Diabetes checks: delays in treatment are reduced when support staff assess eye images

NIHR | October 2021 | Diabetes checks: delays in treatment are reduced when support staff assess eye images

This NIHR Alert explains the findings of a piece of research that suggests that support staff could be trained to read images of the back of the eye (retina) almost as well as ophthalmologists. 

People living with diabetes need regular eye examinations to prevent serious problems with their vision. A shortage of eye specialists (ophthalmologists) is leading to delays in appointments. New research suggests that support staff could be trained to read images of the back of the eye (retina) almost as well as ophthalmologists. 

Most of the support staff in the study were specialist photographers who normally take images of the retina (ophthalmic photographers). The research suggests that they could be trained as ophthalmic graders and take on a new role in the NHS. They could increase capacity and reduce delays in people’s eye assessments (Source: NIHR)

The NIHR Alert can be read in full from the National Institute for Health Research

Purpose

The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient’s evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR.

Design

Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom.

Participants

Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease.

Methods

A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists).

Main Outcome Measures

Primary outcome: sensitivity of the new pathway. Secondary outcomes: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings.

Results

The new pathway showed sensitivity of 97 per cent and specificity of 31 per cent to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images or UWF images, respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images, respectively, for UWF versus 80 per cent and 40 per cent , respectively, for 7-field ETDRS images). Participants preferred ophthalmologists’ assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1 390 per 100 DME visits and between £461 and £1189 per 100 PDR visits.

Conclusions

The new pathway has acceptable sensitivity and would release resources. Users’ suggestions should guide implementation.

Evaluation of a New Model of Care for People with Complications of Diabetic Retinopathy [primary paper]

NIHR: Case study: Fighting diabetes with information

NIHR | March 2021 Case study: Fighting diabetes with information |

40 per cent of people diagnosed with type 2 diabetes report feelings of guilt and depression. A innovative programme at  University College London’s e-Health Unit helps people with type 2 to improve their health through digital health promotion and disease management programmes.

Professor Elizabeth Murray and her team work to help people improve their health through digital health promotion and disease management programmes. At the outset of this research project, Prof Murray and her colleagues knew that despite UK guidelines recommending that newly diagnosed patients be given personalised support to help them manage their disease, this often wasn’t available or was difficult for them to access. After securing funding from NIHR, they were able to develop HeLP-Diabetes (Healthy Living for People with Type 2 Diabetes), an online toolkit designed to help patients and carers affected by diabetes learn more about the condition and find the best ways to manage their own symptoms and blood sugar levels, at their own pace .

Once the tool was developed 374 people with type 2 were recruited, half of this cohort sed the tool, while people in the other group had normal care through their GP and other healthcare staff.

The team found that the online tool improved people’s physical health, helping them to take control and manage their own condition. The group of patients using the tool had better control over their blood sugar levels after 12 months.

And not only did their physical health improve – the group using the online support tool also showed improvements in their mental wellbeing. 

Alan, 71, from Sunderland, has been living with type 2 diabetes for 18 years. “When I was diagnosed it was a shock to the system and I didn’t know anything about type 2 diabetes,” he said. “I wish that a website such as HeLP would have been available for me back then.

“My first piece of advice to anyone diagnosed with any form of diabetes is to learn as much as possible about it. HeLP is a great way to do that – the more you know, the better you can manage your condition.” (Source: NIHR).

Read the case study in full from NIHR

New sub-groups of diabetes could lead to more targeted treatment for people with diabetes in the Asian Indian community

NIHR | 4 March 2021 | New sub-groups of diabetes could lead to more targeted treatment for people in India

The latest NIHR Alert around diabetes highlights the findings of an Indian study that stuided nearly 20 000 patients (ranging from 10 to 97 years of age), who had a diagnosis of diabetes in the last five years. The Alert underlines how people of Indian heritage are at a higher risk of developing type 2 diabetes, and at a younger age, than people from other backgrounds. This research could allow people with the highest risk of complications to be offered more intense treatment. It will prompt research to discover which treatments work best for people in each group.

