High postprandial blood glucose levels are associated with increased mortality, cardiovascular events and development of diabetes in the general population. Interventions targeting postprandial glucose have been shown to prevent both cardiovascular events and diabetes. This study evaluates the efficacy and safety of a novel nutritional supplement targeting postprandial glucose excursions in non-diabetic adults. Sixty overweight healthy male and female participants were recruited at two centers and randomized in a double-blind, placebo-controlled, crossover design. The supplement, a water-based drink containing 2.6g of amino acids (L-Leucine, L-Threonine, L-Lysine Monohydrochloride, L-Isoleucine, L-Valine) and 250 mcg of chromium picolinate, was consumed with a standardized carbohydrate-rich meal. The primary endpoint was the incremental area under the curve (iAUC) for venous blood glucose from 0 to 120 minutes. Secondary endpoints included glucose iAUC 0-180 minutes and the maximum glucose concentration (C max), for both venous and capillary blood glucose. In the intention-to-treat-analysis (n = 60) the supplement resulted in a decreased venous blood glucose iAUC 0-120min compared to placebo, mean (SE) of 68.7 (6.6) versus 52.2 (6.8) respectively, a difference of-16.5 mmol/L•min (95% CI-3.1 to-30.0, p = 0.017). The C max for venous blood glucose for the supplement and placebo were 6.45 (0.12) versus 6.10 (<0.12), respectively, a difference of-0.35 mmol/L (95% CI-0.17 to-0.53, p<0.001). In the per protocol-analysis (n = 48), the supplement resulted in a decreased C max compared to placebo from 6.42 (0.14) to 6.12 (0.14), a difference of-0.29 mmol/L (95% CI-0.12 to-0.47, p = 0.002). No significant differences in capillary blood glucose were found, as measured by regular bedside glucometers. The nutritional supplement drink containing amino acids and chromium improves the postprandial glucose homeostasis in overweight adults without diabetes. Future studies should clarify, whether regular consumption of the

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C. elegans are used to study molecular pathways, linking high glucose levels (HG) to diabetic complications. Persistent exposure of C. elegans to a HG environment induces the mitochondrial formation of reactive oxygen species (ROS) and advanced glycation endproducts (AGEs), leading to neuronal damage and decreased lifespan. Studies suggest that transient high glucose exposure (TGE) exerts different effects than persistent exposure. Thus, the effects of TGE on ROS, AGE-formation and life span were studied in C. elegans. Four-day TGE (400 mM) as compared to controls (0mM) showed a persistent increase of ROS (4-days 286 ± 40 RLUs vs. control 187 ± 23 RLUs) without increased formation of AGEs. TGE increased body motility (1-day 0.14 ± 0.02; 4-days 0.15 ± 0.01; 6-days 0.16 ± 0.02 vs. control 0.10 ± 0.02 in mm/s), and bending angle (1-day 17.7 ± 1.55; 3-days 18.7 ± 1.39; 6-days 20.3 ± 0.61 vs. control 15.3 ± 1.63 in degree/s) as signs of neuronal damage. Lifespan was increased by 27% (21 ± 2.4 days) after one-day TGE, 34% (22 ± 1.2 days) after four-days TGE, and 26% (21 ± 1.4 days) after six-days TGE vs. control (16 ± 1.3 days). These experiments suggest that TGE in C. elegans has positive effects on life span and neuronal function, associated with mildly increased ROS-formation. From the perspective of metabolic memory, hormetic effects outweighed the detrimental effects of a HG environment.

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