Insulin Sensitivity and β-Cell Function Improve after Gastric Bypass in Severely Obese Adolescents

Abstract

Objective To test the hypothesis that insulin secretion and insulin sensitivity would be improved in adolescents after Roux-en-Y gastric bypass (RYGB). Study design A longitudinal study of 22 adolescents and young adults without diabetes undergoing laparoscopic RYGB (mean age 17.1 ± 1.42 years; range 14.5–20.1; male/female 8/14; Non-Hispanic White/African American 17/5) was conducted. Intravenous glucose tolerance tests were done to obtain insulin sensitivity (insulin sensitivity index), insulin secretion (acute insulin response to glucose), and the disposition index as primary outcome variables. These variables were compared over the 1 year of observation using linear mixed modeling. Results In the 1-year following surgery, body mass index fell by 38% from a mean of 61 ± 12.3 to 39 ± 8.0 kg/m2 (P < .01). Over the year following surgery, fasting glucose and insulin values declined by 54% and 63%, respectively. Insulin sensitivity index increased 300% (P < .01), acute insulin response to glucose decreased 56% (P < .01), leading to a nearly 2-fold increase in the disposition index (P < .01). Consistent with improved β-cell function, the proinsulin to C-peptide ratio decreased by 21% (P < .01). Conclusions RYGB reduced body mass index and improved both insulin sensitivity and β-cell function in severely obese teens and young adults. These findings demonstrate that RYGB is associated with marked metabolic improvements in obese young people even as significant obesity persists. Trial registration ClinicalTrials.gov: NCT00360373.

Elevations in the Fasting Serum Proinsulin–to–C-Peptide Ratio Precede the Onset of Type 1 Diabetes

“…Interleukin-1 receptor antagonist treatment in subjects with type 2 diabetes improved insulin secretion and similarly led to reduced PI-to-insulin ratios (26). Finally, in a cohort of obese adolescents who underwent laparoscopic Roux-en-Y gastric bypass, reductions in PI:C ratios were observed concomitant with marked weight loss and improvements in the glucose disposition index (27). …”

Metabolic syndrome in children and adolescents

“…There is some evidence to suggest that bariatric surgery can lead to resolution of associated co-morbidities such as sleep apnea, type 2 diabetes and other cardiovascular risk factors (77,78). Bariatric surgery has also been reported to improve insulin sensitivity and secretion (79). However, RYBG has an increased risk for vitamin D, calcium, and phosphorus malabsorption.…”

Weight loss surgery in adolescents corrects high-density lipoprotein subspecies and their function

“…Specifically, weight loss surgery improves important metabolic parameters such as insulin resistance (8), as well as blood pressure and lipids (5, 6). One important change that occurs following metabolic surgery in both adults and youth is a significant and sustained rise in high density lipoprotein cholesterol (HDL-C) of 40% or greater (9).…”

“…In this current study, we asked whether reduction in weight with metabolic surgery reverses this unhealthy HDL subspecies profile and improves HDL function. This surgical model was chosen for two reasons: 1) significant weight loss and reversal of insulin resistance can be achieved with metabolic surgery in a consistent manner (6, 8), and importantly 2) studying participants pre- and post-surgery allows each subject to serve as his own control thus reducing the number of confounding variables encountered in cross-sectional studies of individuals with a broad range of BMI values.…”