The Experts below are selected from a list of 138 Experts worldwide ranked by ideXlab platform
Fred T. Fiedorek - One of the best experts on this subject based on the ideXlab platform.
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glycemic control with glyburide Metformin tablets in combination with Rosiglitazone in patients with type 2 diabetes a randomized double blind trial
The American Journal of Medicine, 2004Co-Authors: George Dailey, Simon Bruce, Jongsoon Park, Mustafa A Noor, Fred T. FiedorekAbstract:Abstract Purpose To assess the efficacy and safety of adding Rosiglitazone to an established regimen of glyburide/Metformin in patients with type 2 diabetes who had not achieved adequate glycemic control (glycosylated hemoglobin [HbA 1C ] levels >7.0% and ≤10.0%). Methods Following an open-label, lead-in phase to optimize the dosing of glyburide/Metformin tablets, 365 patients randomly received additive therapy comprising Rosiglitazone (4 mg once daily) or placebo for 24 weeks. Based on glycemic response, Rosiglitazone dose was maintained or increased to 4 mg twice daily. Glyburide/Metformin dose was maintained or reduced by 2.5/500 mg for symptomatic hypoglycemia. The primary endpoint was the change in HbA 1C level from baseline to week 24. The proportions of patients achieving HbA 1C levels Results After 24 weeks, therapy with glyburide/Metformin Plus Rosiglitazone resulted in a greater reduction in HbA 1C levels (–1.0%, P P Conclusion In patients with inadequate glycemic control despite established glyburide/Metformin therapy, the addition of Rosiglitazone improves glycemic control, allowing more patients to achieve an HbA 1C level
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Glycemic control with Glyburide/Metformin tablets in combination with Rosiglitazone in patients with type 2 diabetes: a randomized, double-blind trial
The American journal of medicine, 2004Co-Authors: George Dailey, Simon Bruce, Jongsoon Park, Mustafa A Noor, Fred T. FiedorekAbstract:Abstract Purpose To assess the efficacy and safety of adding Rosiglitazone to an established regimen of glyburide/Metformin in patients with type 2 diabetes who had not achieved adequate glycemic control (glycosylated hemoglobin [HbA 1C ] levels >7.0% and ≤10.0%). Methods Following an open-label, lead-in phase to optimize the dosing of glyburide/Metformin tablets, 365 patients randomly received additive therapy comprising Rosiglitazone (4 mg once daily) or placebo for 24 weeks. Based on glycemic response, Rosiglitazone dose was maintained or increased to 4 mg twice daily. Glyburide/Metformin dose was maintained or reduced by 2.5/500 mg for symptomatic hypoglycemia. The primary endpoint was the change in HbA 1C level from baseline to week 24. The proportions of patients achieving HbA 1C levels Results After 24 weeks, therapy with glyburide/Metformin Plus Rosiglitazone resulted in a greater reduction in HbA 1C levels (–1.0%, P P Conclusion In patients with inadequate glycemic control despite established glyburide/Metformin therapy, the addition of Rosiglitazone improves glycemic control, allowing more patients to achieve an HbA 1C level
Silva A Arslanian - One of the best experts on this subject based on the ideXlab platform.
