Risk of Type 2 Diabetes from Antibiotics

Results from a population-based case-control study could support the possibility that antibiotics exposure increases type 2 diabetes risk. There are two types of theories which link antibiotic with type 2 diabetes:

a: patients with type 2 diabetes are more prone to develop infections many years before they become diagnosed with type 2 diabetes and therefore have increased demand for antibiotics

b: antibiotics increase the risk of type 2 diabetes

There are suitable examples in literature that support both the theories, individually.

Concept: The human gut is populated by a dense community of microbes, aptly called, the gut microbiota. As the name suggest, it provides the host body “guts” to hold a battle against many auto-immune diseases like diabetes, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, fibromyalgia, and perhaps some cancers. The human body contains over 10 times more microbial cells than human cells, although the entire microbiome only accounts for about for 1-3% total body mass, with some weight-estimates ranging as high as 1.5 – 2.0 Kgs. Obesity too is believed to be caused by inefficiency of gut microbes. Gut microbiota is unique to each individual, is generally non-pathogenic and they exist in harmony and symbiotically with their hosts. In rare cases even their abnormal growth can cause some alarming situations. In addition, gut bacteria are known to aid the production of certain vitamins - such as vitamins B and K.

The very fact that an infant gut is sterile, and that gut microbiota is unique to each individual makes them good study material to understand the immunity and disease pattern of a person. Antibiotics cause marked alterations in the human gut microbiota with stereotypic declines and expansions in the abundance of certain taxa and incomplete recovery to the initial composition in some individuals. In simple words, antibiotics are able to change the composition and concentration of gut microbes, weakening bodies response against certain disease set. No wonder antibiotic abuse has alarming results.

To understand the consequences of such an absue, Danish researchers conducted a nationwide case-control study to investigate whether use of antibiotics influences the risk of developing type 2 diabetes and, if so, if the effect can be attributed to individual types of antibiotics, individual groups of antibiotics, or the number of antibiotics courses.

Methods: Researchers 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. Researchers obtained information on use of all systemic antibiotics for the cohort between January 1, 1995, and July 1, 2012. Antibiotics were classified into narrow-spectrum or broad-spectrum and bactericidal or bacteriostatic. Exposure was quantified according to number of antibiotic courses before the index date, three different categories were defined; 0-1 antibiotic courses (reference), 2-4 antibiotic courses or greater than/equal to 5 antibiotic courses. Filling a prescription on the same antibiotic within 20 days of the first use was considered as belonging to the same course. Moreover, some certain type of diabetic patients was excluded from the study such as cases with chronic pancreatitis, pancreatic cancer, or polycystic ovary syndrome etc. The analysis conformed to a conventional matched case-control study. The crude and adjusted odd ratios (ORs) for developing type 2 diabetes associated with antibiotic exposure were estimated using conditional logistic regression, controlling for potential confounders.

Results:

1. The OR for type 2 diabetes increased almost linearly with the exposure to antibiotics.

2. Patients with type 2 diabetes redeemed on average 0.8 prescriptions on antibiotics per year compared to 0.5 prescriptions per year among controls.

3. Slightly higher ORs were found for narrow-spectrum and bactericidal antibiotics compared with broad-spectrum and bacteriostatic antibiotics, respectively.

4. Researchers found increased ORs for all groups of antibiotics except for clindamycin.

4. Researchers found a steep increase in OR for type 2 diabetes with increasing exposure to narrow spectrum antibiotics when the exposure to broad-spectrum antibiotics was held fixed. In contrast, there was a relatively unchanged OR for type 2 diabetes with increasing exposure to broad-spectrum antibiotics when exposure to narrow-spectrum antibiotics was fixed.

5. The increased exposure to antibiotics was observed both 5 years before and 5 years after the type 2 diabetes index date for cases.

The authors conclude as “Patients with type 2 diabetes, compared to control subjects free of type 2 diabetes, are overexposed to antibiotics before their diagnosis with type 2 diabetes as defined by the first redemption of a prescription on an oral glucose-lowering agent. However, the possibility that antibiotics exposure increases diabetes risk cannot be excluded and deserves further investigation in interventional studies. In particular, we suggest investigation of commonly used narrow-spectrum penicillins because these drugs are frequently prescribed and showed the highest OR for type 2 diabetes risk.”

Article Citation: Mikkelsen, K. H.; et. al. Use of Antibiotics and Risk of Type 2 Diabetes: A Population-Based Case-Control Study.  J Clin Endocrinol Metab 2015. DOI: 10.1210/jc.2015-2696

To Be, or Not to Be, Well ...... Do You Have Guts to Answer ?