The researchers used cluster k analsysis, compared with earlier cluster reporting, the experts identify two novel subgroups of type 2 diabetes in this population with important implications for prognosis and management. The coexistence of insulin deficiency and insulin resistance seems to be peculiar to the Asian Indian population and is associated with an increased risk of microvascular complications.

The study is important because, with the establishment of such clusters, we will think twice before starting every person with type 2 diabetes on the same standard treatment. This is the approach in current guidelines. But we now know that diabetes in Asian Indians differs from the condition studied in White populations. This is relevant in the clinic not only in India but in countries like UK and US where there is a large Asian Indian community. The clusters tell us which sub-groups have a higher risk of complications and need more aggressive treatment and more frequent screening.

Lead study author Ranjit Mohan Anjana, Vice President &  Viswanathan Mohan, President, Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India

NIHR Alert New sub-groups of diabetes could lead to more targeted treatment for people in India

Full reference: Mohan Anjana, R. et al. | 2021| Novel subgroups of type 2 diabetes and their association with microvascular outcomes in an Asian Indian population: a data-driven cluster analysis: the INSPIRED study| BMJ Open Diabetes Research & Care |

Abstract

Introduction Type 2 diabetes is characterized by considerable heterogeneity in its etiopathogenesis and clinical presentation. We aimed to identify clusters of type 2 diabetes in Asian Indians and to look at the clinical implications and outcomes of this clustering.

Research design and methods From a network of 50 diabetes centers across nine states of India, we selected 19 084 individuals with type 2 diabetes (aged 10–97 years) with diabetes duration of less than 5 years at the time of first clinic visit and performed k-means clustering using the following variables: age at diagnosis, body mass index, waist circumference, glycated hemoglobin, serum triglycerides, serum high-density lipoprotein cholesterol and C peptide (fasting and stimulated). This was then validated in a national epidemiological data set of representative individuals from 15 states across India.

Results We identified four clusters of patients, differing in phenotypic characteristics as well as disease outcomes: cluster 1 (Severe Insulin Deficient Diabetes, SIDD), cluster 2 (Insulin Resistant Obese Diabetes, IROD), cluster 3 (Combined Insulin Resistant and Deficient Diabetes, CIRDD) and cluster 4 (Mild Age-Related Diabetes, MARD). While SIDD and MARD are similar to clusters reported in other populations, IROD and CIRDD are novel clusters. Cox proportional hazards showed that SIDD had the highest hazards for developing retinopathy, followed by CIRDD, while CIRDD had the highest hazards for kidney disease.

Conclusions Compared with previously reported clustering, we show two novel subgroups of type 2 diabetes in the Asian Indian population with important implications for prognosis and management. The coexistence of insulin deficiency and insulin resistance seems to be peculiar to the Asian Indian population and is associated with an increased risk of microvascular complications.

The primary paper avaialble from the BMJ Open Diabetes Resarch & Care

NIHR: People with diabetes with a low risk of developing foot ulcers can be screened less often

NIHR | January 2021 | People with diabetes with a low risk of developing foot ulcers can be screened less often

Current NICE guidance recommends that people with diabetes have their feet screened annually to identify those most at risk of developing foot ulcers.  Now a new NIHR- funded study suggests that annual foot checks could be reduced. It found that people at low risk of developing ulcers do not need yearly reviews, as 1 in 20 patients at low risk of a foot ulcer progressed to medium risk level over a two year period.

The researchers analysed the data of over 10 000 patients in Scotland diagnosed with diabetes, who attended their first screening session in the period from 2009 to 2017. From this they identified each individual’s risk of foot ulceration according to standard risk factors of insensitivity, previous ulcers, and whether pulses in the foot could be felt. They looked at the change over time – from low to moderate risk. They cross-referenced this information with data on ulceration, amputation and death.

The results showed:

  • People with diabetes changed from low to moderate risk slowly
  • Around one in ten changed from low to moderate risk after five years (9.9 %) and eight years (11.3%)
  • Most changes in risk status (94%) were down to nerve damage in the feet (peripheral neuropathy)
  • One in 250 (0.4%) in the low-risk group developed ulcers after two-years; one in a thousand (0.1%) had an amputation (Source: NIHR).

