Smart insulin- The major drawback of Type I is the dependence on regular external doses of insulin. While technology has made it more and more manageable with insulin pens, it results in the patient’s life to be largely centered around their medication. In 2015, researchers at the University of North Carolina devised a glucose-monitoring, insulin-delivery system using nanotechnology and biomedical engineering. The smart insulin patch consists of an array of tiny needles which can be used anywhere on the body to detect glucose levels and release insulin accordingly. The technology is currently undergoing revision and pre-clinical testing.

Islet transplant- Recovering healthy pancreas from cadavers and transplanting islet cells into the liver of the patient is an experimental procedure in practice since 2008 to assist with Type I. However, the success rate of this intervention is low due to rejection by the patient’s immune system and dependence on immune-suppressants which increase the risk of infection. It also does not completely reverse the patient’s insulin-dependence and requires regular low doses of insulin. A variation of this therapy at the University of Miami in 2017 was a successful transplant of pancreatic islet cells into the stomach lining of the patient which resulted in her complete remission from Type I and independence from constant insulin injections.

Stem cell therapy- With the evolution of cell biology techniques, we now have the ability to program immature cells to develop into a specific lineage of cells. Viacyte, a California based biomedical engineered a direct delivery device in April 2017, which when placed under the skin delivers stem cells into the bloodstream. These stem cells are programmed to home into the pancreas and develop into mature insulin-producing cells to replace those eliminated by the immune system. While this device is still in its nascent stages of the trial, it would be a life-saver for patients with highly variable glucose levels and severe risk of hypoglycemia.

Immature beta cells- Another variation of the stem cell therapy may be derived from our ability to now image the pancreatic tissue at unprecedented resolution. Scientists from the University of California, Davis identified an immature population of beta cells which can produce insulin but, unlike mature beta cells, are unaffected by the presence of glucose in the blood since they do not have glucose receptors. This discovery could lead to a deeper understanding of how beta cells function, and these immature cells can be manipulated to produce more insulin to keep the glucose levels in check. In February 2018, researchers at the University of Miami identified the exact anatomical location of pancreatic stem cells which can be stimulated to be glucose-responsive insulin-producing cells. Subsequently, University of California, San Francisco reported that beta cells can be ‘trained’ to adapt to a deficiency in oxygen and nutrients due to exposure before and during the transplantation, ideally ensuring an endless supply of insulin-producing beta cells.

IgM immunotherapy- The antibody IgM has been used as a diagnostic marker for Type I since the early 2000s. A team of researchers at the University of Virginia have found a new role for IgM as a vaccine against Type I autoimmunity. Injecting human IgM into diabetic mice resulted in a reduction of autoimmune reactivity, restoration of the balance of cells in the pancreas and reversal of Type I.

Methyldopa- This is a classic case of serendipity in science. Methyldopa is a clinically approved drug to treat hypertension. Scientists at the University of Colorado and the University of Florida screened all FDA-approved small molecules to check if any of them could prevent the autoimmune pathway of Type I from getting activated and Methyldopa was a successful candidate. After successful experiments on mice and a pilot clinical study, the drug can be developed as a vaccine to prevent Type I in those at risk.

Vaccines- Enteroviral infections are known to cause Type I in newborns by triggering an autoimmune response against islet beta cells. At the University of Finland, scientists have developed a vaccine that can potentially eliminate enteroviruses and thus prevent Type I. Another common vaccine B.C.G. used routinely against tuberculosis has been used by doctors at the Massachusetts General Hospital as a vaccine against Type I. They have been successful in a pilot clinical trial by reducing the insulin dosage to one-third of the patient’s initial requirement even after 5-10 years of the vaccination.

The DiRECT study from the Newcastle University, the UK with 300 diabetics aged 20-65 demonstrated that a severely calorie-restricted diet can result in remission of Type II in around 86% of the patients. This is a very promising result since there is a rapid increase in obesity and Type II. A strict weight loss intervention may be a means of both prevention and cure of Type II diabetes. Interestingly, Lorcaserin, a weight loss drug was reported by Harvard University to reduce the incidence of diabetes and the risk of hypoglycemia in patients being treated for obesity. This is supported by multiple recent findings from the neurobiology community that obesity results in activation of the microglia cells in the brain and results in impaired modulation of hormones and increased glucose levels or resistance to insulin and hence treating obesity would also reduce the likelihood of an array of metabolic disorders.

Wearable technology has translated to better diagnostic and monitoring devices for diabetes. We have had home kits for monitoring blood glucose levels since 1981, but almost all variants require blood by pricking the finger with a lancet. A proof-of-concept study in South Korea of a wearable glucose monitor in the form of contact lenses has been successfully tested in rabbits. The silicon lens has an outward facing LED which is switched off in response to high levels of glucose in the tears as detected by a sensitive nano-sized glucose monitor. While this technology needs more work before it can be available for humans, it is a step in the direction of real-time, non-invasive glucose monitoring. Another variant of the wearable monitor is a color-changing tattoo ink with liquid biosensors developed by MIT and Harvard Medical School which can detect changes in the glucose levels, pH or salt in the interstitial fluid between the cells. This study is currently in research mode with no plans for clinical trials. However, the possibility of using the human skin as an interactive display for physiological monitoring is extremely attractive for developing non-invasive diabetes management products as is the case with an armband that can monitor the glucose in sweat via an ionic sensor. The simple bioengineered product from the University of California, Berkeley is primed for continuous monitoring of not just glucose, but also sodium, potassium, body temperature and other physiological parameters with a fully integrated electronic system that can log and update the data into a mobile device, making non-invasive continuous monitoring a possibility.

