title: GLP-1 Response to Oral Glucose Is Reduced in Prediabetes, Screen-Detected Type 2 Diabetes, and Obesity and Influenced by Sex: The ADDITION-PRO Study.
abstract: The role of glucose-stimulated release of 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), prediabetes (n = 525), 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 prediabetes or type 2 diabetes had 25% lower GLP-1 response to an OGTT, and both men and women with prediabetes or type 2 diabetes had 16-21% lower 120-min GLP-1 concentrations independent of age and obesity. Obese and overweight individuals had up to 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 β-cell function, older age, and lesser 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.
authors: Steno Diabetes Center, Gentofte, Denmark krif@steno.dk.
authors: Kristine
authors: K
authors: Færch
authors: NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Signe S
authors: SS
authors: Torekov
authors: Steno Diabetes Center, Gentofte, Denmark.
authors: Dorte
authors: D
authors: Vistisen
authors: Steno Diabetes Center, Gentofte, Denmark Danish Diabetes Academy, Odense, Denmark.
authors: Nanna B
authors: NB
authors: Johansen
authors: Section for General Practice, Department of Public Health, Aarhus, Denmark.
authors: Daniel R
authors: DR
authors: Witte
authors: NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors: Anna
authors: A
authors: Jonsson
authors: NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors: Oluf
authors: O
authors: Pedersen
authors: NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors: Torben
authors: T
authors: Hansen
authors: Section for General Practice, Department of Public Health, Aarhus, Denmark.
authors: Torsten
authors: T
authors: Lauritzen
authors: Section for General Practice, Department of Public Health, Aarhus, Denmark.
authors: Annelli
authors: A
authors: Sandbæk
authors: NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Jens Juul
authors: JJ
authors: Holst
authors: Steno Diabetes Center, Gentofte, Denmark.
authors: Marit E
authors: ME
authors: Jørgensen
mesh_terms: D000367:Age Factors; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D011236:Prediabetic State / Q000378:metabolism*; D012727:Sex Characteristics; D055105:Waist Circumference
chemical_list: D001786:Blood Glucose; D007328:Insulin; D052216:Glucagon-Like Peptide 1