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Post-intervention Effects of Varying Treatment Arms on Glycemic Failure and Beta-Cell Function in the TODAY Study
2020Co-Authors: Rachelle Gandica, Sonia Caprio, Kristen J Nadeau, Neil H White, Mitchell E. Geffner, Lorraine E. Levitt Katz, Barbara H. Braffett, Jeanie B. Tryggestad, Siripoom Mckay, Silva A ArslanianAbstract:<b>Objective</b>: The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial demonstrated that glycemic failure rates were significantly lower in youth randomized to Metformin Plus Rosiglitazone treatment compared to Metformin alone or Metformin Plus intensive lifestyle intervention. At end of study, Rosiglitazone was permanently discontinued, and routine diabetes care resumed. Herein, we report post-intervention glycemic failure rates in TODAY participants over an additional 36 months of follow-up for the three original treatment arms and describe insulin sensitivity and beta-cell function outcomes. <p><b>Research Design and Methods</b>: A total of 699 participants were randomized during TODAY, of whom 572 enrolled in the TODAY2 observational follow-up. Glycemic failure was defined as HbA1c ≥8% over a 6-month period or inability to wean from temporary insulin therapy within 3 months after acute metabolic decompensation during TODAY or a sustained HbA1c ≥8% over two consecutive visits during TODAY2. Oral glucose tolerance tests were conducted and insulin sensitivity, insulinogenic index, and oral disposition index (oDI) were calculated.</p> <p><b>Results</b>: During the 36 months of TODAY2, glycemic failure rates did not differ among participants by original treatment group assignment. Insulin sensitivity and beta-cell function deteriorated rapidly during the 36 months of TODAY2 routine diabetes care, but did not differ by treatment group assignment.</p> <p><b>Conclusions</b>: The added benefit of preventing glycemic failure by using Rosiglitazone as a second agent in youth-onset type 2 diabetes did not persist after its discontinuation. More work is needed to address this rapid progression to avoid long-term diabetes complications.</p>
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Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial
American journal of kidney diseases : the official journal of the National Kidney Foundation, 2017Co-Authors: Petter Bjornstad, Silva A Arslanian, Laure El Ghormli, Fida Bacha, Steven M Willi, Lori M. Laffel, Ingrid Libman, Edward Nehus, Siripoom V. Mckay, Kristen J NadeauAbstract:Background Diabetic kidney disease is a major cause of premature mortality in type 2 diabetes mellitus (T2DM). Worsening insulin sensitivity independent of glycemic control may contribute to the development of diabetic kidney disease. We investigated the longitudinal association of insulin sensitivity with hyperfiltration and increased albumin excretion in adolescents with T2DM. Study Design Observational prospective cohort study. Setting & Participants 532 TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) participants aged 12 to 17 years with T2DM duration less than 2 years at baseline. The TODAY Study was a multicenter randomized clinical trial that examined the efficacy of 3 treatment regimens (Metformin monotherapy, Metformin Plus Rosiglitazone, or Metformin Plus an intensive lifestyle intervention program) to achieve durable glycemic control. Predictors Natural log–transformed estimated insulin sensitivity (reciprocal of fasting insulin), hemoglobin A1c concentration, age, race-ethnicity, treatment group, body mass index, loss of glycemic control, and hypertension. Outcomes Hyperfiltration was defined as 99th percentile or higher of estimated glomerular filtration rate (≥140mL/min/1.73m2) when referenced to healthy adolescents (NHANES 1999-2002) and albumin-creatinine ratio ≥ 30μg/mg at 3 consecutive annual visits. Results Hyperfiltration was observed in 7.0% of participants at baseline and in 13.3% by 5 years, with a cumulative incidence of 5.0% over 5 years. The prevalence of increased albumin excretion was 6% at baseline and 18% by 5 years, with a cumulative incidence of 13.4%. There was an 8% increase in risk for hyperfiltration per 10% lower estimated insulin sensitivity in unadjusted and adjusted models (P=0.01). Increased albumin excretion was associated with hemoglobin A1c concentration, but not estimated insulin sensitivity. Limitations Longer follow-up is needed to capture the transition from hyperfiltration to rapid glomerular filtration rate decline in youth-onset T2DM. Conclusions Lower estimated insulin sensitivity was associated with risk for hyperfiltration over time, whereas increased albumin excretion was associated with hyperglycemia in youth-onset T2DM.
