Article Text
PDF
Abstract
Background Few studies have examined the impact of weight change in different periods of lifetime on type 2 diabetes risk, and the association of weight loss with type 2 diabetes is unclear. We prospectively investigated the association of weight change since age 20 y and that during middle-to-late adulthood with the incidence of type 2 diabetes.
Methods Subjects were 52 014 men and women aged 45–75 y who participated in the Japan Public Health Center-Based Prospective Study and had no history of diabetes. ORs of self-reported physician-diagnosed type 2 diabetes for weight change between age 20 y and baseline survey (mean age 50.6 y) and during 5 y between baseline and second surveys were estimated using logistic regression analysis.
Results During the 5-year period following 5-year survey, 989 newly diagnosed cases of type 2 diabetes were self-reported. Weight gain from age 20 y was associated with an increased risk of type 2 diabetes. The multivariate-adjusted OR (95% CI) for a weight gain of ≥5 kg versus a stable weight were 2.61 (2.11 to 3.23) in men and 2.56 (1.95 to 3.35) in women. A weight gain of ≥5 kg over the 5-y following the baseline survey was also associated with an increased risk in women. No association with weight loss was observed for either period.
Conclusions These results suggest that long-term weight gain from early adulthood to middle-age increases risk of type 2 diabetes in men and women and that risk is further enhanced by weight gain in later life in women.
- Body weight changes
- cohort studies
- diabetes mellitus
- Japan
- diabetes DI
Statistics from Altmetric.com
Introduction
The worldwide incidence of type 2 diabetes has been increasing due to changes in lifestyle, including decreased physical activity and increased high-calorie food intake.1 Obesity is a known risk factor and the strongest predictor of type 2 diabetes with reports showing a 10-fold increased risk of diabetes in individuals with a high body mass index (BMI) over those with a low BMI.2 Studies conducted on Japanese populations, which have prevalence of type 2 diabetes similar to that of Western populations3 despite a relatively thin body structure,4 have observed a clear dose-response relation between BMI and risk of type 2 diabetes.5 Therefore, weight control is crucial in the prevention of type 2 diabetes.
In addition to sufficient evidence linking type 2 diabetes to obesity assessed at single time points, several studies have reported on the significant role of weight gain in early6–9 and middle-to-late adulthood8 10–14 in the development of type 2 diabetes. Thus far, the impact of weight gain during young adult has been reported to have a stronger impact on risk of type 2 diabetes compared to later periods in adult life in some studies.8 15–17 However, of these four studies, two were of cross-sectional or retrospective design,15 16 two included men only8 16 and only one was conducted among a Japanese population.16 Further, data regarding the impact of weight loss on risk of type 2 diabetes are conflicting. For example, while several studies have reported an association between decreased risk of type 2 diabetes and weight loss in early6 and middle-to-late adulthood,8 13 14 other studies have found no association in either period.7–12 18 19 Therefore, the benefit of weight loss on the prevention of type 2 diabetes in healthy individuals remains elusive.
To assess the role of weight change at different periods of life on the development of type 2 diabetes, we investigated the relation between weight change from age 20 y and during middle-to-late adulthood and the risk of type 2 diabetes using data from a large-scale population-based cohort study in Japan.
Methods
Study population
The Japan Public Health Center-based Prospective (JPHC) Study was launched in 1990 for cohort I and in 1993 for cohort II.20 The participants were residents of 11 public health centres who were aged 40–69 y old at each baseline survey. Study participants were informed about the objectives of the study and those who responded to the survey questionnaire were regarded as consenting to participate in the study. A questionnaire survey was conducted at baseline and at 5- and 10-y follow-up. Information on medical history and health-related lifestyles, smoking, drinking and dietary habits was obtained in each survey. The study was approved by the Institutional Review Board of the National Cancer Center of Japan.
