Nutritional Sciences

Liver can generate palmitic acid to maintain brain health, study suggests

Christopher.Sorensen — Mon, 22 Jan 2024 21:58:42 +0000

Liver can generate palmitic acid to maintain brain health, study suggests

Christopher.Sorensen Mon, 01/22/2024 - 16:58

Cutline

Researchers Richard Bazinet, left, and Mackenzie Smith, right, found that the liver will generate palmitic acid when the brain isn't getting enough through food sources, suggesting the acid's importance to brain health (photo by Temerty Faculty of Medicine)

Jim Oldfield

Topic

Breaking Research

Temerty Faculty of Medicine

Joannah & Brian Lawson Centre for Child Nutrition

Brain

Nutritional Sciences

Research & Innovation

Subheadline

“The results were surprising because when you lower a lipid in the diet, it usually becomes lower in the brain"

Researchers at the 91�Թ� have found that palmitic acid, one of the most common fats in meats and dairy products, as well as human breast milk, is made by the liver and sent to the developing brain when it’s low in the diet.

The preclinical findings underscore the importance of palmitic acid for brain health and point to a need for more research on lowering its levels in infant formula – a step some manufacturers have taken recently to reduce costs and limit the harvest of palm trees, a major source of palmitic acid.

“When we changed the levels of palmitic acid in the diets of developing mice, it didn’t do a thing to the brain,” said Richard Bazinet, principal investigator on the study and a professor and acting chair of the department of nutritional sciences in 91�Թ�’s Temerty Faculty of Medicine.

“The results were surprising because when you lower a lipid in the diet, it usually becomes lower in the brain. But here the liver was able to up-regulate production to ensure the brain gets enough of it, despite extreme differences in dietary intake.”

The findings were published in the journal Nature Communications.

Mackenzie Smith, left, and Richard Bazinet, right (photo by Temerty Faculty of Medicine)

Palmitic acid is a saturated fat that supports brain health in several ways, across the lifespan. It contributes to the structure and function of myelin sheathing, which insulates neural connections and acts as precursor to molecules that regulate inflammation and promote cell signalling.

Scientists have long known that humans and other mammals can get palmitic acid from food or generate it in a process called de novo lipogenesis, which mainly requires glucose for its synthesis. Much less is known about which source the body relies on relative to diet and at different stages of growth and maturity.

Bazinet said the study findings highlight the importance of palmitic acid for brain health at all stages, but especially during development, when need for the fat appears to be highest.

“It’s interesting that although the brain can make palmitic acid, the liver up-regulated it so much. These systemic redundancies are built in, so the body won’t take a chance on not getting enough,” said Bazinet, who is also a researcher at 91�Թ�’s Joannah & Brian Lawson Centre for Child Nutrition.

The results should give pause to manufacturers looking to reduce the amount of palmitic acid in infant formula, said Mackenzie Smith, first author on the study and a doctoral student in the Bazinet lab.

“It’s possible that we can lower levels in formula, which could have a positive ecological impact, but we don’t yet know the potential health effects,” Smith said. “Are there implications for behaviour or development when the liver produces so much? Might there be negative effects for the liver?”

Smith also noted that even in mice that received the lowest amount of palmitic acid through diet, levels of the fat were still higher than those sought by some manufacturers of formula. That discrepancy adds to the rationale for further preclinical studies, as well as research in humans, Smith said.

To uncover the source of palmitic acid in the brains of developing mice, the researchers applied a new carbon isotope technique. Isotopes are different versions of the same chemical element that vary slightly in mass; for their study, the researchers drew on natural differences in carbon isotope ratios in the environment, based on how plants absorb carbon in photosynthesis.

“Most plants use the same path to fix carbon from the atmosphere and have the same carbon ratio, but sugars such as corn and sugar cane – which the liver uses to generate palmitic acid – have a different ratio,” said Smith.

In the brains of mice, a depleted carbon ratio signature indicated a dietary source of palmitic acid, Smith said, whereas an enriched signature suggested de novo lipogenesis.

The researchers were able to track those signatures at many stages throughout mouse development, to determine the liver was the main source of palmitic acid in the developing brain – a finding they corroborated by looking at changes in genetics.

The approach opens new research opportunities. “As opposed to traditional radioactive tracers, which are very expensive, this new technique allows for a cost-effective and long-term study design,” said Smith.

Building on the current study’s findings, researchers in the Bazinet lab are now applying the same technique in tissue from adult human brains. The method could also provide a new way to measure and track the dietary sources of other fats and nutrients, Bazinet said.

“Nutrition researchers often rely on people reporting their food intakes, which can lead to unreliable data,” he added. “Those problems could potentially be flagged with this kind of technology to track the source and amount of added sugars, for example. It could be very fruitful for nutritional science.”

The research was supported by funding from the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes of Health Research and the Canada Research Chairs Program.

Researchers use AI to optimize nutrient consistency in donated breast milk

Christopher.Sorensen — Tue, 21 Nov 2023 17:27:29 +0000

Researchers use AI to optimize nutrient consistency in donated breast milk

Christopher.Sorensen Tue, 11/21/2023 - 12:27

Cutline

A new data-driven framework developed by researchers at 91�Թ� and its hospital partners bypasses the need for a device to analyze donated breast milk (photo by Rogers Hixon Ontario Human Milk Bank)

Safa Jinje

Topic

Breaking Research

Sinai Health

Temerty Faculty of Medicine

Artificial Intelligence

Faculty of Applied Science & Engineering

Nutritional Sciences

Research & Innovation

Subheadline

'The new program ... helps to ensure that each batch of human donor milk meets the protein and calorie needs of preterm infants'

A team of 91�Թ� researchers is leveraging machine learning to optimize the macronutrient content of pooled human donor milk recipes.

The researchers – led by Timothy Chan, a professor in the department of mechanical and industrial engineering in the Faculty of Applied Science & Engineering – introduce their data-driven optimization model in a new paper published in the journal Manufacturing & Service Operations Management.

Chan and his team worked with Mount Sinai Hospital’s Rogers Hixon Ontario Human Milk Bank – which provides donor milk to preterm and sick babies who are hospitalized across Ontario – as well as Deborah O’Connor, a professor in the department of nutritional sciences in the Temerty Faculty of Medicine.

