Large Volume Visceral Fat Removal to Reverse Insulin Resistance in Type Diabetes

Abstract Excess visceral fat VF has been strongly linked with development of insulin resistance and subsequent type diabetes T DM in humans and rodent lipectomy studies have demonstrated that this relationship is causal Among the nearly million US adults affected by T DM disease onset typically appears secondary to weight gain with excess VF considered to be a major driver Lifestyle changes diet and exercise are the first line of treatment for weight management and disease prevention but such efforts have not proven effective over the long term Surgically removing subcutaneous fat by large volume liposuction has been explored as an alternative approach but the vast majority of these studies have failed to consistently demonstrate improvement in metabolic outcomes Therefore targeting the VF depots for removal should be prioritized in order to rapidly and significantly improve metabolic and overall health in humans However due to the heavy vascularization and other delicate structures within and around VF there are currently no feasible methods to perform this procedure Studies targeting the omentum have been conducted with mixed results likely because this depot only accounts for a fraction of total VF mass in an obese human Thus additionally targeting the mesentery and peri renal areas where most VF is harbored may be required to surgically treat T DM To this end we have developed and commercialized a technology in use for removal of cataracts as well as subcutaneous fat depots which we refer to as Tissue Liquefaction Technology TLT Our method is a unique patented approach that delivers low levels of thermal and mechanical energy as a stream of warmed low pressurized and pulsed saline which causes susceptible non connective tissues to undergo a phase transition from solid to liquid while connective tissue protected blood vessels and nerves are unharmed Preliminary data demonstrate our ability to successfully target and remove these deep VF depots in pigs and baboons Thus the Specific Aim of this proposal is to determine feasibility and efficacy of large volume VF removal in the baboon to reverse insulin resistance This will be determined by surgically removing significant quantities of fat from all three VF depots of omentum peri renal mesenteric fat with TLT in overweight and insulin resistant baboons and determining effects on metabolic outcomes using `gold standardandapos techniques including hyperinsulinemic euglycemic clamps DXA MRI MRS and a broad array of plasma metabolites at pre determined intervals over mo follow up We have chosen to study insulin resistant baboons since they are a well validated model of human metabolism and TLT has proven to easily and rapidly liquefy baboon and human VF in our preliminary studies Our expectation is that animals will demonstrate exceptional recoveries free of complications have improved insulin sensitivity without significant regrowth of VF depots or adverse effects on liver and skeletal muscle In summary our technology is a significant step forward for surgical fat removal and if proven successful here may represent a revolutionary treatment option for insulin resistance in T DM and other conditions Narrative Type diabetes affects over million US citizens In nearly percent of this group the type diabetes is secondary to being overweight with excess visceral fat being the primary driver of insulin resistance of type diabetes Despite current treatment advances the type diabetes often leads to death or any number of morbidities This is a project to reverse insulin resistance in diabetic patients by surgically removing visceral fat