Jukka P Koffert1, Kirsi Mikkola2, Kirsi A Virtanen2, Anna-Maria D Andersson3, Linda Faxius3, Kirsti Hällsten2, Mikael Heglind4, Letizia Guiducci5, Tam Pham2, Johanna M U Silvola2, Jenni Virta2, Olof Eriksson6, Saila P Kauhanen7, Antti Saraste8, Sven Enerbäck4, Patricia Iozzo5, Riitta Parkkola9, Maria F Gomez3, Pirjo Nuutila10. 1. Turku PET Centre, University of Turku, Turku, Finland; Department of Gastroenterology, Turunmaa Hospital, Southwest Finland Hospital District, Turku, Finland. 2. Turku PET Centre, University of Turku, Turku, Finland. 3. Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Sweden. 4. Department of Clinical and Medical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE 40530 Gothenburg, Sweden. 5. Institute of Clinical Physiology, National Research Council, Pisa, Italy. 6. Turku PET Centre, University of Turku, Turku, Finland; Department of Biosciences, Åbo Akademi University, Turku, Finland; Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden. 7. Turku PET Centre, University of Turku, Turku, Finland; Division of Digestive Surgery and Urology, Turku University Hospital, Turku, Finland. 8. Turku PET Centre, University of Turku, Turku, Finland; Heart Center, Turku University Hospital, Turku, Finland. 9. Department of Radiology, Turku University, Finland; Department of Radiology, Turku University Hospital, Finland. 10. Turku PET Centre, University of Turku, Turku, Finland; Department of Endocrinology, Turku University Hospital, Turku, Finland. Electronic address: pirjo.nuutila@utu.fi.
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 (1g, b.i.d), rosiglitazone (4mg, 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 12weeks, 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.
RCT Entities:
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 (1g, b.i.d), rosiglitazone (4mg, 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 12weeks, 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.
Authors: Han-Chow E Koh; Stephan van Vliet; Gretchen A Meyer; Richard Laforest; Robert J Gropler; Samuel Klein; Bettina Mittendorfer Journal: Diabetologia Date: 2021-01-29 Impact factor: 10.122
Authors: Han-Chow E Koh; Stephan van Vliet; Terri A Pietka; Gretchen A Meyer; Babak Razani; Richard Laforest; Robert J Gropler; Bettina Mittendorfer Journal: Diabetes Date: 2021-07-15 Impact factor: 9.337