Acute peripheral administration of synthetic human GLP-1 (7–36 amide) decreases circulating IL-6 in obese patients with type 2 diabetes mellitus: A potential role for GLP-1 in modulation of the diabetic pro-inflammatory state?

• We studied effects of GLP-1 on circulating IL-6 in type 2 diabetes.
• GLP-1 infusion caused significant reduction in IL-6.
• IL-6 is linked to obesity and insulin resistance.
• Do GLP-1-based diabetes therapies impact favourably on cardiovascular outcomes?

BackgroundTo explore the effects of acute administration of GLP-1 and GIP on circulating levels of key adipocyte-derived hormones and gut-brain peptides with established roles in energy and appetite regulation, modulation of insulin sensitivity and inflammation.MethodsSix obese male patients with diet-treated type 2 diabetes (T2DM) and 6 healthy lean subjects were studied. The protocol included 4 experiments for each participant that were carried out in randomised order and comprised: GLP-1 infusion at a rate of 1 pmol/kg/min for 4 h, GIP at a rate of 2 pmol/kg/min, GLP-1 + GIP and placebo infusion. Plasma leptin, adiponectin, IL-6, insulin, ghrelin and obestatin were measured at baseline, 15, 60, 120, 180 and 240 min following the start of infusion.ResultsPatients with T2DM had higher baseline IL-6 compared with healthy [day of placebo infusion: T2DM IL-6 mean (SEM) 1.3 (0.3) pg/ml vs 0.3 (0.1) pg/ml, p = 0.003]. GLP-1 infusion in T2DM was associated with a significant reduction in circulating IL-6 [baseline IL-6 1.2 pg/ml vs IL-6 = 0.7 at 120 min, p = 0.0001; vs IL-6 = 0.8 at 180 min, p = 0.001]. There was no significant change in leptin, adiponectin, ghrelin or obestatin compared to baseline on all 4 experimental days in both groups.ConclusionShort-term infusion of supraphysiological concentrations of GLP-1 in T2DM results in suppression of IL-6, a key inflammatory mediator strongly linked to development of obesity and T2DM-related insulin resistance. It remains to be confirmed whether GLP-1-based diabetes therapies can impact favourably on cardiovascular outcomes.