LADA -- Slow Adult Onset Autoimmune Diabetes with Some Type 2 Features

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LADA -- Slow Adult Onset Autoimmune (Type 1) Diabetes with Some Type 2 Features
Graphic from Juvenile autoimmune diabetes: A pathogenic role for maternal antibodies? Matthias von Herrath1 & Jean-Francois Bach2 Nature Medicine 8, 331 - 333 (2002)

Not responding to metformin? Cutting carbs still leaving you with blood sugars much higher than normal? It's possible you have LADA. That's the abbreviation for Latent Autoimmune Diabetes of Adults, a slow developing form of autoimmune diabetes found in people over 35 years old that is often misdiagnosed as Type 2. It has recently become clear that this adult form of autoimmune diabetes is as common as the much better known "Juvenile" form of autoimmune diabetes that is currently called Type 1 Diabetes. (Details HERE)

The reason adults with autoimmune diabetes are often misdiagnosed with Type 2 is that by age 35 many people in the general population, including those who develop autoimmune conditions, are overweight or have developed other signs of insulin resistance and metabolic syndrome." Since doctors have been trained to believe that overweight and metabolic syndrome are diagnostic of Type 2 diabetes they automatically assume any adult who isn't rail thin when given a diabetes diagnosis must have Type 2. This is a problem because diet, exercise and oral drugs, which are the standard treatments for Type 2 are not effective in halting the progression of LADA.

Though LADA is an autoimmune condition like the Juvenile form of Type 1, evidence has emerged that suggests that LADA not quite the same as Type 1 diabetes. People who get LADA have a genetic profile that includes genes also found in people who develop Type 2 diabetes.

Specifically, a study published in February of 2008 found that people diagnosed with LADA had variations in the HLA autoimmunity genes similar to those found in people with Type 1 diabetes but that many of them also had variations of the TCF7L2 gene that has been associated with Type 2 diabetes.

Genetic Similarities Between LADA, Type 1 and Type 2 Diabetes Camilla Cervin et al, Diabetes DOI: 10.2337/db07-0299

This led the researchers to conclude that

LADA shares genetic features with both type 1 (HLA, INS VNTR, and PTPN22) and type 2 (TCF7L2) diabetes, which justifies considering LADA as an admixture of the two major types of diabetes.
This finding was confirmed by a second study published in November of 2008 which found that young people with diabetes who tested negative for GAD Antibodies (i.e. shod no sign of having had an autoimmune attack on their pancreases.)had higher levels of a common Type 2 gene than their peers who tested positive for these antibodies, but that in older people diagnosed with LADA the frequency of that TCF7L2 Type 2 gene was the same as it was in people of that age who were not positive for GAD antibodies. This led the authors to conclude:
Common variants in the TCF7L2 gene help to differentiate young but not middle-aged GADA-positive and GADA-negative diabetic patients, suggesting that young GADA-negative patients have type 2 diabetes and that middle-aged GADA-positive patients are different from their young GADA-positive counterparts and share genetic features with type 2 diabetes.
Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15–34 years) but not in middle-aged (40–59 years) diabetic patients E. Bakhtadze et. al. Diabetologia. DOI 10.1007/s00125-008-1161-2

How LADA Is Treated

Treatment for LADA is different from treatment for Type 2 diabetes because the primary problem is insulin deficiency caused by beta cells that are succumbing to autoimmune attack rather than insulin resistance. This means that the oral drugs given to people with Type 2 diabetes often will have little impact on the blood sugar of a person with LADA. In addition, over a period of 3-5 years, most people with LADA become fully insulin dependent and without supplemental insulin may develop Diabetic Ketoacidosis (DKA), a life-threatening condition.

Because people with LADA often have mildly elevated blood sugar at first diagnosis, there is some debate about whether they should be started immediately on insulin.It was thought in the past that starting insulin treatment as early as possible might stop the autoimmune attack associated with LADA. But recent research investigating whether the use of early insulin can slow the development of classic autoimmune diabetes in children suggests it does not:

Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial. Näntö-Salonen K et al.Lancet. 2008 Nov 15;372(9651):1746-55. Epub 2008 Sep 22.

