day, month to month. In the last three years my labs showed 6.1, 3.9, and 1.2 McIU/mL. The highest was when I weighed the most. The lowest was weighing the least, fasting, and 2 hrs long slow exercise that morning. My doctor did not mind the low insulin value.

  13. Seems like A1C would be a better overall measure of insulin than fasting insulin. My fasting insulin tends to be higher than recommended, but my A1C is fine. I doubt that I can ever get my fasting insulin number as low as it “should” be, because I am one of those people whose insulin level rises naturally before I wake up in the morning, regardless what I eat (the “Dawn Effect”). I don’t worry about it anymore, though, as I think A1C is a more realistic measure of ones insulin levels over time.

  14. (Question) Hi Mark, I hope you will consider a follow-up on the Kitavan. According to sciencebasedmedicine.org, 21% of their calories come from fat, 10% from protein, and a whopping 69% from carbohydrates. How do you jibe their carb intake with your post on hyperinsulinemia? Best Regards