title: Profound defects in β-cell function in screen-detected type 2 diabetes are not improved with glucose-lowering treatment in the Early Diabetes Intervention Program (EDIP).
abstract: BACKGROUND
  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.
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Tamara S
authors.initials: TS
authors.lastname: Hannon
authors.forename: M S
authors.initials: MS
authors.lastname: Kirkman
authors.forename: Yash R
authors.initials: YR
authors.lastname: Patel
authors.forename: Robert V
authors.initials: RV
authors.lastname: Considine
authors.forename: Kieren J
authors.initials: KJ
authors.lastname: Mather
mesh_terms: D020909:Acarbose / Q000627:therapeutic use; D000328:Adult; D015992:Body Mass Index; D003131:Combined Modality Therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy; D003927:Diet, Diabetic; D004038:Diet, Reducing; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D065089:Glycoside Hydrolase Inhibitors / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008019:Life Style; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000178:diet therapy; D050177:Overweight / Q000150:complications* / Q000178:diet therapy; D010353:Patient Education as Topic; D015431:Weight Loss
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D007328:Insulin; D020909:Acarbose
keywords: acarbose; hyperglycaemic clamp; insulin; obesity; oral glucose tolerance test