The UK has just seen it’s hottest July on record, including the highest ever temperature recorded. With climate change in the forefront of our minds, it’s timely that we have two editorials on the sustainability and health. Michael Depledge, emeritus professor of environment and human health at University of Exeter Medical School, and author of...

We know that exercise is good for you - the WHO recommends at least 150 minutes of moderate intensity or 75 minutes of vigorous intensity aerobic physical activity each week. That recommendation is built on evidence that relied on self reporting that may underestimate the amount of lower intensity exercise those people were doing, and at the...

This week the Trump administration has banned the sale of flavoured vapes in the USA. The reason for that is the sudden rash of cases of pulmonary disease, including deaths, linked to vaping. The mechanism by which vaping may be causing damage to the lungs is as yet unclear, and our understanding is hampered by the heterogeneous nature of the...

The BMJ in partnership with The Harvard Global Health Institute has launched a collection of articles exploring how to achieve effective universal health coverage (UHC). The collection highlights the importance of quality in UHC, potential finance models, how best to incentivise stakeholders, and some of the barriers to true UHC. One of those...

Talk Evidence is back, with your monthly take on the world of EBM with Duncan Jarvies and GPs Carl Heneghan (also director for the Centre of Evidence Based Medicine at the University of Oxford) and Helen Macdonald (also The BMJ's UK research Editor). This month Carl talks about evidence that restricting your diet might improve health at a...

Direct-to-consumer genetic tests are sold online and in shops as a way to “find out what your DNA says". They insights into ancestry or disease risks; others claim to provide information on personality, athletic ability, and child talent. However, interpretation of genetic data is complex and context dependent, and DTC genetic tests may produce...

The NHS Practitioner Health Programme - once only for doctors in London, now it’s being rolled out across the NHS to provide the largest, publicly funded, comprehensive physician health service, in the world. However, while helping the individual is essential, systemic change needs to be made to support doctors in our healthcare system. Clare...

Giving staff the confidence to speak out is important in healthcare - It's a key aspect of the WHO patient safety checklist, decreasing incidence of medical error, but it's also important to stop incidents of harassment and abuse which undermine staff and increase burnout. Creating that culture is a difficult task, but two hospitals in the...

A UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week...

A UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week...

UK general election has been called - polling day is on the 12th of December, and from now until then we’re going to be bringing you a weekly election-themed podcast. We want to help you make sense of the promises and pledges, claims and counter-claims, that are being made around healthcare and the NHS out on the campaign trail. This week we're...

As editors, we feel like we’re spending a lot of time taking the superlatives out from articles - amazing, novel, important… But new research on BMJ.com suggests that we might not be doing that great a job, and that for some reason, papers authored by men tend to have more of them - because men put more in, or maybe a bias against woman writing in...

If you read the Christmas BMJ in the last few weeks, you might have noticed a lot around art and health - the way in which engagement in arts can help in prevention and treatment, but can also affect those more nebulous things which really matter to patients - loneliness, self expression, being connected to the wider community. That obviously...

In a British cohort, 30% of patients who had survived childhood cancer had died within 45 years of diagnosis; only 6% were expected to have died. 51% had developed a new primary cancer, but a 26% died of cardiovascular disease - thought to be caused by their treatment. Consequently, efforts to reduce long term mortality have focused on reducing...

Precocious puberty, that is puberty that starts before age 8 in girls and 9 in boys seems to be on the rise, but whether that’s because of an increase in incidence, or greater attention is unknown - what we do know that precocious puberty in girls is commonly idiopathic, while in boys is a red flag for pathology. But either way ther first point of...

In many countries (including the UK and Australia) it is still common practice for hospital doctors to write letters to patients’ general practitioners (GPs) following outpatient consultations, and for patients to receive copies of these letters. However, Hugh Rayner, consultant nephrologist, and Peter Rees, former Chair of the Academy of...

In 2012, Eleni Linos, professor of dermatology at Stanford university, published a systematic review and meta-analysis of the link between non-melanoma cancer and sun-beds. That bit of pretty standard research, and a particular rapid response to it, has kicked of years of work - and in this podcast I talk to Eleni and her colleagues Stanton...

We all know we should be doing more exercise, and one way to do that is by active commuting - journeying to work on foot or by bike. One thing preventing people from taking up cycling is the fear of being involved in road traffic accidents, and that the risk isn't worth the benefit of the extra exercise. It’s even more confusing when air...

As part of our response to the covid-19 pandemic, we’re going to be running a series of discussions with experts about some of the big issues arising from the virus. In this one, we’re asking about the public health response to an outbreak - what’s necessary, and is it possible to go to far. Joining us are Martin Mckee - professor of european...

We’ve published info on Telehealth in primary care - and have been overwhelmed by the response from GPs who are finding it useful. But it’s not only primary care that is dramatically shifting to remote care - routine hospital care is moving online too, so we’ve asked Rowena McCash - GP and out of hours triage trainer joins us to give some tips...

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...

A new podcast from The BMJ, to help GP's feel more connected, heard, and supported. Subscribe on; Apple podcasts - https://bit.ly/applepodsDBI Spotify - https://bit.ly/spotifyDBI Google podcasts - https://bit.ly/googlepodsDBI This week, our topic is fear: we try to get a better understanding of fear, how it affects all of us as clinicians for...

Around the world, as the covid pandemic plays out, and some countries are starting to ease their restrictions, this narrative of the economy and public health being opposing weights on a set of scales keeps returning - they need to be balanced. But before this, a healthy population is very much seen as being supportive of the economy. So is a...

