Diabetes

Posted on Diabetes

New AI-ready dataset released in type 2 diabetes study

Early results suggest broader participant diversity and novel measures will enable new, artificial intelligence-driven insights
Early results suggest broader participant diversity and novel measures will enable new, artificial intelligence-driven insights.

Researchers are releasing the main dataset from an ambitious study exploring the biomarkers and environmental factors that may influence the development of type 2 diabetes. This study involves participants with no diabetes and those at various stages of the condition. The initial findings suggest a rich and unique set of information that differs from previous research.

Data from customized environmental sensors installed in participants’ homes reveal a clear link between disease states and exposure to fine particulate pollution. The collected information also includes survey responses, depression scale scores, eye imaging scans, traditional glucose measurements, and various other biological variables.

These data are intended to be mined by artificial intelligence for novel insights about risks, preventive measures, and pathways between disease and health.

“We observe evidence of diversity among patients with type 2 diabetes, indicating that their experiences and challenges are not uniform. With access to increasingly large and detailed datasets, researchers will have the opportunity to explore these differences in depth,” stated Dr. Cecilia Lee, a professor of ophthalmology at the University of Washington School of Medicine.

She expressed excitement at the quality of the collected data, representing 1,067 people, just 25% of the study’s total expected enrollees.

Lee is the program director of AI-READI (Artificial Intelligence Ready and Equitable Atlas for Diabetes Insights), a National Institutes of Health-supported initiative that aims to collect and share AI-ready data for global scientists to analyze for new clues about health and disease.

The authors restated their aim to gather health information from a more racially and ethnically diverse population than previously measured, and to make the resulting data ready, technically and ethically, for AI mining.

“This discovery process has been invigorating,” said Dr. Aaron Lee, a UW Medicine professor of ophthalmology and the project’s principal investigator. “We’re a consortium of seven institutions and multidisciplinary teams that had never worked together. But we have shared goals of drawing on unbiased data and protecting the security of that data as we make it accessible to colleagues everywhere.”

At study sites in Seattle, San Diego, and Birmingham, Alabama, recruiters are collectively enrolling 4,000 participants, with inclusion criteria promoting balance:

  • race/ethnicity (1,000 each – white, Black, Hispanic and Asian)
  • disease severity (1,000 each – no diabetes, prediabetes, medication/non-insulin-controlled and insulin-controlled type 2 diabetes)
  • sex (equal male/female split)

“Conventionally, scientists are examining pathogenesis — how people become diseased — and risk factors,” Aaron Lee said. “We want our datasets also to be studied for salutogenesis, or factors that contribute to health. So if your diabetes improves, what factors might contribute to that? We expect that the flagship dataset will lead to novel discoveries about type 2 diabetes in both of these ways.”

He added that by collecting more deeply characterizing data from many people, the researchers hope to create pseudo health histories of how a person might progress from disease to full health and from full health to disease. 

The data are hosted on a custom online platform and produced in two sets: a controlled-access set requiring a usage agreement and a registered, publicly available version stripped of HIPAA-protected information.

Posted on Cardiovascular disease, Diabetes

Study shows how high blood sugar increases risk of thrombosis

Discoveries by Brazilian researchers belonging to a FAPESP-supported research center could lead to strategies to prevent cardiovascular disease associated with diabetes
Discoveries could lead to strategies to prevent cardiovascular disease associated with diabetes.

A study conducted at the Center for Research on Redox Processes in Biomedicine (Redoxoma) has enhanced our understanding of how high blood sugar levels (hyperglycemia), a common symptom of diabetes, can lead to thrombosis. The findings, published in the Journal of Thrombosis and Haemostasis, could inform the development of strategies to prevent cardiovascular issues in individuals with diabetes.

“The primary causes of death in Brazil and many other Latin American countries are ischemic events, including heart attacks and strokes, where arterial thrombosis plays a significant role. These cardiovascular disorders can result from various risk factors such as high blood sugar (hyperglycemia), abnormal lipid levels (dyslipidemia), and high blood pressure (hypertension). Among these factors, hyperglycemia is notably associated with an increased risk of cardiovascular disease,” stated Renato Simões Gaspar, the article’s lead author.

