Inflammatory Vigor in Heterogeneity of Type 2 Diabetes (T2D) Development, Severity, and Resolution
Abstract
Modern lifestyle and the types of food we eat are considered to be the most important factors influencing weight gain and obesity development. As approximately one out of three adults and one out of five adolescents in the United States are obese, there has been a strong focus on trying to understand this problem over the past decades. Obesity has similarly affected active military Service members: between 2002 and 2011 obesity rates have risen 61% among military personnel. The direct consequence is that obese individuals are less likely to be medically ready to be deployed, to protect our nation, and are at a greater risk for medical injury among active personnel. Clinically, obesity is a public health problem, as it represents a major risk factor for common and serious medical conditions that include type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), atherosclerotic cardiovascular disease, and diverse cancers. In fact, the Department of Defense spends about $1.5 billion annually on obesity-related healthcare costs for current and former Service members and their families, as well as costs to replace unfit personnel. Notably, the prevalence of T2D and NAFLD has increased three-fold in Veterans in the last decade, with more than one in five patients at high risk for development of advanced disease. In addition, obesity-associated metabolic derangements do not only afflict active and past military personnel, but also impact future recruits and our military readiness — the rates of T2D and NAFLD are expected to quadruple by 2050 in U.S. adolescents. T2D in youth is marked by a more rapid progression requiring lifelong dependency on medication (insulin and others) and marked increases in associated cancers, liver, heart, and blood vessel diseases. The major concern that exists is that despite aggressive attempts to prevent obesity and the progression of associated diseases, the incidence of both will continue to exponentially increase. The gap in our knowledge of the mechanisms that result in T2D and NAFLD in a subset of obese patients may be addressed by a better understanding of the link between cellular metabolism and immune cell activation/function. We currently know that obesity increases inflammation in both animal models as well as in some human patients. What remains unknown is why and how this occurs in only a subset of obese patients. As we now know that the incidence and progression of T2D in obese adolescents is more rapid, and without other factors that contribute to the disease in older adults, studying this obese adolescent population may provide key insights to understanding this problem. Unlike medications that rarely reverse T2D, a large number of adolescent patients who have undergone bariatric surgery not only reverse their T2D, but they do so without the need of supplemental medication. Studying the inflammatory and metabolic pathways that change during this reversal window may identify why and how only a subset of individuals develops T2D and provide potential future therapeutic targets. As the driver of the inflammatory response may be found within organs like the liver or fat around the stomach, surgery uniquely allows us to sample these tissues and compare them to circulating cells in the blood. If we can relate what is seen in the blood to what occurs in these tissues, we will have a simple way to screen and follow patients without the need for surgical samples. Ultimately, our research will help to identify the population at risk, help characterize biomarkers of disease development, explore mechanisms that lead to disease progression, invoke potential therapeutic strategies, and inform of factors underlying disease heterogeneity across ethnic/race/gender lines. Hence, our proposal carries significant conceptual and technical innovations that are coupled with new approaches and mechanistic interrogations. Together, our combined approach represents clear benefits tha
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010392
Entities
People
- Senad Divanovic
Organizations
- United States Army