Pathways to Progress: 2023 TRI Year in Review

At the forefront of innovation, the Translational Research Institute has been a driving force in unraveling the complexities of diabetes and translating groundbreaking discoveries from the lab to real-world applications.

From novel therapies to cutting-edge technologies, our comprehensive review aims to shed light on the profound impact of translational research on understanding, treating, and ultimately preventing diabetes.

This article delves into the collaborative efforts, interdisciplinary approaches, and forward-thinking initiatives that have propelled the Translational Research Institute to the forefront of diabetes research.

FINE-ONE TRIAL
Up to 40 % of individuals with Type 1 diabetes (T1D) develop chronic kidney disease, putting them at risk of kidney failure. Finerenone is approved to reduce the risk of kidney failure in individuals with type 2 diabetes. TRI researchers led the team in the FINE-ONE trial to find out if finerenone will also help people with Type 1 diabetes.
To read the entire study, click here.

DISEASE-MODIFYING THERPIES AND FEATURES LINKED TO TREATMENT RESPONSE IN TYPE 1 DIABETES PREVENTION
Type 1 diabetes is a condition that results from the destruction of a type of cell in the pancreas that produces the hormone insulin, leading to lifelong dependence on insulin injections. T1D prevention remains a challenging goal, largely due to the immense variability in disease processes and progression. Therapies tested to date in clinical trials work only in a subset of individuals, highlighting the need for more tailored prevention approaches. We reviewed clinical trials of therapies targeting the disease process in T1D. While the overall quality of trials was high, studies testing individual features affecting responses to treatments were low. This review reveals a need to carefully plan high-quality analyses of features that affect treatment response in T1D, to ensure that tailored approaches may one day be applied to clinical practice.
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UTILITY AND PRECISION EVIDENCE OF TECHNOLOGY IN THE TREATMENT OF TYPE 1 DIABETES
In the last decade, there have been significant advances in how technology is used in the treatment of people living with Type 1 diabetes. These technologies primarily aim to help manage blood sugar levels. Here, we reviewed research published over the last decade to evaluate the impact of such technologies. We find that various types of novel technologies, such as devices to monitor blood sugar levels continuously or deliver insulin, improve important diabetes-related measures, and can reduce the risk of having low blood sugar levels. Our findings highlight the benefits of novel technologies in the treatment of Type 1 diabetes and identify areas for further research to optimize and personalize diabetes care.
To read the study, click here.

THE PROTEOME AND PHOSPHOPROTEOME OF CIRCULATING EXTRACELLULAR VESICLE-ENRICHED PREPARATIONS ARE ASSOCIATED WITH CHARACTERISTIC CLINICAL FEATURES IN TYPE 1 DIABETES
There are no validated clinical or laboratory biomarkers to identify and differentiate endotypes of Type 1 diabetes or the risk of progression to chronic complications. Extracellular vesicles (EVs) have been studied as biomarkers in several different disease states but have not been well studied in T1D. As the initial step towards circulating biomarker identification in T1D, this pilot study aimed to provide an initial characterization of the proteomic and phosphoproteomic landscape of circulating EV-enriched preparations in participants with established T1D.
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AN OVERVIEW OF DIET AND PHYSICAL ACTIVITY FOR HEALTHY WEIGHT IN ADOLESCENTS AND YOUNG ADULTS WITH TYPE 1 DIABETES: LESSONS LEARNED FROM THE ACT1ON CONSORTIUM
The prevalence of overweight and obesity in young people with Type 1 diabetes now parallels that of the general population. Excess adiposity increases the risk of cardiovascular disease, which is already elevated up to 10-fold in T1D. Sustainable weight management requires both diet and physical activity (PA). A major barrier to weight management in this high-risk population is the challenge of integrating regular PA with day-to-day management of T1D. Specifically, exercise poses a substantial challenge due to the increased risk of hypoglycemia and/or hyperglycemia. Thus, a tremendous opportunity exists to improve exercise participation and cardiometabolic outcomes in this population.
To read the review of dietary strategies, click here.

ASSOCIATIONS OF DIETARY INTAKE WITH THE INTESTINAL MICROBIOTA AND SHORT-CHAIN FATTY ACIDS AMONG YOUNG ADULTS WITH TYPE 1 DIABETES AND OVERWEIGHT OR OBESITY
Diet, a key component of Type 1 diabetes management, modulates the intestinal microbiota and its metabolically active byproducts-including SCFA-through fermentation of dietary carbohydrates such as fiber. However, the diet-microbiome relationship remains largely unexplored in longstanding T1D. Researchers at TRI found that in young adults with longstanding T1D, fiber and carbohydrate intake were associated positively with fecal SCFA but had variable associations with SCFA-producing gut microbes. Controlled feeding studies should determine whether gut microbes and SCFA can be directly manipulated in T1D.
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ESTIMATION OF A MACHINE LEARNING-BASED DECISION RULE TO REDUCE HYPOGLYCEMIA AMONG OLDER ADULTS WITH TYPE 1 DIABETES: A POST HOC ANALYSIS OF CONTINUOUS GLUCOSE MONITORING IN THE WISDM STUDY
The Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) study demonstrated continuous glucose monitoring (CGM) reduced hypoglycemia over 6 months among older adults with Type 1 diabetes compared with blood glucose monitoring. We explored heterogeneous treatment effects of CGM on hypoglycemia by formulating a data-driven decision rule that selects an intervention to minimize the percentage of time for each WISDM participant.
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ASSOCIATIONS OF DISORDERED EATING WITH THE INTESTINAL MICROBIOTA AND SHORT-CHAIN FATTY ACIDS AMONG YOUNG ADULTS WITH TYPE 1 DIABETES
Disordered eating in Type 1 diabetes includes insulin restriction for weight loss with serious complications. Gut microbiota-derived short-chain fatty acids (SCFA) may benefit host metabolism but are reduced in T1D. We evaluated the hypothesis that disordered eating and insulin restriction were associated with reduced SCFA-producing gut microbes, SCFA, and intestinal microbial diversity in adults with T1D.
To read the results, click here.

“NOTHING IS LINEAR”: CHARACTERIZING THE DETERMINANTS AND DYNAMICS OF CGM USE IN OLDER ADULTS WITH TYPE 1 DIABETES
Continuous glucose monitoring (CGM) can reduce hypoglycemia in older adults with Type 1 diabetes. We aimed to characterize factors that influence effective use in this age group. We found the holistic system model underscores that factors and feedback loops driving effective CGM use in older adults are both individualized and change over time, suggesting opportunities for staged and tailored age-specific education and support.
To learn more, click here.