Effects of Treatment of Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes With Metformin Alone or in Combination With Insulin Glargine on β-Cell Function: Comparison of Responses In Youth And Adults
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, Ting Chow, Fadi N Hendee, Namir Katkhouda, Krishan Nayak, Mayra Martinez, Cortney Montgomery, Xinhui Wang, Jun Wu, Sharon L Edelstein, John M Lachin, Ashley Hogan Tjaden, Mark T Tripputi, Santica Marcovina, Jessica Harting, John Albers, Dave Hill, Peter J Savage, Ellen W Leschek, 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, Ting Chow, Fadi N Hendee, Namir Katkhouda, Krishan Nayak, Mayra Martinez, Cortney Montgomery, Xinhui Wang, Jun Wu, Sharon L Edelstein, John M Lachin, Ashley Hogan Tjaden, Mark T Tripputi, Santica Marcovina, Jessica Harting, John Albers, Dave Hill, Peter J Savage, Ellen W Leschek
Abstract
β-Cell dysfunction is central to the pathogenesis of impaired glucose tolerance (IGT) and type 2 diabetes. Compared with adults, youth have hyperresponsive β-cells and their decline in β-cell function appears to be more rapid. However, there are no direct comparisons of β-cell responses to pharmacological intervention between the two age-groups. The Restoring Insulin Secretion (RISE) Adult Medication Study and the RISE Pediatric Medication Study compared interventions to improve or preserve β-cell function. Obese youth (n = 91) and adults (n = 132) with IGT or recently diagnosed type 2 diabetes were randomized to 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin. Hyperglycemic clamps conducted at baseline, after 12 months of medication, and 3 months after medication withdrawal assessed β-cell function as steady-state and maximal C-peptide responses adjusted for insulin sensitivity. Temporal changes in β-cell function were distinctly different. In youth, β-cell function deteriorated during treatment and after treatment withdrawal, with no differences between treatment groups. In adults, β-cell function improved during treatment, but this was not sustained after treatment withdrawal. The difference in β-cell function outcomes in response to medications in youth versus adults supports a more adverse trajectory of β-cell deterioration in youth.
Trial registration: ClinicalTrials.gov NCT01779362 NCT01779375.
© 2019 by the American Diabetes Association.
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Source: PubMed