Type 2 diabetes has long been understood to be a chronic condition that progresses over time, but some internists are challenging that paradigm by aiming to reverse their patients' diabetes.
Susan Wolver, MD, FACP, said she changed how she thought about counseling patients with diabetes after noticing her own weight creeping up despite following the low-fat, eat-less-move-more dietary advice she had doled out for decades. “I realized that maybe it wasn't that my patients weren't following my advice; maybe my advice was wrong,” said Dr. Wolver, an associate professor of medicine at Virginia Commonwealth University School of Medicine in Richmond.
After finding success with a low-carbohydrate diet, she started to practice obesity medicine and pass along what she'd learned to her patients. “What happened next was nothing short of miraculous. I saw people's diabetes improve. I saw people lose weight. I saw people have more energy,” she said. “I saw the same people have more confidence and really change their lives.”
Research indicates the potential for dietary interventions to send type 2 diabetes into remission. Experts explained how they help patients achieve remission and outlined the caveats of their approaches.
Although patients may ask about a “cure” for diabetes, the term “remission” may be more accurate to use, according to a 2009 consensus statement by the American Diabetes Association (ADA). The ADA defined “partial remission” as hyperglycemia below diagnostic thresholds for diabetes for at least one year with no active medication therapy or ongoing procedures. The definition of “complete remission” included the same criteria but with normal glycemic measures, and “prolonged remission” was defined as complete remission for at least five years.
Not uncommonly, remission from type 2 diabetes occurs in patients who have had bariatric surgery. Researchers have found that remission without surgery, however, is rare. In a cohort of 122,781 adults with type 2 diabetes in the Kaiser Permanente Northern California system, the seven-year cumulative incidence of achieving any kind of remission without surgery was only 1.6%, according to a 2014 study in Diabetes Care.
But newer research suggests that, with intensive lifestyle interventions and some help from modern technology, more patients may now have the support they need to achieve and maintain diabetes remission. “In this day and age, there is no question that if one improves one of the pathophysiologic causes of type 2 diabetes, which is insulin resistance, one may be able to normalize blood glucoses,” said endocrinologist Diana B. McNeill, MD, MACP, professor of medicine at Duke University School of Medicine in Durham, N.C.
One fee-based specialty clinic, Virta Health, uses an individualized ketogenic diet, a very low-carb dietary approach (typically <30 g of total carbs per day) used to achieve nutritional ketosis, while providing continuous remote monitoring. Through telemedicine, health coaches provide ongoing support, and physicians keep an eye on medications, symptoms, comorbidities, and patients' daily measurements of blood ketones and fasting and postprandial blood glucose levels.
Most of Virta's patients have employer-sponsored health plans through self-insured employers, such as Purdue University, which offer the service as a fully covered benefit for type 2 diabetes, said ACP Member Jeff Stanley, MD, a Virta physician in Portland, Ore. On the other hand, patients who pay out of pocket incur a monthly fee of $370, plus a $500 starter-kit fee, according to the company's website, which also notes that its costs are not covered by most insurance plans.
In a recent study, Virta researchers compared changes at one year in HbA1c, weight, and diabetes medication use (other than metformin) in 262 adult patients using their model to 87 patients receiving usual care from their doctors and a diabetes education program. On average, those in the intervention group saw their HbA1c levels drop from 7.6% to 6.3% while losing 12% of their body weight and reducing the use of diabetes medications. In contrast, patients in the usual care group had no significant changes in HbA1c, weight, or diabetes medication use, according to results published in February 2018 by Diabetes Therapy.
Dr. Stanley, who has practiced telemedicine for the past two years with Virta, said his No. 1 job is to safely deprescribe medications as patients make dramatic changes to their diets. The need to do so rapidly arises. “There's this common misconception that in order to reverse diabetes or get off the medications, you need to have this large, dramatic weight loss,” he said.