“For a variety of reasons, many hospitalized infants do not have a full supply of mother’s milk. In this instance, human donor milk can be lifesaving particularly as it helps to protect preterm infants from necrotizing enterocolitis, a life-threatening bowel disease,” says Sharon Unger, a neonatologist and the medical director of the Rogers Hixon Ontario Human Milk Bank who is also a professor in Temerty Medicine’s department of nutritional sciences.

“The new program developed by Dr. Chan helps to ensure that each batch of human donor milk meets the protein and calorie needs of preterm infants.”

Currently, many milk banks, including Mount Sinai’s, rely on individual decision-making when pooling donor milk. This presents a significant challenge in producing a consistent donor milk product that contains sufficient macronutrients for premature and sick babies in neonatal intensive care units.

“It takes a lot of time to create these recipes without a defined method,” says Chan, who is also 91�Թ�’s associate vice-president and vice-provost, strategic initiatives.

“While there are studies that show that milk that comes from donors who are early in their postpartum period tends to be more protein-rich, our approach provides a good prediction of the actual macronutrient content that will allow milk bank employees to make better pooling decisions.”

Four beakers hold pooled donor milk at Mount Sinai Hospital’s Rogers Hixon Ontario Human Milk Bank (photo by Rogers Hixon Ontario Human Milk Bank)

Given that milk banks are often non-profit entities operating on lean budgets, a low-cost alternative to obtaining a consistent, nutrient-balanced product could be useful across the entire sector.

While devices known as human milk analyzers can be used to measure the exact macronutrient content of each milk sample at a milk bank, they are costly and require extensive regulatory approval – and are therefore only used by half of all milk banks in North America. On top of that, analyzing every donation is a costly endeavour that is labour- and resource-intensive.

“Our data-driven framework bypasses the need for a device to analyze the donor milk by using an artificial intelligence model to predict the macronutrient content of each donation,” says Rachel Wong, who earned her master’s degree from 91�Թ� Engineering last year and is a lead researcher of the study.

“In addition, by using an optimization model to choose which donations to pool together, we can increase the consistency of macronutrient content in the donor milk product.” 

The multi-phase study included a one-year implementation trial at the Rogers Hixon milk bank that was designed to test whether AI-informed models could help to fill the gap.

In the first phase, researchers collected the necessary data to create a machine learning model to predict the macronutrient content of the pooled recipes, and then designed an optimization model to create the recipes based on macronutrient requirements – that is, the necessary levels of protein and fat.

The team then created a simulation model to test the method before embarking on an experiment in the milk bank, which took place over 16 months in 2021 and 2022.

“Since our study was performed in the milk bank during regular operating hours, rather than in a controlled environment, there were a number of unexpected challenges that we had to adapt to,” Wong says.

“During the COVID-19 pandemic, the volume of donations fluctuated based on the provincial restrictions – during the lockdown periods there was an unprecedented increase in the number and volume of donations.

“We also needed to adapt the AI decisions that had already been proposed to ensure that we abided with the milk bank’s operating protocols.” 

The last phase of the study began by observing the milk bank’s operation for six months and measuring the fat, protein and bacteria levels in the pooled recipes.

For the following six months, the milk bank used the data-driven optimization framework to create the pooled milk recipes. At the end of the year, the researchers compared the optimized recipes to the previous ones to assess which recipes met the macronutrient targets.

“We found that our pooled recipes met the bar for protein and fat simultaneously up to 75 per cent more often, without compromising other factors like an increase in bacteria,” says Chan. “And it took us 60 per cent less time to make the recipes.”

The team’s optimized recipes also have an added benefit for preterm and sick babies, who have underdeveloped digestive systems that make it especially crucial to ensure that the milk they are consuming isn’t overly rich in protein or fat.

Chan’s team is currently working towards expanding the research to measure other nutrients in human donor milk to see if their models can optimize them. The research has won the 2023 Pierskalla Best Paper Award from the Institute for Operations Research and the Management Sciences (INFORMS) and an Excellence in Quality and Safety award from Sinai Health.

“Our ultimate goal is to show that our tool is applicable to other milk banks,” says Chan. “We would like to design a system that can plug into hospital systems to optimize recipes in a way that is sustainable for milk bank staff.”

Wong says that the entire team is grateful to all those who have made the project possible.

“We couldn’t have done this without all of the mothers who donate to the milk bank and the staff who work incredibly hard to provide donor milk to infants across Ontario and beyond,” she says.

“I hope that this research will provide a framework to help milk banks across North America increase the consistency of macronutrient content in their donor milk product. The eventual end goal would be to see a downstream impact of improved growth and developmental outcomes for the infants that receive this donor milk.”   

GTA parents concerned about limited access to school food programs: Researchers

Christopher.Sorensen — Tue, 18 Apr 2023 13:19:09 +0000

GTA parents concerned about limited access to school food programs: Researchers

Christopher.Sorensen Tue, 04/18/2023 - 09:19

Jim Oldfield

Topic

Our Community

Temerty Faculty of Medicine

Joannah & Brian Lawson Centre for Child Nutrition

Graduate Students

Nutritional Sciences

Early results from a 91�Թ� stakeholder study on school food programs find that parents and caregivers in the Greater Toronto Area are concerned about limited access to current programs and the ability of schools to provide culturally appropriate food, among other issues.

Based on online surveys and focus groups, the analysis is part of a larger effort launched by 91�Թ� researchers at the Joannah & Brian Lawson Centre for Child Nutrition called Feeding Kids, Nourishing Minds, which looks at how school food programs function across Canada.

“The need for universality in school food programs has really been a key theme of our research to date,” said Selina Mae Quibrantar, a master’s student in the Temerty Faculty of Medicine who is leading the caregiver analysis with direction from Vasanti Malik, an assistant professor in the department of nutritional sciences. “Universality means broad access to programs, which was a problem before the pandemic and has since worsened – but also local flexibility so that schools can adapt programs for their physical environments and diverse student populations.

“A key goal with Feeding Kids, Nourishing Minds is a broadly inclusive approach, and I hope our study will help enable that – in particular through parental and community knowledge, which is often missing from policymaking on child nutrition.”

Selina Mae Quibrantar says a key theme that has emerged from the stakeholder study focuses on the need for universality in school food programs (photo by Don Campbell)

Preliminary results showed child participation in school food programs in the Greater Toronto Area was about 65 per cent. Many parents and caregivers commented on program reductions, noting less food and fewer days of access per week after the COVID-19 pandemic.

