Abstract
Background
Clinical pathways are changing to incorporate support and appropriate follow-up for people to achieve remission of type 2 diabetes, but there is limited understanding of the prevalence of remission in current practice or patient characteristics associated with remission.
Methods and findings
We carried out a cross-sectional study estimating the prevalence of remission of type 2 diabetes in all adults in Scotland aged ≥30 years diagnosed with type 2 diabetes and alive on December 31, 2019. Remission of type 2 diabetes was assessed between January 1, 2019 and December 31, 2019. We defined remission as all HbA1c values <48 mmol/mol in the absence of glucose-lowering therapy (GLT) for a continuous duration of ≥365 days before the date of the last recorded HbA1c in 2019. Multivariable logistic regression in complete and multiply imputed datasets was used to examine characteristics associated with remission. Our cohort consisted of 162,316 individuals, all of whom had at least 1 HbA1c ≥48 mmol/mol (6.5%) at or after diagnosis of diabetes and at least 1 HbA1c recorded in 2019 (78.5% of the eligible population). Over half (56%) of our cohort was aged 65 years or over in 2019, and 64% had had type 2 diabetes for at least 6 years. Our cohort was predominantly of white ethnicity (74%), and ethnicity data were missing for 19% of the cohort. Median body mass index (BMI) at diagnosis was 32.3 kg/m2. A total of 7,710 people (4.8% [95% confidence interval [CI] 4.7 to 4.9]) were in remission of type 2 diabetes. Factors associated with remission were older age (odds ratio [OR] 1.48 [95% CI 1.34 to 1.62] P < 0.001) for people aged ≥75 years compared to 45 to 54 year group), HbA1c <48 mmol/mol at diagnosis (OR 1.31 [95% CI 1.24 to 1.39] P < 0.001) compared to 48 to 52 mmol/mol), no previous history of GLT (OR 14.6 [95% CI 13.7 to 15.5] P < 0.001), weight loss from diagnosis to 2019 (OR 4.45 [95% CI 3.89 to 5.10] P < 0.001) for ≥15 kg of weight loss compared to 0 to 4.9 kg weight gain), and previous bariatric surgery (OR 11.9 [95% CI 9.41 to 15.1] P < 0.001). Limitations of the study include the use of a limited subset of possible definitions of remission of type 2 diabetes, missing data, and inability to identify self-funded bariatric surgery.
Conclusions
In this study, we found that 4.8% of people with type 2 diabetes who had at least 1 HbA1c ≥48 mmol/mol (6.5%) after diagnosis of diabetes and had at least 1 HbA1c recorded in 2019 had evidence of type 2 diabetes remission. Guidelines are required for management and follow-up of this group and may differ depending on whether weight loss and remission of diabetes were intentional or unintentional. Our findings can be used to evaluate the impact of future initiatives on the prevalence of type 2 diabetes remission.
Author summary
Why was this study done?
- Feasibility of diabetes remission has been demonstrated in research settings and after bariatric surgery, but we do not know how many people in the general population achieve remission of type 2 diabetes.
- Informed decisions need to be made about which people are most likely to achieve and maintain remission; to do this, we need to better understand the characteristics of people who are currently in remission.
- Estimating the prevalence of remission of type 2 diabetes in Scotland in 2019 creates a baseline to evaluate the impact of future initiatives to support remission and for future studies of duration of remission and effect on risk of complications of diabetes.
What did the researchers do and find?
- We calculated how many people were in remission of type 2 diabetes in 2019 in Scotland from a national type 2 diabetes register. This register contains 99% of people with diabetes in Scotland.
- We described the characteristics of people who were in remission of type 2 diabetes compared to people who were not in remission and created a mathematical model that shows the probability of achieving remission in 2019 based on these characteristics.
- We found that about 1 in 20 of people with type 2 diabetes in the study population were in remission of type 2 diabetes.
