There are various types of allergic reactions that we will examine, some of which can have a very profound effect on blood glucose control. The one that can be considered to be part of the normal pathogenesis of diabetes, although not common due to the uses of human DNA insulin, is an allergy to injected insulin.[i] These occurrences have been declining as beef and pork insulins are being replaced.[ii] [iii] Nevertheless this can be a serious problem to those that develop this allergy. Difficulties in blood sugar control and increasing insulin dosages, which progress far more rapidly than the normal pathology of the disease, may be the first symptoms. This may also be accompanied by local injection site irritation with the development of wheals.[iv] Even with some or all of these symptoms present, this condition may still be dismissed by doctors as an expected part of the disease process. While all these suspicions can easily be verified by blood testing for an increase in anti-insulin antibodies, it may take several detours before you arrive at that point. Some of the clues that will lead to this conclusion might be revealed in more common blood testing. A typical complete blood count (CBC) would likely show a definite increase in eosinophil cells, which could denote an allergic response. This result would probably be followed by another blood test for immunoglobulin E (IgE). There are five basic classes of immunoglobulins (IgA, IgD, IgE, IgG and IgM), and a number of different subclasses. They function as specific systemic antibodies in the blood and other body fluids. An elevated IgE value would be a very significant, but not necessarily an inclusive indication of an allergic condition even though it can coincide with an insulin allergy.[v] [vi] Nevertheless, a high value would prompt more investigation, which could lead to allergic testing of a variety of possible allergens. This is when a test for anti-insulin antibodies or specific IgE anti-insulin antibodies should not be overlooked.[vii] There is a common elevation in these values from the uses of injected insulin, but this count will usually be much higher when experiencing this allergy.[viii] [ix] Also, it appears that when anti-insulin antibodies are present to the type of insulin currently being used, they may also be present to other insulins that may have never been used.[x] So, there may be little value in trying to switch to anything other than human insulin, which is the least immuno reactant. Please note that there is a distinct difference between anti-insulin antibodies and auto anti-insulin antibodies. While anti-insulin antibodies are an allergic reaction from injected insulin, auto anti-insulin antibodies are generated from a spontaneous autoimmune response without the interference of exogenous insulin.[xi] This autoimmune reaction is similar in nature to the one that destroys the beta cells in Type I diabetes and it will be discussed in the following chapter.
Now the question is what to do when you have been diagnosed with an anti-insulin allergy? The conventional treatment approach is usually steroids, antihistamines or desensitization therapy. But before you consider any of these therapies it is very important that you conclude what you have is in fact an insulin allergy and not some other related allergy masquerading as an insulin allergy.[xii] Some of the more likely allergens can be the retarding agents used to slow the absorption of insulin. The protamine used in the NPH preparations and the zinc used in the Lente and Ultralente insulins might be at fault, but it appears that a reaction to the protamine is much more common.[xiii] [xiv] The ratio of those that react negatively with NPH insulin as compared with Lente insulins can be as high as 5 to 1.[xv] The other possible reactants include protein impurities or additives in the insulin itself or contaminants in some syringes.[xvi] There have been reports of syringes and pen injectors, which use silicone in their manufacture, causing injection site irritation and local reactions, but again these situations are much less probable of being a cause as compared to NPH insulin. If it is believed that one of the retarding agents is to blame you can switch temporarily to the other or even switch the type of insulin.[xvii] There are two types of synthetic human insulins, Humulin and Novolin. Humulin is based on genetically altered bacteria, while Novolin is produced through a similar process using modified brewers yeast. Although considered identical, there are very subtle differences, which might not provoke an immune response. In fact, the faster acting Humalog (Lispro) insulin shows to be less immuno reactant than Regular insulin, even though they are virtually identical.