Read the full NIHR Alert

Primary paper is available from Diabetic Medicine

NIHR Evidence: Sharing electronic records with patients led to improved control of type two diabetes

NIHR (2020) |Sharing electronic records with patients led to improved control of type two diabetes| 10.3310/alert_42103

A new review has pooled data from over 20 years’ worth of electronic records, its’ analysis indicates that sharing these records with patients with diabetes could help them control their sugar levels.

The review included trials between 1997 and 2017, with patients included in the study having medical conditions such as cancer, hypertension as well as diabetes.

Across all studies in the review safety outcomes were improved for patients who had access to electronic healthcare records, including medicines safety. Researchers also found that most studies found either a reduction in how often patients accessed healthcare, or no change.

Specifically in the case of studies relating to diabetes, multiple studies reported in similar ways, and these results could be pooled. The analysis found that sharing care records with diabetic patients was effective in reducing blood sugar. This is a major predictor of death in type 2 diabetes. A few studies also indicated a positive effect on anxiety, cardiac symptoms and cholesterol levels in the blood (Source: NIHR).

Related:

he full paper: Neves AL and others. Impact of providing patients access to electronic health records on quality and safety of care: a systematic review and meta-analysisBMJ Quality and Safety. 2020;0:1-14.

An editorial on this paper discusses its implications: Sarkar U and Lyles C. Devil in the details: understanding the effects of providing electronic health record access to patients and familiesBMJ Quality and Safety. 2020. doi: 10.1136/bmjqs-2020-011185.

Type 2 diabetes can be reversed with a modest weight loss of 10% or more

NIHR | September 2019 | Type 2 diabetes can be reversed with a modest weight loss of 10% or more

New research led by researchers at the University of Cambridge reports that individuals with a diagnosis of type 2 diabetes who reduced their  weight by one-tenth or more, were able to see their condition go into remission.

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The study followed a cohort (n=867) over time; and found that 257 participants (30%) participants were in remission at five-year follow-up. People who achieved weight loss of 10% or more within the first five years after diagnosis were more than twice as likely to go into remission compared to people who maintained the same weight. The participants in the study who achieved remission did so without intensive lifestyle interventions or extreme calorie restrictions.

“We’ve known for some time now that it’s possible to send diabetes into remission using fairly drastic measures such as intensive weight loss programmes and extreme calorie restriction,” says Dr Hajira Dambha-Miller from the Department of Public Health and Primary Care.

In order to clarify the best way to help patients with type 2 diabetes achieve sustained weight loss, the research team is currently undertaking a study called GLoW (Glucose Lowering through Weight management). The study compares the current education programme offered by the NHS to people after they have been diagnosed, with a programme delivered by WW (formerly Weight Watchers®) (Source NIHR & University of Cambridge)

Read the press release from NIHR 

See also: University of Cambridge Type 2 diabetes remission possible with ‘achievable’ weight loss, say researchers

 

Abstract

Aim

To quantify the association between behaviour change and weight loss after diagnosis of Type 2 diabetes, and the likelihood of remission of diabetes at 5‐year follow‐up.

 

Method

We conducted a prospective cohort study in 867 people with newly diagnosed diabetes aged 40–69 years from the ADDITION‐Cambridge trial. Participants were identified via stepwise screening between 2002 and 2006, and underwent assessment of weight change, physical activity (EPAQ2 questionnaire), diet (plasma vitamin C and self‐report), and alcohol consumption (self‐report) at baseline and 1 year after diagnosis. Remission was examined at 5 years after diabetes diagnosis via HbA1c level. We constructed log binomial regression models to quantify the association between change in behaviour and weight over both the first year after diagnosis and the subsequent 1–5 years, as well as remission at 5‐year follow‐up.

 

Results

Diabetes remission was achieved in 257 participants (30%) at 5‐year follow‐up. Compared with people who maintained the same weight, those who achieved more than or equal to 10% weight loss in the first year after diagnosis had a significantly higher likelihood of remission. In the subsequent 1–5 years, achieving more than or equal to 10% weight loss was also associated with remission.

