Insulin Resistance in a Variety of Diseases

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

Insulin resistance and metabolic syndrome is fast becoming a topic of concern in our society. Recent estimates by the Centers for Disease Control and Prevention (CDC) predict that up to a third of U.S. adults could have a diagnosis of diabetes by 2050, with more than 93% of these diagnoses referring to Diabetes Type 2, or Metabolic Syndrome, which almost always involves some degree of insulin resistance. Many of these cases are predicted to be undiagnosed, and this is because the population is still poorly educated to the physiology of metabolic syndrome and insulin resistance, failing to realize when this syndrome is occurring, and how to prevent it. You may read my article on Metabolic Syndrome and Diabetes to gain a better understanding, but this article will attempt to explain the concept of insulin resistance itself, how it develops, and what you can do to prevent or reverse it. You may also want to utilize Complementary and Integrative Medicine to help with this task, focusing on a holistic and thorough approach that, unlike modern allopathic medicine, seeks to correct the underlying health dysfunctions that cause the problem.

Insulin resistance may currently affect more than a fourth of the population in the United States and may precede a more obvious diabetic state or other disease by 10 years. A single pharmaceutical will not stop this complex process, and a pro-active, thorough, holistic approach to treatment, reversal and prevention is needed. Complementary Medicine should be integrated into standard medical care to prevent this widespread and costly health dysfunction from causing and contributing to a host of common devastating diseases.

Insulin is a protein hormone that is produced mainly in the pancreas, and is central to the hormonal regulation of our metabolism, constantly stimulating a variety of cells to regulate the use of glucose, glycogen, stored fats, and protein amino acids. While insulin is usually described simply, as the hormone that controls blood sugar levels, the variety of metabolic functions that are stimulated by insulin are great. Insulin is also central to the regulation of the steroid hormone metabolism, which operates on a feedback system, and is a crucial component of the metabolism of growth factors, genetic replication, protein signaling, fatty acid synthesis, the breakdown of proteins, clearing of damaged cell organelles (autophagy), amino acid uptake, cellular absorption of potassium, arterial muscle tone, and the secretion of hydrochloric acid in the stomach. Insulin in our brains has been shown to have an array of effects on the central nervous system, playing a role in the central regulation of homeostasis, and indirectly affecting memory and cognition. The effects of insulin have a profound effect on the process of aging, and are central to the longevity of the human organism. While a deficiency of insulin is seen in Diabetes Type 1, which is an autoimmune disorder that destroys insulin producing cells in the pancreas, the more common insulin disorder is Type 2 Diabetes, more properly called Metabolic Syndrome in most cases, where insulin resistance at the fat cell receptors creates an excess of circulating insulin hormone.

In recent years, research has also identified a Type 3 diabetes, or metabolic disorder, related to insulin resistance. Alzheimer's disease, increasing prevalent in industrial societies, and related to a variety of metabolic concerns affecting the brain, is now termed Diabetes Type 3 by a number of prominent experts. In 2012, experts at the University of Pennsylvania, in the U.S., published a study that showed that Alzheimer's disease is often unrelated to findings of high blood sugars in plasma, but is related to insulin resistance in the brain, as well as insulin-like growth factor (IGF). The rate of increase in Alzheimer's disease is correlated with the rate of increase in insulin resistance and Metabolic Syndrome observed in the United States. A landmark study at Brown University and the Rhode Island Hospital in 2008 concluded that: "Altogether, the results from these studies provide strong evidence in support of the hypothesis that Alzheimer's disease represents a form of diabetes mellitus that selectively afflicts the brain...Altogether, the data provides strong evidence that Alzheimer's disease is intrinsically a neuroendocrine disease caused by selective impairments in insulin and insulin-like growth factor signaling mechanisms, including deficiencies in local insulin and insulin-like growth factor production. At the same time it is essential to recognize that Type 2 Diabetes Mellitus and Type 3 Diabetes Mellitus are not solely the end results of insulin/IGF resistance and/or deficiency, because these syndromes are unequivocally accompanied by significant activation of inflammatory mediators, oxidative stress, DNA damage, and mitochondrial dysfunction, which contribute to the degenerative cascade by exacerbating insulin/IGF resistance.." In other words, a holistic approach to therapy is indicated to prevent and treat this Type 3 Diabetes, or Metabolic Syndrome in the brain. Complementary Medicine needs to be integrated into the standard treatment protocol.

