Latent Autoimmune Diabetes Myths: Separating Fiction from Fact (The Patient-Centered Perspective)

Type 1 and LADA
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Latent Autoimmune Diabetes in Adults (LADA) is a term coined by Tuomi et al in 1993 (Footnote 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 (Footnote 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(Footnote 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 fail to use evidence-based medicine and instead 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 (Footnote 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.(Footnote 5)

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.”(Footnote 6)

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 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: 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 some 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 at diagnosis.

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 in people with adult-onset T1D 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.”(Footnote 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.) The exception 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.

My thanks to Natalie for her review and input.

Footnote 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.
Footnote 2: Diabetes Care January 2012 vol. 35 no. Supplement 1 S64-S71.
Footnote 3: Type 1 Diabetes in Adults: Principles and Practice (Informa Healthcare, 2008), page 27.
Footnote 4: “Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype” (DIABETES CARE, VOLUME 36, APRIL 2013).
Footnote 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.
Footnote 6: Type 1 Diabetes Sourcebook, 2013. Anne Peters, MD, and Lori Laffel, MD, MPH, Editors. JDRF and American Diabetes Association. Page 26.
Footnote 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.

1 Like
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Brilliant, as always, Melitta!!

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Thank you so much for sharing. No matter how many shots and high BGL there still are, I sometimes still need that reminder…I have type1 diabetes.

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Yes, thank you! When I was first diagnosed I was SO confused!!! Actually before I was diagnosed but when I knew something was really wrong. It does strike me as odd though that some in the medical community can't wrap their brains around the whole LADA as type 1? Surely, there have always been adults who have become type 1 diabetics later in their adult life. My husband's grandmother was diagnosed as a type 1 in her late 30's and went straight to insulin. That was back in the 60's! Do you think it's those of us whose pancreas hold up a bit longer or who don't go from healthy to DKA overnight might be causing confusion. Honestly, it's crazy. Your articles have really helped me figure out (From the beginning of my diabetes journey) WHAT is going on! :) And I thankful for all the knowledgeable kind people on TuDiabetes too.

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Great post Melitta, We need to keep reminding people of this, it is so important to have correct diagnosis and treatment. I suspect that a lot people who appear to progress rapidly to dka at whatever age really have been having symptoms for a long time prior to that even if it didn't show up in once per year bg readings. Anyway, the main thing is to get the proper treatment initially to avoid deaths and complications. I'm not sure why the term LADA is used by so many when it really is type 1 and it isn't an official diagnosis, I guess that should tell people something maybe. I remember when I read on a British site about LADA being insulin resistant I was like wtf? lol. I'm certainly not insulin resistant and I hadn't heard anyone else with late onset type one say they were.

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For more information about LADA and its common features at diagnosis, please refer to the following link:

http://www.diabetes.ca/documents/for-professionals/DC--MayJune_2008--McInnes,_M.pdf
above is the response I received via Facebook from the Canadian Diabetes Assocition when I posed the question " How is it that many people are misdiagnosed as type 2 PWD and have all the symptoms of type 1 diabetes ??? What guidelines should a GP follow ??? I am mainly referring to the adult community ....this is what a person answered "Because type 1 is juvenile diabetes and if you are passed a certain age you are considered type 2. The range I believe is between 20-25. Otherwise you are considered a type 2. If the medication (metformin etc) doesn't work and it is determined you need insulin, you are still type 2 but insulin dependent" .

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Hi Melitta ...the link covers similar notes you started out with ...I need to pursue the original question more ...IMHO the question what a GP has to look put for has not been answered ...yet . I may have expressed previously , I do know more PWD diagnosed with type 1 as an adult, than I know children ; my Specialist diagnosed a lady at age 65 with type 1 ...we are defenitely not alone !!

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Nel, the response from the person at the Canadian Diabetes Association is SIMPLY HORRIFYING. Since Mary Tyler Moore, Chair of JDRF International, was diagnosed at age 33, does that mean she has Type 2 diabetes? No of course not.

The article that you linked to is very good. Thanks, Nel, for being a champion of PWDs in Canada!

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correction Melitta please ... the person who responded to my question is NOT a paid CDA person ...,I don't know the lady , other than she responded to my FB question and has a Hubby , who was misdiagnosed at age 23 !

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Hi Melitta,

Thank you so much for putting all this information together and for posting it! Thank you for your tireless efforts to help people understand and to help people get correctly diagnosed and treated--and for saving lives!

Best wishes,

marty1492

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Thanks for clarifying, Nel, that it wasn't a paid CDA person. Still, bad information! Thanks again for all the work you do, Nel, the world needs more of you.

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Thanks Melitta for your nice comment !!!! ...and glad we cleared the misunderstanding up ,,,yes it was bad information and one wonders where it came from ...keep on doing too what you are doing soooo well !!

