Association of free-living physical activity measures with metabolic phenotypes in type 2 diabetes at the time of diagnosis. The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS)

Objective: Lifestyle is considered a major determinant of risk of type 2 diabetes (T2D). We investigated whether daily physical activity (DPA) is associated with beta-cell function (BF) and/or insulin sensitivity (IS) in patients with T2D at the time of diagnosis. Methods: In 41 subjects enrolled in the Verona Newly-Diagnosed Type 2 Diabetes Study we assessed: (1) IS, by euglycaemic insulin clamp; (2) BF, estimated by prolonged-OGTT minimal modeling and expressed as derivative and proportional control; (3) DPA and energy expenditure (EE), assessed over 48-hours monitoring by a validated wearable armband system. Results: Study participants (median[IQR]; age: 62 [53-67] years, BMI: 30.8 [26.5-34.3] Kg⋅m-2, HbA1c: 6.7 [6.3-7.3]%; 49.7 [45.4-56.3] mmol/mol) were moderately active (footsteps/day: 7,773 [5,748-10,927]; DPA≥3MET: 70 [38-125] min/day), but none of them exercised above 6 metabolic equivalents (MET). EE, expressed as EETOT (total daily-EE) and EE≥3MET (EE due to DPA≥3MET) were 2,398 [2,226-2,801] and 364 [238-617] Kcal/day, respectively. IS (M-clamp 630 [371-878] μmol/min/m2) was positively associated with DPA and EE, independent of age, sex and BMI (p<0.05). Among the DPA and EE parameters assessed, DPA≥3MET and EETOT were independent predictors of IS in multivariable regression analyses, adjusted for age, sex, BMI (R2=16%, R2=19%, respectively; p<0.01). None of model-derived components of BF was significantly associated with DPA or accompanying EE. Conclusions Our study highlighted moderate levels of DPA and total EE as potential determinants of IS, but not BF, in T2D at the time of diagnosis. Intervention studies are needed to conclusively elucidate the effect of DPA on these features.