Science

Kristian Hallundaek Mikkelsen, Filip Krag Knop, Morten Frost, Jesper Hallas, and Anton Pottegård

Evidence that bacteria in the human gut may influence nutrient metabolism is accumulating. We investigated whether use of antibiotics influences the risk of developing type 2 diabetes and whether the effect can be attributed to specific types of antibiotics. We conducted a population-based case-control study of incident type 2 diabetes cases in Denmark (population 5.6 million) between January 1, 2000, and December 31, 2012. Data from the Danish National Registry of Patients, the Danish National Prescription Registry, and the Danish Person Registry were combined. The odds ratio (OR) associating type 2 diabetes with exposure to antibiotics of any type was 1.53 (95% confidence interval 1.50 –1.55) with redemption of more than or equal to 5 versus 0 –1 prescriptions. Although no individual group of antibiotics was specifically associated with type 2 diabetes risk, slightly higher ORs for type 2 diabetes were seen with narrow-spectrum and bactericidal antibiotics (OR 1.55 and 1.48) compared to broad-spectrum and bacteriostatic types of antibiotics (OR 1.31 and 1.39), respectively. A clear dose-response effect was seen with increasing cumulative load of antibiotics. The increased use of antibiotics in patients with type 2 diabetes was found up to 15 years before diagnosis of type 2 diabetes as well as after the diagnosis. Our results could support the possibility that antibiotics exposure increases type 2 diabetes risk. However, the findings may also represent an increased demand for antibiotics from increased risk of infections in patients with yet-undiagnosed diabetes.