A British Medical Journal (BMJ) investigation into two classes of type 2 diabetes drugs has prompted headlines in the Daily Mail. The newspaper claims, "Diabetes drugs taken by thousands linked to cancer of the pancreas and other serious health problems," going on to allege that drug manufacturers may be trying to hide potentially harmful side effects.

It is important to stress that there is no evidence of any legal or regulatory wrongdoing by any of the drug companies mentioned in the BMJ article.

The BMJ investigation focused on two relatively new classes of type 2 diabetes drugs collectively known as "incretin mimetics". There are two main types of incretin mimetic:

• glucagon-like peptide-1 (GLP-1) agonists, such as exenatide, which help boost insulin production while decreasing blood sugar levels – the drug also has the added benefit of leading to modest weight loss
• dipeptidylpeptidase-4 inhibitors (DPP-4), such as sitagliptin, which block the effects of an enzyme that can have a harmful impact on blood sugar levels

Neither of these drugs are first-line treatments for people with type 2 diabetes. Instead, they tend to be used if first-choice drugs are not working well enough by themselves.

As both types of drugs act on the pancreas, concerns have been raised that they may also have adverse effects on the organ. The article discusses these concerns and the evidence behind them.

This evidence includes the results of animal studies and reports from medicines regulatory agencies which suggest that the drugs may increase the risk of inflammation of the pancreas (pancreatitis) and could also lead to cancerous changes in the tissue of the pancreas, triggering pancreatic cancer.

From the evidence discussed, it does appear that there may be an increased risk of these drugs having adverse effects, but further safety studies are needed to confirm this. People may be reassured that the bodies that regulate medication are aware of the potential risks and will be carefully reviewing the safety of these drugs.

For now, anyone with diabetes who has concerns about their treatment should speak with the healthcare professionals involved in their care. The risk to your health of suddenly stopping treatment for type 2 diabetes are likely to far outweigh any potential risk of harm to your pancreas.

Where did the story come from?

The news stems from an article published in the peer-reviewed British Medical Journal (BMJ) written by Deborah Cohen, the BMJ investigations editor. The article has been made available on an open access basis, so it is free to read or download.

No sources of funding or conflicts of interest are reported.

The article states that, "In the course of this investigation, the BMJ has reviewed thousands of pages of regulatory documents obtained under freedom of information and found unpublished data."

Specific methods for identifying and selecting these documents are not presented in the article, so it is not clear whether all the evidence related to this issue has been considered. The BMJ investigation also raised specific questions directly with drugs manufacturers.

What is the BMJ article about?

Cohen discusses two types of diabetes medication that both work in two main ways:

• increasing the production of insulin, a hormone produced by the pancreas that helps the body's cells take up blood sugar (glucose) to use it for energy
• suppressing glucagon secretion, another hormone released by the pancreas which has the opposite effect of insulin, causing the liver to release its glucose stores to increase blood sugar

The two types of medication under the spotlight are glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors. Neither of these drugs are first-line treatments for type 2 diabetes, but may be considered if first-line treatments are not working effectively on their own.

The GLP-1 agonist group includes two drugs called exenatide and liraglutide. In addition to increasing insulin release and suppressing glucagon, these drugs also slow stomach emptying. For this reason they can also help prevent weight gain.

Currently, GLP-1 agonists may be considered for people whose diabetes has not been controlled by standard first-line treatments, such as metformin and sulfonylurea, and who are obese (BMI above 35kg/m2).

The National Institute for Health and Care Excellence (NICE) currently recommends that treatment with these drugs should only be continued if the person demonstrates adequate blood sugar control and has lost at least 3% of their body weight within six months.

The DPP-4 inhibitor group includes the drugs linagliptin, saxagliptin, sitagliptin and vildagliptin. There are specific types of people who are considered suitable to take these drugs.

Broadly, they may also be prescribed when standard treatment with a combination of first-choice drugs for diabetes (metformin and sulfonylurea) has either failed to control blood sugar, is inappropriate, or alternative diabetes drugs are inappropriate. Again, these drugs should only be continued if there is adequate blood sugar control.

What does the BMJ article say about these diabetes drugs?

Because incretin mimetics stimulate the cells of the pancreas, there is the potential that they may also have adverse effects on the organ.

Recently, experts have had increasing concerns about the safety of incretin mimetics. In February 2013 an independent analysis of health insurance data found that people taking exenatide and sitagliptin were at twice the risk of being admitted to hospital with inflammation of the pancreas (acute pancreatitis) compared with people taking other diabetic drugs.

The actual size of the risk to the individual was low – only 0.6%, or six in every 1,000 people taking the drugs. But even if individual risk is low, health watchdogs have to consider the fact that these types of drugs are taken by hundreds of thousands of people.

In April 2013, analysis of data from the US Food and Drug Administration (FDA) also showed increases in cases of pancreatitis and pancreatic cancer among people taking incretin mimetics compared with those taking other diabetic drugs.

Both the FDA and the European Medicines Agency (EMA) are said to have confirmed to the BMJ that their own analyses also show increased reports of pancreatic cancer with these drugs.

However, the agencies have emphasised that this does not necessarily mean that the drugs directly cause these adverse effects. It could possibly be the case that it is type 2 diabetes itself, rather than the drugs, that is increasing the risk of pancreatic cancer.

In March 2013, both agencies said that they would review study data showing that some organ donors who had taken incretin mimetics have demonstrated pre-cancerous changes in the pancreas.

Despite these findings, the risks are said to be fiercely contested by manufacturers. The drug company Merck has presented data from a pooled review of almost 34,000 people who have taken DPP-4 inhibitors and found no connection with pancreatic cancer.

However, other manufacturers appear to have some concerns about inflammation of the pancreas (pancreatitis) related to the use of these drugs. Bristol-Myers Squibb and AstraZeneca have sent a letter to the UK Medicine and Healthcare products Regulatory Agency (MHRA) saying: "A review of reports of pancreatitis from post-marketing experience revealed that signs of pancreatitis occurred after the start of saxagliptin treatment and resolved after discontinuation, which is suggestive of a causal relationship. Moreover, pancreatitis has been recognised as an adverse event for other DPP-4 inhibitors."

The BMJ article goes on to further discuss the "increasingly fractious debate among scientists and doctors played out last month in the specialty journal Diabetes Care", before going on to discuss the problems that have been observed in animals given the drugs:

• Diabetic rats were given sitagliptin, metformin, or a combination of both drugs. Rats given sitagliptin had problems in their pancreas – enlargement, pancreatitis, or changes in the cells that could indicate early cancerous changes. At an ensuing meeting between experts and manufacturers held at the American Diabetes Association, one expert stated that the results in rats could suggest an increase in the risk of pancreatic cancer and that if the results were true, the future of the drugs could be in doubt. However, he said that, "concern had to be balanced against the lack of data indicating similar effects in humans." Other experts suggested that the rat model used was not reliable.
• A study in mice genetically predisposed to developing pancreatitis and pancreatic cancer found that they developed pancreatitis and pre-cancerous changes more quickly when given exenatide. Another study in non-diabetic rats also showed overgrowth in the cells of their pancreatic ducts when given exenatide. Supporters of the drugs question the methods used in these studies.
• There is disputed evidence from monkeys that suggests that there may be an increase in pancreas weight among young healthy monkeys given liraglutide.

The BMJ article also discusses lawsuits in the USA related to the possible link between exenatide and acute pancreatitis. This led to a judge allowing an independent pathologist to review the manufacturer's slides of slices of pancreas from monkeys treated with exenatide – the manufacturer reportedly initially refused access to these slides. The pathologist found more chronic inflammation and pancreatic disease in the treated monkeys than untreated controls.

A team from the University of California, Los Angeles (UCLA) analysed data from 2004-09 recorded in the FDA adverse event database. It found that the odds of pancreatitis were increased about six- to tenfold with exenatide and sitagliptin, and the odds of pancreatic cancer increased just under threefold with both drugs. The team noted the limitations of their study and advised that it was interpreted with caution.

Industry representatives and medical societies were reported to have heavily criticised the methods of the original study – for example, saying that it did not include information about other factors that could affect the results (potential confounders)

A later analysis by the US Institute for Safe Medication Practices (ISMP) found that all five incretin mimetics were together associated with more than 25 times the rate of pancreatitis than that seen in people with diabetes taking other drugs. The DPP-4 inhibitors were associated with 13.5 times higher rates of pancreatic cancer, and the GLP-1 agonists had rates 23 times higher than other diabetic drugs.

For some of the drugs (linagliptin and saxagliptin) there was only a single case of pancreatic cancer, and changes in risk were not significant.

What did the BMJ article conclude?

The BMJ article raises concerns their investigation found that, despite misgivings about the safety of these drugs, "companies have not done critical safety studies; nor have regulators requested them", and that, "access to raw data that would have helped resolve doubts about the safety of these drugs has been denied".

It says that although the individual pieces of evidence may seem inconclusive, a "more coherent and worrying picture emerges" when they are "considered alongside other emerging and longstanding evidence".

Conclusion

This article presents important concerns that glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors could potentially increase the risk of inflammation and cancerous changes in the pancreas.

The agencies that regulate medicines in Europe and the USA are aware of these issues, and told the BMJ that their analyses show increased reporting of pancreatic cancer among people taking these types of drugs.

