Women with endometriosis have significantly higher rates of depression than women in the general population. That’s according to psychiatrist Dr Kristen Robinson-Barrett. It’s the end of endometriosis month, so Flair spoke to the expert to explore...

Active maintenance of β-cell identity through fine-tuned regulation of key transcription factors ensures β-cell function. Tacrolimus, a widely used immunosuppressant, accelerates onset of diabetes after organ transplantation, but underlying molecular mechanisms are unclear. Here we show that tacrolimus induces loss of human β-cell maturity and β-cell failure through activation of the BMP/SMAD signaling pathway when administered under mild metabolic stress conditions. Tacrolimus-induced phosphorylated SMAD1/5 acts in synergy with metabolic stress–activated FOXO1 through formation of a complex. This interaction is associated with reduced expression of the key β-cell transcription factor MAFA and abolished insulin secretion, both in vitro in primary human islets and in vivo in human islets transplanted into high-fat diet–fed mice. Pharmacological inhibition of BMP signaling protects human β-cells from tacrolimus-induced β-cell dysfunction in vitro. Furthermore, we confirm that BMP/SMAD signaling is activated in protocol pancreas allograft biopsies from recipients on tacrolimus. To conclude, we propose a novel mechanism underlying the diabetogenicity of tacrolimus in primary human β-cells. This insight could lead to new treatment strategies for new-onset diabetes and may have implications for other forms of diabetes.

Taking reps behind Chris Davis at first base, Orioles prospect Ryan Mountcastle became the most high-profile participant yet in the club's grand spring experiment.

Pan American Health Organization (PAHO) director, Dr Carissa Etienne, is warning that lifting COVID-19 restrictions too soon could accelerate the spread of the virus and open the door for a dramatic upsurge in countries of the region. The warning...

HONOLULU (AP) — Hawaii authorities are cracking down on rogue tourists who are visiting beaches, riding personal watercraft, shopping and generally flouting strict requirements that they quarantine for 14 days after arriving. A newlywed...

LONDON — Britain’s minister for the environment, food and rural affairs says Prime Minister Boris Johnson won’t be announcing immediate changes to the country’s coronavirus lockdown when he addresses the nation on Sunday....

BASSETERRE, St Kitts (CMC): ST KITTS AND Nevis Patriots have made some significant changes to their line-up for the upcoming Caribbean Premier League (CPL) season. Captain Carlos Brathwaite has gone to the Jamaica Tallawahs, while the Patriots have...

BMJ Voices is a collection of readers’ experiences of working in the NHS. For this, The BMJ is seeking short audio submissions from UK listeners. These submissions will be published on thebmj.com. Patrick Keating, a GP from Enfield, is concerned that small practices are under pressure to increase list size, but aren't able to muster resources to...

The movement to make data from clinical trials widely accessible has achieved enormous success, and it is now time for medical journals to play their part. From 1 July The BMJ will extend its requirements for data sharing to apply to all submitted clinical trials, not just those that test drugs or devices. The BMJ's Elizabeth Loder explains what...

Doctors considering strike action may worry about the effect on patients. David Metcalfe and colleagues examine the evidence and find that “patients do not come to serious harm during industrial action provided that provisions are made for emergency care.” Read the full analysis: http://www.bmj.com/content/351/bmj.h6231

James Smoliga, from High Point University, North Carolina, and Ken Rundell, from The Commonwealth Medical College, Pennsylvania, join us to discuss how to test for, and manage, exercise induced bronchoconstriction, and particularly how to distinguish it from other respiratory conditions. Read the full review at...

This week, junior doctors in England have taken industrial action for the second time in as many months after failing to reach agreement with the government over their proposed new contract. Tom Moberley and Abi Rimmer, from BMJ Careers, went to the picket lines at Northwick Park Hospital, and University Hospital Lewisham to talk to the doctors,...

Thankfully, electrical injuries are relatively uncommon - but that means that lack of evidence regarding the management of patients who have been electrocuted, which can cause concern for clinicians when these patients present. In this podcast, Cath Brizzel, clinical editor for The BMJ, is joined by one of the authors of a clinical update on the...

We're creating a manifesto for better evidence. The centre for Evidence Based Medicine at the University of Oxford, and the BMJ, are asking what are the problem with medical evidence, and how can we fix them? In this second discussion we went to Nottingham​ University, to find out what the people who create the bread and butter of EBM -...

Trial MVA85A - monkey trials for a booster vaccine for BCG, developed by researchers at Oxford University, is the subject of an investigation published on bmj.com. Experts warn that today’s investigation is just one example of “a systematic failure” afflicting preclinical research and call for urgent action “to make animal research more fit for...

