Essay: Latent autoimmune diabetes in adulthood (LADA)

“Around 3 million people in the UK have diabetes”. Diabetes was once defined as a serious lifelong health condition characterized by impaired glucose metabolism. Diabetes occurs when the amount of glucose in the blood is too high. Glucose levels in the body are controlled by the pancreas. The pancreas has two important systems: the endocrine and the exocrine systems.  The exocrine system plays an important role in the digestive system by releasing digestive enzymes to breakdown component in foods. The endocrine system produces hormones responsible for the control of blood glucose in the blood like insulin and glucagon. Beta cells of the Islets of Langerhans are responsible for the production of insulin.  This hormone is involved in the main two types of diabetes (type 1 and type 2). Type 1 diabetes is also known as insulin dependent diabetes and accounts for 5 % of the population. Patients with type 1 diabetes have an immune system that attacks and destroys their own beta cells. Symptoms of type 1 diabetes include weight loss, frequent urination, increased thirst and hunger, and fatigue.  This type of diabetes is usually diagnosed at a young age and patients with type 1 diabetes become insulin dependent within days or weeks. The diagnosis of type 1 diabetes depends on auto-antibodies levels in the blood against insulin or other components of the insulin producing systems (glutamic acid decarboxylase, tyrosine phosphatase and islet cells). Patients with type 1 diabetes usually have one or more of the islet auto-antibodies. These auto-antibodies include: islet cell antigens (ICAs), glutamic acid decarboxylase autoantibodies (GADAs) or tyrosine posphatase proteins (IA-2s). 90% of the population have the second type of diabetes. Type 2 diabetes is also known as non-insulin dependent diabetes. As its name implies, treatment is not always linked to insulin administration. Type 2 diabetes is when the body does not produce enough insulin or when the body does not respond to available insulin the body (known as insulin resistance). Unlike type 1 diabetes, symptoms of type 2 diabetes develop slower and include increased hunger, urination and thirst, decrease weight, fatigue, irritability and blurred vision. However, diabetes is not solely associated with two types.  Recently, scientists discovered numerous subtypes of diabetes. The most important of which is latent autoimmune diabetes in adulthood (LADA) which was first introduced in 1995.
According to the American Diabetes Association, the prevalence of LADA is more common in patients aged between 40 and 75 years around the world. LADA cases were found to be 6-10% of diabetes cases in the United Kingdom. Around the world, LADA accounts for 2-12% of all cases of diabetes.  LADA is characterized by the presence of islets antibodies at diagnosis and a slow progression of autoimmune beta cell failure. Therefore, it is type 1 diabetes that occurs in adults, with a slow course of onset. This explains why LADA patients are often misdiagnosed as having type 2 diabetes based on the age LADA is diagnosed at. Screening for LADA is still debatable. Some scientists suggest screening anyone newly diagnosed with type 2 diabetes for GAD antibodies. Other scientists suggest screening people aged between 35 and 45 testing positive for GAD and islet cells. Other scientist suggested testing anyone who tests positive for GAD antibodies be screened for auto-antibodies to thyroid and adrenal cells to check for other autoimmune diseases. However, a typical patient with LADA is aged ≥ 30 with low, normal or high BMI and varying degrees of insulin secretion, insulin resistance and metabolic syndrome.
LADA is also known as type 1.5 diabetes because they show both the autoimmune destruction of beta cells of Type 1 diabetes and the insulin resistance characteristic of Type 2 diabetes. Compared to type 1 diabetes, LADA occurs at an older age and does not require insulin for the first three to six months following diagnosis, however up to 80% of the cases will need insulin within the next 5 years of diagnosis. LADA is similar to type 1 diabetes phenotypically and imunogenetically (similar characteristics of autoantibodies). LADA patients have increased frequency of HLA-DQB1 and PTPN22 risk genotypes and alleles which distinguish them from patients with T1D diagnosed after 35 years of age. On the other hand, what makes LADA different from type 2 diabetes is that LADA is defined as an autoimmune condition hence can be distiguised from T2D by a blood tests for antibodies. Also LADA patient have a more severe defect in insulin secretion, while the component of metabolic syndrome are less prevalent.
Signs and symptoms of a LADA develop after the age of 30, this is a common reason why LADA patients are often misdiagnosed as having Type 2 diabetes and receive treatment for type 2 diabetes. Distingshion is only made when eventually, the drug they are taking fails to lower blood glucose levels under control. The symptoms of a LADA patient are divided into two phases. The first symptoms include often feeling tired and hungry after meals and foggy headaches. As LADA develops, the person’s ability to produce insulin will gradually go down and other symptoms start to appear like feeling thirsty, urge to urinate, tingling nerves and blurred vision. To decrease the risk of developing diabetes complications, it is very important to monitor symptoms and hence diagnose diabetes at an early stage. Patients with LADA don’t have standard type 2 diabetes symptoms, including metabolic syndrome indicators and have lower risk of heart problems.