However, the agencies note that it has not been established whether these drugs directly cause the adverse effects seen in the pancreas. Both agencies are reviewing emerging evidence on safety in this area.

For now, anyone with diabetes who has been prescribed these drugs and has concerns should speak with the healthcare professionals involved in their care.

Do not stop taking any diabetes medication unless you are advised to do so by the doctor in charge of your care. If you stop taking this medication without medical advice, you are at a much higher risk of developing complications related to diabetes, such as heart disease, stroke, kidney damage and even blindness, than you are at risk of developing pancreatic cancer.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Diabetes drugs taken by thousands linked to cancer of the pancreas and other serious health problems. Daily Mail, June 10 2013

'Is your caffeine fix making you fat?' is the compelling question posed by the Mail Online website, which goes on to report that a study 'shows five cups of coffee a day could cause obesity.' But the study in question involved mice, not people, and a chemical found in coffee, not coffee itself.

The research explored the effects of a substance called chlorogenic acid (CGA), a component of coffee. The rodents were given CGA to see how it affected their fatness and glucose regulation, which is related to the risk of developing type 2 diabetes.

Mice given a high-fat diet supplemented with CGA appeared to display signs of worse glucose regulation than those given the high-fat diet only, which suggests that consuming high levels of CGA may not be good for you.

Despite this finding, the headline 'five cups of coffee a day could cause obesity' was way off the mark. The study only demonstrated that a high-fat diet made the mice fatter, but did not prove that CGA – and by association coffee – makes you fatter, as the headline implies.

This study alone does not support the notion that coffee causes obesity. Still, drinking five or more cups of caffeinated coffee a day can lead to symptoms such as irritability and insomnia.

Where did the story come from?

The study was carried out by researchers from universities in Australia and Malaysia and was funded by the Australian Research Council.

It was published in the peer-reviewed Journal of Agricultural and Food Chemistry.

Both the Mail Online and The Daily Telegraph's reporting of the study seems pretty wide of the mark. The Telegraph's headline, 'Regular coffee drinkers 'at increased risk of weight gain',' is a major extrapolation of the actual study results.

In mitigation, it appears that their reporting was influenced by an overenthusiastic discussion of the potential implications of the research by the researchers themselves.  

What kind of research was this?

This was a laboratory-based animal study using male mice. The researchers suggest that the increasing prevalence of what is known in the medical profession as "metabolic syndrome" demands new treatments and prevention strategies. 

Metabolic syndrome is the medical term for a combination of diabetes, high blood pressure and obesity. It puts you at greater risk of heart disease, stroke and other conditions affecting blood vessels (cardiovascular diseases)

The researchers point out that human observational studies have consistently linked higher coffee consumption with a lower risk of type 2 diabetes. It is thought that certain dietary polyphenols (organic chemical molecules found in food and drink) can have beneficial effects on several features of metabolic syndrome, such as reducing blood pressure.

Chlorogenic acid (CGA) is one of the most commonly consumed polyphenols in our diet and is a major component of coffee. CGA is also found in fruit such as plums, apples and berries. The researchers wanted to better understand how diet and CGA intake might interact to reduce the risk of certain components of metabolic syndrome, namely obesity, glucose intolerance and insulin resistance.

Insulin is the hormone that controls blood glucose. It is produced when blood glucose levels are high, causing the body's cells to take up glucose and use it for energy. When a person is described as having "glucose intolerance" and "insulin resistance" it means their body's cells are less sensitive to the action of insulin, so they can't regulate their blood sugar as well. This means they are at risk of developing – or may already have – type 2 diabetes.

Animal studies are a useful place to begin to develop a better understanding of the biological underpinnings of diseases. However, mice and men are not identical, so we can't assume positive findings in mice will lead to positive findings in people – this needs to be tested directly in studies involving humans.

What did the research involve?

The researchers designed a study that involved giving male mice a controlled diet over a 12-week period. Mice were either given:

• a normal diet
• a high-fat diet, or 
• a high-fat diet and CGA

The researchers say that they used CGA at a dose that would be realistically attainable through the diet (1g per kg of food), rather than an exceptionally high experimental amount. In their article, they describe how people can obtain up to 1g of CGA from the daily consumption of coffee, but do not specify how many cups or the strength of the coffee.

The researchers tested the effects of the three diets on the following measures of metabolic syndrome:

• high-fat diet-induced obesity – how fat the mice got due to their high-fat diet
• glucose intolerance – an umbrella term for blood glucose levels that are higher than normal
• insulin resistance – when the body fails to respond to the normal actions of the hormone insulin, which is essential for maintaining blood glucose levels within a normal range
• fatty acid oxidation – the process where fats are broken down for energy in a cell
• insulin signalling – essential for maintaining blood glucose levels within a normal range

Their analysis was appropriate and looked at whether the above measures of metabolic syndrome were influenced by the three different diets.

What were the basic results?

The study found that all the mice gained weight in the 12 weeks, with those on the normal diet gaining the least. Compared with mice on the normal diet, both groups on the high-fat diet gained significantly more weight, both with and without CGA.

However, mice given the high-fat diet plus CGA were no slimmer than mice fed a high-fat diet only. This is interesting, as you can buy CGA extracts as a slimming aid, suggesting that it may potentially be less effective than advertised.

Mice given a high-fat diet plus CGA had increased insulin resistance (a bad sign) compared with mice fed a high-fat diet only, which theoretically suggests a higher risk of type 2 diabetes. Likewise, the livers of mice fed a high-fat diet supplemented with CGA appeared to have a poorer fatty acid oxidation process than those given just the high-fat diet.

How did the researchers interpret the results?

Recognising their research was different to what had been found in some previous studies, the researchers concluded that, "Our results do not support the hypothesis that CGA can prevent development of features of the metabolic syndrome."

Conclusion

This rodent research suggests that mice given a high-fat diet supplemented with the polyphenol chlorogenic acid (CGA) fared worse than those given a high-fat diet. But this was only in terms of measures of glucose regulation that are related to the risk of developing type 2 diabetes.

The researchers point out that other studies have found that giving CGA to mice improved measures of their glucose regulation. When there are contradictory results from different studies like this, it can indicate that the biological processes involved are not fully understood. Because of this, these results are not likely to be reliable on their own. A better consensus of what is going on may come through further research into the area.

There are further limitations with this research to consider when thinking about the impact of this study:

• The equation of the amount of CGA given to the mice to five cups of coffee in humans was relatively crude and may not be accurate. However, the researchers did make an effort to give the mice a dose of CGA that they thought might be roughly equivalent to the amount a person could get through drinking coffee, although it wasn't clear what type or strength of coffee this would be.
• The researchers suggest that the results could have been influenced by the bacteria present in the guts of the mice. They suggest the gut bacteria can degrade CGA, which would alter its biological effect in the body. The precise combination of gut bacteria varies from mouse to mouse and person to person. This may account for some of the different results seen in this area of research, and would need to be measured in further studies.

This study represents preliminary research in mice and is a long way from being directly applicable to humans, as some of the media coverage implies. Further research is required to work out if coffee polyphenols are able to protect against metabolic syndrome and type 2 diabetes in humans or, alternatively, if they make people more vulnerable to these conditions.

Established ways of protecting against the harmful effects of metabolic syndrome include:

• losing weight
• getting active 
• eating healthily to keep blood pressure, cholesterol and blood sugar levels under control
• stopping smoking 
• cutting down on alcohol

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Is your caffeine fix making you fat? Study shows five cups of coffee a day could cause obesity. Mail Online, May 28 2013

Regular coffee drinkers 'at increased risk of weight gain'. The Daily Telegraph, May 28 2013

Links To Science

Mubarak A, Hodgson JM, Considine MJ, et al. Supplementation of a High-Fat Diet with Chlorogenic Acid Is Associated with Insulin Resistance and Hepatic Lipid Accumulation in Mice. Journal of Agricultural and Food Chemistry. Published online April 15 2013

‘Children's exposure to traffic pollution could…lead to diabetes' BBC News explains, reporting on a German study.

The study included around 400 children aged 10. Researchers looked at measures of air pollution and proximity to the nearest road at the address each child had lived as a baby.

They also measured each child’s blood sugar and insulin levels.

The second measurement allowed them to calculate each child’s level of insulin resistance – to what extent the cells of the body fail to respond to the hormone insulin (which the body uses to convert blood sugar into energy).

Once insulin resistance reaches a certain level, the symptoms of type 2 diabetes can develop.

The researchers found an association between exposure to air pollution and increased levels of insulin resistance.

However, an association is not the same as proof of a direct causal effect. Living near a busy road would usually imply that a child lives in an urban environment. So there could be a range of environmental factors, other than air pollution, affecting levels of insulin resistance (as well as a wide-range of other possible individual genetic and health-related factors).

The study also does not tell us whether any insulin resistance measured in the child actually had any clinical significance and would lead to a child developing diabetes in later life.

Due to these limitations, further studies in other population samples would be useful.

Where did the story come from?

The study was carried out by researchers from German Center for Diabetes Research and other institutions in Germany, and was funded by German Federal Ministry of Education and Research, and The European Community’s Seventh Framework Programme.

The study was published in the peer-reviewed medical journal Diabetologia.

