Presentation and effectiveness of early treatment of type 2 diabetes in youth: lessons from the TODAY study

Abstract

Objective: The objectives were to (i) describe the characteristics of a large ethnically/racially and geographically diverse population of adolescents with recent-onset type 2 diabetes (T2D), and (ii) assess the effects of short-term diabetes education and treatment with metformin on clinical and biochemical parameters in this cohort.

Research design and methods: Descriptive characteristics were determined for subjects screened for Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) who met criteria for diagnosis of T2D (n = 1092). Changes in clinical and biochemical parameters were determined for those who completed at least 8 wk of the run-in phase of the trial, which included standardized diabetes education and treatment with metformin. Further analysis determined whether these changes differed according to the treatment at screening.

Main outcome measures: Demographic, biochemical measurements, and anthropometrics at screening and changes over 8 wk of run-in were the outcome measures.

Results: Subjects screened for TODAY had a median age of 14 yr and median hemoglobin A1c (HbA1c) of 6.9% (52 mM/M), 2/3 were female, and ethnic/racial minorities were overrepresented. Dyslipidemia and hypertension were common comorbidities. During run-in, HbA1c, body mass index, low-density lipoprotein cholesterol, triglycerides, and blood pressure significantly improved. Nearly all participants on insulin therapy at screening were able to attain target HbA1c following insulin discontinuation.

Conclusions: Treatment with metformin and diabetes education provided short-term improvements in glycemic control and cardiometabolic risk factors in a large adolescent T2D cohort. Nearly all insulin-treated youth could be successfully weaned off insulin with continued improvement in glycemic control.

Keywords: diabetes education; insulin therapy; metformin.

Figure 1

Baseline weight status, HbA1c, and c-peptide by diabetes treatment at screening. Median baseline BMI z-score, HbA1c and c-peptide for all screened subjects with type 2 diabetes and by treatment at screening. Bottoms and tops of the boxes represent the 25^th and 75^th percentiles, respectively.

Figure 2

Median change in BMI z-score, HbA1c, and c-peptide from screening to end of run-in by diabetes treatment at screening. 2a) Median change in BMI z-score, HbA1c, and c-peptide for all subjects who completed at least 8 weeks of run-in. Changes in these parameters based on treatment at screening are also shown. P-values represent overall significance. *P<0.05, ^P<0.0001 2b) Median HbA1c at screening and after 8 weeks of run-in for those not on insulin at screening vs. those on insulin at screening, excluding subjects who were still on insulin at the end of run-in. #P=0.02,^P<0.0001

Figure 3

Change in proportion of subjects with cardiometabolic risk factors from screening to end of run-in. Proportion of those who completed at least 8 weeks of run-in with poor glycemic control or other metabolic abnormalities. *P<0.05, #P<0.01,^P<0.0001