Hypoglycemia limits the glycemic control that can be achieved with insulin and sulfonylureas (SUs) , but we lack evidence from head-to-head studies to guide management. In the GRADE comparative effectiveness study, 5,047 patients with type 2 diabetes (T2DM) of <years’ duration, on metformin monotherapy with HbA1c 6.8-8.5%, were randomized to addition of the SU glimepiride, insulin glargine U-100, sitagliptin, or liraglutide, permitting a direct comparison over 5.0 ± 1.3 (mean ± SD) years of follow-up. Glimepiride was initiated at 1-2 mg/day, glargine at 10-20 units/day, and both were titrated according to algorithms based on self-monitored blood glucose levels. Over 4 years, adjudicated severe hypoglycemia occurred in 2.3% of those randomized to glimepiride vs. 1.4% with glargine, but was less frequent with liraglutide (0.9%) and sitagliptin (0.7%) , p=0.003. During GRADE, HbA1c was measured every 3 months, and if a HbA1c >7.5% was confirmed, “rescue treatment” with glargine and/or aspart was added. We examined management in participants who were unable to keep HbA1c ≤7.5% - whose primary study drug was insufficient - prior to their “rescue”. At 3 mo after randomization, hypoglycemic symptoms or a measured glucose <70 mg/dl within the previous 30 d was reported by 33% of those using glimepiride vs. 15% with glargine (p <0.001) . The mean dose of glimepiride at 3 mo (n=627) and 12 mo (n=337) was 3.4 and 4.2 mg/day, respectively [a 24% increase but considerably submaximal (8 mg) ]. In contrast, the dose of glargine at 3 mo (n=487) and 12 mo (n=337) was 26 and 37 units/day, respectively (a 44% increase, p <0.0vs. glimepiride) . The outcome of a confirmed HbA1c >7.5% was reached in 50% of those using glimepiride, vs. 39% with glargine (p<0.001) . Conclusions: In metformin-treated patients with T2DM, there was more hypoglycemia, less increase in drug dose, and less preservation of glycemic control, with addition of the SU glimepiride compared to glargine; increases in glimepiride dose might have been limited by hypoglycemia. Disclosure L.S. Phillips: Research Support; Abbott Diabetes, AbbVie Inc., Janssen Pharmaceuticals, Inc., Janssen Scientific Affairs, LLC, Pfizer Inc. Other Relationship; Cystic Fibrosis Foundation, Diasyst Inc. E.R. Seaquist: None. C. Baker: None. R.M. Bergenstal: Advisory Panel; Hygieia, Medtronic, Roche Diabetes Care, Zealand Pharma A/S. Consultant; Abbott Diabetes, Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Onduo LLC, Sanofi, United HealthCare Services, Inc. Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi. N.M. Butera: None. J.P. Crandall: Research Support; Abbott. R. Goland: None. S.H. Hox: None. D.S. Hsia: None. M.L. Johnson: Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Jaeb Center for Health Research, Lilly, Medtronic, Novo Nordisk, Sanofi. P. Raskin: None. W. Valencia: None. A.H. Waltje: None. N. Younes: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK098246, U34-DK-088043)
Regression to normal glucose regulation (NGR) has been reported in response to lifestyle modification and medications. In this secondary analysis of the D2d study, a randomized trial of 4,000 IU/d of vitamin D3 vs. placebo, we determined whether vitamin D increased regression to NGR in people with prediabetes. Eligible participants met at least 2-of-3 ADA glycemic criteria for prediabetes (n=2423) and the two groups were similar at baseline. During follow-up, glycemic status was assessed semi-annually with FG and HbA1c and annually with 2-hour glucose after 75-g glucose load (2hPG) . In exploratory analyses that censored follow up at initiation of diabetes/weight-loss medication, stopping trial pills, taking vitamin D above the trial limit, death or withdrawal, we tested for an effect of vitamin D on new-onset NGR, which was defined as the first occurrence of 2 or 3 glycemic criteria in the normal range and none in the diabetes range. Over a median follow-up of 2.5 years, the NGR outcome