The quality of the reporting on the study in the UK media is mixed. The BBC News headline gives an accurate representation of the current study as it includes the all-important word ‘may’. However, the Mail Online’s headline linking air pollution to a child’s risk of developing diabetes may be misleading.

This study has many limitations, not least, that increased levels of insulin resistance in childhood, while a risk factor, is not a guarantee that a child will grow up to develop type 2 diabetes.

Also, the association between childhood and diabetes may confuse some readers into thinking that the study was looking at type 1 diabetes – the form of the condition that normally begins in childhood and where the body’s own immune system destroys the insulin-producing cells, so the person is not able to produce any insulin at all.

What kind of research was this?

This was a cohort study looking at whether there was an association between air pollution and insulin resistance.

The researchers say that previous research has shown that traffic and air pollution may increase the risk of diseases affecting the lungs and cardiovascular system.

This is speculated to be due to exposure to pollution that may trigger oxidative stress (a disruption in the body’s ability to repair cellular damage). Pollution could also lead to low levels of inflammation in certain cells of the immune system and those lining the blood vessels.

Animal studies have also suggested that pollution may make cells of the body more resistant to the action of insulin – the hormone released from the pancreas that helps the body to make use of the glucose in the blood.

The researchers say that no study has yet looked at whether traffic-related air pollution can lead to insulin resistance in school-aged children. This German cohort study aimed to look at the relationship between particulate matter in the air and proximity to the nearest road at the child’s birth address, and the child’s insulin resistance when they reached the age of 10.

The limitations of such a study include it being difficult to conclude that the air pollution at the birth address has directly caused the child’s insulin resistance at age 10.

There may be many other genetic, environmental and health-related factors involved.

The study also does not tell us whether any insulin resistance measured in the child has any clinical significance, and whether it is related to later development of type 2 diabetes in adult life.

What did the research involve?

The researchers included sub-groups of 10-year-old children taking part in two separate birth cohorts in Munich, South Germany and Wesel, West Germany:

• The German Infant Study enrolled almost 6,000 healthy newborns and was a trial looking at the effect of a hypoallergenic infant formulae on a child’s risk of allergy (in addition to looking at other environmental and genetic influences).
• The Lifestyle-Related Factors study included just over 3,000 healthy newborns and was an observational study looking at the effect of lifestyle factors on the child’s immune system and risk of allergies.

The present study included 397 children randomly sampled from these two cohorts (though 82% came from the Munich cohort) who had blood samples taken for insulin and glucose measurement at age 10, and who had information available for air pollution exposure at the time they were born.

To measure pollution exposure at the birth address, the researchers used models to estimate levels of:

• nitrogen dioxide (N02)
• particulate matter of less than 2.5 micrometres in diameter
• particulate matter of less than 10 micrometres in diameter

Particulate matter is the term for a mixture of solid particles and liquid droplets found in the air.

Measurements were taken at selected monitoring sites on three occasions over 14 consecutive days, and in different seasons.

When conducting their analyses, factors taken into account at each monitoring site were location, surrounding land use, population density and traffic patterns.

Other factors taken into account that could have an influence on the results (confounders) related to the individual child included:

• parental education (used as an indicator of socioeconomic status)
• exposure to second-hand smoke
• height and weight at age 10
• whether they had started to go through puberty

What were the basic results?

There were no differences between children in the two cohorts, except that those from Wesel were more likely to have been exposed to second-hand smoke and to be of lower socioeconomic status. Pollutant levels were also higher in Wesel than Munich.

After adjustment for all potential study-centre and child-related confounding factors, each two-point standard deviation increase in nitrogen dioxide levels was associated with a 15.8% increase in insulin resistance (95% confidence interval (CI) 3.8 to 29.1).

Each two-point standard deviation increase in particulate matter of less than 10 micrometres in diameter, was associated with a 17.5% increase in insulin resistance (95% CI 1.9 to 35.6). There was no significant association with particulate matter of less than 2.5 micrometres in diameter.

Distance to the nearest road, as would be expected, was significantly associated with pollutant levels (shorter distance equalled higher levels of nitrogen dioxide and particulate matter). Shorter distance to the road was also associated with increased insulin resistance (each 500 metre decrease in distance to road increased insulin resistance by 6.7%, 95% CI 0.3 to 13.5).

The researchers found that the link between pollution levels and insulin resistance was stronger in children who had not moved from their birth address by age 10.

How did the researchers interpret the results?

The researchers conclude that traffic-related air pollution may increase the risk of insulin resistance in children. They say that the associations observed may have important public health implications despite the small effect seen.

Conclusion

This German study looked at the relationship between air pollution and proximity to the nearest road at the child’s birth address, and the child’s insulin resistance when they were aged 10. Though links were found between increasing levels of nitrogen dioxide and levels of particles less than 10 micrometres in diameter and increasing insulin levels at age 10, there are important limitations to bear in mind:

• Though the researchers have attempted to adjust for many potential confounders, it is difficult to conclude that the air pollution at the birth address has directly caused the child’s insulin resistance at age 10, when there may be many other genetic, environmental and health-related factors involved.
• The confidence intervals around the increase in insulin resistance with each incremental increase in pollutant levels are very wide. For example, each increase in particles of less than 10 micrometres was associated with a 17.5% increase in insulin resistance, but the actual increase could lie anywhere between 1.9% and 35.6%. This means we can have less confidence in the reliability of these estimates.
• The study does not tell us whether any insulin resistance measured in the child has any clinical significance, and whether it will be related to higher risk of developing type 2 diabetes in adult life.
• Also, as mentioned above, the news headlines should not be wrongly interpreted to mean that a child has increased risk of developing type 1 diabetes – the type that readers may associate with start in childhood.  
• Lastly, the results are based on only a relatively small sample of children from two regions in Germany. Studies of much larger samples from different countries would give more weight to any observations.

Overall, this study cannot prove that air pollution increases a child’s risk of developing diabetes, only that there may be an association with insulin resistance.

As it is unlikely that we are going to live in a world free from air pollution anytime soon, the most effective way of reducing your child’s diabetes risk is to encourage them to take plenty of exercise and eat a healthy diet. These types of good habits in childhood often carry on into adulthood meaning that your child is more likely to maintain a healthy weight – a proven method of reducing type 2 diabetes risk.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Diabetes: dirty air 'may raise' insulin resistance risk. BBC News, May 10 2013

Why living near a busy road could be dangerous for your child's health: Traffic pollution linked to diabetes risk in children. Mail Online, May 10 2013

Air pollution could raise diabetes risk. The Daily Telegraph, May 10 2013

Links To Science

Thiering E, Cyrys J, Kratzsch J, et al.  Long-term exposure to traffic-related air pollution and insulin resistance in children: results from the GINIplus and LISAplus birth cohorts (PDF, 278KB). Published online May 9 2013

'One soft drink a day increases Type 2 diabetes risk by a fifth,' The Independent warns, reporting on a European study that has examined the relationship between type 2 diabetes and sugary drinks.

The study – one of the largest of its kind – found strong links between sugary drink consumption and an increase in a person's risk of developing type 2 diabetes. It attempted to assess the potential effects of various soft drinks on diabetes risk, including:

• sugar-sweetened drinks, such as cola
• artificially sweetened drinks, such as diet cola
• fruit juices and nectars (diluted fruit juices that may contain sugar or sweeteners)

The researchers found that people who drank sugar-sweetened drinks were at a higher risk of developing type 2 diabetes. For every additional regular can-sized, sugar-sweetened drink per day, there was an 18% risk of developing the disease. However, drinking artificially sweetened drinks, juices and nectars was not associated with any increased risk.

While this type of research cannot prove a definite cause and effect between sugary drink consumption and diabetes, it does suggest a strong association. As most popular soft drinks now come in a sugar-free alternative, they would certainly seem to be the healthier choice. But a glass of tap water is both healthier and a lot cheaper.

Where did the story come from?

The study was carried out by researchers from Imperial College London and colleagues from eight European countries, and was funded by the European Union.

It was published in the peer-reviewed Diabetologia, the journal of the European Association for the Study of Diabetes, and is freely available to download on an open access basis.

The study was generally covered well by the papers that reported on it. However, many papers reported the increased risk of developing diabetes from drinking sugary drinks as being 22%, which to be fair was included in the press release about the study. The actual risk increase after adjusting for factors such as BMI was 18%.

The Daily Mail also included comments from a spokeswoman for the British Soft Drinks Federation, who sensibly advised that, like most things, soft drinks should be consumed in moderation.

What kind of research was this?

This was a case-cohort study in which researchers used data from a large study looking at how lifestyle and genetic factors interact to increase the risk of developing diabetes. Participants in the study were drawn from the UK, Germany, Denmark, Italy, Spain, Sweden, France and the Netherlands.

The study aimed to evaluate the association between the consumption of sweet drinks (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) and type 2 diabetes in European adults.

The authors point out that the consumption of sugar-sweetened drinks has been associated with an increase in the incidence of type 2 diabetes, but previous research has largely been in US populations. This means that the same association may not necessarily apply to Europe.

Consumption of sugar-sweetened drinks, they point out, may lead to type 2 diabetes because of its effect on weight gain. These drinks also have a 'glycaemic effect' that can lead to rapid spikes in blood glucose, as well as disturbances to the hormone insulin, which normally regulates blood sugar.

The association between diabetes and other types of soft drinks, such as fruit juice and artificially sweetened drinks, is less clear.

