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Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes : Results from a randomized clinical trial

Koffert, Jukka P.; Mikkola, Kirsi; Virtanen, Kirsi A.; Andersson, Anna Maria D.; Faxius, Linda LU ; Hällsten, Kirsti; Heglind, Mikael; Guiducci, Letizia; Pham, Tam and Silvola, Johanna M.U., et al. (2017) In Diabetes Research and Clinical Practice 131. p.208-216
Abstract

Aims Metformin therapy is associated with diffuse intestinal 18F-fluoro-deoxyglucose (FDG) accumulation in clinical diagnostics using routine FDG-PET imaging. We aimed to study whether metformin induced glucose uptake in intestine is associated with the improved glycaemic control in patients with type 2 diabetes. Therefore, we compared the effects of metformin and rosiglitazone on intestinal glucose metabolism in patients with type 2 diabetes in a randomized placebo controlled clinical trial, and further, to understand the underlying mechanism, evaluated the effect of metformin in rats. Methods Forty-one patients with newly diagnosed type 2 diabetes were randomized to metformin (1 g, b.i.d), rosiglitazone (4 mg, b.i.d), or... (More)

Aims Metformin therapy is associated with diffuse intestinal 18F-fluoro-deoxyglucose (FDG) accumulation in clinical diagnostics using routine FDG-PET imaging. We aimed to study whether metformin induced glucose uptake in intestine is associated with the improved glycaemic control in patients with type 2 diabetes. Therefore, we compared the effects of metformin and rosiglitazone on intestinal glucose metabolism in patients with type 2 diabetes in a randomized placebo controlled clinical trial, and further, to understand the underlying mechanism, evaluated the effect of metformin in rats. Methods Forty-one patients with newly diagnosed type 2 diabetes were randomized to metformin (1 g, b.i.d), rosiglitazone (4 mg, b.i.d), or placebo in a 26-week double-blind trial. Tissue specific intestinal glucose uptake was measured before and after the treatment period using FDG-PET during euglycemic hyperinsulinemia. In addition, rats were treated with metformin or vehicle for 12 weeks, and intestinal FDG uptake was measured in vivo and with autoradiography. Results Glucose uptake increased 2-fold in the small intestine and 3-fold in the colon for the metformin group and associated with improved glycemic control. Rosiglitazone increased only slightly intestinal glucose uptake. In rodents, metformin treatment enhanced intestinal FDG retention (P = 0.002), which was localized in the mucosal enterocytes of the small intestine. Conclusions Metformin treatment significantly enhances intestinal glucose uptake from the circulation of patients with type 2 diabetes. This intestine-specific effect is associated with improved glycemic control and localized to mucosal layer. These human findings demonstrate directs effect of metformin on intestinal metabolism and elucidate the actions of metformin. Clinical trial number NCT02526615

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publication status
published
subject
keywords
Glucose uptake, Intestine, Metformin
in
Diabetes Research and Clinical Practice
volume
131
pages
9 pages
publisher
Elsevier
external identifiers
  • scopus:85026543775
ISSN
0168-8227
DOI
10.1016/j.diabres.2017.07.015
language
English
LU publication?
yes
id
b84ff4c9-cd07-475c-8417-2882dd05bbba
date added to LUP
2017-08-22 16:36:51
date last changed
2017-08-23 08:52:18
@article{b84ff4c9-cd07-475c-8417-2882dd05bbba,
  abstract     = {<p>Aims Metformin therapy is associated with diffuse intestinal <sup>18</sup>F-fluoro-deoxyglucose (FDG) accumulation in clinical diagnostics using routine FDG-PET imaging. We aimed to study whether metformin induced glucose uptake in intestine is associated with the improved glycaemic control in patients with type 2 diabetes. Therefore, we compared the effects of metformin and rosiglitazone on intestinal glucose metabolism in patients with type 2 diabetes in a randomized placebo controlled clinical trial, and further, to understand the underlying mechanism, evaluated the effect of metformin in rats. Methods Forty-one patients with newly diagnosed type 2 diabetes were randomized to metformin (1 g, b.i.d), rosiglitazone (4 mg, b.i.d), or placebo in a 26-week double-blind trial. Tissue specific intestinal glucose uptake was measured before and after the treatment period using FDG-PET during euglycemic hyperinsulinemia. In addition, rats were treated with metformin or vehicle for 12 weeks, and intestinal FDG uptake was measured in vivo and with autoradiography. Results Glucose uptake increased 2-fold in the small intestine and 3-fold in the colon for the metformin group and associated with improved glycemic control. Rosiglitazone increased only slightly intestinal glucose uptake. In rodents, metformin treatment enhanced intestinal FDG retention (P = 0.002), which was localized in the mucosal enterocytes of the small intestine. Conclusions Metformin treatment significantly enhances intestinal glucose uptake from the circulation of patients with type 2 diabetes. This intestine-specific effect is associated with improved glycemic control and localized to mucosal layer. These human findings demonstrate directs effect of metformin on intestinal metabolism and elucidate the actions of metformin. Clinical trial number NCT02526615</p>},
  author       = {Koffert, Jukka P. and Mikkola, Kirsi and Virtanen, Kirsi A. and Andersson, Anna Maria D. and Faxius, Linda and Hällsten, Kirsti and Heglind, Mikael and Guiducci, Letizia and Pham, Tam and Silvola, Johanna M.U. and Virta, Jenni and Eriksson, Lars-Olof and Kauhanen, Saila P. and Saraste, Antti and Enerbäck, Sven and Iozzo, Patricia and Parkkola, Riitta and Gomez, Maria F. and Nuutila, Pirjo},
  issn         = {0168-8227},
  keyword      = {Glucose uptake,Intestine,Metformin},
  language     = {eng},
  month        = {09},
  pages        = {208--216},
  publisher    = {Elsevier},
  series       = {Diabetes Research and Clinical Practice},
  title        = {Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes : Results from a randomized clinical trial},
  url          = {http://dx.doi.org/10.1016/j.diabres.2017.07.015},
  volume       = {131},
  year         = {2017},
}