En konstgjord bukspottkörtel ser ut att vara säker och effektiv på kort sikt vid typ 1-diabetes, enligt en metaanalys i tidskriften BMJ. En svensk expert tror att tekniken snart finns på hemmaplan, skriver Maria Gustavsson www.dagensmedicin.se
Det helautomatiserade pumpsystemet har sensorer som kontinuerligt mäter patientens blodglukosvärde och instruerar pumpen om vilka insulindoser som ska avges för att vidhålla en jämn och normal blodsockernivå. Dagens Medicin har tidigare rapporterat om tekniken som godkändes i USA 2016, men ännu inte finns i Europa.
Analysen visar att en konstgjord pankreas nästan ger patienten två och en halv timme extra tid per dygn där blodsockret ligger inom normala gränser. Detta jämfört med patienter som fick standardbehandling, exempelvis i form av en insulinpump.
Resultaten stärker bilden av att självstyrande pumpsystem är säkert och fungerar väl, menar Anders Frid som är docent och överläkare vid Skånes universitetssjukhus i Malmö.
– Att deltagarna med den helautomatiska pumpen ligger kring normalvärdet under så mycket längre tid är av stort värde. Det minskar risken för både akuta och kroniska komplikationer, säger han.
Enligt resultaten var tiden med hypoglykemier, det vill säga en skadligt låg blodsockernivå, 20 minuter kortare per dygn bland patienter med det självstyrande pumpsystemet, jämfört med deltagare som fått standardterapi. Även tiden med hyperglykemier minskade med en konstgjord pankreas.
Men det finns svagheter med analysen, enligt en ledarkommentar som skrivits av bland andra en läkare och en professor från Storbritannien. De påpekar att flera av studierna hade få deltagare och kort uppföljningstid – i majoriteten av publikationer följdes deltagarna under sju dagar eller kortare. Även Anders Frid lyfter dessa delar som svagheter och efterlyser fler och större studier framöver.
– Jag har hört att uppemot 20 000 helautomatiska pumpsystem är i gång i USA i dagsläget. Så det finns ett bra forskningsunderlag, säger han.
När det gäller svensk sjukvård rekommenderade NT-rådet nyligen landstingen att avvakta med introduktion av helautomatiserade pumpsystem tills man har ett bättre kunskapsunderlag. Fast Anders Frid tror att tekniken snart kommer att finnas i Sverige.
– Frågan är inte om utan när. Jag är säker på att svensk sjukvård relativt snart har dessa självstyrande pumpar som kommer att revolutionera behandlingen vid typ 1-diabetes, säger han.
Metaanalysen bygger på 40 randomiserade studier som innefattar fler än 1 000 patienter med typ 1-diabetes. De kom från öppenvården i bland annat Storbritannien och Österrike. Definitionen för en normal blodglukosnivå låg mellan 3,9 och 10 mmol/liter.
Läs mer i abstract och hela artikeln i utan lösenord:
Eleni Bekiari med flera. Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis. BMJ, publicerad online den 18 april 2018. DOI: 10.1136/bmj.k1310
Abstract
Objective
To evaluate the efficacy and safety of artificial pancreas treatment in non-pregnant outpatients with type 1 diabetes.
Design
Systematic review and meta-analysis of randomised controlled trials.
Data sources Medline, Embase, Cochrane Library, and grey literature up to 2 February 2018.
Eligibility criteria for selecting studies Randomised controlled trials in non-pregnant outpatients with type 1 diabetes that compared the use of any artificial pancreas system with any type of insulin based treatment. Primary outcome was proportion (%) of time that sensor glucose level was within the near normoglycaemic range (3.9-10 mmol/L). Secondary outcomes included proportion (%) of time that sensor glucose level was above 10 mmol/L or below 3.9 mmol/L, low blood glucose index overnight, mean sensor glucose level, total daily insulin needs, and glycated haemoglobin. The Cochrane Collaboration risk of bias tool was used to assess study quality.