Katalin Susztak
Jan 1, 2006; 55:225-233
Complications

Dilys J. Freeman
May 1, 2002; 51:1596-1600
Complications

Michael P Stern
Apr 1, 1995; 44:369-374
Perspectives in Diabetes

Mariano J Garcia
Feb 1, 1974; 23:105-111
Original Contribution

Masayuki Saito
Jul 1, 2009; 58:1526-1531
Metabolism

Alan R Saltiel
Dec 1, 1996; 45:1661-1669
Perspectives in Diabetes

Christophe Bonny
Jan 1, 2001; 50:77-82
Islet Studies

Joachim Spranger
Mar 1, 2003; 52:812-817
Pathophysiology

G Perseghin
Aug 1, 1999; 48:1600-1606
Articles

Charles M. Alexander
May 1, 2003; 52:1210-1214
Complications

Miriam Cnop
Dec 1, 2005; 54:S97-S107
Section III: Inflammation and beta-Cell Death

Giulio Marchesini
Aug 1, 2001; 50:1844-1850
Pathophysiology

T Inoguchi
Nov 1, 2000; 49:1939-1945
Articles

Eve Van Cauter
Mar 1, 1992; 41:368-377
Original Article

Ralph A. DeFronzo
Apr 1, 2009; 58:773-795
Banting Lecture

G Xu
Dec 1, 1999; 48:2270-2276
Articles

Paul E Lacy
Jan 1, 1967; 16:35-39
Original Contribution

David E. Cummings
Aug 1, 2001; 50:1714-1719
Rapid Publications

Norikazu Maeda
Sep 1, 2001; 50:2094-2099
Pathophysiology

Thomas A. Buchanan
Sep 1, 2002; 51:2796-2803
Pathophysiology

U.K. Prospective Diabetes Study Group
Nov 1, 1995; 44:1249-1258
Perspectives in Diabetes

Alexandra E. Butler
Jan 1, 2003; 52:102-110
Islet Studies

Gerald M Reaven
Dec 1, 1988; 37:1595-1607
Banting Lecture 1988

Permanent neonatal diabetes mellitus (PNDM) is caused by reduced β-cell number or impaired β-cell function. Understanding of the genetic basis of this disorder highlights fundamental β-cell mechanisms. We performed trio genome sequencing for 44 patients with PNDM and their unaffected parents to identify causative de novo variants. Replication studies were performed in 188 patients diagnosed with diabetes before 2 years of age without a genetic diagnosis. EIF2B1 (encoding the eIF2B complex α subunit) was the only gene with novel de novo variants (all missense) in at least three patients. Replication studies identified two further patients with de novo EIF2B1 variants. In addition to having diabetes, four of five patients had hepatitis-like episodes in childhood. The EIF2B1 de novo mutations were found to map to the same protein surface. We propose that these variants render the eIF2B complex insensitive to eIF2 phosphorylation, which occurs under stress conditions and triggers expression of stress response genes. Failure of eIF2B to sense eIF2 phosphorylation likely leads to unregulated unfolded protein response and cell death. Our results establish de novo EIF2B1 mutations as a novel cause of permanent diabetes and liver dysfunction. These findings confirm the importance of cell stress regulation for β-cells and highlight EIF2B1’s fundamental role within this pathway.

Children at increased genetic risk for type 1 diabetes (T1D) after environmental exposures may develop pancreatic islet autoantibodies (IA) at a very young age. Metabolic profile changes over time may imply responses to exposures and signal development of the first IA. Our present research in The Environmental Determinants of Diabetes in the Young (TEDDY) study aimed to identify metabolome-wide signals preceding the first IA against GAD (GADA-first) or against insulin (IAA-first). We profiled metabolomes by mass spectrometry from children’s plasma at 3-month intervals after birth until appearance of the first IA. A trajectory analysis discovered each first IA preceded by reduced amino acid proline and branched-chain amino acids (BCAAs), respectively. With independent time point analysis following birth, we discovered dehydroascorbic acid (DHAA) contributing to the risk of each first IA, and -aminobutyric acid (GABAs) associated with the first autoantibody against insulin (IAA-first). Methionine and alanine, compounds produced in BCAA metabolism and fatty acids, also preceded IA at different time points. Unsaturated triglycerides and phosphatidylethanolamines decreased in abundance before appearance of either autoantibody. Our findings suggest that IAA-first and GADA-first are heralded by different patterns of DHAA, GABA, multiple amino acids, and fatty acids, which may be important to primary prevention of T1D.

Long-term hyperglycemia in patients with diabetes leads to human serum albumin (HSA) glycation, which may impair HSA function as a transport protein and affect the therapeutic efficacy of anticoagulants in patients with diabetes. In this study, a novel mass spectrometry approach was developed to reveal the differences in the profiles of HSA glycation sites between patients with diabetes and healthy subjects. K199 was the glycation site most significantly changed in patients with diabetes, contributing to different interactions of glycated HSA and normal HSA with two types of anticoagulant drugs, heparin and warfarin. An in vitro experiment showed that the binding affinity to warfarin became stronger when HSA was glycated, while HSA binding to heparin was not significantly influenced by glycation. A pharmacokinetic study showed a decreased level of free warfarin in the plasma of diabetic rats. A preliminary retrospective clinical study also revealed that there was a statistically significant difference in the anticoagulant efficacy between patients with diabetes and patients without diabetes who had been treated with warfarin. Our work suggests that larger studies are needed to provide additional specific guidance for patients with diabetes when they are administered anticoagulant drugs or drugs for treating other chronic diseases.

Tears flowed yesterday down the face of Donaree Anderson, cousin of 15-year-old Nyron Taylor, one of two children shot dead in west Kingston hours apart on Wednesday. Eight-year-old Toya Brown was the other child killed just days into the month...