Hypoglycemic effects of antioxidant-rich plant extracts on postprandial glycemic responses in participants with prediabetes (GLARE study)

Background:  Plant extracts may help to improve glycemic control in individuals with poor glycemic control. However, few studies have been investigated in the prediabetes cohort, which is a high-risk condition for T2DM. Thus, this study aimed to investigate the acute effect of grape seed, rooibos tea, and olive leaf extracts on postprandial blood glucose and insulin in participants with prediabetes.  Methods:  An acute, single-blind, placebo-controlled, non-randomized, crossover study (ACTRN12617000837325) where placebo and extracts of grape seed, rooibos tea and olive leaf standardized for total antioxidant capacity were given separately during an oral glucose tolerance test to participants (n=19, five men and fourteen women, aged 65.0 ± 1.6 years, Body Mass Index (BMI) 27.3 ± 1.1 kg/m 2 ) with prediabetes (Glycated hemoglobin A1c (HbA1c) 42 ± 1 mmol/mol). The primary outcome incremental area under the curve of glucose (iAUC glucose ) was examined with other glycemic measures.  Data was analyzed using linear mixed model for repeated measures. Secondary analysis was conducted by stratifying participants into either a healthier or less healthy subgroup based on the postprandial time to glucose and insulin peaks, with the less healthy subgroup experiencing delayed glucose and/or insulin peaks. Results:  There were no overall significant changes to glucose and insulin measures between all plant extracts and placebo ( p >0.05). Upon secondary analysis, all extracts affected glycemic responses in the less healthy subgroup. Compared to placebo, grape seed reduced plasma iAUC glucose ( p =0.016, 21.9% reduction), 2 h postprandial glucose (2hPG) ( p =0.034, 14.7% reduction) and metabolic clearance rate of glucose (MCR glucose ) ( p =0.016, 16.7% increase). It also improved insulin indices such as 2 h postprandial insulin (2hPI) ( p =0.029, 22.4% reduction) and Stumvoll overall insulin sensitivity index (ISI overall ) ( p =0.028, 15.0% increase). Rooibos tea extract significantly improved β-cell function as demonstrated by the increased oral disposition index (DI) ( p =0.031, 32.4% increase) compared to placebo. Olive leaf extract significantly increased incremental area under the curve of insulin (iAUC insulin ) ( p =0.040, 16.7% increase). Conclusion:  Grape seed, rooibos tea and olive leaf extracts demonstrated acute hypoglycemic benefits in adults with prediabetes and having less healthy metabolic profiles. A chronic study on the plant extracts is warranted to determine their longer-term impact on prediabetes. Trial Registration ID:  ACTRN12617000837325 Keywords:  grape seed extract; rooibos tea extract; olive leaf extract; impaired glycemic control; hyperglycemia; hypoglycemic effects; insulin sensitivity; beta-cell function