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

TY - JOUR

T1 - 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

T2 - The ADDITION-PRO Study

AU - Færch, Kristine

AU - Torekov, Signe S

AU - Vistisen, Dorte

AU - Johansen, Nanna B

AU - Witte, Daniel R

AU - Jonsson, Anna

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Lauritzen, Torsten

AU - Sandbæk, Annelli

AU - Holst, Jens Juul

AU - Jørgensen, Marit E

N1 - © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

PY - 2015/7

Y1 - 2015/7

N2 - 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.

AB - 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.

U2 - 10.2337/db14-1751

DO - 10.2337/db14-1751

M3 - Journal article

C2 - 25677912

SN - 0012-1797

VL - 64

SP - 2513

EP - 2525

JO - Diabetes

JF - Diabetes

ER -