Multiple Metabolic Abnormalities Seen in Lupus Targeting insulin resistance alone won't be enough

When compared with a control group, patients with systemic lupus erythematosus (SLE) had higher insulin resistance and hyperglucagonemia, even when their fasting glucose, glucose response, and skeletal muscle GLUT4 translocation appeared normal, reported Fabiana Benatti, PhD, of the University of Sao Paulo School of Medicine, and colleagues. Specifically, SLE patients who underwent meal tolerance tests (MTT) showed higher: Fasting insulin levels: effect size 1.2 (P=0.01) Homeostatic model assessment of insulin resistance (HOMA IR): effect size 1.1 (P=0.03) Insulin-to-glucose ratio response to MTT: effect size 1.2 (P=0.02) Fasting glucagon levels: effect size 2.7 (P=0.002) Glucagon response to MTT: effect size 2.6 (P=0.0001) The authors noted that one of the most striking findings of the study was that the higher insulin levels in SLE patients were not able to control glucagon production. Although glucose and insulin effectively suppressed glucagon secretion during MTT, the SLE group's glucagon levels remained higher than the control group's levels at all times. The investigators also noted that insulin sensitivity was correlated with inflammation markers C-reactive protein and leptin, which could point to inflammation having a role in insulin resistance in SLE. They added that drugs -- notably, prednisone and hydroxychloroquine -- could have influenced their results. "Corticosteroids have been shown to decrease glucose tolerance by increasing hepatic glucose production and decreasing peripheral glucose uptake via a decrease in skeletal muscle and adipose tissue insulin sensitivity," they stated. "Because 30% of our SLE patients were using prednisone, this could have contributed to the higher insulin resistance observed in this group." In contrast, hydroxychloroquine in SLE patients has been linked to lower levels of fasting glucose and HOMA IR, and reduced risk of type 2 diabetes. The researchers did not observe any association between hydroxychloroquine use and insulin sensitivity. "However, because 70% of our patients were using this medication, it is possible that hydroxychloroquine may have attenuated potential deleterious effects of prednisone on insulin sensitivity," they wrote. https://www.medpagetoday.com/Rheumatology/Lupus/64321?xid=nl_mpt_DHE_2017-04-05&eun=g721819d0r&pos=1