- Compared to people who did not achieve remission, people in remission of type 2 diabetes tended to be older; have a lower HbA1c at diagnosis; have never taken any glucose-lowering medication; have lost weight since the diagnosis of diabetes; and have had bariatric surgery.
What do these findings mean?
- There is a sizeable proportion of people who achieve remission of type 2 diabetes outside research trials and without bariatric surgery. These people should be recognised and coded appropriately so they can be supported by their clinicians. The clinical progress of these people can now be followed by researchers.
- People who have not yet been prescribed drugs to treat diabetes may be the most appropriate group for clinicians to initiate discussions around remission and weight management options.
- Guidelines for supporting people who achieve remission of diabetes must recognise differences between people that lose weight intentionally and those that lose weight because of severe illness. Clinicians also need greater clarity on how to manage older or frailer people who achieve remission criteria.
Citation: Captieux M, Fleetwood K, Kennon B, Sattar N, Lindsay R, Guthrie B, et al. (2021) Epidemiology of type 2 diabetes remission in Scotland in 2019: A cross-sectional population-based study. PLoS Med 18(11):
e1003828.
https://doi.org/10.1371/journal.pmed.1003828
Academic Editor: Ronald C. W. Ma, Chinese University of Hong Kong, CHINA
Received: June 8, 2021; Accepted: September 30, 2021; Published: November 2, 2021
Copyright: © 2021 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: The authors are not permitted to share the data that support the findings of this study directly. Data from the Scottish Care Information – diabetes database are available to accredited researchers who receive approval for data access through a data safe haven from the NHS Scotland Public Benefit and Privacy Panel for Health and Social Care: https://www.informationgovernance.scot.nhs.uk/pbpphsc/.
Funding: MC was was funded by Chief Scientist Office CAF 18/12 (https://www.cso.scot.nhs.uk/personal-awards-initiative/clinical-academic-fellowships/). The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.
Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: BK is national lead for diabetes and chair of the Scottish Diabetes Group which sits directly within the Clinical Priorities team at Scottish Government, member of the Type 2 Diabetes Prevention Oversight group which is a Scottish Government related group, speciality adviser to Chief Medical Officer for diabetes and endocrine. RL has served on advisory boards with Novo Nordisk, Lily and Servier only NS has consulted for Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi, and received grant support from Boehringer Ingelheim, Novartis and Roche, outside the submitted work.
Abbreviations:
2-hr PG,
two-hour plasma glucose; ADA,
American Diabetes Association; AHEAD,
Action for Health in Diabetes; AIC,
Akaike information criterion; BMI,
body mass index; CI,
confidence interval; COVID-19,
Coronavirus Disease 2019; DiRECT,
Diabetes Remission Clinical Trial; DPP-4,
dipeptidyl peptidase 4; DUK,
Diabetes UK; FPG,
fasting plasma glucose; GLP-1,
glucagon-like peptide-1 receptor; GLT,
glucose-lowering therapy; ICD-10,
International Classification of Diseases-10th revision; IDF,
International Diabetes Federation; MAR,
missing at random; MCAR,
missing completely at random; MICE,
Multiple Imputation by Chained Equations; NHS,
National Health Service; NMAR,
not missing at random; OPCS-4,
Office of Population Censuses and Surveys Classification of Interventions and Procedures version 4; OR,
odds ratio; PCDS,
Primary Care Diabetes Society; SCI-Diabetes,
Scottish Care Information-Diabetes; SGLT-2,
sodium glucose cotransporter-2; SIGN,
Scottish Intercollegiate Guidelines Network; SIMD,
Scottish Index of Multiple Deprivation; STROBE,
Strengthening The Reporting of OBservational Studies in Epidemiology; WHO,
World Health Organization
Introduction
