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Worksite-based intensive lifestyle therapy has profound cardiometabolic benefits in people with obesity and type 2 diabetes

ABSTRACT: Weight loss and physical activity are the cornerstones of therapy for type 2 diabetes. However, providing an effective lifestyle intervention is difficult because of limited availability of reliable programs, patient inconvenience, and cost. A worksite setting provides a unique opportunity for lifestyle therapy because it reduces these barriers. We conducted an 8-month randomized controlled trial in persons with obesity and diabetes to determine the therapeutic effects and potential mechanisms of intensive-lifestyle-therapy (energy restriction and supervised exercise training) conducted at the worksite. Intensive-lifestyle-therapy resulted in marked (17%) weight loss, associated with beneficial changes in body composition, cardiorespiratory fitness, muscle strength, glycemic control, β-cell function and insulin sensitivity in the liver, adipose tissue, and skeletal muscle, despite a decrease in diabetes medication use. These beneficial effects were associated with changes in skeletal muscle (increased metabolite content and expression of genes involved in NAD biosynthesis, sirtuin signaling, and mitochondrial biogenesis and function), adipose tissue (decreased expression of genes involved in extracellular matrix remodeling), and a major plasma mediator of insulin resistance (decreased plasma PAI-1). These findings demonstrate that effective intensive-lifestyle-therapy can be implemented at the worksite, and has profound therapeutic, clinical, physiological, and cellular effects in people with obesity and type 2 diabetes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205891 | GEO | 2022/09/08

REPOSITORIES: GEO

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Project description:Background. Differential gene expression in adipose tissue during diet-induced weight loss followed by a weight stability period is not well characterized. Markers of these processes may provide a deeper understanding of the underlying mechanisms. Objective. To identify differentially expressed genes in human adipose tissue during weight loss and weight maintenance after weight loss. Design. RNA from subcutaneous abdominal adipose tissue from nine obese subjects was obtained and analyzed at baseline, after weight reduction on a low calorie diet (LCD), and after a period of group therapy in order to maintain weight stability. Results. Subjects lost 18.8 + 5.4% of their body weight during the LCD and maintained this weight during group therapy. Insulin sensitivity (HOMA) improved after weight loss with no further improvement during weight maintenance. Cyclin-dependent kinase inhibitor 2B (CDKN2B) and JAZF zinc finger 1 (JAZF1), associated with type 2 diabetes, were downregulated. We could also confirm the downregulation of candidates for obesity and related traits, such as tenomodulin (TNMD) and matrix metallopeptidase 9 (MMP9), with weight loss. The expression of other candidates, such as cell death-inducing DFFA-like effector A (CIDEA) and stearoyl-CoA desaturase (SCD) were upregulated during weight loss but returned to baseline levels during weight maintenance. Conclusion. Genes in the adipose tissue are differentially expressed during weight loss and weight maintenance after weight loss. Genes that show sustained regulation may be of potential interest as markers of the beneficial effects of weight loss whereas others seem to be primarily involved in the process of weight loss itself. Nine participants were prescribed a low calorie diet (LCD) containing 1200 kcal/day for approximately three months (101 ± 26 days). Following the weight reduction phase the participants attended a six month follow-up period (167 ± 37 days). By protocol design, subjects were eligible to enter the study if they had lost at least 10% of their initial body weight during the LCD-period and maintained this weight (+5%) after group therapy. Subcutaneous adipose tissue samples were obtained at three time-points: (i) at baseline, (ii) after weight reduction when subjects were no longer losing weight, and (iii) after the group therapy weight maintenance phase.

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Worksite-based intensive lifestyle therapy has profound cardiometabolic benefits in people with obesity and type 2 diabetes

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