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Tidig typ 1-diabetes förkortar kvinnors liv med 18 år
– Samtidigt är det viktigt att tolka studien i ljuset av de enorma framgångar som ägt rum de senaste decennierna, fortsätter han. I dag är behandlingen av typ 1-diabetes mycket god och för varje år som går kommer prognosen att bli bättre. De som lever och insjuknar i dag kan se fram emot ytterligare förbättringar i livslängd och livskvalitet.
Kvinnor som utvecklat typ 1-diabetes före tio års ålder dör i genomsnitt nästan 18 år tidigare än diabetesfria kvinnor. Män i motsvarande situation förlorar närmare 14 levnadsår. Vid diagnos i åldern 26-30 år förkortas livet med i snitt tio år, visar forskning publicerad i tidskriften The Lancet.
– Det här är nedslående och hittills okända siffror. Studien talar för att vi måste anstränga oss ännu mer för att behandla de tidigt drabbade patienterna stringent och på så sätt minska riskerna för komplikationer och förtida död, säger Araz Rawshani, forskare vid institutionen för medicin, Sahlgrenska akademin, och Nationella Diabetesregistret.
Forskningen bygger på ett omfattande material från registret där 27 195 individer med diabetes typ 1 följts under i genomsnitt tio års tid. Gruppen har jämförts med 135 178 diabetsfria kontrollpersoner ur allmänna befolkningen, med samma fördelning när det gäller kön, ålder och hemlän.
Att diabetes typ 1 medför lägre förväntad livslängd är känt sedan tidigare. Fram till nu har det dock varit oklart om och hur mycket åldern vid insjuknandet, samt kön, påverkar såväl livslängd som riskerna för kardiovaskulär sjukdom.
Individanpassad hjälp
Sannolikheten för svår hjärt-kärlsjukdom generellt visade sig vara 30 gånger högre för dem som utvecklat typ 1-diabetes före tio års ålder än för kontrollpersonerna. Vid diabetesdiagnos i åldern 26-30 år ökade motsvarande risk med faktor sex.
En av de högsta noterade riskökningarna i studien gäller hjärtattack hos kvinnor som utvecklat typ 1-diabetes innan de fyllt tio år. Dessa kvinnor löper 90 gånger ökad risk att drabbas jämfört med diabetsfria kontrollerpersoner.
– Studien ökar möjligheterna för ett individanpassat omhändertagande. Vi vet med säkerhet att om vi håller nere blodsockernivåerna på patienterna så minskar riskerna för skador på exempelvis hjärta-kärl, och det är därför viktigt att de som tidigt fått typ 1-diabetes kommer ifråga för både evidensbaserade läkemedel och moderna tekniska hjälpmedel för att mäta blodsocker och ge insulin, säger Araz Rawshani.
Robusta bevis
Diabetes typ 1 är en av de vanligaste kroniska sjukdomar som drabbar barn i Sverige. Flertalet insjuknar i åldern 10-14 år. Antalet diagnoser bland barn ökar och andelen drabbade är bland de högsta i världen, Sverige är tvåa efter Finland. Mellan 50 000 och 60 000 personer i Sverige har sjukdomen.
– Ur patientperspektiv är den här studien enormt viktig. Plötsligt kan vi svara på frågor om komplikationer och förväntad livslängd som vi inte har kunnat tidigare. Nu finns robusta bevis på att överlevnaden i hög grad beror på när i livet man får sjukdomen, och att det är skillnad på män och kvinnor, säger Araz Rawshani.
Forskare från Göteborgs Universitet och NDR intervjuas i TV4 om typ 1 och debutålder
Se inslag från TV4 här utan lösenord
Lancet-artikelns titel
Titel: Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study;
Artikeln som helhet9 sidor utan lösenord
Nedan är den information som England UK diabetesassociation informerar med anledning av studien
Behind the headlines: Type 1 diabetes and heart disease
You might have seen the headlines today linking Type 1 diabetes to a higher risk of heart disease and a shorter life, and more so for those who develop the condition when younger.
We know these stories can be scary. And while they shine an important light on how serious diabetes is, we want you to have the facts about what this might mean for you or your family.
The research
Research has already linked Type 1 diabetes to heart disease, but this research team – across the UK and Sweden – wanted to find out if the age you’re diagnosed has an impact too.
They compared over 27,000 people with Type 1 diabetes to over 135,000 people without diabetes. They followed these people for an average of 10 years, monitoring their health.
They found that people diagnosed with Type 1 diabetes before the age of 10 were 30 times more likely to have heart complications, like a heart attack, than the general population. Women diagnosed before the age of 10 were 60 times more likely to have heart complications than women without diabetes. (We’ll explain why this is below).