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adiponectin insulin sensitivity β cell function and racial ethnic disparity in treatment failure rates in today
Diabetes Care, 2017Co-Authors: Silva A Arslanian, Laure El Ghormli, Fida Bacha, Sonia Caprio, Robin Goland, Morey W Haymond, Lynne L Levitsky, Kristen J Nadeau, Neil H White, Steven M WilliAbstract:OBJECTIVE The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated that glycemic failure rates in the three treatments combined—Metformin Plus Rosiglitazone, Metformin alone, and Metformin Plus lifestyle—were higher in non-Hispanic blacks (NHB; 52.8%) versus non-Hispanic whites (NHW; 36.6%) and Hispanics (H; 45.0%). Moreover, Metformin alone was less effective in NHB versus NHW versus H youth. This study describes treatment-associated changes in adiponectin, insulin sensitivity, and β-cell function over time among the three racial/ethnic groups to understand potential mechanism(s) responsible for this racial/ethnic disparity. RESEARCH DESIGN AND METHODS TODAY participants underwent periodic oral glucose tolerance tests to determine insulin sensitivity, C-peptide index, and oral disposition index (oDI), with measurements of total and high-molecular-weight adiponectin (HMWA). RESULTS At baseline NHB had significantly lower HMWA than NHW and H and exhibited a significantly smaller increase (17.3% vs. 33.7% vs. 29.9%, respectively) during the first 6 months overall. Increases in HMWA were associated with reductions in glycemic failure in the three racial/ethnic groups combined (hazard ratio 0.61, P CONCLUSIONS HMWA is a reliable biomarker of treatment response in youth with type 2 diabetes. The diminutive treatment-associated increase in HMWA in NHB (∼50% lower) compared with NHW and H may explain the observed racial/ethnic disparity with higher therapeutic failure rates in NHB in TODAY.
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Adiponectin, Insulin Sensitivity, β-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY.
Diabetes care, 2016Co-Authors: Silva A Arslanian, Laure El Ghormli, Fida Bacha, Sonia Caprio, Robin Goland, Morey W Haymond, Lynne L Levitsky, Kristen J Nadeau, Neil H White, Steven M WilliAbstract:OBJECTIVE The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated that glycemic failure rates in the three treatments combined—Metformin Plus Rosiglitazone, Metformin alone, and Metformin Plus lifestyle—were higher in non-Hispanic blacks (NHB; 52.8%) versus non-Hispanic whites (NHW; 36.6%) and Hispanics (H; 45.0%). Moreover, Metformin alone was less effective in NHB versus NHW versus H youth. This study describes treatment-associated changes in adiponectin, insulin sensitivity, and β-cell function over time among the three racial/ethnic groups to understand potential mechanism(s) responsible for this racial/ethnic disparity. RESEARCH DESIGN AND METHODS TODAY participants underwent periodic oral glucose tolerance tests to determine insulin sensitivity, C-peptide index, and oral disposition index (oDI), with measurements of total and high-molecular-weight adiponectin (HMWA). RESULTS At baseline NHB had significantly lower HMWA than NHW and H and exhibited a significantly smaller increase (17.3% vs. 33.7% vs. 29.9%, respectively) during the first 6 months overall. Increases in HMWA were associated with reductions in glycemic failure in the three racial/ethnic groups combined (hazard ratio 0.61, P CONCLUSIONS HMWA is a reliable biomarker of treatment response in youth with type 2 diabetes. The diminutive treatment-associated increase in HMWA in NHB (∼50% lower) compared with NHW and H may explain the observed racial/ethnic disparity with higher therapeutic failure rates in NHB in TODAY.
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Effects of Metformin, Metformin Plus Rosiglitazone, and Metformin Plus Lifestyle on Insulin Sensitivity and [Beta]-Cell Function in TODAY: TODAY STUDY GROUP
Diabetes Care, 2013Co-Authors: Silva A Arslanian, Fida Bacha, Sonia Caprio, Robin Goland, Morey W Haymond, Lynne L Levitsky, Laura Pyle, Marisa Payan, Neil H WhiteAbstract:OBJECTIVE-The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial demonstrated that combination therapy with Metformin Plus Rosiglitazone provided superior durability of glycemic control compared with Metformin alone, with significantly lower treatment failure rates (38.6 vs. 51.7%), and Metformin Plus lifestyle was intermediate. Herein we describe the temporal changes in measures of s-cell function and insulin sensitivity over a 4-year period among the three treatments. RESEARCH DESIGN AND METHODS-TODAY participants (699) were tested periodically with an oral glucose tolerance test to determine insulin sensitivity (1/fasting insulin [1/I^sub F^]), insulinogenic index (?I^sub 30^/?G^sub 30^) or C-peptide index (?C^sub 30^/?G^sub 30^), and s-cell function relative to insulin sensitivity (oral disposition index [oDI]). RESULTS-During the first 6 months, Metformin Plus Rosiglitazone exhibited a significantly greater improvement in insulin sensitivity and oDI versus Metformin alone and versus Metformin Plus lifestyle; these improvements were sustained over 48 months of TODAY. Irrespective of treatment, those who failed to maintain glycemic control had significantly lower s-cell function (~50%), higher fasting glucose concentration, and higher HbA^sub 1c^ at randomization compared with those who did not fail. CONCLUSIONS-The beneficial change in insulin sensitivity and the resultant lower burden on s-cell function achieved in the first 6 months with Metformin Plus Rosiglitazone appear to be responsible for its superior glycemic durability over Metformin alone and Metformin Plus lifestyle. However, initial s-cell reserve and HbA^sub 1c^ at randomization are independent predictors of glycemic durability. Therefore, efforts to preserve s-cell function before significant loss occurs and to reduce HbA^sub 1c^ may be beneficial in the treatment of youth with type 2 diabetes.