Of the 140 160 eligible subjects, 113 403 (80.9%) responded to the questionnaire survey at baseline. Of these respondents, 77 540 (68.4%) responded to both the 5 and 10-y follow-up surveys. We excluded 13 872 subjects who met one or more of the following criteria: history of type 2 diabetes; history of cancer, cerebrovascular disease, myocardial infarction, chronic liver disease, or renal disease at baseline and 5-y survey; and BMI of either <14 kg/m2 or ≥40 kg/m2 or with information regarding weight or height missing from the baseline or 5-y survey. After further excluding 106 subjects whose calculated weight change between baseline and 5-y survey exceeded 20 kg and another 11 548 subjects with missing information on weight change since age 20 y (cohort I) or weight at age 20 y (cohort II), 52 014 subjects (22 900 men and 29 114 women; 28 004 in cohort I and 24 010 in cohort II) remained for analysis.
Weight change
Participants completed a self-administered questionnaire at baseline and 5 and 10-y follow-up surveys, which included inquiries into height, body weight, medical history, smoking habit, alcohol consumption, frequency of physical activity, diet and other lifestyle factors. BMI was calculated as weight in kg divided by squared height in metres. In cohort I, weight change since age 20 y was looked at with three response options available (≥5 kg loss, <5 kg change or ≥5 kg gain). In cohort II, body weight at age 20 y was looked at and this information was used to calculate weight change between age 20 y and the baseline survey (mean age of participants 50.6 y), which we refer to ‘weight change during early adulthood’ in this paper. Weight change was then divided into the three categories of ≥5 kg loss, <5 kg change (stable) and ≥5 kg gain in concordance with those of cohort I. To examine potential associations at higher levels of weight change among cohort II subjects, detailed categories of weight change (≥10 kg loss, 5–9.9 kg loss, <5 kg change (stable), 5–9.9 kg gain and ≥10 kg gain) were also created. As weight changed during middle-to-late adulthood, the difference in body weight between the baseline and 5-y surveys was calculated and categorised as ≥5 kg loss, 2.5–4.9 kg loss, <2.5 kg change (stable), 2.5–4.9 kg gain and ≥5 kg gain.
Ascertainment of type 2 diabetes
Cases of type 2 diabetes newly diagnosed during the 5 y following the 5-y survey were determined based on participants' responses to a self-administered questionnaire. At the 10-y survey, study participants were asked if they had ever been diagnosed as diabetic and, if so, when the initial diagnosis was made. As the 5-y survey represented the baseline for this analysis, only subjects who were diagnosed following the 5-y survey (ie, after 1995 for cohort I and 1998 for cohort II) were regarded as incident cases during follow-up.
Details of the validation study for self-reported diabetes have been described elsewhere.21 Briefly, 94% of self-reported diabetes cases were confirmed by examination of medical records.22 On application of this data to the survey results obtained from a JPHC subpopulation (health check-up attendants) whose plasma glucose data were available for assessment, the sensitivity and specificity of self-reported diabetes were estimated to be 82.6% and 99.7%, respectively.
Statistical analyses
Logistic regression analysis was used to assess the association between weight change and incidence of type 2 diabetes. The OR and 95% CI of newly diagnosed type 2 diabetes were estimated for each weight change category with the group of individuals with stable weight (weight change since 20 y: <5 kg; weight change during middle-to-late adulthood: <2.5 kg) acting as the reference. For multivariate analysis, an indicator variable for missing data was created for each covariate. The first model was adjusted for age (year, continuous) and study area (11 areas) only, while the multivariate model was further adjusted for smoking habit (lifetime non-smoker, former smoker or current smoker with a consumption of <20 or ≥20 cigarettes/day), alcohol consumption (non-drinker, occasional drinker or drinker with a consumption of <150, 150–299, 300–449 or ≥450 g ethanol/day for men or a consumption of <150 or ≥150 g ethanol/day for women), frequency of leisure-time physical activity (less than once/month, 1–3 times/month or more than once/week), history of hypertension (yes or no), family history of diabetes mellitus (yes or no) and coffee consumption (almost never, <1 cup/day, 1 cup/day or ≥2 cups/day). Weight change during early adulthood (≥5 kg loss, <5 kg change or ≥5 kg gain) and BMI at the baseline survey (<21, 21–22.9, 23–24.9, 25–26.9 or ≥27 kg/m2) were further adjusted for when assessing the association between weight change during middle-to-late adulthood and type 2 diabetes. Weight change during middle-to-late adulthood (≥5 kg loss, 2.5–4.9 kg loss, <2.5 kg change, 2.5–4.9 kg gain or ≥5 kg gain) was additionally adjusted for in the analysis of the association between weight change during early adulthood and type 2 diabetes. Using cohort II data, which included information on body weight at age 20 y, we conducted a sensitivity analysis by further adding BMI at age 20 y (<21, 21–22.9, 23–24.9, 25–26.9 or ≥27 kg/m2) to the model. Trend association was assessed by assigning ordinal numbers to the categories of weight change. We also conducted an analysis stratified by BMI at the baseline survey (<22 kg/m2 (underweight), 22–24.9 kg/m2 (normal weight) and ≥25 kg/m2 (overweight)), age (<55 y and ≥55 y) or smoking status (non-smoker and smoker). An interaction term of weight change and the above stratifying variables was created and added in the model to assess a statistical interaction. Two-side p values less than 0.05 were regarded as statistically significant. All analyses were conducted using SAS V9.1.
