Development of obesity and metabolic clinical research programs

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

In FY25, we made progresses in the following areas. 1. We continue to accrue study participants in the natural history protocol (000617 NCT05398783) stated in late FY23. The primary aim is to examine the agreement between measured whole-body surface area (BSA) using our new 3D laser scanner (Vitus) and BSA estimated by previously established prediction equations in both healthy children and adults, participants with changes in weight, and those with various forms of disease. We have accrued 140 study participants so far with 121 completed at least one time-point measurements in resting energy expenditure (REE) by hood indirect calorimetry, comprehensive body composition by multiple techniques (dual energy x-ray absorptiometry, air-displacement plethysmography, stable isotopes, and bioelectrical impedance spectroscopy), and BSA by 3D scanning. We have been studying both pediatric healthy volunteers as well as in patients with skeletal dysplasia (altered statues and BSA) and CLN3 inherited nervous system developmental disorder. We have also started two new patient cohorts in patients with chronic graft-versus-host disease after hematopoietic stem cell transplantation (NCI) and with pheochromocytoma and paraganglioma (NICHD). Preliminary analyses using the first 100 study participants have suggested insights into the precision (test-retest reproducibility of the 3D scanner and REE measurements) and validity of body composition measurements (comparability between measurements using different methods). We will need additional data to expand our dynamic range and statistical power before our first manuscript in the coming year. 2. Our ongoing clinical protocol titled Energy expenditure responses to a range of environmental temperatures around the thermal neutral zone (12-DK-0097, NCT01568671) was designed to improve our understanding of dynamic regulation of energy expenditure in response to subtle changes in environmental temperature. We are interested in studying the capacity of (facultative) cold-induced thermogenesis in humans, defined as an increase in energy expenditure (EE or heat production) to a changed environmental temperature. Combined with the ongoing research on brown adipose tissue (BAT) and its role in cold-induced thermogenesis (CIT) in our and other labs, such clinical research is generating substantial interests in the field of energy metabolism and obesity. We measure energy expenditure continuously in a 5-hour period (0800-1300 fasted) in the room calorimeter with randomized environmental temperature ranging between 16 - 31C (61-88F) in 10-13 consecutive days (inpatient). We also carefully measure skeletal muscle shivering, body movements, heart rate, skin and core body temperatures, and stress responses by blood and urinary markers, while controlling for physical activity, clothing, and dietary intake. To date, we successfully studied fifteen (15) healthy lean male volunteers as our normative control group, nine (9) healthy obese male volunteers matched for age and race/ethnicity, sixteen (16) lean female volunteers (11 had repeated measurements in follicular and luteal menstrual phases), thirteen (13) older lean male volunteers (11 with complete data), and thirteen (13) young lean African-American male (12 with complete data) volunteers. The BAT data from lean and obese men were published in 2017; CIT data from lean and obese men was published in 2019. We further compared our data to other cold exposure studies in a publication related to military operations published in 2020. The BAT data from lean women cohort was published in 2020, and CIT data was published in 2024 in PNAS. However, during FY24-25, the temperature control system of the metabolic chambers has been experiencing issues related to aging equipment and instrumentations of the building. We went through several renovations (including switching to an independent heat and cooling system for two of the three chambers), but have not been able to achieve the level of control of the chamber temperatures accurately and consistently as this protocol requires (16-31 deg Celsius with ±0.1 deg variation). Due to this reason, we have not enrolled any new study participants. We have designed and contracted out a new HVAC project planned for FY26 that will hopefully correct these issues and hope to resume enrollment shortly after renovations are complete.