The Problem

It is time that the full scope of Type 1 diabetes is acknowledged, which includes millions of adults who are too frequently misdiagnosed as having Type 2 diabetes, an altogether different disease.

Saturday, June 28, 2014

Latent Autoimmune Diabetes Myths: The Patient-Centered Perspective

Latent Autoimmune Diabetes in Adults (LADA) is a term coined by Tuomi et al in 1993[1] to describe slow-onset Type 1 diabetes.  The NIDDK (U.S. National Institute of Diabetes and Digestive and Kidney Diseases) says LADA is “a condition in which Type 1 diabetes develops in adults.”  The WHO (World Health Organization) includes LADA in the category of Type 1 diabetes.  The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus[2] does not recognize the term LADA; rather, the Expert Committee includes LADA in the definition of Type 1 autoimmune diabetes:  “Type 1 diabetes results from a cellular-mediated autoimmune destruction of the beta-cells of the pancreas. In Type 1 diabetes, the rate of beta-cell destruction is quite variable, being rapid in some individuals (mainly infants and children) and slow in others (mainly adults).”  Most childhood-onset Type 1 diabetes is rapid onset, whereas in adulthood both rapid-onset and slowly progressive Type 1 diabetes occur.  Initially the term LADA was useful to shine light on this group of people with slowly progressive T1D, because people with LADA are so often misdiagnosed as having Type 2 diabetes (an altogether different disease), and because LADA is two to three times more common than classic onset Type 1 diabetes.[3]  However, numerous researchers now favor elimination of the term, instead moving to “autoimmune diabetes” to describe immune-mediated diabetes at all ages.

Type 1 diabetes, including LADA, is characterized by autoimmune destruction of the beta cells of the pancreas.  Markers for the immune-mediated destruction of the beta cells include autoantibody markers glutamic acid decarboxylase autoantibodies (GAD), islet cell cytoplasmic autoantibodies (ICA), insulinoma-associated 2 autoantibodies (IA-2), insulin autoantibodies (IAA), and zinc transporter 8 autoantibodies (ZnT8).  Other autoantibodies may exist but have not yet been discovered.  T1D/LADA is associated with HLA DR3/4 genes.

Despite the fact that LADA is Type 1 diabetes, many in the medical profession/diabetes community irrationally try to say that LADA is somehow not Type 1 diabetes.  Here are the myths versus the facts:

Myth:  Because LADA has a slower onset than classic Type 1 diabetes in children, it is a different disease.
Fact:  Onset of Type 1 diabetes in babies is much more rapid than Type 1 diabetes in teenagers, but no one in the medical community is saying that those teenagers should be kicked out of the Type 1 Club.  It is the disease process, not rate of onset, that defines Type 1 diabetes.

Myth:  People with LADA have genes associated with Type 2 diabetes.
Fact:  A significant percentage of the total population has genes associated with Type 2 diabetes, including people with rapid-onset Type 1 diabetes and LADA.  T1D/LADA is associated with HLA DR3/4 genes.

Myth:  People with LADA have only one autoantibody, GAD65, whereas people with rapid-onset Type 1 diabetes have more autoantibodies.
Fact:  In a recent study of people with adult-onset Type 1 diabetes, 24% had two or more autoantibodies[4], and many children with rapid-onset Type 1 are only GAD positive.  What counts is the presence of ANY autoantibody:  if the person (either child or adult) has been diagnosed with diabetes (fasting blood glucose greater than 125 mg/dl) and the person is positive for any one autoantibody, the person has Type 1 autoimmune diabetes.

Myth:  People with LADA have insulin resistance, so they don’t have Type 1 diabetes.
Fact:  Many people diagnosed with Type 1 diabetes as children develop insulin resistance later in life.  No one kicks them out of the Type 1 Club because they later develop IR.  Recent large-scale studies indicate that people with both classic onset Type 1 diabetes and those with LADA have a similar prevalence of metabolic syndrome to a non-diabetic control group but metabolic syndrome was significantly higher in those with Type 2 diabetes.[5]

Myth:  LADA is a “hybrid” form of Type 1 AND Type 2 diabetes.
Fact:  Some people with LADA have insulin resistance, so they have Type 1 diabetes and insulin resistance.  Most LADAs do not have insulin resistance.  No medical researcher is saying that Type 1 kids who develop insulin resistance have “hybrid” diabetes.  No, the kid has Type 1 diabetes, and so does the adult.

