Posted on Diabetes

Study identifies human microRNAs linked to type 2 diabetes

Study identifies human microRNAs linked to type 2 diabetes
Study identifies human microRNAs linked to type 2 diabetes

MicroRNA (miRNA) molecules in pancreatic islets have been thought to play important roles in type 2 diabetes, but until now scientists have not confidently identified which miRNAs are associated with the disease in humans.

A new study, published Feb. 9 in the journal Proceedings of the National Academy of Sciences, represents the largest study to date of diabetes-linked miRNAs found in human pancreatic islets – groups of cells in the pancreas that secrete insulin and regulate blood glucose levels.

Most prior attempts to comprehensively profile miRNAs (which regulate which genes are turned on and off) in pancreatic islets using next-generation sequencing technology have been done in culture or with rodent models. A few studies conducted with hard-to-acquire human islets were limited by a small number of samples.

The study’s corresponding authors, Praveen Sethupathy ‘03, professor of biomedical sciences in the College of Veterinary Medicine and director of the Center for Vertebrate Genomics at Cornell University, and Dr. Francis Collins, former director of the National Institutes of Health (2009-21) and a senior investigator at the National Human Genome Research Institute at the NIH, had access to a network that supplied nearly 65 human pancreatic islet samples from cadavers for this study.

The robust sample size allowed the researchers to use large-scale, next generation sequencing to identify at least 14 pancreatic islet miRNAs that are implicated in human type 2 diabetes.

“We’ve defined in the largest cohort of human islets to date the miRNAs that might be most relevant for type 2 diabetes,” said Sethupathy, who was a postdoctoral researcher in Collins’ NIH lab from 2008-11.  

“We [also] found that some of the diabetes-associated miRNAs in humans are not ones that have been well-characterized in the previous two decades of studying islets and diabetes in rodent models,” he said.

MiRNAs were first found in animal cells in 2001. Soon after, in 2004, one of the first studies demonstrating their importance to physiology focused on a miRNA that regulates the function of pancreatic islets. Since then, hundreds of studies on miRNAs with potential relevance to pancreatic islets have been published, but few have used human tissue samples and none have been at the scale of this study.

“There’s been long-standing interest to better understand the molecular environment of the pancreas, so that we could get a better handle on what goes awry in diabetes patients and then eventually be able to use that information to develop better therapeutics,” Sethupathy said.

The relatively large sample size helps to reveal the extent of variation in the quantity of miRNAs in the islets, or expression level, across the human population. The researchers also had genetic information on all the patients, which helped them determine a handful of genomic loci underlying variability in miRNA expression, though ultimately this type of inquiry will require many hundreds of samples for a fuller picture. One of these loci was found in the same area of the genome that is associated with type 2 diabetes-related traits, which could suggest a novel mechanism for how type 2 diabetes develops.

Some of the most altered miRNAs in islets from individuals with type 2 diabetes were consistent with those found in previous rodent studies, but there were also some notable differences. “These represent interesting candidates to investigate further in human models of pancreatic islets,” Sethupathy said.

In the future, researchers will need to further invest in the development and study of human models of type 2 diabetes, such as genetically-modified islets or organoids, Sethupathy said.

Posted on Diet

Cognitive health may benefit from balanced meal timing

Cognitive health may benefit from balanced meal timing


Temporal patterns of energy intake among participants in the China Health and Nutrition Study. CREDITHui Chen, Yang Tao, Min-Dian Li, Yuxuan Gu, Jiaxi Yang, You Wu, Dongmei Yu, Changzheng Yuan

Globally, there are approximately 55 million people who suffer from dementia, and the incidence of the disease has steadily increased. The number of the population is expected to triple by 2050, particularly in low- and middle-income countries. Dementia affects not only the quality of life of individuals, but also adds significant economic burdens to families and society.

Epidemiological studies have shown a correlation between the temporal distribution of energy intake during a day (TPEI) and the risk of various chronic diseases such as diabetes and hypertension. However, evidence regarding the relationship between TPEI and cognitive function at the population level is relatively lacking.