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Great post Melitta! I’ve been lurking and learning a lot from you and others here on Tudiabetes during my prolonged and frustrating diagnosis. My endo now says I have autoimmune diabetes and I was unsure what that actually meant, now I know. I am antibody negative but have the gene, family history of adult onset, personal history of other autoimmune issues, and symptoms including unintentional rapid weight loss and signs of neuropathy. My 1st phase response is essentially gone (we looked at both insulin and glucose during my OGTT) so I have elevated post prandials (I’ve gone as high as 275) but I also have been experiencing reactive hypos for about 5 yrs to the point of developing unawareness until I hit 50 so my A1c averages those in and is below 6. Basel insulin is still pretty much intact too which leaves me in a real no-man’s land when trying to get treatment. My doc is going to have me try prandin with meals but is resisting letting me bolus with a rapid acting insulin before meals because of the risk of hypos which, ironically I am already dealing with. I’m hoping the prandin will help me gain back some weight and energy because controlling the spikes with a super low carb diet leaves me tired and causes even more weight loss (my BMI is only 18 rt now, not my normal wt). Funny, before this happened I used to think that diabetes was a pretty clear cut deal, you are either T1 or T2, ha!

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Nice article!

What intrigues(pure curiosity) me is why LADA is so slow compared to normal T1, what is different? better immune system or lower antibodies? I was also dx as LADA with no GAD but IA-2 antibodies with a 1.1 Peptide, I'm curious how much my C Peptide will drop after 1 year.

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I agree Robert, the gradual onset plus the variation in glucose dysregulation from patient to patient in adult onset T1 is interesting and confusing! U of M is partnering with JDRF to look at a new hypothesis…“In this proposed model of T1D, the loss of beta cell function may not be driven by beta cell death, as is widely believed, but rather by the regression of beta cells into a less mature state in which they are no longer able to produce insulin effectively, or at all. Proof of this model could open an entirely new therapeutic strategy, both to prevent T1D and to restore insulin production in individuals with the disease.” Hope they have some success!

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Thank you for presenting the research so clearly and for making the changes in your blog to clarify the information.

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Robert, good question, why is LADA slow onset compared to classic T1D? And remember, too, that babies have much more rapid onset than teenagers--the older you get, the slower (in general) the onset. I had rapid-onset Type 1 diabetes at age 35, but most people diagnosed as adults don't have the extreme symptoms, rapid downhill slide, and DKA that I experienced. Here is some information from "Genetic Analysis of Adult-Onset Autoimmune Diabetes" (Diabetes, Oct 2011): "The slower progression toward autoimmune insulin deficiency in adults is probably due to a lower genetic load overall combined with subtle variation in the HLA class II gene associations and autoreactivity." And in a LADA chapter of a 2011 book (the chapter by Brooks-Worrell and Palmer): "LADA patients have been reported to be more commonly positive for HLA DR3 and DR4 and their associated DQb1 alleles 0201 and 0302, which have been linked to a predisposition to childhood T1D. In contrast, the HLA DR2 and DQb1*0602, which has been associated with protection from childhood T1D, has also been reported to be relatively common in LADA patients. The protection associated with DR2/DQb1*0602 may partially explain the age of onset of LADA versus childhood T1DM."

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This all started gradually for me around the age of 50, four yrs ago but the BG roller-coaster I've been on was only discovered in a random blood test 18 months ago. I do have the 0302 gene but not the protective 0602 and I'm glad I haven't experienced DKA Melitta, but not fitting neatly into a T1 or T2 box has made for a drawn out, confusing, and very tiring couple of years. When I first got sick I underwent many tests with my gastroenterologist because of my 18 yr Celiac history and rapid weight loss. After that it's been one doctor after another basically saying "I don't know", the last one telling me I may need to go to Mayo. We have T1 & T2 diabetes in our family and even though I know it is a difficult disease to manage, I never thought a diagnosis and course of treatment would be that difficult to nail down. I've told the endo I'm seeing now that from my perspective (and perhaps that of many people with diabetes) the classification and diagnostic criteria for diabetes needs to be overhauled, he doesn't disagree.
55 seconds ago

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Great article Melitta! I have struggled to find out more information about this since I first suspected I was LADA instead of Type 2. I wish I had found tudiabetes sooner! I convinced the NP I see to test for the antibodies. She did but she told me later she was expecting them to come back negative. Boy did she get surprised! Funny thing is she still considers me an uncontrolled Type 2. I found an endocrinologist but have to wait another 2 months before I can see him. I plan on sharing some of this info with my NP.

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Kathy, you have Type 1 autoimmune diabetes by definition. Take a look at the various blogs I have written, most of which are about misdiagnosis (people misdiagnosed as having Type 2 diabetes when they actually have Type 1 diabetes). Have you seen my gems from the "Type 1 Diabetes Sourcebook" that is really applicable to you, or my top ten tips for the newly diagnosed person with adult-onset Type 1 diabetes?