 

Conclusion

In a population‐based sample of adults with screen‐detected Type 2 diabetes, weight loss of more than or equal to 10% early in the disease trajectory was associated with a doubling of the likelihood of remission at 5 years. This was achieved without intensive lifestyle interventions or extreme calorie restrictions. Greater attention should be paid to enabling people to achieve weight loss following diagnosis of Type 2 diabetes.

Full reference: Dambha-Miller, H et al | 2019|  Behaviour change, weight loss and remission of type 2 diabetes: a community based prospective cohort study|Diabetic Medicine| DOI: 10.1111/dme.14122 

The article is available in full from Diabetic Medicine

Fish oil supplements do not reduce cardiovascular deaths in people with diabetes without existing vascular disease

NIHR | December 2018 | Fish oil supplements do not reduce cardiovascular deaths in people with diabetes without existing vascular disease

The ASCEND study, which assesses primary cardiovascular prevention for people with any type of diabetes studied the impact of taking Omega-3 fatty acid supplements. In a NIHR Signal which highlights the research, reports that it found taking these supplements makes no difference to cardiovascular outcomes in people with diabetes but without established cardiovascular disease. Serious vascular events like heart attack, stroke or deaths from these occurred in approximately a tenth of participants irrespective of whether they took daily omega-3 or placebo capsules for seven years.

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The results are consistent with a recent large Cochrane review assessing omega-3 fatty acids in any population. Pooled analysis of around 40 high-quality trials of omega-3 supplements similarly found no effect on cardiovascular events or mortality.

The finding supports NICE recommendations that omega-3 fatty acids should not be offered to people with diabetes for the prevention of cardiovascular disease (Source: NIHR).

Full details of the Signal are at NIHR 

Full reference:

ASCEND Study Collaborative Group| 2018|Effects of n− 3 Fatty Acid Supplements in Diabetes Mellitus| New England Journal of Medicine| 379 |16| P. 1540-1550.

Published abstract

Background
Increased intake of n-3 fatty acids has been associated with a reduced risk of cardiovascular disease in observational studies, but this finding has not been confirmed in randomized trials. It remains unclear whether n-3 (also called omega-3) fatty acid supplementation has cardiovascular benefit in patients with diabetes mellitus.
Methods
We randomly assigned 15,480 patients with diabetes but without evidence of atherosclerotic cardiovascular disease to receive 1-g capsules containing either n-3 fatty acids (fatty acid group) or matching placebo (olive oil) daily. The primary outcome was a first serious vascular event (i.e., nonfatal myocardial infarction or stroke, transient ischemic attack, or vascular death, excluding confirmed intracranial hemorrhage). The secondary outcome was a first serious vascular event or any arterial revascularization.
Results
During a mean follow-up of 7.4 years (adherence rate, 76%), a serious vascular event occurred in 689 patients (8.9%) in the fatty acid group and in 712 (9.2%) in the placebo group. The composite outcome of a serious vascular event or revascularization occurred in 882 patients (11.4%) and 887 patients (11.5%), respectively. Death from any cause occurred in 752 patients (9.7%) in the fatty acid group and in 788 (10.2%) in the placebo group. There were no significant between-group differences in the rates of nonfatal serious adverse events.
Conclusions
Among patients with diabetes without evidence of cardiovascular disease, there was no significant difference in the risk of serious vascular events between those who were assigned to receive n-3 fatty acid supplementation and those who were assigned to receive placebo. (Funded by the British Heart Foundation and others; Current Controlled Trials number, ISRCTN60635500 ; ClinicalTrials.gov number, NCT00135226.)

The full article can be requested by Rotherham NHS staff, simply complete the form here 

 

The benefits and harms of aspirin for people with type 2 diabetes are finely balanced

NIHR | December 2018 |The benefits and harms of aspirin for people with type 2 diabetes are finely balanced

The findings of research that studied over 15000 UK adults with either type of diabetes but with no known cardiovascular disease is highlighted in a new NIHR signal.  

The ASCEND randomised controlled trial gave half of the participants either 100mg of aspirin or a sugar tablet. In addition they were also assigned to daily capsules containing n−3 fatty acids or matching placebo. 

Daily aspirin reduced the risk of serious vascular events among people with diabetes, while increasing the risk of major bleeding to a similar extent. Aspirin prevented one person in every 100 from having a heart attack or stroke over seven years, but an additional person per 100 experienced a major bleed.

The ASCEND study is one of three large placebo-controlled trials investigating the effects of 100mg daily aspirin for primary prevention in people without established cardiovascular disease. However, unlike other trials (in healthy older adults), this study found that aspirin had no effect on cancer risk during the study period.

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The finding supports NICE recommendations that aspirin shouldn’t be prescribed to people with diabetes who do not have existing cardiovascular disease (Source: NIHR).

Read the full Signal from NIHR 

Published abstract also available from NIHR 

Self-monitoring of blood glucose provides no important benefit for most people with type 2 diabetes

NIHR | October 2018 | Self-monitoring of blood glucose provides no important benefit for most people with type 2 diabetes

Patients with type 2 diabetes who monitor their blood glucose themselves may see small, short-term improvements in blood sugar control. This is not enough to be clinically important or outweigh the costs and personal inconvenience of long-term self-testing, reports an NIHR Signal. 

The signal highlights a systematic review (SR) that identified 24 recent randomised controlled trials involving more than  5000 people with type 2 diabetes to compare self- monitoring with control strategies where people were not taking insulin.

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Self-monitoring gave a 0.3 percentage point reduction in glycated haemoglobin (HbA1c) at six months. This is just below the 0.4% threshold for a meaningful clinical difference in this measure of average 3-month sugar control. People who had poorer blood glucose control at the start saw a greater benefit. However, there was no difference between the self-monitoring and control groups by 12 months.

The review supports current guideline recommendations that self-monitoring is not routinely used for people with type 2 diabetes controlled on diet or tablets (Source: NIHR).

Read the signal in full from NIHR 

Machry, R. V., Rados, D. V., de Gregório, G. R., & Rodrigues, T. C. |2018|  Self-Monitoring Blood Glucose improves glycemic control in Type 2 Diabetes without intensive treatment: a systematic review and meta-analysis|  Diabetes research and clinical practice| 

Abstract

AIMS: Systematic review and meta-analysis to evaluate the effect of Self-Monitoring of Blood Glucose (SMBG) on glycemic control in patients with type 2 Diabetes (T2D).

METHODS: We searched the Medline, Embase, Cochrane Central, and ClinicalTrials.gov databases up to 20 July 2017. We also performed a manual search of abstracts from recent meetings of the American Diabetes Association and the European Association for the Study of Diabetes.

STUDY SELECTION: randomized controlled trials (RCTs) conducted in patients with T2D comparing any kind of SMBG to a control group. Two independent reviewers assessed the eligibility of references. Influence of SMBG in glycated hemoglobin (HbA1c) was aggregated as weighted mean difference accessed by direct random effect meta-analyses at 12, 24 weeks and 1 year. Sub-analyses were made to assess the effects of previous glycemic control and number of tests performed.

RESULTS: SMBG was associated with a reduction of HbA1c at 12 weeks and 24 weeks, but no difference was found for 1 year. Subgroup analysis including studies with baseline HbA1c greater than 8% showed a higher reduction of HbA1c: -0.83% at 12 weeks, and -0.48%  at 24 weeks, with no difference for 1 year nor for the stratification for number the tests.

CONCLUSION: SMBG seems to lead to a slightly better glycemic control in the short term in patients with T2D. Patients decompensated at baseline appear to have the greatest benefit. PROSPERO register: CRD42016033558.

 

Closed loop insulin pump improves glucose control in hospital for people with type 2

NIHR | November 2018 | ‘Artificial pancreas’ improves glucose control in hospital patients with type 2 diabetes

A closed loop insulin pump, also referred to as an ‘artificial pancreas’   which continuously monitor blood glucose and administer insulin accordingly, can improve blood glucose control among patients with type 2 diabetes admitted to hospital for non-critical care. Those using the system spent about six hours longer in the target range, and this could hasten their recovery and reduce staff workload.

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The randomised controlled trial (RCT) involved  over 100 adults with type 2 diabetes admitted to general wards at two hospitals in the UK and Switzerland, all with raised blood sugar who needed insulin. Two-thirds of patients were already having insulin as part of their usual treatment.  Patients either continued with their usual insulin and glucose lowering treatments, which clinicians adjusted according to  conventional glucose measurements or they were assigned to the intervention and used the closed loop system to deliver insulin.  All patients wore an implanted continuous glucose monitor to record their glucose levels and were followed up after two weeks or until hospital discharge.  The study found that closed loop insulin delivery increased the percentage of time that blood glucose was in the target range of 100-180 mg per decilitre  by about 6 hours per day: 65.8% of the time in range (±16.8%) compared with 41.5% (±16.9%) in the control group, 

Read the signal in full at NIHR 

“The burden of diabetes is increasing, as is the proportion of hospital in-patients with diabetes. This study evaluates an alternative technology an automated closed-loop (also known as Artificial Pancreas) for improving the glucose control among hospital in-patients with diabetes.

The target glucose range was 5.6 to 10.0 mmol/L, with the standard care patients spending 12 hours/day hyperglycaemic (mean glucose 10.4 mmol/L). The closed-loop group spent about six hours more within range and six hours less with glucose levels 10.0 mmol/L or more.

The study highlights the inadequacy of current in-patient diabetes care and suggests that new technologies may allow for in-patient care that is safer and more effective than current clinical approaches.”

Dr HR Murphy, Professor of Medicine (Diabetes and Antenatal Care), Norwich Medical School

Source: NIHR

Abstract 

Background In patients with diabetes, hospitalization can complicate the achievement of recommended glycemic targets. There is increasing evidence that a closed-loop delivery system (artificial pancreas) can improve glucose control in patients with type 1 diabetes. We wanted to investigate whether a closed-loop system could also improve glycemic control in patients with type 2 diabetes who were receiving noncritical care.

Methods In this randomized, open-label trial conducted on general wards in two tertiary hospitals located in the United Kingdom and Switzerland, we assigned 136 adults with type 2 diabetes who required subcutaneous insulin therapy to receive either closed-loop insulin delivery (70 patients) or conventional subcutaneous insulin therapy, according to local clinical practice (66 patients). The primary end point was the percentage of time that the sensor glucose measurement was within the target range of 100 to 180 mg per deciliter (5.6 to 10.0 mmol per liter) for up to 15 days or until hospital discharge.

Results The mean (+/-SD) percentage of time that the sensor glucose measurement was in the target range was 65.8+/-16.8% in the closed-loop group and 41.5+/-16.9% in the control group, a difference of 24.3+/-2.9 percentage points; values above the target range were found in 23.6+/-16.6% and 49.5+/-22.8% of the patients, respectively, a difference of 25.9+/-3.4 percentage points. The mean glucose level was 154 mg per deciliter (8.5 mmol per liter) in the closed-loop group and 188 mg per deciliter (10.4 mmol per liter) in the control group (P less than0.001). There was no significant between-group difference in the duration of hypoglycemia or in the amount of insulin that was delivered (median dose, 44.4 U and 40.2 U, respectively; P=0.50). No episode of severe hypoglycemia or clinically significant hyperglycemia with ketonemia occurred in either trial group.

Conclusions Among inpatients with type 2 diabetes receiving noncritical care, the use of an automated, closed-loop insulin-delivery system resulted in significantly better glycemic control than conventional subcutaneous insulin therapy, without a higher risk of hypoglycemia. (Funded by Diabetes UK and others; ClinicalTrials.gov number, NCT01774565 .).

 

 

 

 

 

Full reference: Bally L, Thabit H, Hartnell S et al. | 2018 |  Closed-loop insulin delivery for glycemic control in noncritical care|  New England Journal of  Medicine | 379| 6| P. 547-56.