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Graphic fromJuvenile autoimmunediabetes: A pathogenic role for maternal

antibodies? Matthias von Herrath1 & Jean-Francois Bach2Nature Medicine 8, 331 - 333

(2002)

What is LADA

Latent Autoimmune Diabetes of Adults (LADA) is a slow developing form of

autoimmune diabetes found in people over 35 years old which is often

misdiagnosed as Type 2.

The reason for this misdiagnosis is that by age 35 many people in the general

population are slightly overweight or may have developed some insulin

resistance or other signs of the metabolic syndrome which doctors associatewith Type 2 diabetes.

In addition, evidence is emerging that suggests that LADA, though it is an

autoimmune disease, is not quite the same as Type 1 diabetes, and, in fact,

has a genetic profile that includes genes also found in people who develop

Type 2 diabetes.

This was made clear in a study published in February of 2008 that reports 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 2diabetes.

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 were negative for

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GAD Antibodies had higher levels of a common Type 2 gene than their peers

who were positive for these antibodies, but that in olderpeople diagnosed

with LADA the frequency of a common 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 notmiddle-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 (1534 years) but not in middle-aged

(4059 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 failing beta cells rather

than insulin resistance. This means that the oral drugs given to people with

Type 2 diabetes often will have very 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 may develop Diabetic

Ketoacidosis (DKA) without insulin--which is 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 startedimmediately 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 Type 1 diabetes suggests it does not:

MedPage Today: Type 1 Diabetes Prevention with Early Insulin a Bust

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 featureof 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.

For now, 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, and because LADA involves an autoimmune attack

which is stimulated by the production of insulin at the beta cells, stimulating

insulin production by the beta cells with drugs may increase the ferocity of

the attack, killing more beta cells.

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So it is very important to get a correct diagnosis so you can avoid the drugs

that stimulate insulin production by the beta cells. These drugs include the

sulfonylureas like Amaryl and Glipizide and may also include the incretin

drugs, Byetta and Januvia because they also stimulate insulin production by

the beta cells.

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 havebeen diagnosed with another autoimmune condition, like Rheumatoid

Arthritis or some Thyroid diseases, it is more likely that your diabetes is also

caused by an autoimmune response.

3. Normal or Near Normal Weight Although there are, indeed, other forms

of Type 2 diabetes that strike people of normal weight as well as non-

autoimmune genetic forms of diabetes that are also misdiagnosed as Type 2

diabetes, most thin people who are incorrectly diagnosed with Type 2

diabetes turn out to have LADA.

So LADA should always be tested for in a thin or normal weight "Type 2,"

especially if blood sugars are extremely high at diagnosis.

However, LADA is usually not a concern for normal weight people

diagnosed with the mild blood sugar irregularity diagnosed as "prediabetes"

unless they have a family history of Type 1 diabetes or other autoimmune

conditions.

4. Failure to Respond to Oral Drugs People with LADA often see swift

deterioration in their blood sugars in the months after a Type 2 diagnosis. If

your blood sugars are getting worse, not better, despite taking oral drugs and

cutting back on carbohydrates, a combination which is usually effective in

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 is that very early

on in the disease process there may be no detectable antibodies, but over time

they may emerge.

The other important test for LADA is the fasting C-peptide test. A very low

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C-peptide result suggests that the beta cells have stopped making insulin,

possibly because they are dead. People with Type 2 diabetes often test with

normal or high levels of C-peptide. So a low C-peptide level is suggestive of

LADA, though it should be confirmed with antibody tests.

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 Type 1s get which will help you

learn how to use insulin to get more normal numbers.

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 it is essential that, no

matter what your doctor tells you, you learnWhat Is a Normal Blood Sugar

and strive to achieveHealthy Blood Sugar Targets.

If your doctor, no matter what their specialty might be, tells you that a 7.0%

A1c is excellent control, please readResearch 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 studieswhich offer those with relatives diagnosed with Type 1 the opportunity to get

free antibody testing. Those who have already tested positive for the

antibodies can be enrolled in studies involving experimental treatments

intended to delay the destruction of beta cells.

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 withtype 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 dietthan it is with a high carbohydrate diet. To learn more about how lowering

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carbs allows you to fine tune your blood sugar control and avoid dangerous

hypos and soaring post-meal blood sugars, readDr. Bernstein's Diabetes

Solution: The Complete Guide to Achieving Normal Blood Sugars. Though

many people with LADA are able to eat higher amounts of carbohydrate than

those that Dr. Bernstein recommends, the principles he explains hold true for

all people with diabetes and reading this book will give you a much betteridea of how to use insulin effectively.

References

Latent autoimmune diabetes of adulthood: Unique features that distinguish it

from types 1 and 2Fadi 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 preventionPaolo Pozzilli, Umberto Di Mario,Diabetes Care

24:1460-1467, 2001.

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