occurred in 343/12 participants in the vitamin D group and 295/1212 in the placebo group; hazard ratio (95%CI) for time-to-NGR for vitamin D was 1.16 (0.99-1.36) . Among those who never met NGR during follow-up (n=1785) , 29% developed diabetes compared to 8.2% among those who met NGR at some point during the study (p<0.01) . At the last encounter, the NGR outcome was observed in 133/1069 participants in the vitamin D group and 102/1050 in the placebo group; incidence rate ratio (95%CI) for vitamin D was 1.26 (0.97-1.63) . When we used the NGR definition from other studies to include only those with normal FG and 2hPG regardless of HbA1c, 90/1037 participants in the vitamin D group and 63/1050 in the placebo group at the last encounter had NGR; incidence rate ratio (95%CI) for vitamin D 1.39 (1.01-1.91) . In conclusion, vitamin D supplementation increased the likelihood of regression to NGR at the last visit, and those who met NGR during the study were less likely to subsequently develop diabetes. Disclosure D.S.Hsia: None. A.G.Pittas: None. D2d research group: n/a. J.P.Nelson: None. E.Vickery: None. N.Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. E.S.Leblanc: n/a. S.H.Kim: Advisory Panel; GI Dynamics, Consultant; Aligos, Research Support; Fractyl Health, Inc. I.Brodsky: None. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. B.Dawson-hughes: None. Funding American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)
The transition period from pediatric to adult care is associated with worsening glycemic control and poor attendance with adult providers, which has only been complicated by the COVID-19 pandemic. Diabetes transition clinics and model programs may improve outcomes, but they remain few in number and underutilized. The aim of our cross-sectional, retrospective study was to compare diabetes control in our diabetes transition clinic (DTC) patients versus those who remained in pediatric endocrine care (non-DTC) over a 5 year period. A random sample of 82 patients ages 16 to 25 years seen in clinic from 9/11/2017 to 9/10/2022 were included. Each patient had at least one visit before and after 3/11/2020, when COVID-19 was declared a global pandemic. Those who attended DTC were similar to the non-DTC group except for insurance status (Table). The DTC group had a mean HbA1c of 8.8% vs. 9.0% (p=0.80) and a mean of 4.1 vs. 3.8 visits (p=0.69); whereas, the non-DTC group had a mean HbA1c of 10% vs. 9.6% (p=0.27) and a mean of 5.2 vs. 4.2 visits (p=0.19) before versus after 3/11/2020. Telehealth visits consisted of 15.7% of the visits in the DTC group versus 13.3% in the non-DTC group after 3/11/2020 (p=0.56). Despite the challenges of the COVID-19 pandemic, patients who moved to DTC during this time maintained glycemic control and continued to attend clinic visits consistently similar to those who remained in pediatric endocrine care. Disclosure D. S. Hsia: None. R. A. Beyl: None. R. Rumsey: None. Funding National Institute of General Medical Sciences (U54GM104940)
Rate of progression from prediabetes to diabetes varies greatly, and better risk stratification would help guide prevention efforts. We evaluated predictors of incident diabetes in the placebo arm (n=1212) of the vitamin D and type 2 diabetes (D2d) study. At baseline, participants met 2 or 3 ADA glycemic criteria for prediabetes (fasting glucose, FPG, 100-125mg/dL; 2-hour glucose during a 75-g OGTT, 2hPG, 140-199 mg/dL; HbA1c, 5.7-6.4%). Diabetes was diagnosed based on semiannual testing. After a median follow up of 2.5 years, 27% met criteria for diabetes. Among those who did and did not develop diabetes, mean BMI (±SD) was similar (32.1 kg/m2 ± 4.4), as well as other demographic factors including age, race, and ethnicity. More men than women developed diabetes (29% vs 23%, p=0.02). Incident diabetes rates differed by prediabetes subgroups (Figure); and those meeting all three prediabetes criteria at baseline (35.4%) were most likely