The investigation was conducted with support from FAPESP during Gaspar’s postdoctoral research and led by Francisco Laurindo, the last author of the article. Laurindo is a professor at the University of São Paulo’s Medical School (FM-USP) in Brazil and is also a member of Redoxoma, a Research, Innovation, and Dissemination Center (RIDC) established by FAPESP at the Institute of Chemistry (IQ-USP). Gaspar currently teaches at the State University of Campinas (UNICAMP).

The authors state that prolonged hyperglycemia and diabetic ketoacidosis increase the risk of thrombosis. This is due to their effects on endothelial dysfunction, which refers to changes in the inner lining of blood vessels. These changes can lead to the binding of platelets to the endothelial cells, triggering the formation of blood clots.

The study showed that peri/epicellular protein disulfide isomerase A1 (pecPDI) regulates platelet-endothelium interaction in hyperglycemia through adhesion-related proteins and alterations in endothelial membrane biophysics.

“We found that a pathway for this PDI in endothelial cells mediates thrombosis in diabetes when hyperglycemia is present, involving a specific molecular mechanism, which we identified,” Laurindo said.

PDI is an enzyme that resides in the endoplasmic reticulum and has the classic function of catalyzing the insertion of disulfide bridges into nascent proteins so that they merge in the correct shape, i.e. so that the amino acid chain folds to form the three-dimensional structure that makes the molecule functional. It is also found in the extracellular space as pecPDI, a pool secreted or bound to the cell surface, in various cell types including platelets and endothelial cells. Studies have shown that pecPDI regulates thrombosis in several models. 

Biochemical and biophysical modifications

To investigate platelet-endothelium interaction in hyperglycemia, the researchers created a model with human umbilical vein endothelial cells cultured in different glucose concentrations to produce normoglycemic and hyperglycemic cells. They assessed PDI’s contribution using whole-cell PDI or pecPDI inhibitors.

The cells were incubated with platelets derived from healthy donors. The platelets adhered almost three times more in hyperglycemic than normoglycemic cells. PDI inhibition reversed this effect, and the researchers concluded that the process is regulated by endothelial pecPDI.

To better understand the result, they investigated biophysical processes such as endothelial cell cytoskeleton remodelling and found that hyperglycemic cells had more well-structured actin filament fibres than normoglycemic cells. They also measured the production of hydrogen peroxide, an oxidizing compound, because reactive oxygen species are mediators of cytoskeleton reorganization and cell adhesion—hyperglycemic cells produced twice as much hydrogen peroxide as normoglycemic cells.

The researchers then investigated whether cytoskeleton reorganization affected cell membrane stiffness since substrate stiffness increases platelet adhesion. Using atomic force microscopy, they demonstrated that hyperglycemic cells were stiffer than normoglycemic cells.

The microscope images also showed the formation of cell elongations with extracellular vesicles that appeared to separate from the elongations. This observation led the researchers to investigate the secretome – the set of proteins secreted by an organism into the extracellular space – to find out whether it included proteins that enhanced platelet adhesion. “The purpose of this experiment was to detect proteins exclusively expressed by or present in hyperglycemic cells and not in controls or cells treated with PDI inhibitors,” Gaspar explained.

They found 947 proteins in the secretome, from which they selected eight with a role in cellular adhesion. They then silenced gene expression for three of these proteins using RNA interference and arrived at two proteins, SLC3A2 and LAMC1, as modulators of platelet adhesion. SLC3A2 is a membrane protein, and LAMC1 is the gamma subunit of laminin 1, a key extracellular matrix component.

Posted on Cognitive dysfunction, Diabetes, Diet

Blood sugar control is a big factor in slowing brain aging! What about the Mediterranean diet?

The Green Mediterranean Diet Shows Promise
The Green Mediterranean Diet Shows Promise

Age-related brain atrophy refers to the gradual loss of neurons and shrinkage of brain tissue, which is a natural part of the ageing process. This condition can contribute to cognitive decline and various neurological issues. While ageing itself cannot be prevented, recent research from an 18-month dietary intervention provides hope that lifestyle and dietary changes may help slow down brain ageing.

Brain age, determined through MRI measurements of the hippocampus and lateral ventricles, reflects the biological aging of the brain, which may differ from a person’s chronological age. Chronological age is simply the number of years a person has lived, while brain age indicates the actual health of the brain. Generally, as we age, the hippocampus tends to shrink, and the lateral ventricles tend to expand, which serve as indicators of brain ageing. Some individuals may have a brain age that is younger or older than their chronological age. A younger brain age suggests better cognitive health, whereas an older brain age may indicate accelerated ageing and an increased risk of cognitive decline.

