Latent autoimmune diabetes in adults (LADA)

Dr Louise Johnson explains why the correct diagnosis can prevent unnecessary complications, especially in latent autoimmune diabetes in adults (LADA).


Diabetes is the world’s fastest growing non-communicable (non-infectious) disease. Diabetes is more diverse than the crude subdivision into Type 1 and Type 2 diabetes.4

LADA, or latent autoimmune diabetes in adults, is a common hybrid form of diabetes with features of both Type 1 and Type 2 diabetes. The incidence of LADA is 2-12% of all cases of diabetes in the adult population.

LADA is a diverse disease characterised by a less intensive autoimmune (antibodies against the pancreas) process than Type 1 diabetes and sharing features of Type 2 diabetes, such as abnormal cholesterol, higher blood pressure and a wider waist circumference.

Autoimmune diabetes is characterised by the presence of specific autoantibodies directed against pancreatic beta cells and initial requirement of insulin therapy.This condition is as prevalent in adulthood as in childhood.

In 1977, Irvine showed that 11% of individuals initially diagnosed as Type 2 diabetes had antibodies against the beta cells.The term LADA was introduced in 1993 and described as a subset of diabetes sharing the autoantibodies of Type 1 diabetes and the phenotype (look like) of Type 2 diabetes.

The diagnosis of LADA is based on three criteria

  1. Adult age of onset of diabetes. Usually older than 30 years of age. The person can have the phenotype (look like) of Type 2 diabetes but there tends to be fewer signs of the metabolic syndrome, such as healthier lipids, lower BMI and better blood pressure profiles.
  2. Autoantibodies against the beta cells of the pancreas, called GAD antibodies.
  3. Insulin requirements within six months after diagnosis.

The early detection of LADA among newly diagnosed Type 2 diabetes patients seems crucial since the autoimmune process against the beta cells of the pancreas can cause rapid beta cell loss if treated wrong. Treatment to prevent beta cell failure is needed and should be implemented early.

Autoantibodies and C-peptide

It is very difficult to distinguish Type 1 diabetes from LADA on a blood test. The antibody load against the beta cell of the pancreas is larger in Type 1 diabetes than in LADA.

The functionality of the beta cell of the pancreas that produce insulin can be measured by C-peptide. This is a blood test that can be done in South Africa. In Type 1 diabetes, the C-peptide is very low or absent where in LADA the C-peptide is low.

The antibody that can be measured to confirm LADA is called glutamic acid decarboxylase autoantibody (GAD). A regular laboratory in South Africa can measure this and if this is positive, it confirms the presence of autoimmunity (antibodies against the pancreas) and if diabetes is also present then this person has LADA.

C-peptide values can be used to help in determining the treatment of LADA patients:

  1. Below 0,3nmol/L – This group needs insulin and can be treated according to the guidelines for Type 1 diabetes with insulin at bedtime and before meals.
  2. More than 0,3 and less than 0,7nmol/L -This is a grey area and it’s suggested to treat this group at first with therapy that preserve beta cells. The classes of medication considered would be: DPP4i (sitagliptin, saxagliptin, vildagliptin) or GLP1-receptor agonist, such as liraglutide, exenatide or dulaglutide. The newer class of SGLT2 inhibitors empagliflozin or dapagliflozin can also be considered in some patients.
  3. C-peptide levels of more than 0,7 nmol/L needs to be treated as insulin resistant patients with metformin and the above-mentioned therapy in 2. Their antibodies need to be repeated to make sure it wasn’t a false positive and their C-peptide levels need to be followed-up.

Treatment strategies for LADA

It’s important to evaluate all newly diagnosed Type 2 diabetes patients with a test for antibodies as to not miss the diagnosis of LADA.

The reason why this is important is that certain Type 2 diabetes drugs can worsen the autoimmunity in the pancreas and accelerate the loss of beta cells. The drugs that should be avoided in LADA patients are sulfonylureas. Drugs such as gliclazide, diaglucide, glimepiride and the rest of the class.

Insulin

This is essential in all people where the C-peptide level is very low or undetectable. Insulin administration supports the declining beta cells and improves the attack of antibodies against the pancreas. This process is called insulinites.

 DiPeptidyl Peptidase 4 (DPP4) inhibitors

This is a class of drugs that work in the gut by inhibiting the enzyme DPP4 that is responsible for secretion of insulin, inhibition of glucagon and production of incretin. Incretin helps to keep the satiety level up and prevent weight gain. In LADA patients, the DPP4 inhibitors protect against beta cell loss. Drugs in this class are vildagliptin, sitagliptin and saxagliptin.

Glucagon Like Peptide Receptor Agonist (GLP RA)

This group of drugs works like the DPP4 inhibitors but are injectable and more potent. They cause weight loss of 4-5kg and a greater reduction in glucose if that is needed. They are also protective against heart disease. Drugs in this class are liraglutide, exenatide and dulaglutide.

The overlap

Patients with LADA show midway features between Type 1 and Type 2 diabetes. Although adults with high GAD antibody tests are clinically closer to Type 1 diabetes than Type 2 diabetes, an overlap does exist. The overlap causes a misdiagnosis of 5-10%. This is the reason that we recommend the testing of antibodies in new type 2 diabetes.5

It’s important to remember that the misdiagnosis of LADA in Type 2 diabetes can lead to an increase of complications due to the fact that glucose control is a lot more difficult in this group, if not treated correctly.

In the new millennium that we are living with available technology, all newly diagnosed Type 2 diabetes patients should have a GAD antibody test. Type 2 diabetes patients that are struggling to control glucose on tablets should also be evaluated. The correct diagnosis can prevent unnecessary complications. Remember information can save a life riddled with complications.


References:

  1. Pieralice S et. al. “Latent autoimmune diabetes in adults: A review on clinical implications and management Diab Metab J 2018;42:451-464
  2. Bluestone JA et. al. Genetics, pathogenesis and clinical interventions in type 1 diabetes” Nature 2010 ;464: 1293 -300
  3. Buzetti et al. Management of Latent autoimmune diabetes I adults: A consensus statement from an International expert panel. Diabetes oct 2020 vol 69
  4. Tuomi T et. al. The many faces of diabetes: a disease with increasing heterogeneity. Lancet 2014, 383;1084
  5. Mishra et. al. 2018 
Dr Louise Loot

MEET THE EXPERT


Dr Louise Johnson is a specialist physician passionate about diabetes and endocrinology. She enjoys helping people with diabetes live a full life with optimal quality. She is based in Pretoria in private practice.


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