Research Profile

Hypertension develops in up to 70% of young people with youth-onset type 2 diabetes, magnifying their lifetime risk of cardiovascular disease and kidney failure. High systolic blood pressure drastically increases long-term cardiovascular risk and is linked to vascular endothelial dysfunction and arterial stiffening. Guidelines recommend a combination of lifestyle modifications and drug therapy to lower blood pressure in the setting of diabetes, yet adherence to lifestyle modifications such as aerobic exercise is poor in persons with youth-onset type 2 diabetes. High-resistance, short-duration inspiratory muscle strength training (IMST) is a novel lifestyle intervention involving 30 inhalations against a resistive load which requires only ~5 min/day and is thus ideal for youth with type 2 diabetes who often struggle with adherence to treatment regimens. The current American Diabetes Association (ADA) Type 2 Diabetes in Youth Innovative Clinical or Translational Sciences Award entitled “Effects of High-Resistance Inspiratory Muscle Strength Training (IMST) on Cardiorenal and Vascular Function in Youth with Type 2 Diabetes” aims to use IMST as an interventional probe to define the responsiveness of the cardiovascular and renal systems including molecular and structural changes in youth with type 2 diabetes and establish the underlying mechanism of action of this novel time- and effort-efficient, highly adherable, and safe lifestyle intervention. The main goal of this study is to determine if IMST can be effectively used by young people with type 2 diabetes to improve health and reduce the future risk of heart and kidney disease.

IMST is a new, safe, and efficient lifestyle intervention that holds promise to lower important blood pressure outcomes in young persons with type 2 diabetes, a group at uniquely high risk of cardiovascular disease, yet understudied and faced with numerous barriers to traditional aerobic exercise. This will be the first IMST trial integrating clinical, pathological, and molecular data, allowing for the assessment of baseline relationships as well as the determination of the mechanistic pathways of IMST in youth-onset type 2 diabetes. We propose state-of-the-art methods to leverage the multi-dimensional data collected from comprehensive, non-invasive advanced cardiovascular and kidney assessments with the goal of fully understanding the complex interplay of mechanisms that are theorized to be modified by IMST in youth-onset type 2 diabetes. We aim to advance our tools for the treatment of young persons with type 2 diabetes beyond medications and current lifestyle interventions to techniques such as IMST which employs resistance training of the diaphragm and accessory respiratory muscles during inhalation to maintain health and reduce the risk for future cardiovascular and renal disease.

As a physician and female with a strong family history of type 2 diabetes, cardiac disease, and kidney disease, I pursued a career in Pediatric Endocrinology with a special interest in diabetes clinical and translational research focusing on efforts to decrease morbidity and mortality in youth and young adults with diabetes through the reduction of early cardiac, vascular, and kidney complications, the leading causes of diabetes-related morbidity and mortality. Research into the effects of hypertension is critical because there is compelling evidence that hypertension magnifies the lifetime risk of cardiovascular disease, kidney failure, and premature death in persons with type 2 diabetes. Additionally, hypertension has been recently shown to have a nearly 70% 15-year cumulative incidence in youth with type 2 diabetes. A combination of lifestyle changes and drug therapy is recommended to lower systolic blood pressure in people with type 2 diabetes, yet adherence to time consuming lifestyle treatments such as aerobic exercise is poor and our current treatments consistently demonstrate low uptake, particularly in youth with type 2 diabetes. My primary research objective, therefore, is to identify innovative treatment methods to reduce long-term diabetes-related vascular complications in young persons with type 2 diabetes, with a particular focus on underserved populations. This ADA-sponsored clinical trial will serve as an important first step in our investigation of IMST in high-risk youth with type 2 diabetes as a tool to reduce future cardiorenal complications, improve quality of life, and reduce long-term morbidity and mortality.

Metabolic syndrome and youth-onset type 2 diabetes represent a complex interplay of factors that cannot be effectively treated without a multidisciplinary approach including medical management and lifestyle modification. Furthermore, youth-onset type 2 diabetes has been shown to have a significantly more aggressive phenotype than adult-onset type 2 diabetes and thus requires prompt identification and initiation of treatments to minimize long-term complications. The future of youth-onset type 2 diabetes research lies in our ability to leverage existing and novel medical and lifestyle treatments to develop a personalized medicine approach for each of our patients. Our initial target population to implement IMST into clinical practice is youth with type 2 diabetes who are at high risk for cardiovascular disease and diabetic kidney disease, but we aspire to expand to other at-risk populations as well (e.g., youth and young persons with an elevated body mass index, chronic kidney disease, prediabetes, type 1 diabetes, etc.). Further, we believe that early success with IMST may promote adherence to healthier lifestyle practices (e.g., aerobic exercise) long term in these at-risk youth. Technologies such as IMST could be broadly applied to urban and rural populations subject to health disparities who lack access to fitness centers and environments conducive to conventional aerobic exercise training or the financial means to purchase expensive home exercise equipment. Thus, we contend that the impact of this study extends well beyond this grant cycle and will spawn future scientific investigations and potentially improve clinical practice and public health.