William T. Cefalu, MD, director of the NIDDK’s Division of Diabetes, Endocrinology, and Metabolic Diseases, discusses type 2 diabetes remission, including recent research into strategies and mechanisms by which people who have diabetes can achieve remission.
Q: What is remission of type 2 diabetes? How do health care professionals define remission and know when a patient has achieved it?
A: People with type 2 diabetes who do not have adequate glycaemic control have an increased risk for diabetes complications. Glycaemic control is monitored by measuring both blood glucose and blood markers assessing antecedent glycaemia such as haemoglobin A1C, which reflects average glucose over the previous months. We define type 2 diabetes remission as having the condition revert to a nondiabetic range as assessed with blood glucose levels or blood glucose markers and staying in that range for at least 6 months when a person isn’t taking any diabetes medications.
It’s important for both health care professionals and people who have type 2 diabetes to realize that significant weight loss either from lifestyle intervention (i.e., diet and exercise) or from certain procedures can result in blood glucose levels decreasing into the nondiabetic range, and that achieving remission can minimize or prevent future complications.
Q: Why do health care professionals use the term “remission” rather than “cure” when discussing type 2 diabetes? What happens to a person’s diabetes when he or she relapses?
A: We don't use the word “cure” when we refer to blood glucose levels reverting back to levels below the threshold used for diagnosis, as you could argue “cure” means completely alleviating the condition. For example, an acute condition seen with infectious diseases such as bronchitis may be considered to be cured with antibiotics. However, in type 2 diabetes, because blood glucose levels are on a continuum and are significantly associated with weight, it is observed that when weight regain occurs, the glucose levels may increase back to the range associated with diabetes diagnosis. So, the correct term is “remission.”
Type 2 diabetes is a progressive disorder, and, at one time, we didn’t think that weight loss or other interventions could allow people with type 2 diabetes to lower their blood glucose levels into the nondiabetic range and to stay there for an extended period of time without medication. However, we now understand that people with type 2 diabetes who lose significant weight and improve other factors related to diabetes can achieve remission.
With sustained weight loss, people may stay in remission for quite some time. However, if they begin to put on weight, their blood glucose levels can increase and return to the diabetic range. They may need diabetes medications or even insulin with weight regain depending on the severity of their type 2 diabetes and their glucose control.
Q: What strategies can lead to remission of type 2 diabetes?
A: The most important factor in achieving remission is weight loss, and two techniques—metabolic surgery and lifestyle changes that restrict calories on a daily basis to achieve weight loss—have been shown to induce remission.
Some studies, dating back many years, have observed that metabolic surgery leads to high rates of type 2 diabetes remission. Recently, the Diabetes Remission Clinical Trial (DiRECT) NIH external link, conducted in primary care practices in the United Kingdom, examined type 2 diabetes remission rates in participants who lost weight, starting with a very low-calorie diet and sustaining the weight loss over time. DiRECT found high rates of type 2 diabetes remission among people who lost a significant amount of weight—more than 10 kg (about 22 pounds)—and sustained the weight loss over 12 to 24 months.
Q: What research is being conducted on remission of type 2 diabetes?
A: Studies have sought to understand the mechanisms of remission. A lot of current research focuses on not only total fat in the body, but also where the fat may be located, referred to as “ectopic fat” (e.g., fat in the liver and pancreas) that may affect normal physiologic function. This research has led to some very interesting observations about potential mechanisms. Weight loss may improve pancreas function, with better insulin secretion and type 2 diabetes remission.
Q: Are some people with type 2 diabetes more likely to achieve remission than others?
A: Three factors that seem to predict success in achieving remission are significant weight loss, baseline pancreatic function, and diabetes duration.
Significant and sustained weight loss—for example, in the range of 10 kg (about 22 pounds) as shown in some studies—is the most important factor. Studies in which participants lost small amounts of weight have shown lower rates of type 2 diabetes remission. However, studies in which participants lost a significant amount of weight—such as DiRECT or studies of metabolic surgery—have shown higher remission rates.
Studies of weight loss through restricting calories or metabolic surgery have found that people with type 2 diabetes who start with greater pancreatic function at baseline, prior to the intervention, are more likely to undergo remission. People who have had shorter diabetes duration are also more likely to undergo remission. Type 2 diabetes is a progressive disease, and, after a long time with diabetes, pancreatic function may decline over time. Thus, observations suggest that after having diabetes for a long period of time, significantly improving pancreatic function and achieving remission may prove to be more difficult, compared to achieving remission early in the natural history of the disease.
Q: How and when should health care professionals talk with patients who have type 2 diabetes about remission? How can health care professionals help patients achieve remission and sustain it over time?
A: First and foremost, you should emphasize the importance of managing blood glucose levels to minimize the complications of type 2 diabetes whether the patient is or is not on medications. Glycaemic control is incredibly important in reducing the risk of complications, and you need to discuss glycaemic control and a goal with the patient. In most cases, this means advising patients to keep their A1C level at 7 percent or below to prevent eye, kidney, and nerve complications. While we have very effective medications to lower blood glucose levels, lifestyle interventions (nutrition and exercise) are a cornerstone of managing diabetes. A balanced diet that achieves weight loss not only improves blood glucose levels but also may reduce cardiovascular risk factors.
Patients should also know that obesity contributes to increased blood glucose levels due to insulin resistance and that the more weight patients put on, that may mean they need more medication. It is important that they know if they lose weight and improve their body’s efficiency, they may require less medication. Let your patients know that if they lose enough weight, particularly during the early phases of type 2 diabetes, they will significantly lower their blood glucose, have less risk for diabetes complications, and may be able to achieve remission.
Overall, with significant weight loss through restricting calories or other strategies, patients have a high likelihood of achieving remission, particularly if they have a greater baseline pancreatic function and have had diabetes for a shorter time.
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