They also found that this early diagnosis had an impact on the average lifespan. In the study, women diagnosed before the age of 10 had an average lifespan 17.7 years shorter than those without diabetes, and 14.2 years shorter for men. This dropped to 10 years if they were diagnosed later in life.
Those numbers can be frightening, but to put them into context we’re going to have to talk about risk.
Our top four need to knows about risk
Risk and certainty are different.
Some people win millions in the lottery. But it’s not inevitable, and the chance it happening is affected by different factors – like how often you play.
It’s the same here: a higher risk of heart disease doesn’t mean you will develop heart disease. There are other factors involved. Which brings us to our second tip.
“30 times higher” sounds scary, but the overall risk is still low.
Let’s go back to the lottery analogy: if you buy 30 lottery tickets, you’re 30 times more likely to win the lottery. But it’s still *incredibly* unlikely that you’ll win.
In this study, the number of times people with Type 1 diabetes actually developed heart complications was still very small, despite the higher risk.
For example, in people diagnosed with Type 1 under the age of 10, a case of heart disease happened to roughly one in 20,000 people over a 10 year period.
Bottom line is it’s still really low. The researchers point out that this could be because people involved in the study were still quite young, and the numbers will increase with age. This is true, but we need to wait and see.
This isn’t about your individual risk.
You’d be forgiven for thinking that the “30 times higher chance of heart disease” or “17.7 years shorter life” headlines apply directly to you. But that’s not the case. This was the average numbers in this particular group of people. Your risk is individual to you, as your journey through life is unique.
You can’t compare apples to oranges.
The research says that people with Type 1 diabetes are 30 times more likely to develop heart disease than people without diabetes, with women being 60 times more likely. So does that mean women have double the risk that men have? Not quite.
This research compared people with and without Type 1 diabetes, and found a 30 times higher risk in one group. They then compared women with and without Type 1 diabetes, and found a 60 times higher risk in one group.
That’s because the starting point risk for women without diabetes is really low – lower than men in fact. So there’s a larger ‘risk gap’ between women with and without Type 1.
Phew! Hope you’re still with us…
Caveats aside, we know Type 1 diabetes is serious
We have to face the fact that people with Type 1 diabetes are more likely to develop harmful complications, like heart or kidney disease, than people without diabetes. But why?
The researchers in this study believe the length of time a person lives with high blood glucose levels will play a role. We know that high blood glucose levels can damage blood vessels around the body, increasing the risk of complications.
The researchers also believe that people diagnosed with Type 1 diabetes very early in life might have a more aggressive form of the condition – making it even harder to hit those blood glucose targets, causing damage to blood vessels around the body.
That’s why it’s so important to keep blood glucose levels within ‘target range’ as much as possible. You can read more about that here.
We’re doing something about it
First off, it’s important to remember the outlook for people with Type 1 diabetes has never been better than it is today. Advances in technology – like Flash and CGM – are giving people with Type 1 diabetes the best possible advances to manage their glucose levels.
There are also other ways to reduce your risk of heart complications in later life, like managing cholesterol and blood pressure levels, or getting help to stop smoking.
We’re also moving towards better, more individualised care – finding people who could most benefit from certain treatments. And research like this helps.
And our scientists are making progress every day with the research breakthroughs of tomorrow. We’re funding over £7.4 million of research across the UK to find ways to reduce the risk of complications for everyone with diabetes, including heart disease.
For example, our scientists are working to improve heart bypass surgery, following the health of teenagers with Type 1 diabetes, and studying genetics to understand why complications develop.
And we’re funding vital research to take us closer to a cure, like working out how to replace insulin-producing cells and keep them safe from the immune attack.
Research will help us to keep on narrowing the gap between people with and without diabetes, until we ultimately reach a world where diabetes can do no harm.
We’re here for you
We hope this research helps to build the evidence base around who is most at risk of complications. In the future, this could improve guidelines for healthcare professionals, so they can provide you with the best care, and lead to more research to reduce the risk of complications.
That said, we know this kind of news is tough.
We hope this blog helps to reassure you and highlight the pioneering research underway to reduce the risk of complications and make sure everyone with diabetes lives as long and healthy a life as possible.
Pressmeddelande från the Lancet finns på
Här står mot slutet
”Professor Sattar adds: ”People with early onset diabetes should more often be considered for cardioprotective drugs such as statins and blood pressure lowering medication when they reach 30-40 years of age. Currently, only around 10-20% of individuals with type 1 diabetes are taking statins by the age of 40. Also, improving glycaemic control and smoking cessation programmes could meaningfully prolong the lives of these individuals. The good news, however, is that recent technological advances are helping younger patients manage their glucose levels better.”
The authors note some limitations including that they did not have information about patients’ glycaemic control before enrolment in the register. What’s more, they only included patients who had the condition for 20 years or less to provide contemporary comparisons of cardiovascular risk that reflect current diabetes management. Key strengths include the large cohort, individual controls, adjustment for diabetes duration, the range of age subgroups, and variety of cardiovascular outcomes. Life expectancy analyses used the entire cohort, regardless of duration of diabetes.