[xviii] If for any reason you try to replace Regular insulin with Humalog keep in mind that about 30% more Humalog is needed to achieve comparable results of Regular insulin. So, it appears that it may not require dramatic differences in the structure of insulin to deceive the immune system. Sometimes a decrease in the insulin dose alone is enough to correct this condition. Improvement in overall control is not uncommon in some Type II diabetes patients, which reduce large insulin doses. There are probably a number of Type I diabetes patients that would fall into this same category but, their reduction needs to be monitored much more closely. A 5% reduction of the total daily insulin dose would be the best place to begin. I have seen escalating insulin doses create glucose control problems that could only be solved by slowly reducing the insulin dose itself. Even though this method of treatment sounds paradoxical, it often quite effective in certain cases. I would suggest you use the different insulin(s) or doses for no less than a week before making a decision on its effect, unless reasonable glucose control can not be achieved. Other non-invasive treatments that might be beneficial in this situation have been aspirin and vitamin C therapy. The uses of aspirin has been quite successful in its ability to desensitize those with an insulin allergy. One of the studies used 1300 mg of enteric coated aspirin three times a day for a week, but found it necessary to continued the dose for the protective effect.[xix] While aspirin is generally consider safe for adults without gastric ulcers, there are still some safety concerns for its uses in children due to the development of Ryes syndrome. Also, due to the very high dose involved, this type of aspirin therapy should be approached very cautiously. Vitamin C has been emerging as the one vitamin that has been proven to be beneficial in virtually every aliment. It appears that large doses of vitamin C can be helpful in the treatment of both allergies and autoimmune conditions.[xx] It is not exactly clear how vitamin C works in these situations but, it may be through some type antihistamine or anti-inflammatory action. The doses would probably be in the order of ten to twenty thousand milligrams a day of vitamin C for an indefinite period. If these treatments fail to resolve this problem it may require the temporary uses of an antihistamine, corticosteroid or desensitization therapy. The current process of insulin desensitization consists of continuous subcutaneous insulin infusion (CSII).[xxi] [xxii] This is accomplished by slowly increasing very small doses of insulin through injection or infusion on an hourly basis. This treatment is usually very effective in treating an insulin allergy and rarely is there ever need to repeat it, except in extreme cases.
There is a completely different aspect to allergies and how they pertain to diabetes patients than what just has been discussed. I believe that this situation is far more common and effects a large number of diabetes patients possibly without them even knowing it. What I am referring to are environmental allergies that may not exhibit any type of external symptoms normally associated with allergies.[xxiii] The only visible indications that occur are elevated blood sugar values, which may be either sporadic or continuous. These reactions are more than likely caused by food but, they can just as easily be the result of airborne allergens such as molds or pollens. Sometimes something as common as a mosquito bite or insect sting can be to blame, especially in a child.[xxiv] Actually, there are a wide variety of potential allergens that we all come in contact with on a daily basis. The difference is however, how each of our body’s own immune system responds to them. An allergic reaction can invoke local and or systemic physiological response to varying severity. These are inflammatory reactions, which can effect skin, breathing, blood pressure, blood sugar and in severe cases cause anaphylactic shock.[xxv] In a non-diabetes patientwith only minimal reactivity to a substance, an allergic reaction can go completely unnoticed. This is because an uncompromised regulatory system can compensate for these minor fluctuations. While in a diabetic, the inability to facilitate these corrective actions due to a greater load on the endocrine system may only result in hyperglycemia. These increased blood sugar values are often dismissed as part of the normal difficulties of controlling a diabetic, but there is always an explanation for hyperglycemia if you chose to find it. But if you are experiencing continual blood sugar control problems and have ruled the amount of food, insulin or oral hypoglycemics dose and hypoglycemic rebounds not to be the problem, you must consider what else could be involved. Normal hormonal releases can account for fair percentage of unexplained glucose spikes in Type I diabetes patients and possibly some Type II diabetes patients. But above the normal basal amounts of hormonal excretions, which should already be adjusted for in your daily treatment, most hormonal spikes are transient. They can appear at any time and usually last several days to a week and in some cases slightly longer. So while hormone releases can be an annoying problem they should not be a chronic one, except during puberty. When investigating a problem like this the next logical place to examine are the things that come in constant exposure with the person. This leads us back to food and environment. A food induced allergic reaction could possibly raise blood sugar by elevating IgE and also by increasing histamine levels.[xxvi] These reactions may translate into high postprandial blood sugar reading or they can take place many hours from the time of consumption making it difficult to determine the cause. A rotation or elimination diet might be helpful in determining the exact culprit. Keep in mind while I use the term food, it can be an additive in a particular type of food that is actually causing the problem. There are literally thousands of different preservatives, colorings, stabilizers, flavorings and antioxidants used in practically every kind of food, any of which has the potential of causing a reaction.