There’s a lot going on in the world at the moment - Ebola’s back, Puerto Rico is without power and the official estimations of death following the hurricane are being challenged. The WHO’s just met to decide what to do about it all, as well as sorting out universal healthcare, access to medicines, eradicating polio, etc etc. To make sense of that...

We at The BMJ care about food, and if our listener stats are to be believed, so do you. In this podcast we’re looking at quality as an important driver of a good diet. At our recent food conference - Food For Thought - hosted in Zurich by Swiss Re we brought researchers in many fields of nutritional science together. We asked people with...

We want clinical trials to be thorough - but Vinay Prasad, assistant professor of medicine at Oregon Health Science University, argues that the problem of overdiagnosis may be as prevalent, in the way we measure disease in our research, as our practice. In this podcast he joins us to discuss the problem, and why he thinks what qualifies as...

You’ll have read in a clinical trial “Most patients had an acceptable adverse-event profile.” Or that a drug “has a manageable and mostly reversible safety profile.” And that “the tolerability was good overall.” In this podcast, Bishal Gyawali (@oncology_bg) joins us to describe what events those terms were actually describing in cancer drug...

Cochrane Austria have been asking the public what they'd like to know about health. Not whether the latest drug is more efficacious, but whether glacier stone power cures hangovers. Gerald Gartlehner, director of the Cochrane Austria Centre joins us to explain what they do, and how their evidence has been received. Read more about the project...

Around half of trials that supported new cancer drug approvals in Europe between 2014 and 2016 were judged to be at high risk of bias, in a new study. Huseyin Naci,assistant professor of health policy a the London School of Economics joins us to talk about why potential bias may mean potential exaggeration of treatment effects, and could be...

Blockchain is the digital technology that underpins cryptocurrencies such as bitcoin, and has been proposed as the digital panacea of our times. But Leeza Osipenko, from the London School of Economics, has thought about how it could actually be used in clinical trials, and what else would need to change in our regulatory environment to make that...

The internecine takes on medical specialty are a common thread in the Christmas BMJ, and this year we're doing it through the lens of driving. Which speciality speeds the most, who has the nicest cars? André Zimerman, soon to be cardiologist, and researcher lets us know - and also why you can't rely on being a doctor to get off a speeding ticket....

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 In our first episode, we discuss the highs and lows of video consultations, and how coronavirus has altered the landscape...

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

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

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

D A Pan
Jun 1, 1997; 46:983-988
Original Article

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

Ralph A DeFronzo
Jun 1, 1988; 37:667-687
Lilly Lecture 1987

JC Henquin
Nov 1, 2000; 49:1751-1760
Articles

DOVER, St Mary: Residents of Epsom and Dover in St Mary are on edge, but have accepted quarantine measures imposed by the Government to curtail the spread of the dreaded coronavirus in that parish. Security checkpoints at both ends of the parish...

It was a double whammy of inconvenience for Sharon Carter, a vendor in Metcalfe Market, Annotto Bay. Carter, who lives in St Catherine, had just recently been relieved of the lockdown in the parish and is now being affected by the quarantine which...

The Senate on Friday paid tribute to distinguished consultant psychiatrist, Frederick Hickling, for his tremendous contribution to persons with intellectual disabilities. Hickling died on Thursday. Senator Dr Saphire Longmore remembered Professor...

PORT OF SPAIN, Trinidad, CMC – Thirty three Trinidad and Tobago nationals who have been stranded in Barbados since March 23 are scheduled to return home on Tuesday. It’s reported that early Tuesday, National Security Minister...

PORT OF SPAIN, Trinidad, CMC – Prime Minister Dr Keith Rowley Saturday dismissed as a “dishonest last gasp and gamble of a dangerously delusional woman” a statement by Opposition Leader Kamla Persad Bissessar calling for him...

PORT OF SPAIN, Trinidad, CMC – The Trinidad and Tobago government Saturday said it had uncovered a plot by persons to defraud the state and that a new mechanism would be put in place Monday in providing rental assistance to people impacted by...

Led by vice president of home clubhouse operations Rick Stowe, who began working for the club in 1981 and became head of the clubhouse in 1997, the Reds have a well-oiled machine with regard to packing up and moving out.

Upon the passing of his physical on Tuesday, the Reds signed infielder/outfielder Derek Dietrich to a Minor League contract with an invitation to big league camp for Spring Training.

THE EDITOR, Madam: On Wednesday at 8:30 a.m., while watching TVJ, I saw Get Moving home workout series. Very good, TVJ and the Ministry of Health, for bringing this workout programme into our homes. Minister Tufton was a participant; he truly...

THE EDITOR, Madam: Words cannot describe my feeling of loss on hearing that prominent psychiatrist Professor Fred Hickling has died. Professor Hickling was one of Jamaica’s treasures through his work in the field of community mental health. His...

