In previous articles, I have discussed the role of metabolic Inflammation in obesity and diabetes. Today, we will narrow down to the specifics of what insulin resistance is, its effects and how metabolic inflammation increases the chances of one developing it.

1. What is Insulin resistance?

Approximately 30% of Americans, and up to 50% in the 60 years and over the bracket, have a silent blood sugar problem known as insulin resistance. Insulin resistance increases the risk for prediabetes, Type 2 diabetes and a host of other serious health problems, including heart attacks, strokes, and cancer.

What therefore is Insulin Resistance? It is when cells in your muscles, body fat and liver start repelling or ignoring the signal being sent out by the hormone, insulin—which is to take glucose from the bloodstream into our cells for breakdown or storage. Glucose, commonly called blood sugar, is the body’s main source of fuel.

1. How does Insulin Resistance Develop?

Some factors that determine insulin resistance are aging and ethnicity but the driving forces seem to be excess body weight, too much belly fat, a lack of exercise, smoking, and even sleep depravity.

With time, and as the insulin resistance develops, more insulin is produced by your body as it tries to fight back. After an accumulated period of time, several years even, the beta cells in your pancreas get worn out because of all the extra work and can no longer keep pace with the increased demand for insulin. Then – years after insulin resistance stealthily started – your blood sugar may spike and you may manifest prediabetes or type 2 diabetes. You are also at risk of developing the non-alcoholic fatty liver disease (NAFLD), a condition that increases your risk for liver damage and heart disease.

2. What are the Signs and Symptoms of Insulin Resistance?

Insulin resistance does not always manifest to the naked eye but here are some signs to look out for:

• A large waist. Experts say the best way to tell whether you’re at risk for insulin resistance involves a tape measure and moment of truth in front of the bathroom mirror. A waist that measures 35 inches or more for women, 40 or more for men (31.5 inches for women and 35.5 inches for men if you’re of Southeast Asian, Chinese or Japanese descent)6 increases the odds of insulin resistance and metabolic syndrome, which is also linked to insulin resistance.
• You have additional signs of metabolic syndrome. According to the National Institutes of Health, in addition to a large waist, if you have three or more of the following, you likely have metabolic syndrome, which creates insulin resistance.
• High triglycerides. Levels of 150 or higher or taking medication to treat high levels of these blood fats.
• Low HDLs. Low-density lipoprotein levels below 50 for women and 40 for men – or taking medication to raise low high-density lipoprotein (HDL) levels.
• High blood pressure. Readings of 130/85 mmHg or higher, or taking medication to control high blood pressure
• High blood sugar. Levels of 100-125 mg/dl (the prediabetes range) or over 125 (diabetes).
• High fasting blood sugar (or you’re on medicine to treat high blood sugar). Mildly high blood sugar may be an early sign of diabetes.
• You develop dark skin patches. If insulin resistance is severe, you may have visible skin changes. These include patches of darkened skin on the back of your neck or on your elbows, knees, knuckles or armpits. This discoloration is called acanthosis nigricans.8

3. Chronic low-grade inflammation and the development of insulin resistance

As early as the 1950’s, there was epidemiological evidence suggesting a correlation between inflammation and insulin-resistant states such as obesity, but the mechanistic links were unknown. In the last decade, however, it has become increasingly evident that obesity and the concomitant development of inflammation are major components of insulin resistance. Studies in human obesity and insulin resistance have revealed a clear association between the chronic activation of pro-inflammatory signaling pathways and decreased insulin sensitivity. For example, elevated levels of tumor necrosis factor-α (TNF), interleukin-6 (IL-6) and interleukin (IL-8) have all been reported in various diabetic and insulin-resistant states. In addition, the inflammatory marker C-reactive protein (CRP), a non-specific acute phase reactant, is commonly elevated in human insulin-resistant states. Also, experiments in naturally occurring rodent models of obesity, knockout and transgenic mice, as well as detailed studies of insulin signaling at the molecular level have begun to elucidate the mechanistic links between obesity-induced inflammation and insulin-resistant states.

4. What Health Conditions are Related to Insulin Resistance?

An estimated 87 million American adults have prediabetes; 30-50% will go on to develop full-blown type 2 diabetes. In addition, up to 80% of people with type 2 diabetes have NAFLD. But those aren’t the only threats posed by insulin resistance.

Thanks to years of high insulin levels followed by an onslaught of cell-damaging high blood sugar, people with insulin resistance, prediabetes, and type 2 diabetes are at high risk for cardiovascular disease. Insulin resistance doubles your risk for heart attack and stroke – and triples the odds that your heart attack or ‘brain attack’ will be deadly, according to the International Diabetes Federation.

Meanwhile, insulin resistance and metabolic syndrome are also linked with higher risk for cancers of the bladder, breast, colon, cervix, pancreas, prostate and uterus.11, 12  The connection: High insulin levels early in insulin resistance seem to fuel the growth of tumors and to suppress the body’s ability to protect itself by killing off malignant cells. 13

Research has also found a strong association between insulin resistance and memory function decline, increasing the risk of Alzheimer’s disease.

5. Can understand the causes of Insulin Resistance aid in future preventive approaches?

As obesity-associated chronic low-grade inflammation is responsible for the decrease of insulin sensitivity, obesity is a major risk factor for insulin resistance and related diseases such as type 2 diabetes mellitus and metabolic syndromes. The state of low-grade inflammation is caused by over-nutrition which leads to lipid accumulation in adipocytes.

Obesity might increase the expression of some inflammatory cytokines and activate several signaling pathways, both of which are involved in the pathogenesis of insulin resistance by interfering with insulin signaling and action. It has been suggested that specific factors and signaling pathways are often correlated with each other; therefore, both of the fluctuations of cytokines and the status of relevant signaling pathways should be considered during studies analyzing inflammation-related insulin resistance.

References

1. NCBI (2007): Inflammation and Insulin Resistance. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246086/
2. Scientific American(2009): Does Inflammation Trigger Insulin Resistance and Diabetes? Retrieved from https://www.scientificamerican.com/article/inflammatory-clues/

3. NCBI (2006): Inflammation and Insulin Resistance. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1483173/
4. org (2008): Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species. Retrieved from https://www.physiology.org/doi/full/10.1152/ajpregu.00561.2007
5. Hindawi (2015): Mechanisms Linking Inflammation to Insulin Resistance. Retrieved from https://www.hindawi.com/journals/ije/2015/508409/

6. Endocrineweb(2019): Insulin Resistance Causes and Symptoms. Retrieved from https://www.endocrineweb.com/conditions/type-2-diabetes/insulin-resistance-causes-symptoms