The Utilization of Gluconeogenesis as a Viable Marker to Assess Health, Injury and Aging
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The Utilization of Gluconeogenesis as a Viable Marker to Assess Health, Injury and Aging

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Abstract

Euglycemia, or the maintenance of blood glucose concentrations in an ever-changing environment, is a tightly regulated process at the intersection of health and disease. Endogenous glucose production, a process to maintain euglycemia, is called gluconeogenesis (GNG). The rate of GNG is highly dynamic and responsive to the body's energetic needs. As such, GNG is an excellent marker for energetic demand that has the potential to serve as a valuable marker for health, disease, and injury. This work highlights the ability of GNG to be used as a vital biomarker to monitor nutritional adequacy during recovery from a traumatic brain injury (TBI) and a biomarker for age-related declines in metabolic flexibility.Acute care post-TBI is a critical time point for practitioners to monitor the health of their TBI patients. During acute TBI recovery, patients often experience a hypermetabolic state characterized by an increased heart rate, ventilation, and blood glucose and lactate concentrations. Often overlooked are the nutritional needs of the patient during acute care, which would lead to the underfeeding of the patient. Thus, a biomarker is needed to adequately measure nutritional adequacy during TBI acute care recovery. Chapters 2 and 3 present data illuminating the use of fractional gluconeogenesis (fGNG) as a viable marker to detect underfeeding post-TBI. fGNG was elevated in the underfed animals post-TBI compared to adequately fed animals post-TBI. Furthermore, TBI, in conjunction with underfeeding, leads to a hypermetabolic state in which protein synthesis changes from a non-injured state, which was not seen in the adequately fed injured animals. Using fGNG post-injury may allow superior nutritional support for a patient recovering from a TBI. By 2060, population predictions estimate that 20% of the world's population will be 60 or older. With an increase in the world's elderly population, it is necessary to understand mechanisms for healthy aging. To increase understanding of the mechanisms of healthy aging, metabolic flexibility and glucose kinetics were measured in an aged population during an oral glucose tolerance test (OGTT). While traditional measurements of metabolic flexibility were unaltered in the aged population studied, glucose kinetics were drastically diminished in the older cohort compared to younger individuals during an OGTT. Furthermore, unlike the younger individuals studied, gluconeogenesis remained elevated in older individuals during an OGTT. The utilization of GNG as a biomarker in the healthy-aged cohort showed signs of hepatic insulin that would not have been detectable using the normal standard of care measurement. The following work explored uses for gluconeogenesis as a viable clinical biomarker to understand caloric adequacy during injury recovery (Chapters 2 and 3) and identified age-related reductions in glucose metabolism (Chapter 4).

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This item is under embargo until March 27, 2025.