ABSTRACT
Objective: The goal of this article was to describe trends in publications (including conference abstracts) and clinical trials that report on glycemic time in range (TIR). Data sources: Reviewed databases included but were not limited to MEDLINE and Embase. Clinical trial registries were also sourced. Study selection: All studies reporting TIR published between 2010 and 2021 were included. Clinical trials reporting TIR that started in or after 2010 were also included. Non-English publications, abstracts, and clinical trials were excluded. Book chapters, nonhuman studies, and studies not reporting TIR were excluded. Data extraction: Manuscript/abstract category, publication year, study region, interventional versus observational role of continuous glucose monitoring (CGM), and clinical trial start and completion dates were captured. Glycemic outcomes reported in publications or trials, including TIR as a primary outcome, A1C, time below range (TBR), and time above range (TAR), were also captured. Results: A total of 373 clinical trials, 531 publications, and 620 abstracts were included in the review. The number of trials, publications, and abstracts reporting TIR significantly increased, particularly between 2018 and 2021, during which time the number of clinical trials, publications, and conference abstracts reporting TIR increased by 6-fold, 12-fold, and 4.5-fold, respectively. About 35-44% of studies reported TIR as a primary outcome. Approximately 54% of clinical trials, 47% of publications, and 47% of conference abstracts reported the role of CGM to be observational. TBR was reported more often than TAR. Conclusion: The marked increase in the number of trials, publications, and abstracts reporting TIR highlights the increasing significance and acceptance of TIR as an outcome measure in diabetes management.
ABSTRACT
The dopamine transporter (DAT) is a crucial regulator of dopaminergic neurotransmission which undergoes constitutive and substrate-mediated trafficking to and from the membrane. Although, considerable research has been done to elucidate the regulation of substrate-stimulated DAT trafficking, less is known about which trafficking proteins are involved in constitutive DAT trafficking. Rab proteins are GTPases known to regulate the trafficking of proteins to and from specific endocytic compartments. Rabs 8 and 11, in particular, are involved in trafficking proteins from intracellular compartments to the plasma membrane. In this study, we sought to determine whether Rabs 8 and 11 would modulate DAT activity and trafficking in N2A neuroblastoma cells. We used Rab mutations known to confer constitutively active or dominant negative activity of these proteins to investigate the role of Rab activity in constitutive DAT trafficking and function. We found that constitutively active Rab 11 upregulates DAT function and surface expression while neither the constitutively active nor the dominant negative mutant of Rab 8 had any effect on DA uptake. Furthermore, immunofluorescence experiments revealed that dominant negative Rab 11 overexpression results in decreased surface DAT indicating a necessary function of Rab 11 in DAT trafficking to the plasma membrane. These data show for the first time a functional role of Rab proteins in the constitutive recycling of DAT to the plasma membrane.
