Approximately 10% of patients with type 2 diabetes suffer from latent autoimmune diabetes in adults (LADA). This study provides a systematic assessment of the pathology of the endocrine pancreas of patients with LADA and for comparison in a first rat model mimicking the characteristics of patients with LADA. Islets in human and rat pancreases were analyzed by immunohistochemistry for immune cell infiltrate composition, by in situ RT-PCR and quantitative real-time PCR of laser microdissected islets for gene expression of proinflammatory cytokines, the proliferation marker proliferating cell nuclear antigen (PCNA), the anti-inflammatory cytokine interleukin (IL) 10, and the apoptosis markers caspase 3 and TUNEL as well as insulin. Human and rat LADA pancreases showed differences in areas of the pancreas with respect to immune cell infiltration and a changed ratio between the number of macrophages and CD8 T cells toward macrophages in the islet infiltrate. Gene expression analyses revealed a changed ratio due to an increase of IL-1β and a decrease of tumor necrosis factor-α. IL-10, PCNA, and insulin expression were increased in the LADA situation, whereas caspase 3 gene expression was reduced. The analyses into the underlying pathology in human as well as rat LADA pancreases provided identical results, allowing the conclusion that LADA is a milder form of autoimmune diabetes in patients of an advanced age.

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.

The ability to switch fuels for oxidation in response to changes in macronutrient composition of diet (metabolic flexibility) may be informative of individuals’ susceptibility to weight gain. Seventy-nine healthy, weight-stable participants underwent 24-h assessments of energy expenditure and respiratory quotient (RQ) in a whole-room calorimeter during energy balance (EBL) (50% carbohydrate, 30% fat) and then during 24-h fasting and three 200% overfeeding diets in a crossover design. Metabolic flexibility was defined as the change in 24-h RQ from EBL during fasting and standard overfeeding (STOF) (50% carbohydrate, 30% fat), high-fat overfeeding (HFOF) (60% fat, 20% carbohydrate), and high-carbohydrate overfeeding (HCOF) (75% carbohydrate, 5% fat) diets. Free-living weight change was assessed after 6 and 12 months. Compared with EBL, RQ decreased on average by 9% during fasting and by 4% during HFOF but increased by 4% during STOF and by 8% during HCOF. A smaller decrease in RQ, reflecting a smaller increase in lipid oxidation rate, during HFOF but not during the other diets predicted greater weight gain at both 6 and 12 months. An impaired metabolic flexibility to acute HFOF can identify individuals prone to weight gain, indicating that an individual’s capacity to oxidize dietary fat is a metabolic determinant of weight change.

The whitening and loss of brown adipose tissue (BAT) during obesity and aging promote metabolic disorders and related diseases. The imbalance of Ca²⁺ homeostasis accounts for the dysfunction and clearance of mitochondria during BAT whitening. Capsaicin, a dietary factor activating TRPV1, can inhibit obesity induced by high-fat diet (HFD), but whether capsaicin inhibits BAT loss and the underlying mechanism remain unclear. In this study, we determined that the inhibitory effects of capsaicin on HFD-induced obesity and BAT whitening were dependent on the participation of SIRT3, a critical mitochondrial deacetylase. SIRT3 also mediated all of the beneficial effects of capsaicin on alleviating reactive oxygen species generation, elevating mitochondrial activity, and restricting mitochondrial calcium overload induced by HFD. Mechanistically, SIRT3 inhibits mitochondrial calcium uniporter (MCU)-mediated mitochondrial calcium overload by reducing the H3K27ac level on the MCU promoter in an AMPK-dependent manner. In addition, HFD also inhibits AMPK activity to reduce SIRT3 expression, which could be reversed by capsaicin. Capsaicin intervention also inhibited aging-induced BAT whitening through this mechanism. In conclusion, this study emphasizes a critical role of the AMPK/SIRT3 pathway in the maintenance of BAT morphology and function and suggests that intervention in this pathway may be an effective target for preventing obesity- or age-related metabolic diseases.

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...

Western Bureau: THE MOBAY City Run organisers have reconsidered the event’s cancellation. Organising committee chair­person Janet Silvera said on Sunday, the day the event was to have taken place, that the seventh staging of the 5K/10K Walk and Run...

The UK’s austerity programme has disproportionately affected children and people with disabilities, says David Taylor-Robinson, a senior clinical lecturer in public health at the University of Liverpool. He joins us to discuss why the evidence shows the vulnerable are hit hardest by the cuts to public services, despite the UN conventions on...

Multimorbidity presents a number of different challenges, for the patients living with the conditions, but also for the health professionals caring for them in systems that often are not designed with these more complex needs in mind. Emma Wallace, general practice lecturer, and Susan Smith, a professor of general practice at the Royal College of...

The UK Parliament's Health Select Committee's recent report on childhood obesity says 1 in 5 children are obese by the time they leave school. The committee calls for legislation to turn the tide by taxing sugary drinks, a pre-watershed ban on junk food advertising, and investment in public health. We joined Sarah Wollaston, conservative MP for...