George Dailey - One of the best experts on this subject based on the ideXlab platform.
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glycemic control with glyburide Metformin tablets in combination with Rosiglitazone in patients with type 2 diabetes a randomized double blind trial
The American Journal of Medicine, 2004Co-Authors: George Dailey, Simon Bruce, Jongsoon Park, Mustafa A Noor, Fred T. FiedorekAbstract:Abstract Purpose To assess the efficacy and safety of adding Rosiglitazone to an established regimen of glyburide/Metformin in patients with type 2 diabetes who had not achieved adequate glycemic control (glycosylated hemoglobin [HbA 1C ] levels >7.0% and ≤10.0%). Methods Following an open-label, lead-in phase to optimize the dosing of glyburide/Metformin tablets, 365 patients randomly received additive therapy comprising Rosiglitazone (4 mg once daily) or placebo for 24 weeks. Based on glycemic response, Rosiglitazone dose was maintained or increased to 4 mg twice daily. Glyburide/Metformin dose was maintained or reduced by 2.5/500 mg for symptomatic hypoglycemia. The primary endpoint was the change in HbA 1C level from baseline to week 24. The proportions of patients achieving HbA 1C levels Results After 24 weeks, therapy with glyburide/Metformin Plus Rosiglitazone resulted in a greater reduction in HbA 1C levels (–1.0%, P P Conclusion In patients with inadequate glycemic control despite established glyburide/Metformin therapy, the addition of Rosiglitazone improves glycemic control, allowing more patients to achieve an HbA 1C level
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Glycemic control with Glyburide/Metformin tablets in combination with Rosiglitazone in patients with type 2 diabetes: a randomized, double-blind trial
The American journal of medicine, 2004Co-Authors: George Dailey, Simon Bruce, Jongsoon Park, Mustafa A Noor, Fred T. FiedorekAbstract:Abstract Purpose To assess the efficacy and safety of adding Rosiglitazone to an established regimen of glyburide/Metformin in patients with type 2 diabetes who had not achieved adequate glycemic control (glycosylated hemoglobin [HbA 1C ] levels >7.0% and ≤10.0%). Methods Following an open-label, lead-in phase to optimize the dosing of glyburide/Metformin tablets, 365 patients randomly received additive therapy comprising Rosiglitazone (4 mg once daily) or placebo for 24 weeks. Based on glycemic response, Rosiglitazone dose was maintained or increased to 4 mg twice daily. Glyburide/Metformin dose was maintained or reduced by 2.5/500 mg for symptomatic hypoglycemia. The primary endpoint was the change in HbA 1C level from baseline to week 24. The proportions of patients achieving HbA 1C levels Results After 24 weeks, therapy with glyburide/Metformin Plus Rosiglitazone resulted in a greater reduction in HbA 1C levels (–1.0%, P P Conclusion In patients with inadequate glycemic control despite established glyburide/Metformin therapy, the addition of Rosiglitazone improves glycemic control, allowing more patients to achieve an HbA 1C level
Michael Aviram - One of the best experts on this subject based on the ideXlab platform.
