For people who struggle with overweight or obesity, receiving a diagnosis of type 2 diabetes (T2D) can feel like a point of no return. Whereas before they might have felt some semblance of control, they are now suddenly facing an intractable, progressive disease that will be with them for the rest of their lives. For the well over 400 million people with T2D globally,[1] however, emerging evidence suggests that this outlook may be outdated. Recent studies have suggested that T2D can actually be reversed, not through novel pharmaceutical treatments but through strict adherence to certain dietary interventions. "Dietary and lifestyle factors are gaining attention for sending type 2 diabetes into remission." Although elements of these studies are still being debated, including the accuracy of the term "reversal," they are nonetheless changing management strategies for this pervasive disease and restoring a measure of autonomy to patients. Diets That Erase Disease Evidence has long shown that remission of T2D can occur after bariatric surgery for the treatment of obesity.[2,3] However, the risks inherent in undergoing this major surgery limited its wide application. Two key recent studies are gaining attention for a more moderate approach to sending T2D into remission: dietary and lifestyle factors. In late 2017, researchers for the Diabetes Remission Clinical Trial (DiRECT)[4]reported findings from 298 people diagnosed with T2D within the past 6 years and not receiving insulin. One half of the patients were randomized to be treated under current best practice guidelines, and the other half to undergo an intensive weight management program requiring them to commit to 3-5 months of a low-calorie liquid diet not surpassing 850 total daily calories, with gradual food reintroduction over the next 2-8 weeks and continual weight-loss support. After 1 year, 24% of participants in the low-calorie diet group experienced weight loss ≥ 15 kg and 46% experienced remission of diabetes, compared with no participants and 4% in the control group, respectively (P < .0001). This study was followed by a separate analysis[5] that showed similarly encouraging results in a cohort of 349 patients diagnosed with T2D approximately 8 years prior. Patients received either usual care (87 patients) or a low-carbohydrate diet (262 patients) accompanied by continuous care that included Web-based consultation with a health coach and medical provider. Sixty percent of those in the low-carbohydrate group achieved an A1c level < 6.5 while taking no diabetes medications or metformin only. Unlike in DiRECT, patients were allowed to take insulin at study onset (30% in the low-carbohydrate group and 46% in the usual care group). After 1 year, patients in the usual care group had no significant changes in study biomarkers. Conversely, 60% of those in the low-carbohydrate group achieved an A1c level < 6.5 while taking no diabetes medications or metformin only. There was also a 12% weight loss, 24% reduction in triglyceride level, 18% increase in high-density lipoprotein cholesterol level, and 39% reduction in C-reactive protein level. According to Sarah Hallberg, DO, the study's principal investigator and medical director of Virta Health and Indiana University Arnett's Medically Supervised Weight Loss Program, the 94% rate of reduction or outright cessation of insulin in this group is particularly noteworthy. "I like to say that although I specialize in diabetes, my primary specialty is in deprescribing," Hallberg says. "The way that we treat T2D is we take a problem whose underlying cause is too much insulin, and then throw more medication at it to increase the insulin even further. It's essentially hitting the speed button on a vicious cycle." Is It 'Reversal,' or Something Else? "These two articles bring back to life, using modern approaches, things that we've known since the 1970s and possibly as early as the 1960s, which is that weight loss is beneficial in preventing diabetes progression and can reverse or improve substantially established diabetes," says Domenico Accili, MD, professor of medicine at Columbia University and director of the Columbia University Diabetes and Endocrinology Research Center in New York City. However, Accili takes a cautious approach when using the term "reversal" to describe these studies' effects. One would have to show that...the underlying pathophysiology that generates the abnormal glucose regulation on a regular diet has actually been improved or reversed. "I don't think that [all] forms of diabetes are reversible at any stage or forever," he says. "In patients with early-stage disease, diabetes can be reversed for some time, but we don't know for how long or at what stage the disease becomes irreversible." It's a point that is echoed by Kevin D. Hall, PhD, chief of the Integrative Physiology Section at the Laboratory of Biological Modeling at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland. In an interview with Medscape, as well as in a recent review paper on the topic he coauthored,[6] Hall notes that "reversal" is a relatively bold term. "In order to make that claim, one would actually have to show that not only was glucose controlled or well-treated, which is the diagnostic marker of diabetes, but that the underlying pathophysiology that generates the abnormal glucose regulation on a regular diet has actually been improved or reversed in some sense," he says. "Therefore, if you reverse those, you would then expect that the person could resume a normal lifestyle, including eating a normal diet while maintaining normal glucose levels." Although he notes that studies such as these represent important progress in the treatment of T2D, Hall cautions for the need for randomized controlled trials testing different diets and for increased phenotyping of the underlying disease. "I would like to see euglycemic hyperinsulinemic clamps with tracers to find out how the different organs are responding to these diet interventions and whether or not most of the effect is occurring in the liver versus the muscle versus adipose tissue," says Hall. For her part, Hallberg has heard the criticism regarding the term "reversal" but finds it a useful description for patients, provided that they understand the full scope of its meaning. "We tell patients every day that we are not curing this disease, though I hope we can someday. If you eat the way you used to, this will come back," she says. A Beacon of Hope In a 2013 review paper,[7] Roy Taylor, MD, principal investigator for DiRECT, reported receiving thousands of emails from patients with T2D after the publication of initial findings from this trial.The concept of T2D reversal had untapped a level of engagement and optimism that many weren't getting from their own doctors. Hallberg also says that when she brings up the topic of T2D reversal with her patients, they tend to exhibit a wide range of new emotions. Elation at hearing that they can tackle their disease head on may soon turn to anger about the time they feel they had lost while not doing so, before eventually settling into determination to move forward. Hallberg says that this determination is evident in the 83% of participants in the low-carbohydrate group who remained in the study at final follow-up. Yet questions remain about whether one diet is superior to other interventions. In addition to the caloric restriction strategies that have been a cornerstone of the research in DiRECT and other studies, data from comparatively smaller analyses of the Mediterranean diet[8] and intermittent fasting[9] have also reported them to result in T2D reversal. There is also an ongoing debate regarding the so-called carbohydrate-insulin model of obesity and its role in T2D, most recently played out in two contrasting editorials published in JAMA Internal Medicine.[10,11] "I'm not saying that the low-carbohydrate diet should be the only option we offer to patients, because that [would also] take control away from them, which is exactly what I want to fight against," says Hallberg. "But this is a nonsurgical intervention that does not force patients to cut calories, which makes it very sustainable." She adds that another advantage of the low-carb diet is that patients can be objectively monitored for adherence through blood ketone levels. Is It Ever Too Late? An important question is whether dietary interventions will cease to prove effective in those with long-term T2D. Beta-cell function is thought to be 50% reduced at the time of diagnosis[7] and to decrease further as time goes on. Within 10 years of receiving a diagnosis of T2D, one half of patients require insulin.[12] Is there a point where it's too late to institute these dietary interventions? "It was once thought that in people with diabetes, insulin-producing cells would slowly die away and contribute to the impairment of glucose metabolism," says Accili. He adds that the current prevailing theories are that beta cells remain dormant in the body until they can be reactivated through various means, or that beta cells do not return to function but rather the existing cells function better. Then there is the question of basic, frustrating physiology. "There is great merit in dietary interventions, but they're difficult to implement," Accili says. "The bottom line is that we're evolutionarily rigged to gain and not lose weight, which is a signal of distress that the body fights tooth and nail." For patients, however, the knowledge that T2D can potentially be reversed might be all the strength they need to fight back. Source