Insulin resistance is a term that refers to the decreased effects of the hormone on cell receptors. Insulin receptors are found on cell membranes and belong to a family of tyrosine kinase receptors, which act by adding a phosphate group to tyrosine molecules on proteins. Insulin receptors are widely distributed in the body, with most cells having some insulin receptors, and some cells having as many as 100,000 receptors. Brain cells are some of the rare examples of cells with no insulin receptors, but even on brain cells insulin has been shown to have indirect effects, with insulin receptors found on the blood vessel cells and brain support cells, or glia. Insulin controls much of the transport of nutrients into the brain, and is central to regulation of brain growth and development, as well as the degree of effect that drugs and other molecules may have on brain cells. Research has found that insulin resistance syndrome increases the risk for developing Alzheimer's disease, and other neurodegenerative disorders. For patients with insulin resistance, though, the most dramatic effects occur in the utilization of nutrients such as glucose, and the degree of fat storage, which results in weight gain and fatty tissue growth. Understanding the physiology of insulin resistance helps the patient to understand what needs to be done to reverse this process and bring the body back to a normal healthy state, with improved energy and gradual weight loss. The benefits of reversal of insulin resistance are many, though, and are worth the efforts by the patient to understand this condition and correct it. A number of types of cancer cells have been shown to contain a high number of insulin receptors as well, and the link between breast and colon cancer and insulin resistance is being explored. Insulin resistance is also now studied in relation to various hormonal, or endocrine, disorders, such as Polycystic Ovary Syndrome, and is implicated in a high percentage of such cases.

Insulin resistance is hard to define precisely. Various health organizations around the world are presently seeking to set a world standard for insulin sensitivity, and the World Health Organization now defines insulin resistance as the lowest 25% of the insulin sensitivity (IS) index for the general population. But determining a normal index for insulin resistance is problematic, as normal insulin sensitivity varies widely with age, ethnicity, obesity, and various hormonal states. Experts are seeking to define a clear range of normal insulin sensitivity by measuring the SI of a large population sample of women who are not obese, have regular menstrual cycles, are not suffering from an adrenal disorder, and have normal circulating androgen levels. While we wait for disagreements in defining insulin resistance to resolve, the population of the United States is experiencing a rapid rise in the estimated incidence of insulin resistance related health problems and diseases. The smart patient tries to take a pro-active approach to their health, understand such endemic health concerns, and take healthy steps to prevent or correct the problem before it is too late.

Signs of Insulin Resistance

One sign of insulin resistance is the presence of a slightly darker skin pigmentation in body folds, such as underarms and groin folds, called acanthosis nigricans. While this skin pigmentation can be caused by other factors, such as genetic propensity, thyroid imbalance, or adrenal disease, including polycystic ovarian syndrome, and with certain drug side effects, the most common cause is insulin resistance. More overt signs of insulin resistance are chronic fatique, both physical and mental, poor memory, poor cognitive function, moodiness, agitation, anxiety, sleepiness or sluggishness immediately after eating meals with a high carbohydrate content, cravings for simple carbohydrates, and weight gain around the midsection. Some additional signs that may or may not be seen in individual cases are irregular menstrual periods, excessive adult acne, skin tags, increases in facial and body hair in women, thinning scalp hair in women, mood swings, depression, increased thirst, and erectile dysfunction in men. In some studies, 30% of women with ovarian cysts have been found to test positive for insulin resistance, and other problems with abnormal tissue growth, such as sleep apnea and fibrocystic breast disorders may have some association. For many women, these signs, such as irregular or skipped menstrual periods before normal perimenopausal years, have long been dismissed as early menopause, but could instead be related to a syndrome with insulin resistance and hormonal imbalance.

Laboratory tests of patients with insulin resistance may or may not show high triglycerides, high blood sugar, excess low-density lipoproteins, deficient high-density lipoproteins, or high C-reactive protein. The blood sugar may fluctuate, and periods of low blood sugar, or hypoglycemic episodes, are common with insulin resistance. The body's metabolism will try to adapt to insulin resistance and maintain fairly normal blood chemistry with higher circulating insulin levels. As the disease progresses, though, fatty accumulation in the liver may create difficulties in maintaining normal metabolic balance, and standard blood tests will then show pathologic, or near pathologic levels. The test for insulin resistance itself, called the euglycemic clamp test, is more expensive than standard blood tests, and at present most insurers are reluctant to pay for this test. The recent passage of the Health Care Reform Act, though, provides for increased incentives for preventative testing and mandates that the patient not be charged for such testing, even as a copayment. We should see some increase in direct laboratory testing for insulin resistance in the near future, especially if patients start demanding these tests. Expanded testing for diabetic states now includes the glucose tolerance test (GTT), and testing for the A1C index (an advanced glycation endproduct), but these tests do not directly correlate with insulin resistance.

