Why Are Doctors Not Interested in Type 2 Diabetes Mellitus Remission?

Heung Yong Jin; Tae Sun Park

doi:10.4093/dmj.2024.0312

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Editorial Why Are Doctors Not Interested in Type 2 Diabetes Mellitus Remission?: Heung Yong Jin, Tae Sun Park; Diabetes & Metabolism Journal 2024;48(4):709-712.
DOI: https://doi.org/10.4093/dmj.2024.0312
Published online: July 26, 2024

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Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Medical School, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea

Corresponding author: Tae Sun Park

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Most medical professionals and patients focus on diabetes as a chronic and progressive disease and are despair and indifferent to the search for a cure. However, many evidences are emerging to support diabetes as an acute condition that requires rapid and appropriate intervention. It is necessary to investigate why the concept of remission, which was introduced a long time ago, has not spread widely to clinical settings and to consider resolving this issue.

The typical management of patients with type 2 diabetes mellitus (T2DM) consists of multifactorial behavioral therapy and drug therapy to prevent complications and maintain quality of life. However, in 2022, a consensus report from the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) proposed that diabetes management should include the following four components: medication for blood sugar management, weight management, cardiovascular risk factor management, and selection of blood sugarlowering drugs to protect the heart and kidneys. Diabetes management should also propose a holistic approach for managing T2DM patients, including 13 management principles, and aim to achieve patient-centered blood sugar management goals accordingly. For this purpose, a seven-step decision-making process was presented [1]. However, to carry out this process, which varies from country to country, multidisciplinary teams including primary care doctors, diabetes specialists, diabetes educators, nutritionists, pharmacists, nurses, and other subspecialists depending on the patient are needed. Successful results are most likely when integrated treatment is performed. However, in Korea, there is no recognized system for managing diabetes education costs or educator qualifications.

The ultimate goal for patients with diabetes and their doctors is cure of diabetes. Despite much effort, no curative method has been found. Biological, surgical, or mechanical methods are used for treatment, although their effectiveness is limited. In allogeneic pancreas transplantation using biological methods, major surgery is required. After transplant, even if immunosuppressants are used throughout the life, the transplanted organ 10-year survival rate is <50%. Pancreatic islet cell transplantation is a simpler surgery than organ transplantation and uses less toxic immunosuppressive therapy; however, more than half of patients must return to insulin treatment within 1 year after surgery. Additionally, continuous immunosuppressive therapy and multiple donors are needed for repeated transplants [2].

Surgical therapy is the most effective method for T2DM patients. Bariatric surgery can result in significant weight loss that reduces insulin resistance. However, obesity surgery and its resulting significant changes in lifestyle habits can produce numerous side effects and complications, and diabetes recurs in most cases.

Another treatment for diabetes is through the mechanical insulin pump, which has been used for decades. This method requires a well-designed closed-loop artificial pancreas and involves many unresolved complications. In addition, continuous blood sugar monitoring with a wearable sensor can improve diabetes management but has not resulted in diseasecure.

Biological, surgical, and mechanical methods for curing diabetes will continue to develop and improve; however, it is unlikely that an innovative and complete method will appear in the near future. Moreover, it is not easy to effectively manage diabetes in the rapidly increasing number of cases using currently available methods, hindering effective control of complications and increasing mortality. In particular, to prevent a decline in quality of life and reduce socioeconomic costs, overall improvement in diabetes management is needed, regarding both individual patients and the health care system. However, there is no system to widely apply efficient evidence-based treatments to patients. Therefore, while patients, diabetologists, diabetes educators, and complications experts work together to search for a cure, continued interest in remission and reduction of diabetes damage is necessary.

T2DM has long been thought to be chronic and irreversible, with more than half of patients requiring insulin after about 10 years in the absence of proper management [3]. However, many studies and reports are refuting this view using new methods that prioritize disease reversal and remission [4,5]. Remission is a term widely used in other diseases, especially cancer. However, while diabetes can seem to be cured after obesity surgery, it can relapse due to subsequent weight gain. As the term ‘cure’ is not yet appropriate for diabetes, the concept of remission was introduced. The criteria for remission of T2DM, published in a joint consensus of the ADA, the American Endocrine Society, and the British Diabetes Association, are a fasting blood sugar level of 126 mg/dL or a (measured or estimated) glycosylated hemoglobin less than 6.5% (which is below the original diagnostic criteria for diabetes). Remission is defined as a return to controlled blood sugar levels for at least three months without the use of hypoglycemic agents. Patients in remission should undergo regular annual review [6].

