Risk of Latent Autoimmune Diabetes in Adults Not Influenced by Infectious Disease Exposure

Jessica Edstorp, MA, MSc

Credit: Karolinska Institutet

Findings from a recent study are dispelling speculation of the association between exposure to infectious disease and risk of latent autoimmune diabetes in adults (LADA).

Despite its genetic and pathophysiological similarities to type 1 diabetes, which is known to be influenced by exposure to infections, results showed infectious disease did not increase the risk of LADA.¹

“Previous studies have primarily or exclusively addressed infections and type 1 diabetes with onset during childhood. Whether infections in adulthood may promote autoimmune diabetes with adult onset has not been investigated,” wrote Jessica Edstorp, MA, MSc, of the Institute of Environmental Medicine at the Karolinska Institutet in Sweden, and colleagues.¹

The most frequent form of adult-onset autoimmune diabetes mellitus and the most prevalent form of autoimmune diabetes as a whole, LADA involves a gradual decrease in insulin production, usually caused by an autoimmune process damaging cells in the pancreas. It shares genetic, immunologic, and metabolic features with both type 1 and type 2 diabetes, although there are also several factors differentiating it from these classifications that merit further research to better understand the best approach to prevention, management, and treatment of LADA.²

To examine the association between diagnosis of infectious disease and risk of LADA, investigators collected data from the Swedish Epidemiological study of risk factors for LADA and type 2 diabetes (ESTRID), a population-based Swedish case-control study involving incident cases of LADA as well as matched controls, and compared it to the history of infectious disease. ESTRID recruited patients through the All New Diabetics in Scania (ANDIS) register and biobank. The present study includes all cases of LADA, type 2 diabetes, and control patients enrolled in ESTRID from 2010–2019.¹

LADA cases included individuals ≥35 years at diagnosis, GADA positive (≥10 U/mL), and with C-peptide concentrations of ≥0.2 nmol/L (IMMULITE) or ≥0.3 nmol/L (Cobas). Individuals with type 2 diabetes were ≥35 years, GADA negative, and had C-peptide concentrations of >0.60 (IMMULITE)/>0.72 (Cobas) nmol/L.¹

Investigators ascertained the history of infectious disease through national and regional patient registers and categorized this information into respiratory, gastrointestinal, herpetic skin and mucous membrane, other, and any infectious disease. Exposure windows 0–1, 1–3, 3–5, and 5–10 years before diabetes diagnosis/matching were used to assess the impact of infectious disease on risk of LADA.¹

The study population included 597 incident cases of LADA, 2065 incident cases of type 2 diabetes, and 2386 controls. Among patients in the LADA cohort, the mean age at diagnosis/matching was 59.1 (IQR 12.3) years and 53.1% were male. Among patients in the type 2 diabetes cohort, the mean age at diagnosis/matching was 63.2 (IQR, 10.4) years and 60.2% were male. Among patients in the control cohort, the mean age at diagnosis/matching was 58.9 (IQR, 13.8) years and 47.3% were male.¹

Upon analysis, investigators found LADA was not associated with infectious disease 1–3, 3–5, or 5–10 years prior to diabetes diagnosis. Specifically, they noted respiratory, gastrointestinal, herpetic skin, and other infectious diseases did not confer an increased risk of LADA.¹

In separate analyses restricted to LADA with HLA high-risk genotypes, similar results were observed. Analyses of LADA individuals with high GADA levels again yielded similar findings. Investigators noted results were similar in analyses of infectious diseases with a dispensed antibiotic and in analyses restricted to diagnoses from inpatient care.¹

Having ≥2 diagnoses of an infectious disease within the same exposure window was not associated with a higher risk of LADA, although investigators pointed out lower respiratory infections in the year before diabetes diagnosis was an exception, where 2 episodes conferred a 4.7-fold increased risk of LADA (95% confidence interval [CI], 1.08-20.15).¹

Further analysis revealed the risk of type 2 diabetes was elevated in individuals with a diagnosis of any infectious disease (odds ratio [OR], 1.26; 95% CI, 1.04-1.53), particularly lower respiratory (OR, 1.57; 95% CI, 1.08-2.28]) or other (OR, 1.37; 95% CI, 1.06-1.78), during the year before diagnosis. An increased risk of type 2 diabetes was also observed among those with lower respiratory infectious disease 1–3 years before diagnosis (OR, 1.40; 95% CI, 1.06-1.86) and gastrointestinal infections 3–5 years before diagnosis (OR, 2.41; 95% CI, 1.21-4.81).¹

“Our research suggests that in contrast to findings in childhood onset type 1 diabetes, an infectious disease diagnosis up to 10 years before does not increase the risk of LADA diagnosis, regardless of the type or severity of the infection,” investigators concluded.¹

References:

1. Edstorp J, Rossides M, Ahlqvist E, et al. Does a prior diagnosis of infectious disease confer an increased risk of latent autoimmune diabetes in adults? Diabetes Metabolism Research and Reviews. https://doi.org/10.1002/dmrr.3758
2. Rajkumar V, Levine SN. Latent Autoimmune Diabetes. StatPearls. June 21, 2022. Accessed December 19, 2023. https://www.ncbi.nlm.nih.gov/books/NBK557897/