While obesity and overweight conditions are associated with insulin resistance and Metabolic Syndrome, overt obesity and overweight conditions are not seen in a majority of cases, and one cannot assume that insulin resistance is not present if there is no obese or overweight condition. Obesity is thought to be the eventual outcome of insulin resistance, not the early cause, in adults, although in children the opposite may be the case for many. Poor dietary habits and overweight conditions due to lack of exercise may create insulin resistance in the child and young adult. Recent studies have found that 30% of slim women with polycystic ovary syndrome have insulin resistance, which demonstrates the complex and varied array of health problems and presentations that may be associated with problems at the insulin receptors. Insulin hormone regulates the high demand of energy usage and lipid metabolism in the developing eggs of the ovaries. Insulin resistance, coupled with a deficiency of D-chiro inositol appears to be the combination of factors that drives excess local testosterone production, hormonal imbalance, and lack of full maturation of ova, which then form numerous cysts and create polycystic ovary syndrome. Poor dietary habits are also associated with insulin resistance, but a variety of other factors are also involved, and even patients with healthy diets may be experiencing insulin resistance. The key to understanding whether you may or may not be affected by insulin resistance is to gain some understanding of the underlying causes and physiology of this health concern, and avoid oversimplification. Gaining such a holistic understanding of your health, and taking a holistic approach to correcting and preventing problems related to insulin resistance will pay off with big health dividends in the future.

The underlying causes and contributors to insulin resistance

While there may be some genetic propensity to insulin resistance, genetic inheritance does not explain the wide incidence of this problem in the population, and there have been no single genes found that are causative of insulin resistance. As the human genome is studied in great detail, scientists find that a complex interaction of genetic attributes are involved in inherited disorders, not single genes on the main 23 chromosome sequence that defines most of our inherited traits. The vast majority of our genetic makeup was previously called junk DNA, but recent research show how these genes affect expression of our main genetic traits, and a large sequence of molecules that surround our genes, called the epigenetic material, has also been found to play a large role in the regulation of the expression of our main genetic material. It is now proven that epigenetic traits may be passed to future generations, but may more easily correct within a few generations if lifestyle and dietary habits are corrected. While it is easy to say that insulin resistance may be inherited, the actual story of genetic inheritance is complicated. Many doctors and patients seem to resign themselves to a health problem when they suspect that a genetic inheritance plays a role. This resignation may provide a simple excuse to just take a pill to try to block the disorder, but it does not present a real and complete picture of the causes of the problem, or the potential corrections.

The real physiological causes of insulin resistance are related to a number of factors, especially inflammatory dysfunction in the fat cells, or white adipose tissue. Fat cells, or adipocytes, manufacture a number of lipid based hormones, as well as inflammatory mediators, or cytokines. These hormones and inflammatory cytokines act by stimulating receptor responses, and many of the receptors may be stimulated by both hormones and cytokines. Research has revealed that the manifestation of Metabolic Syndrome, or Diabetes Type 2 (non-insulin dependant diabetes), may occur years after the onset of insulin resistance, which leads to a cascade of health dysfunctions. When fat cells become insulin resistant, they do not release stored fat, in the form of triglycerides and free fatty acids, which are carried by high-density lipoproteins, as easily, and thus may become enlarged. This may lead to obesity and weight gain, accumulation of fatty tissues in the liver, and other tissue growths. It may also create cells that produce an excess of some inflammatory cytokines, which could become associated with various chronic diseases, especially atherosclerosis and cardiovascular disease. High levels of circulating interleukin-6 and tumor necrosis factor alpha are noted in studies of patients with chronic insulin resistance, and these excesses of inflammatory cytokines are associated with a host of difficult chronic diseases.

Insulin resistance is also seen in skeletal muscle tissues and the liver, which utilizes most of the insulin that our bodies produce. Liver dysfunction and increased liver stress may play an important role in the onset of insulin resistance. Various factors could increase the physiological stress on the liver, but excess processing of pharmaceutical drugs, excess alcohol consumption, recreational drug use, environmental toxins, poor diet, and chronic inflammation are the usual suspects. Free fatty acids (FFA) are implicated in the pathogenesis of insulin resistance, and excess FFA in circulation are associated with liver dysfunction. Free fatty acids are generated mainly in fat cells as the breakdown of stored fat, or lipolysis, is stimulated. Fatty acids can either be bound to other molecules, such as triglycerides, or remain unattached, as free fatty acids. A triglyceride is a combination of fatty acids and glycerol. Free fatty acids are transported by blood proteins, especially albumin, whereas fatty acids bound to triglycerides are transported by lipoproteins. Free fatty acids are important fuel sources for many tissues, and many cells can use either glucose, or blood sugar, or free fatty acids for fuel. Triglycerides are carried to the liver to be converted to fuel in the form of glucose. Excess free fatty acids imply that our cells are unable to utilize glucose efficiently, or that there is a problematic variance in glucose availability, prompting a need for increased free fatty acids as fuel.