About 15% of LADA patients are misdiagnosed as having type 2 diabetes because of the age at which it develops. “The only way to diagnose LADA is with a blood test for islet-cell antibodies,” Islet autoantibodies are chemicals that show up in the bloodstream when beta cells are under attack. An antibody test can measure signs of trouble years before beta cells are totally destroyed , Common antibody blood tests look for glutamic acid decarboxylase antibodies (GADA) – an antibody to an enzyme in beta cells; insulin autoantibodies (IAA) – antibodies that target insulin; and insulinoma-associated-2 autoantibodies (IA-2A) – another antibody to a beta cell enzyme. “If your test is positive for even one antibody, you have autoimmune diabetes,” Dr. Grunberger says. Some doctors also order tests for C-Peptide, a protein associated with insulin levels. While levels are low in type 1s, they will usually be higher with LADA because your body is still producing some insulin. Signs that you may have LADA, instead of type 2, including being thin, having a personal or family history of autoimmune disease, blood sugar levels that keep rising despite a healthy lifestyle and several diabetes drugs, and having healthy blood pressure and cholesterol levels. It is really important to correctly diagnose LADA and differentiate it from both type 1 and type 2 diabetes. Compared to type 1 diabetes, LADA shows the same auto-antibodies, however, the first auto-antibody to emerge is against GAD because it is the first protein to get invaded by the antibodies. Which explain the use of GAD antibodies test as a diagnostic tool. However, given that GAD auto-antibodies are also detected in classical type 1 diabetes, their use to define LADA lacks specificity. Also not all patients have these antibodies. In the very early stages of LADA, it is possible that there are no detectable antibodies, but they can develop over time. Therefore GADA test alone cannot rule out LADA. Results from one test should not be taken as a definitive diagnosis; instead two tests should be used to corroborate results. Therefore, the diagnosis of LADA is currently based on three clinical criteria: adult age at onset of diabetes, presence of circulating islet auto-antibodies (which distinguishes LADA from type 2 diabetes), and insulin dependence at diagnosis (which distinguishes LADA from type 1 diabetes).
People with LADA can experience complications from diabetes. After full insulin dependency, one of the biggest complications that can arise is ketoacidosis, which is the buildup of ketones in the body. Other complications are similar to those associated with Type 2, which include hyperglycemia, retinopathy, and neuropathy. As with type 1 diabetes, ketoacidosis is a threat in people with LADA but one that can be prevented with insulin therapy.
Taking insulin means being exposed to the risk of hypoglycemia and so insulin doses must be managed well to minimise the risk of hypos occurring. The long term complications for LADA are the same as those for type 1 diabetes and therefore notably include heart disease, stroke, retinopathy, nephropathy and neuropathy. Because LADA develops slowly, long term complications could start to develop before the condition has been diagnosed. On the plus side, because the loss of insulin producing beta cells is slower than in juvenile type 1 diabetes, if LADA is diagnosed early and well controlled, it may be easier for people with LADA to avoid complications in their lifetime than for people with type 1 diabetes diagnosed at a younger age.
The first choice of treatment is nutrition related treatment plus exercise. Dietary guidelines for patients with LADA are similar to those for patients with type 1 diabetes. Obese LADA patients should follow a healthy reduced-calorie diet and increase their physical activity levels. Clinicians should advise patients about diet and exercise programs suited to their individual needs and perform follow-up evaluations to insure that patients are adhering to the plan. A healthy, carbohydrate-controlled eating plan along with exercise and weight loss can improve insulin resistance. The second choice of treatment for patients with LADA continues with  anti-diabetic medications commonly used for type 2 diabetes patients. Three classes of medications are used known as thiazolidinediones, GLP-1 receptor agonists, and metformin. These medications help preserve beta cell mass which is important when you have LADA. LADA patients are not prescribed drugs that stimulate ß-cell insulin production. Sulfonylureas, such as glimepiride and glipizide, and incretin drugs, such as sitagliptin (Januvia, Merck) and exanatide (Byetta, Amylin Pharmaceuticals Inc.) should be avoided help blood sugar at first, but slowly poison beta cells. Eventually, LADA patient will require insulin therapy. In the beginning stages of LADA, the body may still be producing insulin, and if a misdiagnosis of Type 2 diabetes has occurred, meal planning and blood glucose lowering medications may help manage blood glucose levels. But, since the same antibodies that are present in Type 1 diabetes are present in LADA, once the body reaches complete insulin dependency, artificial insulin will need to be used to effectively manage blood glucose. Researchers are just beginning to understand the pathophysiology of LADA and are still struggling to come up with a standardized definition for the condition. Early insulin therapy appears to be recommended, but definitive treatment guidelines are not yet available.