Everything You Need to Know About Insulin Resistance

Insulin resistance is an impairment of the normal biologic response to our natural production of insulin, the hormone with which we control blood sugar levels. Insulin resistance is the precursor to the development of diabetes and all of its complications. Insulin is produced in the pancreas and helps glucose in the blood enter and nourish our body tissues. When critical cells in our liver, muscles and fat cells become resistant to, and don’t respond appropriately to the insulin which is released by the pancreas, our blood glucose levels will ultimately rise and the condition progresses to pre-diabetes and then frank diabetes. The single most important factor in the risk for insulin resistance to occur and progress is excess body fat.

When insulin resistance occurs the pancreas produces an excess of insulin in its attempt to control blood glucose with more of the hormone insulin-however this simply cannot ultimately work. The consequence of the excessive production of insulin is an elevated blood level of the hormone insulin, which is called hyperinsulinemia. It is felt that once chronic hyperinsulinemia has developed a person’s body is well on its way to the further worsening of the loss of blood glucose control, ultimately leading to diabetes and all of its negative consequences. It may take years for diabetes to finally be diagnosed in a person, but meanwhile the  metabolic consequences are developing and can be easily measured, leading to the presence of a number of other medical conditions. Hyperinsulinemia results in hypertension (elevated blood pressure), which is a major risk factor for heart disease, as well as kidney and eye disease. Elevated insulin levels are also associated with an abnormal blood lipid panel. Another metabolic consequence is hyperuricemia-elevated uric acid levels- which is the major blood marker for the risk and development of gout. Having a fatty liver,  called Non Alcoholic Fatty Liver disease (NAFL) , occurs particularly in overweight individuals with hyperinsulinemia. Also with insulin resistance there may be an elevation of measurable  inflammatory markers of the body. Yet another serious consequence is called endothelial dysfunction, which is an abnormality of the lining of our blood vessels and  a part of the eventual development of coronary heart disease. Hyperinsulinemia is a  risk for thrombosis and stroke. The predominant consequence of insulin resistance is type 2 diabetes and all of its complications of which there are many, and are very damaging to one’s health and ultimately survival. Because of the widespread obesity problem in the US, and increasingly across the world, weight reduction for those at risk of developing insulin resistance is becoming a primary goal as preventive medicine. Weight reduction is needed for much more than the cosmetic/ social aspect of weight control which have traditionally been the  focus of weight loss programs.


Thankfully, not only is there treatment for hyperinsulinemia, but even better, if one engages in the lifestyle modifications needed to control this condition, hyperinsulinemia can be entirely reversed and the development of diabetes and all of the many associated medical problems mentioned here, may be avoided.  A proper nutritional program emphasizing the reduction of  caloric intake of carbohydrates, regular exercise and weight reduction when advisable, is the recommended treatment.  Success with these lifestyle changes may completely eliminate the need for medications, which would be the next necessary step for those in whom the lifestyle changes are not accomplished.

Recently the role of GLP-1 agonist medications,




originally developed for diabetes and now being used for weight loss, may be an important new weapon in society’s struggle to combat obesity and diabetes, as per this NIH review


Physical activity improves our muscle’s insulin sensitivity and it increases energy expenditure (“calorie burning”) contributing to weight control.


  • Increased visceral fat related to excess body weight
  • The aging process
  • Physical inactivity
  • Nutritional imbalance
  • Medications (glucocorticoids, selective serotonin reuptake inhibitors,)
  • High-sodium diets
    • Glucose toxicity
    • Lipotoxicity from excess circulating free fatty acids

    Genetic Causes of Insulin Resistance. There are a number of rare conditions associated with insulin resistance but one common condition is Polycystic Ovarian Syndrome. This condition is associated with menstrual irregularities, excess hair for females and acne. Although generally thought of as a condition diagnosed and treated by gynecologists, the use of diabetes related medications which work via countering the underlying insulin resistance is becoming more widely practiced.


Studies funded by numerous governmental health associations tell us that insulin resistance syndrome is widespread and becoming more common, just as the nation’s obesity epidemic grows.

