Guo Aili, Daniels Nigel A, Thuma Jean, McCall Kelly D, Malgor Ramiro, Schwartz Frank L
Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio 45701, United States of America; The Diabetes Institute at Ohio University, Athens, Ohio 45701, United States of America.
PLoS One. 2015 Jan 29;10(1):e0117556. doi: 10.1371/journal.pone.0117556. eCollection 2015.
Clinical studies suggest that short-term insulin treatment in new-onset type 2 diabetes (T2DM) can promote prolonged glycemic control. The purpose of this study was to establish an animal model to examine such a "legacy" effect of early insulin therapy (EIT) in long-term glycemic control in new-onset T2DM. The objective of the study was to investigate the role of diet following onset of diabetes in the favorable outcomes of EIT.
As such, C57BL6/J male mice were fed a high-fat diet (HFD) for 21 weeks to induce diabetes and then received 4 weeks of daily insulin glargine or sham subcutaneous injections. Subsequently, mice were either kept on the HFD or switched to a low-fat diet (LFD) for 4 additional weeks.
Mice fed a HFD gained significant fat mass and displayed increased leptin levels, increasing insulin resistance (poor HOMA-IR) and worse glucose tolerance test (GTT) performance in comparison to mice fed a LFD, as expected. Insulin-treated diabetic mice but maintained on the HFD demonstrated even greater weight gain and insulin resistance compared to sham-treated mice. However, insulin-treated mice switched to the LFD exhibited a better HOMA-IR compared to those mice left on a HFD. Further, between the insulin-treated and sham control mice, in spite of similar HOMA-IR values, the insulin-treated mice switched to a LFD following insulin therapy did demonstrate significantly better HOMA-B% values than sham control and insulin-treated HFD mice.
CONCLUSION/INTERPRETATION: Early insulin treatment in HFD-induced T2DM in C57BL6/J mice was only beneficial in animals that were switched to a LFD after insulin treatment which may explain why a similar legacy effect in humans is achieved clinically in only a portion of cases studied, emphasizing a vital role for diet adherence in diabetes control.
临床研究表明，新发2型糖尿病（T2DM）患者短期胰岛素治疗可促进长期血糖控制。本研究的目的是建立一个动物模型，以检验早期胰岛素治疗（EIT）对新发T2DM长期血糖控制的这种“遗留”效应。该研究的目的是调查糖尿病发病后饮食在EIT良好结局中的作用。
因此，给C57BL6/J雄性小鼠喂食高脂饮食（HFD）21周以诱导糖尿病，然后每天接受4周的甘精胰岛素或假皮下注射。随后，小鼠要么继续喂食HFD，要么改为低脂饮食（LFD）并再持续4周。
与喂食LFD的小鼠相比，喂食HFD的小鼠获得了显著的脂肪量，瘦素水平升高，胰岛素抵抗增加（HOMA-IR较差），葡萄糖耐量试验（GTT）表现更差，这在意料之中。与假手术治疗的小鼠相比，接受胰岛素治疗但继续喂食HFD的糖尿病小鼠体重增加和胰岛素抵抗更大。然而，改为LFD的胰岛素治疗小鼠比继续喂食HFD的小鼠表现出更好的HOMA-IR。此外，在胰岛素治疗组和假手术对照组小鼠之间，尽管HOMA-IR值相似，但胰岛素治疗后改为LFD的小鼠的HOMA-B%值确实显著优于假手术对照组和胰岛素治疗的HFD小鼠。
结论/解读：在C57BL6/J小鼠的HFD诱导的T2DM中，早期胰岛素治疗仅对胰岛素治疗后改为LFD的动物有益，这可能解释了为什么在临床研究的部分病例中仅在一部分患者中实现了类似的人类遗留效应，强调了饮食依从性在糖尿病控制中的关键作用。
