LADA - Late Autoimmune Diabetes in Adults

[Translate to Englisch:] Diagnose Diabetes 1 oder 2?
[Translate to Englisch:] © Africa Studio / Fotolia

The term LADA (latent autoimmune diabetes in adults) describes a particular  form of diabetes: As in type 1 diabetes, patients have special autoantibodies, but usually they do not require insulin therapy in the first six months after diagnosis and are older than 35 years.
Often these patients are initially diagnosed with type 2 diabetes. However, the clinical picture  becomes more and more similar to type 1 diabetes. If laboratory tests show autoantibodies in the blood, the doctor diagnoses  LADA – on occasion  years after the first diagnosis. As a rule, autoantibodies against the enzyme glutamate decarboxylase (GAD antibody) occur in LADA.
In most cases, those affected are slimmer than type 2 diabetics, but there are also indications of a metabolic syndrome such as lipid metabolism disorders (hyperlipidemia, increased triglycerides) and high blood pressure. More frequently than classical type 1 diabetics, they carry risk genes for type 2 Diabetes.

 

 

Prevalence and Diagnosis of LADA

Prevalence and diagnosis of LADA
In adults  diagnosed with diabetes , LADA is  about three times more frequent than the classic type 1 diabetes: In the largest European study to date, "Action LADA 7", scientists examined more than 6,000 adults between the ages of 30 and 70 years in the first five years after diagnosis. They detected islet autoantibodies (predominantly GAD antibodies) in 9.7 percent of these patients. These figures are comparable with data from the UK Prospective Diabetes Study (UKPDS). In this study, 10 percent of patients clinically classified as type 2 diabetics had islet antibodies (GAD antibodies).
The definition of a LADA diagnosis remains blurred even today. It should be distinguished from classic type 1 diabetes in which two or more types of islet autoantibodies are present and those affected need to inject insulin from the time of diagnosis. Faulty diet, lack of exercise, and ever-increasing insulin doses can lead to obesity and type 2 diabetes over a period of years, even in patients with type 1 diabetes.
Researchers recommend using the following parameters as diagnostic decision support:
• Age at onset of disease
• Body Mass Index (BMI),
• Antibodies against glutamate decarboxylase (GAD)
• HbA1c as long-term blood glucose value
• HOMA index (Homeostasis Model Assessment) for the detection of possible insulin resistance

Good to know

Not all LADA patients require insulin in the early stage of the disease. Although there are only a few studies on the treatment of LADA, clinical and laboratory chemical parameters provide adequate guidance to diabetologists for appropriate therapy of  each patient.

Therapy of LADA

Does a positive GAD antibody finding in any case mean that the patient – sooner or later – must start insulin therapy?
Various factors play a role here: in general, younger, slimmer people with a Body Mass Index (BMI) of less than 25 kg/m2, a higher long-term blood glucose level HbA1c and a certain genetic high-risk component need insulin early. In addition, the level of GAD antibody concentration, the presence of other autoimmune markers and the extent of residual insulin secretion also play a role.
On average, 70 percent of LADA patients younger than 45 years of age start insulin therapy within six years following diagnosis. If the patients are older than 45 years, on average only 40 percent of them require insulin therapy.
If the concentration of GAD antibodies is relatively low and there are no other islet autoantibodies, it can be assumed that the beta cell mass of the body is still adequate  to continue producing sufficient insulin. In these cases it should be sufficient to monitor the blood glucose level closely and – if necessary – take antidiabetic drugs.

 

 

Individual therapy goals are important

Similar to classic type 2 diabetes the doctor should agree on individual therapy goals with the patient. The so-called incretin-based drugs could help to control  blood sugar level without the risk of hypoglycemia and prevent weight gain. This group of drugs includes GLP-1 analogs that mimic the effect of the intestinal hormone GLP-1. The hormone GLP-1 controls the release of insulin after meals.
However, there is not yet sufficient data on the efficacy of metformin and other diabetes drugs in the treatment of LADA. Research approaches of an early "vaccination" with aluminum-bonded GAD injected under the skin did not produce  positive results .

 

 

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References

  • Hawa, M. et al. & Action LADA 7 Consortium: Adult-Onset Autoimmune Diabetes in Europe is Prevalent with a broad Clinical Phenotype. In: Diabetes Care, 2013; 36:908-913
  • Turner, R. et al.: Prospective Diabetes Study Group, UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. In: Lancet, 1997; 350:1288-1293
  • Tuomi, T. et al.: The many faces of diabetes: A disease with increasing heterogeneity. In: Lancet, 2014, 383:1084-94
  • Zampetti, S.: High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7). In: Eur J Endocrinol, 2014, 71:697-704
  • Krause, S. et al.: GAD Autoantibody Affinity in Adult Patients with latent Autoimmune Diabetes, the Study Participants of a GAD65 Vaccination Trial. In: Diabetes Care, 2014, 37:1675-1680
  • Williams, A. et al.: Detection of Antibodies directed to the N-Terminal Region of GAD is dependent on Assay Format and Contributes to Differences in the Specificity of GAD Autoantibody Assays for Type 1 Diabetes. In: Diabetes, 2015, 65:3239-3246
  • Zhao, Y. et a.: Dipeptidyl peptidase 4 inhibitor sitagliptin maintains β-cell function in patients with recent-onset latent autoimmune diabetes in adults: one year prospective study. In: J Clin Endocrinol Metab, 2014, 99:E876-80
  • Johansen, OE. et al.: C-Peptide Levels in Latent Autoimmune Diabetes in Adults Treated With Linagliptin Versus Glimepiride: Exploratory results from a 2-year, double-blind, randomised, controlled study. In: Diabetes Care, 2014, 37:e11-e12

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19.10.2018

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