Getting It Right for People with Adult-Onset Type 1 Diabetes

Note that I am liberally elaborating off of “Getting It Right for People with LADA,” by Ernest Maddaloni and Paolo Pozzilli (DiabetesVoice, September 2014, Volume 59, Issue 3).  Of course, LADA is the acronym for latent autoimmune diabetes in adults, or slowly progressive Type 1 diabetes.  I appreciate the authors’ advocacy for people with adult-onset Type 1 diabetes—I just took their work several steps further.

Adult-onset Type 1 diabetes can be rapid onset, with marked hyperglycemia and a high risk of diabetic ketoacidosis (DKA), or more slowly progressive (LADA).  Many medical professionals also are not aware that gestational diabetes (GDM) may be a precursor to Type 1 diabetes, not just Type 2 diabetes.  The stress of pregnancy is "the straw that broke the camel's back" and pushes a woman over into overt Type 1 diabetes (autoimmune gestational diabetes).

Type 1 diabetes/LADA is characterized by immune-mediated destruction of the beta cells of the pancreas, leading to severe insulin deficiency requiring exogenous insulin to sustain life.  Type 1 diabetes is a distinct clinical entity from Type 2 diabetes:  according to The Type 1 Diabetes Sourcebook (ADA/JDRF 2013, a reference guide for clinicians), “The pathophysiology of the two diseases [Type 1 diabetes and Type 2 diabetes] differ on a basic pathophysiologic level such that Type 1 diabetes is marked by insulinopenia while Type 2 diabetes is characterized by obesity, hyperinsulinemia, insulin resistance, and relative insulinopenia.”  In other words, the Type 1/LADA phenotype is quite far from the “metabolic syndrome phenotype” so typical of people with Type 2 diabetes. Some people with Type 1 diabetes/LADA may develop insulin resistance, but insulin resistance is not characteristic of Type 1/LADA.

Both rapid onset Type 1 diabetes in adults and LADA are often wrongly diagnosed as Type 2 diabetes, by physicians who assume that an adult with new onset diabetes must be Type 2.  Of course, physicians see a preponderance of Type 2 diabetes in their clinics.  Physicians also frequently assume that a person who is overweight must have Type 2 diabetes, but many people with adult-onset Type 1 diabetes are overweight when they are newly diagnosed. Autoantibody tests for the diabetes-associated autoantibodies (DAA, which include GAD, IA-2, IAA, and ZnT8) can be used to distinguish Type 1 autoimmune diabetes and diabetes due to other causes.  Guidelines assign all patients with DAA, including those with LADA, to Type 1 diabetes, and it is an oxymoron to write about autoantibody-positive Type 2 diabetes (Footnote 1).  The American Association of Clinical Endocrinologists (AACE), in its Clinical Practice Guidelines for Diabetes Mellitus, now states that Type 1 diabetes should be confirmed by the presence of autoantibodies (GAD, IA-2, IAA, ZnT8), to distinguish between Type 1 diabetes and Type 2 diabetes and to determine appropriate treatment.

People with adult-onset Type 1 diabetes/LADA who are misdiagnosed as having Type 2 diabetes are wrongly treated as though they have Type 2 diabetes.  Consistent evidence shows the importance, in terms of clinical outcome, of early initiation of insulin therapy in Type 1/LADA.  Thus, the early clinical recognition of people with adult-onset Type 1 diabetes, as distinct from Type 2 diabetes, is extremely important to guarantee the most suitable treatment in order to preserve beta-cell function, gain optimal metabolic control, and improve long-term outcomes.  A correct diabetes diagnosis is the cornerstone of correct therapy and a wrong diagnosis delays achievement of optimal metabolic control, frustrates patents, and increases the risk of life-changing or fatal complications.

References

Footnote 1:  Diabetes at the crossroads: relevance of disease classification to pathophysiology and treatment.  R. David Leslie, Jerry Palmer, Nanette C. Schloot, Ake Lernmark.  Diabetologia (2016) 59:13-20.