New help for widespread disease

“We must stop looking at type 2 diabetes as a single disease and instead see it as a syndrome including many forms of diabetes,” says Mikael Rydén, professor of clinical and experimental fat tissue research at Karolinska Institutet’s Department of Medicine, Huddinge and senior physician at Karolinska University Hospital.

This is also a fundamental concept behind the new proposal to divide type 2 diabetes into four groups depending on severity and other characteristics.

“The article confirms that, at a genetic level, there are various forms of diabetes. That’s interesting in itself but, it would be even more interesting if we could gain a decent understanding of how different patients respond to various drugs. We currently have nine classes of drug but who should be given what? We’re not quite there yet. However, it is the first step towards what we call personalised medicine,” says Mikael Rydén.

Results must be confirmed

The new division proposed by the Swedish-Finnish research group will not however have any short-term effect; that is not how research works. The results must be confirmed in multiple studies and perhaps then the World Health Organisation (WHO), together with US and European organisations representing specialist diabetes doctors, will eventually sanction a change – but this will take time.

“It will be very interesting to follow this process over the coming decade,” says Mikael Rydén.

The existing division will therefore continue to apply for the foreseeable future and will also be used for the remainder of this article.

Even if diabetes has afflicted humans for thousands of years, researchers have noted an alarming change over recent decades. Diabetes in all its forms is on the rise.

“The number of new cases of type 1 diabetes per year has doubled since the mid-1980s and Sweden and Finland are global leaders in this trend. In addition, the larger group of type 2 diabetes sufferers is also rapidly increasing in size. We published data from the Swedish Prescribed Drug Register in which we compared the total number of number of people getting diabetes between 2007 and 2013, a period during which the percentage of the Swedish adult population diagnosed with diabetes increased from 5.8 to 6.8 percent. I make the figure for 2017 to be 7.8 percent, with type 2 diabetes sufferers being by far the largest group,” says Sofia Carlsson, senior lecturer and epidemiologist at Karolinska Institutet’s Institute of Environmental Medicine.

According to her calculation, over 600,000 Swedes now suffer from diabetes.

“We calculate that the lifetime risk of a Swedish person becoming diabetic is one in five,” she says.

The underlying causes of the increase in type 1 diabetes are unknown. Some researchers highlight the hygiene hypothesis, which proposes that we now live in such clean surroundings that our immune systems are underworked and begin to attack our own bodies. However, this hypothesis is as yet unproven.

The underlying causes of the increase in type 2 diabetes are more apparent. Over the past half century, major social changes have taken place that have increased the risk of developing diabetes. A number of studies have demonstrated that we exercise far less, particularly in terms of everyday exercise. Where once we walked or cycled to work, we now use public transport or take the car, we use the lift or escalator instead of the stairs, and so on.

Being overweight or obese

At the same time, food has become cheaper and access to fast, not always healthy, food has increased dramatically. Being overweight or obese reduces insulin sensitivity, or insulin resistance, increasing the risk of suffering from diabetes.

“We are built to walk a great deal, to eat relatively low-calorie food and to sleep when it gets dark, all of which have now gone out of the window,” says Mikael Rydén.

The ability to store energy when food is plentiful in order to survive periods of famine – once an evolutionary advantage – has now become a deathtrap, among other things leading to an increase in type 2 diabetes.

“We now have the opportunity to pack away calories as never before. A Mars Bar contains 200 kilocalories and one would have to stuff a lot of roots and berries to reach that level,” says Mikael Rydén.

And this change has been rapid. The past 50 years have seen immense changes to both access to food and the need to exercise.

“We have developed a society designed for maximum comfort. Portion sizes are increasing. In the 1970s, when I grew up, the largest bottle of soda available was 33 centilitres; now there are 3 litre bottles – with 10 percent sugar content,” continues Mikael Rydén.

“When you train and exert your muscles, you reprogramme them. Of course, using your muscles makes you stronger but reprogramming also occurs at a molecular level, improving the ability to absorb glucose. The signalling network of the muscles becomes more sensitive, improving the response to insulin. The number of mitochondria increases, meaning that you burn fat more after exercising muscles. Muscle mass also increases after training, which in itself requires a certain amount of energy,” she says.

With regard to the question of which type of training, for example training with weights or cardio, is most beneficial for preventing diabetes and other diseases, her response is unequivocal.