While public health restrictions forced some of those changes as the pandemic began, food inflation costs have since become a significant challenge to school food programs in Toronto and elsewhere, Quibrantar said.

In addition, some schools lack kitchen facilities and volunteers to help prepare food while meeting health and safety guidelines, the study showed.

Caregiver perspectives, especially those from ethnic minority households, have received little attention in child nutrition research, Quibrantar said. Here too, the stakeholder analysis is helping fill a knowledge gap.

The researchers recently ran four focus groups with caregivers from households that identify as South Asian and Southeast Asian, finding that participants stressed the importance of culturally adapted food in school programs. “It’s important to caregivers that children see their own cultures’ food served in schools to foster a sense of belonging and inclusion,” Quibrantar said.

As well, caregivers emphasized the need for an intentional approach when bringing foods from various cultures into school food programs.

“Caregivers want a program that is meaningful and does not run the risk of cultural appropriation,” Quibrantar said. “They instead see programs as a way to teach [children] about cultural heritage and sustainability, such as where a food comes from and how it’s made, or by taking time to learn about a culture while sampling the food.”

Quibrantar has presented early results from a pilot study to colleagues in 91�Թ�’s department of nutritional sciences and plans to share more findings at the Canadian Nutrition Society annual conference in May.

She and researchers from the Feeding Kids, Nourishing Minds project will assemble some of their findings into a dashboard to be shared with other researchers, schools, non-profit groups and policymakers later this year.

Feeding Kids, Nourishing Minds is funded by a $2-million investment from President’s Choice Children’s Charity, and by the Joannah & Brian Lawson Centre for Child Nutrition at the 91�Թ�.

Link between coffee and kidney disease may depend on genetic variant, study finds

Christopher.Sorensen — Tue, 31 Jan 2023 15:58:11 +0000

Link between coffee and kidney disease may depend on genetic variant, study finds

Christopher.Sorensen Tue, 01/31/2023 - 10:58

Cutline

(photo by Nitat Termmee/Getty Images)

Jim Oldfield

Topic

Breaking Research

Temerty Faculty of Medicine

Food

Health

Nutritional Sciences

Research & Innovation

Researchers at the 91�Թ� and University of Padova have found that the association between heavy coffee consumption and kidney dysfunction hinges on a common genetic variation.

In a study, the researchers showed that markers of kidney dysfunction were nearly three times higher in heavy coffee drinkers with a variant of the CYP1A2 gene that makes them slow metabolizers of caffeine than for other heavy coffee drinkers who had a different version of the gene that enables faster caffeine metabolism.

Ahmed El-Sohemy

“We think fast metabolizers can eliminate caffeine from their systems more efficiently and avoid harmful build-ups of caffeine,” said Ahmed El-Sohemy, a professor of nutritional sciences in 91�Թ�’s Temerty Faculty of Medicine. “These individual differences in caffeine metabolism help explain why previous studies on coffee and kidney disease have been inconsistent.”

The study, published in the journal JAMA Network Open, was observational in design and included data from more than a thousand participants in Italy, collected over a decade by Professor Paolo Palatini and colleagues at the University of Padova.

Some previous studies have found that caffeine is associated with impaired kidney function and kidney failure, while others have found that coffee may protect against kidney disease. Few have looked at whether individual genetic differences account for these positive or negative associations.

The amount of caffeine a person consumes also appears to be important. For the current study, risk of kidney dysfunction was only significant in people who drank three or more cups of coffee a day, which is about 300 mg of Italian espresso. Current guidelines in Canada and the US recommend no more than 400 mg per day for healthy adults.

The researchers also found that prevalence of the CYP1A2 gene variant that makes people slow metabolizers of caffeine was similar in both the study group and the general population: roughly 50 per cent.

Many companies and clinics now include CYP1A2 in personalized genetic tests, as different versions of the gene can affect risk for several conditions associated with caffeine consumption.

Sara Mahdavi

“Heart disease, prediabetes and hypertension are all affected by variations in CYP1A2, which can also alter athletic performance,” said Sara Mahdavi, lead author on the study and a former post-doctoral fellow in El-Sohemy’s lab. “We can now be confident that whether or not coffee is deleterious to kidney health depends, in part, on CYP1A2.”

The researchers studied three markers of kidney dysfunction: albuminuria (too much of the protein albumin in urine); hyperfiltration (high glomerular filtration rate in the kidney); and hypertension.

Estimates put the prevalence of kidney disease in Canada at about 13 per cent, with most cases going undiagnosed. Kidney disease is a leading cause of death globally.

“Hopefully, this study will raise awareness about the importance of personalized nutrition recommendations based on individual genetic make-up,” said Mahdavi. “This is an exciting area of research and clinical practice with a very bright future.”

El-Sohemy is the founder and Chief Science Officer of Nutrigenomix Inc., which provides genetic testing for personalized nutrition, including the CYP1A2 gene and caffeine metabolism.

Study suggests honey reduces cardiometabolic risks

Christopher.Sorensen — Thu, 17 Nov 2022 19:11:27 +0000

Study suggests honey reduces cardiometabolic risks

Christopher.Sorensen Thu, 11/17/2022 - 14:11

Cutline

(Photo by Paul J. Richards/AFP via Getty Images)

Jim Oldfield

Topic

Breaking Research

Temerty Faculty of Medicine

Unity Health

Nutritional Sciences

Research & Innovation

Researchers at the 91�Թ� have found that honey improves key measures of cardiometabolic health, including blood sugar and cholesterol levels – especially if the honey is raw and from a single floral source.

The researchers conducted a systematic review and meta-analysis of clinical trials on honey and found that it lowered fasting blood glucose, total and LDL, or “bad,” cholesterol, triglycerides and a marker of fatty liver disease. It also increased HDL or “good,” cholesterol and some markers of inflammation.

Tauseef Khan (photo by Nema McGlynn)

“These results are surprising, because honey is about 80 per cent sugar,” said Tauseef Khan, a senior researcher on the study and a research associate in nutritional sciences at 91�Թ�’s Temerty Faculty of Medicine. “But honey is also a complex composition of common and rare sugars, proteins, organic acids and other bioactive compounds that very likely have health benefits.”

Previous research has shown that honey can improve cardiometabolic health, especially in in vitro and animal studies. The current study is the most comprehensive review to date of clinical trials, and it includes the most detailed data on processing and floral source.

The journal Nutrition Reviews published the findings this week.

