The occurrence of diabetes mellitus at the population level is usually presented as the percentage over a wide age range; for instance, the International Diabetes Federation (IDF) global diabetes atlas uses the age range of 20–70 years1. The most recent IDF estimate predicts that >600 million people will have diabetes mellitus worldwide by 2040 (REF. 1). Although the number and age-adjusted prev- alence estimated for each country is useful for some purposes, these estimates are, for most countries, extrapolations and are not based on real data. In addition, as the onset of type 2 diabetes mellitus (T2DM) is strongly age- dependent, a single point-prevalence estimate covering a wide age range does not provide adequate information about the disease risk within a population.
The prevalence of a disease that is not fatal at onset and affects an individual for a long time (for example, diabetes mellitus) parallels the cumulative number of incident cases at any age. A problem with diabetes mellitus is excess mortality, and therefore the prevalence at old age will not reflect the whole truth about the lifetime risk of developing the disease. The abil- ity to calculate the cumulative risk of develop- ing a disease during an individual’s remaining lifespan (lifetime risk) is highly relevant for epi- demiology and for planning of public-directed care and prevention programmes2–4. In spite of the high and increasing global prevalence of T2DM, which is even higher for prediabetes
competing risk of death. At baseline, partici- pants were stratified for various analyses as follows: those who did not have diabetes mel- litus were included to calculate the lifetime risk of diabetes mellitus (n = 8,844); those free of insulin use were included to calculate life- time risk of insulin use (n = 9,887); indi viduals with prediabetes mellitus were included to study progression to T2DM (n = 1,382); and individuals with T2DM but who did not use insulin were included to study progression to insulin use (n = 1,043).
Participants were followed up at ~4-year intervals from the date of the baseline visit onwards between 1997 and 2012. Cases of prediabetes mellitus and T2DM were veri- fied at baseline and during follow-up visits by use of medical records, blood glucose meas- urements and other documents. Modified WHO guidelines7 were used to define T2DM, prediabetes mellitus and normoglycaemia
(TABLE 1). Diagnoses of prediabetes mellitus and T2DM were verified by study physicians;
however, how possible type 1 diabetes mellitus was excluded by the investigators is unclear.
As no oral glucose tolerance test was carried out, individuals with prediabetes mellitus and T2DM who had elevated post-challenge levels of glucose alone were not identified. According to European data8, half of people with pre- diabetes mellitus and one-fifth of people with T2DM are detected by post-challenge glucose levels alone. The use of nonfasting glucose lev- els might also have led to misclassifications if the time of the last meal was not considered.
Consequently, the lifetime risks presented by Ligthart et al. are certainly underestimates2.
Ligthart and colleagues found that the prev- alence of prediabetes mellitus and T2DM was higher in men than in women and increased mellitus, very few studies have been con-
ducted to estimate the lifetime risk of T2DM, and those that have been carried out are often inadequately structured4–6.
Filling this gap with proper prospective studies that have complete data on different stages of impaired glucose metabolism ranging from prediabetes mellitus to diabetes mellitus, and progression of T2DM to a requirement for insulin therapy is, therefore, important. Such studies will help in estimating the burden of dysglycaemia in the context of overall survival.
The study by Ligthart et al.2, which assessed the lifetime risk of prediabetes mellitus, T2DM and insulin use among 10,050 individ- uals aged ≥45 years living in the Netherlands is one such study. The investigators calcu- lated mortality and the incidence of T2DM during each year of follow-up, adjusting for E P I D E M I O LO G Y
Lifetime risk of diabetes mellitus — how high?
Jaakko Tuomilehto and Suhad Bahijri
Studies on lifetime risk of the range of glucose impairments are scarce.
A new study by Ligthart and colleagues reports that half of all people who initially have normal blood levels of glucose eventually develop prediabetes mellitus and most of these individuals progress to type 2 diabetes mellitus, with 9% eventually requiring insulin therapy.
Refers to Ligthart, S. et al. Lifetime risk of developing impaired glucose metabolism and eventual progression from prediabetes to type 2 diabetes: a prospective cohort study. Lancet Diabetes Endocrinol. http://dx.doi.org/10.1016/
S2213-8587(15)00362-9
Table 1 | Adopted definition of normoglycaemia, prediabetes mellitus and T2DM*
Definition Fasting blood glucose
level (mmol/l) Nonfasting blood
glucose level (mmol/l) Age (mean ± SD) Normoglycaemia (n = 7,462,
74% of total; 59% women) ≤6.0 NA 64.4 ± 9.8
Prediabetes mellitus (n = 1,382, 14% of total;
51% women)
>6.0 to <7.0 >7.7 to <11.1 66.6 ± 9.4
T2DM (n = 1,206, 12% of total;
48% women) >7.0 or use of glucose-
lowering drugs‡ >11.1 or use of glucose-
lowering drugs‡ 67.5 ± 9.6
*In the study population at baseline; information derived from Ligthart, S. et al.2‡Based on interviews and pharmacy dispensing records. NA, not applicable.
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with age. Individuals with prediabetes mel- litus and T2DM had a higher BMI and a more unfavourable lipid profile than individuals with normoglycaemia. People with T2DM were more likely to be smokers and have cardiovascular disease than individuals with normoglycaemia.
