Insulin is a vital hormone that controls the levels of sugar in our bodies. In a nutshell, it removes excess glucose from the blood through a process known as glycogenesis.

However, problems with insulin are at the heart of many medical conditions. Insulin resistance occurs when your cells stop responding to insulin. This means that the effects of insulin cannot be appreciated leading to a buildup of sugar in the bloodstream. About 100 million Americans are affected by insulin resistance. Fortunately,   dietary and lifestyle changes can dramatically improve this condition.

This article explains all you need to know about insulin and insulin resistance.

What Is Insulin?

Insulin is a hormone that is produced by beta cells in the pancreas. Its main function is to regulate the amount of glucose circulating in your bloodstream. However, it also affects fat and protein metabolism. When you eat a slice of bread, which definitely contains carbohydrates, the amount of sugar in your blood increases. Consequently, the beta cells in your pancreas are stimulated to produce insulin. The insulin is released to your bloodstream, where it removes the sugar and stores it in cells. This process results in reduced blood sugar levels.

However, cells sometimes become less sensitive to insulin. When this happens, sugar begins to build up in the bloodstream. Your pancreas produces even more insulin to lower the blood sugar levels. This leads to high insulin levels in your blood, which is referred to as hyperinsulinemia.

Diabetes type 2 occurs when your cells become increasingly resistant to insulin, resulting in a rise in both insulin and blood sugar levels. If this persists for long, your beta cells may become damaged, leading to decreased insulin production.

Insulin resistance is the main cause of type 2 diabetes.

What About Insulin Sensitivity?

Insulin sensitivity is just the opposite of insulin resistance. When you have insulin resistance, it also means that you have low insulin sensitivity. While insulin resistance is harmful to your health, insulin sensitivity is beneficial.

What Causes Insulin Resistance?

Insulin resistance is caused by many factors.

A number of studies have shown that high amounts of free fatty acids in your blood can cause insulin resistance. This is caused by eating too many calories. Being overweight or obese is also linked to insulin resistance. Visceral fat that mostly accumulates around your waist can release free fatty acids into your blood and trigger inflammation. However, even people with moderate weight can develop insulin resistance, possibly due to genetic predisposition.

Other possible causes of insulin resistance include:

• High sugar diet. Artificial sugars have been linked to inflammation and insulin resistance.
• Inactivity. Regular physical activity can reduce insulin resistance by stimulating weight loss.
• Gut microbiota. A disruption in the bacterial environment of your digestive system can cause inflammation and insulin resistance.
• Genetic factors: African American, Hispanic, and Asian peoples are at higher risk for insulin resistance.

What Are The Complications Of Insulin Resistance?

Insulin resistance is the precursor for diabetes type 2 and metabolic syndrome. Metabolic syndrome is a group of risk factors associated with type 2 diabetes and heart disease.

By the time a person is diagnosed with type 2 diabetes, they are likely to have developed chronic insulin resistance. It is estimated that by the time a diagnosis is made, 50% of insulin-producing cells may have lost function. This means that the person is not only resistant to insulin, but they are also unable to produce adequate amounts of insulin.

Insulin resistance is also strongly associated with heart disease, which is the leading cause of death in the US.

Other diseases linked to insulin resistance include:

• Non-alcoholic fatty liver disease (NAFLD)
• Cancer
• Polycystic ovarian syndrome (PCOS)
• Alzheimer’s disease

How To Reduce Insulin Resistance

Weight loss is one of the most effective ways of reducing insulin resistance. Making drastic dietary changes is also necessary so that you are consuming more of the beneficial foods and less of the harmful ones. Exercise also helps to shed off extra weight and maintain health. Lastly, doing away with harmful habits such as smoking and excessive drinking also plays a significant role.

• Engage in regular exercise such as brisk walking or jogging for 30 minutes each day.
• Lose belly fat
• Stop smoking
• Reduce intake of artificial sugar, such as from artificially sweetened beverages
• Increase intake of omega-3 fatty acids

For more on improving insulin sensitivity with dietary changes, read our previous article here.

The bottom line

Insulin resistance is responsible for a number of chronic health complications. Often it can go on undetected for a number of years without causing alarm. When insulin resistance is not detected early enough, it is likely to wreck a person’s health. Fortunately, a number of things can be done to prevent or stop the progression of insulin resistance. If insulin resistance can be prevented we will definitely have millions of people living healthier and more fulfilled lives that are free of disease.

References

1.   NCBI (2005): Dose-response effect of elevated plasma free fatty acid on insulin signaling. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/15919784

2.   CDC (2017): New CDC report: More than 100 million Americans have diabetes or prediabetes. Retrieved from https://www.cdc.gov/media/releases/2017/p0718-diabetes-report.html

3.   NCBI (2005): Dose-response effect of elevated plasma free fatty acid on insulin signaling. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/15919784

4.   NCBI (2013): The Role of Gut Microbiota on Insulin Resistance. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705322/

The more insulin you have, the more fat you accumulate.