What did the research involve?

From the larger study (of 330,234 people), researchers selected 12,403 people who developed type 2 diabetes during the approximately 16 years of the study. Anyone who had existing diabetes at the start of the study was excluded from this group.

A diagnosis of type 2 diabetes was ascertained at each study centre in several ways, including through patients self-reporting and linking to GP and hospital registers, hospital admissions and mortality data. For most countries, researchers sought further evidence for the development of diabetes from a minimum of two independent sources, including independent medical record reviews.

The researchers randomly selected a subgroup of 16,154 individuals from the same study (including 778 who developed diabetes during follow-up) to act as a comparison group. The final sample size was 11,684 type 2 diabetes cases and a subgroup of 15,734 (including 730 diabetes cases).

Both groups had completed dietary questionnaires at baseline assessment, including information about their consumption of soft drinks. For most countries, these were divided into:

• sugar-sweetened soft drinks
• artificially sweetened drinks and juices (100% fruit or vegetables, or concentrates)
• nectars (fruit juices with up to 20% added sugar)

Researchers say there was little standardised information from the different European centres on the distinction between fresh and concentrated fruit juices, or between fruit juices and nectars. These categories were therefore studied in combination. They also excluded Italy, Spain and Sweden from their analyses because data from these countries did not distinguish between the different types of soft drinks.

Sweet drinks were divided into the following categories of average consumption:

• less than one glass a month
• between one and four glasses a month
• more than one to six glasses a week
• one glass a day or more

One glass was equivalent to 250g, the standard serving used in the dietary questionnaire.

Participants also completed questionnaires on other factors that could influence results (confounders), including smoking, alcohol, physical activity and educational level. Body weight and height were measured to calculate body mass index (BMI) and participants were categorised into normal weight, overweight and obese.

Most centres also collected information on any history of chronic conditions, such as high blood pressure, high cholesterol, previous cardiovascular disease, and family history of diabetes.

The researchers used standard statistical methods to analyse the association between soft drink consumption and diabetes. They then adjusted their results for confounders such as lifestyle factors and BMI.

What were the basic results?

They found that one 336g (12oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with a 22% increase in risk of type 2 diabetes (hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.09 to 1.38) and 1.52 (95% CI 1.26 to 1.83), respectively. An incremental risk applies to someone who had one drink (compared with someone who had none), or someone who had two drinks (compared with someone who had one), and so on.

After adjusting for energy intake and BMI, there was still an association between sugar-sweetened soft drinks and type 2 diabetes (HR 1.18, 95% CI 1.06 to 1.32), but the association with artificially sweetened soft drinks was not statistically significant (HR 1.11, 95% CI 0.95 to 1.31).

The participants' juice and nectar consumption was not associated with type 2 diabetes incidence.

How did the researchers interpret the results?

The researchers say the study corroborates previous research on the association between increased incidence of type 2 diabetes and the high consumption of sugar-sweetened soft drinks in European adults, independent of their BMI.

Conclusion

This is a large, well-designed European study that appears to confirm the health risks of regularly consuming soft drinks. However, this study did have some limitations:

• Dietary assessments were carried out only once, at the start of the study, so it did not take account of any changes in people's consumption of soft drinks over the years.
• Consumption of soft drinks was self-reported, which introduces the possibility of error.
• The definition of juices and nectars included drinks both with and without added sugar. As the authors point out, the lack of any association between this category and diabetes should be interpreted with caution.
• The study cannot establish whether the consumption of sugary drinks causes diabetes. Its results may have been affected by various other factors (called confounders), although researchers tried to take account of these.

It's important to stay well hydrated, especially in warmer weather, but water is the healthiest choice for quenching your thirst. Or, if you can't do without soft drinks, there is almost always a sugar-free alternative.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

One soft drink a day increases Type 2 diabetes risk by a fifth. The Independent, April 25 2013

One fizzy drink a day may raise diabetes risk by fifth. The Daily Telegraph, April 25 2013

Diabetes danger in just ONE sugary drink a day: Chance of developing Type 2 increases by a fifth. Daily Mail, April 24 2013

One fizzy drink a day 'raises the risk of diabetes by a fifth'. Metro, April 25 2013

Links To Science

The InterAct consortium. Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct (note – document is in WinZip format). Diabetologia. Published online April 2013

"The Cuban diet – eat less, exercise more – and preventable deaths are halved," is the advice in The Independent.

This is not a new Latin diet and dance fad, but news based on research into how Cuba’s rollercoaster economic history has affected the health of the Cuban people.

During the early 1990s, Cuba suffered an economic downturn due to a tight US embargo on imports and the collapse of the Soviet Union, which had been supporting the country.

This led to a drop in the number of calories consumed in the average Cuban diet. Due to the embargo, petrol became virtually unobtainable, and more than 1 million bicycles were distributed by the government, leading to an increase in physical activity.

These factors contributed to an average weight reduction per citizen of 5.5kg over the course of the five-year economic crisis. During this time there was a significant drop in prevalence of, and deaths due to, cardiovascular diseases, type 2 diabetes and cancers.

But once the crisis was over and people started to eat more and exercise less, these trends began to reverse.

The study suggests that population-wide health initiatives that encourage people to eat less and exercise more could achieve significant positive health outcomes. The question is – how, in an affluent Western democracy, do you encourage people to eat less and exercise more if they are not forced to do so?

Where did the story come from?

The study was carried out by researchers from academic centres in Spain, Cuba and the US. There is no information about external funding.

The study was published in the peer-reviewed British Medical Journal.

It was reported accurately in the papers, although headlines like the Daily Mail’s “Lose weight the CUBAN way” and The Independent’s “The Cuban diet” trivialise the hardship that Cuban people underwent during the time in question. While they did enjoy a drop in cardiovascular disease and diabetes deaths during this period, they also experienced a sharp rise in malnutrition-associated disorders, such as neuropathies (nerve damage).

What kind of research was this?

The paper used data from regular cross-sectional health surveys of the Cuban population and drew on cardiovascular studies, chronic disease registries and vital statistics over three decades, from 1980 to 2010.

Its aim was to evaluate the associations between weight change across the whole Cuban population and the incidence, prevalence and death rates from diabetes and death rates from cardiovascular disease and cancer.

The authors say that the health effects of population-wide changes in body weight on a well-nourished population are unknown.

In Cuba, they point out, marked and rapid reductions in mortality from diabetes and coronary heart disease were observed after the economic crisis of the early 1990s when, in the aftermath of the dissolution of the USSR and during the US embargo on imports, there were severe shortages of both food and fuel.

These led to people eating less, and walking and cycling more (the government distributed more than 1 million bicycles during the crisis).

Since this time, the Cuban economy has shown a modest but constant recovery, especially since 2000.

What did the research involve?

The researchers used a variety of sources including national and regional surveys, to track changes in body weight, physical activity, smoking and daily energy intake between 1980 and 2010.

In particular, the authors drew on four cross-sectional surveys of adults aged 15 to 74, in the city of Cienfuegos, a relatively large city on the south of the island.

The surveys, of between 1,300 and 1,600 adults each, took place in 1991, 1995, 2001 and 2010 and included measurements of height and weight, which were used to assess body mass index.

The researchers also drew on national surveys of 14,304 people in 1995, 22,851 people in 2001, and 8,031 people in 2010, which assessed risk factors for chronic disease. They obtained data on diabetes rates from Cuban health registries spanning the period 1980–2009. They obtained information on mortality from diabetes, coronary heart disease, stroke, cancer and all causes for the period 1980–2010 from the Cuban Ministry of Public Health.

They analysed trends of change in disease prevalence and mortality over time and examined how this was related to changes in body weight.

What were the basic results?

Overall, between 1991 and 1995, the era of the economic crisis, the Cuban population experienced an average 5.5kg reduction in body weight. This was accompanied by rapid declines in death rates from diabetes and heart disease.

Between 1996 and 2002 (that is, with a lag of about five years after the crisis) there was an associated reduction in diabetes and cardiovascular disease mortality:

• diabetes death rates fell by 50% (13.95% annually)
• coronary heart disease (CHD) death rates fell by 34.4% (6.5% annually)
• deaths from all causes fell by 10.5%

After the crisis had passed, there was an average population-wide increase in weight of 9kg per person. In 1995, 33.5% of the population were overweight or obese and this increased to 52.9% by 2010.

This weight regain was followed by an increase in diabetes incidence and mortality:

• From 2006 to 2009, there was a 140% increase in diabetes incidence (new cases) and a 116% increase in diabetes prevalence (total number in the population with the condition).
• From 2002 onwards diabetes mortality increased by 49% (from 9.3 deaths per 10,000 people in 2002 to 13.9 deaths per 10,000 people in 2010).
• A slowing in the rate of decline in mortality from coronary heart disease was also observed.

How did the researchers interpret the results?

The researchers say that an average population-wide weight loss of 5.5kg per person was accompanied by diabetes mortality falling by half and mortality from coronary heart disease falling by a third. Increased body weight following the crisis was associated with an increase in diabetes incidence and mortality and a slowing down in the decline in mortality from CHD.

The authors suggest that a modest reduction in calorie consumption would “reverse the global obesity epidemic” and reduce deaths from diabetes by half and CHD by a third.

