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Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance.
Diabetes. 2008 Mar; 57(3):678-87.D

Abstract

OBJECTIVE

Defects in glucagon-like peptide 1 (GLP-1) secretion have been reported in some patients with type 2 diabetes after meal ingestion. We addressed the following questions: 1) Is the quantitative impairment in GLP-1 levels different after mixed meal or isolated glucose ingestion? 2) Which endogenous factors are associated with the concentrations of GLP-1? In particular, do elevated fasting glucose or glucagon levels diminish GLP-1 responses?

RESEARCH DESIGN AND METHODS

Seventeen patients with mild type 2 diabetes, 17 subjects with impaired glucose tolerance, and 14 matched control subjects participated in an oral glucose tolerance test (75 g) and a mixed meal challenge (820 kcal), both carried out over 240 min on separate occasions. Plasma levels of glucose, insulin, C-peptide, glucagon, triglycerides, free fatty acids (FFAs), gastric inhibitory polypeptide (GIP), and GLP-1 were determined.

RESULTS

GIP and GLP-1 levels increased significantly in both experiments (P < 0.0001). In patients with type 2 diabetes, the initial GIP response was exaggerated compared with control subjects after mixed meal (P < 0.001) but not after oral glucose ingestion (P = 0.98). GLP-1 levels were similar in all three groups in both experiments. GIP responses were 186 +/- 17% higher after mixed meal ingestion than after the oral glucose load (P < 0.0001), whereas GLP-1 levels were similar in both experiments. There was a strong negative association between fasting glucagon and integrated FFA levels and subsequent GLP-1 concentrations. In contrast, fasting FFA and integrated glucagon levels after glucose or meal ingestion and female sex were positively related to GLP-1 concentrations. Incretin levels were unrelated to measures of glucose control or insulin secretion.

CONCLUSIONS

Deteriorations in glucose homeostasis can develop in the absence of any impairment in GIP or GLP-1 levels. This suggests that the defects in GLP-1 concentrations previously described in patients with long-standing type 2 diabetes are likely secondary to other hormonal and metabolic alterations, such as hyperglucagonemia. GIP and GLP-1 concentrations appear to be regulated by different factors and are independent of each other.

Authors+Show Affiliations

Department of Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791 Bochum, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18057091

Citation

Vollmer, Kirsten, et al. "Predictors of Incretin Concentrations in Subjects With Normal, Impaired, and Diabetic Glucose Tolerance." Diabetes, vol. 57, no. 3, 2008, pp. 678-87.
Vollmer K, Holst JJ, Baller B, et al. Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes. 2008;57(3):678-87.
Vollmer, K., Holst, J. J., Baller, B., Ellrichmann, M., Nauck, M. A., Schmidt, W. E., & Meier, J. J. (2008). Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes, 57(3), 678-87.
Vollmer K, et al. Predictors of Incretin Concentrations in Subjects With Normal, Impaired, and Diabetic Glucose Tolerance. Diabetes. 2008;57(3):678-87. PubMed PMID: 18057091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. AU - Vollmer,Kirsten, AU - Holst,Jens J, AU - Baller,Birgit, AU - Ellrichmann,Mark, AU - Nauck,Michael A, AU - Schmidt,Wolfgang E, AU - Meier,Juris J, Y1 - 2007/12/05/ PY - 2007/12/7/pubmed PY - 2008/3/22/medline PY - 2007/12/7/entrez SP - 678 EP - 87 JF - Diabetes JO - Diabetes VL - 57 IS - 3 N2 - OBJECTIVE: Defects in glucagon-like peptide 1 (GLP-1) secretion have been reported in some patients with type 2 diabetes after meal ingestion. We addressed the following questions: 1) Is the quantitative impairment in GLP-1 levels different after mixed meal or isolated glucose ingestion? 2) Which endogenous factors are associated with the concentrations of GLP-1? In particular, do elevated fasting glucose or glucagon levels diminish GLP-1 responses? RESEARCH DESIGN AND METHODS: Seventeen patients with mild type 2 diabetes, 17 subjects with impaired glucose tolerance, and 14 matched control subjects participated in an oral glucose tolerance test (75 g) and a mixed meal challenge (820 kcal), both carried out over 240 min on separate occasions. Plasma levels of glucose, insulin, C-peptide, glucagon, triglycerides, free fatty acids (FFAs), gastric inhibitory polypeptide (GIP), and GLP-1 were determined. RESULTS: GIP and GLP-1 levels increased significantly in both experiments (P < 0.0001). In patients with type 2 diabetes, the initial GIP response was exaggerated compared with control subjects after mixed meal (P < 0.001) but not after oral glucose ingestion (P = 0.98). GLP-1 levels were similar in all three groups in both experiments. GIP responses were 186 +/- 17% higher after mixed meal ingestion than after the oral glucose load (P < 0.0001), whereas GLP-1 levels were similar in both experiments. There was a strong negative association between fasting glucagon and integrated FFA levels and subsequent GLP-1 concentrations. In contrast, fasting FFA and integrated glucagon levels after glucose or meal ingestion and female sex were positively related to GLP-1 concentrations. Incretin levels were unrelated to measures of glucose control or insulin secretion. CONCLUSIONS: Deteriorations in glucose homeostasis can develop in the absence of any impairment in GIP or GLP-1 levels. This suggests that the defects in GLP-1 concentrations previously described in patients with long-standing type 2 diabetes are likely secondary to other hormonal and metabolic alterations, such as hyperglucagonemia. GIP and GLP-1 concentrations appear to be regulated by different factors and are independent of each other. SN - 1939-327X UR - https://www.unboundmedicine.com/medline/citation/18057091/Predictors_of_incretin_concentrations_in_subjects_with_normal_impaired_and_diabetic_glucose_tolerance_ DB - PRIME DP - Unbound Medicine ER -