While ample weight loss may be the key to remission for many patients, it's not necessary for all. Remission varied with weight loss in the cluster-randomized DiRECT study, published in December 2017 by The Lancet. Overall, 36 (24%) of 149 patients assigned to receive a weight management program maintained a weight loss of 33 pounds or more at 12 months, yet 68 (46%) managed to achieve remission, including a handful who lost zero to 11 pounds.
Dr. Wolver said that with dietary changes that target insulin resistance, her patients are able to achieve remission before losing any substantial amount of weight. “In fact, I had one patient recently that I saw that came off of 240 units of insulin in three weeks, so they have yet to lose the recommended amount needed to put diabetes in remission,” she said.
One criticism of the Virta study is that it wasn't a randomized trial. Positive results from two small randomized trials of the ketogenic diet, however, prompted the ADA to add language to its 2018 guidelines noting that clinicians can consider the ketogenic diet as a short-term strategy (up to three or four months) for diabetes if a patient wants to try it.
Another small but longer trial, published in December 2017 by Nutrition and Diabetes, randomized 16 adults to a very low-carb ketogenic diet and 18 adults to a moderate-carb, low-fat, calorie-restricted diet. At 12 months, participants following the ketogenic diet had greater reductions in HbA1c levels (6.6% to 6.1%) than those on the other diet (6.9% to 6.7%), as well as lost more weight and experienced larger reductions in diabetes medication use. Eligible participants had to be willing to eat either diet, be willing to do at-home glucose monitoring, and have sufficient control over their food in order to follow the protocol. Vegans and people taking insulin or more than three oral hypoglycemic medications were excluded from the trial.
“We're seeing that these results can occur even in randomized controlled trials, and then ones that are becoming increasingly long in length,” said Dr. Stanley, adding that two-year data from Virta are forthcoming.
A shift in practice
In 2015, there were more than 100 million people living with diabetes or at increased risk for diabetes in the U.S., according to CDC estimates. In treating these patients, physicians tend to focus on treating and managing the blood glucose without addressing the underlying insulin resistance, according to Manuel Lam, MD, ACP Member, a hospitalist who also sees patients twice a week at a California-based metabolic health clinic.
“In order to think about diabetes as a reversible disease, we really have to think about a paradigm shift in terms of what diabetes is and what we're actually treating,” said Dr. Lam, who uses dietary approaches of a ketogenic diet and intermittent fasting (i.e., restricting calorie consumption to a certain time window) to correct insulin resistance. “If you make the blood sugar look pretty, but you make the insulin resistance worse, then that is not treating the patient's core issue, which is insulin resistance and hyperinsulinemia.”
This shift in thinking is becoming more common as doctors have gained a better understanding of obesity and its treatment options, as well as newer medications, such as glucagon-like peptide (GLP)-1 receptor agonists and sodium glucose co-transporter 2 (SGLT2) inhibitors, that can help patients improve their blood sugars and lose weight at the same time, said Lance Sloan, MD, ACP Member, an endocrinologist and nephrologist.
Before, taking medicines like insulin and sulfonylureas made it even more difficult for patients to lose weight, which meant that doctors failed to address the underlying “VIRAS,” or visceral insulin-resistant adiposity syndrome, he said. “As far as I'm concerned, if your patient's gaining weight at the same time you're lowering the blood sugar, you're only treating half of the picture. You're reducing the risk for microvascular complications, but you're doing nothing to reduce the risk for macrovascular complications,” said Dr. Sloan, who is president and chief medical officer at the Texas Institute for Kidney and Endocrine Disorders in Lufkin, Texas.
To better educate patients, internists and primary care doctors should explain that type 2 diabetes is essentially a disease of too much sugar in the body, not just in the blood, said Jason Fung, MD, a nephrologist who runs an intensive dietary management clinic in Toronto.
“It's a dietary disease, so therefore the treatment demands a dietary solution,” he said. “If we are putting too much sugar in, then we only need do two things: Don't put more sugar in, [and] burn off the sugar in the blood.”
Although a dietary approach to diabetes remission requires consistency, it need not be drastic, said Dr. Fung, who recommends reducing intake of added sugars and refined carbohydrates, avoiding snacking, and practicing intermittent fasting.
