Effect Of Breaking-Up Sedentary Activity On Metabolic Flexibility And Glycemia In Free-Living Overweight/Obese Adults

PURPOSE: Sedentary behavior (SB) triggers an inability to adjust substrate use to substrate availability (metabolic flexibility, MF), which may precede glucose intolerance in the pathogenesis of insulin resistance. We and others have shown that frequent interruptions in SB leads to improved glycemic control, however the underlying role of MF in this process is unknown. This study examined the effects of breaking up SB on MF and glucose metabolism in free-living overweight and obese adults. To distinguish effects of breaking up SB from being physically active, we also studied a group where participants performed a single energy matched continuous bout of exercise. METHODS: Physically inactive, adults (12F/7M, mean±SD; 33±8 yrs, BMI = 29.5±3.3kg/m2) were randomly assigned to a 4 week intervention consisting of brisk walking for 5 min each hour for 10h, 5 d/wk (MICRO), or 4 weeks of an intervention consisting of one continuous 45 min bout of exercise per day, 5d/wk (ONE). Outcomes assessed at baseline and after each intervention included: MF (waking respiratory quotient,RQ, minus sleeping RQ as measured in a whole room calorimeter), insulin sensitivity (SI, IVGTT), 24h glycaemia (continuous glucose monitor), 24h glucose oxidation (U13C glucose tracer), SB, time spent stepping, and performing moderate to vigorous activity (MVPA; ActivPAL and ActiGraph). Groups were similar on all outcome variables at baseline. Linear mixed models evaluated intervention and intervention-by-group effects. RESULTS: MICRO and ONE decreased time sitting (-43.5±93.4 min), increased time stepping (+26.3±44.0 min) and time spent in MVPA (+9.8±17.6 min) (p<0.05 for all). No significant changes were observed in SI, but both interventions decreased fasting insulin and HOMA IR (p<0.05 for both). Compared to ONE, MICRO improved the acute insulin response to glucose (AIRg), lowered 24h glycemic variability, maintained exogenous glucose oxidation, and improved MF (interaction: p<0.05 for all). Improvements in MF were positively associated with changes in SI (r=0.59, p=0.02). CONCLUSIONS: Independent of time sitting and stepping, breaking up SB improves glucose homeostasis and MF. The effects of such an intervention in persons with type 2 diabetes warrants further study.