Conclusion

This is an interesting study that appears to show that modest weight loss within a relatively short period across the whole population is associated with a downward trend in diabetes and reductions in death rates from both diabetes and heart disease.

Similarly, weight regain was associated with an increase in diabetes incidence, prevalence and mortality as well as a slowing down in the decline of cardiovascular deaths.

This type of study draws on many different data sources and, as such, there is a possibility of error. Also, as the authors point out, data was missing on diabetes incidence during the crisis years and diabetes incidence showed wide fluctuations in subsequent years.

It is also difficult to conclude that changes in weight are solely responsible for changes in disease rates as other factors may also have a role. For example, smoking slowly decreased in Cuba during the 1990s.

It is not clear if the findings from the paper can be generalised to other countries. Cuba had, and continues to have, a highly centralised system of government where individual autonomy is limited.

To attempt to enforce a nationwide average reduction in body weight in the UK of 5.5kg per person would probably require a degree of social engineering that most people in this country would find intolerable. As the authors point out, an enforced situation of food and fuel shortages is not something anyone would wish to repeat.

While the study reinforces current health messages about the importance of diet and physical activity and a healthy weight, the best way for governments to attempt to reduce global obesity rates remains unclear.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

The Cuban diet: eat less, exercise more - and preventable deaths are halved. The Independent, April 10 2013

Hard times behind fall in heart disease and diabetes in 90s Cuba, says study. The Guardian, April 9 2013

Lose weight the Cuban way: Economic crisis triggered an average weight loss of 11lb and slashed the risk of heart disease and diabetes. Mail Online, April 9 2013

Losing just 8lb can be a lifesaver. Daily Express, April 10 2013

Links To Science

Franco M, Bilal U, Orduñez P, et al. Population-wide weight loss and regain in relation to diabetes burden and cardiovascular mortality in Cuba 1980-2010: repeated cross sectional surveys and ecological comparison of secular trends. BMJ. Published online April 9 2013

"Stand up if you want to stay healthy, warn researchers," the Daily Mail reports, as a large study has found an association between time spent sitting down and chronic disease.

The study surveyed middle-aged Australian men at one point in time. It found that after adjusting for other factors associated with disease (such as body mass index and physical activity levels) men who said that they sat for more than four hours a day were at increased risk of being diagnosed with a chronic disease, including cancer, heart disease, diabetes and high blood pressure.

When these chronic diseases were examined separately, sitting for more than six hours a day was associated with increased odds of diabetes, and sitting for at least eight hours a day was associated with increased odds of high blood pressure.

However, this study cannot prove that increased time spent sitting down leads to the development of chronic diseases – other factors may have been involved. And it cannot tell whether increased sitting time occurred before or after the development of chronic diseases. People with a chronic disease such as diabetes may have a more sedentary lifestyle as a result of their condition.

Despite its limitations, this study seems to add to the growing body of evidence that physical inactivity is bad for you.

Where did the story come from?

The study was carried out by researchers from the University of Western Sydney, Australia, and Kansas State University in the US. No sources of financial support for this study are explicitly stated.

The study was published in the peer-reviewed International Journal of Behavioural Nutrition and Physical Activity.

The study was reasonably well-reported by The Daily Telegraph and the Daily Mail, but there were several mistakes and omissions in the reporting.

First, both headlines talk about sitting down increasing the risk of cancer. However, although the study found a link between increased time spent sitting and the odds of developing any chronic disease, when cancer was examined by itself no significant association was found. This means the results seen could have been the result of chance.

Second, most of the reporting focused on the potential risk faced by office workers, but the study looked at time spent sitting – not occupation.

The research suggests that all groups of men who spend long parts of the day sitting down – whether they are unemployed, or work as bus drivers or air traffic controllers – have the same potential increase in risk.

What kind of research was this?

This was a cross-sectional study. It aimed to explore the association between sitting time and a range of chronic diseases in middle-aged Australian males.

Cross-sectional studies highlight possible associations between behaviour and health outcomes, but they cannot prove a cause and effect relationship.

Because information in cross-sectional studies is only taken at one point in time, this study cannot determine whether increased sitting time is associated with the development of chronic diseases or whether chronic diseases are associated with increased sitting time.

Cohort studies, where people are followed over time, are needed to determine which came first.

Even in a cohort study it would be difficult to pinpoint time sitting down as the influencing factor on the risk of chronic disease, as various health, lifestyle and behavioural factors may have an effect.

What did the research involve?

This study used information from 63,058 men aged between 45 and 64 years old who were living in New South Wales, Australia.

The men were asked to complete a questionnaire reporting:

• whether they had ever been told by a doctor that they had a chronic disease (cancer – excluding skin cancer, heart disease, diabetes or high blood pressure)
• how much time they spent sitting each day
• how much walking, moderate and vigorous activity they performed each week
• highest educational qualification
• household income
• smoking status
• height and weight (to calculate body mass index)
• functional limitation, which is the extent to which an individual’s health limits their ability to perform daily functional activities (measured using the Medical Outcomes Study Physical Functioning scale)

The researchers then examined the odds of having each, or any, of the following chronic diseases:

• cancer (excluding skin cancer – risk factors for skin cancer are different from those for most other types of cancer)
• heart disease
• diabetes
• high blood pressure

For each chronic disease they calculated the risk associated with the following categories of sitting time:

• less than four hours
• four to less than six hours
• six hours to less than eight hours
• at least eight hours sitting time a day

The researchers adjusted their analyses to account for the following confounders: physical activity, age group, educational qualification, household income, smoking status, BMI and functional limitation.

What were the basic results?

Any chronic disease

The researchers found that increasing sitting time was associated with increased odds of any chronic disease. After adjusting for potential confounders, the researchers found that, compared with men who reported sitting for less than four hours a day, the odds of having any chronic disease were:

• 6% higher in men who reported sitting for between four and six hours a day
• 10% higher in men who reported sitting for between six and eight hours a day
• 9% higher in men who reported sitting for at least eight hours a day

Diabetes and high blood pressure

When chronic diseases were analysed individually, it was found that men who reported sitting for between six and eight hours a day had significantly increased odds (15%) of diabetes compared with men who reported sitting for less than four hours a day. Men who reported sitting for at least eight hours a day also had significantly increased odds of diabetes (21%) and significantly increased odds of high blood pressure (6%) compared with men who reported sitting for less than four hours a day.

Cancer or heart disease

There were no significant associations between sitting time and cancer or heart disease.  

How did the researchers interpret the results?

They state that: “Independent of physical activity, BMI, and additional covariates, sitting time was significantly associated with diabetes and overall chronic disease in this sample of Australian males.”

Conclusion

The results of this study suggest that there is an association between longer periods of time spent sitting down and diabetes and overall chronic disease in middle-aged Australian males.

Previous research has also found that the amount of time spent sitting down (‘sedentary behaviour’) is a risk factor for health, and that this risk factor is independent of the amount of time spent performing physical activity. This large study, which took into account several potential confounding variables, adds to this body of evidence. However, this study has limitations:

• Due to the cross-sectional study design, we cannot tell whether increased sitting time occurs before or after the development of chronic diseases.
• All of the data was self-reported by the men in the study. This means that it could have been affected by recall bias, or by under- or over-reporting.
• Not all people who were invited to complete the questionnaire did so. This means that there could have been a ‘selection bias’ in the recruitment of participants. This could have skewed the results either way – healthy people may have been more likely to respond or, alternatively, men more worried about their health may have been more likely to respond.
• It should also be remembered that this study was performed in middle-aged Australian men, and it is unclear whether the results can be generalised to other populations.

Despite these limitations, this study offers further support for the current physical activity recommendations for adults and the fact that physical inactivity can be bad for you.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Sitting at your desk for six hours a day dramatically increases the risk of cancer and diabetes. Daily Mail, February 20 2013

Sitting down at work 'increases risks of cancer'. The Daily Telegraph, February 20 2013

Links To Science

George ES, Rosenkranz RR, Kolt GS. Chronic disease and sitting time in middle-aged Australian males: findings from the 45 and Up Study. International Journal of Behavioral Nutrition and Physical Activity. Published online February 8 2013

“People with diabetes 48% more likely to suffer heart attack, researchers find”, says The Guardian. Meanwhile, the Daily Mail reports that people with diabetes are “65% more likely to have heart failure than the rest of the population”.

Both stories are based on the most recent report of the National Diabetes Audit, which presents data from England and Wales on the complications that arise due to diabetes.

Diabetes makes it difficult for the body to control blood sugar levels. High blood sugar levels can damage blood vessels and lead to range of complications, such as:

• heart attacks
• heart failure
• stroke
• angina – chest pain that results from a temporary restriction of blood supply to the heart
• kidney disease
• retinopathy – where the retina (the light-sensitive layer of tissue at the back of the eye) is damaged
• foot ulcers, which in the most serious cases, require a section of the foot or lower leg to be amputated

People with type 1 diabetes can also experience a dangerous complication called diabetic ketoacidosis where the body breaks down fat as an alternative source of fuel. Left untreated, diabetic ketoacidosis can be fatal.

The National Diabetes Audit report highlights these complications, as well as deaths in people with diabetes. The audit confirms and quantifies these risks, and provides recommendations on how the NHS can benefit from addressing the complications of diabetes, and how this can improve the lives of people with diabetes.

Who produced the report?

