Inaugural Conference: UKPDS Legacy and Precision Therapy for Type 2 Diabetes Mellitus

Abstract

Diabetes is an endocrine deficiency disease, a logical treatment of which is hormone replacement therapy¹. The 20-year UK Prospective Diabetes Study (UKPDS) ran from 1977 to 1997 and enrolled 5,102 people with newly-diagnosed type 2 diabetes (T2D) from 23 UK hospital centres. It was a factorial-design, randomised, controlled, outcome trial that assigned 3,867 participants to conventional glucose control (primarily with diet) or intensive glucose control with sulfonylurea, basal insulin or metformin (if overweight). The 1,148 participants found to be hypertensive were randomised to less-tight or tight blood pressure control. In 1997, all surviving participants were returned to primary care and entered a 10-year observational post-trial monitoring study.

Key within-trial findings showed that T2D is not a “mild” disease as at diagnosis 50% of patients had complications, highlighting the need to find them earlier. Hyperglycaemia was shown to be an independent modifiable risk factor for coronary heart disease and progressive hyperglycaemia was identified as a fundamental underlying pathology that was shown to be secondary to declining beta cell function over time. Participants with hypertension and T2D were found to be at “doublé jeopardy” with a 45% greater risk of any diabetes related endpoint, compared with normotensive participants, and worsening kidney function was shown to substantially increase the risk of death.