Diet and exercise may play an important role in the pathogenesis of insulin resistance. Consumption of simple carbohydrates, which are broken down too quickly, and stimulate periods of excess insulin release, may result in the periodic need for free fatty acids as fuel for our cells. Consumption of complex carbohydrates would help alleviate this stress. Sedentary lifestyle may also play a role in the pathogenesis of insulin resistance. Numerous studies have shown that insulin sensitivity can be improved by exercise independently from weight reduction and changes in body fat distribution. When the body is inactive for long periods, there is too little stimulation of the insulin signaling mechanisms, and perhaps increased inflammatory stress related to poor circulation and postural strain. This combination describes many in our population today, as more and more people sit at computers for prolonged periods of time without more complex muscular activity, eat simple carbohydrate meals and snacks, drink simple carbohydrate sodas with excess phosphates, and then go home and lay in front of the television without periodic activity or excercise. Periodic activity or exercise will stimulate normal glucose mechanisms and release of various cytokines, such as bradykinin, that have been shown to have a stimulatory effect on glucose uptake. While many of us may increase periodic exercise routines, and try to eat more healthy meals, the most important solution would be to get up and move around and avoid the habit of simple carbohydrate snacks and soft drinks. Increased activity and exercise has also been shown to improve insulin resistance in the liver as well.

It is important to understand, though, that the whole problem must be addressed, and simple changes in diet and lifestyle may not be enough to correct the problems that cause insulin resistance. Each person must understand the various mechanisms that could cause or contribute to this health problem, and take an individualized approach to a protocol that will correct this systemic dysfunction. For example, such underlying health problems as obesity, hypothyroid conditions, chronic inflammatory states, depression, hormonal imbalances, and metabolic disorder, may play a role in the pathogenesis of insulin resistance, and each individual needs to assess these problems and address them uniquely. Ignoring the individual health problems and simply improving the diet and lifestyle may not be enough to fully address the problem. There is no one-size-fits-all approach to systemic problems such as insulin resistance.

Modern medicine has tried to find specific pharmaceutical approaches to blocking aspects of the insulin metabolism, but so far these attempts have failed, or created more side effects than benefits. Recent FDA warnings on such drugs as Avandia, and other drugs, such as glucosidase inhibitors, have prompted much alarm in the medical community. Natural sources of these chemicals, such as Maitake mushrooms, which contain an alpha glucosidase inhibitor, have none of the side effects seen with the pharmaceuticals. A number of herbs and foods have chemicals in them that act as alpha glucosidase inhibitors, including the herbs Zhi mu (Anemarrhena), Wu wei zi (Schisandra), Zi su ye (Perilla leaf), Ge gen (Kudzu), Bilberry, Gentian, Artemesia absinthia, turmeric, fennel, and Vinca minor (with active chemicals protocatechuic acid and puerarin). An array of herbs, foods and nutrient supplements have been studied and proven to have beneficial effects to help correct insulin resistance in other ways as well. Once again, though, with such a complex and systemic problem as insulin resistance, a single herb or nutrient medicinal may not be effective alone, or for all individual patients. A holistic protocol of medicinals, changes in diet and activity routines, and correction of underlying disease mechanisms should be adopted. The Complementary and Integrative Medicine physician, such as a knowledgeable Licensed Acupuncturist, can design such a comprehensive protocol that fits the needs of the individual.

The main problem with the assessment and treatment of insulin resistance, and the reason why a tremendous amount of research has failed to find the specific mechanisms most responsible for this disease, or dysfunction, is that the pathophysiology of insulin resistance is very complicated, and has many physiological factors involved. Once the patient and physician realize the complexity of this problem and agree that a comprehensive holistic strategy needs to be utilized, progress can be made toward a goal of restoring a complex systemic feedback system and eventually resolving symptoms and diseases related to insulin resistance. The following section helps to start your patient education.