Insulin activates the enzyme hexokinase, which phosphorylates glucose, trapping it within the cell, (and inhibits the activity of glucose-6-phosphatase, preventing phosphorylated glucose from being returned to glucose). Insulin also activates several of the enzymes that are directly involved in glycogen synthesis, including phosphofructokinase and glycogen synthase. The net effect of insulin in the presence of an abundant supply of glucose, the liver quickly uptakes glucose and stores it as glycogen, which reduces serum glucose levels. The serum carrying capacity of glucose is approximately 5gm.

As glycogen storage capacity exceeds approximately 500gm (approximately 2,000 calories), the overflow is shunted to lipid. Failing to deplete the glycogen reserve prior to refeeding results in shunting of glucose to lipid. When the liver is saturated with glycogen, any additional glucose taken up by hepatocytes is shunted into pathways leading to the synthesis of fatty acids, which are exported from the liver as lipoproteins. The lipoproteins provide free fatty acids for use in other tissues, including adipocytes, which use them to synthesize triglycerides. Insulin inhibits the breakdown of fat in adipose tissue by inhibiting the intracellular lipase that hydrolyzes triglycerides to release fatty acids.

Insulin facilitates the entry of glucose into adipocytes, and within those cells, glucose can be used to synthesize glycerol. This glycerol, along with the fatty acids delivered from the liver, is used to synthesize triglyceride within the adipocyte.

In the US, 52.3% of the adult population has either type 2 diabetes or prediabetes.

Less than 12.2% of the adult population is metabolically healthy.

Six feedings a day are a recipe for insulin resistance.

Dietary carbs are only necessary if a person is currently taking diabetes medications associated with the risk for hypoglycemia such as insulin or a sulfonylurea, otherwise, there are no essential dietary carbohydrate requirements.

Type 2 Diabetes is triggered by too much insulin, it’s not an insulin deficiency. It’s insulin resistance.

Once the body is in nutritional ketosis, reduced insulin shifts the metabolic pathways to preferentially burn fat stores instead of storing fat stores. This leads to weight loss and can reverse the symptoms of diseases like Type 2 diabetes.

Impaired glucose tolerance and type 2 diabetes mellitus are associated with increased risk of cardiovascular disease.
Postprandial hyperglycemia, with resultant hyperinsulinemia and excessive inflammatory cascade, leading to endothelial dysfunction.

A ‘cheat day’ is often embraced on ketogenic diets, as a reward, presumably activating the dopaminergic hedonic response system, akin to activating the nucleus acumens with a tap of cocaine.

Unfortunately, even one 75 gram dose of glucose while on a “keto” (high fat, low carbohydrate) diet can lead to damaged blood vessels, using a measure of flow-mediated dilation (FMD), arterial stiffness, and diameter, velocity, and flow of the common and internal carotid, and vertebral arteries were assessed in the fasting state and 1 h post glucose consumption.

A “temporary lapse in adherence with consumption of a food causing a glucose spike might lead to acute endothelial damage.” What this suggests?
1. Even low dose infrequent cheat days, once you are on keto, may not be good for your blood vessels.
2. Your blood vessels become more sensitive to glucose after you are on keto?
3. Even an infrequent binge of cocaine once you are clean is probably not a good idea?
4. Metabolic flexibility is diminished as a particular dietary pattern becomes established?

Short-Term Low-Carbohydrate High-Fat Diet in Healthy Young Males Renders the Endothelium Susceptible to Hyperglycemia-Induced Damage. Nutrients, 2019; 11 (3): 489

The longer progression to Type 2 Diabetes can be delayed, even if using oral hypoglycemics, the more cost-effective it is. Most physicians wait until someone’s HgBA1C exceeds 6.5, but this is a mistake.

The following is a cost analysis of early intervention with metformin, compared to delaying treatment until insulin supplementation is required due to B-cell fatigue, assuming similar lifestyle management:

The average wholesale cost of generic metformin is less than $0.05/1,000 mg tablet, so a 30-day supply is $6.00 a month.
The average wholesale insulin cost, when a combination of both long-acting and short-acting insulin is prescribed:
Long-acting insulin: Lantus $431/month
Short-acting insulin: Humalog $533/month
Combined cost: $964/month excluding injection supplies.

One could pay for 160 months of metformin therapy for the same cost as 1 month of insulin therapy.

Our eating patterns can influence insulin production and weight gain, and it’s important to give our bodies time to burn energy from food. Most people eat from the time they wake up until the time they go to bed — typically three main meals, multiple snacks, and often soda in between. This pattern leads to chronic high insulin production, which fatigues the insulin receptors. In addition, insulin is a fat storage hormone, and elevated insulin levels lead to fat accumulation in the liver, creating metabolic inflammation.

