Insulin Resistance: More Drugs MAY not be the answer

By Dr. Brian P. Jakes, Jr.

Insulin resistance is the opposition to insulin at insulin receptor sites on cells located throughout the body. Even if both glucose and insulin are present outside a cell, they cannot permeate the cell membrane effectively. As long as there is an ample supply of insulin and enough functional receptor sites euglycemia can be maintained.

 If either is detrimentally affected hyperglycemia will result. While insulin resistance is primarily associated with Type II diabetes, it has also been implicated in the development of several other conditions.

Insulin resistance and its compensatory hyperinsulinemia appears to be involved in the alteration and elevation of blood pressure, triglycerides and weight.[i] These factors can increase the incidence of hypertension, atherosclerosis, obesity and cardiovascular disease.[ii]  This group of symptoms are referred to as the insulin resistance syndrome or Syndrome X.[iii] 

The action of either stimulating or supplementing insulin through the uses of oral hypoglycemics or injections is truly not a viable treatment and can actually increase resistance[iv] The findings from recent studies might help explain why there are so many complications experienced by Type II diabetes patients.

Type 1 diabetes patients do not appear to be as severely affected by the many forms in which insulin resistance can manifest itself.[v] Usually, their insulin resistance is secondary and is confined to the effects of exogenous insulin injections. Anti-insulin antibodies can develop and render some portion of the injection ineffective, but this amount varies from person to person. Another factor is the nullifying action counterregulartory hormones exert on receptor sites.[vi] These hormones affect both types of diabetes, but usually appear more frequently in Type I diabetics.    Growth hormone, cortisol and epinephrine can cause transient incidents; however, these hormone releases can temporarily devastate blood sugar control in Type I diabetes.

The normal reaction to this is an additional injection of insulin to counter this effect. This is an appropriate response, but sometimes these hormone releases are so severe that even additional insulin may not lower blood sugar. In fact, even with extra insulin blood sugar can still go up.  

This may be a very vivid example of the difficulties in overcoming continued insulin resistance as seen in Type II diabetes. It does not matter how much insulin is available when cells are inhibited from absorbing it.

Obesity and chronic hyperglycemia itself can also impair insulin function in Type I diabetics. 

Type II diabetes is where the occurrences of all of the above conditions are considerably more prevalent. One of the most divisive issues among conventional diabetes researchers and practitioners is whether insulin resistance the primary cause and problem of Type II diabetes. The process of reviewing most of the available evidence makes it difficult to come to another conclusion.[vii] [viii] [ix] [x] [xi]

Until 6 years ago, the only available FDA approved treatments for Type II diabetes were insulin and sulfonylurea hypoglycemics. Giving these to Type II diabetes patients for their condition is effective at first. As hyperglycemia caused by insulin resistance promotes hyperinsulinism, the elevated production and levels of serum insulin will occur.[xii] [xiii] [xiv]

Your body has recognized the high glucose as a problem and has tried to compensate by producing more insulin, but it is ineffective. In fact, recent research is revealing not only a condition of hyperinsulinemia, but hyperproinsulinemia.[xv] [xvi] One theory is that, the over stimulation the beta cells are pumping out a larger percentage of insulin released in premature proinsulin form, which cannot be utilized by cells.

When drug treatment is added you have insulin resistant cells being bombarded with even more insulin they cannot utilize. Studies show that from either of these situations eventually cell receptor sites become more resistant to insulin.[xvii] It is similar to becoming desensitized from the effects of a drug from the repeated uses or abuse of it.

Another controversial issue is; does insulin resistance and or sulfonylurea uses cause pancreatic hyperstimulation that leads to beta cell failure and decreased insulin output in Type II diabetes? I think the overwhelming evidence points to yes. There is a decrease in beta cell function and mass in Type II diabetics as the disease progresses (http://www.diabetesincontrol.com/features/feature55.htm) The actual causes whether it be hyperstimulation, autoimmune or genetic factors have been debated for years.[xviii] [xix]

There are a few studies pointing to genetic or autoimmune involvement in beta cell failure, but there are significantly more favoring exhaustion.[xx] [xxi] [xxii] [xxiii] Simply put hyperstimulation and continual demand without periods of rest in between to heal and repair leads to failure in numerous biological examples.

