Articles
Lifetime risk of developing impaired glucose metabolism and eventual progression from prediabetes to type 2 diabetes: a prospective cohort study

https://doi.org/10.1016/S2213-8587(15)00362-9Get rights and content

Summary

Background

Data are scarce for the lifetime risk of developing impaired glucose metabolism, including prediabetes, as are data for the risk of eventual progression from prediabetes to diabetes and for initiation of insulin treatment in previously untreated patients with diabetes. We aimed to calculate the lifetime risk of the full range of glucose impairments, from normoglycaemia to prediabetes, type 2 diabetes, and eventual insulin use.

Methods

In this prospective population-based cohort analysis, we used data from the population-based Rotterdam Study. We identified diagnostic events by use of general practitioners' records, hospital discharge letters, pharmacy dispensing data, and serum fasting glucose measurements taken at the study centre (Rotterdam, Netherlands) visits. Normoglycaemia, prediabetes, and diabetes were defined on the basis of WHO criteria for fasting glucose (normoglycaemia: ≤6·0 mmol/L; prediabetes: >6·0 mmol/L and <7·0 mmol/L; and diabetes ≥7·0 mmol/L or use of glucose-lowering drug). We calculated lifetime risk using a modified version of survival analysis adjusted for the competing risk of death. We also estimated the lifetime risk of progression from prediabetes to overt diabetes and from diabetes free of insulin treatment to insulin use. Additionally, we calculated years lived with healthy glucose metabolism.

Findings

We used data from 10 050 participants from the Rotterdam Study. During a follow-up of up to 14·7 years (between April 1, 1997, and Jan 1, 2012), 1148 participants developed prediabetes, 828 developed diabetes, and 237 started insulin treatment. At age 45 years, the remaining lifetime risk was 48·7% (95% CI 46·2–51·3) for prediabetes, 31·3% (29·3–33·3) for diabetes, and 9·1% (7·8–10·3) for insulin use. In individuals aged 45 years, the lifetime risk to progress from prediabetes to diabetes was 74·0% (95% CI 67·6–80·5), and 49·1% (38·2–60·0) of the individuals with overt diabetes at this age started insulin treatment. The lifetime risks attenuated with advancing age, but increased with increasing BMI and waist circumference. On average, individuals with severe obesity lived 10 fewer years without glucose impairment compared with normal-weight individuals.

Interpretation

Impaired glucose metabolism is a substantial burden on population health, and our findings emphasise the need for more effective prevention strategies, which should be implemented as soon in a person's life as possible. The substantial lifetime risk of prediabetes and diabetes in lean individuals also supports risk factor control in non-obese individuals.

Funding

Erasmus MC and Erasmus University Rotterdam; Netherlands Organisation for Scientific Research; Netherlands Organisation for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomics Initiative; Netherlands Ministry of Education, Culture and Science; Netherlands Ministry of Health, Welfare and Sports; European Commission; and Municipality of Rotterdam.

Introduction

People with blood glucose concentrations that are raised but below the threshold for type 2 diabetes (ie, people with prediabetes) have an excess risk of diabetes.1, 2, 3 Today, more than 382 million people live with diabetes worldwide and, because of the increasing prevalence of prediabetes and the rapid conversion of prediabetes to type 2 diabetes, the number is predicted to exceed half a billion by 2035.4 Moreover, many patients with diabetes are unable to achieve glycaemic control goals through diet and oral drugs alone, ultimately requiring insulin treatment.5, 6, 7 Previous estimates of the progression from prediabetes to diabetes and ultimately to the need for insulin treatment are scarce and have been limited to annual incidences and absolute risks within a short time period.2

Lifetime risk provides an estimate of the cumulative risk of developing a disease during an individual's remaining lifespan, which is relevant for patients, clinicians, and health-care policy makers.8, 9, 10 A few studies have provided estimates of the lifetime risk of type 2 diabetes in the USA and Australia.10, 11, 12 However, lifetime risk estimates based on accurate and careful documentation of raised blood glucose concentrations, diabetes diagnosis, and diabetes drug use are scarce. Prospective population-based cohort studies with long-term follow-up and detailed data for the full range of impaired glucose metabolism including prediabetes, diabetes, and the eventual need for insulin treatment, allow the estimation of the burden of increased blood glucose concentrations in the context of overall survival.