The National Diabetes Audit is produced by the NHS Information Centre each year. It looks at diabetes care and outcomes throughout England and Wales. The portion of the report covered in the media specifically focuses on complications and deaths related to diabetes. The current report covers the eighth year of the audit, and is based on data from 2010-11.

The National Diabetes Audit collects data from 85% of diabetes patients in England and 54% of patients in Wales. The report also includes data on non-cardiovascular complications, but we will mainly focus on the cardiovascular complications as reported in the media.

What evidence does the report look at?

The audit reviews the risk of several known diabetes complications, comparing risks seen in people with diabetes versus the general population. Most of the complications reviewed are seen after several years of poorly-controlled blood sugar levels, high blood pressure and high cholesterol. The conditions reviewed include:

• Myocardial Infarction (or heart attack), which occurs when the blood supply to part of the heart is interrupted, this results in the death of some heart cells.
• Heart failure, which occurs when the heart cannot pump enough blood to meet the body’s needs. The most common cause of heart failure is a previous heart attack, which caused the death of some areas of heart muscle, meaning the heart can’t pump effectively.
• Angina, which is a chest pain that results from a temporary restriction of blood supply to the heart. These temporary blockages are a sign that the person has coronary heart disease and is at risk of a heart attack due to complete blockage.
• Stroke, which occurs when the blood supply to the brain is disrupted (most commonly due to a blocked blood vessel), and can result in permanent loss of some brain function.

The audit also investigated the risk of death for diabetics compared to the general population.

To assess and compare these risks, the audit collected diabetes patient information from primary care records as well as hospital admissions data. It also collected data from Primary Care Trusts (in England), local health boards (in Wales), and national-level data to compare the number of complications seen specifically in diabetes to that observed in local populations. This gives us an idea of the excess risk for complications and death borne by individuals with diabetes.

The audit included data from nearly 2 million people with diabetes during 2010-11.

What are the main findings of the report?

The audit provides figures which have been statistically adjusted to reflect the demographics of the wider population, enabling comparisons to the rest of the UK on the percentage of people with diabetes who experienced a complication during 2010-11. These figures include:

• 1.38% (69,957) of people with diabetes had an episode of angina
• 1.54% (14,476) were hospitalised for heart attack
• 0.560% (45,001) had heart failure
• 0.036% (17,892) had a stroke

Compared to the prevalence of these conditions in the wider population of England and Wales, the audit found that people with diabetes are at increased risk for all of the conditions. This additional risk varied in size, and included:

• 71.3% increased risk of angina
• 48.0% increased risk of heart attack
• 64.9% increased risk of heart failure
• 24.9% increased risk of stroke

Further analysis revealed that the risk of experiencing any of the cardiovascular complications (heart attack, stroke, angina or heart failure) is higher in men, in older diabetics and in those living in the most deprived areas of the country.

When examining the risk of death during the year, the audit found that there were 24,120 additional diabetes-associated deaths in England and Wales during 2010-11. The risk varied by type of disease, people with type 1 diabetes had a 135% increased risk, and people with type 2 diabetes showed a 36.4% increased risk, compared to the wider population. Additional analysis showed that admission to a hospital for heart failure was the strongest predictor of death, with an increase of 261%.

What information on other types of complications did the report provide?

The audit’s figures for other complications during 2010-11 were:

• 0.074% (9,753) experienced kidney disease severe enough that a transplant or dialysis was required
• 0.23% (3,042) required a minor amputation
• 0.29% (1,731) required a major amputation
• 0.42% (8,472) developed diabetic ketoacidosis
• 0.26% (9,501) developed retinopathy

What recommendations does the report make?

The results of the audit are not too surprising, given that the conditions assessed are known complications of diabetes. However, the extent of the excess risk seen in people with diabetes, combined with the high prevalence of the disease across the UK, may result in a high burden on both the patient and the NHS.

The National Diabetes Audit report says “diabetes care aims to minimise complications (the acute and long-term diseases and premature death) caused by diabetes. Diabetes complications incur the greatest costs of diabetes to the patient and the health service. The risk of complications is reduced if the appropriate NICE-recommended care processes are completed and treatment targets are achieved.” It recommends better co-ordination of diabetes and cardiovascular care.

Given the increased risk of death among diabetics compared to the wider population, the audit report recommends that risk of premature death can be reduced by more action to prevent type 2 diabetes, and to reduce complications by improving diabetes care for all people with diabetes.

Reducing the risk of diabetes-related heart conditions

Diabetes is a major risk factor for cardiovascular conditions. For type 2 diabetes, the first step should be lifestyle changes, such as improving diet and increasing physical activity. If you have diabetes and these lifestyle changes fail to control your condition, your doctor may recommend you start taking diabetes medication.

Diabetics can also work with their GP to assess their risk of cardiovascular conditions, and work to reduce their risk through lifestyle changes, such as managing blood sugar, cholesterol levels, and blood pressure.

Read more about healthier living with diabetes.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

People with diabetes 48% more likely to suffer heart attack, researchers find. The Guardian, December 10 2012

"Shocking": Research shows heart risk is 50% higher in diabetics. Daily Mirror, December 10 2012

Diabetics are almost 50% more likely to have a heart attack than those without the condition. Daily Mail, December 10 2012

Diabetes fuels heart failure risk. BBC News, December 10 2012

"Syrup found in biscuits, ice cream and energy drinks fuelling diabetes on a 'global scale'," reports the Daily Mail, highlighting that countries that use large amounts of fructose corn syrup have diabetes rates "20% higher" than countries where it is less common.

This report comes from an ecological study looking into whether there is a link between diabetes levels and the availability of high fructose corn syrup (HFCS). Availability is a measurement of how much of a substance is produced or imported into a country – it does not automatically relate to consumption.

HFCS is used as a sweetener in a wide range of processed food and drinks, but its use and consumption varies widely between countries.

The study found that countries that produced and sold the most HFCS also had higher levels of diabetes when compared with countries with the lowest levels of HFCS availability.

Prevalence of diabetes was 8.0% in the countries with high HCFS availability, compared with 6.7% in countries with lower availability – a difference of approximately 20%.

However, this informative study has some limitations and did not set out to prove that high levels of HFCS consumption caused an increased prevalence of diabetes. Importantly, it did not show that the people with diabetes were consuming more HFCS.

Ecological studies such as these are useful but should be interpreted alongside other studies looking into associations between dietary intake (including HFCS), weight and diabetes at an individual level, so that a complete picture of the potential relationships involved can emerge.

Biscuit-loving UK readers of the Mail's alarming headline will be pleased to hear that consumption of fructose syrup in this country is negligible – a measly 0.38kg per person per year. In the US a whopping 24.78kg per person per year is consumed – more than 65 times that consumed in the UK.

Where did the story come from?

The study was carried out by researchers from the University of Oxford (UK) and the University of Southern California (US). No funding source was reported.

The study was published in the peer-reviewed journal Global Public Health.

Despite a typically arresting headline, the Daily Mail's reporting of this research is well balanced. Especially useful is the reporting of absolute differences between diabetes rates in the countries: "Rates of diabetes were 8% in high-consuming nations and 6.7% among low consumers – a difference of 20%."

This is useful for readers to get a feel for the magnitude of the difference being talked about.

The usual temptation for media outlets is to only report the headline-grabbing "20% higher" figure without any further explanation, which can leave readers thinking the news is more startling than it actually is.

The Mail should also be praised for including a useful graph that shows readers the sharp differences between HFCS availability in different countries, which is a good visual aid.

What kind of research was this?

This was an ecological study looking at the relationship between the availability of high fructose corn syrup (HFCS) and the prevalence of type 2 diabetes across different countries.

An ecological study is an epidemiological study that analyses data at a population level, rather than at an individual level.

HFCS is a corn syrup modified to increase the level of fructose and is used a lot in some processed foods and beverages as a sweetener to replace sugar, as well as prolong shelf life and appearance.

It is found in a host of items, from soft drinks and breakfast cereals to breads, fast food and yoghurt.

Due to historical and economic reasons – namely a series of US trade tariffs – the use of HFCS is particularly widespread in the US, as it serves as a cheaper substitute for more expensive imported sugar.

The researchers report that a growing body of evidence supports the hypothesis that in addition to overall sugar intake, fructose is especially detrimental to health and increases the risk of type 2 diabetes.

It states that the epidemics of obesity and type 2 diabetes we're currently seeing constitute an "alarming public health concern", and that global increases in the use of HFCS in food and beverage production may be contributing to this.

What did the research involve?

Using published resources, the researchers estimated country level estimates of:

• total sugar availability
• HFCS availability
• total calorie availability
• obesity
• diabetes prevalence 

The information sources used by the researchers included:

• diabetes prevalence – International Diabetes Federation (IDF), Diabetes Atlas (fourth edition) and global estimates reported by the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (GBMRF)
• food availability – the Food and Agriculture Organization of the United Nations (FAOSTAT) database of 200 countries
• HFCS production – an international sugar and sweetener report and data on HFCS quotas for EU countries by F.O. Licht, a commercial organisation that provides information and analysis on some aspects of the global commodity market

Information from 43 different countries was analysed, some of which did not use HFCS at all. The researchers then looked for correlations between the dietary elements (total sugar, HFCS and total calories availability) and the rates of obesity and diabetes.

