Obesity and inactivity, not hyperglycemia, cause exercise intolerance in individuals with type 2 diabetes: Solving the obesity and inactivity versus hyperglycemia causality dilemma.

Obesity, a sedentary lifestyle and type 2 diabetes are intricately linked conditions contributing to reduced exercise tolerance, significant morbidity, and premature deaths. It is unknown whether the reported exercise intolerance associated with type 2 diabetes is a direct result of the hyperglycemia, the impact of a relatively sedentary lifestyle, or increased adiposity. We hypothesize that obesity and inactivity, not hyperglycemia, cause exercise intolerance in individuals with type 2 diabetes. An analysis of the literature and results from the Goto-Kakizaki (GK) rat model of type 2 diabetes strongly support this hypothesis. GK rats were not sedentary or obese when compared with Wistar control rats and did not have exercise intolerance. Specifically, despite being hyperglycemic, GK rats demonstrated a longer treadmill run time to exhaustion (150.6 ± 9.0 vs. 77.2 ± 12.9 min), further distance run (1506 ± 90 vs. 772 ± 129 m), more work performed per gram muscle (44.0 ± 2.8 vs. 21.9 ± 3.8 kgm/g) and a small increase in total vertical work performed when accounting for body mass (116.8 ± 6.3 versus 98.9 ± 15.2 kgm). These results document preserved exercise tolerance in the non-obese, non-sedentary GK rat supporting the hypothesis that the reported exercise intolerance in models of type 2 diabetes is dependent on obesity and inactivity. Solving the obesity and inactivity versus hyperglycemia causality dilemma is important in understanding the development of type 2 diabetes and implications for future pharmacological and life style interventions.