Effect of Medical and Surgical Interventions on α-Cell Function in Dysglycemic Youth and Adults in the RISE Study
Steven E Kahn, Sharon L Edelstein, Silva A Arslanian, Elena Barengolts, Sonia Caprio, David A Ehrmann, Tamara S Hannon, Santica Marcovina, Kieren J Mather, Kristen J Nadeau, Kristina M Utzschneider, Anny H Xiang, Thomas A Buchanan, RISE Consortium, Rise Consortium Investigators:, David A Ehrmann, Karla A Temple, Abby Rue, Elena Barengolts, Babak Mokhlesi, Eve Van Cauter, Susan Sam, M Annette Miller, Steven E Kahn, Karen M Atkinson, Jerry P Palmer, Kristina M Utzschneider, Tsige Gebremedhin, Abigail Kernan-Schloss, Alexandra Kozedub, Brenda K Montgomery, Emily J Morse, Kieren J Mather, Tammy Garrett, Tamara S Hannon, Amale Lteif, Aniket Patel, Robin Chisholm, Karen Moore, Vivian Pirics, Linda Pratt, Kristen J Nadeau, Susan Gross, Philip S Zeitler, Jayne Williams, Melanie Cree Green, Yesenia Garcia Reyes, Krista Vissat, Silva A Arslanian, Kathleen Brown, Nancy Guerra, Kristin Porter, Sonia Caprio, Mary Savoye, Bridget Pierpont, Thomas A Buchanan, Anny H Xiang, Enrique Trigo, Elizabeth Beale, Fadi N Hendee, Namir Katkhouda, Krishan Nayak, Mayra Martinez, Cortney Montgomery, Xinhui Wang, Sharon L Edelstein, John M Lachin, Ashley N Hogan, Santica Marcovina, Jessica Harting, John Albers, Dave Hill, Peter J Savage, Ellen W Leschek, Steven E Kahn, Sharon L Edelstein, Silva A Arslanian, Elena Barengolts, Sonia Caprio, David A Ehrmann, Tamara S Hannon, Santica Marcovina, Kieren J Mather, Kristen J Nadeau, Kristina M Utzschneider, Anny H Xiang, Thomas A Buchanan, RISE Consortium, Rise Consortium Investigators:, David A Ehrmann, Karla A Temple, Abby Rue, Elena Barengolts, Babak Mokhlesi, Eve Van Cauter, Susan Sam, M Annette Miller, Steven E Kahn, Karen M Atkinson, Jerry P Palmer, Kristina M Utzschneider, Tsige Gebremedhin, Abigail Kernan-Schloss, Alexandra Kozedub, Brenda K Montgomery, Emily J Morse, Kieren J Mather, Tammy Garrett, Tamara S Hannon, Amale Lteif, Aniket Patel, Robin Chisholm, Karen Moore, Vivian Pirics, Linda Pratt, Kristen J Nadeau, Susan Gross, Philip S Zeitler, Jayne Williams, Melanie Cree Green, Yesenia Garcia Reyes, Krista Vissat, Silva A Arslanian, Kathleen Brown, Nancy Guerra, Kristin Porter, Sonia Caprio, Mary Savoye, Bridget Pierpont, Thomas A Buchanan, Anny H Xiang, Enrique Trigo, Elizabeth Beale, Fadi N Hendee, Namir Katkhouda, Krishan Nayak, Mayra Martinez, Cortney Montgomery, Xinhui Wang, Sharon L Edelstein, John M Lachin, Ashley N Hogan, Santica Marcovina, Jessica Harting, John Albers, Dave Hill, Peter J Savage, Ellen W Leschek
Abstract
Objective: To compare effects of medications and laparoscopic gastric band surgery (LB) on α-cell function in dysglycemic youth and adults in the Restoring Insulin Secretion (RISE) Study protocols.
Research design and methods: Glucagon was measured in three randomized, parallel, clinical studies: 1) 91 youth studied at baseline, after 12 months on metformin alone (MET) or glargine followed by metformin (G/M), and 3 months after treatment withdrawal; 2) 267 adults studied at the same time points and treated with MET, G/M, or liraglutide plus metformin (L+M) or given placebo (PLAC); and 3) 88 adults studied at baseline and after 12 and 24 months of LB or MET. Fasting glucagon, glucagon suppression by glucose, and acute glucagon response (AGR) to arginine were assessed during hyperglycemic clamps. Glucagon suppression was also measured during oral glucose tolerance tests (OGTTs).
Results: No change in fasting glucagon, steady-state glucagon, or AGR was seen at 12 months following treatment with MET or G/M (in youth and adults) or PLAC (in adults). In contrast, L+M reduced these measures at 12 months (all P ≤ 0.005), which was maintained 3 months after treatment withdrawal (all P < 0.01). LB in adults also reduced fasting glucagon, steady-state glucagon, and AGR at 12 and 24 months (P < 0.05 for all, except AGR at 12 months [P = 0.098]). Similarly, glucagon suppression during OGTTs was greater with L+M and LB. Linear models demonstrated that treatment effects on glucagon with L+M and LB were largely associated with weight loss.
Conclusions: Glucagon concentrations were reduced by L+M and LB in adults with dysglycemia, an effect principally attributable to weight loss in both interventions.
Trial registration: ClinicalTrials.gov NCT01779362 NCT01779375 NCT01763346.
© 2021 by the American Diabetes Association.
Figures
Source: PubMed