Writing in a linked Comment, Marina Basina and David M Maahs, Stanford University (USA) say: ”These data will increase attention towards cardioprotection at younger ages and specifically for those with an earlier age of type 1 diabetes onset. Practitioners need a stronger evidence base, including confirmatory reports from other registries and clinical trials, to clarify proper therapy and translate research findings to care guidelines and clinical practice to improve mortality and cardiovascular disease outcomes for individuals with type 1 diabetes.”
Kommentar och synpunkter från www red DiabetologNytt
1. Värdefulla data men relation till HbA1c hade varit varit en tillgång i studien. I samband med artikel från NDR 2014 N Engl J Med Marcus Lind med flera fanns dessa data med. Ju bättre HbA1c ju bättre prognos, Vid extremt höga HbA1c stiger risken för komplikationer från hjärta-kärl drastiskt
Gruppen med debut 0-10 år har i aktuell artikel närmare 70 mmol/mol i medel-HbA1c, vilket vi idag betraktar som extremt höga värden, skriver Ragnar Hanås. barndiabetesöverläkare UIddevalla i eget uttalande i samband med studien och fortsätter; på riksnivå I Sverige är endast 10% av patienterna på denna nivå enligt senaste årsrapporten. Absoluta HbA1c-nivåer är mycket viktigt, inte minst i debatten om målvärdet 48 mmol/mol. Det finns motivation till fortsatt strävande efter bästa möjliga HbA1c redan från debut, avslutar Ragnar Hanås
Studien bygger på relativa jämförelser mot en helt frisk befolkning. Den absoluta sjukligheten och dödligheten är i absoluta tal extremt låg i denna grupp. Konfidensintervallen är stora i resultat-tabeller i Lancet-studien.
Bra med utförlig info från UK. Deras pediatriska patienter ligger mycket högre än i Sverige men är på väg ner till skillnad mot i USA där man fortsatt har ca 70 i medel-HbA1c.
2. Vårdpropgram för barn-ungdomsdiabetes finns i Sverige sedan 1982 med uppdateringar regelbundet. Senaste vårdprogram från diabetesprofessionen kom för ett år sedan och finns på www utan lösenord
Nytt uppdaterat vårdprogram kring barndiabetes avseende insulinpump och kontinuerlig vägvnadsglukosmätning, CGM och flash-glukos (FGM, Libre) är också framtaget. Målsättning är att de flesta barn och ungdomar nu 2018 ska ha tillgång till dessa hjälpmedel för att uppnå bästa möjliga HbA1c och öka tiden med normala glukosvården, den sk time in range (TIR), och minska risken för låga blodglukos.
Ledtal för antalet patienter per barndiabetessjuksköterska är nationellt i Sverige 75. Viktigt att barndiabetesteamet är komplett och har tillräckligt med läkareresurser liksom barbndiabetesdietist och att det finns tillräckligt med psykosocialt stöd.
3. Föräldrar till barn-ungdomar liksom barn-ungdomar själva gör ett fantastiskt arbete med egenvård. Barndiabetesvården på drygt 40-tal kliniker i Sverige arbetar intensivt med diabetes. Svensk barndiabetesvård är bäst i världen vid internationell jämförelse. Bra måste och kan bli ännu bättre.
Aktuell studie ger underlag för att barndiabetesvården måste prioriteras än mer framöver, både forskningsmässigt och kliniskt, för en ännu bättre diabetesvård. Gapet mellan individer med typ 1 diabetes och frisk befolkning måste minskas.
Nedtill finns utdrag ur artikeln
Nyhetsinfo
www red DiabetologNytt
Abstract
Excess mortality and cardiovascular disease in young adults
with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort
study
Araz Rawshani*, Naveed Sattar*, Stefan Franzén, Aidin Rawshani, Andrew T Hattersley, Ann-Marie Svensson, Björn Eliasson, Soffia Gudbjörnsdottir
Summary
Background
People with type 1 diabetes are at elevated risk of mortality and cardiovascular disease, yet current
guidelines do not consider age of onset as an important risk stratifier. We aimed to examine how age at diagnosis of type 1 diabetes relates to excess mortality and cardiovascular risk.
Methods
We did a nationwide, register-based cohort study of individuals with type 1 diabetes in the Swedish National
Diabetes Register and matched controls from the general population. We included patients with at least one
registration between Jan 1, 1998, and Dec 31, 2012. Using Cox regression, and with adjustment for diabetes duration,we estimated the excess risk of all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, acute myocardial infarction, stroke, cardiovascular disease (a composite of acute myocardial infarction and stroke), coronary heart disease, heart failure, and atrial fibrillation. Individuals with type 1 diabetes were categorised into five groups, according to age at diagnosis: 0–10 years, 11–15 years, 16–20 years, 21–25 years, and 26–30 years.