“The word among public health and nutrition experts has long been that “a sugar is a sugar,” said principal investigator John Sievenpiper, a clinician-scientist at Unity Health Toronto and a 91�Թ� associate professor of nutritional sciences and medicine. “These results show that’s not the case, and they should give pause to the designation of honey as a free or added sugar in dietary guidelines.”

Sievenpiper and Khan emphasized that the context of the findings was critical: clinical trials in which participants followed healthy dietary patterns, with added sugars accounting for 10 per cent or less of daily caloric intake.

“We’re not saying you should start having honey if you currently avoid sugar,” said Khan. “The takeaway is more about replacement – if you’re using table sugar, syrup or another sweetener, switching those sugars for honey might lower cardiometabolic risks.”

The researchers included 18 controlled trials and over 1,100 participants in their analysis. They assessed the quality of those trials and found there was a low certainty of evidence for most of the studies, but that honey consistently produced either neutral or beneficial effects, depending on processing, floral source and quantity.

The median daily dose of honey in the trials was 40 grams, or about two tablespoons. The median length of trial was eight weeks. Raw honey drove many of the beneficial effects in the studies, as did honey from monofloral sources such as Robinia (also marketed as acacia honey) – a honey from False Acacia or Black Locust Trees – and clover, which is common in North America.

Khan said that while processed honey clearly loses many of its health effects after pasteurization – typically 65 degrees Celsius for at least 10 minutes – the effect of a hot drink on raw honey depends on several factors, and likely would not destroy all its beneficial properties.

John Sievenpiper

He also noted other ways to consume unheated honey such as with yogurt, as a spread and in salad dressings.

Future studies should focus on unprocessed honey, Khan said, and from a single floral source. The goal would be higher quality evidence, and a better understanding of the many compounds in honey that can work wonders for health. “We need a consistent product that can deliver consistent health benefits,” said Khan. “Then the market will follow.”

The research was supported by the Canadian Institutes of Health Research, Canada Foundation for Innovation, the Ministry of Research and Innovation's Ontario Research Fund, and Diabetes Canada.

Khan has received prior funding support from the Canadian Institutes of Health Research, the International Life Sciences Institute and the U.S. National Honey Board. For a full list of all researchers’ past funding, see the Declaration of Interest section at the end of the journal article.

91�Թ� report shows food insecurity persists across Canada, varies by province

Christopher.Sorensen — Tue, 16 Aug 2022 14:22:38 +0000

91�Թ� report shows food insecurity persists across Canada, varies by province

Christopher.Sorensen Tue, 08/16/2022 - 10:22

Cutline

A report led by 91�Թ�'s Valerie Tarasuk found that 15.9 per cent of households in 10 provinces experienced some degree of food insecurity between the fall of 2020 and the fall of 2021 (photo by Creative Touch Imaging Ltd./NurPhoto via Getty Images)

Jim Oldfield

Topic

Breaking Research

Temerty Faculty of Medicine

Joannah & Brian Lawson Centre for Child Nutrition

Dalla Lana School of Public Health

Food Security

Nutritional Sciences

Research & Innovation

The latest national data from researchers at the 91�Թ� show that food insecurity in Canada has remained largely unchanged over the last three years, with stark differences among the provinces.

The report, “Household Food Insecurity in Canada 2021,” shows that 15.9 per cent of households across 10 provinces experienced some degree of food insecurity in the year before fall 2021, with little change since 2019. Researchers define food insecurity as inadequate or insecure access to food due to financial constraint.

Professor Valerie Tarasuk

“We’ve seen no palpable improvement in food insecurity for low-income households in Canada,” said Valerie Tarasuk, a professor of nutritional sciences in 91�Թ�’s Temerty Faculty of Medicine, whose research group PROOF led the study with data from Statistics Canada.

During the same period, Quebec had the lowest rate of household food insecurity at 13.1 per cent, while Alberta was highest among the provinces at 20.3 per cent.

“Quebec has emerged with consistently lower food insecurity than other provinces, which I think speaks to the power of provincial policy,” Tarasuk said.

Policy structures and payments for low-income households in Quebec differ from other provinces in several areas, including income support, workplace benefits and child care.

“Social programs in Quebec are targeted to the vulnerable in ways we don’t always see in other provinces,” said Tarasuk, who is also affiliated with 91�Թ�’s Dalla Lana School of Public Health and the Joannah & Brian Lawson Centre for Child Nutrition. “Some focus on families with children, and all are indexed to inflation, which matters hugely at a time like this.”

Quebec has done especially well addressing severe food insecurity, the new report shows. People living in Quebec were less than half as likely (2.8 per cent versus 6.3 per cent) as those in Alberta to experience severe food insecurity, which includes hunger and is most strongly associated with increased health-care spending, poor health outcomes and premature death.

“It’s not like Quebec is off the charts, and we saw hints of this difference before 2019,” said Tarasuk. “But their low rates warrant more study, so we can continue to build on findings by our group and others that show the importance of higher minimum wage and more generous social programs for reducing food insecurity.”

Ontario was middle-of-the-pack for both severe and overall food insecurity, at 4.6 per cent and 16.1 per cent, respectively. That equates to well over two million people living with food insecurity in Ontario, the province with the largest population. Across all provinces, 5.8 million people now live in food-insecure households, including almost 1.4 million children.

The survey does not include people living on Indigenous reserves, but the rate of food insecurity among off-reserve Indigenous Peoples was 30.7 per cent. Other studies have also shown high vulnerability among on-reserve communities.

New data on food insecurity in the territories is not yet available, but the most recent numbers from Statistics Canada in 2020 – which only include moderate and severe food insecurity – are grim: 46.1 per cent in Nunavut, 23.1 per cent in the Northwest Territories and 15.3 per cent in Yukon.

The PROOF report drew on data from 54,000 households in Statistics Canada’s Canadian Income Survey. This is a change for Tarasuk’s team, which had tracked food insecurity since 2011 through the Canadian Community Health Survey. Both surveys employ the Household Food Security Survey Module, but Tarasuk says the income survey has a better response rate and is likely more representative of the Canadian population.

The change has allowed Tarasuk’s group to access data on food insecurity shortly after collection, and to compare numbers annually across all provinces. “Historically, some provinces including Ontario opted out of the survey module in some years, which left holes in the data,” Tarasuk said. “We now get consistent data in almost real time.”