The study found that a decline in HbA1c and key markers of long-term blood sugar levels is associated with significant positive changes in specific brain regions commonly affected by age-related atrophy. It suggests that improved blood sugar control could be one of the most important factors in slowing down age-related brain changes.

Previous research has shown the benefits of the Green Mediterranean (Green-Med) diet, particularly its positive effects on blood sugar control. This diet is rich in polyphenols from plant-based sources such as Mankai—a high-protein aquatic plant—and green tea, while being low in red and processed meats. The current study reinforces these findings, suggesting that the Green-Med diet not only supports metabolic health but may also have protective effects on brain structure and function.

Posted on Cognitive dysfunction, Dementia, Diabetes, Diet, Obesity

Restricting sugar consumption in utero and in early childhood significantly reduces risk of midlife chronic disease

New research shows combined use of sodium glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1-RAs) is likely to offer additional protection against heart and kidney disease in patients with diabetes

A new study has found that a low-sugar diet in utero and in the first two years of life can meaningfully reduce the risk of chronic diseases in adulthood. This provides compelling new evidence of the lifelong health effects of early-life sugar consumption.

A study published in the journal Science reveals that children who had sugar restrictions during their first 1,000 days after conception faced up to a 35% lower risk of developing Type 2 diabetes and a 20% reduced risk of hypertension in adulthood. The research indicates that low sugar intake by mothers during pregnancy was sufficient to lower these health risks, and maintaining sugar restrictions after birth further enhanced the benefits.

Using an unintended “natural experiment” from World War II, researchers at the USC Dornsife College of Letters, Arts and Sciences, McGill University in Montreal, and the University of California, Berkeley, examined how sugar rationing during the war influenced long-term health outcomes.

The United Kingdom introduced limits on sugar distribution in 1942 as part of its wartime food rationing program. Rationing ended in September 1953.

The researchers used contemporary data from the U.K. Biobank, a database of medical histories and genetic, lifestyle and other disease risk factors, to study the effect of those early-life sugar restrictions on health outcomes of adults conceived in the U.K. just before and after the end of wartime sugar rationing.

“Studying the long-term effects of added sugar on health presents challenges,” explains Tadeja Gracner, a senior economist at the USC Dornsife Center for Economic and Social Research and the study’s corresponding author. “It is difficult to identify situations where individuals are randomly exposed to different nutritional environments early in life and tracked over a span of 50 to 60 years. The end of rationing provided us with a unique natural experiment that helped us overcome these obstacles.”

On average, during rationing, sugar intake was about 8 teaspoons (40 grams) per day. When rationing ended, sugar and sweets consumption skyrocketed to about 16 teaspoons (80 grams) per day. 

Notably, rationing did not involve extreme food deprivation overall. Diets generally appeared to have been within today’s guidelines set by the U.S. Department of Agriculture and the World Health Organization, which recommend no added sugars for children under two and no more than 12 teaspoons (50g) of added sugar daily for adults. 

The immediate and large increase in sugar consumption but no other foods after rationing ended created an interesting natural experiment: Individuals were exposed to varying levels of sugar intake early in life, depending on whether they were conceived or born before or after September 1953. Those conceived or born just before the end of rationing experienced sugar-scarce conditions compared to those born just after who were born into a more sugar-rich environment.

The researchers then identified those born in the U.K. Biobank data collected over 50 years later. Using a very tight birth window around the end of sugar rationing allowed the authors to compare midlife health outcomes of otherwise similar birth cohorts.  

While living through the period of sugar restriction during the first 1,000 days of life substantially lowered the risk of developing diabetes and hypertension, for those later diagnosed with either of those conditions, the onset of disease was delayed by four years and two years, respectively. 

Notably, exposure to sugar restrictions in utero alone was enough to lower risks, but disease protection increased postnatally once solids were likely introduced. 

The researchers say the magnitude of this effect is meaningful as it can save costs, extend life expectancy, and, perhaps more importantly, improve quality of life.

In the United States, individuals with diabetes face average annual medical expenses of approximately $12,000. Additionally, an earlier diagnosis of diabetes is associated with a significantly reduced life expectancy; specifically, for each decade that diagnosis occurs earlier, life expectancy decreases by three to four years.

