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Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial

OBJECTIVE: To assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND SETTING: Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design, conducted at 8 hospitals in Denmark. PARTIC...

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Autores principales: Lundby-Christensen, Louise, Vaag, Allan, Tarnow, Lise, Almdal, Thomas P, Lund, Søren S, Wetterslev, Jørn, Gluud, Christian, Boesgaard, Trine W, Wiinberg, Niels, Perrild, Hans, Krarup, Thure, Snorgaard, Ole, Gade-Rasmussen, Birthe, Thorsteinsson, Birger, Røder, Michael, Mathiesen, Elisabeth R, Jensen, Tonny, Vestergaard, Henrik, Hedetoft, Christoffer, Breum, Leif, Duun, Elsebeth, Sneppen, Simone B, Pedersen, Oluf, Hemmingsen, Bianca, Carstensen, Bendix, Madsbad, Sten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771974/
https://www.ncbi.nlm.nih.gov/pubmed/26916685
http://dx.doi.org/10.1136/bmjopen-2015-008377
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author Lundby-Christensen, Louise
Vaag, Allan
Tarnow, Lise
Almdal, Thomas P
Lund, Søren S
Wetterslev, Jørn
Gluud, Christian
Boesgaard, Trine W
Wiinberg, Niels
Perrild, Hans
Krarup, Thure
Snorgaard, Ole
Gade-Rasmussen, Birthe
Thorsteinsson, Birger
Røder, Michael
Mathiesen, Elisabeth R
Jensen, Tonny
Vestergaard, Henrik
Hedetoft, Christoffer
Breum, Leif
Duun, Elsebeth
Sneppen, Simone B
Pedersen, Oluf
Hemmingsen, Bianca
Carstensen, Bendix
Madsbad, Sten
author_facet Lundby-Christensen, Louise
Vaag, Allan
Tarnow, Lise
Almdal, Thomas P
Lund, Søren S
Wetterslev, Jørn
Gluud, Christian
Boesgaard, Trine W
Wiinberg, Niels
Perrild, Hans
Krarup, Thure
Snorgaard, Ole
Gade-Rasmussen, Birthe
Thorsteinsson, Birger
Røder, Michael
Mathiesen, Elisabeth R
Jensen, Tonny
Vestergaard, Henrik
Hedetoft, Christoffer
Breum, Leif
Duun, Elsebeth
Sneppen, Simone B
Pedersen, Oluf
Hemmingsen, Bianca
Carstensen, Bendix
Madsbad, Sten
author_sort Lundby-Christensen, Louise
collection PubMed
description OBJECTIVE: To assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND SETTING: Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design, conducted at 8 hospitals in Denmark. PARTICIPANTS AND INTERVENTIONS: Participants with type 2 diabetes (glycated haemoglobin (HbA(1c))≥7.5% (≥58 mmol/mol), body mass index >25 kg/m(2)) were, in addition to metformin versus placebo, randomised to 18 months open-label biphasic insulin aspart 1–3 times daily (n=137) versus insulin aspart 3 times daily in combination with insulin detemir once daily (n=138) versus insulin detemir alone once daily (n=137), aiming at HbA(1c)≤7.0% (≤53 mmol/mol). OUTCOMES: Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA(1c), insulin dose, weight, and hypoglycaemic and serious adverse events were other prespecified outcomes. RESULTS: Carotid IMT change did not differ between groups (biphasic −0.009 mm (95% CI −0.022 to 0.004), aspart+detemir 0.000 mm (95% CI −0.013 to 0.013), detemir −0.012 mm (95% CI −0.025 to 0.000)). HbA(1c) was more reduced with biphasic (−1.0% (95% CI −1.2 to −0.8)) compared with the aspart+detemir (−0.4% (95% CI −0.6 to −0.3)) and detemir (−0.3% (95% CI −0.4 to −0.1)) groups (p<0.001). Weight gain was higher in the biphasic (3.3 kg (95% CI 2.7 to 4.0) and aspart+detemir (3.2 kg (95% CI 2.6 to 3.9)) compared with the detemir group (1.9 kg (95% CI 1.3 to 2.6)). Insulin dose was higher with detemir (1.6 IU/kg/day (95% CI 1.4 to 1.8)) compared with biphasic (1.0 IU/kg/day (95% CI 0.9 to 1.1)) and aspart+detemir (1.1 IU/kg/day (95% CI 1.0 to 1.3)) (p<0.001). Number of participants with severe hypoglycaemia and serious adverse events did not differ. CONCLUSIONS: Carotid IMT change did not differ between 3 insulin regimens despite differences in HbA(1c), weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results. TRIAL REGISTRATION NUMBER: NCT00657943.
