Early Insulinization to Prevent Diabetes Progression

Abstract

This article reviews data collected from clinical studies regarding the place of early insulin treatment in preservation of β-cell function in type 2 diabetic patients. It emphasizes the stepwise progression of the data, starting with small uncontrolled studies and progressing to larger-scale controlled studies. It summarizes current knowledge in the field, emphasizing the additional information gained from the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial (1). ### Effect of glucotoxicity and lipotoxicity on β-cells Glucotoxicity and lipotoxicity have long been recognized as having a deleterious effect on both β-cell function and insulin action (2–4). Glucolipotoxicity refers to the combined deleterious effects of elevated glucose and free fatty acids on β-cell mass and function (5). Significant progress has been made in recent years toward a better understanding of the cellular and molecular basis of glucolipotoxicity (5–7). Insulin protects the β-cell by inducing rapid reversal of glucolipotoxicity and β-cell rest (8,9). The rapid reversal of glucolipotoxicity by insulin therapy is one of the justifications for early insulin treatment (2–10). ### Treat to target or treat to failure? The importance of avoiding prolonged hyperglycemia in patients with short diabetes duration in order to minimize its negative effect on late microvascular and macrovascular complications has been established (11). Hence, present guidelines (12–16) recommend early initiation of life style changes with or without metformin and subsequent addition of 2nd- and 3rd-line therapy when previous treatments fail to achieve or maintain the goal. The goals in the treatment of hyperglycemia in newly diagnosed type 2 diabetes are to achieve near-normal glucose control as early as possible in order to preserve β-cell function and maintain long-term normoglycemia. The capacity of antidiabetes medication to maintain prolonged glycemic control (glucose durability) is of great importance. In the ADOPT study, rosiglitazone (17) demonstrated the best “glucose durability” compared with sulfonylurea (SU) and metformin. …