Bridging the Gap Between Diabetes and Stroke in Search of High Clinical Relevance Therapeutic Targets

Neuromolecular Med. 2019 Dec;21(4):432-444. doi: 10.1007/s12017-019-08563-5. Epub 2019 Sep 5.

Abstract

Diabetes affects more than 425 million people worldwide, a scale approaching pandemic proportion. Diabetes represents a major risk factor for stroke, and therefore is actively addressed for stroke prevention. However, how diabetes affects stroke severity has not yet been extensively considered, which is surprising given the evident but understudied common mechanistic features of both pathologies. The increase in number of diabetic people, incidence of stroke in the presence of this specific risk factor, and the exacerbation of ischemic brain damage in diabetic conditions (at least in animal models) warrants the need to integrate this comorbidity in preclinical studies of brain ischemia to develop novel therapeutic approaches. Therefore, a better understanding of the commonalties involved in the course of both diseases would offer the promise of discovering novel neuroprotective pathways that would be more appropriated to clinical scenarios. In this article, we will review the relevant mechanisms that have been identified as common traits of both pathologies and that could be, to our knowledge, potential targets in both pathologies.

Keywords: Comorbidity; Glucolipotoxicity; Hyperglycemia; Signaling pathways; Tolerance to brain ischemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain Damage, Chronic / etiology
  • Cardiovascular Diseases / epidemiology
  • Clinical Trials as Topic
  • Comorbidity
  • Diabetes Complications / physiopathology
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / physiopathology*
  • Diet / adverse effects
  • Disease Models, Animal
  • Humans
  • Hyperlipidemias / epidemiology
  • Hyperlipidemias / physiopathology
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Ischemic Stroke / drug therapy
  • Ischemic Stroke / epidemiology
  • Ischemic Stroke / physiopathology*
  • Ischemic Stroke / prevention & control
  • Metabolic Syndrome / epidemiology
  • Metabolic Syndrome / physiopathology
  • Neuroprotective Agents / therapeutic use
  • Obesity / epidemiology
  • Prevalence
  • Risk Factors
  • Sedentary Behavior
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • Hypoglycemic Agents
  • Neuroprotective Agents