Glucagon-Like Peptide-1 (GLP-1) Response to Oral Glucose is Reduced in Pre-diabetes, Screen-detected Type 2 Diabetes and Obesity, and Influenced by Sex: The ADDITION-PRO Study

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Kristine Færch, Signe S Torekov, Dorte Vistisen, Nanna B Johansen, Daniel R Witte, Anna Jonsson, Oluf Pedersen, Torben Hansen, Torsten Lauritzen, Annelli Sandbæk, Jens Juul Holst, Marit E Jørgensen

The role of glucose-stimulated release of glucagon-like peptide-1 (GLP-1) in the development of obesity and type 2 diabetes is unclear. We assessed GLP-1 response to oral glucose in a large study population of lean and obese men and women with normal and impaired glucose regulation. Circulating concentrations of glucose, insulin and GLP-1 during an oral glucose tolerance test (OGTT) were analyzed in individuals with normal glucose tolerance (NGT, n=774), pre-diabetes (n=523) or screen-detected type 2 diabetes (n=163) who attended the Danish ADDITION-PRO study (n=1,462). Compared with individuals with NGT, women with pre-diabetes or type 2 diabetes had 25% lower GLP-1 response to an OGTT, and both men and women with pre-diabetes or type 2 diabetes had 16-21% lower 120-min GLP-1 concentrations independent of age and obesity. Obese and overweight individuals had 20% reduced GLP-1 response to oral glucose compared with normal weight individuals independent of glucose tolerance status. Higher GLP-1 responses were associated with better insulin sensitivity and beta cell function, higher age and lower degree of obesity. Our findings indicate that a reduction in GLP-1 response to oral glucose occurs prior to the development of type 2 diabetes and obesity, which can have consequences for early prevention strategies for diabetes.

Original languageEnglish
JournalDiabetes
Volume64
Pages (from-to)2513-25
Number of pages13
ISSN0012-1797
DOIs
Publication statusPublished - Jul 2015

ID: 132002519