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Causes of Insulin Resistance & Hyperinsulinism

Written by Joe Cohen, BS | Last updated:
Insulin resistance

If you are struggling with chronic health issues – the way I used to – you probably have piles of lab tests that can potentially tell you a lot about your health. Blood glucose may be one of them. However, doctors never had enough time to explain it properly. They will only notice it if the lab flags your test results as outside of normal. But what if all your results are coming back normal, yet you know you are feeling nowhere near healthy? They may even tell you there is nothing wrong with you, and that it’s all in your head – I’ve been there.

The Causes of Insulin Resistance and Hyperinsulinism

The main reason for hyperinsulinism or excessive release of insulin is insulin resistance (IR). Most of the time people get insulin resistance as a result of eating too much and being overweight. Even if you are overweight, they’re ways to increase insulin sensitivity. Usually, if people lose weight their insulin resistance will go down.

One should realize that insulin resistance is a broad term and that you could be insulin sensitive in one way and resistant in another. Fat, muscle, and liver store glucose.

You could be insulin sensitive in your muscles and resistant in your fat cells, in which case you’ll be muscular and lean. This isn’t always optimally healthy.

For example, if you have elevated levels of the inflammatory cytokine TNF-alpha it will cause insulin resistance in fat cells but not muscle cells. This isn’t a good situation even though aesthetically you’ll look good.

Sometimes thin people can also have insulin resistance. PCOS is a relatively common disorder among women, affecting up to 10% of women 12 – 45.

Thin women with PCOS also have insulin resistance. There is also research that suggests that there is a male version of PCOS experienced by a certain percentage of men. PCOS and its associated IR are much easier to detect in women because of overt androgenic signs like facial hair growth, alopecia (balding) and fertility issues, but males can have a similar kind of issue and wouldn’t be noticeable because men all healthy men have facial hair, etc… However, the symptoms can manifest itself as premature balding.

In thin people, IR can in part be caused by an inefficient conversion of Inositol to D-Chiro-Inositol and because of excess inflammation and oxidative stress.

In overweight people who initially were never tired after eating carbs, being overweight is the significantly more likely cause of IR.

Read: What may be the markers of the male equivalent of polycystic ovary syndrome?

About one third of the premature balding men showed the combination of hormonal shifts and higher insulin resistance. This frequency corresponds to the prevalence of PCOS in women.

A significant percentage of people have some level of glucose intolerance and turn to low-carb and other diets.

Carb intolerance can produce negative cognitive effects.

Insulin spikes or hyperinsulinism from insulin resistance can contribute to fatigue, weight gain, and hypoglycemia.

Hypoglycemia is very damaging to the body and contributes to all kinds of cognitive issues.

Below is a list of reasons why insulin would spike. This list is pretty comprehensive, so go through it one by one until you get to the cause.

Everything on this list is from scientific literature, but I just didn’t have time to link out to everything.

Unfortunately, not even a fraction of this information is coherently put together elsewhere (I’m not sure why).

If the reader finds a cause that is unrelated to the ones given below, please do share.

Checking for IR

You can request that your doctor test your blood glucose. Conventional doctors will look at high or low blood glucose levels and not mention anything. Sometimes, a lab result may be in the reference range, but not actually be in the optimal range. Reference ranges are not the same as optimal ranges. This is why even blood glucose in the ‘normal’ range can be unhealthy and indicate that certain processes in the body aren’t optimal.

Reasons for IR


  • Eating too much
  • Not exercising
  • Obesity
  • Psychological stress
  • Sleep deprivation
  • Circadian disruption
  • Hypoglycemia (from refined carbs)

These are the main causes among relatively healthy Americans who mostly eat the SAD diet and are sedentary.

Nutrient Deficiencies

It’s easy to jump to the idea that we are probably deficient in something, but don’t forget that the most common explanation is that we just eat too much.

Associated Hormones/Proteins


  • Palmitic acid [21], a saturated fat
  • Myristic acid, a saturated fat
  • Stearic acid [22], a saturated fat
  • Lauric acid [23], a saturated fat. This causes IR in fat cells.
  • Sodium [24]
  • Cortisol secretion
  • External Toxins (alcohol, cigarette smoke, pollution, etc..)
  • Endotoxins
  • Heavy metals
  • Iron
  • Copper
  • Exercise
  • Heat
  • Cold
  • Alcohol
  • UV
  • Fat


  • Inefficient conversion of myoinositol to D-Chiro-Inositol [25] (PCOS)
  • Chronic inflammation [26], from food sensitivities, infections, etc.
  • Oxidative stress [27](Superoxide, Nitric oxide, H2O2), which can be caused by any number of things such as Hypoxia, Hyperoxia
  • Endocrine abnormalities (particularly of the thyroid gland (hypo and hyper))
  • Problems with gut microbiota [28]
  • Kidney problems
  • Hypertension [29]
  • Liver problems (fatty liver, cirrhosis, etc.)
  • Altered calcium homeostasis [30]
  • Protein deficiency, especially BCAA’s.

Supplements That May Contribute to IR

Additives that cause IR

  • BPA (in canned food)
  • Carrageenan (in almond milk and other fake milk)
  • Tolylfluanid (fungicide used for crops)

Hyperinsulinism Not Related to IR

  • Problems with the hypothalamus, pituitary, adrenal axis that may be a result of other causes besides oxidative stress-induced insulin resistance.
  • Increased GLP-1 levels as a result of low levels of the DPP-4 enzyme, because of the gut malfunctioning. Hyperinsulinism, in this case, is not because of insulin resistance.
  • Other less common causes: cancer -insulinoma, an insulin-secreting tumor of the pancreas. Congenital hyperinsulinism – caused by some genetic mutation.

About the Author

Joe Cohen, BS

Joe Cohen, BS

Joe Cohen flipped the script on conventional and alternative medicine…and it worked. Growing up, he suffered from inflammation, brain fog, fatigue, digestive problems, insomnia, anxiety, and other issues that were poorly understood in traditional healthcare. Frustrated by the lack of good information and tools, Joe decided to embark on a learning journey to decode his DNA and track his biomarkers in search of better health. Through this personalized approach, he discovered his genetic weaknesses and was able to optimize his health 10X better than he ever thought was possible. Based on his own health success, he went on to found SelfDecode, the world’s first direct-to-consumer DNA analyzer & precision health tool that utilizes AI-driven polygenic risk scoring to produce accurate insights and health recommendations. Today, SelfDecode has helped over 100,000 people understand how to get healthier using their DNA and labs.
Joe is a thriving entrepreneur, with a mission of empowering people to take advantage of the precision health revolution and uncover insights from their DNA and biomarkers so that we can all feel great all of the time.


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