Losing weight is often a goal for people with type 2 diabetes, which is strongly associated with being overweight or obese. However, it hasn’t been clear what dieting strategy works best for people with this metabolic disorder.

A new randomized controlled study of people with type 2 diabetes showed that study participants who restricted eating to between noon and 8 p.m. daily lost more weight than those who reduced their overall calorie intake by counting calories. Both dieting strategies produced similar improvements in blood sugar levels.

“Many people find counting calories very hard to stick to in the long term, but our study shows that watching the clock may offer a simple way to decrease calories and lose weight,” said Vicky Pavlou, RDN, a doctoral student at the University of Illinois at Chicago who performed the new research. “Although time-restricted eating is becoming increasingly popular, no other studies have looked at an eight-hour eating window in people with type 2 diabetes.”

Pavlou will present the findings at NUTRITION 2023, the annual flagship meeting of the American Society for Nutrition held July 22-25 in Boston.

Eating only during an eight-hour window has been studied previously for people with obesity. However, the researchers, led by Krista Varady, a professor of nutrition at the University of Illinois at Chicago, wanted to find out if this strategy could be helpful for people with type 2 diabetes.

The study included a group of 75 racially and ethnically diverse people between 18 to 80 years old with obesity and type 2 diabetes. Participants were placed into one of three groups: time-restricted eating, calorie restriction, or control. The people in the time-restricted eating group ate only between noon and 8 p.m. while the calorie restriction group could eat at any time of the day but counted their calories on the MyFitnessPal mobile app with a goal of reducing their caloric intake by 25% of their maintenance calories — the calories needed to maintain their current weight. The control group continued eating their normal diet.

Over the course of the six-month study, the researchers found that the people on the time-restricted eating diet lost 3.55% of their body weight relative to the control group. This would be the equivalent of a person weighing 275 pounds losing just under 10 pounds. The calorie restriction group did not lose any weight relative to the control group. Compared to the control group, blood sugar (HbA1C) levels decreased in both the time-restricted group (-.91%) and the calorie restriction group (-.95%).

The researchers also assessed whether these diet strategies improved cardiometabolic risk factors, but the weight loss achieved with the time-restricted eating did not reach the 5% mark typically necessary for improvement in these factors. Also, the study participants were taking cholesterol and blood pressure medications, which makes it difficult to observe improvements in cardiometabolic risk factors. 

“Our study shows that time-restricted eating can be a good alternative for those with type 2 diabetes who want to lose weight and improve their blood sugar,” said Pavlou. “However, there are multiple types of medications for those with type 2 diabetes, some of which can cause low blood sugar and some that need to be taken with food. Therefore, it is important to work closely with a dietitian or doctor when implementing this dieting approach.”

The discovery of insulin has saved the lives of millions of people with diabetes worldwide, but little is known about the first step of insulin synthesis.

Researchers at the University of Michigan have uncovered part of this mystery. Examining messenger RNAs involved in the production of insulin in fruit flies, they found that a chemical tag on the mRNA is crucial to translating the insulin mRNA into the protein insulin. The alteration of this chemical tag can affect how much insulin is produced. 

The study, conducted by researchers Daniel Wilinski and Monica Dus, is published in the journal Nature Structural and Molecular Biology.

An organism carries DNA—its genes—in each cell of its bodies. Genes are blocks of information that get transcribed into proteins via another molecule called messenger RNAs. These mRNAs are photocopies of DNA—leaving the original DNA untouched—that ferry this protein information into the cytoplasm of cells, where protein is synthesized. The mRNAs are decorated with small molecules called “tags.” These tags can modify how RNAs function and how proteins are produced.

“I like to think of RNA as a Christmas tree,” said Wilinski, a postdoctoral researcher in Dus’ lab in the U-M Department of Molecular, Cellular and Developmental Biology. “Christmas trees are beautiful in the wilderness, but when you bring them inside and put ornaments on them, that decoration is what makes you feel like the tree is part of the season. Same thing with RNA. These decorations on RNA really enhance the way RNA is regulated.”

