Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate data

Prof Dianna J Magliano, D. J. et al | 2021 | Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate data | The Lancet Diabetes & Endocrinology | DOI:https://doi.org/10.1016/S2213-8587(21)00327-2

Summary

Background

Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes.

Methods

In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR).

Findings

In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from –0·5 per cent (95 per cent CI –0·7 to –0·3) in Hungary to –4·2 per cent (−4·3 to –4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of –4·2 per cent (95 per cent CI –4·3 to –4·1) in Hong Kong, –4·0 per cent (−4·8 to –3·2) in South Korea, –3·5 per cent (−4·0 to –3·0) in Taiwan, and –3·6 per cent (−4·2 to –2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from –3·0 per cent (95 per cent CI –3·0 to –2·9; US Medicare) to 1·6 per cent (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources.

Interpretation

All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes.

Funding

US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program

Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate data [abstract only]

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New Type 2 Diabetes Risk Factors Identified

Martin, S. et al | 2021| Estimating the Effect of Liver and Pancreas Volume and Fat Content on Risk of Diabetes: A Mendelian Randomization Study | Diabetes Care | dc211262. https://doi.org/10.2337/dc21-1262

Type 2 diabetes (T2D) is associated with a number of risk factors and now new research, published in Diabetes Care, suggests that increased levels of liver fat and a smaller pancreas volume may also add to a greater risk of developing T2D.

The new study, conducted at Brunel University, used data collected from 32,859 people who underwent an MRI as part of the UK Biobank study. Data from 9358 participants with type 1 diabetes was also collected from various genome-wide association studies.

“People with type 2 diabetes usually have excess fat in their liver and pancreas, the two key organs in the maintenance of the normal level of blood sugar. The genetic analysis we used in this study is the best possible method to test this relationship,” says Dr Yaghootkar. (via MedScape).

OBJECTIVE

Fat content and volume of liver and pancreas are associated with risk of diabetes in observational studies; whether these associations are causal is unknown. We conducted a Mendelian randomization (MR) study to examine causality of such associations.

RESEARCH DESIGN AND METHODS

We used genetic variants associated (P less than 5 × 10−8) with the exposures (liver and pancreas volume and fat content) using MRI scans of UK Biobank participants (n equal to 32 859). We obtained summary-level data for risk of type 1 (9 358 cases) and type 2 (55 005 cases) diabetes from the largest available genome-wide association studies. We performed inverse–variance weighted MR as main analysis and several sensitivity analyses to assess pleiotropy and to exclude variants with potential pleiotropic effects.

RESULTS

Observationally, liver fat and volume were associated with type 2 diabetes (odds ratio per 1 SD higher exposure 2.16 [2.02, 2.31] and 2.11 [1.96, 2.27], respectively). Pancreatic fat was associated with type 2 diabetes (1.42 [1.34, 1.51]) but not type 1 diabetes, and pancreas volume was negatively associated with type 1 diabetes (0.42 [0.36, 0.48]) and type 2 diabetes (0.73 [0.68, 0.78]). MR analysis provided evidence only for a causal role of liver fat and pancreas volume in risk of type 2 diabetes (1.27 [1.08, 1.49] or 27 per cent increased risk and 0.76 [0.62, 0.94] or 24 per cent decreased risk per 1SD, respectively) and no causal associations with type 1 diabetes.

CONCLUSIONS

Our findings assist in understanding the causal role of ectopic fat in the liver and pancreas and of organ volume in the pathophysiology of type 1 and 2 diabetes.

MedScape New Type 2 Diabetes Risk Factors Identified

Estimating the Effect of Liver and Pancreas Volume and Fat Content on Risk of Diabetes: A Mendelian Randomization Study [paper]

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]

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]

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]

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

The Lancet: Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation

Lingvay, I., Sumithran, P., Cohen, R. V., & le Roux, C. W. | 2021 | Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation| The Lancet | https://doi.org/10.1016/S0140-6736(21)01919-X

Obesity is now recognised as a disease that is associated with serious morbidity and increased mortality. One of its main metabolic complications is type 2 diabetes, as the two conditions share key pathophysiological mechanisms. Weight loss is known to reverse the underlying metabolic abnormalities of type 2 diabetes and, as such, improve glucose control; loss of 15 per cent or more of bodyweight can have a disease-modifying effect in people with type 2 diabetes, an outcome that is not attainable by any other glucose-lowering intervention. Furthermore, weight loss in this population exerts benefits that extend beyond glycaemic control to improve risk factors for cardiometabolic disease and quality of life. We review the evidence supporting the role of weight loss in the management of type 2 diabetes and propose that many patients with type 2 diabetes would benefit from having a primary weight-centric approach to diabetes treatment. We discuss the logistical challenges to implementing a new weight-centric primary treatment goal in people with type 2 diabetes.