Taylor’s twin cycle hypothesis explains the process by which excessive energy intake causes T2DM. After obesity surgery, this process causes a marked change in energy balance, leading to rapid remission; however, to maintain this long-term, energy restriction is required. A 2016 Counterbalance study announced that T2DM onsets at a 0.5 g weight of pancreatic fat and is maintained for 6 months when returning to a normal diet. Although symptom remission can occur in all people, it is more common in people with a short duration of diabetes. The The Diabetes Remission Clinical Trial (DiRECT) study used a structured approach with a non-surgical, non-pharmacological, behavior change intervention for initial weight loss, which was delivered as routine care in general practice [7]. In that study, the authors reported greater weight loss to be associated with longer-lasting diabetes remission, and that multiple methods should be explored to prevent weight regain. Very low-calorie diets (VLCDs), such as those in the DiRECT study, are not successful in all patients and produce good long-term results in less than 40% of participants. Return to a normal diet after the VLCD resulted in recurrence of diabetes. A low-carbohydrate diet (LCD) limits carbohydrate intake to 20 to 130 g per day (6% to 26% of total calorie intake). Such a diet plays an important role in the management and remission of T2DM, but further research is needed to optimize and individualize this practice.

Many reports have emerged showing that T2DM can be dramatically improved or remitted by restricting carbohydrate intake. However, limitations of LCD studies include the lack of long-term studies, the absence of weight loss reports, and few studies showing remission of T2DM. Another limitation is that not all patients with T2DM are overweight or obese. Although there are many reports that exercise improves glycemic control, it is very unlikely that exercise will be an effective first-line treatment to achieve remission in T2DM. However, exercise can be helpful during the maintenance phase after resuming a normal calorie intake. In addition, exercise is an essential element of long-term weight control and can help maintain remission. Kim et al. [8] used Korea’s health checkup database and found that 23,156 (20.2%) of 114,874 patients tracked for 5 to 7 years lost more than 5% of their body weight, and 2,429 (2.15%) achieved remission and lost weight within 2 years of T2DM management. The group reported that the weight loss was related to diabetes remission and is more important in obese men younger than 65 years [8].

The 8th edition of the Korean Diabetes Association diabetes treatment guidelines recommend first considering drug selection based on the presence or absence of comorbidities. These guidelines are similar to those published by the ADA or EASD. In Japan Diabetes Society, drug selection is first recommended based on obesity. In contrast, the ADA recommends individualized goals to maintain and achieve weight management goals and then drug administration if that is not successful. However, KDA practice guidelines recommend using drugs to lower blood sugar based on their effects on reducing body weight without considering the etiology of the excess weight (Table 1) [9]. According to the diabetes fact sheet of the KDA, 55.1% of diabetic patients in Korea also have obesity, 63.3% of whom had abdominal obesity [10]. In these situations, insulin sensitizers (pioglitazone, metformin), alpha-glucosidase inhibitors, glucagon-like peptide-1 agonists, and sodium-glucose cotransporter-2 inhibitors can be used as hypoglycemic drugs with important weight loss effects to induce remission of T2DM. However, more diverse combination therapies are needed to achieve appropriate remission with drug therapy for weight loss, and more research is needed to maintain remission. Moreover, lifestyle habits that causes obesity cannot be solved with drug therapy alone and cannot be applied to everyone and maintained for a lifetime. Furthermore, in an evaluation of diabetes management drugs approved from 2011 to 2017, additional benefit was reported in only 16% of patients [11]. In their paper, Kim et al. [12] described that remission requires early treatment of hyperglycemia and significant weight loss before irreversible β-cell changes occur, and that remission should be achieved through an individualized approach. To this end, remission should be the treatment goal for patients with pre-diabetes, newly diagnosed T2DM, and patients who have had T2DM for fewer than 6 years. Additionally, it is essential to educate diabetes management team members to increase their understanding and interest in remission.

The standard treatment methods currently recommended for diabetes management are of little help in preventing the spread of diabetes. Rather than focusing on treatment, an accurate understanding of remission and various approaches to it are needed to manage the T2DM epidemic effectively. Remission in T2DM is new concept that requires a shift in thinking. There is little consensus and few guidelines on the optimal timing, combination, and delivery of interventional therapy to achieve T2DM remission. A personalized, multidisciplinary, and combined step-by-step approach is needed for patients to achieve remission. Through such a process, evidence-based management methods can be personalized for application in the early stages of the disease.

It is time to make efforts to confirm the possibility that T2DM, which is mostly accepted to be a chronic and progressive disease, can be reversed through remission. Although diabetes will likely never be irradicated, the possibility of delayed onset and remission is higher than ever. To maximize remission in Korea, efforts are needed to provide individualized treatment based on active participation of both patients and medical professionals. It is also time for diabetes experts to expose the consequences of the diabetes pandemic to health policy makers and society overall, recognize the need for a change in approach to diabetes, and actively participate in its advancement.

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CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

Table 1.

Clinical recommendations of obesity management for type 2 diabetes mellitus patients by pharmacotherapy

Diabetes association	Clinical recommendations
ADA & EASD	Achievement and maintenance of weight management goals
ADA & EASD	-Set individualized weight management goals
JDS	Select medication to address the diabetes pathology
JDS	-Depends on obesity status
KDA	Use drugs selected to lower blood sugar based on their effects on body weight

ADA, American Diabetes Association; EASD, European Association for the Study of Diabetes; JDS, Japanese Diabetes Society; KDA, Korean Diabetes Association.

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