How Do We Define Cure of Diabetes?

The mission of the American Diabetes Association is “to prevent and cure diabetes and to improve the lives of all people affected by diabetes.” Increasingly, scientific and medical articles (1) and commentaries (2) about diabetes interventions use the terms “remission” and “cure” as possible outcomes. Several approved or experimental treatments for type 1 and type 2 diabetes (e.g., pancreas or islet transplants, immunomodulation, bariatric/metabolic surgery) are of curative intent or have been portrayed in the media as a possible cure. However, defining remission or cure of diabetes is not as straightforward as it may seem. Unlike “dichotomous” diseases such as many malignancies, diabetes is defined by hyperglycemia, which exists on a continuum and may be impacted over a short time frame by everyday treatment or events (medications, diet, activity, intercurrent illness). The distinction between successful treatment and cure is blurred in the case of diabetes. Presumably improved or normalized glycemia must be part of the definition of remission or cure. Glycemic measures below diagnostic cut points for diabetes can occur with ongoing medications (e.g., antihyperglycemic drugs, immunosuppressive medications after a transplant), major efforts at lifestyle change, a history of bariatric/metabolic surgery, or ongoing procedures (such as repeated replacements of endoluminal devices). Do we use the terms remission or cure for all patients with normal glycemic measures, regardless of how this is achieved? A consensus group comprised of experts in pediatric and adult endocrinology, diabetes education, transplantation, metabolism, bariatric/metabolic surgery, and (for another perspective) hematology-oncology met in June 2009 to discuss these issues. The group considered a wide variety of questions, including whether it is ever accurate to say that a chronic illness is cured; what the definitions of management, remission, or cure might be; whether goals of managing comorbid conditions revert to those of patients without diabetes if someone is “cured”; and whether screening for diabetes complications needs to continue in the “cured” patient. Since little or no scientific or actuarial evidence exists to inform the group’s discussions, consensus was difficult to attain in a number of areas. The opinions and recommendations expressed herein are those of the authors and not the official position of the American Diabetes Association. Medically, cure may be defined as restoration to good health, while remission is defined as abatement or disappearance of the signs and symptoms of a disease (3). Implicit in the latter is the possibility of recurrence of the disease. Many clinicians consider true cure to be limited to acute diseases. Infectious diseases could be seen as a model: acute bacterial pneumonia can be cured with antibiotics, but HIV infection, currently, can at best be stated to be in remission or converted to a chronic disease. The consensus group considered the history of childhood acute lymphoblastic leukemia, which evolved from a uniformly fatal disease to one that could be put into remission to one that can now often be considered cured (4). Conversely, chronic myelocytic leukemia is now considered to be in prolonged remission, but not cured, with therapies such as imatinib. For a chronic illness such as diabetes, it may be more accurate to use the term remission than cure. Current or potential future therapies for type 1 or type 2 diabetes will likely always leave patients at risk for relapse, given underlying pathophysiologic abnormalities and/or genetic predisposition. However, terminology such as “prolonged remission” is probably less satisfactory to patients than use of the more hopeful and definitive term “cure” after some period of time has elapsed. Additionally, if cure means remission that lasts for a lifetime, then by definition a patient could never be considered cured while still alive. Hence, it may make sense operationally to consider prolonged remission of diabetes essentially equivalent to cure. This is analogous to certain cancers, where cure is defined as complete remission of sufficient duration that the future risk of recurrence is felt to be very low. Abnormal glucose metabolism leading to hyperglycemia defines the disease diabetes, yet hyperglycemia exists on a continuum and the diagnosis of the disease occurs at levels sufficiently high to be associated with the diabetes-specific complication retinopathy. Should absence of the disease diabetes be defined as glucose values considered within the normal range, sub-diabetic but not necessarily normal glucose values, or the complete absence of underlying abnormal physiology such as insulin resistance or -cell dysfunction or loss? The group modeled its consensus definitions somewhat on terminology that exists for certain malignancies, with hyperglycemia analogous to tumor load. Cancer may initially be put into remission, either partial (substantial reduction in tumor load) or complete (no evidence of tumor). Eventually, the duration of a ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●