Effect of surgical versus medical therapy on estimated cardiovascular event risk among adolescents with type 2 diabetes and severe obesity

Abstract

Background: Cardiovascular disease (CVD) remains the leading cause of mortality in type 2 diabetes (T2D). Better interventions are needed to mitigate the high lifetime risk for CVD in youth T2D.

Objective: To compare 30-year risk for CVD events in 2 cohorts of adolescents with T2D and severe obesity undergoing medical or surgical treatment of T2D.

Setting: Longitudinal multicenter studies at University hospitals.

Methods: A secondary analysis of data collected from the participants with T2D enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS, n = 30) and participants of similar age and racial distribution from the Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY, n = 63) studies was performed. Teen-LABS participants underwent metabolic bariatric surgery (MBS). TODAY participants were randomized to metformin alone or in combination with rosiglitazone or intensive lifestyle intervention, with insulin therapy given for glycemic progression. A 30-year CVD event score developed by the Framingham Heart Study was the primary outcome, assessed at baseline (preoperatively for Teen-LABS), 1 year, and 5 years of follow-up.

Results: Participants with T2D from Teen-LABS (n = 30; mean ± SD age = 16.9 ± 1.3 yr; 70% female; 60% white; body mass index (BMI) = 54.4 ± 9.5 kg/m²) and TODAY (n = 63; 15.3 ± 1.3 yr; 56% female; 71% white; BMI 40.5 ± 4.9 kg/m²) were compared. The likelihood of CVD events was higher in Teen-LABS versus TODAY at baseline (17.66 [1.59] versus 12.11 [.79]%, adjusted P = .002). One year after MBS, event risk was significantly lower in Teen-LABS versus TODAY (6.79 [1.33] versus 13.64 [0.96]%, adjusted P < .0001), and sustained at 5 years follow-up (adjusted P < .0001).

Conclusion: Despite higher pretreatment risk for CVD events, treatment with MBS resulted in a reduction in estimated CVD event risks, whereas medical therapy associated with an increase in risk among adolescents with T2D and severe obesity.

Keywords: Cardiovascular disease; Medical therapy; Metabolic bariatric surgery; Prediction; Severe obesity; Type 2 diabetes.

Fig. 1.

Individual continuous determinants of full and hard cardiovascular disease (CVD) risk scores in Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY) and Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) over 5 years based on observed data line charts for systolic blood pressure (SBP) (mmHg, Fig. 1a), total cholesterol (mg/dL, Fig. 1b), high-density lipoprotein cholesterol (HDL-C) (mg/dL, Fig. 1c) and body mass index (BMI) (kg/m², Fig. 1d). All figures are based on observed data. Error bars indicate 95% confidence intervals of the means. Means and error bars were jittered to avoid overlapping.

Fig. 2.

Individual categorical determinants of full and hard CVD risk scores in TODAY and Teen-LABS over 5 years based on observed data line charts for antihypertensive therapy (antiHTN) medicine (%, Fig. 1a), smoking status (%, Fig. 1b), diabetes status (%, Fig. 1c). All figures are based on observed data. Smoking status at year 1, 3, 4, and 5 were not collected. Diabetes remission was not collected for TODAY cohort (see supplemental Fig. 3 for glycated hemoglobin [HbA1C] trends). Error bars indicate 95% confidence intervals of the mean percentages. Means and error bars were jittered to avoid overlapping.

Fig. 3.

Risk scores in TODAY and Teen-LABS over 5 years. Line charts for full CVD risk (with BMI, Fig. 1a), full CVD risk (without BMI, Fig. 1b), hard CVD risk (with BMI, Fig. 1c) and hard CVD risk (without BMI, Fig. 1d). Risk scores were calculated from model using imputed data. Risk score means and standard errors used in the figure were pooled across imputed data analyses using Rubin’s rule. Error bars indicate 95% confidence intervals of the pooled means. Means and error bars were jittered to avoid overlapping.

Fig. 4.

Group differences in risk scores between TODAY and Teen-LABS participants. Group difference indicates the parameter estimate of group effect (Teen-LABS as reference) in mixed model. Mixed model for baseline risks adjusted for baseline estimated glomerular filtration (eGFR), urine albumin-to-creatinine ratio (UACR), and insulin sensitivity. Mixed models for first and fifth year risks adjusted for baseline CVD risk score, eGFR, UACR, and insulin sensitivity.