Frequent antibiotic use linked to higher type 2 diab...

"Repeated antibiotic use linked to diabetes," BBC News reports.

New research has studied over 200,000 people from the UK who were diagnosed with diabetes between 1995 and 2013. Researchers counted the number of antibiotic prescriptions they had during an average five-year period before they were diagnosed. They compared the number of prescriptions given to an age- and gender-matched control group of over 800,000 people.

They found that people taking antibiotics were more likely to develop diabetes, and those taking more were at a higher risk. For example, people who took five or more antibiotic courses in the five-year period before diagnosis had around a third higher risk of developing type 2 diabetes than those taking no antibiotics.

We should not assume that the results mean antibiotics definitely cause diabetes. It could be the other way round.

Diabetes is known to increase the risk of infection, especially skin and urinary infections, so it could be diabetes leading to antibiotic use, and not vice versa.

Researchers attempted to adjust for this by only looking at antibiotic use for more than one year before a diagnosis of diabetes was made. However, this may not have been long enough.

It should also be noted the researchers did not take into account other factors that could have caused the results, such as the use of other medications known to increase the risk of diabetes and infections, such as steroids.

If you do find yourself having recurring infections, you should discuss the issue with your GP. There may be an underlying cause that needs investigating.

Where did the story come from?

The study was carried out by researchers from the University of Pennsylvania, and Tel-Aviv Sourasky Medical Center and Tel-Aviv University in Israel. It was funded by the US National Institutes of Health.

The study was published in the peer-reviewed European Journal of Endocrinology.

BBC News explained the study well, saying that since people with type 2 diabetes were at a higher risk of developing infections anyway, it was hard to find out which caused which. It quoted professor Jodi Lindsay from St George's, University of London, who explained: "This is a very large and helpful study linking diabetes with antibiotic consumption in the UK, but at this stage we don't know which is the chicken and which is the egg."

While appropriate use of antibiotics is a pressing issue, the study did not look at whether the prescriptions were appropriate or not, they simply counted how many were made.

Read about how a new blood test could help prevent antibiotic misuse – a news story that we published last week.

What kind of research was this?

This was a case-control study looking at whether antibiotic use raised the risk of developing diabetes.

This type of study matches people with a condition, in this case type 2 diabetes, with a control group without the condition who are the same age and sex. They compare many risk factors, in this case antibiotic use, to see if any might be linked with the disease. This type of study can show links between risk factors and disease, but cannot prove cause and effect. This is mainly because it cannot completely control for confounding factors (confounders).

What did the research involve?

Using a UK database of medical records, the researchers picked people diagnosed with diabetes and compared their exposure to antibiotics with people of the same age and sex who did not have a diagnosis of diabetes.

The researchers used medical records from 1995 to 2013 from a UK population-based database called The Health Improvement Network (THIN).

They identified 208,002 people who were diagnosed with diabetes during this time period, excluding people who already had a diagnosis of diabetes and those diagnosed within the first six months of the study.

The control group consisted of 815,576 people who were matched for age and sex with the cases. Importantly, they did not have diabetes at the date the case was diagnosed – called the index date.

Both groups were, on average, 60 years old and there was an even gender split.

Using the medical records, the researchers documented how many outpatient antibiotic prescriptions people had been given more than a year before the index date. They collected information on seven commonly used antibiotics, as well as antiviral and antifungal medications.

They analysed differences in antibiotic use, taking into account the following potential confounders, where available:

body mass index (BMI)
smoking
coronary artery disease
hyperlipidaemia (high cholesterol) that needed to be treated with statins
glucose level before the date of diabetes diagnosis
number of urinary tract, skin and respiratory infections before date of diabetes diagnosis

What were the basic results?

People with diabetes had a higher rate of infection before the diagnosis index date compared to the controls. Urinary infections, for example, occurred in 19.3% of cases, compared with 15.1% of controls.

Analysis not accounting for confounders showed antibiotic use was linked with higher diabetes risk for all seven antibiotics documented, and for both diabetes types. However, this is a simple analysis, and potentially misleading. Analysis taking account of the confounders is more reliable. This showed higher risks only in those taking more than one course of penicillin, cephalosporins, macrolides and quinolones, and showed almost no change in risk for participants with type 1 diabetes. The increase in risk in type 2 diabetes was higher the more antibiotics people had taken.

Treatment with two to five courses of the following antibiotics was associated with an increased risk of diabetes compared to no use of antibiotics, after adjusting the results for the confounders listed above:

8% increase in risk for penicillin (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.05 to 1.11)
11% increase in risk for cephalosporins, such as cefalexin (OR 1.11, 95% CI 1.06 to 1.17)
11% increase in risk for macrolides, such as erythromycin (OR 1.11, 95% CI 1.07 to 1.16)
15% increase in risk for quinolones, such as ciprofloxacin (OR 1.15, 95% CI 1.08 to 1.23)

Taking more than five courses of antibiotics raised the risk to 23% for penicillin and 37% for quinolones, compared to taking none.

There was no increase in risk for antivirals or antifungals.

How did the researchers interpret the results?

The researchers concluded that there is "a higher adjusted risk for type 2 diabetes among individuals with recurrent exposures to penicillin, cephalosporins, macrolides and quinolones". They also found "no increase in adjusted risk for exposure to antiviral or antifungal medications".

Conclusion

This large population-based study found a higher risk of diabetes in people taking between two and five courses of antibiotics over a year before diagnosis. This risk was even higher after more than five courses.

Strengths of the study include its large sample size, direct relevance to the UK, and the accuracy of the data.

Despite the strengths, the study does not prove that antibiotics cause diabetes, as its design cannot prove cause and effect. There are both plausible explanations for how antibiotic use may cause diabetes, and how the development of diabetes may cause more antibiotic use.

For example, people with diabetes are more prone to contracting bacterial infections. It could be that some of the study’s participants were in a prediabetes or undiagnosed diabetes stage when they started taking antibiotics. The researchers tried to take this into account by not including any antibiotic prescription given in the year before diabetes diagnosis, but it is possible that the diagnosis was delayed by more than a year, or signs appeared more than a year before diagnosis.

The second option is that antibiotics contribute to diabetes by altering a person’s microbiota – our internal stock of "good" bacteria and other micro-organisms present in our digestive system.

Other confounders could have accounted for the increased risk found:

Increased use of antibiotics is also common in people who take steroids, such as prednisolone. Steroids are known to increase the risk of diabetes.
Obesity increases the risk of diabetes, but BMI was not available for 30% of the study's participants.
The number of prescriptions of antibiotics was only recorded from 1995 up until the date of diagnosis of diabetes.
As the average age of the participants was 60 at the time of diagnosis, this means, at best, that the study did not capture antibiotic use up to the age of 40.
The study only recorded outpatient prescriptions; it did not include antibiotics given during hospital admissions.

A further limitation of the study was that the main analysis included people with either type 1 or type 2 diabetes. This muddies the water, as they have different causes. Type 1 diabetes is autoimmune and typically starts in childhood or adolescence, and no clear risk factors have been identified (although a viral cause has been suggested). However, type 2 diabetes has a number of risk factors, including family history, ethnic background and obesity.

The study does provide more of an incentive to only take antibiotics when strictly required. Known risk factors for diabetes that you can change include reducing your waistline, maintaining a healthy weight, reducing high blood pressure, eating healthily and taking regular physical exercise.

Read more about how to reduce your diabetes risk.