Studying insulin production in humans or mammals is difficult. In humans, the pancreas is situated behind the liver. It doesn’t regenerate well, and it can’t be sampled in live subjects. But in flies, their insulin cells are actually in their brains, function like neurons, and are physically accessible to researchers. In fruit flies, the researchers looked at a tag called RNA N-6 adenosine methylation, or m6A.

To study the m6A tag, the researchers first identified the RNAs that have the tag. Then they labeled insulin cells with a fluorescent molecule, and used confocal microscopy to visualize how much insulin is produced by the insulin cell. They did this under two conditions: first, they knocked out the m6A enzyme, responsible for decorating the mRNA with m6A tags, in insulin cells. Second, they removed the m6A tags by using CRISPR, a technology used to edit DNA, to mutate the modified As.

In both cases, the flies’ ability to produce insulin was greatly reduced.

“We found that this photocopy of the DNA for insulin, this mRNA, had a specific tag that, when it is present, a ton of the insulin hormone is made,” said Dus, associate professor of molecular, cellular and developmental biology. “But without the signal, flies had much less insulin and developed hallmarks of diabetes.”

This chemical tag is conserved—or unchanged—in fish, mice and humans.

“So it’s likely that insulin production is also regulated through this kind of mechanism in humans,” Wilinski said. “There is an obesity and diabetes epidemic not just in the United States, but across the world. Our finding is another bit of evidence about how this disease happens.”

Dus says the discovery fleshes out the understanding of the biology of insulin and the physiology of diseases of energy homeostasis. Low levels of chemical tags have been observed in people with Type 2 diabetes. Restoring the levels of these tags may also help with combating diabetes and metabolic disease, she says. 

“We have known about insulin as a treatment for a hundred years. We have discovered so much about how insulin is made,” Dus said. “But we know so little about the very basic molecular biology of insulin and how it is regulated. That’s why I think this work is important—it refocuses on insulin, the gene and all the things we still have to discover about it.”

Investigators from Cedars-Sinai have provided new understanding of how diabetes delays wound healing in the eye, identifying for the first time two related disease-associated changes to the cornea.

The findings, published today in the peer-reviewed journal Diabetologia, also identified three therapeutic pathways that reversed these changes and partially restored wound-healing function to the cornea—a discovery that could ultimately inform new treatments for diabetes.

“We have found that diabetes induces more cellular changes than we were aware of previously,” said Alexander Ljubimov, PhD, director of the Eye Program at Cedars-Sinai’s Board of Governors Regenerative Medicine Institute and senior author of the paper. “The discovery does not affect gene sequence but entails specific DNA modifications altering gene expression—what are known as epigenetic alterations.”

More than 37 million people in the United States—11% of the population—have diabetes, a systemic disorder that can result in kidney disease, heart disease, amputation, stroke and nerve damage. Most diabetes drugs are designed to increase glucose tolerance or supply depleted insulin, but do not address molecular and cellular changes or their associated complications.

The new research also identifies for the first time an important role of Wnt-5a, a secreted signaling protein investigators found responsible for corneal wound healing and the function of stem cells—cells capable of differentiating into many cell types.

“Current treatments only address symptoms, so there is an urgent need to understand the molecular mechanisms of diabetes-related wound-healing problems,” said Ruchi Shah, PhD, a scientist in Ljubimov’s lab and the study’s first author. “Understanding of this novel epigenetically regulated wound-healing mechanism could lead to therapeutic treatments that could help patients avoid further long-term ocular health issues.”

Though much focus of diabetic eye disease is on the retina, up to 70% of diabetes patients suffer from problems of the cornea, the transparent, protective exterior surface of the eye. In advanced diabetes, corneal stem cells become dysfunctional, and the cornea heals more slowly and less completely following an injury or procedures such as cataract surgery and laser treatment for diabetic retinopathy.

