Hannon, Tamara S.Kirkman, M. S.Patel, Yash R.Considine, Robert V.Mather, Kieren J.2016-10-062016-10-062014-11Hannon, T. S., Kirkman, Patel, Y. R., Considine, R. V., & Mather, K. J. (2014). Profound Defects in β-Cell Function in Screen-Detected Type 2 Diabetes Are Not Improved with Glucose-Lowering Treatment in the Early Diabetes Prevention Program (EDIP). Diabetes/metabolism Research and Reviews, 30(8), 767–776. http://doi.org/10.1002/dmrr.25531520-7560https://hdl.handle.net/1805/11113BACKGROUND: Few studies have measured the ability of interventions to affect declining β-cell function in screen-detected type 2 diabetes. The Early Diabetes Intervention Programme (ClinicalTrials.gov NCT01470937) was a randomized study based on the hypothesis that improving postprandial glucose excursions with acarbose would slow the progression of fasting hyperglycaemia in screen-detected type 2 diabetes. In the Early Diabetes Intervention Programme, the effect of acarbose plus lifestyle advice on progression of fasting hyperglycaemia over a 5-year period was not greater than that of placebo. However, there was an early glucose-lowering effect of the trial. The objective of the current secondary analysis was to describe β-cell function changes in response to glucose lowering. METHODS: Participants were overweight adult subjects with screen-detected type 2 diabetes. β-cell function was measured using hyperglycaemic clamps and oral glucose tolerance testing. The primary outcome was the change in β-cell function from baseline to year 1, the time point where the maximal glucose-lowering effect was seen. RESULTS: At baseline, participants exhibited markedly impaired first-phase insulin response. Despite significant reductions in weight, fasting plasma glucose (PG) and 2-h PG, there was no clinically significant improvement in the first-phase insulin response. Late-phase insulin responses declined despite beneficial glycaemic effects of interventions. CONCLUSIONS: Insulin secretion is already severely impaired in early, screen-detected type 2 diabetes. Effective glucose-lowering intervention with acarbose was not sufficient to improve insulin secretion or halt the decline of β-cell function.en-USPublisher PolicyDiabetes Mellitus, Type 2physiopathologyHyperglycemiaprevention & controlInsulinsecretionInsulin-Secreting CellsObesitycomplicationsOverweightArticle