Longitudinal Changes in Cardiac Structure and Function From Adolescence to Young Adulthood in Participants With Type 2 Diabetes Mellitus: The TODAY Follow-Up Study

Abstract

Background: Heart failure is a prominent complication of type 2 diabetes mellitus (T2D). The goal of this study was to provide longitudinal data on cardiac structure and function (and cross-sectional comparison to normal-weight and obese controls without T2D) in individuals followed from adolescence with youth-onset T2D.

Methods: In the TODAY study (Treatment Options for Type 2 Diabetes Mellitus in Adolescents and Youth), echocardiograms were performed at study years 4 to 5 and 9 to 10. Echocardiograms were also obtained at years 8 to 9 in a control population of age, race/ethnicity, and sex-matched normal-weight and obese individuals without diabetes mellitus. Study outcomes were measures of left ventricular structure and function. The cohort included 411 participants with T2D, 194 obese controls, and 51 normal-weight controls.

Results: At follow-up, mean participant age was 23 years, 65% women, 20% non-Hispanic white, 35% non-Hispanic black, and 39% Hispanic. Ejection fraction was <52% in 11.7% of male participants with T2D. Diastolic function declined during follow-up in participants with T2D (mitral valve lateral E/Em increased 0.72±0.12 in women and 0.50±0.17 in men; P<0.01) and was significantly higher than obese controls (women, 6.65±1.89 versus 5.66±1.37; men, 6.15±1.90 versus 5.26±1.31; P<0.0001). Predictors of adverse changes included hypertension, obesity, female sex, Hispanic and non-Hispanic black ethnicity, worse glycemic control, and elevated heart rate. Cardiac structural abnormalities, left ventricular hypertrophy, or concentric geometry, were highest in those with T2D (15.8% versus 5.7% obese versus 0% normal weight).

Conclusions: Adverse changes in cardiac structure and function changed significantly from adolescence to early adulthood in participants with youth-onset T2D. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00081328.

Keywords: cardiovascular diseases; epidemiology; heart rate; risk factors.

Figure 1.. TODAY (Treatment Options for Type 2 Diabetes Mellitus in Adolescents and Youth) study flow.

The analyses were performed on the cohort of control participants and on 411 participants with echocardiographic measurements both at the end of the TODAY trial and 5 y later during observational follow-up. Excluded were 14 participants with monogenic diabetes mellitus and 4 participants without risk factor measurements within 3 mo of the echocardiogram. A, Timeline. B, Consolidated Standards of Reporting Trials diagram. *n=113 participants only had a TODAY end of study visit; n=21 participants only had a TODAY follow-up study visit.

Figure 2.. Distribution of left ventricular (LV) geometry at 5-y follow-up in participants and normal-weight and obese controls.

Each cohort was stratified into 4 groups according to LV mass (cutoff at 51 g/m^2.7) and relative wall thickness (cutoff at 0.42): normal, LV hypertrophy (increased LV mass only), concentric geometry (increased relative wall thickness only), and LV hypertrophy with concentric geometry. Data are percentage. LVM indicates left ventricular mass; and T2D, type 2 diabetes mellitus.