The GLP-1 response to glucose does not mediate beta and alpha cell dysfunction in Hispanics with abnormal glucose metabolism. (January 2018)

• Record Type: Journal Article
• Authors: Adams, Elizabeth; Genter, Pauline; Keefe, Emma; Sandow, Kevin; Gray, Virginia; Rotter, Jerome I.; Chen, Yii-Der Ida; Ipp, Eli
• Is Part Of: Diabetes research and clinical practice. Volume 135(2018)
• Page Start: 185
• Page End: 191
• Publication Date: 2018-01
• Subjects: GLP-1 -- Insulinogenic index -- Glucagon suppression index -- Glucose tolerance -- Hispanic; Diabetes -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462
• DOI: 10.1016/j.diabres.2017.11.010
• Languages: English
• ISSNs: 0168-8227

Abstract

Highlights: In Type 2 diabetes (T2D) insulin secretion and glucagon suppression is impaired. We tested if an impaired GLP-1 pathway can account for T2D in Hispanic Americans. Glucose stimulated GLP-1 secretion is similar in non-Hispanic, Hispanic and T2D. In T2D impaired insulin and glucagon responses were found despite normal GLP-1. GLP-1 therapies do not rely on replacement, rather amplification of GLP-1 pathways. Abstract: Aims: Glucagon-like peptide-1 (GLP-1) contributes to insulin secretion after meals. Though Hispanics have increased risk for type 2 diabetes mellitus, it is unknown if impaired GLP-1 secretion contributes to this risk. We therefore studied plasma GLP-1 secretion and action in Hispanic adults. Methods: Hispanic (H; n = 31) and non-Hispanic (nH; n = 15) participants underwent an oral glucose tolerance test (OGTT). All participants were categorized by glucose tolerance into four groups: normal glucose tolerant non-Hispanic (NGT-nH; n = 15), normal glucose tolerant Hispanic (NGT-H; n = 12), impaired glucose tolerant Hispanic (IGT-H; n = 11), or newly diagnosed type 2 diabetes mellitus, Hispanic (T2D-H; n = 8). Results: Glucose-induced increments in plasma GLP-1 (Δ-GLP-1) were not different in NGT-H and NGT-nH (p = .38), nor amongst Hispanic subgroups with varying degrees of glucose homeostasis (p = .6). In contrast, the insulinogenic index in T2D-H group was lower than the other groups (p = .016). Subjects with abnormal glucose homeostasis (AGH), i.e., T2D-H plus IGT-H, had a diminished glucagon suppression index compared to patients with normal glucose homeostasis (NGT-H plus NGT-nH) (p = .035). Conclusions: GLP-1 responses to glucose were similar in Hispanic and Non-Hispanic NGT. Despite similar glucose-induced Δ-GLP-1, insulin and glucagon responses were abnormal in T2D-H and AGH, respectively. Thus, impaired GLP-1 secretion is unlikely to play a role in islet dysfunction in T2D. Although GLP-1 therapeutics enhance insulin secretion and glucagon suppression, it is likely due to pharmacological amplification of the GLP-1 pathways rather than treatment of hormonal deficiency.