Still, there is a lot of evidence that starting insulin early in Type 2 can make control much easier in the future--and since LADA combines genetic feature of both Type 1 and Type 2 diabetes, it is possible that some of the benefit seen in Type 2 may extend to people with LADA. If nothing else, starting insulin early may prevent a person from spending 3 to 5 years with the excessively high post-meal blood sugars that are known to kill beta cells even in the absence of autoimmune attack. So there seems to be no compelling reason for a person with LADA NOT to start insulin early.

Also, several of the oral drugs used to treat Type 2 diabetes stimulate the beta cells to produce insulin. Because it is possible that the autoimmune attack characteristic of LADA may be stimulated by the production of insulin at the beta cells, forcing the beta cells to secrete insulin with insulin stimulating drugs or incretin drugs like Januvia or Victoza, which also stimulate the beta cells to make insulin, may increase the ferocity of the attack, killing more beta cells.

Clearly, if you might have LADA it's important you get a correct diagnosis so you can avoid the drugs that won't stop the progression of your condition and might make it worse.

Indicators that You May Have LADA

1.A family history of Type 1 diabetes. There is a genetic tendency towards developing autoimmune diabetes, so if you have a close family member who has autoimmune diabetes, it is more likely that you have that same genetic make up and the same tendency towards developing autoimmune diabetes.

2. The Presence of Other Autoimmune Conditions If you already have been diagnosed with another autoimmune condition, like Rheumatoid Arthritis, MS, or autoimmune Thyroid disease, it is more likely that your diabetes is also caused by an autoimmune response.

3. Normal or Near Normal Weight Though people who get LADA may be overweight, many are not. And though there are other forms of diabetes that are found in adults of normal weight which are also not classic Type 2 diabetes, most thin and normal weight people who are incorrectly diagnosed with Type 2 diabetes turn out to have LADA. So LADA should always be tested for in people who are thin or of normal weight who are found to have suddenly developed diabetes, especially if their blood sugars are extremely high at diagnosis.

Note, however that LADA is usually NOT the explanation for why normal weight people may be diagnosed with the milder blood sugar irregularity called "prediabetes," unless they have a family history of Type 1 diabetes or other autoimmune conditions. People with the genes that eventually lead to Type 2 often lack the classic diagnostic signs of Type 2, such as obesity, which develop only after they experience years of exposure to "prediabetic" blood sugars which many doctors ignore or fail to treat correctly.

4. Failure to Respond to Oral Drugs People with LADA often see swift deterioration in their blood sugars in the months after their Type 2 diagnosis no matter what they do. If your blood sugars are getting worse despite taking oral drugs and cutting back significantly on your intake of starches and sugars--an approach that is usually effective in controlling Type 2 diabetes, you should demand that your doctor test you for LADA or send you to an Endocrinologist who will do this.

How to Test for LADA

The most common test for LADA is one that looks for GAD (glutamic acid decarboxylase) antibodies. However, a small number of people with autoimmune diabetes will not have GAD antibodies, but they will have islet cell antibodies and/or tyrosine phosphatase antibodies. So a lack of GAD antibodies does not entirely rule out LADA. Another issue to be aware of is that very early in the LADA disease process there may be no detectable antibodies, though they will emerge over time. This may mean it is a good idea to wait for six months after you are diagnosed with diabetes before demanding the expensive antibody tests.

The other common test administered to check for LADA is the fasting C-peptide test. A very low C-peptide result suggests that the beta cells have stopped making insulin, possibly because they are dead. People with Type 2 diabetes usually show normal or high levels of C-peptide. So a very low C-peptide level is suggestive of LADA, though such a result must be confirmed with antibody tests. The C-peptide test is a very crude test that can give notoriously misleading results.