Findings
27195 individuals with type 1 diabetes and 135
178 matched controls were selected for this study.
959 individuals with type 1 diabetes and 1501 controls died during follow-up (median follow-up was 10 years). Patients who developed type 1 diabetes at 0–10 years of age had hazard ratios of 4·11 (95% CI 3·24–5·22) for all-cause mortality, 7·38 (3·65–14·94) for cardiovascular mortality, 3·96 (3·06–5·11) for non-cardiovascular mortality, 11·44 (7·95–16·44) for cardiovascular disease, 30·50 (19·98–46·57) for coronary heart disease, 30·95 (17·59–54·45) for acute myocardial infarction, 6·45 (4·04–10·31) for stroke, 12·90 (7·39–22·51) for heart failure, and 1·17 (0·62–2·20) for atrial fibrillation. Corresponding hazard ratios for individuals who developed type 1 diabetes aged 26–30 years were 2·83 (95% CI 2·38–3·37) for all-cause mortality, 3·64 (2·34–5·66) for cardiovascular mortality, 2·78 (2·29–3·38) for non-cardiovascular mortality, 3·85 (3·05–4·87) for cardiovascular disease, 6·08 (4·71–7·84) for coronary heart disease, 5·77 (4·08–8·16) for acute myocardial infarction, 3·22 (2·35–4·42) for stroke, 5·07 (3·55–7·22) for heart failure, and 1·18 (0 79–177) for atrial fibrillation; hence the excess risk differed by up to five times across the diagnosis age groups. The highest overall incidence rate, noted for all-cause mortality, was 1
9 (95% CI 171–211) per 100000 person-years for people with type 1 diabetes. Development of type 1 diabetes before 10 years of age resulted in a loss of 17·7 life-years (95% CI 145–204) for women and 14·2 life-years (12·1–18·2) for men.
Interpretation
Age at onset of type 1 diabetes is an important determinant of survival, as well as all cardiovascular
outcomes, with highest excess risk in women. Greater focus on cardioprotection might be warranted in people with early-onset type 1 diabetes.
Funding
Swedish Heart and Lung Foundation.
Artikeln i sin helhet som pdf utan lösenord på
Research in context
Evidence before this study
We did a systematic search in PubMed for articles published in
English between Jan 1, 1960, and April 15, 2018. Our search
terms included “type 1 diabetes”, “age at diagnosis”, “age at
disease onset”, “childhood onset”, “late onset”, “debut age”,
“mortality”, “cardiovascular disease”, “coronary artery disease”,
and “myocardial infarction”. We searched for articles by title and
abstract to identify relevant studies. Studies were also sought
within reference lists of eligible studies. We considered studies
that studied associations between age at onset or diagnosis of
type 1 diabetes and cardiovascular disease and survival. Studies
that used diabetes-free controls as comparators were of primary
interest, as such studies address the excess risk conferred by
diabetes. People with type 1 diabetes have a two to five times
increased risk of death and three to seven times increased risk of
coronary heart disease. Several risk factors, notably glycaemic
control, affect survival in type 1 diabetes. The role of age at
disease onset, however, remains weakly studied. European,
American and other guidelines
do not articulate any specific recommendations in relation to age at disease onset,
only duration.
Added value of this study
By studying 27195 individuals with type 1 diabetes and
135 178 matched controls, we show a ubiquitous inverse
association between age at diagnosis and risk of mortality and
cardiovascular disease, independently of diabetes duration.
Patients with type 1 diabetes with disease onset before 10 years
of age had a 30-times increased risk of coronary heart disease and
acute myocardial infarction compared with matched controls.
Women with onset of type 1 diabetes before 10 years of age had a
60-times increased risk of coronary heart disease and 90-times
increased risk of acute myocardial infarction. For acute myocardial
infarction and coronary heart disease, a difference in risk levels of
five times was observed between individuals with onset at age
0–10 years and those with onset at age 26–30 years. Although
absolute risks were low in this cohort, development of type 1
diabetes before 10 years of age resulted in a loss of 17
7 life-years for women and 14 2 life-years for men, whereas years of life lost
were around 10 years with later age at diagnosis.
Implications of all the available evidence
Age at disease onset appears to be an important determinant of
survival and, in particular, of cardiovascular disease in people
with type 1 diabetes. These findings suggest that patients with
earlier-onset type 1 diabetes be offered cardioprotective
medications (statins and blood pressure medications) sooner
than currently practised. Increased efforts towards improved
glycaemia control and, where relevant, smoking cessation, in
such individuals would also be beneficial.
Introduction
Type 1 diabetes is the second most common chronic
disease of childhood, although the disorder can develop
throughout the lifespan.
