Defining remission of type 2 diabetes in research studies: A systematic scoping review

Mireille Captieux, ReginaPrigge, Sarah Wild, Bruce Guthrie

Abstract

Remission has been identified as a top priority by people with type 2 diabetes. Remission is commonly used as an outcome in research studies; however, a widely accepted definition of remission of type 2 diabetes is lacking. A report on defining remission was published (but not formally endorsed) in Diabetes Care, an American Diabetes Association (ADA) journal. This Diabetes Care report remains widely used. It was the first to suggest 3 components necessary to define the presence of remission: (1) absence of glucose-lowering therapy (GLT); (2) normoglycaemia; and (3) for duration ≥1 year. Our aim is to systematically review how remission of type 2 diabetes has been defined by observational and interventional studies since publication of the 2009 report.

Introduction

Type 2 diabetes is a global health priority. By 2045, an estimated 629 million people will be affected by diabetes, of whom 90% to 95% will have type 2 diabetes. Drivers for the twin epidemics of obesity and diabetes lie in complex interactions between obesogenic environments, a biological tendency for weight gain, and an ageing population. The rapid spread of obesity and diabetes worldwide has considerable health implications for the individual and major financial consequences for health service. In 2015, the global economic burden of diabetes was estimated to be US$1.3 trillion, and total costs are estimated to rise to US$2.2 to $2.5 trillion by 2030. Type 2 diabetes has conventionally been considered a lifelong, progressive disease. The concept of reversing type 2 diabetes by metabolic surgery was introduced in the early 1990s.

Methods

Search strategy and selection criteria
We adapted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for scoping reviews to report our systematic review of observational and interventional studies. We included observational and interventional studies involving at least 100 participants with type 2 diabetes in their remission analysis, which examined an outcome of type 2 diabetes remission in adults ≥18 years old, and which had been published in English since 2009 (when the 2009 report was published). These restrictions were decided a priori and were expected to provide a sufficient number of papers specifically focussing on the effect of the 2009 report in reasonably large research studies within our time and resource constraints.

Web content or materials produced outside the traditional academic publishing were not searched as we were interested in how remission was defined in manuscripts that had been peer-reviewed in academic publication and distribution channels. We excluded case reports, systematic reviews, protocols, or reviews. Studies focussing on prediabetes, impaired glucose tolerance, impaired fasting glucose, gestational diabetes, maturity onset diabetes of the young, steroid-induced diabetes, or type 1 diabetes were excluded as beyond the scope of this review.

Discussion

Since the publication of the 2009 report, our analysis of 178 studies conducted in 33 countries identified substantial heterogeneity in how remission is named and defined. We identified 96 unique definitions of remission that reflected heterogeneity in the 3 components relating to GLT (3 unique explicit definitions), glycaemic thresholds (27 unique numeric definitions), and time (13 unique explicit definitions), as well as heterogeneity in different combinations of these 3 components in each definition. The 2009 report was the most widely used guide in defining remission and was referenced in 121 (45%) definitions.

Citation: Captieux M, Prigge R, Wild S, Guthrie B (2020) Defining remission of type 2 diabetes in research studies: A systematic scoping review. PLoS Med 17(10): e1003396. https://doi.org/10.1371/journal.pmed.1003396

Academic Editor: Sanjay Basu, Harvard Medical School, UNITED STATES

Received: June 11, 2020; Accepted: September 29, 2020; Published: October 28, 2020

Copyright:© 2020 Captieux et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data cited within the manuscript is contained within the manuscript and supporting information file. Please access the raw data file at: doi: http://doi.org/10.17605/OSF.IO/F4H3Rurl: https://osf.io/f4h3r/.

Funding: MC is supported by a personal doctoral fellowship from the Chief Scientist Office Grant number: CAF 18/12 Website: https://www.cso.scot.nhs.uk The funder had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: ADA, American Diabetes Association; FPG, fasting plasma glucose; GLT, glucose-lowering therapy; PCOS, polycystic ovarian syndrome; PICOS, participants, interventions, comparisons, outcomes, and study design; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; WHO, World Health Organization; 2-hr PG, 2-hour plasma glucose.