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Research Article Paraoxonase Activity and Expression Is Modulated by Therapeutics in Experimental Rat Nonalcoholic Fatty Liver Disease
2013Co-Authors: M. Grozovski, I. Bersudsky, Rachel Karry, Michael AviramAbstract:Copyright © 2012 O. Hussein et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. The objective of the present study is to investigate the effect of Rosiglitazone, Metformin, ezetimibe, and valsartan (alone or in combinations) on paraoxonase (PON) activity and PON-mRNA expression in nonalcoholic fatty liver disease (NAFLD). Methods. 54 Male Sprague–Dawley rats were divided to 9 groups: chow diet group (15 weeks); methionine-choline-deficient diet (MCDD) group (15 weeks); MCDD-treated groups for the last 6 weeks with either Metformin (M), Rosiglitazone (R), Metformin Plus Rosiglitazone (M+R), ezetimibe (E), valsartan (V), or a combination of R+M+V or of R+M+V+E for a total period of 15 weeks. Results. PON activities in serum and liver were decreased in MCDD rats. PON activity in serum increased significantly in all treatment groups. PON activity in liver was also increased significantly, except only in groups R, E, V, R+M+V, and R+M+V+E. Liver PON3 mRNA expression increased significantly in groups R+M, E, V, R+M+V, and R+M+V+E whereas liver PON2 mRNA expression increased significantly in MCDD, R+M, E, V, R+M+V, and R+M+V+E. Conclusions. PON activities in serum an
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Paraoxonase Activity and Expression Is Modulated by Therapeutics in Experimental Rat Nonalcoholic Fatty Liver Disease
International journal of hepatology, 2012Co-Authors: O. Hussein, Jamal Zidan, K. Abu Jabal, Imad Shams, S. Szvalb, M. Grozovski, I. Bersudsky, Rachel Karry, Michael AviramAbstract:Objective. The objective of the present study is to investigate the effect of Rosiglitazone, Metformin, ezetimibe, and valsartan (alone or in combinations) on paraoxonase (PON) activity and PON-mRNA expression in nonalcoholic fatty liver disease (NAFLD). Methods. 54 Male Sprague–Dawley rats were divided to 9 groups: chow diet group (15 weeks); methionine-choline-deficient diet (MCDD) group (15 weeks); MCDD-treated groups for the last 6 weeks with either Metformin (M), Rosiglitazone (R), Metformin Plus Rosiglitazone (M
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Paraoxonase Activity and Expression Is Modulated by Therapeutics in Experimental Rat Nonalcoholic Fatty Liver Disease
Hindawi Limited, 2012Co-Authors: O. Hussein, Jamal Zidan, Imad Shams, S. Szvalb, M. Grozovski, I. Bersudsky, Rachel Karry, Abu K. Jabal, Michael AviramAbstract:Objective. The objective of the present study is to investigate the effect of Rosiglitazone, Metformin, ezetimibe, and valsartan (alone or in combinations) on paraoxonase (PON) activity and PON-mRNA expression in nonalcoholic fatty liver disease (NAFLD). Methods. 54 Male Sprague–Dawley rats were divided to 9 groups: chow diet group (15 weeks); methionine-choline-deficient diet (MCDD) group (15 weeks); MCDD-treated groups for the last 6 weeks with either Metformin (M), Rosiglitazone (R), Metformin Plus Rosiglitazone (M+R), ezetimibe (E), valsartan (V), or a combination of R+M+V or of R+M+V+E for a total period of 15 weeks. Results. PON activities in serum and liver were decreased in MCDD rats. PON activity in serum increased significantly in all treatment groups. PON activity in liver was also increased significantly, except only in groups R, E, V, R+M+V, and R+M+V+E. Liver PON3 mRNA expression increased significantly in groups R+M, E, V, R+M+V, and R+M+V+E whereas liver PON2 mRNA expression increased significantly in MCDD, R+M, E, V, R+M+V, and R+M+V+E. Conclusions. PON activities in serum and liver were decreased in NAFLD. Treatment with insulin sensitizers, ezetimibe, and valsartan increased PON activity and reduced oxidative stress both in serum and liver
Kathryn Hirst - One of the best experts on this subject based on the ideXlab platform.
