Low dose chloroquine decreases insulin resistance in human metabolic syndrome but does not reduce carotid intima-media thickness

Diabetology & Metabolic Syndrome
Janet B McGillClay F Semenkovich

Abstract

Metabolic syndrome, an obesity-related condition associated with insulin resistance and low-grade inflammation, leads to diabetes, cardiovascular diseases, cancer, osteoarthritis, and other disorders. Optimal therapy is unknown. The antimalarial drug chloroquine activates the kinase ataxia telangiectasia mutated (ATM), improves metabolic syndrome and reduces atherosclerosis in mice. To translate this observation to humans, we conducted two clinical trials of chloroquine in people with the metabolic syndrome. Eligibility included adults with at least 3 criteria of metabolic syndrome but who did not have diabetes. Subjects were studied in the setting of a single academic health center. The specific hypothesis: chloroquine improves insulin sensitivity and decreases atherosclerosis. In Trial 1, the intervention was chloroquine dose escalations in 3-week intervals followed by hyperinsulinemic euglycemic clamps. Trial 2 was a parallel design randomized clinical trial, and the intervention was chloroquine, 80 mg/day, or placebo for 1 year. The primary outcomes were clamp determined-insulin sensitivity for Trial 1, and carotid intima-media thickness (CIMT) for Trial 2. For Trial 2, subjects were allocated based on a randomization seque...Continue Reading

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Citations

Jan 17, 2020·British Journal of Pharmacology·Antigone LazouIoanna Andreadou
Aug 30, 2020·Pathogens and Disease·Vadim MakarovSergei Chepur
Aug 4, 2020·Current Opinion in Pharmacology·Mary C WingardKrishna Singh
Nov 15, 2020·Nature Reviews. Endocrinology·Soo LimMichael A Nauck

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Methods Mentioned

BETA
blood drawing
ELISA

Software Mentioned

ViewForum
GraphPad Prism

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