insights

Many functional and integrative clinicians have had patients with 2 diabetes (T2D) who have lost that diagnosis as a result of sustained lifestyle modifications. Yet up until now, there was little recognition in the wider medical community that such change was possible and no established language to describe this phenomenon. In a sudden reversal of this longstanding trend, late last year, the American Diabetes Association convened an international expert group to officially recognize that such change was possible and propose new terminology to describe it. The result was a consensus report outlining the definition and clinical details of what the group termed diabetes remission.¹ While the report was not intended to establish clinical guidelines, it does put forward a framework for determining when a patient should be considered in remission and what that actually means for their health going forward. Its publication is at least in part the result of many years of ongoing clinical successes by functional medicine clinicians and others who focus on lifestyle change as the primary treatment for T2D. 

When a patient with T2D becomes normoglycemic, there are some complicated issues involved that go beyond whether or not someone is considered “diabetic.” These include: does a patient need to be off all glucose-lowering drugs to be considered in remission? What about other drugs or treatments? How can a clinician safely deprescribe medications as the patients engages in lifestyle changes that normalize glucose levels? Does being euglycemic now mean the risks of diabetic complications are back to normal levels? Does the way in which a patient becomes normoglycemic impact subsequent health risks? (For example, there are many potential complications for those who achieve remission via bariatric surgery). But of course, perhaps the most important factor to appreciate is that without a doubt, normalizing glucose levels is a huge benefit to patients’ health, and the fact that all the major diabetes organizations published this consensus statement is recognition of the increasing numbers of clinicians and patients who together have done just that.  

To summarize the consensus statement, the authors suggest: 

• The term remission be used to describe sustained return to normoglycemia, which should be defined by an HbA1c of <6.5% that occurs spontaneously or following an intervention and that persists for at least three months in the absence of usual glucose-lowering pharmacotherapy.  
• When HbA1c cannot be reliably used, a fasting plasma glucose of FPG <126 mg/dL or eA1C <6.5% calculated from CGM values can be used as alternate criteria.  
• Further testing should be done at least once per year to determine long-term maintenance along with continued routine testing for potential complications of diabetes (e.g., retinopathy, neuropathy). 
• Further research is needed to determine the frequency, duration, and effects on short- and long-term outcomes of T2D remission.¹ 

THE ROLE OF LIFESTYLE 

The report recognizes the importance of lifestyle change as a primary cause of T2D remission and includes the following statement, which is quite in line with what the functional medicine community has been teaching and advocating for decades:  

“Reversal of the adverse effects of poor metabolic control on insulin secretion and action may establish a remission, but other underlying abnormalities persist and the duration of the remission is quite variable. In contrast, when a persistent change of lifestyle leads to remission, the change in food intake, physical activity, and management of stress and environmental factors can favorably alter insulin secretion and action for long periods of time. In this setting, long-term remissions are possible, but not assured.”¹ 

Functional medicine clinicians have several tools for helping patients make personalized lifestyle changes that are both appropriate for their metabolic phenotype and sustainable in the long term based on patient needs and preferences. The Cardiometabolic Food Plan, for example, can be customized for each individual patient, and changes in other modifiable lifestyle factors can also be tailored to the individual, including considering factors such as chronotype and time-restricted eating. Decreasing stress levels and assisting with stress management; increasing physical activity while also decreasing sedentary time; improving sleep quality and quantity; and nurturing supportive social relationships are all important factors in regulating metabolic health, and functional medicine has tools to meet each patient where they are to improve treatment success and sustainability.  

Since its publication, another expert consensus statement was released that uses the above proposed definition of remission and specifically highlights that diet as a primary intervention for T2D can achieve remission in many adults with T2D and is related to the intensity of the intervention.² IFM has long championed dietary change as a first-line intervention for insulin resistance and T2D with dietary plans that are personalized to each patient. That said, the functional medicine approach to cardiometabolic health also comprises the other modifiable lifestyle factors, as well as addressing any identifiable underlying causes such as exposure to toxicants and nutrient insufficiencies that may require supplementation.  