Body chemistry and the etiology of insulin resistance

Research has uncovered a number of key biochemical mechanisms underlying insulin resistance that point to ways of correcting the homeostatic mechanisms that have gone awry. This type of research not only give pharmaceutical researchers clues to new drug mechanisms, but also provides holistic medicine with the knowledge to select treatment protocols that are specific to the biochemical problems and physiological mechanisms that have become problems. High free fatty acid concentrations in blood correlate strongly with insulin resistance, even in the children of patients with Metabolic Syndrome. The accumulation of intracellular lipid metabolites (e.g. diaglycerol) appears to be the driver or trigger of insulin resistance. Your body stores energy mainly in the form of glycerol and triglycerides, and the inability to properly access these stores, and the accumulation of fatty, or lipid, deposits, defines obesity. Decreases in cellular energy, or mitochondrial function, are also seen in studies of patients with insulin resistance, and their children, with mitochondrial ATP production decreased 30%. Research has found that reduced mitochondrial activity may lead to increased accumulation of lipid metabolites, which may trigger the insulin resistance.

Advanced glycation endproducts (AGEs) are lipid metabolites that accumulate and create difficulties for our cells. AGEs can be both consumed in foods and created by the body, and are complex molecules of combinations of fats, proteins and sugars. Formation of AGEs is found to accelerate in patients with Metabolic Syndrome and is associated with insulin resistance, oxidative stress, inflammation and atherosclerosis. Clinical trials by the NIH are presently exploring whether reduction in dietary AGEs will increase insulin sensitivity. Studies have found that accumulation of AGEs, and advanced glycation itself, may act as modulators of insulin resistance, and that subsequent structural and functional abnormalities of the insulin molecule may result. Much study has been devoted to nutritional and herbal formulas that may reduce AGEs and block glycation.

Intracellular lipid metabolites may also react with oxygen to form lipid peroxides, and then oxidant free radicals may be generated. The decreased mitochondrial function may provide for plenty of oxygen singlets for this free radical formation. Oxygen-derived free radicals may cause cell injury when lipid peroxidation reactions on the cell membrane cause both structural alterations and abnormal membrane functions. Free fatty acids, of which there is an excess in insulin dependant subjects, may account for fatty acid radicals which react with oxygen and generate fatty acid peroxy radicals, which in turn may react with other lipids, proteins, or free radicals. Antioxidants may help clear these oxidant free radicals and lipid peroxides. Tryptophan, histidine, Vitamin E tocopherol, and other antioxidants may help to prevent or reverse insulin resistance. The premier intracellular antioxidant is the glutathione produced by the cells, and glutathione peroxidases can enzymatically reduce lipid hypdroperoxides to nonreactive fatty acids. (Fantone & Ward 1982). A separate article on this website explains the glutathione metabolism.

C reactive protein (CRP) is a marker of inflammation and cardiovascular disease, and is associated with insulin resistance in scientific studies. C-reactive protein is released by the liver in response to excess circulating levels of inflammatory cytokines, such as interleukin-6 and tumor necrosis factor alpha (IL6 and TNFalpha), which is secreted by fat cells. CRP is associated wtih insulin resistance, obesity, cardiovascular disease, hypertension, high triglycerides, tissue plasminogen activator, and cellular fibronectin (Yudkin, Stehouwer, Coppack 1998). This implies that chronic inflammation is an important piece of the physiological puzzle of insulin resistance. Holistic study in the field of psychoimmunoneurology has established a strong interrelationship between these cytokines, hormonal imbalance, and imbalance of neurotransmitters in the last 20 years, suggesting that a holistic approach may be needed in the treatment of insulin resistance and Metabolic Syndrome. Further studies of this physiological relationship showed that elevated levels of CRP in relation to IL-6 cytokines probably follows the onset of insulin resistance. Studies in 2005 of subjects between the ages of 10-16 showed that CRP was highly associated with weight in both boys and girls, but was not significantly associated with insulin sensitivity when the subjects' levels were adjusted for body mass index. This is in contrast to adult studies, indicating that high CRP probably results from a chronic condition of insulin resistance. The mechanisms of childhood obesity and insulin resistance could be different from that of adults.

