Type 1.5 Diabetes (LADA)

“It is estimated that more than 50% of persons diagnosed as having non-obesity-related Type 2 Diabetes may actually have LADA.”

LADA refers to Latent Autoimmune Diabetes of Adults. However you might also hear it as Late-onset Autoimmune Diabetes of Adulthood or Aging or Slow Onset Type 1 Diabetes.

Diabetes Type 1.5 is a form of Diabetes Mellitus Type 1 that occurs in adults, often with a slower course of onset. This is also the reason that often adults with LADA may initially be diagnosed as having Type 2 Diabetes based on their age. This particularly happens if they have risk factors for Type 2 Diabetes such as a strong family history or obesity.

The concept of Latent Autoimmune Diabetes Mellitus was first introduced in 1993 to describe Slow Onset Type 1 Autoimmune Diabetes in adults. This followed the concept that Glutamic Acid Decarboxylase Autoantibodies (GADA) were a feature of Type 1 Diabetes and not Type 2 Diabetes.

The symptoms of latent autoimmune Diabetes of adults are similar to those of other forms of Diabetes: such as excessive thirst and drinking, excessive urination, and often blurry vision.

Compared to childhood Type 1 Diabetes, the symptoms develop comparatively slowly.

It can only be treated with the usual oral treatments for Type 2 Diabetes for a certain period of time, after which insulin treatment is usually necessary, as well as long-term monitoring for complications.

Important facts on LADA 

  • Onset: Type 1 Diabetes onsets rapidly and at a younger age than does LADA.
  • Family history: There is often a family history of autoimmune conditions. Contrary to popular belief, some people with latent autoimmune Diabetes of adults do carry a family history for Type 2 Diabetes.
  • Autoantibodies: Persons with Type 1 Diabetes and LADA usually test positive for certain (same) autoantibodies (GAD, ICA, IA-2, ZnT8) that are not present in Type 2 Diabetes. Studies have reported an association of Type 1 Diabetes and LADA with high risk genes, HLA-DR3, HLA-DR4. There are also TCF7L2 genes associated with Type 2 Diabetes with latent autoimmune Diabetes of adults.
  • GAD autoantibodies: Persons with LADA usually test positive for GAD antibodies, whereas in Type 1 Diabetes these antibodies are more commonly seen in adults rather than in children.
  • Insulin resistance: People with LADA have insulin resistance similar to long-term Type 1 Diabetes; some studies showed that people with LADA have less insulin resistance, compared with those with Type 2 Diabetes; however, others have not found a difference.
  • Lifestyle and weight: People with LADA typically have a normal BMI or may be underweight due to weight loss prior to diagnosis. Some people with LADA, however, may be overweight to mildly obese. LADA (Type 1 Diabetes) is an autoimmune disease that cannot be prevented.
  • Prognosis: About 80% of all persons initially misdiagnosed with Type 2 Diabetes, who have GAD antibodies, will become insulin dependent within 3 to 15 years (according to differing LADA sources). Those with both GAD and IA2 antibodies, however, will become insulin dependent sooner. LADA occurs more slowly than classic rapid-onset Type 1 Diabetes, though it progresses towards insulin dependency.
  • Treatment: The treatment for Type 1 Diabetes and LADA is exogenous insulin, to control glucose levels, prevent further destruction of residual beta cells, reduce the possibility of diabetic complications, and prevent death from Diabetic Ketoacidosis (DKA). Although LADA may appear to initially respond to similar treatment (lifestyle and medications if needed) as Type 2 Diabetes, it will not halt or slow the progression of beta cell destruction, and people with LADA will eventually become insulin dependent.

The diagnosis is based on the finding of high blood sugar together with the clinical impression that islet failure rather than insulin resistance is the main cause.

It is estimated that between 6-50% of all persons, depending on population, diagnosed with Type 2 Diabetes and shockingly more than 50% of persons diagnosed as having non-obesity-related Type 2 Diabetes may actually have LADA.

Although it is incredible to say that the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus does not recognize the term LADA; rather, it includes LADA in the definition of Type 1 autoimmune Diabetes.

It is important to note that not all people having LADA are thin or skinny, however there are overweight individuals with LADA who are misdiagnosed because of their weight.

Moreover, it is now becoming evident that autoimmune Diabetes may be highly under-diagnosed in many individuals who have Diabetes, and that the body mass index levels may have rather limited use in connections with latent autoimmune Diabetes.

Glutamic acid decarboxylase autoantibody (GADA), islet cell autoantibody (ICA), insulinoma-associated (IA-2) autoantibody, and zinc transporter autoantibody (ZnT8) testing should be performed on all adults who are not obese who are diagnosed with Diabetes.

Detection of a low C-peptide and raised antibodies against the islets of Langerhans support the diagnosis.

Persons with LADA typically have low, although sometimes moderate, levels of C-peptide as the disease progresses.

Patients with insulin resistance or Type 2 Diabetes are more likely to, though will not always, have high levels of C-peptide due to an over production of insulin.

Glutamic Acid Decarboxylase Antibodies are commonly found in Type 1 Diabetes.

In addition to being useful in making an early diagnosis for Type 1 Diabetes, GADA tests are used for differential diagnosis between LADA and Type 2 Diabetes.

It may also be used for differential diagnosis of gestational Diabetes, risk prediction in immediate family members for Type 1 Diabetes, as well as a tool to monitor prognosis of the clinical progression of Type 1 Diabetes.

Researched, collected and written by Zsolt Szemerszky

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