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Weight change in the management of youth-onset type 2 diabetes: the TODAY clinical trial experience
Pediatric obesity, 2016Co-Authors: Marsha D. Marcus, Philip Zeitler, Kathryn Hirst, Barbara Linder, Denise E. Wilfley, L. El Ghormli, Carolyn E. Ievers-landis, D. J. Van Buren, Natalie Walders-abramsonAbstract:Summary Background The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial documented that Metformin Plus Rosiglitazone, but not Metformin Plus lifestyle intervention, provided superior durability of glycemic control relative to Metformin monotherapy. Objectives We examined weight changes among TODAY participants that completed at least 6 months of treatment, evaluated predictors of lifestyle outcome, and examined whether weight changes were related to cardiometabolic outcomes across treatment arms. Methods The 595 youth with type 2 diabetes, (85.1% of randomized participants aged 11–17 years) completed assessments of weight-related and cardiometabolic measures at months 0, 6, 12 and 24. Repeated measures models were used to investigate associations over time. Results Lifestyle intervention did not enhance outcome relative to Metformin alone and no predictors of response to lifestyle treatment were identified. However, changes in percent overweight across treatment arms were associated with changes in multiple cardiometabolic risk factors, and decreases of ≥ 7% in overweight were associated with significant benefits over 24 months. Conclusions Although adjunctive intensive lifestyle intervention did not improve weight-related outcomes, weight changes in the full TODAY sample were associated with small, but significant improvements in cardiometabolic status, highlighting the importance of optimizing weight management in youth with T2DM.
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Lipid and inflammatory cardiovascular risk worsens over 3 years in youth with type 2 diabetes
Diabetes care, 2013Co-Authors: Ruth S. Weinstock, Sonia Caprio, Kristen J Nadeau, Kathryn Hirst, Kenneth C. Copeland, Samuel S. Gidding, Lorraine E. Levitt Katz, Santica M. Marcovina, David M. NathanAbstract:Type 2 diabetes increases cardiovascular risk. We examined lipid profiles and inflammatory markers in 699 youth with recent-onset type 2 diabetes in the TODAY clinical trial and compared changes across treatment groups: Metformin alone (M), Metformin Plus Rosiglitazone (M+R), and Metformin Plus intensive lifestyle program (M+L). Multiethnic youth with type 2 diabetes received M, M+R, or M+L. Statin drugs were begun for LDL cholesterol (LDL) ≥ 130 mg/dL or triglycerides ≥ 300 mg/dL. Lipids, apolipoprotein B (apoB), LDL particle size, high-sensitivity c-reactive protein (hsCRP), homocysteine, plasminogen activator inhibitor-1 (PAI-1), and HbA1c were measured over 36 months or until loss of glycemic control. LDL, apoB, triglycerides, and non-HDL cholesterol (HDL) rose over 12 months and then stabilized over the next 24 months. Participants with LDL ≥ 130 mg/dL or using LDL-lowering therapy increased from 4.5 to 10.7% over 36 months, while 55.9% remained at LDL goal (<100 mg/dL) over that time. Treatment group did not impact LDL, apoB, or non-HDL. Small dense LDL (particle size, ≤ 0.263 relative flotation rate) was most common in M. Triglycerides were lower in M+L than M, and M+L attenuated the negative effect of hyperglycemia on triglycerides and HDL in females. hsCRP, PAI-1, and homocysteine increased over time. However, hsCRP was lower in M+R compared with M or M+L. Dyslipidemia and chronic inflammation were common in youth with type 2 diabetes and worsened over time. Diabetes treatment, despite some treatment group differences in lipid and inflammatory marker change over time, is generally inadequate to control this worsening risk.
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A clinical trial to maintain glycemic control in youth with type 2 diabetes.