Interested in the full article? Rotherham NHS staff can request this article from their Library & Knowledge Service  

[NICE Consultation] Type 2 diabetes in adults: management – SGLT2 inhibitors for chronic kidney disease (update)

NICE |  September 2021 | Type 2 diabetes in adults: management – SGLT2 inhibitors for chronic kidney disease (update) In development [GID-NG10246]Expected publication date: 24 November 2021

This guidance will partially update the following:

This consultation is open until 29 September 2021 at 5pm

Full details, and consultation documents are available from NICE

Mindfulness in Relation to Diet Quality in Adults with Type 1 and Type 2 Diabetes: Results from Diabetes MILES-The Netherlands

Liu, S. et al | 2021| Mindfulness in Relation to Diet Quality in Adults with Type 1 and Type 2 Diabetes: Results from Diabetes MILES-The Netherlands| Mindfulness | https://doi.org/10.1007/s12671-021-01754-x

The objective of this research was to investigate the associations between dispositional mindfulness and diet quality in Dutch adults with type 1 diabetes (T1DM) or type 2 diabetes (T2DM). They hypothesized that a higher level of mindfulness is related to greater diet quality. In the light of previous research in other populations (Sala et al., 2020), they theorised that each mindfulness facet is positively associated with diet quality. In addition, they evaluated the potential mediating role of emotional distress in these associations.

The researchers found that a higher level of dispositional mindfulness and a higher score on observing were associated with higher diet quality. The results were more robust in people with T1DM. Their findings also suggest that overall mindfulness and the facet of observing are associated with higher diet quality in people with diabetes, independent of emotional distress.

They conclude that their findings suggest that mindfulness, especially observing facet, may relate to a healthier diet in adults with diabetes (Source: Liu et al, 2021).

The full paper is available to read from Mindfulness

Quality of complementary and alternative medicine information for type 2 diabetes: a cross-sectional survey and quality assessment of websites

Ng, J.Y., Nayeni, M. & Gilotra, K. | 2021| Quality of complementary and alternative medicine information for type 2 diabetes: a cross-sectional survey and quality assessment of websites| BMC Complement Med Ther | 21 | 233| https://doi.org/10.1186/s12906-021-03390-3

This study addresses a gap in the literature, it set out to identify and assess the quality of consumer health information presented online for CAM-specific treatment and/or management options for type 2 diabetes mellitus (T2DM). They report that their subset contained low quality consumer health information; noting that the websites included for assessment often failed to provide adequate references to support their health statements (Ng, Nayeni, & Gilotra, 2021).

Abstract

Background

The global prevalence of diabetes mellitus is projected to reach approximately 700 million by the year 2045, with roughly 90–95% of all diabetes cases being type 2 in nature. Patients with type 2 diabetes mellitus (T2DM) frequently seek information about complementary and alternative medicine (CAM) online. This study assessed the quality of publicly accessible websites providing consumer health information at the intersection of T2DM and CAM.

Methods

An online search engine (Google) was searched to identify pertinent websites containing information specific to CAM for T2DM patients, and the relevant websites were then screened with an eligibility criteria. Consumer health information found on eligible websites were then assessed for quality using the DISCERN instrument, a 16-item standardized scoring system.

Results

Across the 480 webpages identified, 94 unique webpages remained following deduplication, and 37 eligible webpages belonged to and were collapsed into 30 unique websites that were each assessed using the DISCERN instrument. The mean overall quality score (question 16) across all 30 assessed websites was 3.55 (SD = 0.86), and the mean summed DISCERN score was 52.40 (SD = 12.11). Eighty percent of websites presented a wide range of CAM treatment options with the associated benefits/risks of each treatment, but in 56.7% of the websites, the sources used to collect information were unreliable.

Conclusion

This study identified, assessed, and presents findings on the quality of online CAM information for T2DM. Although there were several high scoring websites, there was variability across most of the individual DISCERN items in the assessed websites. This study highlights the importance of awareness among healthcare providers regarding the reliability of online information about CAM treatment and management options for T2DM. Healthcare providers should be aware of patients’ information seeking behaviour, guide them in navigating through the content they encounter online, and provide them with resources containing trustworthy and reliable information.

Quality of complementary and alternative medicine information for type 2 diabetes: a cross-sectional survey and quality assessment of websites [primary paper]