{"doi":"10.2337/dc21-0027","title":"Baseline Predictors of Glycemic Worsening in Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes in the Restoring Insulin Secretion (RISE) Study","abstract":"OBJECTIVE To identify predictors of glycemic worsening among youth and adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes in the Restoring Insulin Secretion (RISE) Study. RESEARCH DESIGN AND METHODS A total of 91 youth (10–19 years) were randomized 1:1 to 12 months of metformin (MET) or 3 months of glargine, followed by 9 months of metformin (G-MET), and 267 adults were randomized to MET, G-MET, liraglutide plus MET (LIRA+MET), or placebo for 12 months. All participants underwent a baseline hyperglycemic clamp and a 3-h oral glucose tolerance test (OGTT) at baseline, month 6, month 12, and off treatment at month 15 and month 21. Cox models identified baseline predictors of glycemic worsening (HbA1c increase ≥0.5% from baseline). RESULTS Glycemic worsening occurred in 17.8% of youth versus 7.5% of adults at month 12 (P = 0.008) and in 36% of youth versus 20% of adults at month 21 (P = 0.002). In youth, glycemic worsening did not differ by treatment. In adults, month 12 glycemic worsening was less on LIRA+MET versus placebo (hazard ratio 0.21, 95% CI 0.05–0.96, P = 0.044). In both age-groups, lower baseline clamp-derived β-cell responses predicted month 12 and month 21 glycemic worsening (P < 0.01). Lower baseline OGTT-derived β-cell responses predicted month 21 worsening (P < 0.05). In youth, higher baseline HbA1c and 2-h glucose predicted month 12 and month 21 glycemic worsening, and higher fasting glucose predicted month 21 worsening (P < 0.05). In adults, lower clamp- and OGTT-derived insulin sensitivity predicted month 12 and month 21 worsening (P < 0.05). CONCLUSIONS Glycemic worsening was more common among youth than adults with IGT or recently diagnosed type 2 diabetes, predicted by lower baseline β-cell responses in both groups, hyperglycemia in youth, and insulin resistance in adults.","journal":"Diabetes Care","year":2021,"id":158832,"datarank":1.1627514969714836,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"self_citation_contribution":0.5709993734655481,"citation_network_contribution":0.5917521235059356,"self_endowment_contribution":0.5709993734655481,"citer_contribution":0.5917521235059356,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"citer_count":33,"citers_with_citation_signal":20,"citers_with_endowment":20,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8224,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01779362","NCT01779375"],"figshare":["10.2337/figshare.14368220"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":307253,"name":"Sharon L. 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