Results
Table 1 shows the characteristics of the study population at the 5-y survey, the start of the observation period for type 2 diabetes, stratified according to weight change. More than half of surveyed subjects (52.4% of men and 54.6% of women) gained ≥5 kg during early adulthood (over 30 y). Both men and women who gained a large amount of weight since age 20 y tended to be younger and physically active in their leisure time and tended to have a history of hypertension and family history of diabetes compared to those who lost weight. Men who had lost weight during early adulthood were more likely to be current smokers.
Characteristics at 5-year survey according to weight change*
During the 5-y period between the baseline and 5-y surveys, nearly two-thirds of men and women experienced a slight weight change (<2.5 kg change). Both men and women who gained weight during this period were on average younger, consumed coffee more frequently, were less likely to report a history of hypertension and had a lower baseline BMI survey compared to those who lost weight. Men who gained weight in middle-to-late adulthood were more likely to be a past smoker whereas those who lost weight were more likely to be a current smoker.
During the 5-y period between the 5 and 10-y surveys, we identified 989 new cases (578 men and 411 women) of type 2 diabetes. Table 2 shows the association of weight change from age 20 y to the baseline survey (over 30 y) with incidence of type 2 diabetes. Weight gain during this period was associated with a significantly increased risk of type 2 diabetes in both men and women. The multivariate-adjusted ORs of type 2 diabetes for a weight gain of ≥5 kg versus stable weight were 2.61 (95% CI 2.11 to 3.23) in men and 2.56 (95% CI 1.95 to 3.35) in women. In contrast, no significant association was observed between weight loss since age 20 y and risk of type 2 diabetes in both men and women. We repeated the above analysis using the more detailed categories of weight change in cohort II. Both men and women in the category of the greatest weight gain were found to have the highest risk of type 2 diabetes; the multivariate-adjusted ORs of type 2 diabetes for a weight gain of ≥10 kg versus stable weight (<5 kg change) were 3.87 (95% CI 2.77 to 5.40) in men and 3.64 (95% CI 2.50 to 5.29) in women. Further, a weight gain of 5–9.9 kg was associated with a significantly increased risk in men (OR 1.50, 95% CI 1.01 to 2.22), but not in women.
Association between weight change from age 20 to baseline survey (mean age 50.6 years) and risk of type 2 diabetes
Table 3 shows the ORs of type 2 diabetes according to weight change over 5 y in middle-to-late adulthood. In women, both weight loss and gain were associated with an increased risk of type 2 diabetes in the age- and area-adjusted model. However, the association with weight loss was considerably attenuated after adjustment for covariates, whereas the increased risk associated with a weight gain of ≥5 kg remained statistically significant (vs <2.5 kg change OR 1.79, 95% CI 1.28 to 2.52). In an analysis stratified by BMI level at the baseline survey, overweight women had an increased risk of type 2 diabetes compared to non-overweight women, and this risk was further enhanced by weight gain during the subsequent 5-y period. p Value for interaction between the 5-y weight change and baseline BMI was 0.06, and that between the 5-y weight change and age was 0.81. Among men, neither weight gain nor loss in this period was associated with risk of type 2 diabetes, and no indication of effect modification by age (p for interaction=0.25) or baseline BMI levels (p for interaction=0.45) was observed. In the analysis by smoking, the risk of type 2 diabetes tended to increase with increasing levels of weight gain among non-smokers, whereas it tended to decrease among current smokers (p for interaction=0.11; table 3), although none of the ORs was statistically significant in either group. When we repeated the above analyses among subjects with complete information available for all covariates (n=46 344), similar results were obtained.
