title: An anti-inflammatory sterol decreases obesity-related inflammation-induced insulin resistance and metabolic dysregulation.
abstract: Obesity-related inflammation-induced insulin resistance and metabolic dysregulation were investigated in retrospective analysis of placebo hematologic and metabolic laboratory data from trials associated with increasing chronic low-grade inflammation and body mass index. Studies included healthy subjects and those with progressive stages of metabolic dysregulation, including type 2 diabetes mellitus with uncontrolled hemoglobin A1c. Intrasubject variances in erythroid and metabolic values increased with metabolic dysregulation. Random effects were demonstrated in treatment-naïve diabetes for erythroid, glucose, and HbA1c fluctuations. The anti-inflammatory insulin sensitizer, HE3286, was tested for its ability to decrease obesity-related inflammation-induced insulin resistance and metabolic dysregulation in diabetes. HE3286 significantly decreased erythroid and metabolic variances and improved 1,5-anhydroglucitol (a surrogate of postprandial glucose) compared to the placebo group. HE3286 HbA1c decrease correlated with weight loss and inversely with baseline monocyte chemoattractant protein-1 (MCP-1) in metformin-treated diabetics. Normalization of HbA1c to the 84-day average hemoglobin revealed that HE3286 HbA1c decrease correlated with high baseline MCP-1 and MCP-1 decrease in treatment-naïve diabetics. HE3286 decreased insulin resistance, increased the frequency of decreased day 84 HbA1c in metformin-treated subjects, and decreased day 112 HbA1c in treatment-naïve diabetics. HE3286 may be useful to restore metabolic homeostasis in type 2 diabetes.
authors: Harbor Therapeutics, Inc., San Diego, CA 92122, USA. creading@harbortx.com
authors: Chris L
authors: CL
authors: Reading
authors: Jaime
authors: J
authors: Flores-Riveros
authors: Dwight R
authors: DR
authors: Stickney
authors: James M
authors: JM
authors: Frincke
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000276:immunology*; D013261:Sterols / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D013261:Sterols