[xxvii] Dyes and colorants have been notorious for causing allergic reactions. They have also been implicated in the development of asthma and attention deficit hyperactive disorder (ADHD).[xxviii] [xxix] Colorings like carmine (red E120), tartrazine (yellow No. 5), annatto (orange-yellow) and some different shades of blue have been proven to provoke allergic and asthmatic attacks.[xxx] [xxxi] [xxxii] [xxxiii] Also, some of these dyes are actually derived from natural sources, so just because it is natural does not make it hypoallergenic. Be aware that these dyes and flavorings have also found their way into both prescription and over the counter drugs.[xxxiv] Adverse reactions have also been reported from the ingestion of preservatives like butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), nitrates, and sulfites, and from benzoates and monosodium glutamate (MSG) additives.[xxxv] [xxxvi]
The reason why some diabetes patients might be more prone to these allergies than others may be due to a genetic predisposal. There may be a direct link between food and pollen allergies and Type I diabetes. The first of these studies suggest a connection between food allergies and autoimmune reactions like those that are involved in the development of Type I diabetes.[xxxvii] It points to a hypersensitivity to certain proteins in wheat, rye, barley and soy that may act as trigging agents. Another study shows a possible relationship between pollen and food allergies and specific human leukocyte antigens (HLA).[xxxviii] The significance here is that some of the HLA’s, common in these allergies, appear to be the same ones that might be linked to the development of Type I diabetes. Other ways allergens can pose a problem is when they enter through the nasal or respiratory tract. Usually this will invoke a defensive response with the secretion of mucus. The constant filling of the nasal and sinus cavities with mucus combined with elevated blood sugars of diabetes can create an ideal environment for bacterial or fungal infections.[xxxix] [xl] Nasal allergy reactions can also alter the function of the eustachian tubes, which can increase the incidents of ear infections.[xli] If these types of infections reoccur frequently they can development into a more chronic format. Chronic infections such as these may not manifest any physical symptoms, nor will their effects necessarily appear on routine blood tests. It may require more in depth blood testing or a CT scan to locate the cause. Also, continually using antibiotics to combat these infections can create the condition of antibiotic resistance. As an alternative to antibiotics and if detected in time, immediate uses of the herb echinacea might be able to curtail the infection.[xlii] [xliii] Echinacea is an extremely safe and effective immune system stimulant, which demonstrates both antibacterial and antiviral properties.[xliv] This makes echinacea work equally as well in treating the cold and flu viruses.[xlv] Regardless of what pathologies were involved in development of allergies the condition still must be addressed. Avoidance is the best approach when possible, but it is not always practical in every situation. Conventional treatments are the typical uses of drugs including antihistamines, steroids, and of coarse the allergy shot. There are a wide variety of alternative treatments available for allergies. When food allergies are under investigation one of the first places to start is the digestion system. In some cases decreased production of stomach acid (HCL) or digestive enzymes can cause incomplete digestion of food that might get released into the bloodstream resulting in a reaction.[xlvi] If this condition is diagnosed an oral digestive supplement should be helpful. The uses of probiotics, such as various types of lactobacillus, has been successful in treating imbalances in intestinal flora that could lead to allergic reactions.[xlvii] There are a host of herbs used like feverfew, triphala and goldenseal, just to name a few, to treat allergies but, it is better to identify the particular allergen first to make a more specific herb selection to achieve the desired effect.[xlviii] Other treatments like high dose vitamin C and pollen immunotherapy have proven beneficial in reducing allergic reactions.[xlix] [l] One of the most remarkable therapies I have seen in the treatment of allergies is the Nambudripad Allergy Elimination Technique or NAET. Dr. Devi Nambudripad created a unique treatment that is able to completely eliminate allergies non-invasively. NAET utilizes several other disciplines; kinesiology, chiropractic, acupuncture and acupressure. The treatment begins with muscle testing with specific allergens, then through in uses of primarily acupressure techniques at certain acupuncture points each allergen is addressed and its effect nullified. The patient has to remain free from exposure to this allergen for 24 hours for this treatment to be permanent. The only problem with this therapy is that it can only remove one allergen at a time. There are a number of specially trained chiropractors across the country which offer this treatment.
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.
——————————————————————————–[i] Ross J. Allergy to insulin. Pediatr Clin North Am 1984 Jun;31(3):675-87. [ii] Ganz MA, Unterman T, Roberts M, Uy R, et al. Resistance and allergy to recombinant human insulin.
