Insulin Resistance - Common Contributors

May 6

#1: Sedentary Lifestyle

(low on lean muscle mass) + poor dietary choices (especially if you’re overweight and have lots of visceral fat)

A sedentary lifestyle combined with poor dietary choices, especially in overweight individuals with high visceral fat, can SIGNIFICANTLY contribute to insulin resistance through several interconnected mechanisms.

First off, if you are sedentary you will likely have less lean muscle mass which is crucial for insulin sensitivity. We need to have lean muscle mass for proper glucose disposal.

Not only this, but visceral fat accumulation via poor dietary choices, sedentary lifestyle, and eating high amounts of refined sugar (with a high glycemic index/load) will contribute to systemic inflammation and insulin resistance.

Being sedentary also decreases the activity and expression of GLUT4 transporters in muscle cells sometimes impairing glucose uptake. A lack of physical activity and poor diet will also lead to lipid accumulation, chronic low-grade inflammation, impaired mitochondrial function, and altered gene expression (all of which will reduce insulin sensitivity).

#2: Candida/Fungal Overgrowths

It turns out that the beta glucans from candida have a deteriorating effect on insulin sensitivity via the dectin-1 dependent pathway. Being insulin resistant also makes it more difficult to get RID of the candida overgrowths, showing a somewhat bidirectional relationship between insulin resistance and candida overgrowth.

#3: Gram Negative Bacterial Overgrowths + LPS

Not only will the LPS (an endotoxin) from gram negative bacteria induce chronic low-grade inflammation, but they can also stimulate insulin secretion from the pancreatic beta cells and eventually lead to hyperinsulemia, beta cell exhaustion, and insulin resistance. LPS can also induce hepatic insulin resistance by activating inflammatory pathways in liver cells.

#4: Mitochondrial Dysfunction

Insulin resistance via mitochondrial dysfunction will general stem from factors such as impaired ATP production, increased oxidative stress, the activation of cellular stress responses, altered glucose metabolism in favor of glycolysis, lipid accumulation, chronic inflammation, and altered calcium homeostasis.

#5: Chronic inflammation

Chronic inflammation (especially if related to adipose tissue) will lead to the increased production of pro-inflammatory cytokines such as TNF-a, IL-6, and MCP-1. These cytokines can impair insulin signaling in our tissues and can activate signaling pathways such as JNK and NF-kB that interfere with insulin receptor substrate function (which leads to impaired insulin signaling).

Not only this, but chronic inflammation also negatively affects the liver and our pancreatic beta cells, both of which are needed for proper glucose homeostasis.

#6: Lipotoxicity from excess circulating fatty acids

When excess fatty acids are deposited in non-adipose tissues like liver, muscle, and pancreas, we end up with lipotoxicity.

Certain lipid metabolites such as diacylglycerols and ceramides activate serine kinases that interfere with insulin signaling cascades, reducing glucose uptake and utilization. There is also an inflammatory component to this picture as well that contributes to the reduced function of the liver and pancreatic beta cells in some cases.

#7: Chronic stress

When we experience stress on a chronic basis, we activate our HPA axis and sympathetic nervous system and essentially flood our system with cortisol and catecholamines.

The bottom line is that prolonged high cortisol levels will promote insulin resistance via increasing glucose production in the liver, reducing glucose uptake from peripheral cells, and inhibiting insulin secretion from pancreatic beta cells. Not only this, but chronic stress also can induce oxidative stress, inflammation, neuronal damage, and endoplasmic reticulum stress. All of which can negatively impact glucose homeostasis.

NOTE: This can also be the case if you’re chronically overusing glucocorticoids

#8: Poor circadian health + Eating Late at Night

We have a central clock (the suprachriasmatic nucleus otherwise known as the SCN) and peripheral clocks for many of our organ systems. When we experience circadian disruption, there is an imbalance between our central clocks and our peripheral clocks.

When this happens, we end up with leptin resistance (a precursor to insulin resistance), altered melatonin production, increased inflammation, adipose tissue dysfunction, altered insulin secretion, and sometimes even hepatic insulin resistance. In other words, not having your circadian rhythm dialed is a great way to become leptin resistant and then insulin resistant in the future.

Can you be skinny and insulin resistant??

Yes. It’s actually very possible indeed. While being overweight may increase one’s odds of developing insulin resistance, it doesn’t mean that skinny people are immune to it. It’s very possible that those who appear to be metabolically healthy can have more visceral fat around their pancreas which can contribute to insulin resistance. In this case, you will need to improve your mitochondrial efficiency and the overall efficiency of your aerobic energy systems. Certain forms of cardio such as LISS and HIIT are excellent for this.

Want more info?

Click here for my insulin resistance/blood sugar optimization PROTOCOL

Want to learn more? Here are some studies to look into:

https://www.ncbi.nlm.nih.gov/books/NBK507839/

https://pmc.ncbi.nlm.nih.gov/articles/PMC6358532/

https://pmc.ncbi.nlm.nih.gov/articles/PMC1370926/

https://pmc.ncbi.nlm.nih.gov/articles/PMC8912639/

https://pmc.ncbi.nlm.nih.gov/articles/PMC5934947/

https://pubmed.ncbi.nlm.nih.gov/28292654/

https://pubmed.ncbi.nlm.nih.gov/16321601/

https://pubmed.ncbi.nlm.nih.gov/34836329/

https://pubmed.ncbi.nlm.nih.gov/27329332/