Myth:  LADA is a different disease than classic Type 1 diabetes because people with LADA still have some endogenous insulin production.
Fact:  Among 411 participants in the Joslin Medalists study (those with duration of T1D greater than or equal to 50 years), 67.4% still had detectable C-peptide, meaning they still have some endogenous insulin production.  As stated in The Type 1 Diabetes Sourcebook, “It is often unappreciated that many individuals with T1D will have significant amounts of C-peptide, representing residual beta cell function. The standard teaching that T1D is defined as complete absence of beta cells is inaccurate and is a disservice to both patients and providers.”[6]

Myth:  LADA is a different disease because people with LADA don’t initially require insulin for survival, and people with classic onset Type 1 diabetes immediately require insulin.
Fact:  Prior to 1922, Frederick Allen kept children with rapid-onset Type 1 diabetes alive for 5 years or more with a very low carbohydrate/very low calorie diet.  But now that we have excellent insulins, there is no reason to deny ANY person with Type 1 diabetes/LADA the insulin that they need.

Myth:  LADA describes adult phenotypic Type 2 diabetes.
Fact:  “Phenotype” is the composite of an organism's observable characteristics or traits, and an observant doctor or medical researcher would realize that the traits of a person with LADA are markedly different than the traits of a person with Type 2 diabetes, including the presence of autoantibodies in LADA, which are not present in Type 2 diabetes.  People with LADA are adult phenotypic Type 1 diabetes, based on characteristics and traits.
Myth:  People with LADA can be treated initially with drugs for Type 2 diabetes.
Fact:  In the 1970s in the United States, children with Type 1 diabetes were sometimes initially treated with sulfonylureas for up to 1 year, to keep the child off of insulin injections for as long as possible.  That practice was abandoned, as it should be for people with adult-onset Type 1 diabetes.  Type 1 diabetes, at whatever age it is diagnosed, should be treated with insulin, not with drugs for Type 2 diabetes, an altogether different disease.  Type 2 drugs are not likely to be effective, in any case.  As stated in the Type 1 Diabetes Sourcebook, “starting insulin is the mainstay of therapy” for adults who present acutely with Type 1 diabetes as well as those presenting more indolently.  Regarding adult-onset Type 1 diabetes, the T1D Sourcebook also says, “for those with early T1D, expert opinion recommends either low doses of basal insulin to prevent DKA [diabetic ketoacidosis] or prandial insulin to prevent postprandial hyperglycemia.”  Clinical studies have conclusively demonstrated that early and intensive exogenous insulin therapy controls glucose levels, prevents further destruction of residual beta cells, reduces the possibility of diabetic complications, and prevents death from diabetic ketoacidosis (DKA).

Myth:  A person who is overweight or obese has Type 2 diabetes, and cannot have Type 1 diabetes/LADA.
Fact:  Some children are overweight or obese at diagnosis of Type 1 diabetes.  By the same token some adults are overweight or obese at diagnosis of T1D/LADA.  The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus states, “Although patients are rarely obese when they present with [Type 1 diabetes], the presence of obesity is not incompatible with the diagnosis.”  A Swedish study emphasizes that diagnosis based on “etiology is superior to clinical judgment.”[7]

In researching these myths, one thing that I found to be extremely sad and disturbing is the lack of compassion shown towards those with adult-onset Type 1 diabetes.  Most of the research in journals never considers what might be best for the human being with Type 1 diabetes.  (Often researchers will say there is no reason to initiate insulin therapy at diagnosis, that treatment with drugs for Type 2 diabetes is the first-line treatment, and that autoantibody testing is too expensive to be used for anything more than research studies.  I would remind those researchers First Do No Harm.)  A misdiagnosed adult recently said to me, “I hope that more medical professionals realize how misdiagnosing adults with type 2 diabetes instead of type 1 can be dangerous and carries a very significant mental and physical toll on the newly diagnosed diabetic.” The exception to this lack of compassion is the excellent book by Dr. Anne Peters and Dr. Lori Laffel, Type 1 Diabetes Sourcebook (2013, American Diabetes Association/JDRF), which demonstrates compassion in abundance.  Kudos to those editors.

First published as a blog

[1] Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR. Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Diabetes. 1993;42:359–62.
[2] Diabetes Care January 2012 vol. 35 no. Supplement 1 S64-S71.
[3] Type 1 Diabetes in Adults: Principles and Practice (Informa Healthcare, 2008), page 27.
[4] “Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype” (DIABETES CARE, VOLUME 36, APRIL 2013).
[5] Metabolic Syndrome and Autoimmune Diabetes: Action LADA 3.  Mohammed I. Hawa, Charles Thivolet, Didac Mauricio, Irene Alemanno, Elisa Cipponeri, David Collier, Steven Hunter, Raffaella Buzzetti, Alberto de Leiva, Paolo Pozzilli, Richard David G. Leslie, on behalf of the Action LADA Group.  Diabetes Care. 2009 January; 32(1): 160–164.
[6] Type 1 Diabetes Sourcebook, 2013. Anne Peters, MD, and Lori Laffel, MD, MPH, Editors. JDRF and American Diabetes Association.  Page 26.
[7] “Evaluation of the new ADA and WHO criteria for classification of diabetes mellitus in young adult people (15-34 years) in the Diabetes Incidence Study in Sweden (DISS).” Springer-Verlag, 2003.