Some of the analysis adjusted for the effects of body mass index (BMI), as well as population and gross domestic product (GDP) obtained from International Monetary Fund (IMF) tables.

What were the basic results?

Data on 43 countries was available covering the use of HFCS (kg per year per person) alongside estimates of total sugar intake (kg per year per person), BMI, and the estimates of diabetes prevalence from two separate sources (IDF versus GBMRF).
 
Use of high fructose corn syrup per person

The US was by far the highest consumer of HFCS out of the 43 nations assessed at 24.78kg per year per person, far ahead of second place Hungary at 16.85kg per year per person. The UK was far lower, at 0.38kg per year per person. Fourteen countries registered 0kg per year per person – all except India were European.

Countries with high HFCS availability versus countries with low HFCS availability

The researchers compared measures from those countries with low availability of HFCS (21 countries) versus high availability of HFCS (21 countries). Countries with high availability were defined as having an average value of more than 0.5kg HFCS per person per year.

The average HFCS consumption in the low-availability countries was 0.1kg per person per year, compared with 5.8kg per person per year in the countries classed as having high availability.

The report stated that all indicators of diabetes were higher in countries that had high availability of HFCS compared with those that had low availability. This trend was more significant for the IDF measure of diabetes prevalence.

Countries with high HFCS availability had an average diabetes prevalence of 7.8%, compared with 6.3% in those with low availability (p=0.013). So, the high-availability countries had approximately 20% higher diabetes prevalence than those with low availability (23.8%)

Using estimates of fasting glucose levels to estimate diabetes prevalence showed the difference was 5.33mmol/L in high HFCS availability countries, versus 5.23mmol/L in low availability countries.

Other influencing factors

There were no significant differences between countries of different availability of HFCS (high versus low) for BMI, total calorie intake, cereal intake, total sugar intake and "other sweeteners" intake.

The researchers interpreted this as meaning that the differences in diabetes prevalence may have had more to do with the level of HFCS availability, rather than these additional factors.

How did the researchers interpret the results?

The researchers concluded that, "Our analysis revealed that countries electing to use HFCS in their food supply have a diabetes prevalence that is ~20% higher than that in countries that do not use HFCS […] even after adjusting for country-level estimates of BMI, population and gross domestic product."

They linked their own finding to previous research that they reported "showed that increasing consumption of HFCS in the twentieth century was the primary nutritional factor associated with increasing prevalence of type 2 diabetes."

This led them to warn that, "The increasing popularity of HFCS around the world should, therefore, be considered seriously due to its potential contribution to increases in fructose in the global food supply and its association with the global prevalence of type 2 diabetes."

They also make the point that even modest increases in disease prevalence can have a significant economic impact if a disease is both common and its treatment complex. They state that the health costs of treating diabetes in the US during 2007 was $174bn. A 20% reduction in diabetes prevalence would save $34.8bn, or approximately $95m per day.

Conclusion

This ecological study suggests that countries with a high availability of high fructose corn syrup (HFCS) – defined as more than 0.5kg per person per year – may have higher diabetes levels than those defined as having low HFCS availability.

Countries where availability was defined as high had approximately 20% higher rates of diabetes than those defined as having low availability.

While informative, this study does not prove cause and effect. For example, this study does not show that individuals with diabetes consumed higher levels of HFCS or that this consumption contributed to their diabetes.

Ecological studies such as these need to be interpreted alongside other studies investigating the association between calorie intake (including from HFCS), weight and diabetes at an individual level, so that the full picture of the relationships involved can be established.

Neither HFCS nor diabetes was measured at an individual level, so we cannot assume that the link reported at the country level would be found if the study used individual level data – for example, examining individual diet and diabetes diagnosis.

The low versus high availability of HFCS cut-offs were not justified for clinical or other reasons in the study, and this may have been an arbitrary cut-off.

The choice of where to put this cut-off for low versus high availability and the reasons for such a decision are very important, as selecting a different cut-off point could lead to vastly difference results.

The precise country level estimates of HFCS and diabetes levels are also likely to be subject to significant error that could affect the results.

However, without assessing each information source in detail we cannot say how important this limitation may be, but it is important to be aware of it.

This type of study design is a useful starting point to identify country level trends, but further research is needed at an individual level to explore whether HFCS consumption is linked to diabetes in any way.

Finally, the fact that HFCS availability was relatively low in the UK would suggest that this is less of a public health issue here than in the USA.

However, consumption of HFCS may vary considerably person to person so the Great British biscuit lover should be aware that eating high levels of sugar (HFCS or otherwise) – or indeed fat – is known to have detrimental effects to health.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.

Links To The Headlines

Syrup found in biscuits, ice cream and energy drinks fuelling diabetes on a 'global scale'. Daily Mail, November 27 2012

Links To Science

Goran MI, Ulijaszek SJ, Ventura EE. High fructose corn syrup and diabetes prevalence: A global perspective. Global Public Health. Published online November 27 2012

'Diabetes care depressingly poor, say MPs', is the headline on the BBC News website. This is the damning verdict of a parliamentary report into standards of diabetes care in the NHS. The Public Accounts Committee reported that (in the words of the Daily Mail), “24,000 with diabetes ‘are dying needlessly’”.

The report was published by the Public Accounts Committee (PAC) – an influential group of MPs who have been given an oversight role to help ensure that taxpayers get value for money.

Based on official figures and spoken and written evidence from independent diabetes experts and officials, the PAC has set out recommendations for improved diabetes care in the NHS.

The report indicates that the NHS spent an estimated £3.9 billion on diabetes services in 2009/10. However, 80% of the costs are estimated to come from the management and treatment of avoidable diabetes-related complications, such as kidney disease and foot ulcers.

The report highlights that the number of people with diagnosed and undiagnosed diabetes is 3.1 million, set to rise to 3.8 million by 2020. This projected increase is likely to have a significant impact on NHS resources, the committee says.

The report accepts that there is consensus about what needs to be done for people with diabetes. However, progress in actually delivering the recommended standards and achieving treatment targets has been ‘depressingly poor’, it says.

Who produced the report?

The report, ‘Department of Health: The management of adult diabetes services in the NHS’ has been published by the PAC.

The PAC is made up of MPs appointed by the House of Commons, and is responsible for overseeing government expenditures to ensure transparency, value for money, and accountability in government financial operations.

What are the main findings?

The main findings of the report are:

• an estimated 80% of the costs of diabetes come from the management and treatment of avoidable diabetes-related complications (such as diabetic eye disease and kidney disease)
• the Department of Health estimates that up to 24,000 people with diabetes are dying each year from causes that could be avoided through better management of their condition
• only half of people with diabetes receive all the basic tests to monitor their condition, and failure to carry out these simple checks heightens the risk of developing complications
• less than one in five people with diabetes have achieved the recommended levels for blood glucose, blood pressure and cholesterol
• despite the Department of Health improving information on diabetes, this information is not being used effectively to assess and improve the quality of care
• many people with diabetes develop avoidable complications because they are not effectively supported to manage their condition and do not always receive care from appropriately trained professionals across primary and secondary care
• the projected increase in the diabetic population could have a significant impact on NHS resources

The report states that the reasons these problems have arisen include:

• the fact there is no strong national leadership – each Primary Care Trust is largely ‘left to their own devices’ when it comes to how they decide to tackle diabetes
• there are no effective accountability arrangements for commissioners (those in charge of allocating funds to particular services)
• there are no appropriate performance incentives (rewards, usually financial, designed to encourage best practice) for the providers of diabetes care

Committee chair, Margaret Hodge, is quoted as saying ‘variation in the level of progress across the NHS also means that there is an unacceptable “postcode lottery” of care’.

What evidence did the report consider?

This report used evidence from a report on the management of adult diabetes services in the NHS, England, published earlier this year (May 2012) by the National Audit Office.

When writing their report, the PAC also took into consideration written and oral evidence from expert witnesses and officials from the Department of Health regarding the management of adult diabetes services in the NHS in England.

Written evidence was also submitted by organisations such as Diabetes UK, and the Association of British Clinical Diabetologists.

What recommendations does the report make about diabetes care in the NHS?

Based on the conclusions set out in the report, the PAC wants the Department of Health to set out how improvements on diabetes services will be delivered in future. It recommends that:

• the NHS sets out how it will deliver improvements in diabetes care after the NHS structure changes in March 2013
• the NHS aims to achieve universal coverage of basic tests for people with diabetes so they can monitor their condition 
• clear expected outcomes are set out for 2014/15 targets for the proportion of people with diabetes achieving recommended blood glucose, blood pressure and cholesterol levels within a specific time
• payment systems effectively incentivise good care and better outcomes for people with diabetes
• information on diabetes is used to hold the NHS to account as well as to ensure the costs of diabetes are fully captured and understood
• people with diabetes receive, as a right, multi-disciplinary care from appropriately trained staff, as well as education and support for them to manage their own condition

What can I do if I am concerned about my diabetes? 

Management of diabetes aims to keep blood glucose levels as normal as possible to try to control symptoms and prevent associated complications developing.

Such complications can include:

• damage to the large blood vessels causing cardiovascular disease, such as heart attacks and strokes
• damage to the smaller blood vessels in the eyes, which can impair vision (retinopathy)
• damage to the blood vessels that supply the kidneys, resulting in kidney disease
• nerve damage
• foot ulcers

Read more about the complications of diabetes.