Association between weight change over 5 y during middle-to-late adulthood* with risk of type 2 diabetes
Discussion
In this large-scale population-based prospective study conducted in Japanese men and women, we observed increased incidence of type 2 diabetes associated with weight gain from age 20 y to the baseline survey (over 30 y) in both men and women. Further, weight gain over a 5-y period during middle-to-late adulthood was associated with an increased risk of type 2 diabetes in women but not in men. Weight loss during either period was not associated with a decreased risk of type 2 diabetes, even among subjects with an elevated BMI at the beginning of the weight change measurement period.
Our present finding of an increased risk of type 2 diabetes associated with weight gain during early adulthood is consistent with results of several cohort studies,6–9 despite variation among the studies in the strength of the association as well as the minimum weight gain that showed a significant increase in risk. In the present study (cohort II), a weight gain ≥10 kg versus maintenance of a stable weight (<5 kg change) from age 20 to age 51.4 y (mean age) was associated with 3.9-fold and 3.6-fold increased risk of developing type 2 diabetes for men and women, respectively. In the Nurses' Health Study,6 RR of type 2 diabetes for a weight gain of 11–20 kg from age 18 y to the baseline (aged 30–55 y) versus maintenance of a stable weight (<5 kg change) was 5.5 (95% CI 4.7 to 6.3). In the Health Professionals Follow-up Study,8 the RR for a weight gain of 12–18 kg from age 21–53.3 y (mean age) versus maintenance of a stable weight (<2 kg change) was 3.0 (95% CI 1.8 to 5.2). In both of these studies, a markedly large weight gain (≥20 kg in the former or ≥19 kg in the latter study) was shown to be associated with a 10-fold increased risk of type 2 diabetes. With regard to threshold values observed in the present study, the minimum weight gain found to induce a significant increase in risk of type 2 diabetes was 5 kg (OR, 1.5) for men and 10 kg (OR, 3.6) for women. Previous studies have observed a significant 1.8-fold and 1.9-fold increase in risk with weight gain of ≥3 kg8 and ≥5 kg,6 respectively. Considering these data, we could conclude that a ≥5 kg gain between early adulthood and middle-age confer 1.5-fold or greater risk of type 2 diabetes in later life.
Among women in the present study, a weight gain of ≥5 kg during the 5-y interval observed in middle-to-late adulthood was associated with an increased risk of type 2 diabetes—a finding consistent with those of several previous studies.8 10–14 17 In contrast, we observed no association in men. In the literature, there appears to be no sex difference in the consistency of the association between weight gain during middle-to-late adulthood and type 2 diabetes; a positive association has been observed in four8 11 14 17 of five studies8 11 14 17 18 among men and in two12 17 of four studies11 12 17 19 among women. In the present study population, smoking, a habit much more common in Japanese men than in Japanese women,23 may have diluted the association in men as smoking works to suppress weight gain24 but increase risk of type 2 diabetes.24 25 However, no significant association was observed among non-smoking men in the present study. Thus, other possibilities should be explored to account for the lack of an observed association in men.