Taking a drug that continually stimulates more insulin production exacerbates both the insulin resistance condition and pancreatic function causing premature failure of beta cells. There are several studies that seem to support this theory.

When beta cells in diabetes patients are rendered inactive from a drug treatment, i.e. diazoxide, output from insulin stores increase after drug removal.[xxiv] [xxv] Likewise, it appears that when beta cells are not required to produce insulin due to sufficient exogenous insulin injection they have an opportunity to rest and recover.[xxvi] [xxvii]

Short term insulin therapy may be a strategy used to restore partial insulin secretion in a pancreas that has been exhausted by the uses of oral hypoglycemics.

 Although the causes of insulin resistance in Type II diabetes is not fully elucidated, there appears to be various genetic predispositions that affect a considerable number of Type II patients.[xxviii] [xxix] [xxx] 

Research shows that there is a mutation in insulin receptor genes in some diabetics that could promote endogenous insulin resistance.[xxxi] Defects at insulin receptor sites have been shown to nullify the effects of insulin and cause glucose intolerance and insulin resistance.[xxxii]

The development of anti-insulin receptor anti-bodies that again interfere with the function of insulin at receptor sites has been demonstrated.[xxxiii] [xxxiv] Another study points to a decrease in growth hormones at critical times of development.

One area of research that has been given considerable attention is the investigation of insulin like growth factor 1 (IGF-1). A number of clinical trials with IGF-1 have yielded promising results in the areas of decreasing insulin resistance and possibly improving some diabetic complications in both types of diabetics.[xxxv] [xxxvi] [xxxvii] The problems associated the IGF-1 treatment is that there were side effects significant enough to cause some participants to discontinue therapy. Also, IGF-1 must be administered through daily multiple subcutaneous injections.

Interestingly, there appears some connection between a zinc deficiency and low levels of endogenous IGF-1. Both types of patients are known to excrete abnormal amounts of zinc in their urine, supporting evidence of a deficiency. Supplementation of zinc has been shown to increases IGF-1 levels in several studies.[xxxviii]

Hepatic glucose production is another condition that affects both types of diabetes. The liver controls the amount of glucose production, which is primarily based on insulin availability. As insulin levels increase, hepatic glucose output (HGO) decreases and the inverse is also true.[xxxix]

The outcome in this situation causes the same end results in either type of diabetes, but through different means. Inadequate insulin treatment in Type I will cause a increase in HGO that can only be suppressed by additional insulin injections. While Type II patient usually have sufficient insulin levels, there appears to be environmental influences that interferes with hepatic signaling.

 Vanadyl sulfate, a trace mineral, has shown positive effects in suppressing excessive HGO. The role of free fatty acids (FFA) may help to explain in part the direct environmental link to Type II diabetes.[xl] [xli] FFA's are one of the products of metabolism from dietary fat intake. Elevated serum levels of FFA's seem to inhibit glucose uptake in muscles and fat tissue in a dose dependant fashion that results in insulin resistance.[xlii] [xliii]

This in turn causes an interruption in the normal pathways that allows HGO to go unregulated again causing hyperglycemia.[xliv] Obesity can in itself cause insulin resistance.[xlv] [xlvi]  Exercise is a very effective way to decrease insulin resistance.[xlvii]

Studies using chromium have demonstrated its ability to possibly reduce insulin resistance without any type of adverse side effect. Several herbs have been successful in decreasing insulin resistance and improving glucose tolerance.

 The development of Type II diabetes is multifactoral. These studies begin to help to explain why, for example, only some obese people develop diabetes. Even in the non-diabetic obese there is increased insulin demand to support the additional fat in which constitutes the majority of the weight, but this alone does not cause diabetes. On the other hand, there are otherwise healthy individuals of normal or even below normal weight that develop Type II diabetes.

The common link must be a genetic predisposition that may or may not require an environmental influence to set the disease in motion, but would more than likely accelerate the process.

The use of a registered dietitian, CDE and Physical Trainer can help your patient overcome their insulin resistance.

Dr. Brian P. Jakes, Jr., N.D., C.N.C.  is a Board Certified Doctor of Naturopathy as well as a Certified Nutritional Consultant. In his practice, in Mandeville, LA, Dr. Jakes works with physicians to treat a large number of diabetes patients. This is an excerpt from his upcoming book; "Diabetes: The Essence Of A Cure”

  Click Here For Printable Version