Presentations:

CT-SY23: Introduction
Saturday, Jun 09, 2012, 4:00 PM - 4:05 PM
Griffin P. Rodgers, MD
Bethesda, Maryland

In 1990 the type 2 diabetes pediatric population was fewer than 5% of diabetes patients; by 1995 this had risen to 15-25% depending on the ethnic population of the clinic.  The SEARCH NIH/CDC database for diabetes estimates that the incidence of type 2 diabetes in youth is 3,600 cases/year.  As regards metabolic control, the percent of patients with A1C >9.5% is 40% in type 1 and 55% in type 2 adolescents; it is greater in minorities.  The HEALTHY Trial demonstrated no benefit in this population.  Infants of diabetic mothers, both preexisting and gestational, have increased incidence of obesity and diabetes.

CT-SY23: Outcomes, Interpretation, and Implications of the TODAY Trial
Saturday, Jun 09, 2012, 4:05 PM - 4:45 PM
Philip S. Zeitler, MD, PhD
Aurora, Colorado

In the HAPO and LIFE studies at puberty children with impaired glucose tolerance (IGT), 1/3 converted to normal glucose tolerance, 1/3 had type 2 diabetes and 1/3 had IGT.  The hypothesis of the TODAY trial is that the combination of metformin and rosiglitazone would result in better outcomes that metformin alone or plus lifestyle.  There was a 2-6 week run in with metformin to gage compliance with metformin and self-monitoring with a requirement of an A1C <8.0% at entry.  The primary outcome was an A1C >8.0% or last TODAY visit or an A1C >10.0% or unable to stop insulin given for an acute event.  The population was 20% non-Hispanic white (NHW), 41% African American (AA), 31% Hispanic (H) and 6% American Indian (AI).  Family income was low; 41% were below $25,000/year. Only 17% of parents had any college education; they were of low SDS with frequent psychosocial problems including domestic violence.  The average BMI was 35 and <50% were living with both biologic parents.  At 72 months 45.6% had achieved the primary outcome failure end point; 38.6% in the metformin plus rosiglitazone group; 49.6% in the metformin plus lifestyle group and 51.7% in the metformin alone group.  The average time to failure was 10-12 months.  The mean A1C in the non-failure subjects was 6%.  There was no effect of treatment prior to entering the trial.  The BMI increased in the metformin plus rosiglitazone group; the best weight reduction was seen in the metformin plus lifestyle group.  Visit adherence was 71% overall; 80% in the first year.

Implications/interpretation: Metformin is inadequate treatment and a second agent needs to be added early.  The FDA gave special permission to use rosiglitazone in this study, but the safety of this agent has recently been questioned.  The best second agent is unknown at present.  Lifestyle interventions are of unknown benefit.  Perhaps the only good news from the study is that ½ of the subjects did maintain long-term control.  We need to find out what are these patients’ characteristics.  Finally there are marked gender and racial difference in outcomes.

CT-SY23: Insulin Sensitivity and Secretion Over Time in Youth in the TODAY Trial
Saturday, Jun 09, 2012, 4:45 PM - 5:05 PM
Sonia Caprio, MD
New Haven, Connecticut

The hypothesis for these studies was that metformin plus rosiglitazone would decrease the rate of decline in beta-cell function more than the metformin or metformin plus lifestyle subjects.  There were no baseline differences.  At 6 months the combined metformin and rosiglitazone group had a 10-20% improvement in sensitivity. There was a dramatic decrease in the two other groups.

CT-SY23: Determinants of Durable Glycemic Control in the TODAY Trial
Saturday, Jun 09, 2012, 5:05 PM - 5:25 PM
Kenneth C. Copeland, MD
Oklahoma City, Oklahoma

Two groups were combined failures and non-failures at 48 months. During the study A1C values prior to failure were not predictive; that is, failure was sudden.  There was an increased incidence of depression in the failure group.  There were more borderline cutoff A1Cs in the failure group. The mean change in BMI was small between the two groups; 35+ in the failure group versus 34- in the non-failure group.  Both increased in the study.  Baseline A1C was 5.6% in the non-failure group and 6.4% in the failure group.  On multivariate analysis only baseline A1C and oral glucose tolerance were significant predictors.  Baseline insulin sensitivity was not different.

CT-SY23: Burden of Comorbidities in Youth in the TODAY Trial
Saturday, Jun 09, 2012, 5:25 PM - 5:45 PM
Neil H. White, MD, CDE
St. Louis, Missouri

The main concern was that in these subjects averaging 18 years of age, is that there were changes in their echocardiograms of increased atrial diameter md left ventricle mass.  This is suggestive of early cardiovascular effects even prior to the development of significant traditional cardiovascular risk factors.

COMMENTS: We owe a great deal to these investigators and their volunteer subjects.  Type 2 diabetes is a mostly unstudied epidemic and it effects a vulnerable population as this study so clearly demonstrates.  It appears that early failure is the rule with most occurring in the first year.  While using rosiglitazone was approved for the study, its profile is of concern for such a your population.  The truth is we do not know what second drug to add even though we learned from this study that we need to do more than metformin and lifestyle is we are going to benefit these patients.  I would love your comments on treating this population.