Remarkable improvements in
management and survival have been observed during the
past century. One study showed that the relative risk of
death declined by 29% over a 10-year period.
Yet, mortality in type 1 diabetes is still increased by two to eight
times, which is reflected by a loss of life expectancy at
age 20 years of approximately 12 years.
Cardiovascular
disease is the main driver of morbidity and mortality in
people with type 1 diabetes. European and American
guidelines therefore recommend aggressive manage-
ment of cardiovascular risk factors in people with type 1
diabetes, especially in individuals older than 40 years or
with evidence of microvascular complications.
Yet, these guidelines are not well adhered to in people with type 1
diabetes and even with risk factors within target levels,
people with type 1 diabetes are at elevated risk of mortality
and cardiovascular disease.
At present, no guidelines consider age of onset as a risk stratifier.
Age at diagnosis might be important in type 1 diabetes.
It could carry information about—and thus act as a proxy
for—several important factors, such as total glycaemic
load, varying autoimmune mechanisms, age-related
variations in clinical care, differences in ability to cope
with the disease, and so on. Accordingly, studies have
shown that age at diagnosis can contribute to identification
of subtypes of type 2 diabetes in adults, as well as predict
risk factor trajectories. Furthermore, other evidence
indicates that younger-onset type 2 diabetes is more
harmful than diabetes diagnosed in later life.
By contrast, such data in type 1 diabetes are less
evident.
Because of the paucity of published literature
on this topic, we aimed to do a nationwide, register-based
cohort study to examine how age at diagnosis of type 1
diabetes relates to excess risk of death and cardiovascular
outcomes, while accounting for diabetes duration, using
granular age categories.
Discussion
In this nationwide, register-based cohort study of patients
with type 1 diabetes, we show that age at disease onset is
an important determinant of survival and cardiovascular
disease. The differences in risks related to age of disease
onset were in many cases substantially high. Patients with
type 1 diabetes with disease onset before 10 years of age
had a 30-times increased risk of coronary heart disease
and acute myocardial infarction in their early adult years.
Women with onset of type 1 diabetes before 10 years of age
had a 60-times increased risk of coronary heart disease
and 90-times increased risk of acute myocardial infarction,
in the same early adult period. Onset of type 1 diabetes
before 10 years of age was associated with a 12-times
increased risk of heart failure over the same period, and
mortality risks, relative to age-matched and sex-matched
controls, differed by 128% (difference in excess risk for
diabetes onset at 0–10 years
vs 25–30 years of age). Notably,
although the relative risks were substantially high,
absolute risks were low throughout. This finding can be
explained by the fact that we studied a relatively young
cohort (mean age 29 years). However, in our previous
the exception of heart failure). This increased risk can,
to some extent, be explained by the fact that women in the
general population have a low risk of these events,
compared with men. Hence, the higher excess risks in
women with type 1 diabetes do not necessarily translate
into higher absolute risks compared with their male
counterparts.
Our data add to the limited information available about
long-term survival in type 1 diabetes in relation to age at
disease onset. Conway and colleagues compared
mortality in 162 individuals with type 1 diabetes with
onset in childhood (<20 years) versus 313 individuals with
onset in young adulthood (20–29 years); no marked
differences in mortality or coronary artery disease were
noted, although the small sample offered low statistical
power. In a bigger study, Harjutsalo and colleagues
examined coronary heart disease mortality in individuals
with early-onset (0–14 years) and late-onset (15–29 years)
type 1 diabetes. They reported that coronary heart disease
mortality was 28 times greater in individuals with early-
onset type 1 diabetes than in those with late-onset
type 1 diabetes. The authors suggested that this increased
risk might be explained by the longer duration of diabetes
in those with early-onset type 1 diabetes. Our study, which
had individual controls, adjustment for duration, more
age subgroups, as well as a range of cardiovascular
disease outcomes, shows that mortality in people with
type 1 diabetes is uniformly and markedly elevated when
compared with the general population.
Although the explanations for our findings are likely to
be multifaceted, diabetes duration is likely to have a key
role; even though we adjusted for duration more robustly
than other studies, complete adjustment is impossible.
Duration of diabetes is a component of total glycaemic
load. Defined as the cumulative exposure of the
vasculature to glucose, glycaemic load is a function of
diabetes duration and glycaemic variability. The longer
the duration of diabetes, the greater the glycaemic load
and thus the damage (analogous to the area under the
curve for exposure to LDL cholesterol).
It is also clear from our data that coronary arteries seem especially
vulnerable to hyperglycaemia, perhaps more so when
hyper glycaemia commences early in life (<10–15 years).
