The results of our study indicate that at comparable levels of body weight, nutritional intake and insulin sensitivity, obese AA had higher fasting and stimulated GLP-1 and insulin concentrations compared to Caucasians. In agreement with other reports,2
our findings support a direct effect of octreotide on β-cell activity. Our findings also suggest that octreotide reduces glucose-stimulated GLP-1 response, which further contributes to the insulin suppression.
Octreotide equally suppressed β-cell activity and GLP-1 response in both racial groups. However, after 24 weeks of octreotide-LAR, β-cell activity, insulin and GLP-1 concentrations remained higher in AA than Caucasians.
Our results do not explain whether the above variations are associated with EIA hyperactivity, GLP-1 hypersecretion, differences in metabolic clearance or their combinations. Increased GLP-1 levels may account for the enhanced first and second phase of insulin secretion in AA and the exacerbated insulin response in obese subjects. GLP-1 promotes adipogenesis through its effects on insulin sensitivity, stimulation of fatty acid synthesis in adipose tissue9
and attenuation of the lipolytic action of glucagons.10,11
Obese animals and humans have increased GLP-1 concentrations in response to fat and glucose intake1,12,13
and an exacerbated insulin secretion in response to lower concentration of GLP-1.14
The higher prevalence of CVD and T2DM in AA may be explained by the hyperinsulinemic state fostered by higher GLP-1 concentrations as well as through direct GLP-1 mediation. GLP-1 receptors are present in the heart, and the infusion of GLP-1 causes an increase in the blood pressure and heart rate, which persists even after Adrenergic and cholinergic blockade Infusion of exendins 9–39 (a GLP-1 antagonist) prevents the rise in the blood pressure and heart rate, indicating a potential direct Cardiovascular effects of GLP-1.15–19
GLP-1 receptor (GLP-1R) desensitization may play a role in the genesis of T2DM and consequently the secretory activity of the β-cells. The accumulation of GLP-1 after DPPIV degradation in the circulation may also induce T2DM. GLP-1 (9–36) amide could antagonize the antidiabetes effects of GLP-1 (7–36).20
The validity of these pathogenetic mechanisms in humans in vivo
remains to be determined.
Although energy intake during the study was significantly affected in both groups as suggested by the analysis of food records; changes in body weight and BMI did not reflect the magnitude of such restriction. When asked to record dietary intake, individuals may modify their eating habits or represent their diet in a more positive way, including under-reporting intake. No between-group differences in energy and macronutrients intake were observed at any time point. Based on the findings that both groups reported similar reductions in energy and macronutrient intake, we assume that any inaccuracy in self-reporting dietary intake was reflected in both groups.
In conclusion, obese AAs have higher fasting and stimulated GLP-1 and insulin concentrations compared to Caucasians. Octreotide may affect insulin secretion by both a direct β-cell effect as well as mediating GLP-1 response. Racial differences in GLP-1 concentrations or activity may be one mechanism contributing to the higher prevalence of hyperinsulinemia-associated disorders, including obesity, CVD and type II diabetes in AAs.