Twenty years ago a comprehensive National Health and Nutrition Examination Survey showed insulin resistance affects about 22% of United States (US) adults older than 20 years. A more recent analysis of NHANES data from 2021 found that 40% of US adults aged 18 to 44 are insulin-resistant . During this time it has been widely recognized that pediatric obesity is increasing as is the prevalence of type 2 diabetes in a younger population than has generally been associated with it.  Insulin resistance affects all races.

Insulin resistance is thought to precede the development of frank Type 2 diabetes by 10 to 15 years, however the negative associated health consequences associated with it are all developing as during that period of time.

According to the review published by the Mayo clinic  https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193 the symptoms of type 2 diabetes develop very slowly. As these  changes occur over a long period of time, many people who have insulin resistance and are on their way to the development of diabetes will not realize that they are suffering from the following ,which are warning signs. When symptoms are present, they may include:

  • Increased thirst.
  • Frequent urination.
  • Increased hunger.
  • Fatigue.
  • Blurred vision.
  • Slow-healing sores.
  • Frequent infections.
  • Numbness or tingling in the hands or feet.
  • Areas of darkened skin, usually in the armpits and neck.

The development of insulin resistance  results in impairment of the mechanism by which circulating blood glucose enters the body tissues, especially skeletal muscle. As a consequence,especially when combined with excess calorie intake, more insulin is required to try to get  glucose into these tissues. The resulting hyperinsulinemia further contributes to insulin resistance, and a vicious cycle continues of worsening hyperinsulinemia, until the pancreas is no longer able to meet the insulin demand created by insulin resistance, and the blood glucose rises, and pre-diabetes and diabetes then become apparent by measuring the blood  marker HgA1C.

In addition to diabetes diseases associated with insulin resistance, obesity, and cardiovascular disease, the microvascular complications of diabetes, neuropathy, retinopathy, and nephropathy ensue.  These are manifested as follows:

According to the NIH, since cardiovascular disease is the leading cause of disability and death in our society, a majority of the nation’s health care costs will increasingly be taken up by the increasing epidemic of obesity, diabetes and its cardiovascular consequences.


The 3 primary sites of insulin resistance are the skeletal muscle, liver, and adipose tissue. In a state of chronic caloric surplus, the tissues in the body become resistant to insulin signaling. Skeletal muscle is a large reservoir for circulating glucose, accounting for up to 70% of glucose disposal as measured by the hyperinsulinemic-euglycemic clamp. The direct result of muscle insulin resistance is decreased glucose uptake by muscle tissue. Glucose is shunted from muscle to the liver, where de novo lipogenesis (DNL) occurs. With increased glucose substrate, the liver develops insulin resistance as well. Higher rates of DNL increase plasma triglyceride content and create an environment of excess energy substrate, which increases insulin resistance throughout the body, contributing to ectopic lipid deposition in and around visceral organs. 

History and Physical

The clinical presentation of insulin resistance is variable concerning both history and physical examination findings. It depends on the subset of insulin resistance present, the duration of the condition, the level of beta-cell function, and the individual’s propensity for secondary illnesses due to insulin resistance. Common presentations include:

Associated Diseases

  • Non-alcoholic fatty liver disease (NAFLD)
  • Metabolic syndrome
  • Prediabetes or type 2 diabetes
  • Polycystic ovarian syndrome (PCOS)
  • Obesity
  • Microvascular disease (retinopathy, neuropathy, or nephropathy)
  • Macrovascular disease (stroke, PAD, and CAD)

Associated Symptoms

  • Hypertension
  • Hyperlipidemia
  • Gender and ethnicity-specific increased waist circumference
  • The stigmata of PCOS (menstrual irregularities, hirsutism, acne, and alopecia)
  • Acanthosis nigricans (see Image. Acanthosis Nigricans)
  • The stigmata of one of several genetic syndromes that include insulin resistance syndromes
  • Type A or type B insulin resistance syndrome
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