Researchers are constantly adding to what we know about managing this serious health threat
By Wendy Haaf
Mario Miceli will be the first to tell you that when he was diagnosed with Type 2 diabetes about a decade ago, he didn’t think it was a big deal.
“My view was, if I wasn’t having to take needles, then it mustn’t be that serious,” recalls the retired Burnaby, BC, insurance executive, now 57. “There wasn’t a lot of discussion about the complications.” Miceli was also reluctant to test his blood sugar; not only did he dislike inflicting the pain of finger jabs on himself, he also wanted to hide his health issue from the people around him. “I didn’t want to admit to my diabetes, so I wouldn’t test when I was at the office; in fact, I didn’t even carry a kit,” he says. Because he was very career-focused back then, he says, “I thought it would matter if I was seen as someone with Type 2 diabetes, because there’s a stigma attached to it—people think you’ve caused this yourself.” (That notion is false. “You don’t get Type 2 diabetes unless you’re genetically susceptible,” says Dr. Hertzel Gerstein, a professor of medicine and the Population Health Institute chair in diabetes research at McMaster University in Hamilton, ON.)
While Type 2 diabetes, which affects roughly one in five Canadians over 60, is no less serious today than it was when Miceli was first diagnosed, in just the past few years, there’s been a burst of new therapies for reducing the risk for common complications such as heart attack, stroke, kidney failure, nerve damage, amputations, and vision loss. In this same period, there have also been leaps forward in technological tools for helping to manage blood-sugar levels, as well as advances in knowledge about measures that can prevent Type 2 diabetes or even push it into remission.
“We’re living in a remarkable time in the diabetes world,” says Dr. Stewart Harris, a professor and the Diabetes Canada chair in diabetes management at Western University’s Schulich School of Medicine & Dentistry in London, ON.
Bloodless Continuous Monitoring
No doubt one of the innovations most welcome by people with Type 2 diabetes is a move away from the finger lancet: you no longer need to prick your finger to test your blood-sugar level.
“You wear these little patches about the size of a toonie on the side of your arm,” Harris explains. (The devices are known as continuous glucose monitors, or CGMs.) Each contains a tiny sensor that sits just beneath the skin, where it measures blood-glucose levels. The CGM translates the result into an electrical signal and sends the information to “a Bluetooth reader, which is either your phone or a glucose meter,” Harris says.
This gives you the power to check your blood-sugar level at any time, as often as you like, and detect patterns. “So now, we’re not just looking at keeping our blood sugar in check, but monitoring how long in a 24-hour session we’re within the desired range,” Miceli says. This provides the opportunity to experiment to find out which foods cause your blood-sugar level to surge, since two people might react very differently to the same food.
For Miceli, for example, one of the worst offenders turned out to be white rice. “I’m a huge sushi fan, and sure enough, the rice in sushi is the one that hits me,” he says. With that knowledge, someone can either switch to a different food—sashimi, in Miceli’s case—or calibrate the portion size that will keep his or her blood sugar within range. (Unfortunately, provincial health plans don’t cover the ongoing costs of CGM devices: typically close to $2,500 a year, according to Diabetes Canada, with each sensor—about $90 each—lasting about two weeks.) In Harris’s clinic, “These sensors have been a tremendous tool to reinforce the old basics of lifestyle management,” he says. (All the tasks involved in managing Type 2 diabetes, such as having to stop and think about what you’re putting in your mouth before every meal or snack, eats up a lot of mental bandwidth.)
Promising Strategies for Inducing Remission
“It’s become very established within the last five years that if people happen to be particularly heavy, then bariatric [weight-loss] surgery can cause diabetes remission in 30, 40, or even 50 per cent of people,” Gerstein says. “That remission can last, often, not forever, but for a long time.” Since this remission typically occurs before patients shed a substantial amount of weight as a result of the procedure, scientists are trying to unravel the underlying explanation so that they can find a way to replicate the effect non-surgically.
Researchers, including Gerstein and his colleagues, are also “testing drug regimens that don’t require that much weight loss to see if these can work to produce remission, as well,” Gerstein says.
Scientists in Alberta are taking a slightly different approach, building on previous research demonstrating that following a low-energy diet (LED)—in the neighbourhood of 900 calories a day, and typically achieved using meal-replacement bars or shakes—for a set period may pave a similar path. “In some studies, 50 per cent of people with Type 2 diabetes achieved remission,” explains Normand Boulé, a professor and the associate dean of graduate programs in the Faculty of Kinesiology, Sport, and Recreation at the University of Alberta in Edmonton. (Factors linked with increased odds of success include recent diabetes onset, good blood-sugar control, and loss of about 15 per cent of excess body weight.)
In one such trial, called the DiRECT study, 46 per cent of subjects provided with low-energy diets for three to five months before returning to more regular daily caloric intakes achieved remission, “yet many were able to sustain these remission rates for almost two years,” Boulé observes. A possible contributor to this result is that, in studies of low-energy diets, “liver fat can be reduced by 30 per cent in a short amount of time,” Boulé notes. “The liver can play an important role in insulin resistance and releasing glucose out into the circulation,” he explains. (One of the problems in Type 2 diabetes is that the cells in the body become increasingly less able to use insulin to process glucose—a phenomenon known as insulin resistance.)
It’s long been known that exercise can improve blood-sugar control and, with modest weight loss, reduce the odds by about half that pre-diabetes will progress to bona fide Type 2 diabetes within five years. Boulé is interested in finding out whether adding exercise could overcome two of the drawbacks to weight loss via LED alone. In this scenario, “about 25 per cent of the weight loss happens to be lean body mass,” he explains. Since older adults have often already lost substantial lean muscle mass—key to maintaining independence—this further loss “is something to be a little concerned about,” Boulé says. Moreover, LEDs obviously don’t improve fitness, and poor fitness is “a strong predictor of heart disease, which is the No. 1 killer of people with Type 2 diabetes.