Chronic body acidity has long been linked to insulin resistance and metabolic syndrome. Uric acid excess, which is also linked to gout and kidney stone formation, has been associated with metabolic syndrome and insulin resistance since the early twentieth century. Studies cited below have shown how high fructose corn syrup, now the most prevalent commercial sweetener, has the ability to raise circulating uric acid levels in the body, and this has been linked to metabolic syndrome and insulin resistance as a potential cause. A typical diet of high meat consumption with minimal intake of alkalizing vegetables and fruits creates an acidic environment in our body that enhances the risk of developing insulin resistance. While a single change in our diet, such as the avoidance of high fructose corn syrup, will not completely reverse insulin resistance and metabolic syndrome, it is an important part of the overall protocol. Our main alkalizer in the body is calcium, and calcium imbalances are very prevalent in our society, especially with aging. Calcium is the most highly regulated molecule in our body, and a number of hormonal factors are involved in its tight regulation, including the hormone Vitamin D3, and thyroid and parathyroid hormones. The endemic deficiency of D3 in the population, and the widespread incidence of subclinical hypothyroid and hyperparathyroid disorders is thus undirectly linked to the large increase in incidence of insulin resistance and metabolic syndrome. Once again, a holistic approach to treatment and prevention is needed to fully address this problem.

Research has uncovered that an array of factors that produce insulin resistance at cell receptors, including excess PPARgamma, TNFalpha, IL-6, resistin, excess free fatty acids, deficient adiponectin, and either excess or deficiency of leptin. Despite a monumental amount of research, modern science still does not fully understand the precise nature of the defects that lead to insulin resistance and metabolic syndrome, but we do know that it is a complex multifactorial pathological mechanism. The array of factors in the body that cause insulin resistance relate to chronic inflammatory imbalance, metabolic imbalance, and hormonal imbalance. We might call it an immunohormonal metabolic imbalance. Adiponectin is a protein hormone secreted by fat cells that modulates a variety of metabolic processes, including glucose regulation and breakdown of free fatty acids. Resistin and leptin are also hormones secreted by fat cells that act as inflammatory mediators, and link inflammation with insulin resistance, metabolic syndrome and obesity. PPARg are proteins activated by kinins (inflammatory mediators) to stimulate peroxisomes (detox and antioxidant activity), as well as to modulate lipid binding, fatty acid metabolism and insulin receptor functions. Further reading on these subjects may be found in the web article on this website entitled Obesity.

More specific research of insulin receptor dysfunctions has noted a local problem that could be a key factor, the deficiency of D-chiro inositol (DCI) IPG in relation of the myoinositol IPG. These two companion molecules reside on the surface of both fat cells and immature eggs in the ovaries, and are activated by insulin receptors, which act to cleave these two chemicals for the cell membrane so that they may enter the cell and promote both glucose usage and storage (glycogen stores) and release testosterone. When the enzyme epimerase is inhbited or deficient, the body may not be able to make enough DCI, and food sources are limited (buckwheat is a source). Supplementation with DCI has produced some rather dramatic benefits for patients with insulin resistance, obesity and polycystic ovarian syndrome in limited human randomized clinical trials so far. In double-blind studies, women with PCOS who received DCI experienced the following statistically significant benefits when compared with a control group: lowered free and total testosterone, lowered blood pressure, increased insulin sensitivity and a corresponding improvement in glucose disposal, and increased frequency of ovulation (see research study links below).

Treatment options in Complementary Medicine for insulin resistance

A complete, thorough, and holistic protocol is needed to treat or prevent insulin resistance, as indicated by the variety of physiological factors that are associated with each other in this disease. The patient must be evaluated on in individual basis, and related health problems must be addressed in the overall therapy. If needed, diet and lifestyle changes should be initiated to insure success. Since normal weight loss is problematic with insulin resistance, simple dieting is not the key. Educating the patient to the effects of healthy foods and a balanced diet is important. Inclusion of alkalizing fresh vegetables and whole grains, avoidance of simple carbohydrates, and selection of healthy fats in the diet are essential, along with increased and regular activity, and habits of mild exercise. Inclusion of healthy plant proteins in the diet is proving essential to reversing insulin resistance as well, as amino acid imbalances are frequently found in patients with insulin resistance. A variety of herbs and nutrient medicines have been found to benefit the treatment protocols with insulin resistance. These should be prescribed by a professional with extensive medical school training, such as a Naturopathic Doctor or Licensed Acupuncturist and Herbalist. Such professional prescription also insures that trusted professional supplements and herbal medicines are taken, as this industry is not regulated in the United States and increasingly we see introduction of products on the commercial market that are tested and do not contain what is stated on the label (see the article entitled Herbal and Nutrient Medicine: Quality Assurance on this website).