Prolonged obesity has been suggested to impair insulin secretion and increase resistance to glucose uptake.26 If this activity does indeed exist, a weight increase in early adulthood may have a greater impact on the development of type 2 diabetes than one in later lifetime. However, few studies have assessed the association of type 2 diabetes with both weight changes from young-to-middle adult age and in later life.8 15–17 The previous study8 has assessed the association of type 2 diabetes with both weight change from age 21 y to the baseline (aged 40–75 y) and from baseline to 10 y later, and demonstrated a more pronounced association between risk of type 2 diabetes and weight gain from age 21 y than weight gain in later life—a finding similar to that of the present study. Several reports have evaluated the impact of weight gain over a constant length of period at various ages on type 2 diabetes risk. In a study conducted on middle-aged Japanese men,16 weight gain between age 20 and 25 y was significantly associated with an increased risk of type 2 diabetes, whereas weight gain after age 25 y was not. Two other studies have also shown that weight gain during early adulthood was more strongly associated with an increased risk of type 2 diabetes than that at later stages of adulthood.15 17 The findings from the present and previous studies emphasise the impact of weight gain during young adult ages on the pathogenesis of type 2 diabetes.26
Contrary to our expectations, type 2 diabetes risk was not decreased among people who had experienced weight loss, even those who were initially overweight, compared to those whose weight was stable during middle-to-late adulthood. This finding is in line with observations in several cohort studies10–12 18 19 but contradicts findings in other studies.8 13 14 Intervention studies have demonstrated a protective effect of weight reduction against type 2 diabetes in overweight people with impaired glucose tolerance.27 28 However, this protective effect has not been demonstrated in overweight people with no glucose abnormalities, and our present results do not support a role of weight loss in the prevention of type 2 diabetes in an otherwise apparently healthy population.
Strengths of the present study include its large sample size, the population-based prospective design, and our adjustment of known and suspected risk factors of type 2 diabetes. In addition, we excluded those subjects with serious diseases that may have caused or contributed to weight change. Several limitations to the present study warrant mention. First, the type 2 diabetes diagnosis was ascertained by a self-report. However, a validation study conducted on the study population found a fairly good agreement and, thus, this methodology may have had only a negligible or no effect on the results. Second, the use of self-reported weight and height may be of concern. However, BMI calculated using self-reported data was confirmed to be highly correlated with that obtained by actual measurements. Among study participants who provided health check-up data, which included measured height and weight (11 274 men and 21 196 women), Spearman rank correlation coefficients between self-reported and actual measured BMI were 0.89 for men and 0.90 for women. Although we have no data regarding the validity of the recalled weight at age 20 y, a previous study conducted on middle-aged Japanese people demonstrated a high correlation between recalled and actual measured weight at age 25 y.29 Third, we had no information about whether or not weight loss was intentional and were unable to test the hypothesis that intentional weight loss decreases risk of type 2 diabetes.30 Fourth, the results obtained in subgroup analysis may be due to chance and, thus, should be interpreted with caution. Finally, we observed an increased risk of type 2 diabetes associated with weight loss in women and in some subgroups of men. Although we excluded subjects with a history of type 2 diabetes at the start of follow-up, the influence of a pre-clinical diabetic state on weight change, especially weight loss, could not be ruled out, leaving a possibility that the observed association is due to a reverse causality.
In conclusion, we observed an increased incidence of type 2 diabetes associated with weight change during early adulthood (over 30 y) in both men and women. A 5-y weight gain during middle-to-late adulthood was also associated with an increased risk of type 2 diabetes in women but not in men. In the interest of preventing onset of type 2 diabetes, obesity prevention should be initiated during early adulthood and continued throughout a person's life.
What is already known on this subject
Obesity and weight gain have been linked to an increased risk of type 2 diabetes. However, few studies have addressed the impact of weight change in different periods of lifetime on type 2 diabetes risk and the association of weight loss with type 2 diabetes is unclear.
What this study adds
This study suggest that long-term weight gain from early adulthood to middle-age increases risk of type 2 diabetes in men and women, and that risk is further enhanced by weight gain in later life in women. In the interest of preventing onset of type 2 diabetes, obesity prevention should be initiated during early adulthood and continued throughout a person's life.
Acknowledgments
The authors thank all the staff members in each study area and in the central office for their painstaking efforts in conducting the baseline and follow-up research. We thank Drs Kyoko Kirii (International Medical Center of Japan) and Masayuki Kato (Japan Foundation for the Promotion of International Medical Research Cooperation) for their helpful discussions.
