This large-scale longitudinal study showed that men who had remission of overweight between 7 and 13 years of age and had subsequently maintained a normal weight in early adulthood had a risk of type 2 diabetes similar to that among men with normal weights at all of these ages. Men who had had remission of overweight between 13 years of age and early adulthood had a risk of type 2 diabetes that was higher than that among men who had never been overweight but lower than that among men who had been overweight at all the ages examined.

Thus, our data showed that in this study population, men who had been overweight in childhood had a lower risk of type 2 diabetes if they had had remission of overweight before puberty (i.e., before 13 years of age). Remission of overweight after that age but before early adulthood was associated with a risk of type 2 diabetes that was markedly lower than that among men who had been overweight at every age. Overweight around puberty and early adulthood was associated with higher risks of type 2 diabetes than was overweight only in early adulthood. Since overweight during puberty appears to be a particularly important factor involved in increasing the risk of type 2 diabetes in middle and late adulthood, normalization of BMI before these ages may reduce this risk.

The results of our study documenting changes in BMI throughout puberty based on measured weights and heights are supported by other studies, but direct comparisons are difficult.4,5 Two other studies defined patterns of overweight during childhood and at two other ages.4,5 However, one study included only women,4 and the other lacked power to estimate associations with sufficient reliability.5 Neither study examined risks beyond 58 years of age.4,5 Those studies may have had bias due to the use of information reported by the participants and due to the use of overweight patterns that included adult BMI values measured close in time to the diagnosis of type 2 diabetes.4,5 Other studies investigating whether child or adult BMI was a more important factor influencing the risk of type 2 diabetes in midlife have generally concluded that adult BMI matters more; however, those studies did not examine the effects of remission of overweight or obesity.22-25 Thus, it has been unclear whether remission of overweight before puberty, a period suitable for preventive interventions in schools, could alter the positive association between childhood overweight and type 2 diabetes.

We found that men who had been obese at 7 years of age but only overweight in early adulthood had a risk of type 2 diabetes that was 3.5 times as high as that in men who had had stable BMIs in the 25th to 49th percentiles. Similarly, in a study involving a British cohort, remission of obesity between childhood (7 to 16 years of age) and adulthood (23 to 45 years of age) was associated with a risk of type 2 diabetes that was 5 times as high as that among persons who had never been obese.8 In contrast, studies of remission of obesity between 4 to 19 years of age and adulthood have shown a nonsignificant difference in the risk of type 2 diabetes (relative risk, 1.3 [95% CI, 0.4 to 4.1]6; odds ratio, 1.4 [95% CI, 0.7 to 2.8]7). Conversely, we found that an increase in BMI between 7 years and early adulthood increased the risk of type 2 diabetes. Within adult BMI groups, the risk tended to be higher among men who had had a lower BMI at 7 years of age than among men in whom the BMI had remained stable, which suggested that size and weight-gain patterns matter. Our results are in accord with studies that have shown that extreme weight gains from early infancy onward increase the risk of type 2 diabetes.26,27

We observed that men who had been obese during childhood but had had subsequent remission of obesity and had been overweight as young men had a considerably lower risk of type 2 diabetes than did persistently obese men. Furthermore, if the men had a normal weight by early adulthood, their risk of type 2 diabetes was similar to that among men who had had stable BMIs in the 25th to 49th percentiles. Our results show a graded and reversible effect of child overweight and obesity and indicate that patterns of increases in BMI matter, findings that support increased vigilance in men with large increases in BMI from childhood onward to mitigate the risk of type 2 diabetes.

Although the inverse association between socioeconomic status and the risk of type 2 diabetes in adult life has been well established,11,12 previous studies of remission of overweight and type 2 diabetes did not examine potential interactions.4-8 Our results apply to all levels of cognitive ability and socioeconomic status, since we did not find interactions with intelligence-test scores or education. Moreover, despite strong inverse associations between indicators of socioeconomic status and type 2 diabetes, which has also been reported in other studies,6 our results suggest that overweight increases the risk of type 2 diabetes through pathways that are unrelated to intelligence or education, since adjustment for these factors only minimally changed our results.

It is biologically plausible that excess weight in childhood leads to type 2 diabetes through the early development of insulin resistance.28 Unsurprisingly, we found stronger associations between patterns of overweight and type 2 diabetes that was diagnosed at 30 to 60 years of age than between patterns of overweight and type 2 diabetes that was diagnosed in late adulthood (>60 to 76 years of age). This difference is probably attributable to a decrease in the correlation between child BMI and adult BMI as adult age increases.29 Moreover, aging processes may outweigh the effects of BMI on the risk of type 2 diabetes at older ages.

Our study has several strengths, including the large sample size and mandatory examinations with weight and height measured at all ages, which limited the potential for information biases associated with recall of childhood body size.30 In addition, the men were followed until ages at which the incidence of type 2 diabetes is high and for more than 18 years longer than in previous studies.4-8

Our study has certain limitations. Although midlife and later-life factors are important in the underlying causes of type 2 diabetes,31 information on later-life BMI was unavailable; however, it may be a mediator rather than a confounder. Information on potential early-life explanatory factors, such as pubertal timing and parental social class, was not available. We do not have information available about what caused the weight changes and cannot preclude that it was disease-driven weight loss; however, such weight loss is very rare at these ages. Although the analysis of missing data showed some significant differences between the men who were included in our analysis and those for whom data were missing (Table S10 in the Supplementary Appendix), the absolute differences were small and were probably due to procedural factors rather than to selection bias.15

The fact that we used registry-based information on type 2 diabetes means that patients who were treated exclusively in primary care and persons who had not received a diagnosis were not included in our study. Whereas the completeness of the National Patient Register over a 5-year period is moderate (sensitivity, 64%), the positive predictive value of a diabetes diagnosis is very high (97%).32 In the context of the Danish system, the long study period increases the likelihood of capturing cases, since most persons with type 2 diabetes eventually appear in the hospital register. However, the recorded age at diagnosis may be delayed to an unknown degree, because the age at the first hospital admission is used as a proxy for the age at onset. Moreover, BMI is a proxy for adiposity,33 so we do not know whether the changes in the risk of type 2 diabetes are due to changes in lean mass or fat mass. Furthermore, we had no pertinent anthropometric data on women. However, two smaller studies showed no differences according to sex in associations between overweight patterns from childhood through adulthood and the risk of type 2 diabetes.5,7 Whether there are sex-related differences in the risk of type 2 diabetes after changes in weight status during childhood and adolescence remains to be investigated.

In Denmark, it is legally required that all young men be examined for conscription when they turn 18 years of age.15 Hence, our results are representative of Danish men born during the study period. Contemporary populations who are exposed to more obesogenic environments have a higher prevalence of overweight than our study population, and remission rates may be lower.34 Nonetheless, because the associations we found between patterns of overweight and the risk of type 2 diabetes were strong and applied to all men regardless of their cognitive abilities or educational levels, it is likely that our results apply to contemporary children with overweight who have remission of overweight before early adulthood.

Our results suggest that the adverse effects of childhood overweight at 7 years of age on the risk of type 2 diabetes are reduced by remission of overweight before puberty and maintenance of a normal weight until early adulthood, whereas the adverse effects of obesity at 7 years of age or overweight at 13 years of age are only partly reversible. Moreover, overweight during the period spanning puberty, from 13 years of age to early adulthood, irrespective of overweight at 7 years, is associated with a higher risk of type 2 diabetes than is development of overweight by early adulthood.