No overall risk between antibiotic exposure and LADA

The triggers for the autoimmune reaction preceding latent autoimmune diabetes in adults (LADA), apart from heritability, remain unclear. Antibiotic use has been suggested as a potential trigger. Evidence links frequent antibiotic use to an increased risk of childhood-onset type 1 diabetes in some studies, though others report no association. For type 2 diabetes, higher antibiotic doses, more frequent use, and longer durations have been associated with an increased risk. Therefore, the authors wanted to investigate whether antibiotic exposure is associated with an increased risk of developing latent autoimmune diabetes in adults or type 2 diabetes.

Researchers used data from the ESTRID study, Sweden (LADA: n=597, type 2 diabetes: n=2065, matched controls: n=2386) and the HUNT study, Norway (LADA: n=82, type 2 diabetes: n=1279, matched controls: n=2050). Antibiotics were categorized as broad-spectrum, narrow-spectrum, or a combination of both. Phenoxymethylpenicillin was the most dispensed antibiotic in both ESTRID and HUNT cohorts. Antibiotic dispensations from 1–5 years prior to the index date were analysed, with the index date defined as the diagnosis or participation date in ESTRID and the diagnosis year in HUNT. Exposure windows were categorized into 0 to <1, 1–5, 6–10, and 0–10 years before the index date. Antibiotic exposure was assessed based on the number of prescriptions, duration of consecutive use, and cumulative exposure days, calculated using the dispensed quantity and defined daily dosage (DDD). Cumulative exposure data were only available for ESTRID due to data limitations in HUNT. 

The study found no overall increased risk of LADA associated with exposure to antibiotics in the year prior to diagnosis (OR 1.15) or within one to five years before diagnosis (OR 0.98). However, an elevated risk for LADA was observed for individuals exposed to narrow-spectrum antibiotics 6–10 years prior to diagnosis (OR 1.39), a result driven by the Swedish data. No link was found between antibiotic exposure and type 2 diabetes risk within a similar timeframe.

These findings suggest that while broad-spectrum antibiotic use is not associated with increased LADA risk, narrow-spectrum antibiotic exposure might warrant further investigation. The study highlights the need for more research to understand potential long-term effects of certain antibiotics on autoimmune diabetes risk.

First author of the study is Jessica Edstorp, who completed her doctoral degree in the ESTRID group.

Publication

Exposure to antibiotics and risk of latent autoimmune diabetes in adults and type 2 diabetes: results from a Swedish case-control study (ESTRID) and the Norwegian HUNT study.
Edstorp J, Rossides M, Ahlqvist E, Alfredsson L, Askling J, Di Giuseppe D, Grill V, Sorgjerd EP, Tuomi T, Åsvold BO, Carlsson S
Diabetologia 2024 Oct;():