RESULTS

In the retrospective study, subjects with LADA were significantly younger than type 2 diabetic subjects (median age 46.2 vs. 60.8 years, P < 0.0001) with a majority (64%) having diabetes diagnosed before the age of 50. The median BMI was lower in subjects with LADA compared with type 2 diabetic subjects, but a majority of both subjects with LADA and type 2 diabetes were in the overweight or obese category (BMI ≥25.0 kg/m2). Acute symptoms (polydipsia and/or polyuria and/or weight loss) were present in a majority of subjects with LADA, being significantly more frequent than in type 2 diabetic subjects (67 vs. 28%, P < 0.0001). A family history of type 1 diabetes was more common in subjects with LADA, whereas a family history of type 2 diabetes was similar in subjects with LADA and type 2 diabetes. A family or personal history of DR3- and/or DR4-related autoimmune diseases was more common in LADA. The most common associated autoimmune disease in patients with LADA was thyroid autoimmune disease and in relatives was type 1 diabetes.

On the basis of these findings, five distinguishing clinical features were significantly more frequent in subjects with LADA than in subjects with type 2 diabetes at diagnosis. These were 1) age of diabetes onset <50 years, 2) acute symptoms of polydipsia and/or polyuria and/or unintentional weight loss before diagnosis, 3) BMI <25 kg/m2, 4) a personal history of DR3- and/or DR4-related autoimmune disease, and 5) a family history of DR3- and/or DR4-related autoimmune disease. A majority (75%) of subjects with LADA and a minority (24%) of type 2 diabetic subjects had at least two distinguishing clinical features (LADA clinical risk score ≥2).

A multivariate analysis confirmed that age of diabetes onset <50 years (OR 1.85, P < 0.0001), acute symptoms (1.34, P < 0.0001), BMI <25 kg/m2 (1.29, P < 0.003), and a personal history of autoimmune disease (1.14, P = 0.0143) were independently associated with a diagnosis of LADA. In this form of analysis, family history of autoimmune disease was not independently associated with LADA. A multivariate LADA clinical risk score was determined based on the OR coefficients from the logistic regression model. The formula for calculating the multivariate LADA clinical score was [1.85 (if age of onset <50 years) + 1.29 (if BMI <25 kg/m2) + 1.37 (for the presence of acute symptoms) + 1.14 (for the presence of a personal history of autoimmune disease)]. The multivariate LADA clinical risk score was compared with the original five-point LADA clinical risk score using a ROC plot. The performance of the clinical risk scores was similar (five-point LADA clinical risk score AUC = 0.81 vs. multivariate LADA clinical risk score AUC = 0.84). The optimal cutoff point for the five-point LADA clinical risk score was ≥2 (sensitivity of 75% and specificity of 77%), and for the multivariate LADA the clinical risk score was ≥1.37 (sensitivity of 76% and specificity of 77%).

In the prospective study, a majority (86 of 130) of subjects had none or one distinguishing clinical feature. The presence of two or more distinguishing clinical features (LADA clinical score risk ≥2) had a 90% sensitivity and 71% specificity for detecting LADA. A LADA clinical risk score ≥2 identified 9 of 10 subjects with LADA and a LADA clinical risk score of ≤1 prospectively identified 86 of 120 GADA− type 2 diabetic subjects. Also, a LADA clinical risk score ≤1 was highly reliable for excluding LADA, with 86 of 87 patients who had a LADA clinical score of ≤1 being GADA− (negative predictive value 99%). The multivariate LADA clinical risk score (cutoff ≥1.37) had a similar sensitivity of 90% but lower specificity of 56% for detecting LADA.