The New England journal of medicine, 2012Co-Authors: Philip Zeitler, Silva A Arslanian, Laura Pyle, Kathryn Hirst, Barbara Linder, Kenneth C. Copeland, Leona Cuttler, David M. Nathan, Sherida E. Tollefsen, Denise E. WilfleyAbstract:Background Despite the increasing prevalence of type 2 diabetes in youth, there are few data to guide treatment. We compared the efficacy of three treatment regimens to achieve durable glycemic control in children and adolescents with recent-onset type 2 diabetes. Methods Eligible patients 10 to 17 years of age were treated with Metformin (at a dose of 1000 mg twice daily) to attain a glycated hemoglobin level of less than 8% and were randomly assigned to continued treatment with Metformin alone or to Metformin combined with Rosiglitazone (4 mg twice a day) or a lifestyle-intervention program focusing on weight loss through eating and activity behaviors. The primary outcome was loss of glycemic control, defined as a glycated hemoglobin level of at least 8% for 6 months or sustained metabolic decompensation requiring insulin. Results Of the 699 randomly assigned participants (mean duration of diagnosed type 2 diabetes, 7.8 months), 319 (45.6%) reached the primary outcome over an average follow-up of 3.86 years. Rates of failure were 51.7% (120 of 232 participants), 38.6% (90 of 233), and 46.6% (109 of 234) for Metformin alone, Metformin Plus Rosiglitazone, and Metformin Plus lifestyle intervention, respectively. Metformin Plus Rosiglitazone was superior to Metformin alone (P=0.006); Metformin Plus lifestyle intervention was intermediate but not significantly different from Metformin alone or Metformin Plus Rosiglitazone. Prespecified analyses according to sex and race or ethnic group showed differences in sustained effectiveness, with Metformin alone least effective in non-Hispanic black participants and Metformin Plus Rosiglitazone most effective in girls. Serious adverse events were reported in 19.2% of participants. Conclusions Monotherapy with Metformin was associated with durable glycemic control in approximately half of children and adolescents with type 2 diabetes. The addition of Rosiglitazone, but not an intensive lifestyle intervention, was superior to Metformin alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; TODAY ClinicalTrials.gov number, NCT00081328.).
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Characteristics of Adolescents and Youth With Recent-Onset Type 2 Diabetes: The TODAY Cohort at Baseline
The Journal of clinical endocrinology and metabolism, 2010Co-Authors: Kenneth C. Copeland, Philip Zeitler, Kathryn Hirst, Barbara Linder, Mitchell E. Geffner, Janine A. Higgins, Santica M. Marcovina, Cindy Guandalini, Francine R. Kaufman, Paul McguiganAbstract:Context: The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort represents the largest and best-characterized national sample of American youth with recent-onset type 2 diabetes. Objective: The objective of the study was to describe the baseline characteristics of participants in the TODAY randomized clinical trial. Design: Participants were recruited over 4 yr at 15 clinical centers in the United States (n = 704) and enrolled, randomized, treated, and followed up 2–6 yr. Setting: The study was conducted at pediatric diabetes care clinics and practices. Participants: Eligible participants were aged 10–17 yr inclusive, diagnosed with type 2 diabetes for less than 2 yr and had a body mass index at the 85th percentile or greater. Interventions: After baseline data collection, participants were randomized to one of the folllowing groups: 1) Metformin alone, 2) Metformin Plus Rosiglitazone, or 3) Metformin Plus a lifestyle program of weight management. Main Outcome Measures: Baseline data presented include demographics, clinical/medical history, biochemical measurements, and clinical and biochemical abnormalities. Results: At baseline the cohort included the following: 64.9% were female; mean age was 14.0 yr; mean diabetes duration was 7.8 months; mean body mass index Z-score was 2.15; 89.4% had a family history of diabetes; 41.1% were Hispanic, 31.5% were non-Hispanic black; 38.8% were living with both biological parents; 41.5% had a household annual income of less than $25,000; 26.3% had a highest education level of parent/guardian less than a high school degree; 26.3% had a blood pressure at the 90th percentile or greater; 13.6% had a blood pressure at the 95th percentile or greater; 13.0% had microalbuminuria; 79.8% had a low high-density lipoprotein level; and 10.2% had high triglycerides. Conclusions: The TODAY cohort is predominantly from racial/ethnic minority groups, with low socioeconomic status and a family history of diabetes. Clinical and biochemical abnormalities and comorbidities are prevalent within 2 yr of diagnosis. These findings contribute greatly to our understanding of American youth with type 2 diabetes.