The role of insulin resistance in peripheral vascular disease – Quantum Medicine Update
Paul Yanick, Jr.
Insulin Resistance Syndrome (IRS) plays a primary role in the initiation and perpetuation of disorders of the human vascular system. IRS is an impaired metabolic response to our body’s own insulin so that active muscle cells decrease their uptake of glucose. This causes blood insulin levels to be higher. In turn, higher insulin equates to fat cells not being able to give up their energy stores to let us lose weight. This disorder is associated with obesity, vascular disorders, abnormal triglycerides, glucose intolerance (syndrome “X”) and Type 2 diabetes mellitus.
Excess fat in the midriff (apple-shaped physiognomy), an increased waist-to-hip ratio and an androgenic shift in hormone metabolism is common in IRS patients. Moreover, when the body cannot metabolize glucose in a natural and normal fashion, the complications include heart disease, stroke, end-stage renal disease, peripheral arterial disease, and nerve damage. (1-7)
IRS is a consequence of the breakdown of homeostatic mechanisms via glucoregulatory substances, including insulin, glucagon, insulin-like-growth factor, somatostatin, human growth hormone, cortisol, and the catacholamines. Binding of insulin to its receptors promotes tissue uptake of glucose (this physiology increases transport of glucose receptors to the cell surface and by increasing the activity of the intrinsic tyrosine kinase type enzymes which phosphorylate glucose once it is inside the cell).
A high percentage of patients with hypertension are estimated to have insulin resistance. The main problem is that this condition can exist unrecognized and metabolic damage can occur before a full blown Type 2 diabetes is finally diagnosed. Insulin resistant diabetics are 2-5 times more likely to die from heart attack or stroke than are non diabetics. (1-7)
Failure to treat IRS results in abnormalities in glucose and lipid (blood fats) metabolism, obesity, and high blood pressure. In fact, this cluster of abnormalities has been called Syndrome X, and the Deadly Quartet.
Insulin resistance is a reduced sensitivity in the tissues of the body to the action of insulin, which brings glucose into tissues to be used as a source of energy. And, when insulin resistance, or reduced insulin sensitivity, is present the body attempts to overcome this resistance by secreting more insulin from the pancreas. The result of this compensatory physiology: hyperinsulinemia (high insulin levels in the blood) results in the development of Type II, or non-insulin dependent, diabetes because the pancreas eventually fails to sustain this increase insulin secretion. According to Jennifer B. Marks, MD of the University of Miami School of Medicine, insulin resistance contributes directly to abnormalities in blood lipids–cholesterol and triglycerides. (7)
Compensating for IRS is critical as this syndrome is typically characterized by varying degrees of glucose intolerance, abnormal cholesterol and/or triglyceride levels, high blood pressure, and upper body obesity, all independent risk factors for cardiac disease. IRS combined with other stressors, the aging process, a sedentary lifestyle, and genetic susceptibility lead to increased cardiovascular (heart and blood vessels) disease risk. Experts agree that the mere presence of any one major feature alone substantially increases the risk of heart disease, but when they occur together the risk is magnified way out of proportion at the contribution of any one single factor. This was strikingly demonstrated by the PROCAM (Prospective Cardiovascular Munster) Study, in which the relationship between these cardiac risk factors and the incidence of heart attack over a four year period was examined in 2,754 men aged 40-65 years. This comprehensive study demonstrated:
1. the presence of diabetes or high blood pressure alone increased the risk of heart attack by 2.5 times.
2. when both IRS or diabetes and high blood pressure were present, the risk was increased 8 times. An abnormal lipid profile increased the risk 16 times; when abnormal lipid levels were present with high blood pressure and/or diabetes, the risk was 20 times higher.
Most people with IRS or diabetes can be controlled so that they are not at increased risk for the many complications of diabetes such as heart attacks, strokes, blindness, deafness, amputations, kidney failure and burning foot syndrome. Here’s the critical point about IRS:
* Too much insulin constricts arteries to cause heart attacks, and stimulates the brain and liver to increase appetite and manufacture fat.
* IRS puts an individual at very high risk for a heart attack and is associated with storing fat in the belly, rather than the hips; having high blood triglyceride levels and low level of the good HDL cholesterol; high blood pressure and an increased tendency to form clots.
Diabetes can be viewed as advanced IRS. Glucoregulatory substances are controlled by nutrients, mainly because of their influence on gene expression. A breakdown of these homeostatic mechanisms can result from autoimmune destruction of the insulin-secreting beta cells in the Islets of Langerhans as found in juvenile-onset (type-1) diabetes or from a deficit in the production or reception of insulin.