Another possible explanation for our findings is that
patients with a younger age of onset have a more severe
and rapid loss of β-cells, which contributes to increased
glycaemia. Studies of the pancreas of patients who die
soon after a diagnosis of diabetes show that those
diagnosed before the age of 7 years have severe loss of
residual insulin-containing islets compared with those
diagnosed after the age of 13 years, who retain around
40% of insulin-containing islets.
A different type of insulitis is seen in these two subgroups: those diagnosed
before the age of 7 years have a high proportion of CD20
B lymphocytes (CD20Hi), whereas those diagnosed after
the age of 13 years have a low proportion (CD20Lo).
This observation implies that the two forms of insulitis
progress differentially and that the patients diagnosed
before age 7 years with a CD20Hi profile lose their β-cells
at a more rapid rate than do those diagnosed later.
Moreover, children and adolescents with type 1 diabetes
start to exhibit subclinical cardiovascular disease abnor
-malities after 10 years of disease duration, as shown
through numerous methodologies.
Our data suggest a need to better target cardiovascular
risk in those with childhood-onset type 1 diabetes. There
are readily available and effective means to mitigate the
risk of coronary events—notably, statins, blood pressure
lowering medication, insulin pumps, continuous glucose
measurement, and so on. Data from clinical trials suggest
that cardiovascular disease reductions in people with type
1 diabetes receiving statins are almost identical in
magnitude to those seen in people with type 2 diabetes,
whereas observational data suggest that statin use
markedly lowers cardiovascular disease risk in people
with type 1 diabetes.
Evidence from the adDIT trial
supports an effect of angiotensin-converting enzyme
(ACE) inhibitors to lessen microalbuminuria and statins
to lower lipids when prescribed in adolescence, without
causing any short-term harm.
We are not advocating giving statins or ACE inhibitors
to children with type 1 diabetes, but our data in conjunction
with previous observations suggest greater consideration
of statins once individuals with early-onset type 1 diabetes
reach 30–40 years of age. Based on the available data, as
well as previous work in Scotland,only around 10–20%
of individuals with type 1 diabetes appear to be on statins
by 40 years of age, and more than half have systolic blood
pressure greater than 120 mm Hg. Some guidelines
include long duration of diabetes (ie, >20 years) as a
reason to consider statins in patients aged 30–40 years
with type 1 diabetes.
However, such patients—who would
have been diagnosed before 10–20 years of age—also have
the highest risks of acute myocardial infarction and lose
most life-years as a result of their diabetes, as shown by
our present findings. We believe physicians might need to
reconsider more complete targeting of cholesterol, blood
pressure, and glycaemia in patients with earlier-onset type
1 diabetes when these patients reach 30–40 years of age, if
possible and as clinically indicated. We appreciate that
ACE inhibitors are teratogenic and that statins are also
not recommended for women planning a pregnancy,
although no clear data are available as yet for the risks of
statins. Thus, some caution in women with type 1 diabetes
is needed; even so, improved blood pressure control
without ACE inhibitors in women, improved glycaemia
control, and smoking cessation in such groups could
meaningfully extend life expectancy in those with earlier-
onset diabetes. Such interventions given earlier in life
increase life expectancy to the greatest extent,
and some interventions (eg, statins) have legacy effects.
In other words, although short-term risks are low to modest, given
the young age of onset of type 1 diabetes, the lifetime risks
will be high and thus the gains from preventive therapies
will be greatest when commenced earlier in life.
Our study had several limitations. We did not have
information about patients’ glycaemic control before
enrolment in the register. We used an epidemiological
definition of type 1 diabetes, which implies that
misclassification of diabetes type is possible. However,
a validation study has shown that the epidemiological
classification is highly reliable.
Furthermore, we excluded
patients with diabetes duration of more than 20 years in
order to compute reliable regression models; this
approach slightly restricts the permitted inferences but it
does not affect the reliability of the estimates. Neither did
this restriction affect calculation of life-years lost, since
those analyses included all patients (no restriction was
applied with regard to diabetes duration: ie, almost all
individuals with type 1 diabetes were included).
In conclusion, independently of diabetes duration, age
at onset of type 1 diabetes appears to be an important
determinant of survival and all cardiovascular outcomes.
Early-onset type 1 diabetes is associated with up to 30 times
increased risk of serious cardiovascular outcomes, with
risk levels being 90 times higher for women with early-
onset diabetes, who also die around 18 years earlier than
their diabetes-free counterparts. These findings advance
the arguments for wider and earlier use of cardioprotective
agents in this population.
Lancet 2018;392:477-86
Från Patientorganisation Svenska Diabetesförbundet www.diabetes.se
Modern behandling ger längre liv och färre komplikationer
− Idag har personer med diabetes goda förutsättningar att hålla blodsockret i balans och leva ett långt och gott liv. Vi arbetar för att öka resurser till forskning och för att alla i hela landet ska erbjudas bästa och effektivast möjliga vård, säger Diabetesförbundets ordförande Cajsa Lindberg, med anledning av en ny forskningsstudie från Göteborgs universitet som visar att diabetesdebut före tio års ålder förkortar livslängden.