HEALTH OUTCOMES 

The question remains as to what happens to patients after they are in remission. Obviously, lifestyle changes need to be maintained for patients to remain in remission in most cases, but there is still the question of how the body responds after a short or extended period of hyperglycemia. We know that tight glycemic control among those with T2D has some benefits but does not reduce risk for all the adverse health outcomes associated with diabetes,^3,4 with some evidence pointing to glucose variability as an important factor.⁵ Presumably, when a patient is in remission, some of the metabolic damage done from hyperglycemia (and perhaps hypoglycemia due to overtreatment) remains.⁶ This metabolic memory is addressed in the remission report, in which the authors state that even after a remission, all of the classic complications of diabetes can still occur; however the citation they provide for this is from a follow-up of bariatric surgery patients, and no mention of continuing risk following sustained lifestyle change is made. Based on this reasoning, the authors recommend continued screening for all diabetes complications and state there is no long-term evidence that these can be discontinued.  

It seems likely that there may be differences among patients currently in remission from T2D in risk for subsequent complications and related comorbidities that may depend on several factors, including the length of time they had uncontrolled diabetes (as well as partially or even well-controlled diabetes) and the method used to induce remission. We may begin to think of such risk as we do with former smokers, whose risk of smoking-related illnesses doesn’t disappear when they quit, so we use pack-years as a measure of risk; for former diabetics, it might be hyperglycemic years or something similar that we use as a measure of ongoing risk.   

Finally, it should also be noted that insulin levels and sensitivity are not included in the definition of T2D remission, and neither are any other related markers of health such as blood lipids, inflammatory signaling molecules, adiposity, or organ damage. Continued monitoring of such markers where indicated may be considered, and further research should investigate how T2D remission interacts with these factors. 

SUMMARY 

It is encouraging to see recognition of the potential for T2D remission among the leading diabetes organizations and at least some measure of understanding that lifestyle is important in achieving this goal. The assertion that lifestyle change is a primary driver of such change in most cases is further validation of this fact. Functional medicine clinicians, with their primary focus on sustainable lifestyle change to prevent and treat T2D and other dysfunction, are leading the way in helping patients achieve remission. Future research will tell us more about how lifestyle change may impact the ongoing risks of those in remission.  

References

1. Riddle MC, Cefalu WT, Evans PH, et al. Consensus report: definition and interpretation of remission in type 2 diabetes. Diabetes Care. 2021;44(10):2438-2444. doi:10.2337/dci21-0034 
2. Rosenfeld RM, Kelly JH, Agarwal M, et al. Dietary interventions to treat type 2 diabetes in adults with a goal of remission: an expert consensus statement from the American College of Lifestyle Medicine. Am J Lifestyle Med. 2022;16(3):342-362. doi:10.1177/15598276221087624 
3. Huang D, Refaat M, Mohammedi K, Jayyousi A, Al Suwaidi J, Abi Khalil C. Macrovascular complications in patients with diabetes and prediabetes. Biomed Res Int. 2017;2017:7839101. doi:10.1155/2017/7839101 
4. Rodríguez-Gutiérrez R, Montori VM. Glycemic control for patients with type 2 diabetes mellitus: our evolving faith in the face of evidence. Circ Cardiovasc Qual Outcomes. 2016;9(5):504-512. doi:10.1161/CIRCOUTCOMES.116.002901 
5. Zhou Z, Sun B, Huang S, Zhu C, Bian M. Glycemic variability: adverse clinical outcomes and how to improve it? Cardiovasc Diabetol. 2020;19(1):102. doi:10.1186/s12933-020-01085-6 
6. Ceriello A. The emerging challenge in diabetes: the “metabolic memory.” Vascul Pharmacol. 2012;57(5-6):133-138. doi:10.1016/j.vph.2012.05.005