The lifetime risk estimates, which reflect the remaining risk at the index age (at baseline) to the age of last observation were calculated for index ages 45, 55, 65, 75 and 85 years by use of a modified version of survival ana lysis that takes the competing event of death into account. In individuals with normoglycae- mia at baseline, the incidence of prediabetes mellitus and mortality per 1,000 person-years was 20.4 (95% CI 19.3–21.6) and 23.9 (95%
CI 22.7–25.2), respectively. Among individuals who did not have diabetes mellitus at baseline, the incidence of diabetes mellitus was 11.9 (95% CI 11.1–12.7) and the death rate was 24.5 (95% CI 23.4–25.7). In people with T2DM not using insulin at baseline, the incidence of new insulin use was 3.4 (95% CI 3.0–3.9).
Taking all factors into account, Ligthart and colleagues calculated that almost half of indi- viduals aged 45 years with normoglycaemia will develop prediabetes mellitus during their lifespan (remaining lifetime risk), and almost one-third of these will eventually develop T2DM, with 9.1% requiring insulin use2.
Increasing baseline age, BMI and waist cir- cumference increased the risk of developing prediabetes mellitus or T2DM, but not of insu- lin use. Obesity reduced the number of years lived with normal glucose metabolism. Among individuals with prediabetes mellitus at base- line, T2DM incidence and mortality per 1,000 person-years was 43.0 (95% CI 39.2–47.2) and 26.0 (95% CI 23.0–29.3), respectively, and the lifetime risk of individuals aged 45 years with prediabetes mellitus progressing to T2DM was 74.0% (95% CI 67.6–80.5). In individuals with T2DM who had never been treated with insulin at baseline, the incidence rate of insulin use was 24.0 (95% CI 20.8–27.7) and the lifetime risk for individuals aged 45 years with T2DM to start insulin treatment was 49.1% (95% 38.2–60.0).
To compare lifetime risks with absolute risks in a shorter time period, the 10-year risks for prediabetes mellitus, T2DM and insulin use were also calculated. In individuals aged 45 years at baseline, 8.4% (95% CI 5.4–11.4) with normal glucose levels developed pre- diabetes mellitus, 3.4% (95% CI 2.1–4.8) developed T2DM and 0.5% (0.0–1.0) started insulin therapy.
Even though the study of Ligthart et al.
has limitations inherent to long-term cohort studies, it provides much needed information in a poorly researched area and raises alarm regarding the high lifetime risk of middle-aged adults with normoglycemia developing T2DM and the even higher risk among individuals with prediabetes mellitus. Prediabetes mellitus is usually undetected in any population but, unlike diabetes mellitus, can be reversed or the progression to T2DM postponed if adequately managed9. Without preventive intervention, the 10-year risk of T2DM among individuals with prediabetes is ~50%10.
Without preventive intervention, the 10‑year risk of T2DM among individuals with prediabetes is ~50%
Jaakko Tuomilehtois at the Center for Vascular Prevention, Danube University Krems, Dr Karl Dorrek Strasse, 30, 3500 Krems, Austria;Dasman Diabetes Institute, Al‑Soor Street, Dasman 15462, Kuwait;
Chronic Disease Prevention Unit, National Institute for Health and Welfare, Mannerheimintie 166, 00271 Helsinki, Finland; and at Saudi Diabetes Research Group, King Fahd Medical Research Center, King Abdulaziz University, PO Box 80200, Jeddah 21589, Saudi Arabia.
Suhad Bahijri is at the Saudi Diabetes Research Group, King Fahd Medical Research Center, King Abdulaziz University, PO Box 80200, Jeddah 21589, Saudi Arabia.
Correspondence to J.T.
jaakko.tuomilehto@donau‑uni.ac.at doi:10.1038/nrendo.2015.227
Published online 4 Jan 2016 1. International Diabetes Federation. IDF diabetes atlas: 7th edition. [online], http://www.diabetesatlas.org/ (2015).
2. Ligthart, S. et al. Lifetime risk of developing impaired glucose metabolism and eventual progression from prediabetes to type 2 diabetes: a prospective cohort study. Lancet Diabetes Endocrinol. http://dx.doi.org/
10.1016/S2213‑8587(15)00362‑9 (2015).
3. Lloyd‑Jones, D. M., Larson, M. G., Beiser, A. &
Levy, D. Lifetime risk of developing coronary heart disease. Lancet 353, 89–92 (1999).
4. Feuer, E. J. et al. The lifetime risk of developing breast cancer. J. Natl Cancer Inst. 85, 892–897 (1993).
5. Narayan, K. M. et al. Lifetime risk for diabetes mellitus in the United States. JAMA 290, 1884–1890 (2003).
6. Gregg, E. W. et al. Trends in lifetime risk and years of life lost due to diabetes in the USA, 1985–2011:
a modelling study. Lancet Diabetes Endocrinol. 2, 867–874 (2014).
7. Magliano, D. J. et al. Lifetime risk and projected population prevalence of diabetes. Diabetologia 51, 2179–2186 (2008).
8. World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia.
[online], http://www.who.int/diabetes/publications/
Definition%20and%20diagnosis%20of%20diabetes_
new.pdf (2006).
9. Paulweber, B. et al. A European evidence‑based guideline for the prevention of type 2 diabetes.
Horm. Metab. Res. 42, S3–S36 (2010).
10. Lindström, J. et al. Improved lifestyle and decreased diabetes risk over 13 years: long‑term follow‑up of the randomised Finnish Diabetes Prevention Study (DPS).
Diabetologia 56, 284–293 (2013).
Competing interests statement The authors declare no competing interests.
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