Summary Type 1 diabetes is a chronic autoimmune disease characterised by insulin deficiency and resultant hyperglycaemia. Knowledge of type 1 diabetes has rapidly increased over the past 25 years, resulting in a broad understanding about many aspects of the disease, including its genetics, epidemiology, immune and β-cell phenotypes, and disease burden. Interventions to preserve β cells have been tested, and several methods to improve clinical disease management have been assessed. However, wide gaps still exist in our understanding of type 1 diabetes and our ability to standardise clinical care and decrease disease-associated complications and burden. This Seminar gives an overview of the current understanding of the disease and potential future directions for research and care.

Type 1 diabetes

Type 1 diabetes.

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.

https://www.bmj.com/content/bmj/361/bmj.k1310.full.pdf

Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis

Advances in technology for management of type 1 diabetes.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(18)30024-2.pdf

Objective
To compare the effectiveness of insulin pumps with
multiple daily injections for adults with type 1
diabetes, with both groups receiving equivalent
training in flexible insulin treatment.
Design
Pragmatic, multicentre, open label, parallel group,
cluster randomised controlled trial (Relative
Effectiveness of Pumps Over MDI and Structured
Education (REPOSE) trial).
Setting
Eight secondary care centres in England and Scotland.
Participants
Adults with type 1 diabetes who were willing to
undertake intensive insulin treatment, with no
preference for pumps or multiple daily injections.
Participants were allocated a place on established
group training courses that taught flexible intensive
insulin treatment (“dose adjustment for normal
eating,” DAFNE). The course groups (the clusters) were
then randomly allocated in pairs to either pump or
multiple daily injections.
Interventions
Participants attended training in flexible insulin
treatment (using insulin analogues) structured around
the use of pump or injections, followed for two years.
Main outcome measures
The primary outcomes were a change in glycated
haemoglobin (HbA1c) values (%) at two years in
participants with baseline HbA1c value of ≥7.5%
(58 mmol/mol), and the proportion of participants
achieving an HbA1c value of <7.5%. Secondary
outcomes included body weight, insulin dose, and
episodes of moderate and severe hypoglycaemia.
Ancillary outcomes included quality of life and
treatment satisfaction.
Results
317 participants (46 courses) were randomised (156
pump and 161 injections). 267 attended courses and
260 were included in the intention to treat analysis,
of which 235 (119 pump and 116 injection) had
baseline HbA1c values of ≥7.5%. Glycaemic control
and rates of severe hypoglycaemia improved in both
groups. The mean change in HbA1c at two years was
−0.85% with pump treatment and −0.42% with
multiple daily injections. Adjusting for course, centre,
age, sex, and accounting for missing values, the
difference was −0.24% (−2.7 mmol/mol) in favour of
pump users (95% confidence interval −0.53 to 0.05,
P=0.10). Most psychosocial measures showed no
difference, but pump users showed greater
improvement in treatment satisfaction and some
quality of life domains (dietary freedom and daily
hassle) at 12 and 24 months.
Conclusions
Both groups showed clinically relevant and long
lasting decreases in HbA1c, rates of severe
hypoglycaemia, and improved psychological
measures, although few participants achieved glucose
levels currently recommended by national and
international guidelines. Adding pump treatment to
structured training in flexible intensive insulin
treatment did not substantially enhance educational
benefits on glycaemic control, hypoglycaemia, or
psychosocial outcomes in adults with type 1 diabetes.
These results do not support a policy of providing
insulin pumps to adults with poor glycaemic control
until the effects of training on participants’ level of
engagement in intensive self management have been
determined.
Trial registration
Current Controlled Trials ISRCTN61215213.

/pdf/relative-effectiveness-of-insulin-pump-treatment-over-201bzxg5o7.pdf

Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes : cluster randomised trial (REPOSE)

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Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes : cluster randomised trial (REPOSE)