There were an estimated 463 million people with diabetes in the world in 2019, of whom 90% to 95% have type 2 diabetes [1]. By 2045, it is estimated that there will be 700 million people in the world with diabetes. Drivers for the global rise in diabetes prevalence include increasing numbers of people aged 65 years of age; urbanisation; increasing prevalence of obesity; and improved survival of people with diabetes [2,3]. Remission of type 2 diabetes (defined broadly as the achievement of normal glycaemic measures without glucose-lowering therapy (GLT)) may be one way to flatten this upward trend. Position statements or recommendations for practice have been published by the Primary Care Diabetes Society (PCDS) [4], the International Diabetes Federation (IDF) [5], and a multidisciplinary group of experts [6] in 2019, 2017, and 2009, respectively. The PCDS states that “remission can be achieved when a person with type 2 diabetes achieves 1. Weight loss; 2. HbA1c <48 mmol/mol (6.5%) or FPG <7.0 mmol/l (126mg/dL) on two occasions separated by six months; 3. Following complete cessation of all GLT.” [4] (p. 74). The IDF states that “remission is defined by most guidelines as an HbA1c below 6% (42 mmol/mol) without medication for 6 months or more” [5] (p. 21).” Buse and colleagues define remission as “achieving glycaemia below the diabetic range in the absence of active pharmacologic or surgical therapy.” Three types of remission are explicitly defined: partial remission, complete remission, and prolonged remission (cure) with a minimum duration of 1 year for partial and complete remission [6] (p. 2134). Riddle and colleagues define remission as “HbA1c <6.5% (48 mmol/mol) measured at least 3 months after cessation of glucose-lowering pharmacotherapy” (p. 1) [7] (at least 6 months after starting a lifestyle intervention) [7]. We have previously shown that there were at least 96 unique definitions of diabetes remission used in the research literature from 2009 to 2020 [8].
In the early 1990s, remission was demonstrated in people with type 2 diabetes after bariatric surgery [9]. This challenged the perception of type 2 diabetes as a chronic progressive disease. Two recent trials have additionally shown that it is also possible to achieve remission of type 2 diabetes through weight loss using very low calorie diets [10,11]. The Diabetes Remission Clinical Trial (DiRECT) was the first trial to use a low calorie diet intervention to assess type 2 diabetes remission as a primary outcome. Participants were between 20 and 65 years of age, with body mass index (BMI) 27 to 45 kg/m2, and within 6 years since diabetes diagnosis. After 2 years of follow-up, they reported remission of 36% in their intervention group and 3% in their control group [12]. This nonsurgical approach has the potential to make remission of type 2 diabetes more widely feasible without the adverse long-term effects of bariatric surgery. Since the publication of these trials, achieving remission of type 2 diabetes has been identified as a top priority by people with diabetes and their carers [13]. United Kingdom governments have recently included remission of type 2 diabetes in their long-term type 2 diabetes frameworks [14,15], and the American Diabetes Association (ADA) Standards of Medical Care has, for the first time, included guidance on prescribing very low calorie diets to improve glycaemic control and promote remission of diabetes [16]. The National Health Service (NHS) in England and Scotland are currently introducing the use of very low calorie diets for obese people with type 2 diabetes in routine clinical care [14]. The recent finding that type 2 diabetes is independently associated with increased odds of death with Coronavirus Disease 2019 (COVID-19) may further accelerate interest in achieving remission of type 2 diabetes [17].
Although remission of type 2 diabetes has been observed in trial settings and following bariatric surgery, it is unclear how common remission is in normal care. Estimating prevalence of type 2 diabetes remission is needed to inform allocation of resources and creation of new clinical pathways to support this group of people to stay in remission. Prevalence estimates also provide context for clinical decision-making, for example, identifying groups for whom remission is most likely to be achievable in order to target limited resources for intensive lifestyle management. Additionally, evaluating the impact of new clinical pathways to support remission of type 2 diabetes requires understanding of patterns of remission prior to introduction of new services.
Our aims…
Epidemiology of type 2 diabetes remission in Scotland in 2019: A cross-sectional