Specific-Sized HA35 in Preventing the Transition from Prediabetes to Diabetes
Abstract
More than 7 in 10 Veterans who receive Department of Health (VA) care are obese or overweight, putting them at high risk for the development of complications of metabolic syndrome, including type 2 diabetes and non-alcoholic fatty liver disease. There is a growing appreciation that obesity is a condition of low-grade chronic inflammation, termed metaflammation; metaflammation ultimately leads to the development of more severe complications, including diabetes. Metaflammation is associated with changes in the gastrointestinal tract when people eat high-fat diets and/or when they become overweight. These changes are characterized by shifts in different population of microbes in the gut as well as a deterioration of the barrier function of the gut. In healthy people, the gut acts as a barrier or divider between the bugs (microbes) in our gut and our organs. When this barrier is lost, the body responds as if there is an infection and mounts an immune response. That is why metaflammation in obesity/pre-diabetes is referred to as a “sterile” inflammation, since there is really no infection. Understanding the mechanisms by which obesity results in this deleterious chronic inflammatory state has remained elusive. There is an urgent need to understand the mechanisms by which obesity results in metaflammation in order to facilitate the development of therapeutic approaches to prevent the progression of early stages of metabolic syndrome/pre-diabetes in Veterans to more severe diseases, such as type 2 diabetes. We have been studying the protective effects of a carbohydrate, hyaluronic acid of a specific 35 kD size (HA35), on the gut in mouse models of obesity/type 2 diabetes. Our team discovered that HA35 is one of the gut protective molecules found in breast milk; HA35 increases gut integrity and defense systems both in mice and healthy humans. When we give HA35 to mice, it prevents some of the early effects of high-fat diet on gut integrity, liver injury, and inflammation. Here we propose to extend these studies to longer term high-fat diet feeding, as well as determine how HA35 can protect the gut and decrease inflammation. Importantly, medical-grade HA for device use is commercially manufactured (Lifecore, LLC), and our team has just published the results of a National Institutes of Health-funded human study (ClinicalTrials.gov: NCT02867605) (Bellar, et al., Nutrients, 2019, doi: 10.3390/nu11051135) finding that HA35 is safe and tolerable in lean and obese healthy volunteers, increasing the likelihood for a rapid translation of our work to clinical studies in pre-diabetic/obese or diabetic Veterans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010235
Entities
People
- Carol Dela Motte
Organizations
- Cleveland Clinic
- United States Army