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Insulin secretion rate in response to GLP-1 correlates with insulin resistance in healthy adults
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In healthy individuals, the production of insulin in response to glucagon-like peptide-1 corresponds to insulin resistance, according to recent findings.
However, significant differences in beta-cell susceptibility to glucagon-like peptide-1 (GLP-1) appear to exist independent of insulin sensitivity, according to the researchers.
In the study, David A. D’Alessio, MD, of Duke University Medical Center Division of Endocrinology, and colleagues evaluated young adults aged 19 to 36 years with obesity (n = 8; 5 men) or who were lean (n = 10; 5 men) to determine the sensitivity of insulin secretion to GLP-1. Participants were healthy, had no family history of diabetes and used no medications with the exception of birth control.
The researchers collected fasting blood samples from all participants and then administered an infusion of 20% dextrose to achieve a target blood glucose level of 7.2 mmol/L. After 85 minutes of hyperglycemia, GLP-1 infusion was administered and incrementally increased every 25 minutes. The researchers took blood samples at scheduled times to evaluated plasma levels of insulin, C-peptide and GLP-1.
The researchers found that the mean fasting glucose was 4.5 mmol/L in lean participants and 4.8 mmol/L in those with obesity. Compared with lean participants, those with obesity had significantly higher homeostasis model assessment for insulin resistance (HOMA-2IR; P = .001). In both groups, there was a linear increase in insulin secretion rate (ISR) in proportion to stepwise increases of GLP-1, but participants with obesity had a greater slope of ISR in response to GLP-1 compared with lean participants (P < .001).
A significant association was seen between beta-cell sensitivity to GLP-1 and insulin resistance (P = .001) and correction for HOMA-2IR revealed no difference in the slopes of ISR and GLP-1 levels between the groups (P = .98).
“What is surprising is the magnitude of the difference between high and low GLP-1 responders in this group of normal subjects,” the researchers wrote. “Because we only studied each subject once we cannot say for sure how much of this variation in beta-cell GLP-1 sensitivity is a persistent characteristic of these individuals. However, our results, and the accumulation of genotype-phenotype interactions in GLP-1 responsiveness have implications for the use of GLP-1 agonists in diabetes.” – by Jennifer Byrne
Disclosure: D’Alessio reports various financial ties with Boehringer-Ingelheim, Intarcia, Janssen, Lilly, Merck, Novo Nordisk and Roche.
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