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Five-year kidney outcomes of bariatric surgery differ in severely obese adolescents and adults with and without type 2 diabetes.

ABSTRACT: Bariatric surgery improves markers of kidney health in severe obesity, yet it is unclear if kidney disease outcomes differ according to age at surgery. Therefore, we examined health effects of Roux-en-Y gastric bypass between 161 adolescents and 396 adults participating in two related but distinct studies. Primary outcomes were elevated urine albumin-to-creatinine ratio (UACR) of 30 mg/g or more and hyperfiltration (an estimated glomerular filtration rate of 135 ml/min/1.73m² or more). Analyses were stratified by the presence of pre-operative type 2 diabetes. Adolescents with pre-operative type 2 diabetes had a significantly increased prevalence of elevated UACR prior to surgery compared to adults (22.5 vs. 9.0%). Resolution of elevated UACR following surgery differed between adolescents and adults with type 2 diabetes, with adolescents experiencing a significantly earlier improvement following surgery. Adolescents without pre-operative type 2 diabetes demonstrated a significantly increased prevalence of UACR prior to surgery compared to adults (9.4 vs. 4.5%), with no improvement occurring in either group post-operatively. Adolescents with pre-operative type 2 diabetes had a significantly increased prevalence of hyperfiltration that remained throughout the study period, whereas hyperfiltration prevalence was similar among those without type 2 diabetes. Thus, adolescents with pre-operative type 2 diabetes experienced earlier attenuation of elevated UACR compared to adults with pre-operative type 2 diabetes in response to gastric bypass.

SUBMITTER: Bjornstad P

PROVIDER: S-EPMC7183894 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Severe obesity is a growing, worldwide burden and conventional therapies including radical change of diet and/or increased physical activity have limited results. Bariatric surgery has been proposed as an alternative therapy showing promising results. It leads to substantial weight loss and improvement of comorbidities such as type 2 diabetes. Increased adiposity is associated with changes in epigenetic profile, including DNA methylation. We investigated the effect of bariatric surgery on clinical profile, DNA methylation, and biological age estimated using Horvath's epigenetic clock. RESULTS:To determine the impact of bariatric surgery and subsequent weight loss on clinical traits, a cohort of 40 severely obese individuals (BMI = 30-73 kg/m2) was examined at the time of surgery and at three follow-up visits, i.e., 3, 6, and 12 months after surgery. The majority of the individuals were women (65%) and the mean age at surgery was 45.1 ± 8.1 years. We observed a significant decrease over time in BMI, fasting glucose, HbA1c, HOMA-IR, insulin, total cholesterol, triglycerides, LDL and free fatty acids levels, and a significant small increase in HDL levels (all p values < 0.05). Epigenome-wide association analysis revealed 4857 differentially methylated CpG sites 12 months after surgery (at Bonferroni-corrected p value < 1.09 × 10-7). Including BMI change in the model decreased the number of significantly differentially methylated CpG sites by 51%. Gene set enrichment analysis identified overrepresentation of multiple processes including regulation of transcription, RNA metabolic, and biosynthetic processes in the cell. Bariatric surgery in severely obese patients resulted in a decrease in both biological age and epigenetic age acceleration (EAA) (mean = - 0.92, p value = 0.039). CONCLUSIONS:Our study shows that bariatric surgery leads to substantial BMI decrease and improvement of clinical outcomes observed 12?months after surgery. These changes explained part of the association between bariatric surgery and DNA methylation. We also observed a small, but significant improvement of biological age. These epigenetic changes may be modifiable by environmental lifestyle factors and could be used as potential biomarkers for obesity and in the future for obesity related comorbidities.

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Five-year kidney outcomes of bariatric surgery differ in severely obese adolescents and adults with and without type 2 diabetes.

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