Current Challenges to Overcome in the Management of Type 2 Diabetes Mellitus and Associated Neurological Disorders

Abstract

The increasing worldwide prevalence of type 2 diabetes mellitus (T2DM) and associated neurological disorders (NDs), such as Alzheimer disease and Parkinson's disease, have raised concerns about increasing health care and financial burden. Due to the overwhelming growth rate of T2DM and its strong association with NDs, there is an ever-growing and an urgent need to improve the diagnosis and management of the disease. Major hurdles in the management of T2DM comprise of striving for glycemic targets, polypharmacy, patient adherence and clinical inertia. The challenges occurring in the treatment of T2DM are mainly attributed to the complex heterogeneous nature of the disease and its close association with a wide variety of neurological, metabolic and cardiovascular disorders. To overcome these challenges, authors propose to focus on the treatment strategies that employ shared pathogenesis and common molecular denominators involved in the aetiology of T2DM and associated NDs. Impaired insulin signalling (as a result of perturbed redox status), insulin resistance and mitochondrial dysfunction are key molecular events that may lead to the pathogenesis of T2DM and associated NDs. However, effective management of these therapeutic strategies requires holistic experimental evidence from animal as well as clinical human studies. Therefore, a shift in the treatment paradigm from single point glycemic control to shared pathogenesis control would be an ideal approach to combat the alarming progression of diabetes and associated NDs. Therapeutic interventions focused on shared molecular pathogenesis, along with effective glycemic control, may provide protection from associated NDs.

Preservation Analysis of Macrophage Gene Coexpression Between Human and Mouse Identifies PARK2 as a Genetically Controlled Master Regulator of Oxidative Phosphorylation in Humans

“…The OXPHOS pathway was of particular interest as several OXPHOS genes were annotated as susceptibility disease genes, in particular for diabetes and Alzheimer, Huntington, and Parkinson diseases ( Table 2 ). These results are consistent with recent works reporting that oxidation phosphorylation could represent a key mechanism related to mitochondrial dysfunction pathway that could explain the association between type 2 diabetes and neurological disorders ( Gibson 2005 ; Khan et al 2014 ; Hao et al 2015 ). Oxidative phosphorylation is an important component of mitochondrial function, and the later has previously been shown to be conserved between mouse and human brain transcriptome ( Miller et al 2010 ).…”

<p>Anti-Diabetic Effect of Telmisartan Through its Partial PPARγ-Agonistic Activity</p>

“…Current management of DM is associated with major hurdles, comprising polypharmacy, striving for glycemic targets, patient adherence, and clinical inertia. 48 In spite of many anti-diabetic drugs being available, adequate control of diabetic hyperglycemia often remains difficult to achieve. 49 In T2DM, intense control of glycemia generally requires the addition of insulin to oral agents, which is consistently accompanied by weight gain.…”

The Increase of HIV-1 Infection, Neurocognitive Impairment, and Type 2 Diabetes in The Rio Grande Valley

“…The connection between T2D diabetes and neurological disorders arises from various disease manifestations across different populations [85][86][87][88][89]. In addition, there is a strong correlation between HIV infection and T2D with respect to chronic immune activation, endothelial dysfunction, inflammation, and associated neurological disorders [90][91][92][93].…”