Race affects insulin and GLP-1 secretion and response to a long-acting somatostatin analogue in obese adults

Abstract

OBJECTIVE: This study investigated (1) the effect of octreotide-LAR (Sandostatin-LAR s Depot; Novartis) on the enteroinsular axis in a biracial cohort of severely obese adults, (2) whether octreotide suppression of insulin secretion occurs by both a direct b-cell effect and through mediating a glucagon-like peptide 1 (GLP-1) response, and (3) whether differences in GLP-1 concentrations could explain racial differences in insulin concentrations. IntroductionHyperinsulinemia is the hallmark of obesity and several of the obesity-related diseases including type II diabetes mellitus (T2DM) and cardiovascular disease (CVD). Whether the hyperinsulinemia is primary or secondary to obesity is still in debate. African-Americans (AA) have a higher prevalence of obesity, T2DM and CVD, and higher resting and stimulated insulin concentrations than obese Caucasians, which cannot be explained by the severity of obesity or the degree of insulin sensitivity. The enteroinsular axis (EIA) is responsible for 450% of the postprandial insulin release, and glucagon-like peptide-1 (GLP-1) is the major determinant of early insulin secretion in response to a mixed meal. 1 It has been suggested that the somatostatin analogue, octreotide, decreases glucose-stimulated insulin response in a dose-dependent way through a specific subset of somatostatin receptors on pancreatic b cells. [2][3][4][5] This study investigated (1) the effect of octreotide-LAR (Sandostatin-LAR s Depot; Novartis) on the EIA in a biracial cohort of severely obese adults, (2) whether octreotide suppression of insulin secretion occurs by both a direct b-cell effect and through mediating GLP-1 response, and (3) whether differences in GLP-1 concentrations could explain racial differences in insulin concentrations. Materials and methods

A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion

“…29 This pathway is unresponsive to suppression of the voltage-gated calcium channel by octreotide, and could account for the relative lack of effect of octreotide in African Americans. 30 Alternatively, African Americans exhibit reduced hepatic insulin clearance; 31,32 thus, insulin levels drop only marginally in response to insulin suppression, 21 which could abrogate octreotide's effect on hyperinsulinemia. Lastly, obese African Americans have been shown to possess greater subcutaneous and less visceral fat than their Caucasian counterparts matched for BMI.…”

Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels

“…The therapeutic use of SSA such as octreotide and lanreotide, which mainly act via an inhibition of SSTR2 and 5, does not lead solely to an inhibition of somatotrophic pituitary cells, but they ubiquitously stimulate the receptors and convey complex metabolic effects which are currently only clarified in part. This primarily shows detrimental effects on glucose metabolism if there is a genetic predisposition for metabolic diseases (34).…”

Glucagon-like peptide-1 profile during oral glucose tolerance test in young people

“…The San Antonio Heart Study showed that people with normal fasting glucose and normal OGTT result whose blood glucose values failed to return to fasting levels during the OGTT had an increased risk of developing diabetes in the future compared with those whose glycaemia returned to fasting values within 30, 60 or 120 min [22]. The only study regarding GLP-1 concentration at various measuring points in the three-hour OGTT was carried out by Velasquez-Mieyer et al [15] in a group of obese, otherwise healthy people, including among others Caucasians subjects. The curve illustrating changes in GLP-1 levels (in pmol/L) presented in this paper shows that there are no significant differences between values measured at different time points during the OGTT, which is consistent with our results (showed in ng/mL).…”

“…It is very difficult to refer to the GLP-1 values from various studies because, even though commercially available ELISA assays are calibrated against the standards with the same concentration ranges (from 0 to 50), the concentration units (ng/mL, pg/mL or pmol/L) are different [15,16,23,24]. Recalculation leads to ambiguous results, making it impossible to compare the absolute values obtained by different authors.…”

“…In the available literature there are only scarce data on changes in the GLP-1 profile during the OGTT [8,15,16] and its relation to the presence of a variable number of features determining the diagnosis of metabolic syndrome (MS). However, there are no studies that refer to changes in GLP-1 levels depending on the time required for return of blood glucose values to fasting level and the shape of the curve.…”