The researchers note that these numbers underscore the value of early interventions that could delay or prevent this disease.

Experts continue to raise concerns about children’s long-term health as they consume excessive amounts of added sugars during their early life, a critical period of development. Adjusting child sugar consumption, however, is not easy—added sugar is everywhere, even in baby and toddler foods, and children are bombarded with TV ads for sugary snacks, say the researchers.

“Parents need information about what works, and this study provides some of the first causal evidence that reducing added sugar early in life is a powerful step towards improving children’s health over their lifetimes,” says study co-author Claire Boone of McGill University and University of Chicago.  

Co-author Paul Gertler of UC Berkeley and the National Bureau of Economics Research adds: “Sugar early in life is the new tobacco, and we should treat it as such by holding food companies accountable to reformulate baby foods with healthier options and regulate the marketing and tax sugary foods targeted at kids.” 

This study is the first of a larger research effort exploring how early-life sugar restrictions affected a broader set of economic and health outcomes in later adulthood, including education, wealth, and chronic inflammation, cognitive function and dementia. 

Posted on A to Z of Medical Conditions, Diabetes, Obesity

Brighter nights and darker days could lead to an early grave

Are you protecting your children’s eyes from the sun this summer?

A study of more than 13 million hours of data collected from light sensors worn by 89,000 people has found exposure to bright nights and dark days is associated with an increased risk of death.

Researchers investigated whether personal day and night light and lighting patterns that disrupt our circadian rhythms predicted mortality risk.

Published in the journal Proceedings of the National Academy of Sciences, the findings indicate that individuals exposed to high levels of light at night faced a 21% to 34% increased risk of death. In contrast, those exposed to high levels of daylight experienced a 17% to 34% decrease in their risk of death.

“Exposure to brighter nights and darker days can disrupt our circadian rhythms. This disruption can lead to various health issues, including diabetes, obesity, cardiovascular disease, mental health problems, and an increased risk of death,” explains Professor Sean Cain, a senior author and sleep expert from Flinders University.

“These new insights into the potential adverse impact of light have shown us just how important personal light exposure patterns are for your health.”

Associate Professor Andrew Phillips, co-senior author, states that nighttime light exposure disrupts circadian rhythms by shifting their timing (phase-shift) and weakening the signal (amplitude suppression) of the central circadian ‘pacemaker,’ which regulates circadian rhythms throughout the body.

“Disruption to the body’s circadian rhythms is linked to the development of metabolic syndrome, diabetes, and obesity and is also strongly implicated in the development of cardiometabolic diseases, including myocardial infarction, stroke and hypertension,” says Associate Professor Phillips.

“The observed relationships of night light exposure with mortality risk may be explained by night light disrupting circadian rhythms, leading to adverse cardiometabolic outcomes.

“Our findings clearly show that avoiding night light and seeking daylight may promote optimal health and longevity, and this recommendation is easy, accessible and cost-effective,” adds Associate Professor Phillips.

The study authors from FHMRI Sleep Health investigated the relationship between personal light exposure and the risk of all-cause and cardiometabolic mortality in 89,000 participants from the UK Biobank, aged between 40 and 69. Metrics were recorded using wrist-worn sensors, and the National Health Service collected the participants’ mortality data over an approximate follow-up period of eight years.

Sleep duration, sleep efficiency, and midsleep were estimated from motion data. At the same time, cardiometabolic mortality was defined as any cause of death corresponding to diseases of the circulatory system or endocrine and metabolic diseases.

The research also showed a disrupted circadian rhythm predicted higher mortality risk, which the authors were able to determine using computer modelling. Findings accounted for age, sex, ethnicity, photoperiod, and sociodemographic and lifestyle factors.

Lead author Dr Daniel Windred says that the findings demonstrate the importance of maintaining a dark environment during the late night and early morning hours, when the central circadian ‘pacemaker’ is most sensitive to light, and seeking bright light during the day to enhance circadian rhythms.

“Protection of lighting environments may be significant in those at risk for circadian disruption and mortality, such as in intensive care or aged-care settings,” says Dr Windred.

“Across the general population, avoiding night light and seeking daylight may lead to a reduction in disease burden, especially cardiometabolic diseases, and may increase longevity.”