The new data has also enabled soon-to-be-published studies from Tarasuk’s lab on the Canada Child Benefit and Employment Insurance relative to food insecurity. The research will add to the large body of evidence on how federal and provincial policies can reduce food insecurity by improving incomes of low-income households.

Data based on the Canadian Income Survey show higher rates of food insecurity than those collected in the Canadian Community Health Survey. But Tarasuk cautioned against comparing the two data sets and drawing the conclusion that food insecurity has worsened between 2018 and 2021.

Tarasuk said it was surprising that food insecurity did not appear to worsen during the pandemic, and that quick action by governments to introduce income supports may have prevented more widespread food insecurity.

But she is quick to stress that the problem hasn’t gotten better – and could soon get a lot worse. “The situation now is that inflation and prices are skyrocketing,” Tarasuk said. “People with severe food insecurity will suffer more deprivation, and more often turn to acts of desperation in the face of hunger. That’s the urgent challenge for policymakers.”

The research was supported by the Canadian Institutes of Health Research.

John Dick and Zulfiqar Bhutta win Canada Gairdner Awards

Christopher.Sorensen — Tue, 05 Apr 2022 13:20:56 +0000

John Dick and Zulfiqar Bhutta win Canada Gairdner Awards

Christopher.Sorensen Tue, 04/05/2022 - 09:20

Cutline

John Dick and Zulfiqar Bhutta have been honoured with 2022 Canada Gairdner Awards, the country’s most prestigious awards for medical and health science (photos courtesy of Images by Delmar and The Hospital for Sick Children)

Jim Oldfield

Topic

Our Community

Princess Margaret Cancer Centre

Temerty Faculty of Medicine

Pediatrics

Dalla Lana School of Public Health

Gairdner Award

Hospital for Sick Children

Molecular Genetics

Nutritional Sciences

Research & Innovation

University Health Network

Two researchers at the 91�Թ� and its hospital partners – one a stem cell biologist, the other a global health researcher – have been honoured with 2022 Canada Gairdner Awards, the country’s most prestigious awards for medical and health science.

John Dick was recognized with a Gairdner International Award for the discovery of leukemic stem cells and later work on the diagnosis and treatment of acute myeloid leukemia. He first received the news from Janet Rossant, president and scientific director of the Gairdner Foundation, earlier this year.

“When Janet called, it was definitely an ‘Oh my gosh’ moment,” said Dick, a professor of molecular genetics at 91�Թ�’s Temerty Faculty of Medicine and a senior scientist at Princess Margaret Cancer Centre, University Health Network.

“I recall being asked to sit on an evaluation panel for the Gairdners in the early 1990s, not long after setting up my lab in Toronto. That seemed like the epitome of achievement and I never imagined in my wildest dreams that one day I’d receive a Gairdner award.”

The John Dirks Canada Gairdner Global Health Award went to Zulfiqar Bhutta for his research on community-based and policy interventions in child and maternal health, especially among vulnerable populations.

“I’m very pleased and grateful,” said Bhutta, a professor in the departments of nutritional sciences and pediatrics at Temerty Medicine and at the Dalla Lana School of Public Health, and the director of the Centre for Global Child Health and a senior scientist at The Hospital for Sick Children.

“There are not many awards for research in global or public health, and the Gairdners occupy a special place in Canada and globally,” said Bhutta, who moved to Toronto in 2013 and maintains a research group at the Aga Khan University in Pakistan. “It really is a pinnacle and most humbling.”

John Dick: Growing Toronto’s stem cell legacy

Dick and his lab were the first to discover and describe leukemia stem cells, which can self-renew and drive both cancer growth and relapse after treatment.

Those findings have led to new clinical approaches for acute myeloid leukemia and related blood cancers, and spurred research on the role of stem cells in solid tumours of the colon, breast and brain, among other sites.

Dick said he didn’t set out to discover leukemia stem cells, but instead began by “plugging away” at basic science on the blood system in mice, experimenting with ways to put genes into stem cells.

In a key advance in the late 1980s, Dick’s lab developed a way to transplant human blood stem cells into immune-deficient mice. This “xenograft assay” was a world-first and enabled Dick and other researchers to track and test the human cells’ growth and replication, albeit in the living system of the mouse.

At the same time, Dick’s lab created the first xenograft models of human leukemia and developed a method to purify leukemia stem cells, allowing for detailed comparisons of those cells and leukemia cells without stem-like properties.

“Most people thought those early experiments wouldn’t work,” said Dick. “But lo and behold some of them worked beautifully, and we were able to characterize leukemia stem cells and non-stem cells. Leukemia is a caricature of normal development and we exploited that.”

Dick and his team began counting individual cells – much like James Till and Ernest McCulloch after their discovery of stem cells in Toronto in 1961, Dick noted. They made the startling finding that stem cells are extremely rare in acute myeloid leukemia – roughly one in a million, in a given population of leukemia cells.

They later found that relapse of acute myeloid leukemia is linked to the survival of leukemia stem cells after therapy and, using patient blood samples, they showed that leukemia stem cells that cause relapse are already present in the blood the day the patient first shows up at the clinic and before therapy begins.

Dick’s lab eventually developed a 17-gene “stemness score” that physicians use to predict patient risk and outcomes, which increasingly helps guide therapeutics. “It’s a new kind of approach for effective patient-specific intervention, which is gratifying,” Dick said.

Dick credits many colleagues for his successes, starting with the trainees in his lab. He said their technical skills and passion were critical, and that their ideas were often essential.

“For most of our findings, no one had the right ideas,” Dick said. “We just threw our thoughts in a melting pot – the good and the bad, and the resulting fusion took us in completely unexpected directions. In that intellectual foment, trainees have contributed so much. They’ve been the best post-docs and graduate students you could imagine.”

He also thanked his clinical collaborators at Princess Margaret Cancer Centre and other hospitals, as well as his colleagues at 91�Թ�.

“Human disease is the best sourcebook for raising and testing research questions, so I needed that constant interchange with clinicians,” Dick said. “But I benefited hugely from the intellectual rigour and collegiality of my colleagues in molecular genetics. I don’t think I could have done this work anywhere but Toronto.”

Zulfiqar Bhutta: Thinking big for the smallest and vulnerable

Bhutta’s career began in neonatology in Pakistan, but he soon expanded his focus beyond infants.

“I realized you can’t work with babies without working with mothers – and the moment you start working with mothers, you get to social determinants of health,” said Bhutta, the first 91�Թ� faculty member to win the John Dirks Canada Gairdner Global Health Award.

