Diagnosis and treatment of latent autoimmune diabetes in adults still evolving
Latent autoimmune diabetes in adults (LADA) is a complex autoimmune form of diabetes that is sometimes referred to as type 1.5 diabetes. LADA is often mistakenly diagnosed and treated as type 2 diabetes.1 To better understand LADA, it helps to know some basic information about both type 1 and type 2 diabetes.
Diabetes: Types 1 and 2
Type 1 diabetes is fairly uncommon and is only found in about 5% of patients with diabetes.2 Pateints that have type 1 diabetes cannot produce insulin. Type 1 diabetes symptoms include frequent urination, extreme hunger or thirst, weight loss and extreme fatigue or irritability. Symptoms tend to come on suddenly and more severely than with type 2 diabetes.3
Although patients with type 1 diabetes may develop the condition at any time, it is typically diagnosed early in childhood or adolescence. Patients with type 1 diabetes become insulin dependent very rapidly — usually within days or weeks.4
Patients with type 2 diabetes produce insulin, but the body is unable to use it. Blood glucose levels rise as glucose accumulates in the blood. Unlike with type 1 diabetes, symptoms may develop very slowly over a period of years. Many patients have type 2 diabetes and do not know it.
Type 2 diabetes symptoms include increased thirst and urination. Although hunger can increase, patients with this type of diabetes may lose weight because the body burns muscle and fat for energy in place of glucose. Increased urine glucose levels indicate calorie loss. Fatigue and irritability are common, and vision may become blurry.
Patients with type 2 diabetes are slow to heal when injured and have lower resistance to infection.3 This can lead to serious complications, such as kidney damage and loss of feet or limbs from foot ulcers.
Obesity, a sedentary lifestyle, high blood pressure and a high-fat diet are risk factors for type 2 diabetes. Certain ethnic groups, such as blacks and Native Americans, are also at greater risk.
LADA is distinguished from type 2 diabetes by the presence of islet autoantibodies that are common to type 1 diabetes.
Patients with type 1 diabetes commonly have one or more of four islet autoantibodies — islet cell antigens (ICAs), glutamic acid decarboxylase autoantibodies (GADAs) or tyrosine phosphatase proteins (IA-2s) — whereas patients with LADA typically only have one autoantibody. LADA patients have a far less incidence of IA-2 and ICA autoantibodies than patients with type 1.5
Results from a study by Stenström et al indicate that patients who developed type 2 diabetes that had two or three autoantibodies experienced severe deterioration of ß-cell function within five years, whereas patients with type 2 diabetes that had only one autoantibody did not develop severe ß-cell dysfunction until 12 years later. Five study patients that did not initially have autoantibodies at the time of diabetes diagnosis developed autoantibodies further in the study, which suggested that some patients may have an even later onset of severe ß-cell dysfunction after 12 years.6
The Immunology of Diabetes Society released the following criteria to determine if patients have LADA, specifying that patients be: aged at least 30 years or older, positive for at least one of the autoantibodies found in type 1 diabetes and free from insulin treatment for the first six months after diagnosis.5
A study by Palmer et al that was published in Diabetes in December 2005, compared insulin resistance in patients with LADA, type 2 diabetes and patients without any type of diabetes. They found that LADA and patients with type 2 diabetes had comparable glycemic control. BMI was positively correlated with increased insulin resistance. After correcting for BMI, LADA patients and type 2 diabetes patients were significantly more insulin resistant than the normal control subjects.5
Accurately diagnosing LADA can be difficult and proper treatment depends on distinguishing LADA from type 2 diabetes. Results from one test should not be taken as a definitive diagnosis; instead two tests should be used to corroborate results.
Performing a GADA antibody test is the most common method of diagnosing LADA, but 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.
Distinguishing LADA from patients with type 2 diabetes is important to ensure that 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.7
There is no single optimal treatment for LADA.
Results of a 2010 study by Thunander et al indicate that early insulin therapy in LADA is both safe and preserves metabolic control, but the results did not significantly confirm better ß-cell function preservation compared with conventional treatment.8 However, a 2007 Cochrane review that evaluated seven different insulin studies in patients with LADA concluded that the evidence is not compelling to support insulin administration.9
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.
Clinicians should also treat patients with LADA for cardiovascular risk factors, as these patients have a similar risk for coronary heart disease and cerebrovascular disease as patients with type 2 diabetes.10
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.
Roma Lightsey is a freelance medical writer. She has a B.A. in communications, as well as a B.S.N. Currently, Lightsey works as an R.N. in a large city hospital and is pursuing her M.S.N.
7. Näntö-Salonen K, et al. Lancet 2008; DOI:10.1016/S0140-6736(08)61310-0.Myhill P, Davis WA, Bruce DG et al. Diabetic Medicine. 2008; 25: 1245–1250.