Forskare vid Göteborgs universitet har tillsammans med Nationella Diabetesregistret idag släppt en forskningsstudie som visar att barn som insjuknat i typ 1-diabetes före tio års ålder får förkortad livslängd med 14 till 18 år jämfört med friska personer, vilket gett stort genomslag i medias rapportering.
Karin Åkesson är barnläkare och ansvarig för kvalitetsregistret för barn och ungdomar med diabetes, Swediabkids.
− Vi ska inte glömma bort att diabetes är en allvarlig sjukdom, men idag har vi goda möjligheter att hjälpa människor att hålla en mycket bättre blodsockerkontroll än vad man kunnat göra tidigare.
De data som används i studien baseras på personer som fick diabetes för många år sedan, men siffrorna visar på vikten av att vi måste ta hand om dem och hjälpa till att minska riskerna för hjärt- och kärlsjukdom.
Åkesson påpekar att siffrorna i studien är historiska, och inte handlar om barn som får diabetes idag. Det går inte heller att koppla de statistiskt beräknade siffrorna till individnivå.
− Du behöver inte tänka att ditt barn dör 18 år tidigare.
Enligt Karin Åkesson publiceras många positiva forskningsresultat och det finns ett stort antal studier som visar på allt större möjligheter till god blodsockerkontroll.
− Utvecklingen mot bättre behandling går fort med nya smarta pumpar samt nya mediciner och möjligheterna till bra behandling blir ännu större i framtiden, säger Åkesson.
Araz Rawshani, forskaren bakom studien, menar att trots nedslående siffror så ska de tolkas i ljuset av de stora framgångar som skett de senaste decennierna.
− Idag är behandlingen av typ 1-diabetes mycket god och den blir bättre för varje dag. För varje år som går kommer prognosen att bli bättre och de som lever och insjuknar idag kan se fram emot ytterligare förbättringar i livslängd och livskvalitet, säger Araz Rawshani.
Diabetesförbundet och Diabetesfonden arbetar dagligen för att främja forskning och för att alla patienter ska få tillgång till de senaste tekniska hjälpmedlen och medicinerna.
− Att personer med diabetes lever kortare är i sig inte nytt för oss. Vårt fokus ligger på att se till att alla som har diabetes får bästa möjliga behandling och att det kommer in så mycket pengar till diabetesforskning som möjligt. Väldigt mycket positivt har hänt bara de senaste åren vad gäller tekniska hjälpmedel och nya effektiva mediciner, vilket också ger förutsättningar för ett längre liv med färre risker för komplikationer. Vi arbetar stenhårt för att se till att alla personer med diabetes ska ha samma tillgång till effektivast möjliga behandling, säger Cajsa Lindberg.
From www.medscape.com
Patients diagnosed at a young age with type 1 diabetes have a far greater risk of developing cardiovascular disease and dying early compared with the general population than has previously been appreciated, with such patients losing more than a decade of life, new registry data reveal.
Araz Rawshani, MD, PhD, department of molecular and clinical medicine, Institute of Medicine, University of Gothenburg, Sweden, studied more than 27,000 patients with type 1 diabetes and 135,000 matched controls. The research was published online in the Lancet on August 9.
They found that patients diagnosed with type 1 diabetes at 0 to 10 years of age had quadruple the risk of dying early from any cause compared with controls and were over seven times as likely to die from cardiovascular disease, leading to a loss in life expectancy of approximately 18 years in women and 14 years in men.
Moreover, patients with type 1 diabetes were 30 times more likely to develop coronary heart disease and myocardial infarction than controls. They were also 12 times more likely to end up with heart failure and 11 times more likely to have a stroke.
These estimates are far higher than those included in a recent statement by the American Heart Association (AHA) and American Diabetes Association (ADA), which did not include age as a risk stratifier.
The magnitude of loss of life expectancy in individuals diagnosed with type 1 diabetes at age up to 10 years in this new study ”is something that we did not fully appreciate before,” noted coauthor Naveed Sattar, MD, Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK, in a Lancetpress release.
Patients Diagnosed in Childhood Must Take Cardioprotective Drugs Earlier
One of the most important implications of these new findings, says Rawshani, is that people with type 1 diabetes mush start taking cardioprotective drugs, such as statins and blood pressure lowering agents, early.
While acknowledging absolute mortality and disease rates in the current study were low, he said that ”age at disease onset appears to be an important determinant of survival as well as cardiovascular outcomes in early adulthood, warranting consideration of earlier treatment with cardioprotective drugs.”
”Currently, only around 10% to 20% of individuals with type 1 diabetes are taking statins by the age of 40,” Sattar stressed.
