ABSTRACT
Exercise is recommended in the treatment of type 2 diabetes and can improve insulin sensitivity. However, previous evidence suggests that exercise at different times of the day in people with type 2 diabetes may have opposing outcomes on glycaemia. Metformin is the most commonly prescribed initial pharmacological intervention in type 2 diabetes, and may alter adaptions to exercise. It is unknown if there is an interaction between metformin and diurnal exercise outcomes. We aimed to investigate glycaemic outcomes of moderate intensity morning vs. evening exercise in people with type 2 diabetes being prescribed metformin monotherapy. In this study, nine males and nine females with type 2 diabetes undergoing metformin monotherapy (age 61 ± 8.2 years, mean ± SD) completed a 16-week crossover trial including 2-week baseline recording, 6 weeks randomly assigned to a morning exercise (07.00-10.00 h) or evening exercise (16.00-19.00 h) and a 2-week wash-out period. Exercise arms consisted of 30 min of walking at 70% of estimated max heart rate every other day. Glucose levels were measured with continuous glucose monitors and activity measured by wrist-worn monitors. Food-intake was recorded by 4-day food diaries during baseline, first and last 2 weeks of each exercise arm. There was no difference in exercise intensity, total caloric intake or total physical activity between morning and evening arms. As primary outcomes, acute (24 h) glucose area under the curve (AUC), was lower (P = 0.02) after acute morning exercise (180.6 ± 68.4 mmol/l) compared to baseline (210.3 ± 76.7 mmol/l); and there were no differences identified for glucose (mmol/l) between baseline, morning and evening exercise at any specific time point when data were analysed with two-way ANOVA. As secondary outcomes, acute glucose AUC was significantly lower (P = 0.01) in participants taking metformin before breakfast (152.5 ± 29.95 mmol/l) compared with participants taking metformin after breakfast (227.2 ± 61.51 mmol/l) only during the morning exercise arm; and during weeks 5-6 of the exercise protocol, glucose AUC was significantly lower (P = 0.04) for participants taking metformin before breakfast (168.8 ± 15.8 mmol/l), rather than after breakfast (224.5 ± 52.0 mmol/l), only during morning exercise. Our data reveal morning moderate exercise acutely lowers glucose levels in people with type 2 diabetes being prescribed metformin. This difference appears to be driven by individuals that consumed metformin prior to breakfast rather than after breakfast. This beneficial effect upon glucose levels of combined morning exercise and pre-breakfast metformin persisted through the final 2 weeks of the trial. Our findings suggest that morning moderate intensity exercise combined with pre-breakfast metformin intake may benefit the management of glycaemia in people with type 2 diabetes. KEY POINTS: Morning moderate exercise acutely lowers glucose levels in people with type 2 diabetes being prescribed metformin. This difference appears to be driven by individuals that consumed metformin prior to breakfast rather than after breakfast. Morning exercise combined with pre-breakfast metformin persistently reduced glucose compared to morning exercise combined with post-breakfast metformin through the final week (week 6) of the intervention. Our study suggests it may be possible to make simple changes to the time that people with type 2 diabetes take metformin and perform exercise to improve their blood glucose.
ABSTRACT
RATIONALE: Interstitial lung disease (ILD), a leading cause of morbidity and mortality in rheumatoid arthritis (RA), is highly prevalent, yet RA-ILD is underrecognized. OBJECTIVES: To identify clinical risk factors, autoantibodies, and biomarkers associated with the presence of RA-ILD. METHODS: Subjects enrolled in Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) and American College of Rheumatology (ACR) cohorts were evaluated for ILD. Regression models were used to assess the association between variables of interest and RA-ILD. Receiver operating characteristic curves were generated in BRASS to determine if a combination of clinical risk factors and autoantibodies can identify RA-ILD and if the addition of investigational biomarkers is informative. This combinatorial signature was subsequently tested in ACR. MEASUREMENTS AND MAIN RESULTS: A total of 113 BRASS subjects with clinically indicated chest computed tomography scans (41% with a spectrum of clinically evident and subclinical RA-ILD) and 76 ACR subjects with research or clinical scans (51% with a spectrum of RA-ILD) were selected. A combination of age, sex, smoking, rheumatoid factor, and anticyclic citrullinated peptide antibodies was strongly associated with RA-ILD (areas under the curve, 0.88 for BRASS and 0.89 for ACR). Importantly, a combinatorial signature including matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly increased the areas under the curve to 0.97 (P = 0.002, BRASS) and 1.00 (P = 0.016, ACR). Similar trends were seen for both clinically evident and subclinical RA-ILD. CONCLUSIONS: Clinical risk factors and autoantibodies are strongly associated with the presence of clinically evident and subclinical RA-ILD on computed tomography scan in two independent RA cohorts. A biomarker signature composed of matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly strengthens this association. These findings may facilitate identification of RA-ILD at an earlier stage, potentially leading to decreased morbidity and mortality.
