| Title |
Antidiabetogenic effects of hydroxychloroquine on insulin sensitivity and beta cell function: a randomised trial
|
|---|---|
| Published in |
Diabetologia, July 2015
|
| DOI | 10.1007/s00125-015-3689-2 |
| Pubmed ID | |
| Authors |
Mary Chester M. Wasko, Candace K. McClure, Sheryl F. Kelsey, Kimberly Huber, Trevor Orchard, Frederico G. S. Toledo |
| Abstract |
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. 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. 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 HbA1c (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. 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 NCT01326533 Funding This study was funded by National Institutes of Health no. 5R21DK082878, UL1-RR024153 and UL-1TR000005. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 33% |
| Unknown | 4 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 67% |
| Practitioners (doctors, other healthcare professionals) | 1 | 17% |
| Scientists | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 114 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 114 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 18 | 16% |
| Student > Bachelor | 16 | 14% |
| Student > Master | 10 | 9% |
| Other | 8 | 7% |
| Student > Ph. D. Student | 6 | 5% |
| Other | 22 | 19% |
| Unknown | 34 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 37 | 32% |
| Nursing and Health Professions | 9 | 8% |
| Biochemistry, Genetics and Molecular Biology | 6 | 5% |
| Agricultural and Biological Sciences | 5 | 4% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 4% |
| Other | 13 | 11% |
| Unknown | 39 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 13. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 February 2024.
All research outputs
#2,722,423
of 24,631,014 outputs
Outputs from Diabetologia
#1,382
of 5,283 outputs
Outputs of similar age
#34,558
of 268,848 outputs
Outputs of similar age from Diabetologia
#17
of 74 outputs
Altmetric has tracked 24,631,014 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,283 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 24.4. This one has gotten more attention than average, scoring higher than 73% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 268,848 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 74 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.