Research in context

Evidence before this study

Lifetime risk estimates provide the cumulative risk of developing a disease during an individual's remaining lifespan. Previously, lifetime risk estimates have only been reported for overt type 2 diabetes on the basis of questionnaire data and not directly from a population with a long follow-up. Progression rates from prediabetes to diabetes have mostly been estimated for 10 years and not for the rest of an individual's remaining lifespan. So far, no previous study has included the direct calculation of the lifetime risks of developing the full range of impaired states of glucose metabolism by use of empirical data from a prospective population-based cohort study.

Added value of this study

Our findings showed that, in a well defined European population with long-term follow-up, half the normoglycaemic population eventually developed prediabetes, and most individuals with prediabetes eventually progress to overt type 2 diabetes. Furthermore, the lifetime risk to use insulin treatment for an individual aged 45 years not using insulin was 9%, suggesting that a high proportion of our population eventually uses insulin. Obesity substantially increased the lifetime risk of developing diabetes and attenuated the number of life-years lived with a healthy glucose metabolism. However, lean individuals also had a substantial lifetime risk of diabetes.

Implications of all the available evidence

The burden that impaired glucose metabolism exerts on the population is substantial and effective prevention strategies should be implemented as soon in a person's life as possible. The substantial lifetime risks of prediabetes and diabetes in lean individuals also support the implementation of risk factor control in non-obese individuals. Furthermore, the large proportion of individuals that will eventually use insulin treatments reflects the high health-care burden of type 2 diabetes.

In this long-term follow-up study, we used mortality rates and incidences of disease during every year of life, taking into account the competing risk of death, to assess the lifetime risk of prediabetes, diabetes, and insulin use in a large prospective population-based cohort study of individuals aged 45 years and older. Additionally, we estimated the lifetime risk of individuals with prediabetes eventually developing diabetes and for patients with diabetes ultimately progressing to insulin use.

Section snippets

Study design and population

This study is embedded within the framework of the Rotterdam Study, a prospective cohort study of the community-dwelling population aged 45 years and older in Rotterdam, Netherlands. The study design of the Rotterdam Study has been described in detail previously.13 Briefly, in 1990 all inhabitants of a well defined district of Rotterdam were invited to participate, of whom 7983 (78%) agreed to participate. The study was extended in 2000, with a second cohort of individuals who had reached the

Results

We used data from 10 050 participants of the Rotterdam Study. The mean age of the population was 65·2 years (SD 9·8) and 5685 (57%) participants were women. Of the 10 050 participants at baseline, 7462 (74%) had normoglycaemia, 1382 (14%) had prediabetes, and 1206 (12%) had diabetes (table 1). At baseline, prevalences of prediabetes and type 2 diabetes increased with advancing age in both men and women and were higher in men than in women (appendix p 7). Individuals with prediabetes and

Discussion

Our data suggest that the lifetime risk of developing prediabetes for a normoglycaemic individual aged 45 years is one in two, and one in three non-diabetic individuals aged 45 years will develop diabetes. Three-quarters of individuals with prediabetes at age 45 years will eventually progress to diabetes, and half of the patients with diabetes at the same age will start insulin treatment. Furthermore, obesity substantially affects the risk of progressing from prediabetes to diabetes and

References (32)

  • KMV Narayan et al.

    Lifetime risk for diabetes mellitus in the United States

    JAMA

    (2003)
  • DJ Magliano et al.

    Lifetime risk and projected population prevalence of diabetes

    Diabetologia

    (2008)
  • A Hofman et al.

    The Rotterdam Study: 2014 objectives and design update

    Eur J Epidemiol

    (2013)
  • MJG Leening et al.

    Methods of data collection and definitions of cardiac outcomes in the Rotterdam Study

    Eur J Epidemiol

    (2012)
  • Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation

    (2006)
  • Waist circumference and waist-hip ratio

  • Cited by (0)

    Contributed equally

    View full text