to develop diabetes (log-rank p <0.001). There were no differences in the incident diabetes rate among those people meeting only 2 of the prediabetes criteria (Figure). Also, area under the receiver operator characteristic curves for incident diabetes at 36 months increased when all 3 criteria were used in the diagnosis (0.736) vs only FPG and HbA1c (0.686). We conclude that ‘prediabetes’ is heterogeneous, and the 2hPG may refine diabetes risk and guide intervention strategies in adults with high-risk prediabetes. Disclosure S. H. Kim: Advisory Panel; GI Dynamics, Consultant; Aligos, Research Support; Fractyl Health, Inc. D. S. Hsia: None. E. S. Leblanc: Other Relationship; Dexcom, Inc. M. Staten: None. R. Chatterjee montgomery: Research Support; Bristol-Myers Squibb Company, Epigenomics AG. N. Rasouli: Research Support; Novo Nordisk, Eli Lilly and Company, Somalogic. V. R. Aroda: Consultant; Applied Therapeutics Inc., Fractyl Health, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Other Relationship; Janssen Pharmaceuticals, Inc., Research Support; Applied Therapeutics Inc., Eli Lilly and Company, Fractyl Health, Inc., Novo Nordisk, Sanofi. A. G. Pittas: None. Funding National Institutes of Health (U01DK098245)
Understanding the association between glycemia and A1c by race can improve screening for prediabetes and type 2 diabetes (T2D) . This association was examined cross-sectionally in 1016 Black and 2658 White persons screened for D2d (mean age 60; fasting glucose [FG] 1mg/dL; A1c 5.9%) . Of these, 22with at least 2-of-3 ADA glycemic criteria for prediabetes (mean age 60, FG 1mg/dL, A1c 5.9%, 28% Black) were followed longitudinally for median 2.5 years with annual OGTT and semi-annual FG and A1c. Numerical integration methods were used for the estimation of area under the OGTT-derived glucose curve (AUC) . Mean A1c was estimated for a given AUC quintile using linear regression for Whites, Blacks, and Asians. Adjusting for covariates, the A1c was higher by 0.2-0.25% among Black vs. White participants with similar glycemia in all AUC quintiles. During follow-up, Black participants were more likely to be diagnosed with T2D based on A1c; White participants were more likely to be diagnosed by FG. The absolute increase in A1c over time according to baseline AUC-glucose quintiles differed by race. Compared to White participants, Black participants in lower baseline AUC quintiles had greater increases in A1c over time, while A1c increased similarly in White and Black persons in the two highest baseline AUC quintiles. In summary, Black participants had higher A1c than White participants for similar degree of glycemia defined by AUC; the glycemic criteria contributing to the diagnosis of T2D differed by race; and there were AUC by racial interactions in A1c increase over time. Disclosure E.S.Leblanc: n/a. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. J.P.Nelson: None. D.S.Hsia: None. D2d research group: n/a. A.G.Pittas: None. R.Chatterjee montgomery: Research Support; Bristol-Myers Squibb Company, Epigenomics AG. N.Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. M.K.Rhee: Research Support; Kowa Company, Ltd. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck & Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. C.Desouza: Advisory Panel; AstraZeneca, Bayer AG, Novo Nordisk A/S, Consultant; Asahi Kasei Corporation. L.M.Neff: Employee; Eli Lilly and Company, Research Support; Amryt Pharma Plc, Novo Nordisk, Stock/Shareholder; Eli Lilly and Company. A.L.Peters: Advisory Panel; Abbott Diabetes, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Shouti, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Other Relationship; Omada Health, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Leona M. and Harry B. Helmsley Charitable Trust, Stock/Shareholder; Teladoc Health. Funding American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)
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