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 has...

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...

The UK general election is happening this week, and you’ve probably made your mind up which MP you’re voting for already - and maybe the NHS has influenced that decision. This year has seen an increase in the number of doctors running for parliament, and in this podcast we find out what motivates doctors to step away from clinical practice, and...

If you’re lucky enough to not be back at work, you might be feeling like you need to quickly refresh your medical knowledge - and this podcast the BMJ’s education editors take you on a whistlestop tour through the BMJ’s education articles of 2019. Tom Nolan (GP in London) is joined by Navjoyt Ladher (GP in London), Anita Jain (GP in India) and...

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...

The NHS is a world leader in sustainable healthcare - and it's the staff who have have been leading the charge. The For A Greener NHS campaign is asking everyone who has made a change to the way they work, to submit evidence and help shape the whole organisation's response to the climate emergency. In this podcast, Isobel Braithwaite, public...

As we cover the covid-19 outbreak, we want to hear some of the stories from the frontline - And who better to heart of what this pandemic is doing to the profession in the UK, than some of the people who write regularly for The BMJ? In this first one, we wanted to look specifically at acute care - those at the sharp end of the response, so we're...

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...

As the pandemic plays out - hospitals are reconfigured to increase critical care capacity, outpatient clinics become virtual, and elective procedures delayed. How are these affecting care for those who are in hospital but don't have covid-19? In this podcast, Matt Morgan,honorary senior research fellow at Cardiff University, consultant in...

In this week’s episode, we discuss bystander guilt, convergence, brain hacks and “how you can sneeze on someone’s brain from anywhere in the world”. How can GPs cope with the myriad worries around treating patients during the current pandemic, both on the frontline and in general practice? How do we recognise and break unhelpful anxious behaviour...

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

EJ Kurth-Kraczek
Aug 1, 1999; 48:1667-1671
Articles

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

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

Cindy J.M. Loomans
Jan 1, 2004; 53:195-199
Complications

Marc Prentki
Mar 1, 1996; 45:273-283
Original Article

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

R A DeFronzo
Dec 1, 1981; 30:1000-1007
Original Contribution

C. Ronald Kahn
Aug 1, 1994; 43:1066-1085
Banting Lecture

D Koya
Jun 1, 1998; 47:859-866
Articles

Roger H Unger
Aug 1, 1995; 44:863-870
Perspectives in Diabetes

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

The Diabetes Control and Complications Trial Research Group
Feb 1, 1997; 46:271-286
Original Article

The Diabetes Control and Complications Trial Research Group
Aug 1, 1995; 44:968-983
Original Article

JW Baynes
Jan 1, 1999; 48:1-9
Articles

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

ME Griffin
Jun 1, 1999; 48:1270-1274
Articles

John W Baynes
Apr 1, 1991; 40:405-412
Perspectives in Diabetes

Steven E Kahn
Nov 1, 1993; 42:1663-1672
Original Article

Michael Brownlee
Jun 1, 2005; 54:1615-1625
Banting Lecture 2004

National Diabetes Data Group
Dec 1, 1979; 28:1039-1057
Articles

Night shift work, behavioral rhythms, and the common MTNR1B risk single nucleotide polymorphism (SNP), rs10830963, associate with type 2 diabetes; however, whether they exert joint effects to exacerbate type 2 diabetes risk is unknown. Among employed participants of European ancestry in the UK Biobank (N = 189,488), we aimed to test the cross-sectional independent associations and joint interaction effects of these risk factors on odds of type 2 diabetes (n = 5,042 cases) and HbA_1c levels (n = 175,156). Current shift work, definite morning or evening preference, and MTNR1B rs10830963 risk allele associated with type 2 diabetes and HbA_1c levels. The effect of rs10830963 was not modified by shift work schedules. While marginal evidence of interaction between self-reported morningness-eveningness preference and rs10830963 on risk of type 2 diabetes was seen, this interaction did not persist when analysis was expanded to include all participants regardless of employment status and when accelerometer-derived sleep midpoint was used as an objective measure of morningness-eveningness preference. Our findings suggest that MTNR1B risk allele carriers who carry out shift work or have more extreme morningness-eveningness preference may not have enhanced risk of type 2 diabetes.

