LADA diabetes is a slowly progressive disorder of carbohydrate metabolism of autoimmune origin, manifesting in adulthood. The symptoms are similar to the manifestations of diabetes mellitus in general: increased thirst, polyuria, pollakiuria, hunger, constant fatigue and drowsiness. Weight loss is characteristic. Diagnostics is carried out by laboratory methods, including the determination of blood glucose, HbA1c, C-peptide, antibodies to beta cells, GAD, insulin, tyrosine phosphatase. Treatment requires the appointment of insulin injections, insulin sensitizers, incretins.
E13 Other specified forms of diabetes mellitus
Latent autoimmune diabetes of adults (LADA diabetes) It is a common, but insufficiently studied form of diabetes mellitus (DM). In a separate group, he was singled out by Australian diabetologists T. Tuomi and P. Zimmet in 1993. LADA–diabetes has signs of both type 1 and type 2 diabetes: autoimmune genesis and the need for insulin therapy bring it closer to the first, with the second – manifestation in adulthood (25-50 years). In this regard, it is sometimes called “type 1.5 diabetes”, “insulin-dependent type 1 diabetes”. The prevalence of latent diabetes in the structure of DM varies from 1-2% among Asians to 4-13% among Europeans. Women get sick a little more often.
The basis of the development of LADA diabetes is a genetic predisposition. Thus, the HLA alleles DRB1*04, DRB1*03, DQB1*0302 and combinations DRB1*04-DQA1*0301, DRB1*04-DQB1*0302 are most common in adults with autoimmune latent DM. In addition to high-risk alleles, protective (protective) combinations of haplotypes that make the course of the disease less aggressive have also been studied.
Other significant contributing factors are polymorphic markers: Ala17Thr of the cytotoxic T lymphocyte serinesterase gene (CTLA4), 23HphI of the insulin gene (INS), R620W of the tyrosine phosphatase gene of lymphoid cells (PTPN22), rs7903146 of the transcription factor 7L2 gene (TCF7L2), etc.
In the family history of patients, there are more indications of type 2 diabetes in the closest relatives. There is also the presence of other autoimmune diseases, both in the patient himself and in his relatives (Hashimoto’s thyroiditis – in 25% of patients, celiac disease – in 19%). It is possible that LADA is part of an autoimmune polyglandular syndrome. In women who have had gestational diabetes, LADA develops in a quarter of cases.
At risk for the development of latent diabetes are persons:
- with low birth weight;
- being overweight at a young age;
- abusing caffeinated and sugar-containing beverages, alcohol, smoking;
- suffering from hypodynamia.
Viral infections (Coxsackie virus, etc.), psychoemotional stress can act as triggers causing manifestation.
The disease develops due to the destruction of islet β-cells of the pancreas by autoreactive cytotoxic (CD8+) and effector (CD4+) lymphocytes. In the blood of LADA patients there are specific autoantibodies to pancreatic glutamate decarboxylase, pancreatic islet cells, less often – At to tyrosine phosphatase and insulin. A genetically mediated autoimmune reaction leads to the gradual destruction and loss of the functional mass of insulin-producing cells, a decrease in insulin production and the formation of hyperglycemia.
In general, the pathological process proceeds milder, and the progression of insulin insufficiency is slower than in classical DM1. There is a correlation between the titer of anti-GAD and the rate of development of insulin deficiency: the higher the level of antibodies, the earlier the need for exogenous insulin arises. Insulin resistance, which occurs under the influence of behavioral factors, plays a significant role in the mechanism of LADA development.
During the pathomorphological examination of the pancreas in the early stage of LADA, there is an inflammatory reaction of individual insular lobules (insulitis), their lymphohistiocytic infiltration and destruction, less often hypertrophy. As diabetes progresses, the islets undergo atrophy and sclerosis.
In modern endocrinology, there are two types of adult LADA diabetes, depending on the predominance of signs of DM1 or DM2:
- LADA 1 – debuts at a young age; it is characterized by high antibody titers, rapid destruction of pancreatic islet cells and early need for insulin therapy;
- LADA 2 – develops at a more mature age, progresses slowly; patients have an increased BMI, metabolic syndrome, dyslipidemia.
Latent autoimmune diabetes mellitus in children (LADC) and in boys (LADY-like) are also described. Some authors consider all these types of diabetes to be varieties of type 1 diabetes.