”Also, improving glycemic control and smoking cessation programs could meaningfully prolong the lives of these individuals,” he added, noting, ”the good news, however, is that recent technological advances are helping younger patients manage their glucose levels better.”
In an accompanying editorial, Marina Basina, MD, and David M. Maahs, MD, PhD, division of endocrinology, Stanford University, California, describe the results as a ”step forward” in understanding the impact of early type 1 diabetes diagnosis on mortality and cardiovascular disease risk.
But noting limitations of this study, more data are still needed to guide therapy decisions, they argue.
While Rawshani and colleagues call for earlier initiation of cardioprotective medications, they ”specifically state that they do not advocate prescribing statins or angiotensin-converting enzyme inhibitors to children with type 1 diabetes,” the editorialists point out.
They ”instead argue for greater consideration of these treatments once individuals with type 1 diabetes reach 30 to 40 years of age, consistent with adult AHA and ADA guidelines.”
Four Times Higher Risk of Early Death in Those With Type 1 Diabetes
To examine how age at diagnosis of type 1 diabetes is related to the risk of death and cardiovascular outcomes, the researchers gathered data on individuals included in the Swedish National Diabetes Register between 1998 and 2012.
They divided them into five groups by age at diagnosis: 0 to 10 years, 11 to 15 years, 16 to 20 years, 21 to 25 years, and 26 to 30 years. These patients were matched with five nondiabetic controls randomly selected from the Swedish population and matched for age, sex, and county, to account for geographical differences.
Socioeconomic information, coexisting conditions, and dates and causes of death were gathered from Statistics Sweden, Swedish Inpatient Registry, and Cause of Death Register for all individuals in Sweden, with follow-up to the end of 2014.
The team included 27,195 patients with type 1 diabetes and 135,178 matched controls who were a mean age of approximately 29 years and of whom 56% were men. Over a median follow-up of 10 years, 959 patients with type 1 diabetes and 1501 controls died.
The all-cause mortality rate was typically low, with a highest overall incidence of 1.90/100,000 person-years in patients with type 1 diabetes and 0.60/100,000 person-years among controls.
Researchers calculated that patients who developed type 1 diabetes up to the age of 10 years had a substantially higher risk of all-cause mortality than controls, at a hazard ratio (HR) of 4.11, rising to 7.38 for cardiovascular mortality. For noncardiovascular mortality, the HR was 3.96.
Patients with type 1 diabetes diagnosed in the first decade of life also had an increased risk of developing cardiovascular disease compared with controls, at an HR of 11.44, as well as coronary heart disease, at an HR of 30.50, acute myocardial infarction (HR, 30.95), heart failure (HR, 12.90), stroke (HR, 6.45), and atrial fibrillation (HR, 1.17).
Individuals who developed type 1 diabetes at 26 to 30 years also had an increased risk of mortality and cardiovascular disease, although the HRs were lower in each case, with a five fold difference across diagnostic age groups.
The team estimates that men diagnosed with type 1 diabetes at age 0 to 10 years lost 14.2 years of life, at an average life expectancy of 69.1 years versus 83.3 years in controls.
Women with type 1 diabetes diagnosed in childhood lost 17.7 years, at an average life expectancy of 70.9 years versus 88.6 years in controls.
Among patients with type 1 diabetes diagnosed at 26 to 30 years of age, men lost an average of 9.4 years of life compared with controls, while women lost 10.1 years.
Women with type 1 diabetes also had higher risks of developing cardiovascular disease than men.
”Sobering” Statistics Add to Data Needed to Improve Outcomes
The authors believe that the increased risk of cardiovascular-related death in patients with type 1 diabetes diagnosed at a younger age could be because loss of pancreatic beta-cells is more severe and rapid in these patients than those diagnosed later in life.
They point out, however, that their study has several limitations, such as a lack of data on how cardiovascular disease risk factors, such as HbA1c levels, blood pressure, and cholesterol, and their treatment affected outcomes.
In addition, the absolute mortality and cardiovascular disease rates were low as a result of the young average age of the participants and relatively short duration of type 1 diabetes, limiting their wider applicability.
In their editorial, Basina and Maahs say these new data ”are sobering, have implications for therapy, and are a further impetus to delay, prevent, and cure type 1 diabetes.”
However, they note that ”practitioners need a stronger evidence base, including confirmatory reports from other registries and clinical trials, to clarify proper therapy and translate research findings to care guidelines and clinical practice, to improve mortality and cardiovascular disease outcomes.”
Therefore, any resulting recommendations in this article on the timing of treatment initiation in patients with type 1 diabetes ”are more opinion based than evidence based,” they comment.
Still, Basina and Maahs believe that the current results ”will increase attention towards cardioprotection at younger ages and specifically for those with an earlier age of type 1 diabetes onset.”