Previous studies in animal models have shown that the disruption in meal timing can cause alterations in clock rhythms in the hippocampus, thereby affecting cognitive function. According to a short-term intervention trial of 96 young adults, dividing equal amounts of food into four meals between 9 am and 3 pm could improve cognitive function compared to eating twice between 9 am and 3 pm. However, long-term study is lacking about the TPEIs and cognitive function.

Recently, Drs Changzheng Yuan and Dongmei Yu at Zhejiang University published a paper in Life Metabolism entitled “Temporal patterns of energy intake and cognitive function and its decline: a community-based cohort study in China” Based on the China Nutrition Health Survery (CHNS) public database, a total of 3,342 participants were included in this study, who were middle-aged and older adults (mean age 62 years) from nine provinces in China with a baseline age ≥ 55 years.

The researchers used: 1) A data-driven k-means algorithm to identify six patterns of TPEIs, including “evenly-distributed” pattern, “breakfast-dominant” pattern, “lunch-dominant” pattern, “dinner-dominant” pattern, “snack-rich” pattern, and “breakfast-skipping” pattern; 2) Cognitive function was assessed using the modified Telephone Interview for Cognitive Status (TICS-m), comprising immediate and delayed word recalls (20 points), backward counting (2 points), and serial-7 subtraction test (5 points). The total global cognitive score ranged from 0 to 27, with a higher score representing a better cognitive function; 3) The correlation of TPEIs to cognitive function over 10 years was assessed using linear mixed models (LMMs), which was adjusted for age, gender, residence, total energy, physical activity, smoking status, alcohol consumption, household income, education level, and body mass index (BMI).

The result showed that, compared with those with “evenly-distributed” pattern, the long-term cognitive function scores were significantly lower in those who had unbalanced TPEIs, especially those with “breakfast-skipping” pattern. Thus, maintaining balanced TPEIs has potentially positive effects on cognitive health, whereas skipping breakfast may significantly increase the risk of cognitive decline in middle-aged and older adults. In conclusion, this study highlights the importance of optimal TPEIs in cognitive function.

Posted on Cancer, Diabetes

Wear and forget: an ultrasoft material for on-skin health devices

With cancer, diabetes and heart disease among the leading causes of disability and death in the United States, imagine a long-term, in-home monitoring solution that could detect these chronic diseases early and lead to timely interventions. 

Zheng Yan


Zheng Yan CREDIT University of Missouri

Zheng Yan and a team of researchers at the University of Missouri may have a solution. They have created an ultrasoft “skin-like” material — that’s both breathable and stretchable — for use in the development of an on-skin, wearable bioelectronic device capable of simultaneously tracking multiple vital signs such as blood pressure, electrical heart activity and skin hydration.

“Our overall goal is to help improve the long-term biocompatibility and the long-lasting accuracy of wearable bioelectronics through the innovation of this fundamental porous material which has many novel properties,” said Yan, an assistant professor in the Department of Chemical and Biomedical Engineering and the Department of Mechanical and Aerospace Engineering.

Made from a liquid-metal elastomer composite, the material’s key feature is its skin-like soft properties.

“It is ultrasoft and ultra-stretchable, so when the device is worn on the human body, it will be mechanically imperceptible to the user,” Yan said. “You cannot feel it, and you will likely forget about it. This is because people can feel about 20 kilopascals or more of pressure when something is stretched on their skin, and this material creates less pressure than that.”

Its integrated antibacterial and antiviral properties can also help prevent harmful pathogens from forming on the surface of the skin underneath the device during extended use.

“We call it a mechanical and electrical decoupling, so when the material is stretched, there is only a small change in the electrical performance during human motion, and the device can still record high-quality biological signals from the human body,” Yan said.

While other researchers have worked on similar designs for liquid-metal elastomer composites, Yan said the MU team has a novel approach because the breathable “porous” material they developed can prevent the liquid metal from leaking out when the material is stretched as the human body moves.

The work builds on the team’s existing proof of concept, as demonstrated by their previous work including a heart monitor currently under development. In the future, Yan hopes the biological data gathered by the device could be wirelessly transmitted to smartphone or similar electronics for future sharing with medical professionals.