Testing a very low-carbohydrate adaption of the Diabetes Prevention Program among adults with prediabetes: study protocol for the Lifestyle Education about prediabetes (LEAP) trial.

BACKGROUND: The Center for Disease Control and Prevention's National Diabetes Prevention Program (NDPP) aims to help individuals with prediabetes avoid progression to type 2 diabetes mellitus (T2DM) through weight loss. Specifically, the NDPP teaches individuals to follow a low-fat, calorie-restricted diet and to engage in regular physical activity to achieve ≥ 5% body weight loss. Most NDPP participants, however, do not achieve this weight loss goal, and glycemic control remains largely unchanged. One promising opportunity to augment the NDPP's weight loss and glycemic effectiveness may be to teach participants to follow a very low-carbohydrate diet (VLCD), which can directly reduce post-prandial glycemia and facilitate weight loss by reducing circulating insulin and enabling lipolysis. To date, there have been no high-quality, randomized controlled trials to test whether a VLCD can prevent progression to T2DM among individuals with prediabetes. The aim of this study is to test the effectiveness of a VLCD version the NDPP (VLC-NDPP) versus the standard NDPP. We hypothesize the VLC-NDPP will demonstrate greater improvements in weight loss and glycemic control. METHODS: We propose to conduct a 12-month, 1:1, randomized controlled trial that will assign 300 adults with overweight or obesity and prediabetes to either the NDPP or VLC-NDPP. The primary outcome will be glycemic control as measured by change in hemoglobin A1c (HbA1c) from baseline to 12 months. Secondary outcomes will include percent body weight change and changes in glycemic variability, inflammatory markers, lipids, and interim HbA1c. We will evaluate progression to T2DM and initiation of anti-hyperglycemic agents. We will conduct qualitative interviews among a purposive sample of participants to explore barriers to and facilitators of dietary adherence. The principal quantitative analysis will be intent-to-treat using hierarchical linear mixed effects models to assess differences over time. DISCUSSION: The NDPP is the dominant public health strategy for T2DM prevention. Changing the program's dietary advice to include a carbohydrate-restricted eating pattern as an alternative option may enhance the program's effectiveness. If the VLC-NDPP shows promise, this trial would be a precursor to a multi-site trial with incident T2DM as the primary outcome. TRIAL REGISTRATION: NCT05235425. Registered February 11, 2022.

The Effect of Attrition on Reported Diabetes Remission Rates Following Roux-en-Y Gastric Bypass: a Sensitivity Analysis.

OBJECTIVE: Attrition, or loss to follow-up, is a common problem in studies of type 2 diabetes remission following roux-en-Y gastric bypass (RYGB) and is often correlated with weight loss. Thus, reported rates of remission may be inflated by attrition bias. We investigate the effect of attrition bias on reported diabetes remission rates following RYGB. METHODS: Using sensitivity analyses, we identified sets of attrition and remission rates that produced simulated outcomes within 95% confidence intervals of the reported outcomes from five studies of diabetes remission following RYGB. RESULTS: Potential attrition bias varied greatly, yielding possible remission rates of diabetes ranging from 20 to 40% at 1 year. For studies with the attrition greater than ~ 20%, estimates that ignored attrition overestimated diabetes remission rates. Kaplan-Meier estimates were less affected by attrition. Potential for bias was most evident in the study with the largest sample size. CONCLUSION: Researchers, clinicians, and policymakers can measure potential attrition bias in clinical studies. In the case of remission of diabetes following RYGB, the potential bias in reported remission rates is generally less than 10%, varies considerably among studies, and is primarily driven by attrition rate and study size. Studies with very large sample sizes may provide a narrow confidence interval around a biased estimate.

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

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.

Improving diabetes processes of care in managed care.

OBJECTIVE: To evaluate the impact of systematic patient evaluation and patient and provider feedback on the processes and intermediate outcomes of diabetes care in Independent Practice Association model internal medicine practices. RESEARCH DESIGN AND METHODS: Nine practices providing care to managed care patients were randomly assigned as intervention or comparison sites. Intervention-site subjects had Annual Diabetes Assessment Program (ADAP) assessments (HbA(1c), blood pressure, lipids, smoking, retinal photos, urine microalbumin, and foot examination) at years 1 and 2. Comparison-site subjects had ADAP assessments at year 2. At Intervention sites, year 1 ADAP results were reviewed with subjects, mailed to providers, and incorporated into electronic medical records with guideline-generated suggestions for treatment and follow-up. Medical records were evaluated for both groups for the year before both the year 1 and year 2 ADAP assessments. Processes and intermediate outcomes were compared using linear and logistic mixed hierarchical models. RESULTS: Of 284 eligible subjects, 103 of 173 (60%) at the Intervention sites and 71 of 111 (64%) at the comparison sites participated; 83 of 103 (81%) of the intervention-site subjects returned for follow-up at year 2. Performance of the six recommended assessments improved in intervention-site subjects at year 2 compared with year 1 (5.8 vs. 4.3, P = 0.0001) and compared with comparison-site subjects at year 2 (4.2, P = 0.014). No significant changes were noted in intermediate outcomes. CONCLUSIONS: The ADAP significantly improved processes of care but not intermediate outcomes. Additional interventions are needed to improve intermediate outcomes.