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LIFE EXPECTANCY, MORTALITY, PREVENTION OF COMPLICATIONS AND HOPE

Henk-Jan Aanstoot, pediatrician

Disturbing statistics on diabetes were presented in the Dutch press in October 2021

In October 2021 disturbing statistics on diabetes were presented in the Dutch press: ‘The life expectancy of people with type 1 diabetes [T1D; discussed in the remainder of this article] is on average 13 years shorter and for type 2 diabetes [T2D] on average four years shorter than in people without diabetes’ (1). For many people this came as a shock, confronting them with the still-existing complications of diabetes which are often a difficult subject in the consulting room: everyone is aware of potential complications but they are not often discussed. Although important, the subject is often pushed to the background, not visible, frightening, disturbing, difficult and above all ‘worries for later’. Because complications are increasingly preventable, they should be discussed more often. This blog discusses life expectancy, mortality, prevention of complications and new possibilities. After the shock generated by these data it is time for new developments and hope! THINGS CAN BE DIFFERENT!

 

Then, yesterday and now

We have known about these worrying data from many countries surrounding us that have long-standing and well-functioning diabetes registration systems. These studies (3-5) have already made it clear that one hundred years after the discovery of insulin the treatment of diabetes still does not sufficiently protect against the development of acute and chronic complications. Since the early 90s we have known that good glucose control prevents complications and thus premature death. Fortunately, we are getting better at controlling glucose.

These life expectancy studies allow retrospective assessment of the impact of diabetes on the life expectancy of those people who have died. The people studied started receiving diabetes care about 15-40 years ago, at which time the treatment was completely different. Insulin twice a day, not everyone had a glucose meter (only urine measurement of glucose), glucose measurements only in case of problems and a daily profile once every 1-2 months, hardly any insulin pumps, no real long- or short-acting insulins. It was hard work regulating your glucose in those days.

In a 2015 study on more than 21,000 people with T1D in Scotland an 11-year reduction in life expectancy was observed (4, 6). In addition to HbA1c, severe hypoglycemia, diabetes duration, smoking and high blood pressure also played a role. The large Swedish National Diabetes Registry (NDR: almost 34,000 people with T1D) showed a clear association between the average HbA1c over many years and the risk of serious complications and death as a result (3). Other research in Sweden from 2019 also showed that life expectancy was 10-12 years shorter among adults who had developed T1D as a child (5), but improved (7). But again, yesterday is not now.

 

Complications = abnormal glucose

Fortunately much has changed in the last 2 decades. Hence the NIVEL study cannot predict life expectancy for people who were diagnosed less than 10 years ago or for a 5-year-old child who has just been diagnosed. Likely their outlook is better, which is confirmed by the scientific literature. In the past 15 years, the number of people achieving a relatively safe HbA1c (< 7.5%/58 mmol/mol) at Diabeter has risen from 17% (of 1,071 people with T1D in 2010) to 51% ten years later (of 2,952 people with T1D in 2020). In fact, a large worldwide study showed that even currently in many countries only around 30% of people with diabetes achieve this target of 7.5%/58 mmol/mol (8). A large Finnish study (9, 10) reported the impact of glucose control on complications and mortality. From 1969 to 1999, 5,396 people with T1D were followed in different cohorts of 5 year, dependent on year of diagnosis. The 1965-1969 group showed most complications whereas the 1995-199 group showed fewest complications. Despite these improvements there is still a need for even better glucose control.

It is of course of paramount importance to combat the factors that contribute most to the risk of cardiovascular disease. Most importantly these are HbA1c (i.e. glucose regulation), abnormal fat metabolism and diabetic kidney disease. The conclusion of the Finnish researchers was clear: optimal glucose control and timely treatment of (early signs of) complications are the most important factors to prevent complications and early death. And it’s never too late for that. They also point out that the risk of heart failure in women with T1D has not decreased over time. That is why special attention for the female heart is also necessary in care and research in type 1 diabetes.

 

Complications and T1D: result of too much/not enough/fluctuating glucose

In addition to the chronic complications discussed here, it is also important to mention the acute complications and effects of diabetes and glucose: high values ​​and low values, but also fluctuating values, ​​affect your acuity, mental capacity, concentration, fitness and sleep quality. Back to the chronic complications. These often first show as microvascular complications: blood vessel damage of the microvasculature affecting the retina, kidneys and nerves, resulting in serious consequences such as blindness, kidney failure and lack of sensation in feet (possibly leading to wounds and even amputation). In addition there are macrovascular complications: damage to large blood vessels with serious consequences often leading to death, such as strokes (cerebral haemorrhages/ infarctions), heart attacks and heart diseases (e.g. heart failure) and blood circulation problems in the feet and legs (leading to infections/amputations, etc). This mortality is usually preceded by serious morbidity of these organs and body parts.

