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January 17, 2023



Allergies are the immune responses to substances that are not generally harmful. These substances are known as allergens which can cause allergic reactions by skin contact (poison plants, animal scratches, pollen and latex, some cosmetics), injection (bee sting), ingestion (nuts & shellfish, some foods), and inhalation (pollen, dust, molds and mildew, animal dander (skin flares/fur/hair)). The common symptoms of allergies are dry cough, itchy and watering eyes, a sore throat, sneezing, running nose, and throat clearing. Severe allergies can cause hives, rashes, breathing problems, asthma, and changes in blood pressure.


Allergic reactions are classified into four types: 

  • Type I: Anaphylaxis, wheal, and flare. These are Immunoglobulin E (IgE) antibody-mediated allergic reactions 
  • Type II: Erythema (skin redness), edema (puffiness in the skin due to accumulation of body fluids). These are cytotoxic reactions mediated by Immunoglobulin G (IgG) or Immunoglobulin M (IgM) antibodies 
  • Type III: These are immune complex-mediated allergic reactions 
  • Type IV: Erythema and induration. These are delayed reactions mediated by cellular immunity 


According to statistics, 0.1–3% of insulin-treated diabetics are affected by insulin allergy. The symptoms may be localized itching and rash to severe anaphylaxis. Anaphylaxis is defined as a serious, life-threatening hypersensitivity reaction that rapidly develops as a multi-organ allergic reaction. Both type 1 and type 2 diabetic patients show insulin-related hypersensitive reactions. 


Three types of reactions – localized reaction, systemic/generalized reaction, and insulin resistance – are associated with insulin allergy.

  • Localized reactions: These are presented as a 'wheal and flare' appearance, which appears as redness of skin occurring within 30 minutes of insulin administration, and lasts for about 2 hours. Localized reactions might be IgE-mediated.
  • Systemic reactions: These are rare and serious reactions associated with symptoms such as generalized urticaria (hives; raised itchy skin rashes), nausea, angioedema (painless swelling under the skin), asthma, hypotension (low blood pressure), cardiac risks, gastrointestinal cramps, bronchospasm (narrowing of airways of lungs) and shock.
  • Insulin resistance: It is a rare allergic reaction but may develop if insulin antibodies (IgG) nullify the effects of administered insulin, leading to hyperglycemia (raised blood sugar levels), thereby requiring very large insulin doses. Insulin resistance increases the risk of the individual developing long-term complications of diabetes and management can be challenging.

Symptoms of early reactions

Early hypersensitivity reactions are mediated by IgE- or IgG antibodies varying from local reactions to serious anaphylaxis. Early reactions might occur within minutes or an hour after insulin injection. The common symptoms of early reactions include rapidly developing erythema at the injection site, local urticaria (hives-itchy blisters and rash), angioedema, diarrhea, and cardiovascular symptoms that can also occur as hypotension and anaphylaxis.

Symptoms of late reactions

Late reactions generally develop with Type III and Type IV immune reactions. Type III reactions are non-erythematous (occurring without skin redness) reactions developing within 6–8 hours and lasting until 48 hours after the injection. Type IV reactions usually occur after 24 hours and last 4–7 days, generally characterized by nodules.


Primary approach

The skin prick test (SPT) and intracutaneous test (ICT) are the traditional methods of evaluating insulin allergy. The measurement of total IgE, insulin-specific IgE, and anti-insulin antibodies (IgG) in addition to SPT or ICT is advised. For IgE-mediated reactions, SPT and IgE antibody measurements are required. However, erythema and induration are IgG-mediated allergic reactions for which anti-insulin IgG titers should be measured. The patient's history should include the assessment of the specific symptoms following injection if symptoms are systemic, concurrent drugs, the presence of chronic urticaria, and if previously used insulin preparations were well-tolerated. 

Differential diagnosis

Differential diagnosis is generally advised for acute and chronic urticaria. The patient's history should include concomitant medications, infections, and physical stimuli. Diseases such as psoriasis and atopic dermatitis should be considered. 


Allergy medicines such as decongestants, antihistamines, steroids, and allergen immunotherapy might affect blood sugar levels. 

The Counter (OTC) Allergy Medicine

Many OTC sprays, syrups, chewable, capsules, cough drops, and pills are laden with sugar, artificial colors, and flavors. So it is advised to check labels for sugar-free, blood pressure-friendly allergic medicine that will help control your symptoms.


Anti-histamines are used specifically to treat nasal congestion, sneezing, irritated throat, hives, or runny, itchy eyes. Anti-histamines should be avoided in diabetic patients unless recommended by the physician as these agents can cause drowsiness and people might fall asleep and miss a meal causing hypoglycemia or low blood sugar.


Decongestants can cause constriction/tightening of blood vessels which raises blood pressure.


  • A careful patient history before re-initiating insulin therapy after the stoppage, especially a history of allergies such as drug allergies and previous treatment with insulin 
  • Recording the time passed between the administration of insulin and the start of the reaction, a precise description of the reaction episode, the treatment used, and tolerability of the treatment. 
  • Skin and blood tests to identify the specific allergen(s) (if required) 
  • Switching to a different insulin brand and observing the response 
  • Desensitization under supervision with resuscitation equipment available (if needed) 
  • Inspecting the insulin injection technique and the insulin sites.

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