Appendix
Members of the Japan Public Health Center-Based Prospective Study Group (JPHC Study, principal investigator: S Tsugane) are S Tsugane, M Inoue, T Sobue and T Hanaoka, National Cancer Center, Tokyo, Japan; J Ogata, S Baba, T Mannami, A Okayama and Y Kokubo, National Cardiovascular Center, Osaka, Japan; K Miyakawa, F Saito, A Koizumi, Y Sano, I Hashimoto, T Ikuta and Y Tanaba, Iwate Prefectural Ninohe Public Health Center, Iwate, Japan; Y Miyajima, N Suzuki, S Nagasawa, Y Furusugi and N Nagai, Akita Prefectural Yokote Public Health Center, Akita, Japan; H Sanada, Y Hatayama, F Kobayashi, H Uchino, Y Shirai, T Kondo, R Sasaki, Y Watanabe, Y Miyagawa and Y Kobayashi, Nagano Prefectural Saku Public Health Center, Nagano, Japan; Y Kishimoto, E Takara, T Fukuyama, M Kinjo, M Irei and H Sakiyama, Okinawa Prefectural Chubu Public Health Center, Okinawa, Japan; K Imoto, H Yazawa, T Seo, A Seiko, F Ito, F Shoji and R Saito, Katsushika Public Health Center, Tokyo, Japan; A Murata, K Minato, K Motegi and T Fujieda, Ibaraki Prefectural Mito Public Health Center, Ibaraki, Japan; K Matsui, T Abe, M Katagiri and M Suzuki, Niigata Prefectural Kashiwazaki and Nagaoka Public Health Center, Niigata, Japan; M Doi, A Terao, Y Ishikawa and T Tagami, Kochi Prefectural Chuo-higashi Public Health Center, Kochi, Japan; H Sueta, H Doi, M Urata, N Okamoto and F Ide, Nagasaki Prefectural Kamigoto Public Health Center, Nagasaki, Japan; H Sakiyama, N Onga, H Takaesu and M Uehara, Okinawa Prefectural Miyako Public Health Center, Okinawa, Japan; F Horii, I Asano, H Yamaguchi, K Aoki, S Maruyama, M Ichii and M Takano, Osaka Prefectural Suita Public Health Center, Osaka, Japan; Y Tsubono, Tohoku University, Miyagi, Japan; K Suzuki, Research Institute for Brain and Blood Vessels Akita, Akita, Japan; Y Honda, K Yamagishi, S Sakurai and N Tsuchiya, Tsukuba University, Ibaraki, Japan; M Kabuto, National Institute for Environmental Studies, Ibaraki, Japan; M Yamaguchi, Y Matsumura, S Sasaki and S Watanabe, National Institute of Health and Nutrition, Tokyo, Japan; M Akabane, Tokyo University of Agriculture, Tokyo, Japan; T Kadowaki, Tokyo University, Tokyo, Japan; M Noda and T Mizoue, International Medical Center of Japan, Tokyo, Japan; Y Kawaguchi, Tokyo Medical and Dental University, Tokyo, Japan; Y Takashima and M Yoshida, Kyorin University, Tokyo, Japan; K Nakamura, Niigata University, Niigata, Japan; S Matsushima and S Natsukawa, Saku General Hospital, Nagano, Japan; H Shimizu, Sakihae Institute, Gifu, Japan; H Sugimura, Hamamatsu University, Shizuoka, Japan; S Tominaga, Aichi Cancer Center Research Institute, Aichi, Japan; H Iso, Osaka University, Osaka, Japan; M Iida, W Ajiki and A Ioka, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan; S Sato, Chiba Prefectural Institute of Public Health, Chiba, Japan; E Maruyama, Kobe University, Hyogo, Japan; M Konishi, K Okada and I Saito, Ehime University, Ehime, Japan; N Yasuda, Kochi University, Kochi, Japan; and S Kono, Kyushu University, Fukuoka, Japan.
References
Footnotes
Funding This work was supported by Grants-in-Aid for Cancer Research (19shi-2) and a Health Sciences Research Grant (Comprehensive Research on Cardiovascular Diseases H19-016) from the Ministry of Health, Labour and Welfare of Japan.
Competing interests None.
Patient consent Obtained.
Ethics approval The study was approved by the Institutional Review Board of the National Cancer Center of Japan.
Provenance and peer review Not commissioned; externally peer reviewed.