To identify the epigenetic changes discovered in this study—changes not hard-wired into the genome from birth, but introduced later—Ljubimov and his team compared cells from the corneas from six diabetic patients with those of five healthy donors. They found that in diabetic corneas, the protein product of the WNT5A gene was repressed. Additionally, in diabetic samples, they found an increase in the microRNA that inhibits WNT5A.

The team of scientists then induced wounds to corneal cells in culture and corneal organ cultures, and tested three interventions designed to normalize Wnt-5a protein expression. They added the Wnt-5a protein directly; they introduced a DNA methylation inhibitor, originally approved to treat cancer; and they targeted microRNA levels with a novel gene therapy approach using a nanoscale compound. The team developed the compound, which uses synthetic molecules to block the microRNA, as a substitute for a viral gene therapy they found to be toxic to stem cells.

All three therapeutic methods, in the diabetic samples, stimulated stem cell marker production and improved tissue regeneration, accelerating wound healing.

“Novel therapies to reverse epigenetic effects could improve corneal function, and may also prove significant in other diabetic complications,” said Clive Svendsen, PhD, director of the Board of Governors Regenerative Medicine Institute and study co-author. “This work certainly helps move the field forward.”

“Our goal is to develop topical, sustained-release drugs for corneal wound healing,” said Ljubimov. “Drugs that are FDA [Food and Drug Administration] approved and could be easily applied may be one of the most promising approaches for effective future therapies.”

An extract from dahlia flower petals has been found to stabilise blood sugar levels of diabetes patients in University of Otago-led clinical trials.

A team led by neuroendocrinologist Associate Professor Alexander Tups, of the Centre for Neuroendocrinology, showed that the inhibition of brain inflammation – brought about by the excess consumption of a Western diet – markedly improves blood sugar regulation.

His team then went on to discover an anti-inflammatory plant molecule that acts in the brain and potently improves the ability of the body to process blood sugar.

“We then found that the dahlia plant is a cultivatable source of this molecule and that it contains two additional plant molecules that enhanced the effect of the original one. This specifically blocked brain inflammation and improved blood sugar regulation in preclinical trials,” Associate Professor Tups says.

About 25 per cent of the adult population in Aotearoa have prediabetes – a condition where blood glucose levels are slightly elevated, indicating that a person is at risk of progressing to type 2 diabetes. Without intervention about 70 per cent of people go on to develop type 2 diabetes later in life.

In a randomised controlled cross-over clinical trial on participants with prediabetes or type 2 diabetes, researchers were able to show that the dahlia extract considerably improved blood sugar regulation.

In preclinical animal studies researchers were able to reverse brain inflammation, improve sensitivity to the hormone insulin in the brain and improve blood sugar regulation.

The project started with a grant in 2015 in collaboration with Plant and Food Research and eight years on he considers it a career high, he says.

“As scientists, often our work finishes when we find the mechanism of how something works. So in this case finding three compounds that occur in a flower that in combination improved blood sugar regulation was a dream come true.

“Impaired blood sugar regulation is a debilitating condition affecting millions of people around the world.  I hope and I really believe that the outcome of our intensive research will benefit people suffering from this condition.”   

The technology has been patented and the research team has worked with Otago Innovation Limited (OIL) and external stakeholders to bring a natural dahlia-extract supplement to the market, aiming to support normal blood sugar and insulin levels.

OIL project lead Dr Graham Strong says the collaboration brings together diverse perspectives, knowledge, and expertise, leading to an innovative and science-based nutraceutical product.

“This diversity, along with our and other stakeholder investment, resulted in the launch of a product we are very proud to be associated with.

“The product provides a unique blend of nutritional compounds to support normal blood sugar and insulin levels. The trials showed that this will be useful for those diagnosed with prediabetes or type 2 diabetes to help stop the progression of the condition,” he says.