An improved model of type 2 diabetes with effects on glucose tolerance, neuropathy and retinopathy with and without obesity

Abstract

RationaleType 2 diabetes (T2D) costs billions of dollars annually, is also associated with pain (diabetic neuropathy), as well as retinopathy, lower urinary tract/urinary bladder dysfunction, depression, and systemic inflammation, affecting quality of life for patients. To that end, animal models are utilized to explore potential treatments, but may not reflect the complexity of the condition. ObjectiveWe aimed to test an improved model of T2D that more closely mimics the clinical mechanisms and symptoms in an outbred strain of mouse. FindingsMale and female CD-1 mice (n = 72) were fed one of four diets: regular chow (REG), our Standard American Diet (SAD), a revised SAD (SAD2), or the commonly-used high-fat diet (HFD). Overall, HFD- and SAD-fed mice had significant weight gain and increased fat mass. Following injury, the SAD- and SAD2-fed mice showed protracted recovery, but the HFD-fed mice did not. Similarly, SAD- and SAD2-fed mice showed impaired retinal function compared to REG-fed mice, but the HFD-fed mice did not. ConclusionsThe SAD and SAD2 more closely model the problematic dietary intake and subsequent clinical symptoms associated with T2D. Potential Impact of studyThe adjusted SAD2 may be a better representation of a human-translatable diet than the SAD and HFD, and may allow for increased advances in the investigation of T2D-related symptoms.