brief history of the UK Prospective Diabetes Study: RURY R HOLMAN, FOR THE UKPDS GROUP

Abstract

The UK Prospective Diabetes Study (UKPDS) epidemiological findings confirmed that T2DM is not a “mild” disease, with roughly 50% of patients having clinically evident complica- tions at diagnosis, emphasising the need for its early detection and treatment. Hyperglycaemia was identified as an independent coronary heart disease risk factor, with progressive hyperglycaemia shown to be a major pathophysiological feature of T2DM, driven by declining beta-cell function. People with T2DM and hypertension were found to be at double jeopardy for any diabetes endpoint, and worsening kidney function was shown to increase the risk of death substantially. The UKPDS 20-year trial results were the first to demon- strate that diabetic complications are not inevitable but can be prevented by more intensive blood glucose control and by metformin therapy, changing T2DM management guide- lines worldwide. The UKPDS also showed that tighter blood pressure control prevents diabetic complications; the benefits of the glucose and blood pressure interventions are additive. The UKPDS 10-year post-trial monitoring study was the first to identify the T2DM glycaemic and metformin legacy effects, with early more intensive therapy having continuing benefits long after the trial terminated. The trial demon- strated the need to achieve good glycaemic control as early as possible to minimise the risk of future complications.