“Intermittent fasting is one of the easiest methods that anybody can understand and does not require special clinics: Just don't eat for a period of time,” he said. “It seems obvious that if you don't eat, your blood sugars will drop. … I think that standard advice for diabetics (50% carbs, low-fat, eat six times a day) is completely disastrous.”
Despite following everything by the book on diabetes management, Priyanka Wali, MD, an internist practicing in San Francisco, noticed her patients' numbers wouldn't improve unless they changed their diets. But residency and medical school offered little education about nutrition, she said, and it wasn't until becoming certified in obesity medicine that she learned basic macronutrient metabolism and the benefits of a strict low-carb diet for diabetes.
Most patients don't want to have diabetes, incur its complications, or manage the condition with medications indefinitely, said Dr. Wali. When a patient is at increased risk for diabetes, she discusses its complications very early on and how to reverse them before they become permanent, such as end-organ damage.
“I'll say, ‘Fortunately, we can turn this ship around, and we can reverse all of this if you change your diet,’” Dr. Wali said. “Usually by that point, in most cases, the patient and I are on the same page, and then we work on it together and I educate them about the diet aspect of it.” In April, she joined Virta in a part-time capacity.
Carbs are not the only enemy afoot, noted Dr. McNeill. As type 2 diabetes rates have rapidly grown in recent decades, so has the abundance of processed foods. “We keep talking carbs, but I actually think it's processed foods. I think it's taking food from its natural form and putting all this stuff in it to make it taste better, including and not excluding artificial sweeteners. … What is that doing to our bodies?” Dr. McNeill said.
Dr. Sloan added that since extreme diets tend to be hard to follow in the long term, he gives simple recommendations, like eating vegetables instead of the “four bad whites”: white sugar, white flour, white rice, and white potatoes.
However, ACP Member Brian Lenzkes, MD, an internist practicing in San Diego, said he tried a very low-carb diet himself in 2017, proceeded to lose 45 pounds, and found it enjoyable to maintain. Although some may call a low-carb diet for diabetes radical, it's actually a return to old ways, he said. When a patient brought in a medical textbook from 1911, Dr. Lenzkes noticed that the recommendation for diabetes was a high-fat, low-carb diet. “That's all they had—they had no insulin until 1921,” he said.
Since then, insulin has become a mainstay in managing severe diabetes. In 13 years of practice, Dr. Lenzkes said he had previously never taken a patient with diabetes off insulin. “I've had 11 people come off insulin over the last year by watching their carbs,” he said.
Dr. Wolver recalled a young patient who was referred to her after a first diagnosis of diabetes with an HbA1c of 11.1%, a level that traditionally warrants treatment with insulin. “But I know after decades of practice that … if she was started on insulin, she would never come off insulin,” she said. Instead, Dr. Wolver started the patient on metformin and a low-carb diet and, after three months, the patient lost 24 pounds and her HbA1c dropped to 6.1%. “Her life would be so different if I or a colleague had treated her 10 years ago,” she said, acknowledging that she has an advantage over primary care doctors because most patients she sees are already motivated to make lifestyle changes and improve their diabetes.
Insulin levels in the body are also important, but doctors rarely check fasting insulin levels, said Dr. Lenzkes, who now does so in his patients with diabetes and those who are struggling with their weight.
“It's like your check-engine light. When your insulin's super high, it tells you that you might not be in trouble now, but the pancreas just can't keep making insulin like that,” he said. “That's when we start getting this insulin resistance problem, and then people start getting diabetes.” Dr. Wali said she also checks her patients' insulin levels.
However, Dr. Stanley said he does not routinely check patients' insulin levels, even though the test can be very useful. “Depending on people's health coverage, it can be a fairly expensive test, and it's not one that's widely adopted,” he said. “It would be great if it was more broadly available and less expensive.”
