In a recent study published in Vaccines, researchers reported that Pfizer’s BNT162b2 vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) does not affect the honeymoon phase of type 1 diabetes (T1D).

Study: BNT162b2 mRNA COVID-19 Vaccine Does Not Impact the Honeymoon Phase in Type 1 Diabetes: A Case Report. Image Credit: Maria Kaminska/Shutterstock

Diabetes has been considered a risk factor for coronavirus disease 2019 (COVID-19) morbidity and mortality. Although existing COVID-19 vaccines have significantly reduced morbidity and mortality, numerous reports of vaccination-induced hyperglycemia (ViHG) and other associated complications have surfaced.

Various studies have reported that some T1D patients experience a transient instability of blood glucose levels following COVID-19 vaccination, which resolves in a few days. However, the impact of SARS-CoV-2 vaccination on the clinical remission phase of T1D, known as the honeymoon phase, remains unclear.

The study and findings

In the present study, researchers described the case of a T1D patient who received the BNT162b2 vaccine during the honeymoon phase. The subject was a 24-year-old Italian man diagnosed with T1D in July 2020 after severe hyperglycemia with moderate diabetic ketoacidosis (DKA) requiring hospitalization.

The patient was initially treated with intravenous insulin and subcutaneous insulin after DKA resolution. A nutrition specialist prescribed a Mediterranean diet (1.8-kilo calories/day). The patient was discharged after five days of admission. The total daily insulin dose was reduced progressively at outpatient follow-up visits due to frequent fasting and postprandial hypoglycemic episodes.

Low-dose basal insulin was maintained after 30 days. The subject underwent a mixed meal tolerance test (MMTT) two months after DKA onset and hyperglycemia resolution. The fasting connecting peptide (C-peptide) value was 0.74 ng/ml, and the peak value was 2.95 ng/ml. The patient already transitioned to the honeymoon phase, indicated by an insulin dose-adjusted hemoglobin A1c (IDAA1c) [a marker for clinical remission of T1D] value of 5.66.

Laboratory tests such as complete blood count, lipid profile, markers of liver, thyroid, and kidney function markers, and those of celiac disease and thyroid autoimmunity were unremarkable. Fourteen months after T1D diagnosis, during a follow-up MMTT, the subject showed preserved residual beta-cell function.

The case was still on a low insulin dosage. The subject received the first BNT162b2 vaccine on December 13, 2021, and the second on January 3, 2022. After the first dose, the patient experienced deteriorating glucose control; that is, the frequency of postprandial hyperglycemic episodes increased moderately, and this trend was particularly aggravated after the second vaccination. This prompted the resumption of mealtime insulin injections for a week.

Ambulatory glucose profile was obtained from subcutaneous glucose sensor at 1) 21 days pre-first vaccination, 2) 21 days post-first dose, 3) 21 days post-second dose, and 4) 42 days post-second vaccination. The authors noted that glucose control deterioration ensued from vaccination, particularly more evident after administering the second dose.

No significant episodes of hypoglycemia were observed during the follow-up visits, and no adverse events occurred after the first or second vaccination. During an MMTT three months after the second vaccination, that is, 19 months post-T1D onset, the authors unexpectedly observed that the patient was still in the honeymoon phase. This was confirmed by an IDAA1c value of 6.1. There were no substantial changes in the residual endogenous insulin secretion or daily insulin requirements.

Chemiluminescent microparticle immunoassay was performed three months post-administration of the second dose. It revealed the presence of high anti-SARS-CoV-2 neutralizing immunoglobulin G (IgG) antibody titers and the absence of neutralizing IgM antibodies, indicating that the humoral antibody response against SARS-CoV-2 was robust following a two-dose regimen.


The authors reported that vaccination with two doses of the BNT162b2 vaccine does not negatively impact the honeymoon phase or the function of residual beta cells. Vaccination caused only a temporary ViHG without significantly influencing the course of the honeymoon phase. The vaccine did not trigger or exacerbate islet autoimmunity. These results may encourage SARS-CoV-2 vaccination among T1D patients during their honeymoon phase and help overcome the vaccine skepticism observed in many such patients.

Nevertheless, it is critical to delineate in large prospective studies the immunometabolic impact and safety of the vaccine in T1D patients during the honeymoon phase. The researchers suggested that T1D patients should be appropriately counseled about the possibility of transient ViHG and strictly surveilled post-vaccination during outpatient visits.

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