 

Complications, Glucose and Aging

I often hear: ‘But complications are just part of having T1D, right?’. Complications may seem like a ‘regular part’ of T1D, but they are not: if you can regulate glucose properly, the risk decreases and if you would have normal glucose values, they would no longer occur. At least, not compared with people without T1D, because everyone ages of course and in many respects T1D complications resemble accelerated aging (which also induces similar complications). Blood vessel walls need to stay in good shape and preferably have a surface that is as smooth as possible. The cells that line the blood vessels (endothelial cells) are repaired if necessary. Normally, the body has a repair capacity for about 70-80 years, taking into account hereditary differences between people. However, environmental factors like high blood pressure, smoking, high LDL cholesterol will lead to increased blood vessel damage. In case of T1D, abnormal glucose levels also cause increased damage, thus requiring increased repairs, accelerating depletion of repair capacity. Other factors like blood pressure, fats and lack of exercise also play a role in both T1D-related complications and aging in general.

The thought ‘it is just part of diabetes’ is even reflected in the NIVEL report: ‘People with T1D die 13 years earlier; addressing complications timely can improve quality of life’. All true, but we should, and we can, prevent complications! And if you’re already afflicted by diabetes complications, of course as much as possible must be done to halt or treat them.

 

Complications arise slowly: how to halt them?

It usually takes about 10-20 years for the first problems to become detectable. However, blood vessel and nerve damage starts much earlier, as shown by Josine van der Heyden’s PhD research at Diabeter. It was shown that after about 6 years of diabetes, abnormalities in blood vessels and nerves can already be seen in teenagers (11-13).

Initially it was doubted if good glucose control could prevent complications. As early as 1993 the large American ‘Diabetes control and Complications study’ (DCCT)(14) unequivocally established that glucose was indeed the cause of micro- and macrovascular complications. Many complications were even halted and partly reversed by good glucose control. In the following years these findings were confirmed in further follow-up studies (DCCT/EDIC studies)(15). It was found that the 9-year intensive treatment (lower HbA1c: mean 7.0%/53 mmol/mol) reduced the risk of cardiovascular disease by 42% compared to the control group (HbA1c mean 9.0 %/75 mmol/mol)(14). That 2% (20 mmol/mol) HbA1c difference almost halved the risk of microvascular complications! In short: better regulation resulted in fewer complications and a longer life. The solution sounds simple: improve/normalize your glucose levels. But with at least 42 factors involved that’s a tough job. However, technology will provide a solution.

 

Glucose regulation: use more technology! It’s already possible!

Of course, the NIVEL report and research will hopefully lead to even more awareness about the major consequences of diabetes on health and quality of life, as the Diabetes Fund states in their message. To their comment ‘The figures underline the great importance of scientific research and treatments’ I would like to add that solutions are already available: new treatment techniques are already yielding unprecedented good results. However, they are not applied sufficiently, due to significant limitations in reimbursement, doubts about usefulness and application and perhaps also unfamiliarity with the possibilities and the beneficial effects. This has to change because the future without complications has already started!

In short, if we want to further improve life expectancy and prevent complications, the mission is clear: better glucose control, striving for almost normal glucose values. I am convinced that (for most people with T1D) this is only possible using technology. ‘Manual’ glucose control with pen/pump/glucose meter and even using ‘standalone’ continuous glucose sensors (RT-CGM and Flash Glucose Monitoring [FGM]) does not provide sufficient glucose control and is too complex and demanding. After all, it’s not just about knowing your glucose level, but about how to then adjust insulin dose, nutrition, activities and more, based on that glucose level.

 

Towards a Complication-free future: safe glucose control, the first step

That ‘safe zone’ of glucose control has now been agreed internationally and has been incorporated into the (international) guideline. This guideline, already established as a target for the use of continuous glucose sensors (CGM) (17), has now been adopted by international organizations as a guideline for the treatment of all adults with type 1 diabetes (18). For children with T1D, the HbA1c target was already 7.0%/53 mmol/mol. It’s time for the Netherlands to start working towards these targets!! The following treatment goals have therefore been established:

– HbA1c < 7%/< 53 mmol/l

– Glucose values between 3.9 and 10 mmol/l at least 70% of the time per day (Time In Range [TIR]: >16.8 hours per day = 24 hours).

