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Comparative effectiveness of bariatric surgery vs. nonsurgical treatment of type 2 diabetes among severely obese adults.

ABSTRACT: Although all weight-loss approaches may improve insulin sensitivity in type 2 diabetes, bariatric surgery is believed to be the only reliable means of achieving diabetes remission. We conducted a retrospective cohort study to compare rates of diabetes remission, relapse and all-cause mortality among severely obese individuals with diabetes who underwent bariatric surgery vs. nonsurgically treated individuals. Severely obese adults with uncontrolled or medication-controlled diabetes who underwent bariatric surgery or received usual medical care from 2005 to 2008 in three health care delivery systems in the United States were eligible. Diabetes status was identified using pharmacy, laboratory, and diagnosis information from electronic medical records. A propensity approach and exclusion criteria identified 1395 adults with diabetes who had bariatric surgery and 62,322 who did not. Most procedures were Roux-en-Y gastric bypass (72.0% laparoscopic; 8.2% open); 4.4% were gastric banding, 2.4% sleeve gastrectomy, and 13.2% were other procedures. At two years, bariatric subjects experienced significantly higher diabetes remission rates [73.7% (95% CI: 70.6, 76.5)] compared to nonsurgical subjects [6.9% (95%CI: 6.9, 7.1)]. Age, site, duration of diabetes, hemoglobin A1c level, and intensity of diabetes medication treatment were significantly associated with remission. Bariatric subjects also experienced lower relapse rates than nonsurgical subjects (adjusted HR: 0.19; 95% CI: 0.15-0.23) with no higher risk of death (adjusted HR: 0.54; 95% CI: 0.22-1.30). We conclude that bariatric surgery can effectively induce remission of diabetes among most severely obese adults, and this treatment approach appears to be superior to nonsurgical treatment in inducing diabetes remission.

SUBMITTER: Arterburn D

PROVIDER: S-EPMC4632526 | biostudies-literature | 2013 Jul-Aug

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.

Project description:BackgroundObservational studies have shown improvement in patients with type 2 diabetes mellitus after bariatric surgery.MethodsIn this randomized, nonblinded, single-center trial, we evaluated the efficacy of intensive medical therapy alone versus medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy in 150 obese patients with uncontrolled type 2 diabetes. The mean (±SD) age of the patients was 49±8 years, and 66% were women. The average glycated hemoglobin level was 9.2±1.5%. The primary end point was the proportion of patients with a glycated hemoglobin level of 6.0% or less 12 months after treatment.ResultsOf the 150 patients, 93% completed 12 months of follow-up. The proportion of patients with the primary end point was 12% (5 of 41 patients) in the medical-therapy group versus 42% (21 of 50 patients) in the gastric-bypass group (P=0.002) and 37% (18 of 49 patients) in the sleeve-gastrectomy group (P=0.008). Glycemic control improved in all three groups, with a mean glycated hemoglobin level of 7.5±1.8% in the medical-therapy group, 6.4±0.9% in the gastric-bypass group (P<0.001), and 6.6±1.0% in the sleeve-gastrectomy group (P=0.003). Weight loss was greater in the gastric-bypass group and sleeve-gastrectomy group (-29.4±9.0 kg and -25.1±8.5 kg, respectively) than in the medical-therapy group (-5.4±8.0 kg) (P<0.001 for both comparisons). The use of drugs to lower glucose, lipid, and blood-pressure levels decreased significantly after both surgical procedures but increased in patients receiving medical therapy only. The index for homeostasis model assessment of insulin resistance (HOMA-IR) improved significantly after bariatric surgery. Four patients underwent reoperation. There were no deaths or life-threatening complications.ConclusionsIn obese patients with uncontrolled type 2 diabetes, 12 months of medical therapy plus bariatric surgery achieved glycemic control in significantly more patients than medical therapy alone. Further study will be necessary to assess the durability of these results. (Funded by Ethicon Endo-Surgery and others; ClinicalTrials.gov number, NCT00432809.).

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Comparative effectiveness of bariatric surgery vs. nonsurgical treatment of type 2 diabetes among severely obese adults.

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