Your metabolism exists in two states – the “fed” (insulin high) state and the “fasted” (insulin low) state. Either we are storing food energy (increasing storage), or we are burning stored energy (decreasing storage or fat lysis). If we start eating the minute we roll out of bed and do not stop until we go to sleep, we spend almost all our time in the fed state. Over time, we gain weight, because we have not allowed our body time to burn stored food energy.

Time-restricted feeding can reduce high insulin levels, which can reverse type 2 diabetes. It’s important to understand some facts about insulin and how it works.

First, insulin is fat storage and a growth hormone. It reduces circulating glucose by converting it to glycogen storage first, which then overflows to fat storage. Eating carbohydrates causes insulin release and thereby increases fat storage, especially in the liver. The more fat you store in the liver, the more insulin resistant you become, which can lead to prediabetes and increase the likelihood of becoming obese. Constant feeding (three meals and two snacks per day) keeps your insulin levels high and causes you to gain weight. You release insulin even if you eat artificial sugars, and the circulating glucose causes fat storage.

By contrast, time-restricted feeding reduces constant high insulin levels, permitting the liver to stop storing fat, and resensitizes the liver to insulin, which reverses fatty liver and reverses type 2 diabetes.

There are other things, but it’s literally that simple: The higher your insulin level and the longer the time period it is high for, the fatter you get. The more insulin resistant you get, the more fatty liver you get.

This is true whether you are producing your own insulin by eating all the time, or you are injecting insulin. Type 1 diabetics, who don’t produce any insulin, are thin until they start getting injectable insulin.

Nearly the worst advice we give to patients is “six small meals.” In reality, time-restricted feeding is the key to lowering insulin. Lowering insulin production immediately stops fat storage and decompresses the liver. The easiest way to do this is to eliminate one meal and at other meals eat food that is satiating, higher in fat and protein.

Can anxiety and depression unexpectedly improve when treating insulin resistance with metformin? I am an interventional pain physician in the urban core. More than 90% of my patients with chronic unrelenting pain also have metabolic syndrome with insulin resistance, and more than 90% also have significant anxiety and depression. I had always assumed that the anxiety and depression were related to socioeconomic conditions or comorbidity of chronic pain — until I started aggressively treating their insulin resistance.

Undertreatment, I found that lifestyle modification and interventional techniques certainly improved their pain, but their anxiety seemed to persist. However, when I added metformin to treat insulin resistance and metabolic syndrome, the anxiety and depression seemed to immediately improve, unexpectedly. A recent mouse study sheds light on why this might be.

People with diabetes are known to have an increased risk for mood disorders such as depression and anxiety; the underlying mechanisms may be the neurotransmitter serotonin, or it may be an issue of gut-induced vagal signaling with reduced heart rate variability. Tryptophan is a necessary precursor for serotonin, and if tryptophan’s entry into the brain is reduced, it also reduces serotonin production. This mouse study demonstrated that metformin reduced the amino acids that impair the entry of tryptophan into the brain, increasing tryptophan entry and subsequently increasing serotonin. Additionally, metformin’s antidepressant-like effects were accompanied by improved neurotransmission in the hippocampus.

J Zemdegs, et al. The Journal of Neuroscience, 2019; 2904-18.

Our weight depends on a variety of factors, but one secret to a healthy weight is found in awareness of the role the hormone insulin plays in fat storage.

It is wrongly assumed that consuming excessive calories is the root cause of obesity. However, a calorie of food energy has different metabolic fates depending upon the hormonal stimulation. That same calorie may be used to generate body heat or stored as body fat. It can also act as a signaling molecule to trigger a secondary response. The gut microbiome then interacts with the consumed molecules first and creates its own signaling to the human host and affects metabolic pathways, increasing or decreasing nutrient availability.

Obesity is a disease of failed energy partitioning, not one of total energy intake, and one of the primary drivers of this partitioning is the hormone insulin. Insulin is specifically a fat storage growth hormone. The mere presence of insulin causes an immediate metabolic shift from using fat as a fuel source, to storing circulating glucose to glycogen for a total of about 500 grams. Once the initial glycogen stores are full, then glucose is converted to fat storage, a nearly unlimited storage capacity.

Insulin is specifically a fat storage growth hormone. The higher your insulin and the more often your insulin spikes determine your fat storage, not the number of calories you eat.

Individuals experience significantly different changes in blood glucose levels (as shown by using a continuous glucose monitor) after eating the same foods. Some patients with normal blood glucose levels experience after-meal glycemic spikes that are in the diabetic range.

A person’s gut microbiome more accurately predicts the individual spike in blood glucose after eating than just knowing a food’s calories or carbohydrates. Eran Segal and Eran Elinav from the Weizmann Institute of Science, Rehovot, Israel, developed an algorithm, described in the journal Cell, that used microbiome data as well as other factors, such as age, sex, height, hip circumference, and physical activity, to predict after-meal glycemic responses in people who did not have diabetes.

In essence, food labeling remains a mythical beast. It is the personalized dietary intervention that drives the individual insulin response.

DOI:https://doi.org/10.1016/j.cell.2015.11.001