The effects of hydroxychloroquine on insulin sensitivity, insulin clearance and inflammation in insulin-resistant adults: A randomized trial.
AIM
To determine the effect of hydroxychloroquine (HCQ) on skeletal muscle and liver insulin sensitivity, insulin clearance, inflammation and adipokines.


METHODS
Insulin-resistant adults without rheumatic disease were randomized to 13 weeks of HCQ (400 mg/day) versus placebo (double-blinded). Primary outcomes were changes in skeletal muscle and liver insulin sensitivity assessed by hyperinsulinaemic-euglycaemic clamp and stable-isotope tracer methods. Secondary outcomes included insulin clearance, inflammation biomarkers and adipokines.


RESULTS
Compared with placebo, HCQ significantly improved skeletal muscle insulin sensitivity by 26% (p = .019) and enhanced systemic glucose clearance (p = .025). By contrast, HCQ had no effect on hepatic insulin sensitivity. HCQ did not affect insulin clearance but decreased circulating IL-6 (p = .01) and increased adiponectin (p = .045). There were no effects on leptin, RBP-4, FGF-21 or C-reactive protein.


CONCLUSIONS
HCQ selectively enhances insulin sensitivity and glucose disposal in skeletal muscle, without affecting hepatic insulin sensitivity or insulin clearance. These findings offer a mechanistic explanation for the antidiabetic properties of HCQ and suggest that this medication might be useful in conditions linked to insulin resistance such as type 2 diabetes.
['Toledo|Frederico G S|FGS|0000-0002-6570-9948', 'Miller|Rachel G|RG|0000-0003-1845-8477', 'Helbling|Nicole L|NL|', 'Zhang|Yingze|Y|', 'DeLany|James P|JP|']
D000328:Adult D003924:Diabetes Mellitus, Type 2 D006801:Humans D006886:Hydroxychloroquine D007249:Inflammation D007328:Insulin D007333:Insulin Resistance
randomized trial insulin resistance type 2 diabetes antidiabetic drug clinical physiology