Such complications can affect people with both type 1 diabetes (who rely on insulin) and type 2 diabetes (who are commonly managed – at least initially – with diet control and oral diabetes medications).

If you have type 2 diabetes, you will need to look after your health very carefully. Caring for your health will make treating your diabetes easier and will minimise your risk of developing serious complications of diabetes, such as heart disease and retinopathy. The following are all important factors in diabetes care:

• self care – which includes things you can do each day to stay fit and maintain good physical and mental health
• attending regular reviews with your diabetes care team
• maintaining a healthy diet high in fibre, fruit and vegetables, and low in fat, salt and sugar
• exercise regularly, for example, you should aim to do at least 150 minutes of moderate-intensity activity, such as cycling or fast walking, each week
• not smoking
• limiting alcohol intake

If you have been diagnosed with diabetes, your GP will be able to explain your condition to you in detail and help you to try and understand and manage your condition.

Read more about diabetes and living with diabetes on NHS Choices.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.

Links To The Headlines

Diabetes care depressingly poor, say MPs. BBC News, November 6 2012

24,000 with diabetes 'are dying needlessly': Fewer than half of patients get vital checks, say MPs. Daily Mail, November 6 2012

Diabetes UK: 'NHS failings on care baffling'. ITV News, November 6 2012

Diabetes kills 24,000 sufferers a year in care postcode lottery. Daily Express, November 6 2012

‘Sitting for long periods increases the risk of diabetes, heart disease and death, researchers suggest’ BBC News reports.

The news is based on the findings of a review which summarised the results of all the observational studies that had looked at the association between the time spent sitting or lying down whilst awake (sedentary behaviour) and the risk of diabetes, cardiovascular disease, and death due to cardiovascular disease (such as heart attack) or any cause.

The link between worsening health outcomes and time spent sitting first became apparent in the 1950s when researchers found that London bus drivers were twice as likely to have heart attacks as their bus conductor colleagues.

The researchers were concerned that, due to changes in lifestyle and employment, the health problems associated with sedentary behaviour are likely to have worsened. They cite the findings of a 2011 study showing that the average adult now spends 50-60% of their day in sedentary pursuits.

The main findings of the study were that, compared to the shortest time spent sedentary, the longest time spent sedentary was associated with a:

• 112% increase in risk of diabetes
• 147% increase in cardiovascular events
• 90% increase in death due to cardiovascular events
• 49% increase in death due to any cause

This study cannot show that sedentary behaviour is the direct cause of the increases in risk. Nevertheless, it certainly seems to reinforce the recommendations that adults should perform at least 150 minutes of moderate-intensity aerobic activity every week.

Our ancestors did not have had to worry about going to the gym when they were spending 12 hours a day working in a coal mine or picking turnips. These days, however, for most of us, the working day provides very little opportunity for exercise and so we need to compensate for that fact.

Where did the story come from?

The study was carried out by researchers from Loughborough University and the University of Leicester. The primary author is being funded for a PhD in the Department of Cardiovascular Sciences, University of Leicester.

The study was published in the peer-reviewed medical journal Diabetologia.

The research was well-reported by the BBC, Daily Mail and Daily Express.

Both the Mail and the BBC included a number of useful quotes from the researchers involved in the study. For example, Professor Stuart Biddle (one of the research team, and Professor of Physical Activity and Health at Loughborough University), is quoted as saying ‘'There are many ways we can reduce our sitting time, such as breaking up long periods at the computer at work by placing our laptop on a filing cabinet (and then use them while standing up). We can have standing meetings, we can walk during the lunch break, and we can look to reduce TV viewing in the evenings by seeking out less sedentary behaviours’.

What kind of research was this?

This was a systematic review and meta-analysis looking at the association between the time spent sitting or lying down whilst awake, and the risk of diabetes, cardiovascular disease, and death due to cardiovascular disease (such as heart attack or heart failure) or any cause.

This study design is the best way to summarise what all of the existing research says on a research question. However, even a well-conducted systematic review (which this was) that has identified all relevant observational studies is likely to contain inherent limitations due to the differences in the study design, included populations, method of assessing exposures and outcomes, and duration of follow-up.

Such studies also cannot demonstrate cause and effect as there may be other confounding factors associated with both sedentary behaviour and disease risk (for example smoking, alcohol, diet, or socioeconomic factors) which the individual studies may not all have taken into account.

What did the research involve?

The researchers searched literature databases for cross-sectional and prospective cohort studies looking at the association between the time spent sitting or lying down whilst awake and health outcomes in adults.

The researchers assessed the quality of the studies. They then extracted data on the outcomes associated with the highest sedentary time compared with the lowest, and pooled the results of the studies. Where available, the researchers extracted the results that had adjusted for the greatest number of potential confounding factors that may be influencing the results (for example age, sex, education, smoking status, and diet).

What were the basic results?

The researchers included 18 studies (with a total of 794,577 participants) that had examined the association between the time spent sitting down and the risk of health outcomes (16 prospective cohort studies and two cross-sectional studies). The studies examined the association between sedentary time and diabetes (ten studies), cardiovascular disease (three studies), cardiovascular mortality (eight studies), and all-cause mortality (eight studies).

The studies were performed in a range of countries, including Australia, England, Canada, Germany, Japan, Scotland and the US. The researchers judged 15 of the studies to be of high quality.

All of the studies used a self-reported measure of sedentary time.

After pooling the results of the studies, the researchers found that the greatest time spent sitting compared with the lowest time spent sitting was associated with a:

• 147% increase in the risk of cardiovascular events (relative risk [RR] 2.47; 95% confidence interval [CI] 1.44 to 4.24)
• 112% increase in the risk of diabetes (RR 2.12; 95% credible interval [CrI] 1.61 to 2.78) - a credible interval differs from a confidence interval, in that rather than being based purely on the data provided by the study, it also takes into account prior data
• 90% increase in the risk of cardiovascular mortality (hazard ratio [HR] 1.90; 95% CrI 1.36 to 2.66)
• 49% increase in the risk of all-cause mortality (HR 1.49; 95% CrI 1.14 to 2.03)

Despite the fact that the studies were from a range of countries, and that each study was performed differently, the time spent sedentary was consistently associated with poorer health outcomes.

The researchers then limited their analyses to only include results that had controlled for the amount of physical activity people performed.

Although this changed the relative risks and hazard ratios, it did not change the conclusions: that sedentary time is associated with an increased risk of poor health outcomes. This suggests that the increase in risk seen is not due to the fact that people who spend longer sitting also perform lower amounts of moderate to vigorous physical activity.

How did the researchers interpret the results?

The researchers conclude that “sedentary time is associated with an increased risk of diabetes, cardiovascular disease, and cardiovascular and all-cause mortality; the strength of the association is most consistent for diabetes”. The researchers go on to propose that the results of their study suggest “that substituting sedentary behaviour with standing or light-intensity physical activity may reduce the risk of chronic disease and mortality, independently to the amount of [moderate-to-vigorous intensity physical activity] taken”.

Conclusion

In this systematic review, the results of all observational studies which have looked at the association between the time spent sitting or lying down whilst awake and the risk of diabetes, cardiovascular disease, and death due to cardiovascular disease or any cause, were pooled. This was done in order to determine the risks associated with sedentary behaviour.

Increased sedentary behaviour was associated with increased risk of all health outcomes.

The researchers also found that this effect was not mediated by the amount of moderate-to-vigorous physical activity people performed, and suggest that to reduce risk of diabetes, cardiovascular disease and death, people should try and substitute sedentary behaviour with standing or light-intensity physical activity.

As one researcher put it in a interview, “You can go for a 30 minute run every day, but if you're sitting around for the rest of the day, you're not doing yourself any favours.”

A systematic review and meta-analysis, like this study, is the best way to summarise what all of the existing research says on a research question. Still, both techniques, and this study, are subject to a number of inherent limitations:

• cross-sectional and cohort studies – the analysis which the study was based on – can never prove a direct casual effect, just detect association
• there may be other confounding factors not taken into account, such as age, smoking, alcohol, diet, presence of other (comorbid) diseases, and socioeconomic factors (though the researchers did try to take such factors into account whenever possible)
• all of these studies relied on self-reporting on sedentary behaviour – self-reporting is notoriously prone to inaccuracies
• each of the studies analysed and reported sedentary behaviour in different ways

Despite these limitations, this was a well-conducted and useful study. It would strongly suggest that many of us need to find ways to compensate for our desk-job lifestyles.

Performing moderate-to-intense physical activity (at least 150 minutes per week) and minimising the amount of time spent sitting is already recommended by the Department of Health. In addition, decreasing the amount of time we spend sitting, for example by holding ‘standing meetings’ could also be beneficial.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.

Links To The Headlines

Sitting for long periods 'is bad for your health'. BBC News, October 15 2012

Having a desk job leads to a shorter life as sitting down all days doubles the risk of diabetes and heart attacks. Daily Mail, October 15 2012

Sitting At A Desk At Work All Day Could Be A Risk To Health. Daily Express, October 15 2012

Links To Science

Wilmot EG, Edwardson CL, Achana FA, et al. Sedentary time in adults and the association with diabetes, cardiovascular disease and death: systematic review and meta-analysis. Diabetologia. Published online August 14 2012