medwireNews: The failure of intensive medication to halt beta-cell decline in children with early type 2 diabetes occurs despite them having better baseline beta-cell and alpha-cell function than newly diagnosed adults, say the RISE researchers.
Presenting the beta-cell findings at the 55th EASD Annual Meeting in Barcelona, Spain, Silva Arslanian (University of Pittsburgh, Pennsylvania, USA) reported that, at baseline, the 85 youth RISE participants, who all had prediabetes or newly diagnosed type 2 diabetes, were significantly more likely than 353 newly diagnosed adults to have a biphasic glucose response curve, at 18.8% versus 8.2%.
This biphasic response, comprising a rise in C-peptide level followed by a slight fall and then a second increase during an oral glucose tolerance test, is considered the most healthy response curve, explained Arslanian. A monophasic curve is less healthy, reflecting reduced insulin sensitivity and beta-cell function, and an incessant increase the least healthy.
Among participants with biphasic or monophasic curves, the youth participants had better beta-cell function than the adults did. However, insulin sensitivity was lower in the youth than adult participants for all categories of glucose response curve.
The presenter pointed out that in the primary RISE analyses, intensive treatment with insulin glargine followed by metformin slowed the decline in beta-cell function in adults but not in children, despite the latter now proving to have the better function at baseline.
The current results also show that intensive treatment did not cause a shift to a healthier glucose response curve in either children or adults.
Conference delegates also heard comparisons of the RISE adult medication and adult gastric banding studies, presented by David Ehrmann (University of Chicago, Illinois, USA).
These showed that there were minimal changes in beta-cell function as a result of either medication or gastric banding, despite the marked weight loss experienced by people who underwent surgery, although this group did exhibit improved insulin sensitivity.
The exception was in people who took liraglutide plus metformin, which resulted in clear increases in insulin secretion but without an accompanying rise in the capacity of the cells to secrete insulin, which Ehrmann noted could be detrimental to the beta cells over time.
In the same session, Steven Kahn (University of Washington, Seattle, USA) presented preliminary data on alpha-cell function, which the team measured in the same manner as beta-cell function, but measuring levels of glucagon instead of C-peptide.
Fasting glucagon and its acute response were inversely related to insulin sensitivity, so the more insulin-sensitive an individual was, the more sensitive their alpha cells were to suppression by glucose.
This may suggest that alpha cells, like peripheral tissue, become insulin resistant in people with type 2 diabetes, said Kahn.
But at any insulin sensitivity fasting glucagon and the acute glucagon response to arginine were both lower in the youth participants, indicating that their alpha cells were more effectively suppressed by glucose.
Kahn said that the hyper-responsive beta cells in youth with type 2 diabetes could hypothetically be an effect of dysfunctional alpha cells, “given that glucagon can stimulate the beta cell.”
But he said their results refute this. “If anything we see the opposite, suggesting they are better regulated under conditions to reduce glucagon in youth, to deal with what’s going on with their glucose concentrations.”
Intensive treatment did not affect alpha-cell function in youth participants. In adults, however, fasting glucagon and its acute response both declined in those given liraglutide, with this effect persisting for at least 3 months after stopping the medication, and both measures also improved in those who underwent surgery.
Kahn said that this could be a direct effect of liraglutide on alpha cells, but could also be mediated via its effects on beta cells.
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EASD 2019; Barcelona, Spain: 16–20 September