Beta cell function in the early stages of type 1 diabetes: still a long way ahead of us.

The clinical onset of type 1 diabetes (namely stage 3 type 1 diabetes [T1D]) is preceded by a relatively prolonged pre-symptomatic phase featured by islet autoimmunity [1] with (Stage 2 T1D) or without (Stage 1 T1D) dysglycaemia. While islet autoimmunity is the hallmark of the underlying autoimmune process, very little evidence is available for the metabolic changes that accompany the loss of functional beta cell mass. Indeed, a steep decline of C-peptide - a surrogate marker of beta cell function - is measurable only ~6 months before the onset of Stage 3 T1D [2]. Disease modifier drugs have, there-fore, a very limited window of intervention because we lack of effective methods to track beta cell function over time and to identify early changes of insulin secretion that precedes dysglycaemia [3, 4] and clinically symptomatic diabetes. Herein, we will revise current approaches to longitudinally track beta cell function over time before the onset of Stage 3 T1D, which might be suitable for monitoring the risk for diabetes progression as well as the effectiveness of disease modifier treatments.