The hallmarks of the pathology of insulin resistance are contained in the concept of Metabolic Syndrome, addressed on another article on this website. This problem needs to be treated persistently and with a thorough holistic approach to address all of the metabolic, inflammatory, and neurohormonal dysfunctions. The main sites of insulin resistance are the fatty liver and muscle fat tissues. A wide variety of Traditional Chinese herbs and formulas have been found to be effective in treatment, and a number of studies are cited below. The medical texts and databases of phytochemicals that are used by Licensed Acupuncturists and herbalists that practice TCM offer the physician and patient proven natural chemistry to reverse insulin resistance. Many of the herbs that are found useful are commonly used to treat other medical conditions as well, showing that general treatment from a TCM practitioner can have many unseen benefits that are important to the health. Of course, quality and dependability of the herbs and formulas are important, as the FDA in the U.S. still refuses to adopt international protocols to regulate this industry, mainly due to lobbying by the pharmaceutical industry. The professional TCM physician utilizes herbal products that are from professional companies that insure quality. Purchase of these products from the retail stores by the patient is often problematic.

Naturopathic research is revealing a host of significant nutrient medicinal effects that aid in the treatment of insulin resistance as well. Reduction of glycation and advanced glycation endproducts (AGEs) is important in the protocol, and nutrient formulas based on sound research have been formulated to achieve this goal. L-carnosine and other amino acids, P5P, and N-acetyl cystine are some of the key nutrients that may help the body reverse AGEs. A host of nutrient extracts have been proven effective in beneficially altering lipid metabolism, including policosanol, gugulipid, pomegranate extract, and bitter melon extract. Sytrinol is derived from palm, citrus and pomegranate and is proven to promote leptin balance and act as a cellular antioxidant. Tocotrienols are Vitamin E metabolites proven to balance lipids and cholesterol, and exert potent antioxidant cardioprotectant and neuroprotectant effects. Red rice yeast extract has proven to be a potent normalizer of cholesterol metabolism, but a quality professional product is necessary for a dependable effect. Non-alcoholic fatty liver disease and iron overload toxicity, which creates an imbalance of amino acids with dysfunction of the liver enzymes responsible for this mechanism, is also linked to insulin resistance, and a number of nutrient medicines to aid homocysteine metabolism and balance, and to balance omega-6 and omega-3 essential fatty acids in the diet, may be helpful. The full array of research is extensive and the smart patient will choose a Complementary Medicine physician with knowledge in this area to guide an individualized therapeutic protocol.

Diet and exercise routines are very important in the overall protocol, and can be easily tailored to suit the individual. Research has revealed how children need to have a healthy diet and excercise routine to achieve metabolic flexibility, or the ability of skeletal muscle to switch between utilizing lipids as fuel when there is insufficient carbohydrate. When children consume carbohydrates throughout the day and do not routinely exercise the skeletal muscles, this mechanism of metabolic flexibility becomes impaired and leads to insulin resistance, obesity and metabolic syndrome. We cannot continue to ignore basic physiology in our lives, and the science of our bodies and the homeostatic mechanisms that are important to our health should be a significant subject taught to our children in school. Understanding of physiological science is perhaps the most pertinent knowledge in our lives, yet we continue to ignore the science of our bodies as a society. Understanding will bring improved societal habits and lifestyle.

Once again, the important health concerns in our lives cannot be simplified to a short explanation and treated with a miracle drug, herb or nutrient pill. A complete and thorough holistic regimen needs to be adopted to prevent or reverse insulin resistance, and the knowledgeable Complementary and Integrative Medicine (CIM) physician, especially the Licensed Acupuncturist or TCM physician, is able to guide and individualize this therapy.