Results
40 studies (1027 participants with data for 44 comparisons) were included in the meta-analysis. 35 comparisons assessed a single hormone artificial pancreas system, whereas nine comparisons assessed a dual hormone system. Only nine studies were at low risk of bias. Proportion of time in the near normoglycaemic range (3.9-10.0 mmol/L) was significantly higher with artificial pancreas use, both overnight (weighted mean difference 15.15%, 95% confidence interval 12.21% to 18.09%) and over a 24 hour period (9.62%, 7.54% to 11.7%). Artificial pancreas systems had a favourable effect on the proportion of time with sensor glucose level above 10 mmol/L (−8.52%, −11.14% to −5.9%) or below 3.9 mmol/L (−1.49%, −1.86% to −1.11%) over 24 hours, compared with control treatment. Robustness of findings for the primary outcome was verified in sensitivity analyses, by including only trials at low risk of bias (11.64%, 9.1% to 14.18%) or trials under unsupervised, normal living conditions (10.42%, 8.63% to 12.2%). Results were consistent in a subgroup analysis both for single hormone and dual hormone artificial pancreas systems.
Conclusions
Artificial pancreas systems are an efficacious and safe approach for treating outpatients with type 1 diabetes. The main limitations of current research evidence on artificial pancreas systems are related to inconsistency in outcome reporting, small sample size, and short follow-up duration of individual trials.
What is already known on this topic
• Individual studies have shown artificial pancreas use to be safe and efficacious in inpatients, patients under close monitoring, and outpatients with type 1 diabetes
• The US Food and Drug Administration recently approved artificial pancreas use for patients aged 14 years and older with type 1 diabetes
• Previous meta-analyses on artificial pancreas systems have provided limited findings, mainly owing to the low number of studies incorporated and heterogeneous definitions of outcomes
What this study adds
• In view of all the available evidence from randomised controlled trials, artificial pancreas treatment significantly improves glycaemic control while reducing the burden of hypoglycaemia in outpatients with type 1 diabetes
• Results are consistent for people using artificial pancreas systems unsupervised under normal living conditions, and for both single hormone and dual hormone systems
• The current research evidence on artificial pancreas systems is limited by inconsistency in outcome reporting, small sample size, and short follow-up duration of individual trials
Implications
Our study highlights some pitfalls in the conduct and reporting of artificial pancreas trials. Many trials had a short duration or were designed to assess the feasibility or safety, rather than long term effectiveness. Despite existing guidance, we noted significant variation in outcomes assessed and metrics used.71 Research groups should report a minimum set of agreed outcome measures and respective metrics.666768 To ensure the clinical relevance and feasibility of this core outcome set, it is crucial that its development involves all key stakeholders, including patients, their families, clinicians, researchers, statisticians, methodologists, industry representatives, regulatory authorities, and funders.
To maximise the yield of information and to facilitate analysis and synthesis of evidence overall, the use of a common repository for data on individual patients could be agreed on.7273 Such repositories would facilitate free dissemination of raw trial data, allowing for replication of previous research findings using various analysis approaches (for example, a repeated measures analysis) of clinically relevant outcomes. Moreover, to enhance the external validity of evidence, future trials should broaden inclusion criteria and recruit more heterogeneous populations, including ethnic minorities.
The performance of current artificial pancreas systems could be enhanced by the optimisation of system components. Use of novel insulin analogues with faster pharmacokinetics,74 the development of glucagon preparation stable at room temperature, and integration of artificial pancreas components into one device could further enhance user experience and artificial pancreas usefulness, and thus increase uptake. Future research should explore the potential differences between individual components (algorithms, continuous glucose monitoring) and determine their clinical relevance.
Upcoming trials should clarify the differences between single hormone and dual hormone systems, and explore artificial pancreas use in relevant groups of people with type 2 diabetes such as those with inpatient hyperglycaemia.75 Moreover, the effect of artificial pancreas use on quality of life and on reducing patient burden should be further explored,76 considering that patients with type 1 diabetes and their carers have shown a positive attitude towards artificial pancreas systems.777879 Finally, to support adoption, cost effectiveness should be assessed to allow for reimbursement by various healthcare systems, and ensure that adequate infrastructure exists.
Conclusions
Our systematic review and meta-analysis has shown that artificial pancreas systems are an efficacious and safe treatment approach for people with type 1 diabetes, leading to increased time in near normoglycaemic range, and reduced time in hypoglycaemia and hyperglycaemia. The results were verified for all types of artificial pancreas and in all sensitivity analyses. Further research with rigorous studies, cooperation of research groups in terms of outcome reporting, and cost effectiveness data are required to verify these findings and support adoption of artificial pancreas systems in clinical practice.
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