Diabetes mellitus, inflammation, obesity: proposed treatment pathways for current and future therapies.
OBJECTIVE
To review the pathophysiology, pharmacology, and current or future therapies under study for use in treating diabetes mellitus, inflammation associated with diabetes mellitus, and/or obesity related to diabetes mellitus, through 1 of 4 investigational pathways: adiponectin, ghrelin, resveratrol, or leptin.


METHODS
A literature search using MEDLINE (1966-December 12, 2009), PubMed (1950-December 12, 2009), Science Direct (1994-December 12, 2009), and International Pharmaceutical Abstracts (1970-December 12, 2009) was performed using the terms adiponectin, ghrelin, resveratrol, leptin, inflammation, obesity, and diabetes mellitus. English-language, original research, and review articles were examined, and citations from these articles were assessed as well.


METHODS
Clinical studies and in vitro studies were included in addition to any Phase 1, 2, or 3 clinical trials.


RESULTS
Mechanistic pathways regarding adiponectin, ghrelin, resveratrol, and leptin are of interest as future treatment options for diabetes mellitus. Each of these pathways has produced significant in vitro and in vivo clinical data warranting further research as a possible treatment pathway for diabetes-related inflammation and/or obesity reduction. While research is still underway to determine the exact effects these pathways have on metabolic function, current data suggest that each of these compounds may be of interest for future therapies.


CONCLUSIONS
While several pathways under investigation may offer additional benefits in the treatment of diabetes mellitus and associated impairments, further investigation is necessary for both investigational and approved therapies to ensure that the impact in new pathways does not increase risks to patient safety and outcomes.
Department of Pharmacotherapy, Washington State University, Pullman, 99164, USA. tsonnett@wsu.edu
Travis E
TE
Sonnett
Terri L
TL
Levien
Brian J
BJ
Gates
Jennifer D
JD
Robinson
R Keith
RK
Campbell
D052242:Adiponectin / Q000037:antagonists & inhibitors / Q000502:physiology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000188:drug therapy*; D054439:Ghrelin / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy*; D020738:Leptin / Q000037:antagonists & inhibitors / Q000502:physiology; D009765:Obesity / Q000188:drug therapy*; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use
D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D019440:Anti-Obesity Agents; D000975:Antioxidants; D054439:Ghrelin; D007004:Hypoglycemic Agents; D020738:Leptin; D013267:Stilbenes; D000077185:Resveratrol