J Allergy Clin Immunol 1990 Jul;86(1):45-51.[iii] Linana JJ, Montoro FJ, Hernandez MD, Basomba A, et al. Adverse reactions to insulin. An Med Interna 1997 Jul;14(7):369-72. [iv] Tokarska L, Dziatkowiak H, Nizankowska E. Allergy to insulin. Pol Tyg Lek 1994 Jan 3-17;49(1-3):39-42. [v] Madacsy L, Feher A, Kassay L. High IgE levels in diabetes patientchildren without atopy or insulin allergy. Acta Paediatr Hung 1987;28(3-4):209-13. [vi] Velcovsky HG, Federlin KF. Insulin-specific IgG and IgE antibody response in type I diabetes patientsubjects exclusively treated with human insulin (recombinant DNA). Diabetes Care 1982 Nov-Dec;5 Suppl 2:126-8. [vii] Petersen KG, Khalaf A, Naithani V, Gattner H, Kerp L. Diabetes Res Clin Pract 1989 Jun 20;7(1):41-6. [viii] Frechtel G, Cardoso AI, Llera AS, Poskus E, Alonso A, Ruiz M. A case of allergy to human insulin associated with high IgG/IgE ratio for specific antibodies. J Investig Allergol Clin Immunol 1994 Nov-Dec;4(6):320-3. [ix] Child DF, Johansson SG. IgE antibody studies in a case of generalized allergic reaction to human insulin. Allergy 1984 Nov;39(8):630-3. [x] Tosoni C, Cattaneo R, Valentini U, Rocca L, et al. Prevalence and clinical meaning of insulin-specific IgE antibodies. Medicina 1990 Oct-Dec;10(4):396-8. [xi] Sodoyez JC, Koch M, Sodoyez-Goffaux F. Insulin antibodies: methodology and clinical implications. Diabete Metab 1991 Mar-Apr;17(2):255-69. [xii] Kim R. Anaphylaxis to protamine masquerading as an insulin allergy. Del Med J 1993 Jan;65(1):17-23. [xiii] Dykewicz MS, Kim HW, Orfan N, Yoo TJ, Lieberman P. Immunologic analysis of anaphylaxis to protamine component in neutral protamine Hagedorn human insulin. J Allergy Clin Immunol 1994 Jan:93(1 Pt 1):117-25. [xiv] Takatsuki H, Ishii H, Yamauchi T, Nakashima N, et al. A case of insulin allergy: the crystalline human insulin may mask its antigenicity. Diabetes Res Clin Pract 1991 May;12(2):137-9. [xv] Nell LJ, Thomas JW. Frequency and specificity of protamine antibodies in diabetic and control subjects. Diabetes 1988 Feb;37(2):172-6. [xvi] Grammer L. Insulin allergy. Clin Rev Allergy 1986 May;4(2):189-200. [xvii] Plantin P, Sassolas B, Guillet MH, Tater D, Guillet G. Cutaneous allergic accidents caused by insulin. Current aspects apropos of 2 cases. Ann Dermatol Venereol 1988;115(8):813-7. [xviii] Kumar D. Lispro analog for treatment of generalized allergy to human insulin. Diabetes Care 1997 Sep;20(9):1357-9. [xix] Holdaway IM, Wilson JD. Cutaneous insulin allergy responsive to oral desensitisation and aspirin.
Br Med J 1984 Dec 8;289(6458):1565-6.[xx] Kodama M, Kodama T. Vitamin C and the genesis of autoimmune disease and allergy (review). In Vivo 1995 May-Jun;9(3):231-8. [xxi] Spijker AJ, Poortman J, Thijssen JH, Erkelens DW. Decrease of circulating insulin antibodies in two patients treated with continuous subcutaneous infusion of human insulin (recombinant DNA). Diabetes Care 1982 Nov-Dec;5 Suppl 2:171-4. [xxii] Nagai T, Nagai Y, Tomizawa T, Mori M. Immediate-type human insulin allergy successfully treated by continuous subcutaneous insulin infusion. Intern Med 1997 Aug;36(8):575-8. [xxiii] Coombs RR, McLaughlan P. Allergenicity of food proteins and its possible modification. Ann Allergy 1984 Dec;53(6 Pt 2):592-6. [xxiv] Korman SH, Jabbour S, Harari MD. Multiple hornet (Vespa orientalis) stings with fatal outcome in a child. J Paediatr Child Health 1990 Oct;26(5):283-5. [xxv] Moneret-Vautrin DA, Kanny G. Food hypersensitivities. Rev Prat 1996 Apr 15;46(8):961-7. [xxvi] MacDonald SM, Lichtenstein LM. Histamine-releasing factors and heterogeneity of IgE. Springer Semin Immunopathol 1990;12(4):415-28. [xxvii] Simon RA. Adverse reactions to food additives. N Engl Reg Allergy Proc 1986 Nov-Dec;7(6):533-42. [xxviii] Boris M, Mandel