The honeymoon phase: intersection of metabolism and immunology

Purpose of review Even though the honeymoon phase in type 1 diabetes mellitus has been well known, its underlying pathogenic mechanisms remain poorly described. The common explanation that it occurs due to 'beta-cell rest' on initiation of insulin therapy seems inadequate based on recent observations and studies and its underlying immunological aspects overlooked. Recent findings In this article, we will review the metabolic and immunological aspects of the honeymoon phase and we will present our current model of the pathophysiology of this phase. Our view is that it is one of many phases of remission occurring basically due to development of adaptive immune tolerance along the course of type 1 diabetes. We will also review new findings of the interplay between metabolic factors (ambient glucose level) and immune function. Summary The honeymoon phase provides a unique model to understand the pathogenesis of type 1 diabetes. Research to unravel its immune pathogenesis is needed. It may turn out that the optimum form of intervention in type 1 diabetes is one that combines enhancement of antigen-specific adaptive immune tolerance with optimized metabolic control in order to keep cytotoxic T cells anergic.