Effect of Surgical Versus Medical Therapy on Diabetic Kidney Disease Over 5 Years in Severely Obese Adolescents With Type 2 Diabetes

Abstract

Objective: To compare diabetic kidney disease (DKD) rates over 5 years of follow-up in two cohorts of severely obese adolescents with type 2 diabetes (T2D) undergoing medical or surgical treatment for T2D.

Research design and methods: A secondary analysis was performed of data collected from obese participants of similar age and racial distribution enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) and the Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY) studies. 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. Glycemic control, BMI, estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), and prevalence of hyperfiltration (eGFR ≥135 mL/min/1.73 m²) and elevated UAE (≥30 mg/g) were assessed annually.

Results: Participants with T2D from Teen-LABS (n = 30, mean ± SD age, 16.9 ± 1.3 years; 70% female; 60% white; BMI 54.4 ± 9.5 kg/m²) and TODAY (n = 63, age 15.3 ± 1.3 years; 56% female; 71% white; BMI 40.5 ± 4.9 kg/m²) were compared. During 5 years of follow-up, hyperfiltration decreased from 21% to 18% in Teen-LABS and increased from 7% to 48% in TODAY. Elevated UAE decreased from 27% to 5% in Teen-LABS and increased from 21% to 43% in TODAY. Adjusting for baseline age, sex, BMI, and HbA_1c, TODAY participants had a greater odds of hyperfiltration (odds ratio 15.7 [95% CI 2.6, 94.3]) and elevated UAE (27.3 [4.9, 149.9]) at 5 years of follow-up.

Conclusions: Compared with MBS, medical treatment of obese youth with T2D was associated with a higher odds of DKD over 5 years.

Trial registration: ClinicalTrials.gov NCT00081328 NCT00474318.

Figure 1

BMI, HbA_1c, insulin sensitivity, and triglycerides over 5 years in TODAY and Teen-LABS. Line charts for BMI (P < 0.0001) (A), HbA_1c (P < 0.0001) (B), insulin sensitivity (P = 0.0012) (C), and triglycerides (P < 0.0001) (D). Error bars indicate ±SEM. Means and error bars were jittered to avoid overlapping. P values are provided for the test of trajectory difference between groups over the study period (i.e., test for the existence of group ∗ time interaction terms).

Figure 2

eGFR, UACR, SBP, and DBP over 5 years in TODAY and Teen-LABS. Line charts for eGFR-FAS (P = 0.0243) (A), UACR (medians and IQRs) (B), SBP (P < 0.0001) (C), and DBP (P = 0.0245) (D). Error bars indicate ±SEM except for UACR. Means and error bars were jittered to avoid overlapping. P values are provided for the test of trajectory difference between groups over the study period (i.e., test for the existence of group ∗ time interaction terms). All models were adjusted for baseline age, sex, BMI, HbA_1c, insulin sensitivity, and antihypertensive medication use.

Figure 3

Hyperfiltration, elevated UAE, and hypertension over 5 years in TODAY and Teen-LABS. Line charts for hyperfiltration (P = 0.0364) (A), elevated UAE (P = 0.0003) (B), and hypertension (P = 0.0002) (C). Error bars indicate ±SE. Prevalence and error bars were jittered to avoid overlapping. P values are provided for the test of trajectory difference between groups over the study period (i.e., test for the existence of group ∗ time interaction terms). Hyperfiltration and elevated UAE were adjusted for baseline age, sex, BMI, HbA_1c, insulin sensitivity, triglycerides, and antihypertensive use. Baseline antihypertensive use was not included in model for hypertension because of collinearity.

Figure 4

Odds of DKD and hypertension at year 5. Forest plot for ORs of group effect. Teen-LABS is the reference group. The x-axis is in log scale. ORs on the left-hand side of 1 favor TODAY; ORs on the right-hand side of 1 favor Teen-LABS. Hyperfiltration, elevated UAE, and incident hyperfiltration models were adjusted for baseline age, sex, BMI, HbA_1c, insulin sensitivity, triglycerides, and antihypertensive medication use. Baseline antihypertensive medication use was not included in hypertension and incident hypertension models because of collinearity.