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Clinical Screening Tool Developed for Identifying Type 1&1/2 Diabetes Adult Latent Autoimmune Diabetes

Posted: Wednesday, May 24, 2006

The presence of 2 or more clinical risk factors for latent autoimmune diabetes in adults (LADA) may be useful for identifying adults at high risk for LADA who require islet antibody testing, a new report suggests.

LADA is defined as the presence of adult-onset diabetes with circulating islet antibodies but without an initial requirement for insulin therapy, according to the researchers, led by Spiros Fourlanos, MD, with the Walter and Eliza Hall Institute of Medical Research, in Parkville, Victoria, Australia.

"Diagnosing LADA has treatment implications because of the high risk of progression to insulin dependency," the authors note in the May 2006 issue of Diabetes Care. "In the UKPDS [UK Prospective Diabetes Study], a majority of adults with diabetes, who had detectable GADAs, required insulin treatment within 6 years of diagnosis," the researchers note.

Currently, no recommendations for islet antibody testing exist for patients with adult-onset diabetes. Thus, Dr Fourlanos and colleagues sought to develop a clinical screening tool to identify adults at high risk of developing LADA who might require islet antibody testing.

They retrospectively interviewed 102 patients diagnosed with LADA who had positive results for the glutamate decarboxylase (GAD) antibody, as well as 111 patients with type 2 diabetes who had negative results for GAD antibody. Participants were between 30 and 75 years of age.

Several clinical features were recorded, including age of onset, acute symptoms of hyperglycemia, body mass index, and history of autoimmune disease. Responses between the 2 patient groups were compared.

Researchers classified a given feature as being a "distinguishing clinical feature" of LADA if it was significantly more frequent in patients with LADA than in those with type 2 diabetes who had negative results for GAD antibody.

The researchers found that 5 clinical features were more frequent in patients with LADA: age of onset younger than 50 years (P < .0001); acute symptoms (P < .0001); body mass index less than 25 kg/m2 (P < .0004); personal history of autoimmune disease (P = .011); and family history of autoimmune disease (P = .024).

A subsequent prospective study of adults with newly diagnosed diabetes (n = 130) was conducted to identify whether the LADA clinical risk score could, in fact, identify the presence of LADA.

In the prospective study, the presence of 2 or more of the distinguishing clinical features identified in the retrospective study (LADA clinical risk score of 2 or more) demonstrated a sensitivity of 90% and a specificity of 71% for identifying LADA among patients in the prospective study. In addition, the negative predictive value for LADA clinical risk score of 0 or 1 was 99%.

According to the authors, LADA is a slowly progressive autoimmune form of type 1 diabetes characterized by adult-onset diabetes (usually age older than 30 years), circulating islet antibodies (usually to GAD), and initial lack of insulin requirement. Ten percent of adults with diabetes have LADA. Patients with LADA experience marked loss of beta-cell function within 3 years of diagnosis, which eventually results in insulin dependence. Patients with LADA are prone to insulin deficiency and often require rapid escalation of oral hypoglycemic treatment or earlier use of insulin. The use of a screening tool for identifying LADA early may improve glycemic control, but currently clinicians tend to test for LADA using islet antibodies only if they suspect LADA based on normal body weight.

"This is the first report of a clinical screening tool to distinguish LADA from type 2 diabetes in adults presenting with diabetes," the researchers write. "This clinical screening tool should increase the identification of autoimmune diabetes in adults and hopefully improve clinical management of their disease," the investigators add.

Tools for Practice

A majority of subjects with LADA have at least 2 of 5 distinguishing clinical features consisting of diabetes onset before 50 years, acute symptoms, body mass index less than 25 kg/m2, and a personal or familial history of autoimmune disease.
A LADA risk score of 2 or less has a 90% sensitivity and 71% specificity for diagnosis of LADA, whereas a risk score of 1 or less is associated with 99% negative predictive value.

 

Source: Diabetes In Control: Diabetes Care. 2006;29:970-975

 
 
 
 
 
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