For more than three decades, Bhutta’s research has influenced policy and practice in global child and maternal health through implementation science, research synthesis and trials, as well as studies of malnutrition and obesity, among other approaches.

“I’ve learned as I went along, but I’ve been fortunate to work in a variety of areas, often on large-scale projects, with opportunities to make a difference in the short- and long-term,” said Bhutta, who is also affiliated with 91�Թ�’s Joannah & Brian Lawson Centre for Child Nutrition.

Bhutta and his colleagues at Aga Khan University provided some of the first scientific evidence on the impact of “lady health workers” in community-based interventions in Pakistan. The government of Benazir Bhutto began employing the workers in the mid-1990s, with the goal of reducing child and maternal risk factors and deaths.

Bhutta and his team helped evaluate those interventions in a series of cluster randomized trials – a method common in public health that allows researchers to compare program impacts across groups or clusters of people. Among their findings: using chlorhexidine for cord care during home births reduced neonatal infection and death – and public-sector community health workers working in rural populations could indeed help reduce perinatal fatalities.

They also showed that when women began to visit health facilities, facility-based births increased. Moreover, they found that women’s embrace of the community health system did not falter after the formal period of the intervention ended.

“That’s diffusion of innovation, when improvements become ingrained,” said Bhutta. “People said that women would suffer de-development after the initial intervention, but that did not happen. The lesson was that when you increase capacity around women’s health, you can move away and they never look back.”

Bhutta and his team provided evidence for expansion of the community-based worker model in Pakistan and countries in the Global South, but their work also highlighted the limits of what those workers can achieve.

“You can’t do much about a woman who is bleeding to death without access to a facility with a blood bank,” Bhutta said. “I’ve seen many efforts to upgrade community interventions to physician-level care fall flat because community workers are not physicians.”

Many of those failures were closely linked to social determinants of health, Bhutta said. He recalled that in a Pakistani hospital where his wife worked in the 1990s, pregnant women kept arriving dead at the hospital despite living just a few kilometres away. It turned out the delays were often due to an imbalance in decision-making power between males in females, a lack of money for transport or misunderstanding of the severity of the medical crisis.

“These problems don’t have a biomedical solution,” said Bhutta. “They need education, women’s empowerment, and building social and economic resources at the community level.”

Today, Bhutta continues to pursue research on child and maternal health in the Global South and among marginalized populations in high-income countries. But he is broadening his focus further to address another social determinant of health: climate change.

“I would like to work on solutions to climate change for the poorest of poor before countries agree and develop policy,” said Bhutta. “People are dying now from food shortages and heat shocks. I want to help bring communities together on a self-help basis to promote innovations without the need for external supports. Watch that space.”

The Gairdner Foundation was established in 1957 to recognize research that impacts human health and has since given 402 awards to scientists around the world. About a quarter of those researchers later received Nobel Prizes. The foundation gives seven awards annually. Each recipient receives $100,000 and participates in public lectures, research symposia and other outreach events. The foundation is supported by the Government of Canada.

Nuts are not linked to weight gain: 91�Թ� study

Christopher.Sorensen — Wed, 22 Sep 2021 20:39:08 +0000

Nuts are not linked to weight gain: 91�Թ� study

Christopher.Sorensen Wed, 09/22/2021 - 16:39

Cutline

(Photo by Grace Cary via Getty Images)

Jim Oldfield

Topic

Breaking Research

Temerty Faculty of Medicine

Alumni

Nutritional Sciences

Research & Innovation

Researchers at the 91�Թ� have found that nuts do not contribute to weight gain.

The review of quality research on links between nuts, fat consumption and body weight was recently published in the journal Obesity Reviews and is among the most comprehensive to date.

It provides further evidence that long-standing concerns about nuts and weight gain – often found in popular media and clinical nutrition guidelines – are unwarranted, the researchers say.

Stephanie Nishi

“Overall, we found there is no association between nuts and weight gain, and in fact some analyses showed higher nut intake associated with reductions in body weight and waist circumference,” said lead author Stephanie Nishi, who was a doctoral student in nutritional sciences in the Temerty Faculty of Medicine at the time of the study.

“This study really hits home the idea that nuts can be a good option for people with diabetes or cardiovascular risk, but also for all individuals broadly as part of a healthy eating plan, without caveats.”

The researchers pooled the results of 121 clinical trials and prospective studies, with over half a million participants in total. They then used a widely accepted system called GRADE (Grading of Recommendations Assessment, Development and Evaluation) to gage the quality of the studies.

“We found the certainty of evidence was high for trials and moderate for observational studies,” said John Sievenpiper, principal investigator on the study and an associate professor of nutritional sciences and medicine at the Temerty Faculty of Medicine.

“That’s a good indication of no harm from nuts relative to weight gain – no more than any other foods – and there may indeed be a benefit of weight loss in addition to the other widely acknowledged health benefits of nuts.”

Many nutrition and clinical guidelines for diabetes and heart disease recommend nuts as part of a healthy approach to eating. They include the Mediterranean, Portfolio, vegetarian or plant-based and DASH (Dietary Approaches to Stop Hypertension) dietary patterns.

Yet, global consumption of nuts is far below those guidelines, and when people do meet the bar, it’s often through peanuts. A typical serving of nuts is 28 to 42 grams (1 to 1.5 ounces), or what fits in the palm of an adult hand – and many guidelines suggest one serving per day.

“We’ve seen consumption of nuts increase in some areas over the last decade, especially middle- and high-income countries, but most people could better realize their benefits,” said Sievenpiper, adding he eats more than a handful most days.

“Always good to practise what you preach,” he said.

John Sievenpiper

Sievenpiper said the study was a massive amount of work. It was led by Nishi during more than four years of her doctoral studies and encompassed many types of nuts, as well as people with various health conditions and statuses.

In related work, Sievenpiper is running a clinical trial on heart health and the Portfolio diet, with nuts as a core pillar. Earlier this year, his lab found that a calorie labelled is not the same as a calorie digested and absorbed, when people consume almonds.

Nishi is now studying nuts, cognitive performance and vascular health in the lab of Jordi Salas Salvadó at Spain’s University of Rovira i Virgili.

“I didn’t used to eat many nuts, but now I’m surrounded by almonds and macadamias – so eating more,” Nishi said. “Especially due to the evidence supporting their health benefits, but also because of their versatility in the kitchen and on the go.”