The Mexican cavefish has been established as a new model organism for studying diabetes. It’s a blind fish that lives deep in the sea with no access to light and food for long periods of time. It has evolved to survive these harsh conditions by having an insatiable appetite and insulin receptors which do not respond in the presence of high blood sugar. As a result, the cavefish is severely diabetic but can function normally. While this physiological make-up is fatal to humans, understanding the function of the glucose regulation in cavefish may be vital to developing novel therapies for diabetes management and cure.

With medical technology advancing fast, we may be looking at a future with the potential to decrease healthcare costs worldwide to deal with diabetes in its diagnosis, management, and prevention.

Sahana Shankar is a Ph.D. candidate in Structural and Molecular Biology at Academia Sinica, Taiwan. When she is not extracting protein, she loves to travel, read and writes scicomm articles. Her passion is to translate the science in fascinating research papers in health and medicine into common parlance. She believes understanding the science behind the world around us is indispensable to our engagement with it. She has contributed to Brainwave, a children’s science magazine from the Amar Chitra Katha family and Newslaundry, an independent news portal.

Christopher Fetsch, an assistant professor of neuroscience at Johns Hopkins and a researcher in the university’s Zanvyl Krieger Mind/Brain Institute studies how the brain makes decisions by weighing information coming in from the various senses. He knows elite athletes are making these choices faster and more accurately – at least when it comes to decisions related to their sport.

Take an Olympic skier– They’re flying down the slope and see a gate. Do they go left or right? It’s a seemingly easy choice, but a very tough computational challenge for the brain. The skier must evaluate what they see ahead as they move. The feel of the snowpack, their speed, the tilt of their body. But because they’ve skied slopes like this thousand of times, by the time they’re on an Olympic course, at that gate, their brains know just how to merge this disparate sensory information. Though the brain of someone who’s never skied would be at a loss, the Olympian’s brain has expertise at this precise equation of speed and snow. In about the time it takes to blink, the skier has settled on an informed plan. The entire run is a sequence of these decisions.

“What set elite athletes apart from us is not necessarily their body, their strength or their agility, Fetsch says. “What really sets apart the gold medalists from just the also-rans is the quickness and flexibility with which their brains are converting input from their senses into commands to move their muscles. These rapid-fire decisions that a skier gains extra hundredth second and has to make going down the slope.”

Kathleen Cullen, a professor of Biomedical Engineering and co-Director of the Johns Hopkins Center for Hearing and Balance says when Olympic figure skaters, snowboarders and ski jumpers execute breathtaking spins and flips; they pull them off because of two fundamental improvements in the way their brains work.

First, their brains have built intricate models for the sensory input that comes in during a proper triple Salchow or Lutz.

Everyone’s brain builds models – typically for ordinary tasks like walking down the street or climbing stairs. But years and years of practising elaborate, disorienting moves has forged considerably more complex models in the brains of elite athletes, Cullen says. While an Olympian is rotating or upside-down, their brain is crunching data coming in from the eyes with what the inner ear knows about motion and spatial orientation and combining it with even more information from the nerves and muscles. If the flip is on point, the brain knows. If it’s not, the brain knows how to fix it.

“Think of a snowboarder doing a double McTwist or some daring manoeuvre that gives us all the chills,” Cullen says. “What they’ve done is they’ve practised that manoeuvre over and over and over again. So that they’ve built a very sophisticated model of the sensory flow they expect during that routine. And what’s also very unique about these athletes is when there’s a mismatch between what they expect and what actually occurred, rather than panicking, they can recalibrate on the fly to deal with the new constraints.”

Next, the brains of Olympians have learned to ignore sensory signals that make regular people dizzy. Dizziness happens after spinning because the inner ear sends an incorrect signal to the brain. In everyday life, the inner ear sensors responsible for this error provide our perception of rotation and generate eye movements that help keep the world looking stable as we move through it. But when we stop spinning, inner ear fluid keeps moving due to inertia. And also makes the eyes continue to move. We feel like the world is still whirling. But Olympians, skaters, in particular, do not. Their brains have changed to quash the feeling.

If you look at athletes who do a lot of spinning in training, what they’ve learned to do is suppress this false input,” Cullen says. “Over time their brain develops this ability.”

According to Vikram Chib, assistant professor of biomedical engineering–
Take two equally talented, trained and fit Olympians. If

Chib could compare their brain scans. He’d have a good idea about which one is most likely to choke under pressure during the games. It’s whoever is most excited about winning gold, and all the pride, glory and potential cash that comes with it. Chib studies how incentives motivate performance. He’s found that when people are playing for high stakes, those likely to choke have wild swings of activity in an area deep in the brain that encodes the value. In these people, the bigger the incentive, the more the area lights up. But once they start the activity where money is on the line, that activity plummets. The same way it would when someone thinks about losing. That neural deactivation can affect the player’s motor skills – and they choke.

“Think of a hockey player taking a penalty shot,” Chib says. “They might think to themselves, I’m going to score. But when they actually take the shot, they become worried about the possibility of failure and they miss. We think that the areas of the brain that are responsible for encoding reward. And potential gains and losses are what’s coming online and interfering with their motor performance. Even a hockey player who trains thousands upon thousands of hours. These worries about loss or gain can interfere with their performance.”

The athletes most likely to bring home a medal, Chib says, are either hard-wired to keep their cool when the stakes are high, or they’ve found a way to get mentally in the zone.

“We found when you frame things appropriately; your neural activity stays pretty constant. You don’t get really amped up for high gains or really depressed for losses,” he says. “The people that can maintain very stable reward activity tend to be the ones that don’t choke under pressure.”

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