Acute Hyperglycemia After Influenza Vaccination in a Patient With Type 2 Diabetes

A 41-year-old Caucasian man (height 170.2 cm, weight 101.6 kg) with a history of type 2 diabetes without microvascular complications contacted a pharmacist-led outpatient referral clinic to report elevated blood glucose after receiving a trivalent inactivated influenza vaccine (Seqirus Pty Ltd., Parkville, Victoria, Australia), 0.5 mL intramuscularly. He reported feeling fatigued and groggy 2 hours after vaccination and having a blood glucose level of 264 mg/dL 6 hours after vaccination. The patient’s self-monitoring of blood glucose (SMBG) log entries are depicted in Table 1.

The patient denied any signs and symptoms of infection or changes in diet. He recalled that on the day of vaccination he ate four small blueberry breakfast biscuits (36 g carbohydrates) with a non–sugar-sweetened drink for breakfast, lamb with rice and salad for lunch, and chicken with green beans for dinner. These were typical meals for him.

The patient’s medical history included type 2 diabetes (diagnosed in 2001), gastroesophageal reflux disease, allergic rhinitis, and osteoarthritis. One month earlier, at his regular appointment, his SMBG results averaged 109 mg/dL fasting, 122 mg/dL before lunch, and 124 mg/dL postprandial, all within American Diabetes Association–recommended target ranges (6) (Table 2). Three weeks before his vaccination, the patient had an A1C of 7.2%, blood glucose of 120 mg/dL, serum creatinine of 0.81 mg/dL, and calculated creatinine clearance of 136 mL/min (using the Cockcroft-Gault equation with adjusted body weight of 80.3 kg) (7,8). He reported adherence to his medication regimen, which included glipizide 5 mg twice daily with meals and omeprazole 20 mg every morning. He was not taking any over-the-counter or herbal products. His family history included a father with type 2 diabetes but otherwise nothing contributory.

The patient lives at home with his wife and daughter. He reported social alcohol use only and denied tobacco or illicit substance use.

Hyperglycemia has been reported in post-marketing surveillance of influenza vaccinations. However, several limitations to the VAERS, especially its voluntary nature, result in under-reporting and inconsistencies in reporting. In addition, details related to events vary significantly among reports, with much of the data unconfirmed (9). Because of the nature of these reports, we cannot assume that they all occurred in people with diabetes. However, diabetes is characterized by a loss of homeostatic glucose control secondary to insulin secretory defects and increased resistance; given both the documented loss of homeostatic glucose control and the high frequency of glucose monitoring in people with diabetes, it is likely that most of the reported instances of post-vaccination hyperglycemia would have been in people with diabetes.

Transient fluctuations in blood glucose are multifactorial. In this case presented here, one probable mechanism for the hyperglycemia is stimulation of the immune system resulting in some degree of stress response. Physiologic stress, whether from surgery, infection, injury, or acute illness, has the potential to increase counterregulatory hormone levels. Most notable among these are epinephrine and cortisol, which increase in response to stress and result in elevated blood glucose. People with diabetes are unable to rapidly counteract such elevations in blood glucose. Thus, mild physiologic stressors could potentially lead to observable hyperglycemia.

Our patient’s diabetes was well controlled with sulfonylurea monotherapy, indicating relatively preserved insulin secretion and sensitivity. As observed from the patient’s SMBG results, the influenza vaccine had a substantial hyperglycemic effect that normalized within 72 hours and did not require intervention.

With our analysis of the report revealing no other contributory factors, it seems likely that the observed hyperglycemia was associated with the vaccination. Potential limitations to this conclusion include the absence of blood glucose readings from post-vaccination days 2 to 3 and our reliance on the patient’s SMBG results and verbal recall of diet and medication adherence. However, our patient historically exhibited consistent blood glucose control and was actively involved in his disease management. Based on previous interactions, we have no reason to doubt the information reported to us or the ability of our patient to accurately report this event.

The purpose of this case report is to alert health care professionals about this potential effect, which is not described in vaccine package inserts or commonly used drug databases. We agree with the vaccination recommendations for people with diabetes and believe that the benefit outweighs the risk of transient, acute hyperglycemia. Patient knowledge and involvement remain the cornerstones of diabetes management. Therefore, it is important to educate patients and alleviate concerns that may arise during their routine SMBG, while emphasizing the importance of vaccines. We do not recommend changes in pharmacotherapy or SMBG frequency after vaccination because such changes would place an unnecessary burden on patients. Our hope is that future research may shed more light on this phenomenon and enhance understanding vaccination in people with diabetes for both patients and health care professionals.

No potential conflicts of interest relevant to this article were reported.