TY - JOUR
TI - Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data
AU - Gabriel, R.
AU - Abdelkader, N.B.
AU - Acosta, T.
AU - Gilis-Januszewska, A.
AU - Gómez-Huelgas, R.
AU - Makrilakis, K.
AU - Kamenov, Z.
AU - Paulweber, B.
AU - Satman, I.
AU - Djordjevic, P.
AU - Alkandari, A.
AU - Mitrakou, A.
AU - Lalic, N.
AU - Colagiuri, S.
AU - Lindström, J.
AU - Egido, J.
AU - Natali, A.
AU - Pastor, J.C.
AU - Teuschl, Y.
AU - Lind, M.
AU - Silva, L.
AU - López-Ridaura, R.
AU - Tuomilehto, J.
JO - PLOS ONE
PY - 2020
VL - 15
TODO - 4
SP - null
PB - Public Library of Science
SN - null
TODO - 10.1371/journal.pone.0231196
TODO - biological marker;  linagliptin;  linagliptin plus metformin;  metformin;  linagliptin;  metformin, adult;  aged;  Article;  clinical protocol;  cognition;  controlled study;  depression;  diabetes mellitus;  diabetic retinopathy;  diet;  double blind procedure;  early intervention;  Early Treatment Diabetic Retinopathy Study Score;  endothelium;  fatty liver;  female;  human;  hyperglycemia;  impaired glucose tolerance;  inflammation;  kidney disease;  lifestyle;  major clinical study;  male;  microangiopathy;  multicenter study;  neuropathy;  pancreas islet beta cell;  pancreas islet cell function;  physical activity;  prevalence;  prevention study;  quality of life;  randomized controlled trial;  risk factor;  scoring system;  skin conductance;  symptom;  treatment duration;  clinical trial;  complication;  diabetic complication;  diabetic nephropathy;  diabetic neuropathy;  diabetic retinopathy;  electrodermal response;  epidemiology;  Europe;  hyperglycemia;  international cooperation;  methodology;  microcirculation;  middle aged;  non insulin dependent diabetes mellitus;  patient selection, Aged;  Diabetes Complications;  Diabetes Mellitus, Type 2;  Diabetic Nephropathies;  Diabetic Neuropathies;  Diabetic Retinopathy;  Double-Blind Method;  Europe;  Female;  Galvanic Skin Response;  Humans;  Hyperglycemia;  International Cooperation;  Life Style;  Linagliptin;  Male;  Metformin;  Microcirculation;  Middle Aged;  Patient Selection;  Research Design;  Risk Factors
TODO - Objectives To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes. Methods Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial. Participants Males and females aged 45-74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey. Intervention Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: Composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function. Results One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%. Conclusions ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with prediabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes. © 2020 Gabriel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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