Abstract
ABSTRACTPeripheral neuropathy (neuropathy) is a common complication of obesity and type 2 diabetes in children and adolescents. To model this complication in mice, 5-week-old male C57BL/6J mice were fed a high-fat diet to induce diet-induced obesity (DIO), a model of prediabetes, and a cohort of these animals was injected with low-dose streptozotocin (STZ) at 12 weeks of age to induce hyperglycemia and type 2 diabetes. Neuropathy assessments at 16, 24 and 36 weeks demonstrated that DIO and DIO-STZ mice displayed decreased motor and sensory nerve conduction velocities as early as 16 weeks, hypoalgesia by 24 weeks and cutaneous nerve fiber loss by 36 weeks, relative to control mice fed a standard diet. Interestingly, neuropathy severity was similar in DIO and DIO-STZ mice at all time points despite significantly higher fasting glucose levels in the DIO-STZ mice. These mouse models provide critical tools to better understand the underlying pathogenesis of prediabetic and diabetic neuropathy from youth to adulthood, and support the idea that hyperglycemia alone does not drive early neuropathy.This article has an associated First Person interview with the first author of the paper.
Highlights
According to a recent study released by the Centers for Disease Control and Prevention (CDC) as part of the Youth Risk Behavior Surveillance System, 15.6% of adolescents in the US are overweight and an additional 14.8% are obese
Metabolic phenotyping Our study consisted of three groups of C57BL/6J mice: control mice fed a standard diet (SD mice), mice fed a high-fat (HF) diet to induce diet-induced obesity (DIO) (DIO mice), and DIO mice injected with STZ (DIO-STZ mice) to model T2D (Fig. 1A)
We longitudinally phenotyped neuropathy in non-genetic murine models of prediabetes (DIO) and type 2 diabetes (DIO-STZ) over a period spanning adolescence to adulthood
Summary
According to a recent study released by the Centers for Disease Control and Prevention (CDC) as part of the Youth Risk Behavior Surveillance System, 15.6% of adolescents in the US are overweight and an additional 14.8% are obese (www.cdc.gov). Of the 27,000 participants in The SEARCH for Diabetes in Youth study (SEARCH), the Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA. Received 1 October 2018; Accepted 9 November 2018 incidence of type 2 diabetes is as high as 8.9% in youth between 10 and 19 years of age. Among those with type 2 diabetes, the most prevalent complication is neuropathy, present in over 22% of the study population (Jaiswal et al, 2017; Jensen and Dabelea, 2018)
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