Symptoms of LADA diabetes
In its manifestations, LADA resembles other forms of diabetes. Pathognomonic signs include hunger, increased appetite (polyphagia), frequent urination, increased diuresis (polyuria), dry mouth and unquenchable thirst (polydipsia). Patients report weight loss, constant fatigue, dizziness, dryness and itching of the skin. During the examination, hyperglycemia and glucosuria are detected.
The debut of symptoms falls on the fourth decade of life. As a rule, the disease develops in people with reduced or normal body weight. 1-2 years after diagnosis, patients with LADA require the appointment of insulin therapy.
In patients of the first group (LADA 1), there is an increased level of glycosylated hemoglobin and low-density lipoproteins, which is a risk factor for atherosclerotic damage to the vessels of the heart, brain, and peripheral arteries. Later administration of insulin therapy is associated with a more rapid development of vascular pathologies. Typical diabetic complications in patients with LADA occur statistically more often than in type 2 diabetes. They include diabetic retinopathy, neuropathy, nephropathy. Ketoacidosis is not characteristic (sometimes develops with LADA type 1).
Latent autoimmune diabetes of the adult type is often mistaken for DM 2. Accurate verification of the form of the disease requires the consultation of an experienced endocrinologist-diabetologist, a thorough clinical and laboratory examination. The clinical diagnostic criteria for latent diabetes are:
- the age of the demonstration is over 30 years old;
- BMI <25 kg/m2;
- presence of autoantibodies as a marker of autoimmune activity;
- no dependence on insulin for at least six months after diagnosis.
Laboratory tests help to confirm the diagnosis of LADA with the greatest accuracy:
- Determination of autoantibodies. The presence of At-GAD65 in adult patients with advanced diabetes is a prerequisite for the diagnosis of latent autoimmune diabetes. At the same time, the higher the titers of At to GAD, the faster insulin deficiency develops in the future. Other variants of antibodies may also be detected: more often – ICA, rarely – IA-2 and IAA.
- Study of markers of carbohydrate metabolism. In LADA type diabetes, blood glucose, insulin resistance index (but lower than in DM2), glycated hemoglobin are increased. Glucosuria may be detected in the urine. The basal and stimulated concentration of C-peptide is reduced, which indicates an absolute deficiency of endogenous insulin.
- Other studies. HLA genotyping and determination of lymphocyte subpopulations is rarely used in clinical practice and is usually performed for scientific purposes.
A thorough and balanced diagnosis makes it possible to distinguish between LADA and other forms of diabetes:
- insulin – dependent diabetes;
- insulin-independent diabetes;
- secondary SD.
Treatment of LADA diabetes
The principles of treatment of latent diabetes in adults are similar to the treatment of DM1. First of all, the importance of modifying behavioral factors is explained to patients: diet, increased physical activity. Hypoglycemic drugs are not prescribed for LADA, since they contribute to the rapid depletion of the β-cells of the pancreas.
It is generally recognized today to switch to insulin therapy as early as possible, which provides good control of glycemia and prolongs the functional activity of β-insulocytes. Currently, along with insulin, the appointment of thiazolidinediones and incretins is considered justified. They have a protective effect on beta cells and reduce the need for insulin.
To prevent hypo- and hyperglycemia, patients need to conduct regular self-monitoring of blood sugar, learn how to independently administer subcutaneous insulin and adjust its dose taking into account concomitant factors. All data should be entered in the diary of self-control. You can learn this by attending diabetes school.
In experimental studies, a certain immunomodulatory effect was shown by the use of the DiaPep277 vaccine based on heat shock proteins. It was also possible to cause an increase in endogenous insulin secretion in LADA with the help of anti-CD3-monoclonal antibodies. Another study reported that subcutaneous injections of GAD65 antigen allowed to increase basal secretion of C-peptide. All these methods require further evaluation for safety and long-term effectiveness.
Prognosis and prevention
Latent diabetes has a more aggressive course than DM2, is accompanied by rapid development of insulin deficiency and early need for the introduction of exogenous insulin. However, a competent and responsible approach to your health allows you to learn how to live with LADA, reduce the risk of severe systemic complications.
Since autoimmune diabetes belongs to the category of genetically determined diseases, measures for its prevention have not been developed. At the same time, the risk of developing LADA can be reduced by giving up harmful addictions and eating habits.