In 2020, when information is literally glued to our fingertips, technological innovations fill the stratosphere, the economy is reeling. Under the catastrophic effects of the coronavirus pandemic, one has no choice but to be creative – be creative...

The engaging storyline and realness of the characters in Barbara Jenkins’ De Rightest Place makes it a book you breeze through in a matter of days. Set mainly in and around a bar called De Rightest Place, in the environs of a working-class...

Obesity-associated type 2 diabetes mellitus (T2DM) entails insulin resistance and loss of β-cell mass. Adipose tissue mitochondrial dysfunction is emerging as a key component in the etiology of T2DM. Identifying approaches to preserve mitochondrial function, adipose tissue integrity, and β-cell mass during obesity is a major challenge. Mitochondrial ferritin (FtMT) is a mitochondrial matrix protein that chelates iron. We sought to determine whether perturbation of adipocyte mitochondria influences energy metabolism during obesity. We used an adipocyte-specific doxycycline-inducible mouse model of FtMT overexpression (FtMT-Adip mice). During a dietary challenge, FtMT-Adip mice are leaner but exhibit glucose intolerance, low adiponectin levels, increased reactive oxygen species damage, and elevated GDF15 and FGF21 levels, indicating metabolically dysfunctional fat. Paradoxically, despite harboring highly dysfunctional fat, transgenic mice display massive β-cell hyperplasia, reflecting a beneficial mitochondria-induced fat-to-pancreas interorgan signaling axis. This identifies the unique and critical impact that adipocyte mitochondrial dysfunction has on increasing β-cell mass during obesity-related insulin resistance.

Branched esters of palmitic acid and hydroxystearic acid (PAHSA) are anti-inflammatory and antidiabetic lipokines that connect glucose and lipid metabolism. We aimed to characterize involvement of the 5-PAHSA regioisomer in the adaptive metabolic response of white adipose tissue (WAT) to cold exposure (CE) in mice, exploring the cross talk between glucose utilization and lipid metabolism. CE promoted local production of 5- and 9-PAHSAs in WAT. Metabolic labeling of de novo lipogenesis (DNL) using ²H₂O revealed that 5-PAHSA potentiated the effects of CE and stimulated triacylglycerol (TAG)/fatty acid (FA) cycling in WAT through impacting lipogenesis and lipolysis. Adipocyte lipolytic products were altered by 5-PAHSA through selective FA re-esterification. The impaired lipolysis in global adipose triglyceride lipase (ATGL) knockout mice reduced free PAHSA levels and uncovered a metabolite reservoir of TAG-bound PAHSAs (TAG estolides) in WAT. Utilization of ¹³C isotope tracers and dynamic metabolomics documented that 5-PAHSA primes adipocytes for glucose metabolism in a different way from insulin, promoting DNL and impeding TAG synthesis. In summary, our data reveal new cellular and physiological mechanisms underlying the beneficial effects of 5-PAHSA and its relation to insulin action in adipocytes and independently confirm a PAHSA metabolite reservoir linked to ATGL-mediated lipolysis.

Reduced storage of dietary fatty acids (DFAs) in abdominal adipose tissues with enhanced cardiac partitioning has been shown in subjects with type 2 diabetes (T2D) and prediabetes. We measured DFA metabolism and organ partitioning using positron emission tomography with oral and intravenous long-chain fatty acid and glucose tracers during a standard liquid meal in 12 obese subjects with T2D before and 8–12 days after bariatric surgery (sleeve gastrectomy or sleeve gastrectomy and biliopancreatic diversion with duodenal switch). Bariatric surgery reduced cardiac DFA uptake from a median (standard uptake value [SUV]) 1.75 (interquartile range 1.39–2.57) before to 1.09 (1.04–1.53) after surgery (P = 0.01) and systemic DFA spillover from 56.7 mmol before to 24.7 mmol over 6 h after meal intake after surgery (P = 0.01), with a significant increase in intra-abdominal adipose tissue DFA uptake from 0.15 (0.04–0.31] before to 0.49 (0.20–0.59) SUV after surgery (P = 0.008). Hepatic insulin resistance was significantly reduced in close association with increased DFA storage in intra-abdominal adipose tissues (r = –0.79, P = 0.05) and reduced DFA spillover (r = 0.76, P = 0.01). We conclude that bariatric surgery in subjects with T2D rapidly reduces cardiac DFA partitioning and hepatic insulin resistance at least in part through increased intra-abdominal DFA storage and reduced spillover.

21 July 2014

15 November 2016

5 December 2017

Lower-income countries are in many ways more ‘circular’ than their developed-economy counterparts – the question is how to turn this into a development opportunity.