The prevalence of insulin resistance, type II diabetes, obesity and co-morbidities of the metabolicsyndrome is rising. More than 120M US adults are living with diabetes or are pre-diabetics. This carries a hugefinancial burden, which was estimated at ~$404B in 2019. Visceral fat (but not subcutaneous) and specificallythe mesenteric fat, was shown to have a major role in the pathophysiology of insulin resistance and diabetes. Fat cells are more sensitive to low temperatures compared to any other cell type. Fat solidifies at a highertemperature than the freezing temperature of water, forming needle like structures that promote cell death.Induction of fat cell death by low temperatures (cryolipolysis) is already detected at a temperature of +100C. Thisrelatively high temperature is making cryolipolysis an attractive approach to induce mesenteric fat mass loss asa new treatment modality to reduce Insulin resistance and diabetes in patients with visceral obesity. Our objective is to test the feasibility and safety of a novel approach and device to reduce the mass of themesenteric fat using cold temperatures, as a new treatment option to reverse insulin resistance and the incidenceof diabetes. Hypothesis: excessive mesenteric fat is a major contributor to the progression of insulin resistance, diabetes,and the metabolic syndrome. Cold temperatures delivered into the mesenteric fat will promote fat cells losswithout injuring surrounding tissues and without any significant side effects. The decrease in mesenteric fat willhave beneficial effects on insulin resistance, diabetes progression, and the metabolic syndrome. To test ourhypothesis, we propose the following Specific Aims: 1A. To utilize computational heat transfer methods based on Finite Element Analysis (FEA) to model fatthermal cycle for different device temperatures, shapes, materials, and treatment duration. 1B. To validate acutesafety and thermal cycle to be used in in-vivo chronic safety and feasibility studies (Aim 2). 2. In the Ossabaw pig model of insulin resistance, to evaluate the safety and feasibility of mesenteric fatcryolipolysis on insulin resistance progression. Milestones: Successfully modeling the thermal cycle in visceral fat will be considered as a first milestone.Building a cryolipolysis prototype device and in vivo validation of tissue temperatures calculated in 1A will be thesecond milestone. Seven days post-procedure survival without complications will be considered as the thirdmilestone. Successfully and safely reducing the mesenteric fat mass and reversing the progression of insulinresistance (Aim 2) will be the fourth milestone. The successful completion of these studies will show thatcryolipolysis of mesenteric fat is a safe and effective way to treat insulin resistance. The device developed, andthe results obtained, will pave the way for optimal device design and safety and efficacy studies utilizingenvisioned protocols to be eventually translated in human trials.
Public Health Relevance Statement: Project Narrative This proposal is focused on the development and feasibility evaluation of a
novel cryolipolysis technology, aimed at treating insulin resistance by reducing the mass of the
mesenteric visceral fat.
Project Terms: <21+ years old> | | | 