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Lifestyle therapy (energy restriction and exercise) is the cornerstone of therapy for people with type 2 diabetes (T2D) but is difficult to implement. We conducted an 8-month randomized controlled trial in persons with obesity and T2D (17 women and 1 man) to determine the therapeutic effects and potential mechanisms of intensive lifestyle therapy on cardiometabolic function. Intensive lifestyle therapy was conducted at the worksite to enhance compliance and resulted in marked (17%) weight loss and beneficial changes in body fat mass, intrahepatic triglyceride content, cardiorespiratory fitness, muscle strength, glycemic control, β cell function, and multi-organ insulin sensitivity, which were associated with changes in muscle NAD+ biosynthesis, sirtuin signaling, and mitochondrial function and in adipose tissue remodeling. These findings demonstrate that intensive lifestyle therapy provided at the worksite has profound therapeutic clinical and physiological effects in people with T2D, which are likely mediated by specific alterations in skeletal muscle and adipose tissue biology. [Display omitted] • Worksite-based intensive lifestyle therapy (ILT) causes marked weight loss • ILT markedly improves β cell function and multi-organ insulin sensitivity • Metabolic effects are associated with changes in muscle and adipose tissue biology Mihoko et al. report that intensive lifestyle therapy provided at the worksite causes marked weight loss, increased cardiorespiratory fitness and muscle strength, and improved physiological factors involved in the pathogenesis of T2D (β cell function, multi-organ insulin sensitivity, and skeletal muscle/adipose tissue biology) in people with obesity and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: To determine leg intermuscular (IMAT) and subcutaneous (SQAT) adipose tissue and their relationships with muscle performance and function in obese adults with and without type 2 diabetes and peripheral neuropathy (T2DMPN). Methods: Seventy-nine age-matched obese adults were studied, 13 T2DM, 54 T2DMPN, and 24 obese controls. Leg fat (%IMAT, %SQAT) volumes were quantified using MRI. Ankle plantar flexion (PF) torque and power were assessed with isokinetic dynamometry. Physical function was assessed with 9-item Physical Performance Test (PPT), 6-minute walk distance, single-limb balance, and time to ascend 10 stairs. One-way ANOVAs determined group differences, and multiple regression predicted PPT score from disease status, % IMAT, and PF power. Results: T2DMPN participants had 37% greater IMAT volumes and 15% lower SQAT volumes than controls (p =.01). T2DMPNand T2DMshowed reduced PF torque and power compared to controls. T2DMPNparticipants had lower PPT score, 6-minute walk, single-limb balance, and stair climbing than controls (all p < .05). %IMAT volume correlated inversely, and %SQAT correlated directly, with PPT. Leg %IMAT and disease status predicted 49% of PPT score. Conclusions: T2DMPN may represent a shift in adipose tissue accumulation from SQAT to IMAT depots, which is inversely associated with muscle performance and physical function. [ABSTRACT FROM AUTHOR]