Koffert Jukka P, Mikkola Kirsi, Virtanen Kirsi A, Andersson Anna-Maria D, Faxius Linda, Hällsten Kirsti, Heglind Mikael, Guiducci Letizia, Pham Tam, Silvola Johanna M U, Virta Jenni, Eriksson Olof, Kauhanen Saila P, Saraste Antti, Enerbäck Sven, Iozzo Patricia, Parkkola Riitta, Gomez Maria F, Nuutila Pirjo
Turku PET Centre, University of Turku, Turku, Finland; Department of Gastroenterology, Turunmaa Hospital, Southwest Finland Hospital District, Turku, Finland.
Turku PET Centre, University of Turku, Turku, Finland.
Diabetes Res Clin Pract. 2017 Sep;131:208-216. doi: 10.1016/j.diabres.2017.07.015. Epub 2017 Jul 20.
Metformin therapy is associated with diffuse intestinal 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.
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.
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.
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.
在临床诊断中，使用常规氟代脱氧葡萄糖（FDG）-正电子发射断层扫描（PET）成像时，二甲双胍治疗与弥漫性肠道FDG积聚有关。我们旨在研究二甲双胍诱导的肠道葡萄糖摄取是否与2型糖尿病患者血糖控制的改善相关。因此，我们在一项随机安慰剂对照临床试验中比较了二甲双胍和罗格列酮对2型糖尿病患者肠道葡萄糖代谢的影响，并且，为了解潜在机制，评估了二甲双胍对大鼠的作用。
41例新诊断的2型糖尿病患者在一项为期26周的双盲试验中被随机分为二甲双胍组（1克，每日两次）、罗格列酮组（4毫克，每日两次）或安慰剂组。在正常血糖高胰岛素血症期间，使用FDG-PET在治疗期前后测量组织特异性肠道葡萄糖摄取。此外，大鼠用二甲双胍或赋形剂治疗12周，并在体内和通过放射自显影测量肠道FDG摄取。
二甲双胍组小肠葡萄糖摄取增加2倍，结肠增加3倍，且与血糖控制改善相关。罗格列酮仅轻微增加肠道葡萄糖摄取。在啮齿动物中，二甲双胍治疗增强了肠道FDG保留（P = 0.002），其定位于小肠的粘膜肠上皮细胞。
二甲双胍治疗显著增强2型糖尿病患者循环中肠道葡萄糖摄取。这种肠道特异性作用与血糖控制改善相关且定位于粘膜层。这些人体研究结果证明了二甲双胍对肠道代谢的直接作用，并阐明了二甲双胍的作用机制。临床试验编号NCT02526615。
