OBJECTIVEType 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).RESEARCH DESIGN AND METHODSMultiethnic 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.RESULTSLDL, 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.CONCLUSIONSDyslipidemia 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.

OBJECTIVETo identify factors that predict medication adherence and to examine relationships among adherence, glycemic control, and indices of insulin action in TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth).RESEARCH DESIGN AND METHODSA total of 699 youth 10–17 years old with recent-onset type 2 diabetes and ≥80% adherence to metformin therapy for ≥8 weeks during a run-in period were randomized to receive one of three treatments. Participants took two study pills twice daily. Adherence was calculated by pill count from blister packs returned at visits. High adherence was defined as taking ≥80% of medication; low adherence was defined as taking <80% of medication. Depressive symptoms, insulin sensitivity (1/fasting insulin), insulinogenic index, and oral disposition index (oDI) were measured. Survival analysis examined the relationship between medication adherence and loss of glycemic control. Generalized linear mixed models analyzed trends in adherence over time.RESULTSIn this low socioeconomic cohort, high and low adherence did not differ by sex, age, family income, parental education, or treatment group. Adherence declined over time (72% high adherence at 2 months, 56% adherence at 48 months, P < 0.0001). A greater percentage of participants with low adherence had clinically significant depressive symptoms at baseline (18% vs. 12%, P = 0.0415). No adherence threshold predicted the loss of glycemic control. Longitudinally, participants with high adherence had significantly greater insulin sensitivity and oDI than those with low adherence.CONCLUSIONSIn the cohort, the presence of baseline clinically significant depressive symptoms was associated with subsequent lower adherence. Medication adherence was positively associated with insulin sensitivity and oDI, but, because of disease progression, adherence did not predict long-term treatment success.

OBJECTIVETo determine whether clinically accessible parameters early in the course of youth-onset type 2 diabetes predict likelihood of durable control on oral therapy.RESEARCH DESIGN AND METHODSTODAY was a randomized clinical trial of adolescents with type 2 diabetes. Two groups, including participants from all three treatments, were defined for analysis: 1) those who remained in glycemic control for at least 48 months of follow-up and 2) those who lost glycemic control before 48 months. Outcome group was analyzed in univariate and multivariate models as a function of baseline characteristics (age, sex, race/ethnicity, socioeconomic status, BMI, waist circumference, Tanner stage, disease duration, depressive symptoms) and biochemical measures (HbA1c, C-peptide, lean and fat body mass, insulin inverse, insulinogenic index). Receiver operating characteristic curves were used to analyze HbA1c cut points.RESULTSIn multivariate models including factors significant in univariate analysis, only HbA1c and insulinogenic index at randomization remained significant (P < 0.0001 and P = 0.0002, respectively). An HbA1c cutoff of 6.3% (45 mmol/mol) (positive likelihood ratio [PLR] 3.7) was identified that optimally distinguished the groups; sex-specific cutoffs were 6.3% (45 mmol/mol) for females (PLR 4.4) and 5.6% (38 mmol/mol) for males (PLR 2.1).CONCLUSIONSIdentifying youth with type 2 diabetes at risk for rapid loss of glycemic control would allow more targeted therapy. HbA1c is a clinically accessible measure to identify high risk for loss of glycemic control on oral therapy. Adolescents with type 2 diabetes unable to attain a non–diabetes range HbA1c on metformin are at increased risk for rapid loss of glycemic control.