CONCLUSIONS

A retrospective study of clinical parameters at diagnosis in adult-onset diabetes revealed that a majority of subjects with LADA had at least two of five distinguishing clinical features (age of onset <50 years, acute symptoms, BMI <25 kg/m2, personal history of autoimmune disease, or family history of autoimmune disease) compared with a minority of type 2 diabetic subjects. In a prospective validation study, the presence of at least two distinguishing clinical features (LADA clinical risk score ≥2) at diagnosis had 90% sensitivity and 71% specificity for detecting LADA. Furthermore, the presence of less than two distinguishing clinical features (LADA clinical risk score ≤1) was a highly reliable method for excluding LADA (negative predictive value 99%). This clinical screening method is superior to the current popular clinical practice of only screening patients with a BMI <25 kg/m2 for GADAs. Using this normal BMI cutoff as the sole criterion in the prospective study would result in a 30% sensitivity, because a majority of subjects with LADA are overweight or obese.

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This is the first report of a clinical screening tool to distinguish LADA from type 2 diabetes in adults presenting with diabetes. We carefully dissected clinical features at presentation of diabetes in adults, given that previous reports of clinical features suggested that there is no one consistent distinguishing clinical feature that discriminates LADA from type 2 diabetes. An earlier age of onset in LADA compared with type 2 diabetes was documented in a large study but not in other smaller studies. BMI was lower in LADA compared with type 2 diabetes in the UKPDS cohort as well as in several other studies, but this difference was not seen in smaller studies. Presentation with acute symptoms was investigated in one study, which showed that they were more frequent in subjects with LADA than in those with type 2 diabetes. Addressing family history of diabetes, another study showed no difference in either type 1 diabetes or type 2 diabetes in subjects with LADA compared with type 2 diabetic subjects. It was interesting that a family history of type 2 diabetes did not necessarily signify that an individual had type 2 diabetes, given that a majority (57%) of our subjects with LADA had a family history of type 2 diabetes with an overall frequency similar to that of the type 2 diabetic subjects (55%). There have been no reports on the frequency or family history of DR3- and/or DR4-related autoimmune disease in LADA. Thus, what seems clear from previous studies is that no one clinical feature reliably discriminates LADA from type 2 diabetes.