Fenugreek Saponins Lower HOMA‐IR Estimate in Insulin‐Resistant Subjects: A Randomized, Placebo‐Controlled, Study
Authors: Nair Sreejayan , Wang Qiurong , Smith Derek , Bisha Bledar , Robinson Timothy J , Nair Rama P 
Published: June 2021

BackgroundType 2 Diabetes Mellitus (T2DM) is growing at epidemic proportions worldwide. Insulin resistance, defined as an impaired responsiveness of the body to insulin, is a pre‐diabetic stage in the transition from obesity to full‐blown diabetes. Recent studies from our lab demonstrated that furostanolic saponins (FS) isolated from the spice fenugreek improved glucose tolerance and reduced hepatic steatosis in high‐fat diet‐fed, obese mice.ObjectiveThe objective of this study was to evaluate the effect of supplementation of fenugreek FS on cardiometabolic parameters in insulin resistant, obese subjects.MethodsThis was a single center, double‐blind, randomized, placebo‐controlled, parallel‐arm, pilot study in overweight/obese (body mass index>25Kg/m2) young (mean age 27.1±6.1y), otherwise healthy, male and female subjects who satisfied any two of the following three inclusion criteria: i) hemoglobin A1c >5.6% ii) a two‐hour post‐glucose challenge blood‐glucose level > 125 mg/dL and iii) Homeostatic Model Assessment‐insulin resistance (HOMA‐IR) value of >2.5 (fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5). Following informed consent, health‐screening and satisfaction of the inclusion/exclusion criterial, 28‐participants were randomly assigned to receive either placebo (microcrystalline cellulose) or FS (500 mg twice daily) capsules for a period of 12‐weeks. Anthropometric measurements, blood pressure, fasting blood glucose, fasting serum insulin, hemoglobin A1c, lipids, ALT, AST, C‐reactive proteins were determined at baseline and following 12‐week intervention. Body fat composition was determined by dual energy X‐ray absorptiometry. Serum cytokine levels were determined by a Bio‐Plex Pro Human Cytokine 8‐Plex assay. Data were analyzed by a nonparametric bootstrap analysis and the difference of simulated data from treatment and placebo were compared to test for significance. All runs were included in the calculation of 95% confidence interval.ResultsOf the 28 recruited, 25 subjects completed the study. No adverse events were reported, except for one subject who dropped form the study complaining of mild stomach discomfort. No changes were observed between pre‐ and post‐intervention in mean body mass, systolic or diastolic blood pressure, fasting glucose, hemoglobin A1c, lipid‐panel, serum transaminases, and cytokine levels in subjects receiving either the placebo or FS. In contrast, a significant reduction in HOMA‐IR was observed in subjects who received FS compared to those who received the placebo. Additionally, a trend towards lowering of serum insulin levels was observed in the group that received FS.ConclusionTwelve‐week supplementation with fenugreek saponins resulted in reduction in markers of insulin resistance in obese, insulin‐resistant subjects, warranting future studies with FS in overt‐diabetic subjects.Support or Funding InformationSupported by the NIH through the National Institute of General Medical Sciences (NIGMS) #1U54GM104944‐01A1 under the Institutional Development Award (IDeA) program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.