Association between skeletal muscle mitochondrial dysfunction and insulin resistance in patients with rheumatoid arthritis: a case-control study.

BACKGROUND: Insulin resistance affects a substantial proportion of patients with rheumatoid arthritis (RA). Skeletal muscle mitochondrial dysfunction results in the accumulation of lipid intermediates that interfere with insulin signaling. We therefore sought to determine if lower oxidative phosphorylation and muscle mitochondrial content are associated with insulin resistance in patients with RA. METHODS: This was a cross-sectional prospective study of RA patients. Matsuda index from the glucose tolerance test was used to estimate insulin sensitivity. Mitochondrial content was measured by citrate synthase (CS) activity in snap-frozen muscle samples. Mitochondrial function was measured by using high-resolution respirometry of permeabilized muscle fibers and electron transport chain complex IV enzyme kinetics in isolated mitochondrial subpopulations. RESULTS: RA participants demonstrated lower insulin sensitivity as measured by the Matsuda index compared to controls [median 3.95 IQR (2.33, 5.64) vs. 7.17 (5.83, 7.75), p = 0.02]. There was lower muscle mitochondrial content among RA vs. controls [median 60 mU/mg IQR (45, 80) vs. 79 mU/mg (65, 97), p = 0.03]. Notably, OxPhos normalized to mitochondrial content was higher among RA vs. controls [mean difference (95% CI) = 0.14 (0.02, 0.26), p = 0.03], indicating a possible compensatory mechanism for lower mitochondrial content or lipid overload. Among RA participants, the activity of muscle CS activity was not correlated with the Matsuda index (ρ = - 0.05, p = 0.84), but it was positively correlated with self-reported (IPAQ) total MET-minutes/week (ρ = 0.44, p = 0.03) and Actigraph-measured time on physical activity (MET rate) (ρ = 0.47, p = 0.03). CONCLUSIONS: Mitochondrial content and function were not associated with insulin sensitivity among participants with RA. However, our study demonstrates a significant association between muscle mitochondrial content and physical activity level, highlighting the potential for future exercise interventions that enhance mitochondrial efficiency in RA patients.

Fingernail and toenail clippings as a non-invasive measure of chronic cortisol levels in adult cancer survivors.

PURPOSE: Cancer survivors are at greater risk of comorbidities and functional decline due to physiological and psychological stress which can be measured by salivary cortisol. If saliva is used, multiple samples must be collected to accurately quantify long-term stress; however, fingernail (FN) and toenail (TN) clippings offer an opportunity to measure retrospective cortisol levels in a non-invasive manner. METHODS: Three sets of FN and TN clippings were collected at 12-month intervals in conjunction with saliva samples from cancer survivors (n = 109) participating in two clinical trials. FN and TN samples were stored at room temperature (RT); a subset underwent additional processing and freezing before analysis. Cortisol levels were determined via enzyme immunoassay, and correlation coefficients were generated to determine overall correspondence of the individual measures. RESULTS: Matched RT and frozen samples were highly correlated for TN (r = 0.950, p = 5.44 × 10-37) and FN (r = 0.784, p = 1.05 × 10-10). Correlations between RT FN and TN were statistically significant (r = 0.621, p = 3.61 × 10- 17), as were frozen FN and TN (r = 0.310, p = 0.0283). RT, but not frozen TN and FN correlated with salivary cortisol (r = 0.580, p = 1.65 × 10- 16 and r = 0.287, p = 0.00042 for TN and FN, respectively). CONCLUSIONS: FN and TN cortisol levels correlate with salivary cortisol in adult cancer survivors and may offer a less invasive and convenient means for measuring chronic cortisol levels.