What To Do If You Think You Have LADA

If you have LADA, you'd do best to get treated by an endocrinologist who specializes in treating Type 1 diabetes, as you will need an up-to-date insulin regimen and the kind of diabetes education given only to people with Type 1 diabetes. This will teach you how to get the best results when using insulin. Do NOT let a family doctor who primarily treats adults with Type 2 prescribe insulin for your LADA as most family doctors use outdated, imprecise methods to prescribe insulin which leave people with much higher than necessary blood sugar. These methods cause unnecessary suffering for people with Type 2 but are even worse for people with autoimmune diabetes who have almost no working beta cells left.

If you can't get treatment from an endocrinologist, demand formal "diabetes education" with a certified diabetes educator. These professionals also understand the correct way to dose insulin. With a diagnosis of autoimmune diabetes your insurer should pay for this education. Do not let an uncertified "diabetes nurse" practicing out of a general practitioner's office teach you how to use insulin!

People with LADA may also qualify for an insulin pump under many insurance plans. Some may find a pump very helpful for getting tighter control.

It is important to note that people with LADA have the same risk of damaging their organs by running higher than normal blood sugar as do people with other forms of diabetes. This means that once you have learned how to use an insulin regimen consisting of both a basal and mealtime insulin component it is essential that, no matter what your doctor tells you, you learn What Is a Normal Blood Sugar and strive to achieve, as much as is possible, Healthy Blood Sugar Targets.

If your doctor, no matter what their specialty might be, tells you that a 7.0% A1c is excellent control, please read Research Connecting Blood Sugar Level with Organ Damage. The best blood sugar level for a person with insulin-dependent diabetes is the lowest level they can achieve without experiencing hypos--with hypos being defined as blood sugars under 70 mg/dl.

Free Antibody Testing Available from TrailNet

An organization called Type 1 Diabetes TrialNet is sponsoring several studies which offer those with relatives diagnosed with Type 1 the opportunity to get free antibody testing. To be eligible for the screening test you must meet one of the following criteria:
  • 1 to 45 years of age and have a brother, sister, child, or parent with type 1 diabetes

  • 1 to 20 years of age and have a cousin, aunt, uncle, niece, nephew, half sibling, or grandparent with type 1 diabetes
More information about the TrialNet screening and studies can be found at:
Type 1 Diabetes TrialNet: Information for Study Participants

Are There Dietary Interventions For LADA?

Unlike the case with Type 2 diabetes, it is usually not possible to reverse or control LADA with carbohydrate restriction alone. That said, it is much easier to make insulin work when you are eating a lower carbohydrate diet than it is with a high carbohydrate diet. To learn more about how lowering carbs allows you to fine tune your blood sugar control and avoid dangerous hypos and soaring post-meal blood sugars, read Dr. Bernstein's Diabetes Solution: The Complete Guide to Achieving Normal Blood Sugars. Though many people with LADA are more comfortable eating at higher intakes of carbohydrate than what Dr. Bernstein recommends, the principles he explains about matching insulin to the foods you eat hold true for all people with diabetes. Reading this book will give you a much better idea of how to live with autoimmune diabetes and use insulin effectively.


Latent autoimmune diabetes of adulthood: Unique features that distinguish it from types 1 and 2 Fadi Nabhan, MD; Mary Ann Emanuele, MD; Nicholas Emanuele, MD. Postgraduate Medicine Vol 117, No 3, Mar 2005.

Genetic Similarities Between Latent Autoimmune Diabetes in Adults, Type 1 Diabetes, and Type 2 Diabetes. Camilla Cervin et. al. Diabetes 57:1433-1437, 2008

Autoimmune Diabetes Not Requiring Insulin at Diagnosis (Latent Autoimmune Diabetes of the Adult) Definition, characterization, and potential prevention Paolo Pozzilli, Umberto Di Mario, Diabetes Care 24:1460-1467, 2001.
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