Lipodystrophies are a group of disorders characterized by absence or loss of adipose tissue and abnormal fat distribution, commonly accompanied by metabolic dysregulation. Although considered rare disorders, their prevalence in the general population is not well understood. We aimed to evaluate the clinical and genetic prevalence of lipodystrophy disorders in a large clinical care cohort. We interrogated the electronic health record (EHR) information of >1.3 million adults from the Geisinger Health System for lipodystrophy diagnostic codes. We estimate a clinical prevalence of disease of 1 in 20,000 individuals. We performed genetic analyses in individuals with available genomic data to identify variants associated with inherited lipodystrophies and examined their EHR for comorbidities associated with lipodystrophy. We identified 16 individuals carrying the p.R482Q pathogenic variant in LMNA associated with Dunnigan familial partial lipodystrophy. Four had a clinical diagnosis of lipodystrophy, whereas the remaining had no documented clinical diagnosis despite having accompanying metabolic abnormalities. We observed a lipodystrophy-associated variant carrier frequency of 1 in 3,082 individuals in our cohort with substantial burden of metabolic dysregulation. We estimate a genetic prevalence of disease of ~1 in 7,000 in the general population. Partial lipodystrophy is an underdiagnosed condition. and its prevalence, as defined molecularly, is higher than previously reported. Genetically guided stratification of patients with common metabolic disorders, like diabetes and dyslipidemia, is an important step toward precision medicine.

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.

The cardiovascular benefits of fibrates have been shown to be heterogeneous and to depend on the presence of atherogenic dyslipidemia. We investigated whether genetic variability in the PPARA gene, coding for the pharmacological target of fibrates (PPAR-α), could be used to improve the selection of patients with type 2 diabetes who may derive cardiovascular benefit from addition of this treatment to statins. We identified a common variant at the PPARA locus (rs6008845, C/T) displaying a study-wide significant influence on the effect of fenofibrate on major cardiovascular events (MACE) among 3,065 self-reported white subjects treated with simvastatin and randomized to fenofibrate or placebo in the ACCORD-Lipid trial. T/T homozygotes (36% of participants) experienced a 51% MACE reduction in response to fenofibrate (hazard ratio 0.49; 95% CI 0.34–0.72), whereas no benefit was observed for other genotypes (P_interaction = 3.7 x 10^–4). The rs6008845-by-fenofibrate interaction on MACE was replicated in African Americans from ACCORD (N = 585, P = 0.02) and in external cohorts (ACCORD-BP, ORIGIN, and TRIUMPH, total N = 3059, P = 0.005). Remarkably, rs6008845 T/T homozygotes experienced a cardiovascular benefit from fibrate even in the absence of atherogenic dyslipidemia. Among these individuals, but not among carriers of other genotypes, fenofibrate treatment was associated with lower circulating levels of CCL11—a proinflammatory and atherogenic chemokine also known as eotaxin (P for rs6008845-by-fenofibrate interaction = 0.003). The GTEx data set revealed regulatory functions of rs6008845 on PPARA expression in many tissues. In summary, we have found a common PPARA regulatory variant that influences the cardiovascular effects of fenofibrate and that could be used to identify patients with type 2 diabetes who would derive benefit from fenofibrate treatment, in addition to those with atherogenic dyslipidemia.

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.

Western Bureau: Some displaced Iberostar employees in Rose Hall, St James, are angry with their employer, charging that they have been unable to benefit from the Government’s COVID-19 relief programme because of the hotel’s failure to pay over...

Latoya Rose used the last $3,000 she had to invest in 26 baby chicks and feed with the hope of turning a profit after they matured. Last Friday, as the Spaldings resident went to her coop to feed the chickens, they were all gone. “When I don’t see...

An application earlier this year by Mahoe Gaming Enterprises Limited (MGEL) has not benefited from any preferential treatment by the Betting, Gaming and Lotteries Commission (BGLC). That was the finding of ex-commissioner of the Integrity...

It was not the landing the Jamaicans who arrived at Kingston’s Norman Manley International Airport on Wednesday evening would want again. The 43 Jamaican ship workers of the Marella Discovery 2 were among the 115 people aboard the TUI charter flight that touched down amid the Kingston breeze and evening sunset.

“I know this has been some difficult times for us with the pandemic, but I know we are going to get through this together – Jamaica together. We are going to continue our social distancing. We are going to continue practising our incredible hygiene...

The wet weather last Saturday (May 2) could not dampen the spirits of award-winning gospel artiste and ordained evangelist Kevin Downswell as he ventured into the St Catherine community of Central Village, where he spent some of his formative years...

Scores of people who turned up yesterday at the Pavilion Mall to collect their government-issued compassionate grants at Western Union made a mockery of physical distancing as they converge on the financial institution. There were long lines...

Director of the Pan American Health Organization (PAHO), Dr Carissa F. Etienne, today called for accelerated and expanded testing for COVID-19 in countries of the Americas. “We need a clearer view of where the virus is circulating and how...

WASHINGTON, CMC – The World Bank has predicted the sharpest decline of remittances to Latin America and the Caribbean, saying that global remittances on a whole are projected to fall by about 20 percent in 2020 due to the economic crisis...

Director of the Pan American Health Organization (PAHO), Carissa Etienne, today urged for vaccination programmes to continue during the COVID-19 pandemic. “If we fall behind on routine immunisations, particularly for children, we risk...

OLIEVENHOUTBOS, South Africa (AP) — Thousands of people stood in line for hours on Saturday in a South African township waiting for handouts of food. The scene has repeated for days in one of the world’s most unequal countries as...