Defective Glucagon-Like Peptide 1 Secretion in Prediabetes and Type 2 Diabetes Is Influenced by Weight and Sex. Chicken, Egg, or None of the Above?

Glucagon-like peptide 1 (GLP-1) is considered to be the primary incretin hormone, released in response to food ingestion and contributing to meal assimilation. GLP-1 is a powerful insulin secretagogue, stimulating insulin secretion and suppressing glucagon secretion in a glucose-dependent manner (1), and indeed, numerous pharmacologic agents use the GLP-1 pathway to produce effective glucose-lowering therapy (2). Given the antidiabetogenic actions of GLP-1, it is a reasonable question to wonder whether defects in GLP-1 secretion contribute to the pathogenesis of type 2 diabetes. Over the years, multiple studies have examined this question. However, the evidence to suggest decreased GLP-1 secretion in prediabetes and diabetes has been mixed at best, with decreased (3–5), normal (6,7), or increased (8) GLP-1 concentrations reported in subjects with prediabetes or type 2 diabetes.Subsequently, Nauck et al. (9) undertook a meta-analysis of studies comparing active and total GLP-1 in people with diabetes and weight-matched control subjects and concluded that after an oral glucose challenge or after a mixed meal, the integrated, incremental concentrations of GLP-1 did not differ between patients with type 2 diabetes and control subjects. GLP-1 concentrations were unaffected by weight or age. In addition, we examined active and total GLP-1 concentrations in 165 …