“The study we’re preparing for is called the RESET for Remission Trial,” Boulé says. At two sites in Canada—the University of Alberta in Edmonton and McGill University in Montreal—and at another at the University of Leister in England, the study will follow volunteers aged 18 to 40 who have been diagnosed with Type 2 diabetes within the past six years, are overweight or obese, and have been tested to have glycated hemoglobin (A1C) levels—a valuable indicator of glycemic treatment effectiveness—between 6.5 and 10 per cent. (An A1C test gives an estimate of A1C blood-sugar readings over the three previous months.) “We’re looking at the effect on diabetes remission in this population after 24 weeks of a low-energy diet and supervised exercise training,” Boulé explains. “We’re also interested in looking at changes in body composition—hopefully exercise can maintain some of that lean body mass—as well as physical function, fitness, quality of life, and cardiovascular health,” he says.
Another study, already under way, “is called the FED—Fasted Exercise for Type 2 Diabetes—trial,” says Jordan Rees, a Ph.D. student in the University of Alberta’s Faculty of Kinesiology, Sport, and Recreation. Over 16 weeks, volunteers aged 30 to 75 “will come into the lab to complete walking sessions,” Rees says. Participants will be randomized to one of two groups: half will exercise in a fasting state—before eating breakfast—and half will do so after eating. Researchers want to find out “how exercise and nutrient timing might affect blood sugar,” Rees says.
One rationale for tinkering with nutrient timing is that your muscle cells need extra glucose when you exercise, and once they use up the supply circulating in your blood, with no food in the gut, the liver—which is a kind of energy reservoir—has to step in and release sugar. “We’re trying to see if we can deplete the energy reserves in the liver,” Boulé says. “In both studies, we’ll be collaborating with people who do magnetic resonance imaging [MRI] studies of the liver to see how liver fat is changing.”
Since it’s becoming increasingly evident that Type 2 diabetes is a diverse disease that doesn’t affect only older inactive people who are overweight or obese, but also “happens in younger people, very active people, and in people who are not obese,” Boulé says, the hope is that studies such as the one he’s involved in will eventually “help us tailor different interventions in a logical way for different people with Type 2 diabetes.”
A Move to More Individualized Treatment
In recent years, some people have criticized the current approach to treating Type 2 diabetes as placing too heavy an emphasis on A1C levels. For example, members of the Therapeutics Initiative at the University of British Columbia in 2017 reviewed the evidence to answer the question “Is the current glucocentric approach to managing Type 2 diabetes misguided?”
“The short answer is, Yes,” says Alan Cassels, the organization’s communications director. “It drives doctors crazy because they can’t give enough drugs to people to lower their blood sugar enough, and it drives patients crazy because they’re constantly chasing a lower number.” In fact, in randomized controlled trials comparing people who achieved lower target blood sugar (“tight control”) with those whose numbers stayed within a somewhat higher bracket (“conventional control”), “the people with tight control do worse—there’s more harm than benefit to tight control,” Cassels says. (The harm is mostly related to occasions when blood-sugar levels drop dangerously low.)
Another criticism, Mario Miceli says, is that “in Canada, we tend to have a cookie-cutter approach to how we manage Type 2 diabetes.” For instance, a conventional protocol might be: Start with drug A; if that medication doesn’t work, try drug B. However, a new document from the American Diabetes Association may herald a shift in approach. In 2020, the organization issued a monograph for primary-care providers who treat Type 2 diabetes (Gerstein and Harris are co-authors) advocating a more person-centred approach to care, taking into account coexisting conditions such as heart disease, heart failure, and kidney disease, along with a patient’s socio-economic situation and whether he or she has drug coverage (of course, this last condition is not as relevant in Canada, given our Medicare system).
Medications for Preventing Complications
Another exciting development is an accumulation of research showing that two relatively new classes of diabetes drug offer important benefits beyond lowering blood sugar.
One group, called GLP-1 (glucagon-like peptide 1) receptor agonists, are once-weekly injectable medications. “Data has emerged in the last few years about the tremendous benefits that they provide, both in people who have had previous heart attacks and strokes,” Harris explains, “and also in people at high risk for heart attack, stroke, and premature death.” Additionally, they bring “weight loss—sometimes substantial weight loss,” Harris says. (In fact, “they may mimic some of the effects of bariatric surgery in this way,” Gerstein notes.) What’s more, they carry “no risk for low sugar unless someone is on coexisting insulin,” Harris continues, and “they lower blood pressure.”
The second class of drugs, called SGLT2 (sodium-glucose cotransporter 2) inhibitors, “are pills that actually make you pee out sugar in the urine,” Gerstein says. “In people with diabetes, they can reduce premature death, heart failure, heart disease, kidney failure, and kidney disease,” he adds. “In fact, these have been the first new therapies for kidney disease in the past 25 or 30 years.”
But SGLT2 inhibitors don’t help only people with diabetes or kidney disease. “Some trials in non-diabetic patients have demonstrated these are heart-failure-treating drugs, whether you have diabetes or not,” Harris says. “They reduce hospitalizations and death from heart failure by 30 to 40 per cent.” That’s no small thing, since “the mortality rate from heart failure is about 50 per cent within five years,” he adds. “So these are an exciting addition to help people live longer and healthier.”
And that, after all, is the name of the game. “The goal is to improve quality of life, reduce harm, and improve the outlook for people with Type 2 diabetes,” Gerstein says. “The research is always trying to make that simpler and easier.”