Nick Oliver, consultant diabetologist at Imperial Healthcare NHS Trust and Philippa Cooper, who has type I diabetes, join us to explain how structured education works for patients, and give tips on self management. Read the full review: http://www.bmj.com/content/352/bmj.i998

"I say to all Australian doctors - young, old, the political and the apolitical - that on this depends not just our ethical credibility as a profession, but our shared humanity. " Following the leaked emails published in The Guardian newspaper, alleging abuse of asylum seekers detained by the Australian government on the Pacific island of Nauru,...

The UK government published its report Childhood Obesity: a Plan for Action, in August 2016. A new analysis article takes them to task for the inadequacy of that response to a growing problem. Neena Modi is a professor of neonatal medicine, at Imperial College London, and president of the Royal College of Paediatrics and Child Health, and joins...

Around 1 in 10 children and young people worldwide have mental health difficulties that substantially affect their lives. Child mental health services often concentrate on risk reduction, at the expense of the wider aspects of a child's wellbeing. As part of the high integrity healthcare series, this podcast focuses on novel ways of providing...

The BMJ has published a series of articles, taking an in-depth look at health in South Asia. In this collection, authors from India, Pakistan, Nepal, Bangladesh, Sri Lanka, and Afghanistan collaborate to identify evidence-based solutions to shape health policy and interventions, and drive innovations and research in the region. In this podcast,...

The world bank was set up in 1944. In the aftermath of the second world war, the institution was there to give loans to countries rebuilding after the conflict. Their first loan went to France - but with stipulations about repayment that set a tone for future funds. A new series, authored by Devi Sridhar, and her team from the University of...

If you google "The NHS" you'll see screaming headlines from the Daily Mail about cost and waste - debate in parliament is about how much of our GDP we should be spending - and each year, hospital trusts go cap in hand to ask for more funding. Against this backdrop, a new analysis, and a first in a series, published on bmj.com, looks at what it...

Its now widely agreed that one of the key ways of reducing the current high level of "waste " in biomedical research is to focus it more squarely on addressing the questions that matter to patients - and the people and medical staff that care for them. In this interview, Tessa Richards - the BMJ's patient partnership editor, talks to...

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...

Cardiovascular factors are associated with risk of stroke - and those factors can be mediated by lifestyle and by genetic make up. New research published by The BMJ sets out to explore how these risks combine, and we're joined on the podcast by two of the authors - Loes Rutten-Jacobs, senior postdoctoral researcher at the German Center for...

Susan Greenhalg is a research professor of chinese society in Harvard’s department of anthropology - not a natural fit for a medical journal you may think, but recently she has been looking at the influence of Coca Cola on obesity policy in China. She has written up her investigation in an article published on bmj.com this week, and joins us in...

Helen Macdonald and Carl Heneghan are back again talking about what's happened in the world of evidence this month. They start by talking about how difficult a task it is to find evidence that's definitely practice changing, what GPs can learn from Malawian children with nonsevere fast-breathing pneumonia, how radiation dosage varies...

It can be difficult to know what to do when a person in severe psychological distress presents to a general practice or community clinic, particularly if they are behaving aggressively, or if they are refusing help. Most patients who are acutely disturbed present no danger to others, however situations can evolve rapidly. Frontline staff need to...

Stroke mortality rates have been declining in almost every country, and that reduction could result from a decline in disease occurrence or a decline in case fatality, or both. Broadly - is that decline down to better treatment or better prevention. Olena Seminog, a researcher, and and Mike Rayner, professor of population health, both from the...

Fertility awareness based methods of contraception are increasingly being used for pregnancy prevention. In the US, the proportion of contraceptive users who choose such methods has grown from 1% in 2008 to approximately 3% in 2014.  Relative to other methods of pregnancy prevention, however, substantial misinformation exists around fertility...

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...

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...

There comes a tipping point in all campaigns when the evidence is overwhelming and the only way to proceed is with action. According to David Williams, it’s time to tackle the disproportionate effects of race on patients in the UK. David Williams, from Harvard University, developed the Everyday Discrimination Scale that, in 1997, launched a new...

We know that the number of people living with multiple health conditions is rising year on year, and yet training, guidelines, organisations and physical spaces in healthcare still largely focus on single diseases or organ systems. The means that patients in the NHS are often treated as if their conditions exist in isolation, and that their care...

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...

Joseph G. Yu
Oct 1, 2002; 51:2968-2974
Obesity Studies

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

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

Cindy J.M. Loomans
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Complications

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

Marc Prentki
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Original Article

Joachim Spranger
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Pathophysiology

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

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

Giulio Marchesini
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Pathophysiology

Gökhan S Hotamisligil
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Perspectives in Diabetes

D Dabelea
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Articles

C. Ronald Kahn
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Banting Lecture

T Inoguchi
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Articles

Ralph A. DeFronzo
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Banting Lecture

Roger H Unger
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Perspectives in Diabetes

Richard S Surwit
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Original Article

J. Denis McGarry
Jan 1, 2002; 51:7-18
Banting Lecture 2001

Andreas Festa
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Complications

Thomas A. Buchanan
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Pathophysiology

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