FS. Foods and additives are common causes of the attention deficit hyperactive disorder in children. Ann Allergy 1994 May;72(5):462-8. [xxix] Miller ME, Lummus ZL, Bernstein DI. Occupational asthma caused by FD&C blue dye no.2. Allergy Asthma Proc 1996 Jan-Feb;17(1):31-4. [xxx] Acero S, Tabar AI, Alvarez MJ, Garcia BE, et al. Occupational asthma and food allergy due to carmine. Allergy 1998 Sep;53(9):897-901. [xxxi] Dipalma JR. Tartrazine sensitivity. Am Tam Physician 1990 Nov;42(5):1347-50. [xxxii] Mikkelsen H, Larsen JC, Tarding F. Hypersensitivity reactions to food colours with special reference to the natural colour annatto extract (butter colour). Arch Toxicol Suppl 1978;(1):141-3. [xxxiii] Chadwick BL, Hunter ML, Evans MT, Hunter B. Allergic reaction to the food dye patent blue. Br Dent J 1990 May 19;168(10):386-7. [xxxiv] Kumar A, Rawlings RD, Beaman DC. The mystery ingredients: sweeteners, flavorings, dyes, and preservatives in analgesic/antipyretic, antihistamine/decongestant, cough and cold, antidiarrheal, and liquid theophylline preparations. Pediatrics 1993 May;91(5):927-33. [xxxv] Wuthrich B. Adverse reactions to foods additives. AnnAllergy 1993 Oct;71(4):379-84. [xxxvi] Goodman DL, McDonnell JT, Nelson HS, Vaughan TR, Weber RW. Chronic urticaria exacerbated by the antioxidant food preservatives, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). J Allergy Clin Immunol 1990 Oct;86(4 Pt 1):570-5. [xxxvii] Kitts D, Yuan Y, Joneja J, Scott F, et al. Adverse reactions to food constituents: allergy, intolerance, and autoimmunity. Can J Physiol Pharmacol 1997 Apr;75(4):241-54. [xxxviii] Boehncke WH, Loeliger C, Kuehnl P, Kalbacher H, Bohm BO, Gall H. Identification of HLA-DR and –DQ alleles conferring susceptibility to pollen allergy and pollen associated food allergy. Clin Exp Allergy 1998 Apr;28(4):434-41. [xxxix] Hanson LA, Soderstrom R, Avanzini A, Bengtsson U, et al. Immunogloblin subclass deficiency. Pediatr Infect Dis J 1988 May;7(5 Suppl):S17-21. [xl] Dockhorn RJ. Clinical studies of food allergy in infants and children. Ann Allergy 1987 Nov;59(5 Pt 2):137-40. [xli] Bernstein JM. The role of IgE-mediated hypersensitivity in the development of otitis media with effusion. Otolaryngol Clin North Am 1992 Feb;25(1):197-211. [xlii] Barrett B, Vohmann M, Calabrese C. Echinacea for upper respiratory infection. J Fam Pract 1999 Aug;48(8):628-35. [xliii] Wustenberg P, Henneicke-von Zepelin HH, Kohler G, Stammwitz U. Efficacy and mode of action of an immunomodulator herbal preparation containing Echinacea, wild indigo, and white cedar. Adv Ther 1999 Jan-Feb;16(1):51-70. [xliv] Brinkeborn RM, Shah DV, Degenring FH. Echinaforce and other Echinacea fresh plant preparations in the treatment of the common cold. A randomized, placebo controlled, double-blind clinical trial. Phytomedicine 1999 Mar;6(1):1-6. [xlv] Henneicke-von Zepelin H, Hentschel C, Schnitker J, Kohnen R, et al. Efficacy and safety of a fixed combination phytomedicine in the treatment of the common cold (acute viral respiratory tract infection): results of a randomised, double blind, placebo controlled, multicentre study. Curr Med Res Opin 1999;15(3):214-27. [xlvi] Ciprandi G, Canonica GW. Incidence of digestive diseases in patients with adverse reactions to foods. Ann Allergy 1988 Nov;61(5):334-6. [xlvii] Goldin BR. Health benefits of probiotics. Br J Nutr 1998 Oct;80(4):S203-7. [xlviii] Bielory L, Lupoli K. Herbal interventions in asthma and allergy. J Asthma 1999;36(1):1-65. [xlix] Kodama M, Kodama T. Vitamin C and the genesis of autoimmune disease and allergy (review). In Vivo 1995 May-Jun;9(3):231-8. [l] Kelso JM, Jones RT, Tellez R, Yunginger JW. Oral allergy syndrome successfully treated with pollen immunotherapy. Ann Allergy Asthma Immunol 1995 May;74(5):391-6.