Considering the enormous complexity of IRS and the current lack of effective treatment, it is of critical importance that effective botanical medicines be combined in a way that supports insulin’s function and reception at receptor sites.
IRS causes accelerated molecular and tissue aging by a process called glycation, a process whereby carbohydrate molecules react with protein molecules to form advanced glycation endproducts (AGEs). The buildup of AGEs causes tissue to stiffen and lose elasticity. In fact, glycation causes glucose to react with hemogloblin in the blood, forming hemogloblin A1c, a diagnostic test for diabetes.
As AGEs increase, so does oxidative stress. With oxidative stress, proteins are cross-linked and can cause plague to build up in the circulatory system. Moreover, IRS and its associated higher insulin levels:
1. increase the expression of pro-inflammatory cytokines such as interleukin-1 and interleukin-6, that activate of the arachidonic acid cascade, producing pro-inflammatory 2-series prostaglandins
2. decrease the proper metabolism of essential fatty acids, thereby inhibiting the production of the anti-inflammatory 1-series prostaglandins.
AGEs accumulate in the skin, arteries, kidney, and blood in IRS patients. When the enzyme glucose-6-phosphte dehydrogenase (G6PD) is genetically altered, oxidative stress reactions increase even more. And, to make matters worse, oxidative injury amplifies as antioxidants are not regenerated. Such is the case in the G6PD inactivation of the pentose pathway that allows glutathione (GSH) to be regenerated and nicotinamide-adenine dinucleotide phosphate (NAHPH) to be produced.
GSH acts as a coenzyme to glutathione.insulin transhydrogenase which deactivates excess insulin in the liver and pancreas. (9) Hence, one should be cautious in using supplemental GSH or GSH precursors in advanced IRS or diabetes. Ideally, the Hexose Monophosphate Shunt in the absence of a G6PD deficiency will regenerate GSH stores to ample levels without the need for GSH supplementation.
Taurine, a biliary-conjugating antioxidant, exerts a powerful effect on the normalization of cholesterol. A deficiency leads to impaired taurine conjugation of bile because of a decrease in taurocholic bile salts thus aggravating the IRS effects on EFA metabolism. A zinc-taurine conjugate stabilizes cell membranes and insulin receptors and zinc is a constituent of insulin. It may be that some cases of IRS involve a distortion of insulin receptors due to a zinc or taurine deficiency.
The hormonal pattern in IRS is predominantly androgenic, especially in women. In fact, researchers have reported that insulin levels are a more reliable indicator of body fat deposition that estrogen levels. (10)
Botanical Solutions to IRS
Botanical combinations that modulate gene expression, support glucoregulation, and provide effective nutritional support for pancreatic function are rare in clinical practice. Our experiences supplementing with organic chromium, vanadium and zinc were disappointing as only minimal improvement was noted in a small percentage of IRS patients. After nearly a decade of researching and clinically testing many different combinations of botanical medicines, our clinical research has found the following botanical combination effective in the botanical/nutritional support of IRS patients:
1. Galega officinalis, the botanical name for an herb called goat’s rue, which has been used in Europe for centuries for the treatment of diabetes (this European and Asian plant is totally different from North American goat’s rue which has no effect on insulin). The leaves of this plant contain active ingredients called guanides that are responsible for its antidiabetic effects. It has been the subject of pharmaceutical research but because guanides can’t be patented, pharmaceutical chemists synthesized derivatives called biguanides. Bi-guanides have been patented for use as antidiabetic agents and are found in metformin sold as an insulin sensitizer (Glucophage[R]). Galega officinalis helps to restore insulin sensitivity, regulate blood sugar, and regenerate pancreatic cells, all without the side effects of the drug. However, its anti-diabetic effects are minimal unless it is combined with herbal synergists that address the entire endocrine picture of IRS. (11-14)
2. Cinnamon contains hundreds of constituents, one of which is a polyphenol called methylhydroxychalcone polymer (MHCP). MHCP enhances the function of insulin. Polyphenols inhibit the constriction of blood vessels in CV disease. (15,20)
3. Turmeric–a powerful COX-2 inhibitor and antioxidant. It stimulates glutathione S-transferase and is a strong anti-inflammatory herb that counters the negative biomolecular and biochemical effects of IRS. (20,28)
