Effects of Empagliflozin-Induced Glycosuria on Weight Gain, Food Intake and Metabolic Indicators in Mice Fed a High-Fat Diet.

BACKGROUND: Sodium glucose-linked transporter 2 (SGLT2) inhibitors promote glucose, and therefore calorie, excretion in the urine. Patients taking SGLT2 inhibitors typically experience mild weight loss, but the amount of weight loss falls short of what is expected based on caloric loss. Understanding the mechanisms responsible for this weight loss discrepancy is imperative, as strategies to improve weight loss could markedly improve type 2 diabetes management and overall metabolic health. METHODS: Two mouse models of diet-induced obesity were administered the SGLT2 inhibitor empagliflozin in the food for 3 months. Urine glucose excretion, body weight, food intake and activity levels were monitored. In addition, serum hormone measurements were taken, and gene expression analyses were conducted. RESULTS: In both mouse models, mice receiving empagliflozin gained the same amount of body weight as their diet-matched controls despite marked glucose loss in the urine. No changes in food intake, serum ghrelin concentrations or activity levels were observed, but serum levels of fibroblast growth factor 21 (FGF21) decreased after treatment. A decrease in the levels of deiodinase 2 (Dio2) was also observed in the white adipose tissue, a primary target tissue of FGF21. CONCLUSION: These findings suggest that compensatory metabolic adaptations, other than increased food intake or decreased physical activity, occur in response to SGLT2 inhibitor-induced glycosuria that combats weight loss, and that reductions in FGF21, along with subsequent reductions in peripheral Dio2, may play a role.

Mental health disparities.

Mental health disparities have received increased attention in the literature in recent years. After considering 165 different health disparity conditions, the Federal Collaborative for Health Disparities Research chose mental health disparity as one of four topics warranting its immediate national research attention. In this essay, we describe the challenges and opportunities encountered in developing a research agenda to address mental health disparities in the United States. Varying definitions of mental health disparity, the heterogeneity of populations facing such disparity, and the power, complexity, and intertwined nature of contributing factors are among the many challenges. We convey an evolving interagency approach to mental health disparities research and guidance for further work in the field.

Lessons learned from the Uniontown Community Health Project.

OBJECTIVE: To compile lessons learned from the Uniontown Community Health Project. METHODS: Lessons-learned information was gathered from project staff and community volunteers. RESULTS: Analysis led to the identification of 6 lessons: (a) Establish personal working relationships in communities; (b) find a local community coordinator to lead efforts; (c) be patient in implementing a community health advisor (CHA) model; (d) be flexible and emphasize simplicity when implementing community activities; (e) recognize that meeting research goals requires compromise; and (f) plan transfer of project activities to the community from the beginning. CONCLUSION: These lessons may benefit others implementing CHA programs.