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.
