*3.2. Glucose, Insulin, and C-Peptide*

The lack of effect on blood glucose could be due, on the one hand, to the lack of effect on body weight [28] and, on the other hand, to taking the supplement once a day rather than three times a day (before breakfast, lunch, and dinner), as performed De Martin et al. [26]. There is a possibility that a single administration of the supplement intake during the day might have resulted in a less pronounced effect on the activities of intestinal α-amylase and α-glucosidase and, therefore, on the absorption of the glucose and blood levels.

It should also be considered that blood glucose is maintained primarily because of regulated pancreatic insulin secretion. In this respect, C-peptide is a byproduct of insulin synthesis from pro-insulin. It is secreted by pancreatic β-cells in equal amounts with insulin; however, unlike insulin, C-peptide is not extracted by the liver and has a constant peripheral clearance. It is considered a valuable and precise biomarker of insulin secretion due to its longer time life in circulation (20 to 30 min for C-peptide versus 5 min for insulin) [29]. Moreover, C-peptide hypersecretion occurred in prediabetic and diabetic patients in the fasting state and in the early and late phases of the OGTT [30]. In this context, a reduction in plasma C-peptide in these patients is desirable. In this study, we observed a modest decrease of C-peptide at the late phase of OGTT in participants consuming brown seaweed extract, suggesting a potential for reduced insulin secretion in the long term, thereby decreasing the risk for developing glucose intolerance and type 2 diabetes [31,32].

This effect may be associated with phlorotannins, polyphenolic compounds found in brown seaweeds only, and fucoidan, found as a sulfated polysaccharide in brown marine algae, known to decrease the α-amylase and α-glucosidase activities and, therefore, the digestion and assimilation of glucose [17,18,20,33]. This may result, in the long term, in an improvement of pancreatic function and, ultimately, in a reduction of glucose intolerance seen in prediabetic patients. Our results are in good agreement, but less pronounced than those of De Martin et al. [26] and Derosa et al. [27], who have recently reported a decrease in glycemia, insulin secretion, insulin resistance [26], and postprandial glycemia [27] following a 12-week consumption of 712.5 mg of *Ascophyllum nodosum* and *Fucus vesiculosus* extract with the addition of chromium picolinate. In light of these studies [26,27], it is important to consider that the presence of picolinate chromium, known as a hypoglycemic agent, could have accentuated the impact of the *Ascophyllum nodosum* and *Fucus vesiculosus* extract on glycemic response. Furthermore, in both previous studies [26,27], the effects were more pronounced after 6 months than after 3 months of treatment with an additional reduction of fasting plasma glucose, glycated hemoglobin, and insulin resistance. The differences in the impact of the extract on glucose homeostasis observed in the present study and the two former studies [26,27] could be explained by the frequency and doses, duration of the trial, and use of picolinate of chromium in the previous studies. However, our study is one of few to have explored the effects of brown seaweed extract alone and show that there is a beneficial impact, albeit modest, of the brown seaweed extract per se, without chromium picolinate, on insulin secretion.