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spelling pubmed-47719742016-03-01 Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial Lundby-Christensen, Louise Vaag, Allan Tarnow, Lise Almdal, Thomas P Lund, Søren S Wetterslev, Jørn Gluud, Christian Boesgaard, Trine W Wiinberg, Niels Perrild, Hans Krarup, Thure Snorgaard, Ole Gade-Rasmussen, Birthe Thorsteinsson, Birger Røder, Michael Mathiesen, Elisabeth R Jensen, Tonny Vestergaard, Henrik Hedetoft, Christoffer Breum, Leif Duun, Elsebeth Sneppen, Simone B Pedersen, Oluf Hemmingsen, Bianca Carstensen, Bendix Madsbad, Sten BMJ Open Diabetes and Endocrinology OBJECTIVE: To assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND SETTING: Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design, conducted at 8 hospitals in Denmark. PARTICIPANTS AND INTERVENTIONS: Participants with type 2 diabetes (glycated haemoglobin (HbA(1c))≥7.5% (≥58 mmol/mol), body mass index >25 kg/m(2)) were, in addition to metformin versus placebo, randomised to 18 months open-label biphasic insulin aspart 1–3 times daily (n=137) versus insulin aspart 3 times daily in combination with insulin detemir once daily (n=138) versus insulin detemir alone once daily (n=137), aiming at HbA(1c)≤7.0% (≤53 mmol/mol). OUTCOMES: Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA(1c), insulin dose, weight, and hypoglycaemic and serious adverse events were other prespecified outcomes. RESULTS: Carotid IMT change did not differ between groups (biphasic −0.009 mm (95% CI −0.022 to 0.004), aspart+detemir 0.000 mm (95% CI −0.013 to 0.013), detemir −0.012 mm (95% CI −0.025 to 0.000)). HbA(1c) was more reduced with biphasic (−1.0% (95% CI −1.2 to −0.8)) compared with the aspart+detemir (−0.4% (95% CI −0.6 to −0.3)) and detemir (−0.3% (95% CI −0.4 to −0.1)) groups (p<0.001). Weight gain was higher in the biphasic (3.3 kg (95% CI 2.7 to 4.0) and aspart+detemir (3.2 kg (95% CI 2.6 to 3.9)) compared with the detemir group (1.9 kg (95% CI 1.3 to 2.6)). Insulin dose was higher with detemir (1.6 IU/kg/day (95% CI 1.4 to 1.8)) compared with biphasic (1.0 IU/kg/day (95% CI 0.9 to 1.1)) and aspart+detemir (1.1 IU/kg/day (95% CI 1.0 to 1.3)) (p<0.001). Number of participants with severe hypoglycaemia and serious adverse events did not differ. CONCLUSIONS: Carotid IMT change did not differ between 3 insulin regimens despite differences in HbA(1c), weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results. TRIAL REGISTRATION NUMBER: NCT00657943. BMJ Publishing Group 2016-02-25 /pmc/articles/PMC4771974/ /pubmed/26916685 http://dx.doi.org/10.1136/bmjopen-2015-008377 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Diabetes and Endocrinology
Lundby-Christensen, Louise
Vaag, Allan
Tarnow, Lise
Almdal, Thomas P
Lund, Søren S
Wetterslev, Jørn
Gluud, Christian
Boesgaard, Trine W
Wiinberg, Niels
Perrild, Hans
Krarup, Thure
Snorgaard, Ole
Gade-Rasmussen, Birthe
Thorsteinsson, Birger
Røder, Michael
Mathiesen, Elisabeth R
Jensen, Tonny
Vestergaard, Henrik
Hedetoft, Christoffer
Breum, Leif
Duun, Elsebeth
Sneppen, Simone B
Pedersen, Oluf
Hemmingsen, Bianca
Carstensen, Bendix
Madsbad, Sten
Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial
title Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial
title_full Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial
title_fullStr Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial
title_full_unstemmed Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial
title_short Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial
title_sort effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised copenhagen insulin and metformin therapy (cimt) trial
topic Diabetes and Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771974/
https://www.ncbi.nlm.nih.gov/pubmed/26916685
http://dx.doi.org/10.1136/bmjopen-2015-008377
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