Information Resources

  1. The National Institutes of Health maintains a National Diabetes Information Clearinghouse that provides basic information on insulin resistance:
  2. The American Diabetes Association's Journal of Diabetes published a study in 2004 that shows that insulin resistance is seen in both obese and non-obese patients, and that a related hormone, adiponectin, is more associated with problems at the insulin receptors than with obesity itself:
  3. The RCMAR, an NIH sponsored resource center based at UCLA, provides a reliable explanation of current estimates of insulin resistance and current testing methods, including the euglycemic clamp test:
  4. Assessing insulin sensitivity is explained on this 2003 website of the RCMAR (Resource Center for Minority Aging):
  5. As far back as 1995, researchers, such as these at Stanford University School of Medicine and the Department of Veterans Affairs Medical Center, realized that insulin resistance and the associated metabolic syndrome are key aspects of the growing incidence of non-insulin-dependent diabetes, hypertension, and coronary heart disease:
  6. In 2008, a landmark study by Brown University and the Rhode Island Hospital clearly showed that Alzheimer's disease could be called Type 3 diabetes, with a high correlation with insulin resistance and insulin-like growth factor (IGF) resistance in the brain causing the disease, along with oxidant stress, inflammatory imbalance, and mitochondrial dysfunction. It is noteworthy to consider that local insulin deficiency and deficiency of IGF may also contribute to Alzheimer's, implicating metabolic stresses and adverse pharmaceutical effects as well:
  7. These same researchers, in 2005, at Stanford University School of Medicine, found that the pathologies related to insulin resistance included abnormally shaped low-density lipoproteins, elevated plasminogen activator inhibitor, increased fibrinogen accumulation, increased sympathetic nervous activity, increased salt sensitivity, and subsequent changes in the arterial lining associated with atherosclerosis. Excess circulating levels of several inflammatory markers and cytokines were also associated, which could link insulin resistance to a number of diseases besides cardiovascular disease:
  8. A 2006 study at Yale University School of Medicine utilized magnetic resonance spectroscopy to examine cellular mechanisms in patients with insulin resistance, and found that reduced mitochondrial activity led to accumulation of lipid metabolites that triggered dysfunctions related to insulin resistance:
  9. A 2008 study at the University Hospital Maastricht, in the Netherlands, found that advanced glycation endproducts (AGEs) likely interfere in the complex pathways of insulin signaling and contribute to the pathogenesis of insulin resistance by altering the structure and function of the insulin molecule:
  10. A 2001 study at the Imperial College School of Medicine and the Royal Free and University College Medical School of London found that C reactive protein (CRP) is highly associated with insulin resistance in both Asian and European White populations:
  11. A 2015 study at the Kawasaki Medical School in Okayama, and the Kinki University Hospital Clinical Research Center, in Sayama, Japan, found that amino acid imbalance is found in a majority of patients with insulin resistance and non-alcoholic fatty liver disease, and that excess circulating tyrosine is a marker for this imbalance, reflecting advancement of the disease to the fibrotic stage. Excess tyrosine levels occur when the liver does not break down the amino acid tyrosine efficiently, or when the homocysteine metabolism is stressed and depends on increased tyrosine because the pathway to create homocysteine from cysteine and methionine is deficient. Problems with iron homeostasis may also result in excess circulating tyrosine, as iron is a cofactor for the conversion of phenylalanine to tyrosine, and iron overload toxicity is highly linked to non-alcoholic fatty liver disease:
  12. A 2009 New York Times article reveals research that finds a low-acid diet with reduction of meat and simple starches and high consumption of alkiline fresh vegetables to significantly prevent and reverse osteoporosis, prevent cardiovascular disease, and diabetes:
  13. A 2006 study at the University of Florida reveals how high fructose corn syrup, the most used commercial sweetener, may raise circulating uric acid levels and be causative of metabolic syndrome and insulin resistance:
  14. Transfats have been linked to insulin resistance at the University of Reading in England in 2010:
  15. In 2008, researchers at the Pennington Biomedical Research Center at Louisiana State University noted that Traditional Chinese Medicine (TCM) presents excellent treatment options in the treatment of Metabolic Syndrome:
  16. A 2009 study in Korea found that the Chinese herb Mu Dan Pi (Moutan Cortex, or Paeonia suffruticosa) stimulated liver enzymes that enhanced glycogen synthesis and glucose metabolism in insulin resistant liver cells:
  17. A 2005 study at Xi'an Jiaotong University in Xi'an, China found that the Chinese herb Sanguis draxonis (Xeu jie, Dragon's blood resin) significantly improved insulin resistance in animal studies:
  18. Another 2005 study in Taiwan found that the herb Siberian Ginseng (Acanthopanax senticosus, Ci wu jia) was able to improve insulin sensitivity significantly in animal studies:
  19. Researchers in Taiwan in 2005 also found that ginseng could improve insulin sensitivity to treat or prevent insulin resistance in animal studies:
  20. A 2007 study at the University of Heidelberg, Germany, found that the amino acid L-carnosine may significantly improve glucose metabolism in Type 2 diabetes, or Metabolic Syndrome, and improve the A1C index, a marker of AGE excess:
  21. A 2010 study at the University of Southern California found that L-carnosine exerted anti-glycation effects that should benefit human patients to reduce AGEs (advanced glycation endproducts) and thus reverse insulin resistance:
  22. D-chiro inositol deficiency has been linked to insulin resistance and obesity in cases of polycystic ovary syndrome:
  23. 1999 human studies of D-chiro inositol in the treatment of polycystic ovary syndrome in obesity by the Virginia Commonwealth University Department of Medicine at the Medical College of Virginia, found that D-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations.: