Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis

Nazarzadeh, M., Bidel, Z., Canoy, D., Copland, E., Wamil, M., Majert, J., … & Trialists’Collaboration, B. P. L. T. | 2021 | Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis | The Lancet398 | 10313 | P. 1803-1810.

This meta-analysis used large-scale individual participant data from randomised controlled trials to investigate the effect of blood pressure lowering and the differential effects of five major classes of antihypertensives on risk of new-onset type 2 diabetes. A fixed level of 5 mm Hg reduction in systolic blood pressure reduced the risk of diabetes by 11 per cent. This treatment effect constituted quantitatively and qualitatively diverging effects of major antihypertensive drug classes. In analysis of specific drug classes versus placebo, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers had the strongest protective effect on the risk of diabetes. For calcium channel blockers no material effect was found, while β blockers and thiazide diuretics increased the risk.

The experts behind this study suggest that their findings indicate that blood pressure lowering can help prevent diabetes in addition to its well established beneficial effects in reducing cardiovascular events. The relative magnitude of reduction per 5 mm Hg systolic blood pressure lowering was similar to those reported for prevention of major cardiovascular events, which will strengthen the case for blood pressure reduction through lifestyle interventions known to reduce blood pressure, and blood pressure lowering treatments with drugs, and possibly device therapies (Source: Nazarzadeh et al, 2021).

Summary

Background

Blood pressure lowering is an established strategy for preventing microvascular and macrovascular complications of diabetes, but its role in the prevention of diabetes itself is unclear. We aimed to examine this question using individual participant data from major randomised controlled trials.

Methods

We performed a one-stage individual participant data meta-analysis, in which data were pooled to investigate the effect of blood pressure lowering per se on the risk of new-onset type 2 diabetes. An individual participant data network meta-analysis was used to investigate the differential effects of five major classes of antihypertensive drugs on the risk of new-onset type 2 diabetes. Overall, data from 22 studies conducted between 1973 and 2008, were obtained by the Blood Pressure Lowering Treatment Trialists’ Collaboration (Oxford University, Oxford, UK). We included all primary and secondary prevention trials that used a specific class or classes of antihypertensive drugs versus placebo or other classes of blood pressure lowering medications that had at least 1000 persons-years of follow-up in each randomly allocated arm. Participants with a known diagnosis of diabetes at baseline and trials conducted in patients with prevalent diabetes were excluded. For the one-stage individual participant data meta-analysis we used stratified Cox proportional hazards model and for the individual participant data network meta-analysis we used logistic regression models to calculate the relative risk (RR) for drug class comparisons.

Findings

145 939 participants (88 500 [60·6%] men and 57 429 [39·4%] women) from 19 randomised controlled trials were included in the one-stage individual participant data meta-analysis. 22 trials were included in the individual participant data network meta-analysis. After a median follow-up of 4·5 years (IQR 2·0), 9883 participants were diagnosed with new-onset type 2 diabetes. Systolic blood pressure reduction by 5 mm Hg reduced the risk of type 2 diabetes across all trials by 11% (hazard ratio 0·89 [95% CI 0·84–0·95]). Investigation of the effects of five major classes of antihypertensive drugs showed that in comparison to placebo, angiotensin-converting enzyme inhibitors (RR 0·84 [95% 0·76–0·93]) and angiotensin II receptor blockers (RR 0·84 [0·76–0·92]) reduced the risk of new-onset type 2 diabetes; however, the use of β blockers (RR 1·48 [1·27–1·72]) and thiazide diuretics (RR 1·20 [1·07–1·35]) increased this risk, and no material effect was found for calcium channel blockers (RR 1·02 [0·92–1·13]).

Interpretation

Blood pressure lowering is an effective strategy for the prevention of new-onset type 2 diabetes. Established pharmacological interventions, however, have qualitatively and quantitively different effects on diabetes, likely due to their differing off-target effects, with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers having the most favourable outcomes. This evidence supports the indication for selected classes of antihypertensive drugs for the prevention of diabetes, which could further refine the selection of drug choice according to an individual’s clinical risk of diabetes.

Funding

British Heart Foundation, National Institute for Health Research, and Oxford Martin School.

The Lancet Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis [paper]

Dexamethasone Increases Diabetes Complications but Still Saves Lives

via MedScape | 12 November 2021 | Dexamethasone Increases Diabetes Complications but Still Saves Lives

Research presented earlier this month at The Society for Endocrinology’s annual conference, SfE BES 2021, suggests that  when dexamethasone is prescribed to hospitalised COVID-19 patients with diabetes may increase their risk of developing steroid-induced dysglycaemia but it does not prevent them from experiencing the life-saving benefits of the drug, suggests a real-world UK analysis.

Data on more than 2250 patients treated in the first and second waves of the pandemic showed that, in patients with diabetes, dexamethasone increased the risk of dysglycaemia more than 20-fold.

However, patients with dexamethasone-associated complications did not have an increased risk of death, and overall the drug was shown to reduce the risk of admission to intensive care or death within 30 days of admission by 56 per cent (Source: MedScape).

The full news story is available from MedScape

Diabetes NHS Long Term Plan Commitments ‘Met and Exceeded’

McCall, B. | 11 November 2021 | MedScape

Outcomes in diabetes are something to be proud of, said England’s National Specialty Advisor for Diabetes, addressing the opening session of the Diabetes Professional Conference 2021.

He added that the last decade had seen rates of amputations, cardiovascular disease, and hospital admissions all drop significantly, and much of this had been led by primary care as well as specialty services.

Professor Partha Kar, national specialty advisor for diabetes, together with Professor Jonathan Valabhji, national clinical director for diabetes and obesity, presented the annual update on the NHS England Diabetes and Obesity Programmes at the meeting, held in-person in London.

The update was dominated by the effect of the pandemic on delivery of care from the perspective of both clinicians and patients. Prof Valabhji pointed out that faced with the onslaught of COVID and the desperate need for a solution, the emphasis was on disentangling the unknowns at that time. “In severe outcomes there was a clear association between COVID and HbA1c, and BMI in the obese range. Our rich NHS datasets have provided info that other countries’ can’t do.” (Source: MedScape).

Read the full article from MedScape

Annual diabetes care processes and mortality using data from the National Diabetes Audit

Holman, N. et al | 2021 | Completion of annual diabetes care processes and mortality: A cohort study using the National Diabetes Audit for England and Wales | Diabetes Obesity & Metabolism | https://doi.org/10.1111/dom.14528

In England and Wales, the National Diabetes Audit (NDA) collects patient-level data on people with diagnosed diabetes. The present study assesses whether recorded care processes completion was associated with mortality over the subsequent decade after adjustment for the risk factors that the care processes uncover, individual demographic characteristics and comorbidities. This resulting paper, published in the journal Diabetes, Obesity & Metabolism highlights that individuals with diabetes who have fewer routine care processes have higher mortality.

Abstract

Aim

To conduct an analysis to assess whether the completion of recommended diabetes care processes (glycated haemoglobin [HbA1c], creatinine, cholesterol, blood pressure, body mass index [BMI], smoking habit, urinary albumin, retinal and foot examinations) at least annually is associated with mortality.

Materials and methods

A cohort from the National Diabetes Audit of England and Wales comprising 179 105 people with type 1 and 1 397 790 people with type 2 diabetes, aged 17 to 99 years on January 1, 2009, diagnosed before January 1, 2009 and alive on April 1, 2013 was followed to December 31, 2019. Cox proportional hazards models adjusting for demographic characteristics, smoking, HbA1c, blood pressure, serum cholesterol, BMI, duration of diagnosis, estimated glomerular filtration rate, prior myocardial infarction, stroke, heart failure, respiratory disease and cancer, were used to investigate whether care processes recorded January 1, 2009 to March 31, 2010 were associated with subsequent mortality.

Results

Over a mean follow-up of 7.5 and 7.0 years there were 26 915 and 388 093 deaths in people with type 1 and type 2 diabetes, respectively. Completion of five or fewer, compared to eight, care processes (retinal screening not included as data were not reliable) had a mortality hazard ratio (HR) of 1.37 (95 Over a mean follow-up of 7.5 and 7.0 years there were 26 915 and 388 093 deaths in people with type 1 and type 2 diabetes, respectively. Completion of five or fewer, compared to eight, care processes (retinal screening not included as data were not reliable) had a mortality hazard ratio (HR) of 1.37 (95 per cent confidence interval [CI] 1.28-1.46) in people with type 1 and 1.32 (95 per cent CI 1.30-1.35) in people with type 2 diabetes. The HR was higher for respiratory disease deaths and lower in South Asian ethnic groups. confidence interval [CI] 1.28-1.46) in people with type 1 and 1.32 (95 per cent CI 1.30-1.35) in people with type 2 diabetes. The HR was higher for respiratory disease deaths and lower in South Asian ethnic groups.

Conclusions

People with diabetes who have fewer routine care processes have higher mortality. Further research is required into whether different approaches to care might improve outcomes for this high-risk group.

Completion of annual diabetes care processes and mortality: A cohort study using the National Diabetes Audit for England and Wales [paper]

Scotland to rollout diabetes test for Type 1 patients

via BBC News | 31 October 2021 | Scotland to rollout diabetes test for Type 1 patients

Misdiagnosed Type 1 diabetes patients could be freed from the need to take insulin after a new test is rolled out.

Scotland will become the first country to offer the C-peptide blood test to all patients who have had a Type 1 diagnosis for at least three years.

The test shows how much insulin a patient’s body is producing itself. A pilot by NHS Lothian allowed some people who had been taking insulin to stop or reduce the treatment. The test will be available from 1 November.

C-peptide testing, which has been used as part of diagnosis for some patients for many years, can help distinguish whether a patient has Type 1 or Type 2 diabetes.

BBC News Scotland to rollout diabetes test for Type 1 patients

Risks of and From SARS-CoV-2 Infection and COVID-19 in People With Diabetes: a Systematic Review of Reviews #Covid19RftLks

Hartmann-Boyce, J. et al | 2021| Risks of and From SARS-CoV-2 Infection and COVID-19 in People With Diabetes: a Systematic Review of Reviews | Diabetes Care | dc210930 |  DOI: 10.2337/dc21-0930

In this review of reviews, the reviewers set out to synthesize the evidence regarding the extent to which people with diabetes (PWD) are at increased risk of SARS-CoV-2 infection and/or from suffering its complications, including associated mortality. In particular, we set out to analyze evidence on the following questions:

  1. Is diabetes associated with increased risk of acquiring SARS-CoV-2?
  2. Is diabetes associated with hospitalization with COVID-19?
  3. Is diabetes associated with the severity (including intensive care unit [ICU] admission, death, and
    other composite measures of severity) of COVID-19 outcomes?
  4. Are there differences in outcomes of SARS-CoV-2 infection within the population of PWD?

They report that their overview of reviews provides consistent evidence from multiple metaanalyses that diabetes is a risk factor for severe disease and death from COVID-19.

Abstract

Background This review was commissioned by the World Health Organization and presents a summary of the latest research evidence on the impact of coronavirus disease 2019 (COVID-19) on people with diabetes (PWD).

Purpose To review the evidence regarding the extent to which PWD are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or of suffering its complications, including associated mortality.

Data Sources We searched the Cochrane COVID-19 Study Register, Embase, MEDLINE, and LitCOVID on 3 December 2020.

Study Selection Systematic reviews synthesizing data on PWD exposed to SARS-CoV-2 infection, reporting data on confirmed SARS-CoV-2 infection, admission to hospital and/or to intensive care unit (ICU) with COVID-19, and death with COVID-19 were used.

Data Extraction One reviewer appraised and extracted data; data were checked by a second.

Data Synthesis Data from 112 systematic reviews were narratively synthesized and displayed using effect direction plots. Reviews provided consistent evidence that diabetes is a risk factor for severe disease and death from COVID-19. Fewer data were available on ICU admission, but where available, these data also signaled increased risk. Within PWD, higher blood glucose levels both prior to and during COVID-19 illness were associated with worse COVID-19 outcomes. Type 1 diabetes was associated with worse outcomes than type 2 diabetes. There were no appropriate data for discerning whether diabetes was a risk factor for acquiring SARS-CoV-2 infection.

Limitations Due to the nature of the review questions, the majority of data contributing to included reviews come from retrospective observational studies. Reviews varied in the extent to which they assessed risk of bias.

Conclusions There are no data on whether diabetes predisposes to infection with SARS-CoV-2. Data consistently show that diabetes increases risk of severe COVID-19. As both diabetes and worse COVID-19 outcomes are associated with socioeconomic disadvantage, their intersection warrants particular attention.

Risks of and From SARS-CoV-2 Infection and COVID-19 in People With Diabetes: a Systematic Review of Reviews

Mortality Risk of Antidiabetic Agents for Type 2 Diabetes With COVID-19: A Systematic Review and Meta-Analysis #Covid19RftLks

Kan, C. et al | 2021| Mortality Risk of Antidiabetic Agents for Type 2 Diabetes With COVID-19: A Systematic Review and Meta-Analysis| Frontiers in Endocrinology | https://doi.org/10.3389/fendo.2021.708494

The reviewers of this systematic review and meta-analysis investigate the associations of antidiabetic agents with mortality in patients with type 2 diabetes mellitus (T2DM) who have COVID-19. The authors conclude that metformin and sulfonylurea treatments could be associated with reduced mortality risk, while insulin treatment could be associated with enhanced mortality risk, in patients with T2DM who had COVID-19. However, DPP-4 inhibitor treatment could not be associated with mortality risk in these patients. The results of this meta-analysis should be interpreted carefully because of the limitations of included studies, although the effects of sulfonylurea and DPP-4 inhibitors should be more fully evaluated in subsequent studies. Further larger trials should also be done to confirm these results and especially other diabetes drugs including SGLT2 inhibitors and DPP-4 inhibitors (Source: Kan et al, 2021).

Aims: We conducted a systematic review and meta-analysis to assess various antidiabetic agents’ association with mortality in patients with type 2 diabetes (T2DM) who have coronavirus disease 2019 (COVID-19).

Methods: We performed comprehensive literature retrieval from the date of inception until February 2, 2021, in medical databases (PubMed, Web of Science, Embase, and Cochrane Library), regarding mortality outcomes in patients with T2DM who have COVID-19. Pooled OR and 95 per cent CI data were used to assess relationships between antidiabetic agents and mortality.

Results: Eighteen studies with 17,338 patients were included in the meta-analysis. Metformin (pooled OR, 0.69; P equal to 0.001) and sulfonylurea (pooled OR, 0.80; P equal to 0.016) were associated with lower mortality risk in patients with T2DM who had COVID-19. However, patients with T2DM who had COVID-19 and received insulin exhibited greater mortality (pooled OR, 2.20; P equal to 0.002). Mortality did not significantly differ (pooled OR, 0.72; P equal to 0.057) between DPP-4 inhibitor users and non-users.

Conclusions: Metformin and sulfonylurea could be associated with reduced mortality risk in patients with T2DM who have COVID-19. Furthermore, insulin use could be associated with greater mortality, while DPP-4 inhibitor use could not be. The effects of antidiabetic agents in patients with T2DM who have COVID-19 require further exploration.

Systematic Review Registration: PROSPERO (identifier, CRD42021242898).

Mortality Risk of Antidiabetic Agents for Type 2 Diabetes With COVID-19: A Systematic Review and Meta-Analysis [pdf]

NIHR: Call for ‘international efforts’ to examine link between COVID-19 and new-onset diabetes #Covid19RftLks

NIHR | October 2021 | Call for ‘international efforts’ to examine link between COVID-19 and new-onset diabetes 

A comprehensive review led by ARC East Midlands has explored ‘COVID-19, hyperglycemia and new-onset diabetes’.

An international team of researchers have been involved and have commented that early identification and treatment of people who fall into this category could improve their long-term outcomes.

Professor Kamlesh Khunti, Director of ARC East Midlands and Professor of Primary Care Diabetes and Vascular Medicine at the University of Leicester, said: “Given we are still in the midst of a global COVID-19 pandemic, we are likely to see even larger numbers of people globally with new-onset diabetes. International efforts need to be established to study COVID-19 associated new-onset diabetes with follow-up of large numbers of patients.”

Several studies conducted during the pandemic have reported that COVID-19 is associated with hyperglycaemia in people with and without known diabetes. The authors of this latest research also acknowledge that the phenomenon of new-onset diabetes following admission to hospital has been seen previously with other viral infections. 

The perspective, published in the American Diabetes Association’s journal, Diabetes Care, explores the possible reasons for the link between COVID-19 and new-onset diabetes.

The authors discuss four possible explanations:

  • Pre-existing undiagnosed diabetes. People admitted to hospital may have had undetected diabetes prior to admission, which could be a result of recent weight gain due to lifestyle changes and worsening of hyperglycaemia due to self-isolation; social distancing; reduced physical activity; and poor diet linked to mental health issues.
  • Stress hyperglycaemia and new-onset diabetes following acute illness. The phenomenon of hyperglycaemia and new-onset diabetes following admission to hospital with acute illness has previously been identified. In COVID-19, stress hyperglycaemia may be even more severe due to the cytokine storm – an inflammatory syndrome.
  • Viral infections and new-onset diabetes. Viral infections may have an effect on the pancreas. Previous studies have reported acute inflammation in the pancreas due to other viruses.
  • In hospital steroid-induced hyperglycaemia. Steroid-induced hyperglycaemia is common in hospitalised patients. Previous studies have shown that between 53 and 70 per cent of non-diabetic individuals develop steroid-induced hyperglycaemia(Source: NIHR).

Related:

COVID-19, Hyperglycemia, and New-Onset Diabetes

National Pregnancy in Diabetes Audit Report 2020

Health Quality Improvement Partnership | October 2021 | National Pregnancy in Diabetes Audit Report 2021

The National Pregnancy in Diabetes Audit measures the quality of antenatal care and pregnancy outcomes for women with pre-gestational diabetes. HQIP has published its report for 2020.

Key findings from the audit report:

There are now more pregnancies in women with type 2 diabetes, than in women with type 1 diabetes (54 per cent of diabetes’ pregnancies, compared to 47 per cent in 2014).

Women with type 2 diabetes face additional healthcare inequalities and are frequently not prepared for pregnancy (reduced use of insulin and folic acid before pregnancy), and

Despite the additional challenges of supporting women with diabetes during the COVID-19 pandemic, pregnancy outcomes are comparable in 2019 and 2020.

Image source: HQIP The first mage shows a sonographer, ultrasound and an expectant couple. The second shows a pregnant women preparing a selection of healthy foods

The report makes three recommendations

  1. Dedicated pre-pregnancy co-ordinators focused on enhanced provision of contraception and support for pregnancy preparation are recommended to improve glycaemic management and 5mg folic acid supplementation before pregnancy, especially in women with type 1 and type 2 diabetes, living in the most deprived regions.
  2. We found fewer preterm births, large for gestational age (LGA) birthweight, neonatal care admissions and perinatal deaths in women with HbA1c less than 43mmol/mol from 24 weeks gestation, both in the current 2019-2020 and recent datasets*. NICE guidelines [NG3 Diabetes in pregnancy: management from preconception to the postnatal period], recommend use of continuous glucose monitoring (CGM) in type 1 diabetes. Data are now needed to evaluate whether Libre or CGM use will improve glucose levels, target HbA1c attainment and neonatal health outcomes in pregnant women with type 2 diabetes.
  3. Access to structured education, weight management and diabetes prevention programmes for women (Source: HQIP).

National Pregnancy in Diabetes (NPID) Audit Report 2020

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]