There are caveats to consider when attempting remission of type 2 diabetes. First, know that any approach used for diabetes reversal, whether it's a ketogenic diet, severe caloric restriction, or bariatric surgery, can produce rapid and dramatic effects, Dr. Stanley noted. “So it's important that people have a way to monitor for patients who are on medications,” he said.
Many patients have heard of low-carb or ketogenic diets in newspapers or on TV, which raises concerns for Dr. Wolver, especially if patients are on medications.
“Usually the first day I start someone on this diet, if their A1c is well controlled, I'll probably halve their insulin before they've even lost an ounce,” she said. “So if they go and try this on their own without any appropriate guidance, it could be very concerning.”
The same goes for patients who are on blood pressure medications, especially diuretics, since diuresis typically occurs at the start of the diet, Dr. Wolver added.
In general, there are few contraindications to a very low-carb diet, although some people do have rare genetic issues with fat metabolism, Dr. Stanley said. “In general, that's something someone would know from infancy, and it's not something that we routinely see,” he said. Other contraindications are glycogen storage diseases and porphyria, which is rare but can occur in adulthood, Dr. Stanley said.
Still, patients need to be self-motivated to make lifestyle changes, noted Dr. Sloan. “They're not completely on their own. Hopefully, they'll have a team of a physician and maybe a dietitian and maybe others that can help educate them correctly, but … the kind of expert piece and program that can help them be successful is sometimes hard for them to find,” he said.
Yet insurance companies often interfere with medication recommendations and clinical decision making by creating barriers to patients and physicians obtaining newer, nongeneric medicines that have been shown to improve blood glucose control, reduce weight, and decrease the risk of hypoglycemia and cardiorenal disease, said Dr. Sloan. “These medications are complementary to diet and exercise and can help motivate a patient to stick with a diet and exercise program,” he said.
Although SGLT2 inhibitors may not be the best choice for people on severely restricted ketogenic diets, the drug class can be safely used in people on low-carb diets, Dr. Sloan noted. In general, the longer one has diabetes, the more difficult it is to achieve remission, he added.
Another caveat is in documenting remission, according to Dr. McNeill. “I think we have to be careful because … the minute I pull a diagnosis off of a list, we stop thinking about it,” she said.
In cases where a patient is able to achieve normoglycemia, removing diabetes from the problem list may allow patients to be viewed differently by insurers, Dr. McNeill noted. However, she emphasized the importance of noting a history (perhaps “history of hyperglycemia—resolved”), which may become relevant for monitoring purposes or if, for example, a future course of high-dose steroids causes the patient to develop hyperglycemia. “I'm less worried about the diagnosis,” she said. “I'm more worried about the side effects of having hyperglycemia: the cardiovascular and renal side effects, the neuropathy. I want those to be prevented.”
Experts agreed that continuous support is integral to maintaining diabetes remission. In particular, a mental health component of care is crucial to address such issues as cravings, motivation, emotional eating, and stress management, added Dr. Wolver, whose obesity medicine practice team includes health psychologists, who specialize in the behavioral, social, and other factors that affect physical health.
“I think the biggest game-changer of low-carb is it really takes away hunger, so all the rest is the mental health part of trying to stick to something long-term in the face of a society that, quite frankly, reveres and celebrates sugar and carbohydrates,” she said.
Maintaining lifestyle changes is notoriously difficult but possible if patients have the desire and the tools to succeed in the long term, experts said. Patients need individualized advice that works for them in addition to ongoing support in order to achieve successful diabetes remission, said Dr. Stanley.
“It requires ongoing lifestyle intervention. It's not something where all of a sudden it's a magic pill and then someone no longer has diabetes,” he said.
Dr. Wolver said that in the future, diabetes remission will be facilitated by telemedicine, an element she plans on adding to her own practice.
“That is absolutely the key to success: frequent, individualized contact,” she said, adding that she's particularly excited to see patients at night in their homes, where they can “walk” her to their refrigerators and pantries. “Hopefully, we'll be able to start to move the needle and make this much more mainstream, because what we're doing changes people's lives.”