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Reconciliation of Type 2 Diabetes Remission Rates in Studies of Roux-en-Y Gastric Bypass.

ABSTRACT: OBJECTIVE:Bariatric surgery may induce remission of type 2 diabetes in obese patients. However, estimates of remission rates reported in the literature range from 25 to 81%, contributing to the uncertainty patients and physicians both face as they assess treatment options. This analysis attempts to reconcile the seemingly disparate rates of diabetes remission reported in studies of Roux-en-Y gastric bypass (RYGB) surgery. It examines variation in the methodologies used to derive the estimates and proposes outcomes that should be reported by all studies. RESEARCH DESIGN AND METHODS:A literature review yielded 10 large (n > 100), recent (index surgery since 2000) studies of diabetes remission after RYGB. These studies differed in definitions of remission (partial vs. complete), lengths of follow-up (1 year vs. ≥3 years), reported outcomes (cumulative vs. prevalent remission), and risks of attrition bias. RESULTS:Reported rates of partial remission were 10-30 percentage points higher than rates of complete remission. Study duration explained 69% of the variability in cumulative remission rates, plateauing at 3 years. Adjustment for attrition increased the explained variability to 87%. Attrition-adjusted, 3-year cumulative, complete remission rates ranged from 63 to 65%; however, this does not account for relapse. Attrition-adjusted, 3-year prevalent complete remission rates that accounted for relapse were 23%. CONCLUSIONS:Variations in reported rates of diabetes remission after RYGB are primarily related to definitions and study duration. Future studies should report both cumulative and prevalent remission to aid decision making and more easily compare studies.

SUBMITTER: Isaman DJ

PROVIDER: S-EPMC5127233 | biostudies-other | 2016 Dec

REPOSITORIES: biostudies-other

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Reconciliation of Type 2 Diabetes Remission Rates in Studies of Roux-en-Y Gastric Bypass.

Isaman Deanna J M DJ Rothberg Amy E AE Herman William H WH

Diabetes care 20161013 12

<h4>Objective</h4>Bariatric surgery may induce remission of type 2 diabetes in obese patients. However, estimates of remission rates reported in the literature range from 25 to 81%, contributing to the uncertainty patients and physicians both face as they assess treatment options. This analysis attempts to reconcile the seemingly disparate rates of diabetes remission reported in studies of Roux-en-Y gastric bypass (RYGB) surgery. It examines variation in the methodologies used to derive the esti ...[more]

PMID: 27737910

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Project description:About 60% of patients with type 2 diabetes achieve remission after Roux-en-Y gastric bypass (RYGB) surgery. No accurate method is available to preoperatively predict the probability of remission. Our goal was to develop a way to predict probability of diabetes remission after RYGB surgery on the basis of preoperative clinical criteria.In a retrospective cohort study, we identified individuals with type 2 diabetes for whom electronic medical records were available from a primary cohort of 2300 patients who underwent RYGB surgery at the Geisinger Health System (Danville, PA, USA) between Jan 1, 2004, and Feb 15, 2011. Partial and complete remission were defined according to the American Diabetes Association criteria. We examined 259 clinical variables for our algorithm and used multiple logistic regression models to identify independent predictors of early remission (beginning within first 2 months after surgery and lasting at least 12 months) or late remission (beginning more than 2 months after surgery and lasting at least 12 months). We assessed a final Cox regression model with a consistent subset of variables that predicted remission, and used the resulting hazard ratios (HRs) to guide creation of a weighting system to produce a score (DiaRem) to predict probability of diabetes remission within 5 years. We assessed the validity of the DiaRem score with data from two additional cohorts.Electronic medical records were available for 690 patients in the primary cohort, of whom 463 (63%) had achieved partial or complete remission. Four preoperative clinical variables were included in the final Cox regression model: insulin use, age, HbA1c concentration, and type of antidiabetic drugs. We developed a DiaRem score that ranges from 0 to 22, with the greatest weight given to insulin use before surgery (adding ten to the score; HR 5·90, 95% CI 4·41–7·90; p<0·0001). Kaplan-Meier analysis showed that 88% (95% CI 83–92%) of patients who scored 0–2, 64% (58–71%) of those who scored 3–7, 23% (13–33%) of those who scored 8–12, 11% (6–16%) of those who scored 13–17, and 2% (0–5%) of those who scored 18–22 achieved early remission (partial or complete). As in the primary cohort, the proportion of patients achieving remission in the replication cohorts was highest for the lowest scores, and lowest for the highest scores.The DiaRem score is a novel preoperative method to predict the probability of remission of type 2 diabetes after RYGB surgery.Geisinger Health System and the US National Institutes of Health.

Project description:OBJECTIVE:Roux-en-Y gastric bypass surgery (RYGB) improves the first phase of glucose-stimulated insulin secretion (GSIS) in patients with type 2 diabetes. How it does so remains unclear. Farnesoid X receptor (FXR), the nuclear receptor of bile acids (BAs), is implicated in bariatric surgery. Moreover, the transient receptor potential ankyrin 1 (TRPA1) channel is expressed in pancreatic ?-cells and involved in insulin secretion. We aimed to explore the role of BAs/FXR and TRPA1 in improved GSIS in diabetic rats after RYGB. METHODS:RYGB or sham surgery was conducted in spontaneous diabetic Goto-Kakizaki (GK) rats, or FXR or TRPA1 transgenic mice. Gene and protein expression of islets were assessed by qPCR and western blotting. Electrophysiological properties of single ?-cells were studied using patch-clamp technique. Binding of FXR and histone acetyltransferase steroid receptor coactivator-1 (SRC1) to the TRPA1 promoter, acetylated histone H3 (ACH3) levels at the TRPA1 promoter were determined using ChIP assays. GSIS was measured using enzyme-linked immunosorbent assays or intravenous glucose tolerance test (IVGTT). RESULTS:RYGB increases GSIS, particularly the first-phase of GSIS in both intact islets and GK rats in vivo, and ameliorates hyperglycemia of GK rats. Importantly, the effects of RYGB were attenuated in TRPA1-deficient mice. Moreover, GK ?-cells displayed significantly decreased TRPA1 expression and current. Patch-clamp recording revealed that TRPA1-/- ?-cells displayed a marked hyperpolarization and decreased glucose-evoked action potential firing, which was associated with impaired GSIS. RYGB restored TRPA1 expression and current in GK ?-cells. This was accompanied by improved glucose-evoked electrical activity and insulin secretion. Additionally, RYGB-induced TRPA1 expression involved BAs/FXR-mediated recruitment of SRC1, promoting ACH3 at the promoter of TRPA1. CONCLUSIONS:The BAs/FXR/SRC1 axis-mediated restoration of TRPA1 expression plays a critical role in the enhanced GSIS and remission of diabetes in GK rats after RYGB.

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Reconciliation of Type 2 Diabetes Remission Rates in Studies of Roux-en-Y Gastric Bypass.

Publications

Reconciliation of Type 2 Diabetes Remission Rates in Studies of Roux-en-Y Gastric Bypass.

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