Antidiabetogenic effects of hydroxychloroquine on insulin sensitivity and beta cell function: a randomised trial.
Diabetologia
; 58(10): 2336-43, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26197707
ABSTRACT
AIMS/HYPOTHESIS:
Hydroxychloroquine (HCQ), an antimalarial drug with anti-inflammatory properties, is employed in rheumatic diseases. In observational studies, patients with rheumatic diseases treated with HCQ have a lower risk of developing diabetes. However, the physiological mechanisms remain unexplained. We hypothesised that HCQ may have favourable effects on insulin sensitivity and/or beta cell function.METHODS:
This was a randomised, double-blind, parallel-arm (placebo vs HCQ 400 mg/day) trial at the University of Pittsburgh. Randomisation was conducted by a computer system with concealment by sealed envelopes. Treatment duration was 13 ± 1 weeks. Randomised participants (HCQ n = 17; placebo n = 15) were non-diabetic volunteers, age >18, overweight or obese, with one or more markers of insulin resistance. All participants were included in intention-to-treat analysis. Outcomes were changes in insulin sensitivity and beta cell function measured by intravenous glucose tolerance tests and minimal model analysis.RESULTS:
There was a positive change in insulin sensitivity with HCQ but not placebo (mean ± SEM +20.0% ± 7.1% vs -18.4% ± 7.9%, respectively; p < 0.01; difference 38.3% ± 10.6%; 95% CI 17%, 60%). Improvement in beta cell function was also observed with HCQ but not placebo (+45.4% ± 12.3% vs -19.7% ± 13.6%; p < 0.01; difference 65% ± 19%; 95% CI 27%, 103%). There were modest treatment effects on fasting plasma glucose and HbA(1c) (p < 0.05) but circulating markers of inflammation (IL-6, IL-1, TNF-α, soluble intercellular adhesion molecule) were not affected in either group. In contrast, adiponectin levels increased after HCQ treatment but not after placebo (+18.7% vs +0.7%, respectively; p < 0.001). Both low- and high-molecular-weight adiponectin forms accounted for the increase. There were no serious or unexpected adverse effects. CONCLUSIONS/INTERPRETATION:
HCQ improves both beta cell function and insulin sensitivity in non-diabetic individuals. These metabolic effects may explain why HCQ treatment is associated with a lower risk of type 2 diabetes. An additional novel observation is that HCQ improves adiponectin levels, possibly being a mediator of the favourable effects on glucose metabolism. Our findings suggest that HCQ is a drug with considerable metabolic effects that warrant further exploration in disorders of glucose metabolism. TRIAL REGISTRATION Clinicaltrials.gov NCT01326533FUNDING:
This study was funded by National Institutes of Health no. 5R21DK082878, UL1-RR024153 and UL-1TR000005.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Células Secretoras de Insulina
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Sobrepeso
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Hidroxicloroquina
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article