The research was supported by the PSI Graham Farquharson Knowledge Translation Fellowship and the Banting & Best Diabetes Centre Sun Life Financial New Investigator Award. For a full list of all researchers' funding sources, see the journal article.

From detecting earthquakes to preventing disease: 27 91�Թ� research projects receive CFI funding

Christopher.Sorensen — Thu, 12 Aug 2021 19:35:43 +0000

From detecting earthquakes to preventing disease: 27 91�Թ� research projects receive CFI funding

Christopher.Sorensen Thu, 08/12/2021 - 15:35

Cutline

In a 91�Թ� Engineering lab, rock samples are subjected to the stress, fluid pressure and temperature conditions they experience in nature (photo courtesy of Sebastian Goodfellow)

Tyler Irving

Topic

Our Community

Institute of Biomedical Engineering

Princess Margaret Cancer Centre

Temerty Faculty of Medicine

Resarch & Innovation

Donnelly Centre for Cellular & Biomolecular Research

Cell and Systems Biology

Biochemistry

Chemistry

Dalla Lana School of Public Health

Earth Sciences

Faculty of Applied Science & Engineering

Faculty of Arts & Science

Laboratory Medicine and Pathobiology

Mount Sinai Hospital

Nutritional Sciences

Psychology

St. Michael's Hospital

91�Թ� Mississauga

91�Թ� Scarborough

University Health Network

UTIAS

Sebastian Goodfellow, a researcher at the 91�Թ�, listens for hidden signals that the ground is about to move beneath our feet.

That includes so-called “induced” earthquakes that stem from human activities such as hydraulic fracturing (‘fracking’) and enhanced geothermal systems.

“Think of the cracking sounds a cube of ice makes when you drop it in a cup of warm water, or the sound a wooden stick makes when you bend it until it breaks,” says Goodfellow, an assistant professor in the department of civil and mineral engineering in the Faculty of Applied Science & Engineering.

“This occurs as a consequence of sudden localized changes in stress, and we study these microfracture sounds in the lab to understand how rock responds to changes in stress, fluid pressure and temperature.”

While the frequency of these sonic clues is beyond the range of human hearing, they can be picked up with acoustic emission sensors. The challenge, however, is that scientists must listen continuously for hours in the absence of a method to predict when they will occur.

“We’re talking about more than a terabyte of data per hour,” says Goodfellow. “We use a form of artificial intelligence called machine learning to extract patterns from these large waveform datasets.”

Goodfellow’s study of induced seismicity project is one of 27 at 91�Թ� – and nine from 91�Թ� Engineering – to share more than $8.2 million in funding from the Canada Foundation for Innovation’s John R. Evans Leaders Fund (Read the full list of researchers and their projects).

Named for the late 91�Թ� President Emeritus John R. Evans, the fund equips university researchers with the technology and infrastructure they need to remain at the forefront of innovation in Canada and globally. It also helps Canadian universities attract top researchers from around the world.

“From sustainable electric transportation and engineering of novel materials to non-invasive neuro-imaging and applications of AI in public health, 91�Թ� researchers across our three campuses are advancing some of the most important discoveries of our time,” said Leah Cowen, 91�Թ�’s associate vice-president, research.

“Addressing such complex challenges often requires cutting-edge technology, equipment and facilities. The support provided by the Canada Foundation for Innovation will go a long way towards enabling our researchers’ important work.”

Goodfellow’s team will use the funding to buy a triaxial geophysical imaging cell fitted with acoustic emissions sensors as well as hardware for high-frequency acquisition of acoustic emissions data. The equipment will enable them to carry out controlled experiments in the lab, test better algorithms and develop new techniques to turn the data into insights – all to better understand processes that lead to induced earthquakes.

By learning more about how these tiny cracks and pops are related to larger seismic events such as earthquakes, the team hopes to help professionals in a wide range of sectors make better decisions. That includes industries that employ underground injection technologies – geothermal power, hydraulic fracturing and carbon sequestration, among others – along with the bodies charged with regulating them.

“Up until now, our poor understanding of the causal links between fluid injection and large, induced earthquakes limited the economic development of these industries,” says Goodfellow.

“Our research will help mitigate the human and environmental impacts, leading to new economic growth opportunities for Canada.”

Here is the full list of 27 91�Թ� researchers who received support for their projects:

Cristina Amon, department of mechanical & industrial engineering in the Faculty of Applied Science & Engineering: Enabling sustainable e-mobility through intelligent thermal management systems for EVs and charging infrastructure

Jacqueline Beaudry, department of nutritional sciences in the Temerty Faculty of Medicine and Lunenfeld-Tannenbaum Research Institute at Sinai Health: Role of pancreatic and gut hormones in energy metabolism

Swetaprovo Chaudhuri, 91�Թ� Institute for Aerospace Studies in the Faculty of Applied Science & Engineering: Kinetics-transport interaction towards deposition of carbon particulates in meso-channel supercritical fuel flows

Mark Currie, department of cell and systems biology in Faculty of Arts & Science: Structural Biology Laboratory

Marcus Dillon, department of biology at 91�Թ� Mississauga: The evolutionary genomics of infectious phytopathogen emergence

Landon Edgar, department of pharmacology and toxicology in the Temerty Faculty of Medicine: Technologies to interrogate and control carbohydrate-mediated immunity

Gregory Fairn, department of biochemistry in the Temerty Faculty of Medicine and St. Michael’s Hospital: Advanced live cell imaging and isothermal calorimetry for the study immune cell dysfunction and inflammation

Kevin Golovin, department of mechanical and industrial engineering in the Faculty of Applied Science & Engineering: Durable Low Ice Adhesion Coatings Laboratory

Sebastian Goodfellow, department of civil and mineral engineering in the Faculty of Applied Science & Engineering: A study of induced seismicity through novel triaxial experiments and data analysis methodologies

Giovanni Grasselli, department of civil and mineral engineering in the Faculty of Applied Science & Engineering: Towards the sustainable development of energy resources - fundamentals and implications of hydraulic fracturing technology

Kristin Hope, department of medical biophysics in the Temerty Faculty of Medicine and Princess Margaret Cancer Centre, University Health Network: Characterizing and unlocking the therapeutic potential of stem cells and the leukemic microenvironment

Elizabeth Johnson, department of psychology at 91�Թ� Mississauga: Baby Brain and Behaviour Lab (BaBBL) – electrophysiological measures of infant speech and language development