– Glucose values below 3.9 mmol/l, but not below 3.0 mmol/l (moderate hypoglycemia) no more than 4% of the time (Time Below Range [TBR]: <58 min per 24 hours), with glucose values lower than 3.0 mmol/l (severe hypoglycemia) limited to 1% of that time.

– Glucose values above 10.0 and 13.9 mmol/l (hyperlgycemia) no more than 25% of the time (Time Above Range [TAR]:  <6 hours per day), with glucose values exceeding 13.9 mmol/mol for a maximum of 5% of that time.

– Aim for a glucose variation, expressed in coefficient of variation (CV), of ≤ 36%

 

This is a clear first step that should lead to better outcomes and, of course, a longer life with T1D. The requirements are stricter for women with T1D who are, or want to become, pregnant. However, for elderly people and people with additional risk factors the targets are slightly less clear. It should also be realized that these guidelines are goals and that in the joint decision-making process between people with diabetes and the treatment teams, individual goals will be agreed.

 

‘Oops, how will I ever manage that…..?’: with technology

I hear people thinking: ‘Wonderful goals, but how will I ever achieve them or can I ever achieve them with my situation/history?’ This is where the story of technology and automation comes in. In my previous blog I described my vision. Manual operation, i.e. monitoring your sensor all day, swipe your FGM, then adjust pump or pen, take extra carbohydrates, eat less, move more/less etc., is difficult to sustain >25 x a day, but this is necessary to get into the safe zone (19). And while it sometimes seems that we are waiting for the perfect ‘artificial pancreas’, the technology has already come a long way in terms of automating all those steps: pump + continuous glucose sensor + computer algorithm = Automatic Insulin Delivery (AID). And it works! Even if you still need to bolus to compensate for the carbohydrates you eat, hence the term ‘hybrid closed-loop system’.

 

‘Side effects’ of automatic insulin delivery: quality of life!

I’ve been in this business for a while and I’ve never seen such good results. Where 10 years ago we had people with T1D who achieved an almost normal HbA1c with great difficulty and at the expense of many hypoglycemia events. There are now three, and soon six, such hybrid systems on the market (plus so-called ‘open source’ systems of course) and we are now seeing a significant improvement in glucose control among users, whether they were previously on a pump/sensor or on multiple daily injection (insulin pen). For example, where the earlier methods provided a TIR of 40-60%, the first major studies showed a TIR 75-80% with these hybrid systems and sometimes even higher, coinciding with very few hypoglycemia episodes and HbA1c < 7.0% / 53 mmol/mol. And last but not least: users’ quality of life skyrockets in all sorts of areas including sleep, work, school, relationships, etc.

 

Finally

Of course, eventually we want a fully automatic version or, better yet, cure. But we can’t wait for them to arrive. The cost would be too high, in terms of suffering, problems and complications. The research by NIVEL/RIVM may concern the past, even currently the damage caused by T1D is still very much an issue. The treatment results in too many complications, suffering and misery. My conclusions are clear:

– Type 1 diabetes remains dangerous and the course is too uncertain.

– Future and life expectancy are determined by past glucose control

– It’s never too late to improve glucose control

– Today’s technology can provide significant improvement in glucose control and (finally) bring people with T1D into the safe zone with the ‘side effect’ of a better quality of life

– Finally: it is of course everyone’s own choice to opt for technology and automation, but every step in that direction can help people with T1D to get closer or in the safe zone towards a future without complications.

"By the way: WHO CAN EXPLAIN TO ME WHY, SEEING ALL SCIENTIFIC LITERATURE, GUIDELINES, EXPERIENCE AND THE DANGER OF DOING NOTHING, such AID therapies are hardly reimbursed in the Netherlands??? And why someone first needs to deteriorate before such systems are reimbursed? And why CGM is not reimbursed anymore once HbA1c has improved?" -

References

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    2. Petrie JR. Cardiovascular disease in type 1 diabetes: the elephant in the clinic. Cardiovasc Endocrinol Metab. 2019;8(1):1-2.
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    8. McKnight j LM, Wild S, Scottish Diabetes Research Network Epidemiology Group,. Glycaemic control of Type 1 Diabetes in clinical practice early in the 21st century: an international comparison. EASD; Barcelona2013. p. S22.
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