4. Gurmur means “sugar destroyer” in Ayurvedic Medicine and assists in the regeneration of insulin-producing beta cells. Gymnema Sylvestre has been used in India for more than 2000 years to control the presence of carbohydrates in urine and diabetes. It has also been used as a stimulant, laxative, diuretic, and stomachic, anti-anthelmintic. It decreases the harmful effects of insulin and is used in treatment of obesity and to control glucose level of diabetes. Its regular use will help keep blood sugar level within acceptable limits. It curbs the craving for sugars and acts in the taste buds in the oral cavity as well as in the intestine. It contains Gymnemic Acid and atomic arrangement of gymnemic acid molecules are similar to that of glucose molecules. Gymnemic Acid molecules fill the receptor locations on the taste buds thereby preventing activation of taste buds by sugar molecules present in the food, thus, curbing the sugar craving. Similarly, gymnemic acid molecules fill the receptor location in the absorptive external layers of the intestine thereby preventing the sugar molecules absorption by the intestine which results in low blood sugar level. (16)
5. Guggulipid is used in Ayruvedic medicine practiced in India for centuries. One study entitled “Clinical Trials On Guggulipid: A Hypolipidemic Agent” published in The Journal of Association of Physicians in India in 1989 showed that guggulipid had a very strong effect in decreasing triglycerides (fats) as well as LDL (bad cholesterol) levels while increasing HDL (good cholesterol) levels in human subjects. It has these functional effects because it may cause an increase in thyroid hormone levels (both T4 and T3). The Indian Journal of Medical Research in 1986 documented the fat lowering effects of gugulipid. (14,15) Alterations in the cell membrane lipid composition and membrane fluidity influence hormone transport, hormone responsiveness, and the activity of membrane-bound enzymes and receptors. Since dietary fat intake has been shown to influence the composition of cell membrane phospholipids, Guggulipid can improve insulin action and insulin binding to receptors. (21-22)
6. Bitter Melon–The unripe fruit of Momordica charantia, also known as bitter melon or karela has known anti-diabetic properties and phytochemistry. Clinical studies have documented that it improves glucose tolerance without increasing blood insulin levels. In vivo studies in laboratory animals and in vitro studies of enzmes, tissues, and cells indicate that it acts as an insulin secretagogue and exerts insilinomimetic effects. Bitter melon is rich in steroidal glycosides, insulino-mimetic lectins, alkaloids. (16)
7. Herbal Synergists–Endocrine support of sugar regulation is further achieved by the use of the following herbal synergists: Nettle, mullein, white oak bark, aloe vera (inner leaf extract), opuntia cactus, kelp, Uva ursi, slippery elm, and neem leaves. This proprietary blend of herbs contains phytonutrients that enhance or amplify the effects of the principal botanicals while supporting intracrine, paracrine, and autocrine functions. Moreover, it is rich in organic magnesium which has been shown to significantly increase insulin sensitivity and support the patient with peripheral vascular disease. (23-28)
According to Mark Feinglos, MD “Despite exhaustive efforts to better manage patients with Type 2 diabetes mellitus, attempts at maintaining normal glucose levels in these patients remains unsatisfactory. This continues to pose a real challenge to physicians as the prevalence of this disease in the United States continues to rise.” (12)
Early identification of people who may be at risk for the insulin resistance syndrome–people who are overweight, those who have a parent or sibling with Type II diabetes, women who had diabetes which occurred during pregnancy, or those with poor sugar regulation–is of primary clinical importance in the prevention of associated pathologies. Then, once the syndrome is identified, clinicians would want to look for the presence of other abnormalities. So, if a patient has high blood pressure and is overweight, a search for diabetes and lipid abnormalities should be part of his or her comprehensive evaluation. And, it means prescribing natural treatment (appropriate not just for the primary problem) but treatment which will hopefully benefit, or at least not worsen, any of the other conditions which may also be present. Such an approach provides multiple risk factor intervention–treatment aimed aggressively at reducing all cardiac risk factors which may exist.
The infinitely complex web of insulin and its global functions in the body require the myriad compounds in botanicals that are blended to act in concert with the neuroendocrine system. These neuroendocrine modulators and their multiplicities of herbal actions provide a natural approach to caring for people with insulin resistance syndrome and related peripheral vascular disease. Moreover, this multifaceted approach to risk factor management is essential if we are to meet and overcome the real health danger which accompanies this constellation of IRS abnormalities–cardiovascular disease.
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Paul Yanick, Jr.
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