By Seema Gupta, MD, MSPH
Clinical Assistant Professor, Department of Family and Community Health, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV
Dr. Gupta reports no financial relationship to this field of study.
SYNOPSIS: In a population-based, case-control study of incident type 2 diabetes cases, researchers found that more frequent users of antibiotics were more likely to be diagnosed with type 2 diabetes than those who had taken the drugs infrequently.
SOURCE: Mikkelsen KH, et al. Use of antibiotics and risk of type 2 diabetes: A population-based case-control study. J Clin Endocrinol Metab 2015;100:3633-3640.
Since their discovery in the 1920s, antibiotics have transformed our ability to manage infectious diseases. Today, antimicrobials are one of the most commonly prescribed medication classes in the United States. However, it is estimated that more than half of antibiotics prescribed for patients visiting a clinic are inappropriate. In fact, more than 25% of prescriptions are for conditions for which antibiotics are rarely indicated and tend to be more often broad-spectrum.1 Substantial evidence indicates that many prescriptions are for viral illnesses, for which antibiotics provide no benefit.2 Similarly, 30-50% of antibiotic use in hospitals is unnecessary or inappropriate. Considerable geographical variation in outpatient antibiotic prescribing rates has been observed. The inappropriate use and overuse of antibiotics are major drivers of antibiotic resistance, leading to a significant public health threat. Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die as a direct result of these infections. In addition, antibiotics cause one out of five emergency department visits for adverse drug events (ADEs) and are the most frequent cause of ADEs in children.3,4
Similar to the antibiotic issue, type 2 diabetes mellitus (T2DM) also represents a major public health challenge, in large part due to the rising epidemic of obesity. T2DM is associated with significant comorbidities and healthcare costs. The latest research suggests that microbes that colonize the human gut may play key contributory roles to the development of obesity and metabolic syndromes, such as T2DM.5 Since antibiotics also cause marked alterations in the human gut microbiota, some observational studies have linked exposure to antibiotics with the development of obesity.6
Mikkelsen et al conducted a population-based, case-control study to investigate whether the use of antibiotics influences the risk of developing T2DM. The researchers utilized three national registries in Denmark to track patients’ antibiotic prescriptions between 2000 and 2012: 170,504 who had T2DM and 1.36 million who did not.
Researchers found that T2DM patients treated filled on average 0.8 antibiotic prescriptions per year compared to 0.5 prescriptions per year among controls. The more antibiotics patients utilized, the more likely they were to have T2DM. Compared with having filled none to one prescription for antibiotics, those who filled two to four prescriptions had a 21% higher risk (95% confidence interval [CI], 1.19-1.23) for T2DM, and those who filled five or more had a 53% higher risk (95% CI, 1.50-1.55). Slightly higher odds ratios were found for narrow-spectrum and bactericidal antibiotics compared with broad-spectrum and bacteriostatic antibiotics, respectively. The increased use of antibiotics in patients with T2DM was found up to 15 years before diagnosis of T2DM as well as after the diagnosis.
COMMENTARY
This study seems to support findings of others in the field that an increased risk for developing T2DM may occur with more exposure to antibiotics. Indeed, several studies suggest that antibiotics may drive changes in glucose homeostasis, insulin sensitivity, and adipose tissue metabolism by altering the gut microbiota.7 Antibiotics have been traditionally used in agriculture to achieve weight gain in livestock. However, it is also important to consider another possibility. Patients with T2DM are more susceptible to infections and may naturally take more antibiotics. The study demonstrates that these patients may be more prone to developing infections many years before they become diagnosed with T2DM. This may be attributed to developing an increased risk of infections during pre-diabetes, a condition often co-existing with being overweight or obese, which precedes T2DM development. While the study demonstrates an association between antibiotic use and T2DM, it does not establish a causation, and further research is needed. However, it provides another possible reason why we should be leaders in promoting antimicrobial stewardship in order to optimize antibiotic use for achieving the best clinical outcomes while minimizing adverse events and the emergence of resistance.
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Bailey LC, et al. Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr 2014;168:1063-1069.
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Geurts L, et al. Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: Novel insights into molecular targets and interventions using prebiotics. Benef Microbes 2014;5:3-17.