“Above all, whatever training you do is the best,” she says.

Health effects of weight training

Anna Krook explains that research is less advanced into the health effects of weight training than cardio, making it hard to compare the two forms of training, although she does allow herself a qualified guess.

“If one solely looks at insulin sensitivity, in all likelihood they are roughly equally beneficial; however, cardio has a number of additional positive effects on other organs, so it might be somewhat better. At the same time, weight training can be more achievable for the elderly, and the retention of muscle mass is an extremely important parameter for avoiding fall accidents and remaining independent,” she says.

Anna Krook also points out that some studies have suggested that not everyone responds equally well to physical activity, although she believes that this is simply a matter of identifying the correct exercise.

“It may be that the right training for the right individual is key,” she says.

Currently, many patients with type 2 diabetes are prescribed physical activity by their doctor, something that large studies have shown to have an excellent effect, sometimes even better than drug treatments. The problem is that these studies are often very ambitious in scope, with physiotherapists, behavioural therapists, doctors and nurses assisting in encouraging participants to actually carry out the planned physical activities. However, when this is translated into Swedish primary healthcare, the resources are often lacking.

“In healthcare, we must prioritise the sickest individuals meaning that in practice, preventative measures fall by the wayside, even though in the long-term it may be these that offer the greatest benefits in terms of survival and quality of life,” says Mikael Rydén.

When it comes to patients with type 1 diabetes, the choice of medication is not especially complicated. Patients must be prescribed insulin in various forms.

“Type 1 diabetes is caused by the failure of the body’s own insulin-producing cells, leaving one in need of substitution therapy. What we attempt to do is to as far as possible replicate the body’s own secretion of insulin.” says Jan Bolinder, professor of clinical diabetes research at Karolinska Institutet’s Department of Medicine, Huddinge.

This is achieved by using long-acting basal insulin that provides the body with the necessary base level of insulin. Fast-acting mealtime insulin is then added in the form of an injection immediately prior to eating, to deal with the rise in blood sugar levels caused by the meal.

Over the years, insulin molecules have been modified, thus refining the treatment, although it remains fundamentally the same.

Changes in the field of type 1 diabetes have primarily been on the technical side, in the form of insulin pumps and glucose sensors.

Instead of injecting insulin using a syringe or pen, a pump can be used that can be controlled by the patient. Insulin pumps have proven particularly successful for diabetic children, among other things due to their improved glucose control, avoidance of needles, simpler dosing of mealtime insulin and constant availability of insulin.

“Approximately two-thirds of all [diabetic] children and adolescents in Sweden have pumps, while the equivalent figure for type 1 diabetic adults is approximately one quarter,” says Jan Bolinder.

Checking their own blood sugar

In parallel with the development on the pump, there have also been rapid developments in terms of patients checking their own blood sugar levels. Patients have long had the ability to monitor their blood sugar with a pinprick and blood glucose meter. However, the problem is that blood sugar levels vary so much over the course of the day that individual measurements provide a fairly poor image of reality. Glucose sensors have now been developed that can be inserted beneath the skin to automatically measure glucose levels (sugar) more or less continuously.

“A continuous correct value is always available, as well as a graph of sugar checks over recent hours that shows the curve of blood sugar levels. This allows you to monitor trends; whether sugar levels are on the way up or down and perhaps are at risk of becoming dangerously low, so that one can take preventative measures,” says Jan Bolinder.

These sensors have evolved to include alarms of various kinds that can warn the user if sugar levels are too high or low, so that proactive measures can be taken. Glucose sensors have been an even greater success than insulin pumps, and in Sweden they are used by six of seven children and six of ten adults.

“The launch of a simpler and cheaper sensor system that requires active reading by the user has contributed greatly to this paradigm shift for self-monitoring. Clinical studies have also documented that the use of sensors leads to improved control of sugar levels, reduced risk for low blood sugar and, not least, an improved quality of life,” explains Jan Bolinder.

The latest development is the linking of sensors and pumps, providing a more self-contained monitoring system that functions somewhat like an artificial pancreas. Hybrid closed-loop systems are now available that can reduce the supply of insulin if sugar levels are threating to sink too low, as well as increase supply if the tendency is towards rising dangerously. The system works automatically overnight and between meals. However, the patient still needs to manually dose mealtime insulin using the pump.