Regression to the Mean Contributes to the Apparent Improvement in Glycemia 3.8 Years After Screening: The ELSA-Brasil Study

Abstract

Objective: Glycemic regression is common in real-world settings, but the contribution of regression to the mean (RTM) has been little investigated. We aimed to estimate glycemic regression before and after adjusting for RTM in a free-living cohort of adults with newly ascertained diabetes and intermediate hyperglycemia (IH).

Research design and methods: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a cohort study of 15,105 adults screened between 2008 and 2010 with standardized oral glucose tolerance test and HbA_1c, repeated after 3.84 ± 0.42 years. After excluding those receiving medical treatment for diabetes, we calculated partial or complete regression before and after adjusting baseline values for RTM.

Results: Regarding newly ascertained diabetes, partial or complete regression was seen in 49.4% (95% CI 45.2-53.7); after adjustment for RTM, in 20.2% (95% CI 12.1-28.3). Regarding IH, regression to normal levels was seen in 39.5% (95% CI 37.9-41.3) or in 23.7% (95% CI 22.6-24.3), depending on use of the World Health Organization (WHO) or the American Diabetes Association (ADA) definition, respectively; after adjustment, corresponding frequencies were 26.1% (95% CI 22.4-28.1) and 19.4% (95% CI 18.4-20.5). Adjustment for RTM reduced the number of cases detected at screening: 526 to 94 cases of diabetes, 3,118 to 1,986 cases of WHO-defined IH, and 6,182 to 5,711 cases of ADA-defined IH. Weight loss ≥2.6% was associated with greater regression from diabetes (relative risk 1.52, 95% CI 1.26-1.84) and IH (relative risk 1.30, 95% CI 1.17-1.45).

Conclusions: In this quasi-real-world setting, regression from diabetes at ∼4 years was common, less so for IH. Regression was frequently explained by RTM but, in part, also related to improved weight loss and homeostasis over the follow-up.

Figure 1

Scatter plots of baseline and follow-up glycemic values and estimated parameters of linear regression for FPG (A), 2-h PG (B), and glycated hemoglobin (HbA_1c) (C). The dark line is the 45° diagonal; the fine line is the predicted fit. Additional graphs show details of central portions. D, diabetes; N, normal.

Figure 2

Proportions of participants with diabetes and IH at baseline and their glycemic regression at follow-up, before and after adjustments for RTM. Top, diabetes at baseline. Bottom, IH at baseline. The size of the circles illustrates the relative reduction in baseline cases after accounting for RTM.