Review
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World J Diabetes. Oct 15, 2014; 5(5): 697-710
Published online Oct 15, 2014. doi: 10.4239/wjd.v5.i5.697
Targeting inflammation in diabetes: Newer therapeutic options
Neeraj Kumar Agrawal, Saket Kant
Neeraj Kumar Agrawal, Saket Kant, Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India
Author contributions: Agrawal NK and Kant S made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; drafting the article and revising it critically for important intellectual content; and final approval of the version to be published.
Correspondence to: Dr. Neeraj Kumar Agrawal, Associate Professor, Department of Endocrinology and Metabolism, Institiute of Medical Sciences, Banaras Hindu University, Pandit Madan Mohan Malviya Rd, Varanasi 221005, India. drnkavns@gmail.com
Telephone: +91-941-5224741 Fax: +91-542-2367568
Received: December 27, 2013
Revised: April 24, 2014
Accepted: May 29, 2014
Published online: October 15, 2014
Processing time: 232 Days and 18.3 Hours
Abstract

Inflammation has been recognised to both decrease beta cell insulin secretion and increase insulin resistance. Circulating cytokines can affect beta cell function directly leading to secretory dysfunction and increased apoptosis. These cytokines can also indirectly affect beta cell function by increasing adipocyte inflammation.The resulting glucotoxicity and lipotoxicity further enhance the inflammatory process resulting in a vicious cycle. Weight reduction and drugs such as metformin have been shown to decrease the levels of C-Reactive Protein by 31% and 13%, respectively. Pioglitazone, insulin and statins have anti-inflammatory effects. Interleukin 1 and tumor necrosis factor-α antagonists are in trials and NSAIDs such as salsalate have shown an improvement in insulin sensitivity. Inhibition of 12-lipo-oxygenase, histone de-acetylases, and activation of sirtuin-1 are upcoming molecular targets to reduce inflammation. These therapies have also been shown to decrease the conversion of pre-diabetes state to diabetes. Drugs like glicazide, troglitazone, N-acetylcysteine and selective COX-2 inhibitors have shown benefit in diabetic neuropathy by decreasing inflammatory markers. Retinopathy drugs are used to target vascular endothelial growth factor, angiopoietin-2, various proteinases and chemokines. Drugs targeting the proteinases and various chemokines are pentoxifylline, inhibitors of nuclear factor-kappa B and mammalian target of rapamycin and are in clinical trials for diabetic nephropathy. Commonly used drugs such as insulin, metformin, peroxisome proliferator-activated receptors, glucagon like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors also decrease inflammation. Anti-inflammatory therapies represent a potential approach for the therapy of diabetes and its complications.

Keywords: Inflammation; Insulin resistance; Diabetes; Neuropathy; Retinopathy; Nephropathy

Core tip: The burden of diabetes and its complications is increasing worldwide. To control this pandemic, drugs targeting different areas of the pathogenesis of diabetes and its complications are needed. Inflammation plays a key role in the natural history of diabetes during the progression from pre-diabetes to diabetes, including decreased beta cell secretory capacity and insulin resistance. Insulin resistance is an important part of the metabolic syndrome and plays a role in the pathogenesis of various macrovascular complications. Drugs targeting inflammatory pathways represent a fresh approach in the treatment of diabetes and its complications.