Omar Khan, Institute of Biomedical Engineering in the Faculty of Applied Science & Engineering and department of immunology in the Temerty Faculty of Medicine: Combination ribonucleic acid treatment technology lab

Marianne Koritzinsky, department of radiation oncology in the Temerty Faculty of Medicine and Princess Margaret Cancer Centre, University Health Network: Targeted therapeutics to enhance radiotherapy efficacy and safety in the era of image-guided conformal treatment

Christopher Lawson, department of chemical engineering & applied chemistry in the Faculty of Applied Science & Engineering: The Microbiome Engineering Laboratory for Resource Recovery

Fa-Hsuan Lin, department of medical biophysics in the Temerty Faculty of Medicine and Sunnybrook Research Institute: Integrated non-invasive human neuroimaging and neuromodulation platform

Vasanti Malik, department of nutritional sciences in the Temerty Faculty of Medicine: Child obesity and metabolic health in pregnancy – a novel approach to chronic disease prevention and planetary health

Rafael Montenegro-Burke, Donnelly Centre for Cellular and Biomolecular Research and department of molecular genetics in the Temerty Faculty of Medicine: Mapping the dark metabolome using click chemistry tools

Robert Rozeske, department of psychology at 91�Թ� Scarborough: Neuronal mechanisms of dynamic emotional behavior

Karun Singh, department of laboratory medicine and pathobiology in the Temerty Faculty of Medicine and Toronto Western Hospital, University Health Network: Stem cell models to investigate brain function in development and disease

Corliss Kin I Sio, department of Earth sciences in the Faculty of Arts & Science: Constraining source compositions and timescales of mass transport using femtosecond LA-MC-ICPMS

Helen Tran, department of chemistry in the Faculty of Arts & Science: Macromolecular bioelectronics encoded for self-assembly, degradability and electron transport

Andrea Tricco, Dalla Lana School of Public Health: Expediting knowledge synthesis using artificial intelligence – CAL®-Synthesi.SR Dashboard

Jay Werber, department of chemical engineering and applied chemistry in the Faculty of Applied Science & Engineering: The Advanced Membranes (AM) Laboratory for Sustainable Water Management and Resource Recovery

Haibo Zhang, department of physiology in the Temerty Faculty of Medicine and St. Michael’s Hospital: Real time high-resolution imaging and cell sorting for studying multi-organ repair and regeneration after lung injury

Gang Zheng, department of medical biophysics in the Temerty Faculty of Medicine and Princess Margaret Cancer Centre, University Health Network: Preclinical magnetic resonance imaging for targeted brain tumour therapies

Shurui Zhou, department of electrical and computer engineering in the Faculty of Applied Science & Engineering: Improving collaboration efficiency for fork-based software development

Low-glycemic diet reduces cardiometabolic risks for people with diabetes: 91�Թ� study

Christopher.Sorensen — Thu, 12 Aug 2021 16:54:53 +0000

Low-glycemic diet reduces cardiometabolic risks for people with diabetes: 91�Թ� study

Christopher.Sorensen Thu, 08/12/2021 - 12:54

Cutline

(Photo by Sharon Pittaway via Unsplash)

Topic

Temerty Faculty of Medicine

Alumni

Diabetes

Nutritional Sciences

Research & Innovation

A low-glycemic diet results in small but important improvements in cardiometabolic risk factors, including blood sugar levels and body weight, for people with diabetes, according to a 91�Թ� study analyzing multiple clinical trials.

The improvements were evident over and above existing drug or insulin therapy, suggesting that a low-glycemic diet might be especially useful as an add-on treatment to help people with diabetes achieve therapeutic targets.

The glycemic index (GI) rates how quickly different foods affect blood sugar levels. White breads and highly processed foods have a high glycemic load, while whole foods, vegetables and fruits tend to rate lower.

John Sievenpiper

“Diet and lifestyle modifications are foundational for managing diabetes, but for patients who require insulin or other medications, dietary patterns with a low GI are likely to improve blood glucose control as well as cholesterol levels, body weight and markers of inflammation,” said John Sievenpiper, an associate professor in the departments of nutritional sciences and medicine at 91�Թ�’s Temerty Faculty of Medicine and the study’s principal investigator.

The study, published in the journal The BMJ, included more than 1,600 participants with type 1 or 2 diabetes from over two dozen randomized, controlled trials that looked at the effect of low-GI diets in diabetes. Participants were mostly middle-aged, overweight or obese with moderately controlled type 2 diabetes treated with drugs or insulin.

The researchers saw reductions in risk factors such as fasting glucose, low-density lipoprotein (LDL) cholesterol, triglycerides, body weight, systolic blood pressure and C-reactive protein (a chemical associated with inflammation), but not blood insulin levels, high-density lipoprotein (HDL) cholesterol or waist circumference.

“We predict that these reductions would translate to an important reduction of risk for major cardiovascular events, the leading cause of death in people with diabetes,” said Sievenpiper, who is also a staff physician and scientist at St. Michael’s Hospital, Unity Health Toronto. “So there is clearly an opportunity for patients to benefit by shifting to low-GI dietary patterns.”

The glycemic index was developed by 91�Թ� Professor David Jenkins and colleagues in the 1980s. He and other researchers have shown that low-GI foods, which include fruits and vegetables, as well as many pulses and whole grains, can help keep blood sugar levels steady and reduce the risk of heart disease in people with diabetes.

Clinical guidelines for diabetes treatment across the world recommend a low-GI diet, although the last guideline from the European Association for the Study of Diabetes is more than 15 years old and researchers have conducted many trials since then.

Laura Chiavaroli

The researchers, including first author and post-doctoral fellow Laura Chiavaroli, found that the certainty of evidence was high for reduction in blood sugar levels and moderate for most other outcomes.

They point out limitations that may have affected their results, including imprecision in the evidence for the effect of low glycemic index dietary patterns on LDL cholesterol and waist circumference, and the small number of available trial comparisons for blood pressure and inflammatory markers.

Yet, they write that, overall, the evidence supports existing recommendations for the use of low-GI dietary patterns in the management of diabetes.

The study was funded by the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes, the Canadian Institutes of Health Research, Canada Foundation for Innovation and the Ministry of Research and Innovation’s Ontario Research Fund.

The study is the largest and most comprehensive synthesis to date, and will help inform an update to the European Association for the Study of Diabetes’s guideline.